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Sample records for multiple fluav subtypes

  1. Naturally occurring Influenza A virus subtype H1N2 infection in a Midwest United States mink (Mustela vison) ranch.

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    Yoon, Kyoung-Jin; Schwartz, Kent; Sun, Dong; Zhang, Jianqiang; Hildebrandt, Hugh

    2012-03-01

    Influenza A virus (FLUAV) causes acute respiratory disease in humans and a variety of animal species. The virus tends to remain within the species of origin; nonetheless, naturally occurring cross-species transmission of FLUAV has been periodically documented. Multiple cross-species transmissions of FLUAV have been reported from companion animals and captive wild animals, neither of which is historically considered as natural hosts of FLUAV. In the fall of 2010, mink (Mustela vison) inhabiting a 15,000-head mink farm in the Midwest United States experienced persistent severe respiratory distress and nose and/or mouth bleeding. Mink losses averaged approximately 10 animals per day. Six dead mink at 6 months of age were submitted to the Iowa State University Veterinary Diagnostic Laboratory for diagnostic investigation. Gross and microscopic examinations revealed that all 6 mink had hemorrhagic bronchointerstitial pneumonia. Hemolytic Escherichia coli was isolated from lungs, probably accounting for hemorrhagic pneumonia. All animals tested negative for Canine distemper virus and Aleutian mink disease virus. Interestingly, FLUAV of H1N2 subtype, which contained the matrix gene of swine lineage, was detected in the lungs. Serological follow-up on mink that remained in the ranch until pelting also confirmed that the ranch had been exposed to FLUAV of H1 subtype (δ clade). The case study suggests that FLUAV should be included in the differential diagnosis when mink experience epidemics of respiratory disease. Since the source of FLUAV appeared to be uncooked turkey meat, feeding animals fully cooked ration should be considered as a preventive measure.

  2. Integrative Analysis of Prognosis Data on Multiple Cancer Subtypes

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    Liu, Jin; Huang, Jian; Zhang, Yawei; Lan, Qing; Rothman, Nathaniel; Zheng, Tongzhang; Ma, Shuangge

    2014-01-01

    Summary In cancer research, profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Cancer is diverse. Examining the similarity and difference in the genetic basis of multiple subtypes of the same cancer can lead to a better understanding of their connections and distinctions. Classic meta-analysis methods analyze each subtype separately and then compare analysis results across subtypes. Integrative analysis methods, in contrast, analyze the raw data on multiple subtypes simultaneously and can outperform meta-analysis methods. In this study, prognosis data on multiple subtypes of the same cancer are analyzed. An AFT (accelerated failure time) model is adopted to describe survival. The genetic basis of multiple subtypes is described using the heterogeneity model, which allows a gene/SNP to be associated with prognosis of some subtypes but not others. A compound penalization method is developed to identify genes that contain important SNPs associated with prognosis. The proposed method has an intuitive formulation and is realized using an iterative algorithm. Asymptotic properties are rigorously established. Simulation shows that the proposed method has satisfactory performance and outperforms a penalization-based meta-analysis method and a regularized thresholding method. An NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements is analyzed. Genes associated with the three major subtypes, namely DLBCL, FL, and CLL/SLL, are identified. The proposed method identifies genes that are different from alternatives and have important implications and satisfactory prediction performance. PMID:24766212

  3. Multiple estrogen receptor subtypes influence ingestive behavior in female rodents.

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    Santollo, Jessica; Daniels, Derek

    2015-12-01

    Postmenopausal women are at an increased risk of obesity and cardiovascular-related diseases. This is attributable, at least in part, to loss of the ovarian hormone estradiol, which inhibits food and fluid intake in humans and laboratory animal models. Although the hypophagic and anti-dipsogenic effects of estradiol have been well documented for decades, the precise mechanisms underlying these effects are not fully understood. An obvious step toward addressing this open question is identifying which estrogen receptor subtypes are involved and what intracellular processes are involved. This question, however, is complicated not only by the variety of estrogen receptor subtypes that exist, but also because many subtypes have multiple locations of action (i.e. in the nucleus or in the plasma membrane). This review will highlight our current understanding of the roles that specific estrogen receptor subtypes play in mediating estradiol's anorexigenic and anti-dipsogenic effects along with highlighting the many open questions that remain. This review will also describe recent work being performed by our laboratory aimed at answering these open questions. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Multiple Receptor Subtypes for the CGRP Super-Family

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    R. Quirion

    2001-01-01

    Full Text Available Molecular evidence for the existence of multiple receptors for CGRP has been rather difficult to obtain. Over 10 years after suggesting the existence of at least two classes (CGRP1 and CGRP2 of CGRP receptors on the basis of pharmacological data[1], molecular data on the CGRP2 receptor subtype are still lacking as well as potent and selective antagonists. The situation is somewhat different for the functional CGRP1 subtype which is likely composed of diverse subunits CRLR, RAMP1 and possibly RCP[2]. Moreover, BIBN 4096BS was recently reported as the first nonpeptide highly potent CGRP1 receptor antagonist[3]. However, in situ hybridization and receptor autoradiographic data have clearly shown the existence of major mismatches (e.g., cerebellum between the discrete localization of CRLR, RAMP1, and specific CGRP binding sites supporting the existence of CGRP receptor subtypes. Functional studies have also provided evidence in that regard (for a recent review: [4]. Accordingly, additional studies aiming at cloning additional CGRP receptors are certainly warranted. Similarly, recent evidence from various laboratories including ours suggests the existence of more than one class (CRLR and RAMP2 of adrenomedullin receptors at least in the rat brain. In contrast, most evidence suggests the existence of a single class of amylin receptors. In brief, it appears that multiple receptors or receptor complexes do exist for CGRP and related peptides but their composition is apparently unique among the GPCR super-family and additional data are needed to fully establish the molecular organization of each subtype. Supported by CIHR of Canada.

  5. Evidence of multiple introductions of HIV-1 subtype C in Angola.

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    Afonso, Joana Morais; Morgado, Mariza G; Bello, Gonzalo

    2012-10-01

    HIV-1 subtype C is the most prevalent group M clade in southern Africa and some eastern African countries. Subtype C is also the most frequent subtype in Angola (southwestern Africa), with an estimated prevalence of 10-20%. In order to better understand the origin of the HIV-1 subtype C strains circulating in Angola, 31 subtype C pol sequences of Angolan origin were compared with 1950 subtype C pol sequences sampled in other African countries. Phylogenetic analyses reveal that the Angolan subtype C sequences were distributed in 16 different lineages that were widely dispersed among other African strains. Ten subtype C Angolan lineages were composed by only one sequence, while the remaining six clades contain between two and seven sequences. Bayesian phylogeographic analysis indicates that most Angolan clades probably originated in different southern African countries with the exception of one lineage that most likely originated in Burundi. Evolutionary analysis suggests that those Angolan subtype C clades composed by ≥ 2 sequences were introduced into the country between the late 1970s and the mid 2000s. The median estimated time frame for the origin of those Angolan lineages coincides with periods of positive migration influx in Angola that were preceded by phases of negative migratory outflow. These results demonstrate that the Angolan subtype C epidemic resulted from multiple introductions of subtype C viruses mainly imported from southern African countries over the last 30years, some of which have been locally disseminated establishing several autochthonous transmission networks. This study also suggests that population mobility between Angola and southern African countries during civil war (1974-2002) may have played a key role in the emergence of the Angolan subtype C epidemic. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Characteristic MRI findings in multiple system atrophy: comparison of the three subtypes

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    Naka, H.; Ohshita, T.; Murata, Y.; Imon, Y.; Mimori, Y.; Nakamura, S. [Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima (Japan)

    2002-03-01

    We reviewed MRI findings in 29 patients with probable multiple system atrophy (MSA) to see whether there were common and or less common neuroradiological findings in the various clinical subtypes. We divided the patients into three clinical subtypes according to initial and predominant symptoms: 14 with olivopontocerebellar atrophy (OPCA), eight with the Shy-Drager syndrome (SDS) and seven with striatonigral degeneration (SND). The patients showed atrophy of the brain stem and cerebellum, high signal on T2-weighted images of the base of the pons and middle cerebellar peduncles, high and low signal on T2-weighted images of the putamen and atrophy of frontal and parietal lobes. The degree of atrophy of the middle cerebellar peduncle and cerebellum was greater in OPCA patients and a high-signal lateral rim to the putamen more frequent in SND. However, all findings were observed in all subtypes, and the degrees of atrophy of the putamen and pons and the frequency of high signal in the base of the pons were similar in the subtypes. We also found atrophy of the cerebral hemispheres, especially the frontal and parietal lobes, but its degree was not significantly different in the various subtypes. Our findings suggest that, although MSA can be divided clinically into three subtypes, most of the features on MRI are common and overlap in the subtypes, independently of the clinical presentation. (orig.)

  7. The Effectiveness of Using a Multiple Gating Approach to Discriminate among ADHD Subtypes

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    Simonsen, Brandi M.; Bullis, Michael D.

    2007-01-01

    This study explored the ability of Systematically Progressive Assessment (SPA), a multiple gating approach for assessing students with attention-deficit/hyperactivity disorder (ADHD), to discriminate between subtypes of ADHD. A total of 48 students with ADHD (ages 6-11) were evaluated with three "gates" of assessment. Logistic regression analysis…

  8. Autonomic dysfunction in different subtypes of multiple system atrophy.

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    Schmidt, Claudia; Herting, Birgit; Prieur, Silke; Junghanns, Susann; Schweitzer, Katherine; Globas, Christoph; Schöls, Ludger; Reichmann, Heinz; Berg, Daniela; Ziemssen, Tjalf

    2008-09-15

    Multiple system atrophy (MSA) can clinically be divided into the cerebellar (MSA-C) and the parkinsonian (MSA-P) variant. However, till now, it is unknown whether autonomic dysfunction in these two entities differs regarding severity and profile. We compared the pattern of autonomic dysfunction in 12 patients with MSA-C and 26 with MSA-P in comparison with 27 age- and sex-matched healthy controls using a standard battery of autonomic function tests and a structured anamnesis of the autonomic nervous system. MSA-P patients complained significantly more often about the symptoms of autonomic dysfunctions than MSA-C patients, especially regarding vasomotor, secretomotor, and gastrointestinal subsystems. However, regarding cardiovascular, sudomotor pupil, urogenital, and sleep subsystems, there were no significant quantitative or qualitative differences as analyzed by autonomic anamnesis and testing. Our results suggest that there are only minor differences in the pattern of autonomic dysfunction between the two clinical MSA phenotypes. (c) 2007 Movement Disorder Society.

  9. A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

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    Garcia-Rodriguez, Consuelo; Razai, Ali; Geren, Isin N; Lou, Jianlong; Conrad, Fraser; Wen, Wei-Hua; Farr-Jones, Shauna; Smith, Theresa J; Brown, Jennifer L; Skerry, Janet C; Smith, Leonard A; Marks, James D

    2018-03-01

    Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (K D ). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had K D values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018.

  10. A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes

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    Consuelo Garcia-Rodriguez

    2018-03-01

    Full Text Available Human botulism is most commonly caused by botulinum neurotoxin (BoNT serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS. A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD. By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633 is in pre-clinical development with an investigational new drug (IND application filing expected in 2018.

  11. Meta-analytic framework for sparse K-means to identify disease subtypes in multiple transcriptomic studies.

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    Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George

    Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K -means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups.

  12. Mimotopes selected with neutralizing antibodies against multiple subtypes of influenza A

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    Zhong Yanwei

    2011-12-01

    Full Text Available Abstract Background The mimotopes of viruses are considered as the good targets for vaccine design. We prepared mimotopes against multiple subtypes of influenza A and evaluate their immune responses in flu virus challenged Balb/c mice. Methods The mimotopes of influenza A including pandemic H1N1, H3N2, H2N2 and H1N1 swine-origin influenza virus were screened by peptide phage display libraries, respectively. These mimotopes were engineered in one protein as multi- epitopes in Escherichia coli (E. coli and purified. Balb/c mice were immunized using the multi-mimotopes protein and specific antibody responses were analyzed using hemagglutination inhibition (HI assay and enzyme-linked immunosorbent assay (ELISA. The lung inflammation level was evaluated by hematoxylin and eosin (HE. Results Linear heptopeptide and dodecapeptide mimotopes were obtained for these influenza virus. The recombinant multi-mimotopes protein was a 73 kDa fusion protein. Comparing immunized infected groups with unimmunized infected subsets, significant differences were observed in the body weight loss and survival rate. The antiserum contained higher HI Ab titer against H1N1 virus and the lung inflammation level were significantly decreased in immunized infected groups. Conclusions Phage-displayed mimotopes against multiple subtypes of influenza A were accessible to the mouse immune system and triggered a humoral response to above virus.

  13. Identification of Multiple Subtypes of Campylobacter jejuni in Chicken Meat and the Impact on Source Attribution

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    John A. Hudson

    2013-09-01

    Full Text Available Most source attribution studies for Campylobacter use subtyping data based on single isolates from foods and environmental sources in an attempt to draw epidemiological inferences. It has been suggested that subtyping only one Campylobacter isolate per chicken carcass incurs a risk of failing to recognise the presence of clinically relevant, but numerically infrequent, subtypes. To investigate this, between 21 and 25 Campylobacter jejuni isolates from each of ten retail chicken carcasses were subtyped by pulsed-field gel electrophoresis (PFGE using the two restriction enzymes SmaI and KpnI. Among the 227 isolates, thirteen subtypes were identified, the most frequently occurring subtype being isolated from three carcasses. Six carcasses carried a single subtype, three carcasses carried two subtypes each and one carcass carried three subtypes. Some subtypes carried by an individual carcass were shown to be potentially clonally related. Comparison of C. jejuni subtypes from chickens with isolate subtypes from human clinical cases (n = 1248 revealed seven of the thirteen chicken subtypes were indistinguishable from human cases. None of the numerically minor chicken subtypes were identified in the human data. Therefore, typing only one Campylobacter isolate from individual chicken carcasses may be adequate to inform Campylobacter source attribution.

  14. Transmission of single and multiple viral variants in primary HIV-1 subtype C infection.

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    Vladimir Novitsky

    2011-02-01

    Full Text Available To address whether sequences of viral gag and env quasispecies collected during the early post-acute period can be utilized to determine multiplicity of transmitted HIV's, recently developed approaches for analysis of viral evolution in acute HIV-1 infection [1,2] were applied. Specifically, phylogenetic reconstruction, inter- and intra-patient distribution of maximum and mean genetic distances, analysis of Poisson fitness, shape of highlighter plots, recombination analysis, and estimation of time to the most recent common ancestor (tMRCA were utilized for resolving multiplicity of HIV-1 transmission in a set of viral quasispecies collected within 50 days post-seroconversion (p/s in 25 HIV-infected individuals with estimated time of seroconversion. The decision on multiplicity of HIV infection was made based on the model's fit with, or failure to explain, the observed extent of viral sequence heterogeneity. The initial analysis was based on phylogeny, inter-patient distribution of maximum and mean distances, and Poisson fitness, and was able to resolve multiplicity of HIV transmission in 20 of 25 (80% cases. Additional analysis involved distribution of individual viral distances, highlighter plots, recombination analysis, and estimation of tMRCA, and resolved 4 of the 5 remaining cases. Overall, transmission of a single viral variant was identified in 16 of 25 (64% cases, and transmission of multiple variants was evident in 8 of 25 (32% cases. In one case multiplicity of HIV-1 transmission could not be determined. In primary HIV-1 subtype C infection, samples collected within 50 days p/s and analyzed by a single-genome amplification/sequencing technique can provide reliable identification of transmission multiplicity in 24 of 25 (96% cases. Observed transmission frequency of a single viral variant and multiple viral variants were within the ranges of 64% to 68%, and 32% to 36%, respectively.

  15. CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes.

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    Timucin Avsar

    Full Text Available Multiple sclerosis (MS is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179. Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5 which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5 system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10 pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5. An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.

  16. Different loss of dopamine transporter according to subtype of multiple system atrophy

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    Kim, Hae Won [Keimyung University Dongsan Medical Center, Department of Nuclear Medicine, Daegu (Korea, Republic of); Keimyung University, Department of Nuclear Medicine, School of Medicine, Jung-gu, Daegu (Korea, Republic of); Kim, Jae Seung; Oh, Minyoung; Oh, Jungsu S.; Lee, Sang Joo; Oh, Seung Jun [University of Ulsan College of Medicine, Department of Nuclear Medicine, Asan Medical Center, Songpa-gu, Seoul (Korea, Republic of); Chung, Sun Ju; Lee, Chong Sik [University of Ulsan College of Medicine, Department of Neurology, Asan Medical Center, Seoul (Korea, Republic of)

    2016-03-15

    The aim of this study was to evaluate whether striatal dopamine transporter (DAT) loss as measured by {sup 18}F-fluorinated-N-3-fluoropropyl-2-b-carboxymethoxy-3-b-(4-iodophenyl) nortropane ([{sup 18}F]FP-CIT) PET differs according to the metabolic subtype of multiple system atrophy (MSA) as assessed by [{sup 18}F]FDG PET. This retrospective study included 50 patients with clinically diagnosed MSA who underwent [{sup 18}F]FP-CIT and [{sup 18}F]FDG brain PET scans. The PET images were analysed using 12 striatal subregional volume-of-interest templates (bilateral ventral striatum, anterior caudate, posterior caudate, anterior putamen, posterior putamen, and ventral putamen). The patients were classified into three metabolic subtypes according to the [{sup 18}F]FDG PET findings: MSA-P{sub m} (striatal hypometabolism only), MSA-mixed{sub m} (both striatal and cerebellar hypometabolism), and MSA-C{sub m} (cerebellar hypometabolism only). The subregional glucose metabolic ratio (MR{sub gluc}), subregional DAT binding ratio (BR{sub DAT}), and intersubregional ratio (ISR{sub DAT}; defined as the BR{sub DAT} ratio of one striatal subregion to that of another striatal subregion) were compared according to metabolic subtype. Of the 50 patients, 13 presented with MSA-P{sub m}, 16 presented with MSA-mixed{sub m}, and 21 presented with MSA-C{sub m}. The BR{sub DAT} of all striatal subregions in the MSA-P{sub m} and MSA-mixed{sub m} groups were significantly lower than those in the MSA-C{sub m} group. The posterior putamen/anterior putamen ISR{sub DAT} and anterior putamen/ventral striatum ISR{sub DAT} in the MSA-P{sub m} and MSA-mixed{sub m} groups were significantly lower than those in the MSA-C{sub m} group. Patients with MSA-P{sub m} and MSA-mixed{sub m} showed more severe DAT loss in the striatum than patients with MSA-C{sub m}. Patients with MSA-C{sub m} had more diffuse DAT loss than patients with MSA-P{sub m} and MSA-mixed{sub m}. (orig.)

  17. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

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    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi

    2016-01-01

    Objective A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Methods Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zeala...

  18. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

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    Nakayama, A.; Nakaoka, H.; Yamamoto, K.; Sakiyama, M.; Shaukat, A.; Toyoda, Y.; Okada, Y.; Kamatani, Y.; Nakamura, T.; Takada, T.; Inoue, K.; Yasujima, T.; Yuasa, H.; Shirahama, Y.; Nakashima, H.; Shimizu, S.; Higashino, T.; Kawamura, Y.; Ogata, H.; Kawaguchi, M.; Ohkawa, Y.; Danjoh, I.; Tokumasu, A.; Ooyama, K.; Ito, T.; Kondo, T.; Wakai, K.; Stiburkova, B.; Pavelka, K.; Stamp, L.K.; Dalbeth, N.; Sakurai, Y.; Suzuki, H; Hosoyamada, M.; Fujimori, S.; Yokoo, T.; Hosoya, T.; Inoue, I.; Takahashi, A.; Kubo, M.; Ooyama, H.; Shimizu, T.; Ichida, K.; Shinomiya, N.; Merriman, T.R.; Matsuo, H.; Andres, M; Joosten, L.A.; Janssen, M.C.H.; Jansen, T.L.; Liote, F.; Radstake, T.R.; Riches, P.L.; So, A.; Tauches, A.K.

    2017-01-01

    OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were

  19. Heterosubtypic immunity to influenza A virus infections in mallards may explain existence of multiple virus subtypes.

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    Neus Latorre-Margalef

    Full Text Available Wild birds, particularly duck species, are the main reservoir of influenza A virus (IAV in nature. However, knowledge of IAV infection dynamics in the wild bird reservoir, and the development of immune responses, are essentially absent. Importantly, a detailed understanding of how subtype diversity is generated and maintained is lacking. To address this, 18,679 samples from 7728 Mallard ducks captured between 2002 and 2009 at a single stopover site in Sweden were screened for IAV infections, and the resulting 1081 virus isolates were analyzed for patterns of immunity. We found support for development of homosubtypic hemagglutinin (HA immunity during the peak of IAV infections in the fall. Moreover, re-infections with the same HA subtype and related prevalent HA subtypes were uncommon, suggesting the development of natural homosubtypic and heterosubtypic immunity (p-value = 0.02. Heterosubtypic immunity followed phylogenetic relatedness of HA subtypes, both at the level of HA clades (p-value = 0.04 and the level of HA groups (p-value = 0.05. In contrast, infection patterns did not support specific immunity for neuraminidase (NA subtypes. For the H1 and H3 Clades, heterosubtypic immunity showed a clear temporal pattern and we estimated within-clade immunity to last at least 30 days. The strength and duration of heterosubtypic immunity has important implications for transmission dynamics of IAV in the natural reservoir, where immune escape and disruptive selection may increase HA antigenic variation and explain IAV subtype diversity.

  20. MicroRNA expression in multiple myeloma is associated with genetic subtype, isotype and survival

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    Pezzella Francesco

    2011-05-01

    Full Text Available Abstract Background MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including hematological malignancies. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM is only poorly understood. We therefore used microarray analysis to elucidate the complete miRNome (miRBase version 13.0 of purified tumor (CD138+ cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS and 9 controls. Results Unsupervised cluster analysis revealed that MM and MGUS samples have a distinct microRNA expression profile from control CD138+ cells. The majority of microRNAs aberrantly expressed in MM (109/129 were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell malignancies revealed a surprising degree of similarity (~40% suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59% of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14 and t(11;14 and del(13q. Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis and correctly predicted these abnormalities in > 85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS in MM, ten of which were significant by univariate (logrank survival analysis. Conclusions In summary, this work has identified aberrantly expressed microRNAs associated with the

  1. Identification of Subtype Specific miRNA-mRNA Functional Regulatory Modules in Matched miRNA-mRNA Expression Data: Multiple Myeloma as a Case

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    Yunpeng Zhang

    2015-01-01

    Full Text Available Identification of miRNA-mRNA modules is an important step to elucidate their combinatorial effect on the pathogenesis and mechanisms underlying complex diseases. Current identification methods primarily are based upon miRNA-target information and matched miRNA and mRNA expression profiles. However, for heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between subtypes, leading to differences in clinical behavior. In order to explore the pathogenesis of each subtype, it is important to identify subtype specific miRNA-mRNA modules. In this study, we integrated the Ping-Pong algorithm and multiobjective genetic algorithm to identify subtype specific miRNA-mRNA functional regulatory modules (MFRMs through integrative analysis of three biological data sets: GO biological processes, miRNA target information, and matched miRNA and mRNA expression data. We applied our method on a heterogeneous disease, multiple myeloma (MM, to identify MM subtype specific MFRMs. The constructed miRNA-mRNA regulatory networks provide modular outlook at subtype specific miRNA-mRNA interactions. Furthermore, clustering analysis demonstrated that heterogeneous MFRMs were able to separate corresponding MM subtypes. These subtype specific MFRMs may aid in the further elucidation of the pathogenesis of each subtype and may serve to guide MM subtype diagnosis and treatment.

  2. Non-motor symptoms and the quality of life in multiple system atrophy with different subtypes.

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    Zhang, LingYu; Cao, Bei; Ou, RuWei; Wei, Qian-Qian; Zhao, Bi; Yang, Jing; Wu, Ying; Shang, HuiFang

    2017-02-01

    The differences in non-motor symptoms (NMS) and quality of life (QOL) between MSA patients with different subtypes remain unknown, so do the determinants of poor QOL in both subtypes. A total of 172 MSA patients were enrolled in the study. NMS of patients with MSA were assessed using the non-motor symptoms scale (NMSS) and Parkinson's Disease Questionnaire-39 item version (PDQ-39) was used to evaluate the QOL of patients with MSA. The most prevalent NMS domain was urinary (91.3%) in both subtypes. The mood/apathy domain was more severe in MSA-P than MSA-C patients (P sleep/fatigue symptoms and gastrointestinal symptoms were determinants of poor QOL in MSA-P patients. While in MSA-C patients, longer disease duration, disease severity and mood/apathy symptoms were determinants of poor QOL. NMS are more severe and prevalent in MSA-P patients, especially for mood/apathy and gastrointestinal symptoms. There is a close relationship between NMS and QOL in both MSA subtypes. Disease severity, longer disease duration and severe NMS are determinants of poor QOL in MSA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.

    Science.gov (United States)

    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi; Shimizu, Seiko; Higashino, Toshihide; Kawamura, Yusuke; Ogata, Hiraku; Kawaguchi, Makoto; Ohkawa, Yasuyuki; Danjoh, Inaho; Tokumasu, Atsumi; Ooyama, Keiko; Ito, Toshimitsu; Kondo, Takaaki; Wakai, Kenji; Stiburkova, Blanka; Pavelka, Karel; Stamp, Lisa K; Dalbeth, Nicola; Sakurai, Yutaka; Suzuki, Hiroshi; Hosoyamada, Makoto; Fujimori, Shin; Yokoo, Takashi; Hosoya, Tatsuo; Inoue, Ituro; Takahashi, Atsushi; Kubo, Michiaki; Ooyama, Hiroshi; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi; Merriman, Tony R; Matsuo, Hirotaka

    2017-05-01

    A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study. In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (pgout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (p meta =3.58×10 -8 ). Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Use of multiple molecular subtyping techniques to investigate a Legionnaires' disease outbreak due to identical strains at two tourist lodges.

    Science.gov (United States)

    Mamolen, M; Breiman, R F; Barbaree, J M; Gunn, R A; Stone, K M; Spika, J S; Dennis, D T; Mao, S H; Vogt, R L

    1993-10-01

    A multistate outbreak of Legionnaires' disease occurred among nine tour groups of senior citizens returning from stays at one of two lodges in a Vermont resort in October 1987. Interviews and serologic studies of 383 (85%) of the tour members revealed 17 individuals (attack rate, 4.4%) with radiologically documented pneumonia and laboratory evidence of legionellosis. A survey of tour groups staying at four nearby lodges and of Vermont-area medical facilities revealed no additional cases. Environmental investigation of common tour stops revealed no likely aerosol source of Legionella infection outside the lodges. Legionella pneumophila serogroup 1 was isolated from water sources at both implicated lodges, and the monoclonal antibody subtype matched those of the isolates from six patients from whom clinical isolates were obtained. The cultures reacted with monoclonal antibodies MAB1, MAB2, 33G2, and 144C2 to yield a 1,2,5,7 or a Benidorm 030E pattern. The strains were also identical by alloenzyme electrophoresis and DNA ribotyping techniques. The epidemiologic and laboratory data suggest that concurrent outbreaks occurred following exposures to the same L. pneumophila serogroup 1 strain at two separate lodges. Multiple molecular subtyping techniques can provide essential information for epidemiologic investigations of Legionnaires' disease.

  5. Comparative analysis of the pituitary and ovarian GnRH systems in the leopard gecko: signaling crosstalk between multiple receptor subtypes in ovarian follicles.

    Science.gov (United States)

    Ikemoto, Tadahiro; Park, Min Kyun

    2007-02-01

    GnRH regulates reproductive functions through interaction with its pituitary receptor in vertebrates. The present study demonstrated that the leopard gecko possessed two and three genes for GnRH ligands and receptors, respectively, though one of the three receptor subtypes had long been thought not to exist in reptiles. Each receptor subtype showed a distinct pharmacology. All types of ligands and receptors showed different expression patterns, and were widely expressed both inside and outside the brain. This report also shows a comparison of the pituitary and ovarian GnRH systems in the leopard gecko during and after the egg-laying season. All three receptor subtypes were expressed in both the whole pituitary and ovary; however, only one receptor subtype could be detected in the anterior pituitary gland. In situ hybridization showed spatial expression patterns of ovarian receptors, and suggested co-expression of multiple receptor subtypes in granulosa cells of larger follicles. Co-transfection of receptor subtypes showed a distinct pharmacology in COS-7 cells compared with those of single transfections. These results suggest that distinct signaling mechanisms are involved in the pituitary and ovarian GnRH systems. Seasonal and developmental variations in receptor expression in the anterior pituitary gland and ovarian follicles may contribute to the seasonal breeding of this animal.

  6. Genetic association of multiple sclerosis with the marker rs391745 near the endogenous retroviral locus HERV-Fc1: analysis of disease subtypes

    DEFF Research Database (Denmark)

    Hansen, Bettina; Oturai, Annette Bang; Harbo, Hanne F

    2011-01-01

    We have previously described the occurrence of multiple sclerosis (MS) to be associated with human endogenous retroviruses, specifically the X-linked viral locus HERV-Fc1. The aim of this study was to investigate a possible association of the HERV-Fc1 locus with subtypes of MS. MS patients......-Fc1 locus (p = 0.003), while primary progressive disease was not. The ability to see genetic differences between subtypes of MS near this gene speaks for the involvement of the virus HERV-Fc1 locus in modifying the disease course of MS....

  7. Revisiting the Phylogeny of the Animal Formins: Two New Subtypes, Relationships with Multiple Wing Hairs Proteins, and a Lost Human Formin.

    Science.gov (United States)

    Pruyne, David

    2016-01-01

    Formins are a widespread family of eukaryotic cytoskeleton-organizing proteins. Many species encode multiple formin isoforms, and for animals, much of this reflects the presence of multiple conserved subtypes. Earlier phylogenetic analyses identified seven major formin subtypes in animals (DAAM, DIAPH, FHOD, FMN, FMNL, INF, and GRID2IP/delphilin), but left a handful of formins, particularly from nematodes, unassigned. In this new analysis drawing from genomic data from a wider range of taxa, nine formin subtypes are identified that encompass all the animal formins analyzed here. Included in this analysis are Multiple Wing Hairs proteins (MWH), which bear homology to formin N-terminal domains. Originally identified in Drosophila melanogaster and other arthropods, MWH-related proteins are also identified here in some nematodes (including Caenorhabditis elegans), and are shown to be related to a novel MWH-related formin (MWHF) subtype. One surprising result of this work is the discovery that a family of pleckstrin homology domain-containing formins (PHCFs) is represented in many vertebrates, but is strikingly absent from placental mammals. Consistent with a relatively recent loss of this formin, the human genome retains fragments of a defunct homologous formin gene.

  8. Entry inhibitor-based microbicides are active in vitro against HIV-1 isolates from multiple genetic subtypes

    International Nuclear Information System (INIS)

    Ketas, Thomas J.; Schader, Susan M.; Zurita, Juan; Teo, Esther; Polonis, Victoria; Lu Min; Klasse, Per Johan; Moore, John P.

    2007-01-01

    Inhibitors of viral entry are under consideration as topical microbicides to prevent HIV-1 sexual transmission. Small molecules targeting HIV-1 gp120 (BMS-378806) or CCR5 (CMPD167), and a peptide fusion inhibitor (C52L), each blocks vaginal infection of macaques by a SHIV. A microbicide, however, must be active against multiple HIV-1 variants. We therefore tested BMS-C (a BMS-378806 derivative), CMPD167, C52L and the CXCR4 ligand AMD3465, alone and in combination, against 25 primary R5, 12 X4 and 7 R5X4 isolates from subtypes A-G. At high concentrations (0.1-1 μM), the replication of most R5 isolates in human donor lymphocytes was inhibited by > 90%. At lower concentrations, double and triple combinations were more effective than individual inhibitors. Similar results were obtained with X4 viruses when AMD3465 was substituted for CMPD167. The R5X4 viruses were inhibited by combining AMD3465 with CMPD167, or by the coreceptor-independent compounds. Thus, combining entry inhibitors may improve microbicide effectiveness

  9. A guild of 45 CRISPR-associated (Cas protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes.

    Directory of Open Access Journals (Sweden)

    Daniel H Haft

    2005-11-01

    Full Text Available Clustered regularly interspaced short palindromic repeats (CRISPRs are a family of DNA direct repeats found in many prokaryotic genomes. Repeats of 21-37 bp typically show weak dyad symmetry and are separated by regularly sized, nonrepetitive spacer sequences. Four CRISPR-associated (Cas protein families, designated Cas1 to Cas4, are strictly associated with CRISPR elements and always occur near a repeat cluster. Some spacers originate from mobile genetic elements and are thought to confer "immunity" against the elements that harbor these sequences. In the present study, we have systematically investigated uncharacterized proteins encoded in the vicinity of these CRISPRs and found many additional protein families that are strictly associated with CRISPR loci across multiple prokaryotic species. Multiple sequence alignments and hidden Markov models have been built for 45 Cas protein families. These models identify family members with high sensitivity and selectivity and classify key regulators of development, DevR and DevS, in Myxococcus xanthus as Cas proteins. These identifications show that CRISPR/cas gene regions can be quite large, with up to 20 different, tandem-arranged cas genes next to a repeat cluster or filling the region between two repeat clusters. Distinctive subsets of the collection of Cas proteins recur in phylogenetically distant species and correlate with characteristic repeat periodicity. The analyses presented here support initial proposals of mobility of these units, along with the likelihood that loci of different subtypes interact with one another as well as with host cell defensive, replicative, and regulatory systems. It is evident from this analysis that CRISPR/cas loci are larger, more complex, and more heterogeneous than previously appreciated.

  10. Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes

    OpenAIRE

    Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho

    2015-01-01

    Objective Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. Methods A GWAS was conducted with 945 patients with clinically defined gout and 1213 contr...

  11. Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes.

    Science.gov (United States)

    Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho; Ogata, Hiraku; Tatsukawa, Seishiro; Yin, Guang; Okada, Rieko; Morita, Emi; Naito, Mariko; Tokumasu, Atsumi; Onoue, Hiroyuki; Iwaya, Keiichi; Ito, Toshimitsu; Takada, Tappei; Inoue, Katsuhisa; Kato, Yukio; Nakamura, Yukio; Sakurai, Yutaka; Suzuki, Hiroshi; Kanai, Yoshikatsu; Hosoya, Tatsuo; Hamajima, Nobuyuki; Inoue, Ituro; Kubo, Michiaki; Ichida, Kimiyoshi; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

    2016-04-01

    Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. A GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls. Five gout susceptibility loci were identified at the genome-wide significance level (pgenes (ABCG2 and SLC2A9) and additional genes: rs1260326 (p=1.9×10(-12); OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10(-23); OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10(-9); OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case-control ORs for two distinct types of gout (r=0.96 [p=4.8×10(-4)] for urate clearance and r=0.96 [p=5.0×10(-4)] for urinary urate excretion). Our findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  12. The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder.

    Science.gov (United States)

    Malki, Karim; Keers, Robert; Tosto, Maria Grazia; Lourdusamy, Anbarasu; Carboni, Lucia; Domenici, Enrico; Uher, Rudolf; McGuffin, Peter; Schalkwyk, Leonard C

    2014-05-07

    Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study. Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic 'stress' protocols (maternal separation and Unpredictable Chronic Mild Stress) to model 'reactive' depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of 'endogenous' depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium. In the mouse 'reactive' model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the 'endogenous' rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing. Our results suggest that 'endogenous' and 'reactive' subtypes of depression are associated with largely

  13. CTL epitope distribution patterns in the Gag and Nef proteins of HIV-1 from subtype A infected subjects in Kenya: Use of multiple peptide sets increases the detectable breadth of the CTL response

    Directory of Open Access Journals (Sweden)

    Birx Deborah L

    2006-04-01

    Full Text Available Abstract Background Subtype A is a major strain in the HIV-1 pandemic in eastern Europe, central Asia and in certain regions of east Africa, notably in rural Kenya. While considerable effort has been focused upon mapping and defining immunodominant CTL epitopes in HIV-1 subtype B and subtype C infections, few epitope mapping studies have focused upon subtype A. Results We have used the IFN-γ ELIspot assay and overlapping peptide pools to show that the pattern of CTL recognition of the Gag and Nef proteins in subtype A infection is similar to that seen in subtypes B and C. The p17 and p24 proteins of Gag and the central conserved region of Nef were targeted by CTL from HIV-1-infected Kenyans. Several epitope/HLA associations commonly seen in subtype B and C infection were also observed in subtype A infections. Notably, an immunodominant HLA-C restricted epitope (Gag 296–304; YL9 was observed, with 8/9 HLA-CW0304 subjects responding to this epitope. Screening the cohort with peptide sets representing subtypes A, C and D (the three most prevalent HIV-1 subtypes in east Africa, revealed that peptide sets based upon an homologous subtype (either isolate or consensus only marginally improved the capacity to detect CTL responses. While the different peptide sets detected a similar number of responses (particularly in the Gag protein, each set was capable of detecting unique responses not identified with the other peptide sets. Conclusion Hence, screening with multiple peptide sets representing different sequences, and by extension different epitope variants, can increase the detectable breadth of the HIV-1-specific CTL response. Interpreting the true extent of cross-reactivity may be hampered by the use of 15-mer peptides at a single concentration and a lack of knowledge of the sequence that primed any given CTL response. Therefore, reagent choice and knowledge of the exact sequences that prime CTL responses will be important factors in

  14. Protection against Multiple Subtypes of Influenza Viruses by Virus-Like Particle Vaccines Based on a Hemagglutinin Conserved Epitope

    Directory of Open Access Journals (Sweden)

    Shaoheng Chen

    2015-01-01

    Full Text Available We selected the conserved sequence in the stalk region of influenza virus hemagglutinin (HA trimmer, the long alpha helix (LAH, as the vaccine candidate sequence, and inserted it into the major immunodominant region (MIR of hepatitis B virus core protein (HBc, and, by using the E. coli expression system, we prepared a recombinant protein vaccine LAH-HBc in the form of virus-like particles (VLP. Intranasal immunization of mice with this LAH-HBc VLP plus cholera toxin B subunit with 0.2% of cholera toxin (CTB* adjuvant could effectively elicit humoral and cellular immune responses and protect mice against a lethal challenge of homologous influenza viruses (A/Puerto Rico/8/1934 (PR8 (H1N1. In addition, passage of the immune sera containing specific antibodies to naïve mice rendered them resistant against a lethal homologous challenge. Immunization with LAH-HBc VLP vaccine plus CTB* adjuvant could also fully protect mice against a lethal challenge of the 2009 pandemic H1N1 influenza virus or the avian H9N2 virus and could partially protect mice against a lethal challenge of the avian H5N1 influenza virus. This study demonstrated that the LAH-HBc VLP vaccine based on a conserved sequence of the HA trimmer stalk region is a promising candidate vaccine for developing a universal influenza vaccine against multiple influenza viruses infections.

  15. The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma

    International Nuclear Information System (INIS)

    Ronchetti, D; Todoerti, K; Tuana, G; Agnelli, L; Mosca, L; Lionetti, M; Fabris, S; Colapietro, P; Miozzo, M; Ferrarini, M; Tassone, P; Neri, A

    2012-01-01

    Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may have a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM) by profiling purified malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCLs) and 4 normal controls. Overall, a global sno/scaRNAs downregulation was found in MMs and, even more, in sPCLs compared with normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the translocation/cyclin D4 (TC4) MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by an imprinting center at 15q11, which, however, resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information to the bio-molecular complexity of plasma cell dyscrasias

  16. Optimization of a multi-gene HIV-1 recombinant subtype CRF02AG DNA vaccine for expression of multiple immunogenic forms

    International Nuclear Information System (INIS)

    Ellenberger, Dennis; Li Bin; Smith, James; Yi Hong; Folks, Thomas; Robinson, Harriet; Butera, Salvatore

    2004-01-01

    We developed an AIDS vaccine for Western and West-Central Africa based on a DNA plasmid vector expressing HIV-1 recombinant subtype CRF02 A G gag, pol, and env genes. To optimize the production of noninfectious HIV-like particles (VLPs) and potentially improve the effectiveness of the vaccine, we generated four potential vaccine constructs: the parental (IC2) and three modifications (IC25, IC48, and IC90) containing mutations within the HIV protease. While the parental construct IC2 expressed aggregates of Gag proteins, the IC25 construct resulted in the production of immature VLPs (the core comprises unprocessed Pr 55Gag ). The remaining two constructs (IC48 and IC90) produced mature VLPs (the core comprises processed capsid p24) in addition to immature VLPs and aggregates of Gag proteins. VLPs incorporated significant levels of mature gp120 envelope glycoprotein. Importantly, the mature VLPs were fusion competent and entered coreceptor-specific target cells. The production of multiple antigenic forms, including fusion-competent VLPs, by candidate DNA vaccine constructs may provide immunologic advantages for induction of protective cellular and humoral responses against HIV-1 proteins

  17. Identification of Subtype Specific miRNA-mRNA Functional Regulatory Modules in Matched miRNA-mRNA Expression Data: Multiple Myeloma as a Case

    OpenAIRE

    Zhang, Yunpeng; Liu, Wei; Xu, Yanjun; Li, Chunquan; Wang, Yingying; Yang, Haixiu; Zhang, Chunlong; Su, Fei; Li, Yixue; Li, Xia

    2015-01-01

    Identification of miRNA-mRNA modules is an important step to elucidate their combinatorial effect on the pathogenesis and mechanisms underlying complex diseases. Current identification methods primarily are based upon miRNA-target information and matched miRNA and mRNA expression profiles. However, for heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between subtypes, leading to differences in clinical behavior. In order to explore the pathogenesis of each subtype, it i...

  18. Seizure induces activation of multiple subtypes of neural progenitors and growth factors in hippocampus with neuronal maturation confined to dentate gyrus

    Energy Technology Data Exchange (ETDEWEB)

    Indulekha, Chandrasekharan L.; Sanalkumar, Rajendran [Neuro Stem Cell Biology Laboratory, Department of Neurobiology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695 014 (India); Thekkuveettil, Anoopkumar [Molecular Medicine, Biomedical Technology Wing, Sree Chitra Thirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala (India); James, Jackson, E-mail: jjames@rgcb.res.in [Neuro Stem Cell Biology Laboratory, Department of Neurobiology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695 014 (India)

    2010-03-19

    Adult hippocampal neurogenesis is altered in response to different physiological and pathological stimuli. GFAP{sup +ve}/nestin{sup +ve} radial glial like Type-1 progenitors are considered to be the resident stem cell population in adult hippocampus. During neurogenesis these Type-1 progenitors matures to GFAP{sup -ve}/nestin{sup +ve} Type-2 progenitors and then to Type-3 neuroblasts and finally differentiates into granule cell neurons. In our study, using pilocarpine-induced seizure model, we showed that seizure initiated activation of multiple progenitors in the entire hippocampal area such as DG, CA1 and CA3. Seizure induction resulted in activation of two subtypes of Type-1 progenitors, Type-1a (GFAP{sup +ve}/nestin{sup +ve}/BrdU{sup +ve}) and Type-1b (GFAP{sup +ve}/nestin{sup +ve}/BrdU{sup -ve}). We showed that majority of Type-1b progenitors were undergoing only a transition from a state of dormancy to activated form immediately after seizures rather than proliferating, whereas Type-1a showed maximum proliferation by 3 days post-seizure induction. Type-2 (GFAP{sup -ve}/nestin{sup +ve}/BrdU{sup +ve}) progenitors were few compared to Type-1. Type-3 (DCX{sup +ve}) progenitors showed increased expression of immature neurons only in DG region by 3 days after seizure induction indicating maturation of progenitors happens only in microenvironment of DG even though progenitors are activated in CA1 and CA3 regions of hippocampus. Also parallel increase in growth factors expression after seizure induction suggests that microenvironmental niche has a profound effect on stimulation of adult neural progenitors.

  19. Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes.

    Science.gov (United States)

    Newman-Tancredi, Adrian; Cussac, Didier; Quentric, Yann; Touzard, Manuelle; Verrièle, Laurence; Carpentier, Nathalie; Millan, Mark J

    2002-11-01

    Although certain antiparkinson agents interact with serotonin (5-HT) receptors, little information is available concerning functional actions. Herein, we characterized efficacies of apomorphine, bromocriptine, cabergoline, lisuride, piribedil, pergolide, roxindole, and terguride at human (h)5-HT(1A), h5-HT(1B), and h5-HT(1D) receptors [guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding], and at h5-HT(2A), h5-HT(2B), and h5-HT(2C) receptors (depletion of membrane-bound [(3)H]phosphatydilinositol). All drugs stimulated h5-HT(1A) receptors with efficacies (compared with 5-HT, 100%) ranging from modest (apomorphine, 35%) to high (cabergoline, 93%). At h5-HT(1B) receptors, efficacies varied from mild (terguride, 37%) to marked (cabergoline, 102%) and potencies were modest (pEC(50) values of 5.8-7.6): h5-HT(1D) sites were activated with a similar range of efficacies and greater potency (7.1-8.5). Piribedil and apomorphine were inactive at h5-HT(1B) and h5-HT(1D) receptors. At h5-HT(2A) receptors, terguride, lisuride, bromocriptine, cabergoline, and pergolide displayed potent (7.6-8.8) agonist properties (49-103%), whereas apomorphine and roxindole were antagonists and piribedil was inactive. Only pergolide (113%/8.2) and cabergoline (123%/8.6) displayed pronounced agonist properties at h5-HT(2B) receptors. At 5-HT(2C) receptors, lisuride, bromocriptine, pergolide, and cabergoline were efficacious (75-96%) agonists, apomorphine and terguride were antagonists, and piribedil was inactive. MDL100,907 and SB242,084, selective antagonists at 5-HT(2A) and 5-HT(2C) receptors, respectively, abolished these actions of pergolide, cabergoline, and bromocriptine. In conclusion, antiparkinson agents display markedly different patterns of agonist and antagonist properties at multiple 5-HT receptor subtypes. Although all show modest (agonist) activity at 5-HT(1A) sites, their contrasting actions at 5-HT(2A) and 5-HT(2C) sites may be of particular significance to their

  20. Assessing possible DSM-5 ASD subtypes in a sample of victims meeting caseness for DSM-5 ASD based on self-report following multiple forms of traumatic exposure.

    Science.gov (United States)

    Hansen, Maj; Armour, Cherie; Wang, Li; Elklit, Ask; Bryant, Richard A

    2015-04-01

    Acute stress disorder (ASD) was introduced into the DSM-IV to recognize early traumatic responses and as a precursor of PTSD. Although the diagnostic criteria for ASD were altered and structured more similarly to the PTSD definition in DSM-5, only the PTSD diagnosis includes a dissociative subtype. Emerging research has indicated that there also appears to be a highly symptomatic subtype for ASD. However, the specific nature of the subtype is currently unclear. The present study investigates the possible presence of ASD subtypes in a mixed sample of victims meeting caseness for DSM-5 ASD based on self-report following four different types of traumatic exposure (N=472). The results of latent profile analysis revealed a 5-class solution. The highly symptomatic class was marked by high endorsement on avoidance and dissociation compared to the other classes. Findings are discussed in regard to its clinical implications including the implications for the pending the ICD-11 and the recently released DSM-5. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Verified Subtyping with Traits and Mixins

    Directory of Open Access Journals (Sweden)

    Asankhaya Sharma

    2014-07-01

    Full Text Available Traits allow decomposing programs into smaller parts and mixins are a form of composition that resemble multiple inheritance. Unfortunately, in the presence of traits, programming languages like Scala give up on subtyping relation between objects. In this paper, we present a method to check subtyping between objects based on entailment in separation logic. We implement our method as a domain specific language in Scala and apply it on the Scala standard library. We have verified that 67% of mixins used in the Scala standard library do indeed conform to subtyping between the traits that are used to build them.

  2. Circulation of multiple subtypes of bovine viral diarrhoea virus type 1 with no evidence for HoBi-like pestivirus in cattle herds of southern Italy.

    Science.gov (United States)

    Lanave, G; Decaro, N; Lucente, M S; Guercio, A; Cavaliere, N; Purpari, G; Padalino, I; Larocca, V; Antoci, F; Marino, P A; Buonavoglia, C; Elia, G

    2017-06-01

    Pestiviruses of cattle include bovine viral diarrhoea 1 (BVDV-1) and 2 (BVDV-2) plus an emerging group, named HoBi-like pestivirus. In the present paper, the results of an epidemiological survey for pestiviruses circulating in cattle in southern Italy are presented. Molecular assays carried out on a total of 924 bovine samples detected 74 BVDV strains, including 73 BVDV-1 and 1 BVDV-2 viruses. Phylogenetic analysis carried out on partial 5'UTR and N pro sequences revealed the presence of 6 different subtypes of BVDV-1 and a single BVDV-2c strain. BVDV-1 displayed a high level of genetic heterogeneity, which can have both prophylactic and diagnostic implications. In addition, the detection of BVDV-2c highlights the need for a continuous surveillance for the emergence of new pestivirus strains in cattle farms in southern Italy. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Blastocystis Isolates from Patients with Irritable Bowel Syndrome and from Asymptomatic Carriers Exhibit Similar Parasitological Loads, but Significantly Different Generation Times and Genetic Variability across Multiple Subtypes.

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    Gie-Bele Vargas-Sanchez

    Full Text Available Blastocystis spp is a common intestinal parasite of humans and animals that has been associated to the etiology of irritable bowel syndrome (IBS; however, some studies have not found this association. Furthermore, many biological features of Blastocystis are little known. The objective of present study was to assess the generation times of Blastocystis cultures, from IBS patients and from asymptomatic carriers. A total of 100 isolates were obtained from 50 IBS patients and from 50 asymptomatic carriers. Up to 50 mg of feces from each participant were cultured in Barret's and in Pavlova's media during 48 h. Initial and final parasitological load were measured by microscopy and by quantitative PCR. Amplicons were purified, sequenced and submitted to GenBank; sequences were analysed for genetic diversity and a Bayesian inference allowed identifying genetic subtypes (ST. Generation times for Blastocystis isolates in both media, based on microscopic measures and molecular assays, were calculated. The clinical symptoms of IBS patients and distribution of Blastocystis ST 1, 2 and 3 in both groups was comparable to previous reports. Interestingly, the group of cases showed scarce mean nucleotide diversity (π as compared to the control group (0.011±0.016 and 0.118±0.177, respectively, whilst high gene flow and small genetic differentiation indexes between different ST were found. Besides, Tajima's D test showed negative values for ST1-ST3. No statistical differences regarding parasitological load between cases and controls in both media, as searched by microscopy and by qPCR, were detected except that parasites grew faster in Barret's than in Pavlova's medium. Interestingly, slow growth of isolates recovered from cases in comparison to those of controls was observed (p<0.05. We propose that generation times of Blastocystis might be easily affected by intestinal environmental changes due to IBS probably because virulent strains with slow growth may be

  4. H-1 MR spectroscopy of the brain in multiple sclerosis subtypes with analysis of the metabolite concentrations in gray and white matter : initial findings

    NARCIS (Netherlands)

    Sijens, PE; Mostert, JP; Oudkerk, M; De Keyser, J

    Many MR spectroscopy (MRS) studies of multiple sclerosis (MS) have focussed on metabolism in normal-appearing white matter (NAWM) and in white matter lesions (WML). In this study, eight patients suffering from primary or secondary progressive MS (PPMS/SPMS) and seven patients with

  5. Morphologic Subtypes of Hepatocellular Carcinoma.

    Science.gov (United States)

    Torbenson, Michael S

    2017-06-01

    Hepatocellular carcinomas can be further divided into distinct subtypes that provide important clinical information and biological insights. These subtypes are distinct from growth patterns and are on based on morphologic and molecular findings. There are 12 reasonably well-defined subtypes as well as 6 provisional subtypes, together making up 35% of all hepatocellular carcinomas. These subtypes are discussed, with an emphasis on their definitions and the key morphologic findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Systematic analysis of fly models with multiple drivers reveals different effects of ataxin-1 and huntingtin in neuron subtype-specific expression.

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    Risa Shiraishi

    Full Text Available The fruit fly, Drosophila melanogaster, is a commonly used model organism for neurodegenerative diseases. Its major advantages include a short lifespan and its susceptibility to manipulation using sophisticated genetic techniques. Here, we report the systematic comparison of fly models of two polyglutamine (polyQ diseases. We induced expression of the normal and mutant forms of full-length Ataxin-1 and Huntingtin exon 1 in cholinergic, dopaminergic, and motor neurons, and glial cells using cell type-specific drivers. We systematically analyzed their effects based on multiple phenotypes: eclosion rate, lifespan, motor performance, and circadian rhythms of spontaneous activity. This systematic assay system enabled us to quantitatively evaluate and compare the functional disabilities of different genotypes. The results suggest different effects of Ataxin-1 and Huntingtin on specific types of neural cells during development and in adulthood. In addition, we confirmed the therapeutic effects of LiCl and butyrate using representative models. These results support the usefulness of this assay system for screening candidate chemical compounds that modify the pathologies of polyQ diseases.

  7. Increased pathogenicity and shedding in chickens of a wild bird-origin low pathogenicity avian influenza virus of the H7N3 subtype following multiple in vivo passages in quail and turkey.

    Science.gov (United States)

    Cilloni, Filippo; Toffan, Anna; Giannecchini, Simone; Clausi, Valeria; Azzi, Alberta; Capua, Ilaria; Terregino, Calogero

    2010-03-01

    In order to investigate viral adaptation mechanisms to poultry, we performed serial in vivo passages of a wild bird low pathogenicity avian influenza isolate of the H7N3 subtype (A/mallard/Italy/33/01) in three different domestic species (chicken, turkey, and Japanese quail). The virus under study was administered via natural routes at the dose of 10(6) egg infective dose50/ 0.1 ml to chickens, turkeys, and quails in order to investigate the clinical susceptibility and the shedding levels after infection. Multiple in vivo passages of the virus were performed by serially infecting groups of five naive birds of each species, with samples collected from a previously infected group. Quails and turkeys were susceptible to infection for 10 serial passages, whereas chickens were susceptible to two cycles of infection only. Infection of chicken with the quail- and turkey-adapted viruses showed an increased pathogenicity and/or shedding, causing more severe clinical signs and/or higher levels of viral excretion compared to the original strain. The data obtained herein suggest that infection of selected avian species may facilitate the adaptation of avian influenza viruses originating from the wild bird reservoir to chicken. This is the first time turkey has been shown to act as a species in which a virus from the wild reservoir can increase its replication activity in other domestic species.

  8. Pathological Gambling Subtypes

    Science.gov (United States)

    Vachon, David D.; Bagby, R. Michael

    2009-01-01

    Although pathological gambling (PG) is regarded in the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) as a unitary diagnostic construct, it is likely composed of distinct subtypes. In the current report, the authors used cluster analyses of personality traits with a…

  9. Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Kirstin B. Langer

    2018-04-01

    Full Text Available Summary: Retinal ganglion cells (RGCs are the projection neurons of the retina and transmit visual information to postsynaptic targets in the brain. While this function is shared among nearly all RGCs, this class of cell is remarkably diverse, comprised of multiple subtypes. Previous efforts have identified numerous RGC subtypes in animal models, but less attention has been paid to human RGCs. Thus, efforts of this study examined the diversity of RGCs differentiated from human pluripotent stem cells (hPSCs and characterized defined subtypes through the expression of subtype-specific markers. Further investigation of these subtypes was achieved using single-cell transcriptomics, confirming the combinatorial expression of molecular markers associated with these subtypes, and also provided insight into more subtype-specific markers. Thus, the results of this study describe the derivation of RGC subtypes from hPSCs and will support the future exploration of phenotypic and functional diversity within human RGCs. : In this article, Langer and colleagues present extensive characterization of RGC subtypes derived from human pluripotent stem cells, with multiple subtypes identified by subtype-specific molecular markers. Their results present a more detailed analysis of RGC diversity in human cells and yield the use of different markers to identify RGC subtypes. Keywords: iPSC, retina, retinal ganglion cell, RGC subtype, stem cell, ipRGC, alpha RGC, direction selective RGC, RNA-seq

  10. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate...... that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure...

  11. Influenza A Subtyping

    Science.gov (United States)

    Kaul, Karen L.; Mangold, Kathy A.; Du, Hongyan; Pesavento, Kristen M.; Nawrocki, John; Nowak, Jan A.

    2010-01-01

    Influenza virus subtyping has emerged as a critical tool in the diagnosis of influenza. Antiviral resistance is present in the majority of seasonal H1N1 influenza A infections, with association of viral strain type and antiviral resistance. Influenza A virus subtypes can be reliably distinguished by examining conserved sequences in the matrix protein gene. We describe our experience with an assay for influenza A subtyping based on matrix gene sequences. Viral RNA was prepared from nasopharyngeal swab samples, and real-time RT-PCR detection of influenza A and B was performed using a laboratory developed analyte-specific reagent-based assay that targets a conserved region of the influenza A matrix protein gene. FluA-positive samples were analyzed using a second RT-PCR assay targeting the matrix protein gene to distinguish seasonal influenza subtypes based on differential melting of fluorescence resonance energy transfer probes. The novel H1N1 influenza strain responsible for the 2009 pandemic showed a melting profile distinct from that of seasonal H1N1 or H3N2 and compatible with the predicted melting temperature based on the published novel H1N1 matrix gene sequence. Validation by comparison with the Centers for Disease Control and Prevention real-time RT-PCR for swine influenza A (novel H1N1) test showed this assay to be both rapid and reliable (>99% sensitive and specific) in the identification of the novel H1N1 influenza A virus strain. PMID:20595627

  12. Subtyping adolescents with bulimia nervosa.

    Science.gov (United States)

    Chen, Eunice Y; Le Grange, Daniel

    2007-12-01

    Cluster analyses of eating disorder patients have yielded a "dietary-depressive" subtype, typified by greater negative affect, and a "dietary" subtype, typified by dietary restraint. This study aimed to replicate these findings in an adolescent sample with bulimia nervosa (BN) from a randomized controlled trial and to examine the validity and reliability of this methodology. In the sample of BN adolescents (N=80), cluster analysis revealed a "dietary-depressive" subtype (37.5%) and a "dietary" subtype (62.5%) using the Beck Depression Inventory, Rosenberg Self-Esteem Scale and Eating Disorder Examination Restraint subscale. The "dietary-depressive" subtype compared to the "dietary" subtype was significantly more likely to: (1) report co-occurring disorders, (2) greater eating and weight concerns, and (3) less vomiting abstinence at post-treatment (all p'sreliability of the subtyping scheme, a larger sample of adolescents with mixed eating and weight disorders in an outpatient eating disorder clinic (N=149) was subtyped, yielding similar subtypes. These results support the validity and reliability of the subtyping strategy in two adolescent samples.

  13. Pure type systems with subtyping

    NARCIS (Netherlands)

    Zwanenburg, J.; Girard, J.-Y.

    1999-01-01

    We extend the framework of Pure Type Systems with subtyping, as found in F = ¿ . This leads to a concise description of many existing systems with subtyping, and also to some new interesting systems. We develop the meta-theory for this framework, including Subject Reduction and Minimal Typing. The

  14. Does Subtype Matter? Assessing the Effects of Maltreatment on Functioning in Preadolescent Youth in Out-of-Home Care

    Science.gov (United States)

    Petrenko, Christie L. M.; Friend, Angela; Garrido, Edward F.; Taussig, Heather N.; Culhane, Sara E.

    2012-01-01

    Objectives: Attempts to understand the effects of maltreatment subtypes on childhood functioning are complicated by the fact that children often experience multiple subtypes. This study assessed the effects of maltreatment subtypes on the cognitive, academic, and mental health functioning of preadolescent youth in out-of-home care using both…

  15. Subtypes of Patients Experiencing Exacerbations of COPD and Associations with Outcomes

    Science.gov (United States)

    Arostegui, Inmaculada; Esteban, Cristobal; García-Gutierrez, Susana; Bare, Marisa; Fernández-de-Larrea, Nerea; Briones, Eduardo; Quintana, José M.

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition characterized by occasional exacerbations. Identifying clinical subtypes among patients experiencing COPD exacerbations (ECOPD) could help better understand the pathophysiologic mechanisms involved in exacerbations, establish different strategies of treatment, and improve the process of care and patient prognosis. The objective of this study was to identify subtypes of ECOPD patients attending emergency departments using clinical variables and to validate the results using several outcomes. We evaluated data collected as part of the IRYSS-COPD prospective cohort study conducted in 16 hospitals in Spain. Variables collected from ECOPD patients attending one of the emergency departments included arterial blood gases, presence of comorbidities, previous COPD treatment, baseline severity of COPD, and previous hospitalizations for ECOPD. Patient subtypes were identified by combining results from multiple correspondence analysis and cluster analysis. Results were validated using key outcomes of ECOPD evolution. Four ECOPD subtypes were identified based on the severity of the current exacerbation and general health status (largely a function of comorbidities): subtype A (n = 934), neither high comorbidity nor severe exacerbation; subtype B (n = 682), moderate comorbidities; subtype C (n = 562), severe comorbidities related to mortality; and subtype D (n = 309), very severe process of exacerbation, significantly related to mortality and admission to an intensive care unit. Subtype D experienced the highest rate of mortality, admission to an intensive care unit and need for noninvasive mechanical ventilation, followed by subtype C. Subtypes A and B were primarily related to other serious complications. Hospitalization rate was more than 50% for all the subtypes, although significantly higher for subtypes C and D than for subtypes A and B. These results could help identify

  16. Do COPD subtypes really exist? COPD heterogeneity and clustering in 10 independent cohorts

    NARCIS (Netherlands)

    Castaldi, Peter J; Benet, Marta; Petersen, Hans; Rafaels, Nicholas; Finigan, James; Paoletti, Matteo; Marike Boezen, H; Vonk, Judith M; Bowler, Russell; Pistolesi, Massimo; Puhan, Milo A; Anto, Josep; Wauters, Els; Lambrechts, Diether; Janssens, Wim; Bigazzi, Francesca; Camiciottoli, Gianna; Cho, Michael H; Hersh, Craig P; Barnes, Kathleen; Rennard, Stephen; Boorgula, Meher Preethi; Dy, Jennifer; Hansel, Nadia N; Crapo, James D; Tesfaigzi, Yohannes; Agusti, Alvar; Silverman, Edwin K; Garcia-Aymerich, Judith

    Background COPD is a heterogeneous disease, but there is little consensus on specific definitions for COPD subtypes. Unsupervised clustering offers the promise of 'unbiased' data-driven assessment of COPD heterogeneity. Multiple groups have identified COPD subtypes using cluster analysis, but there

  17. Frequency of Natural Resistance within NS5a Replication Complex Domain in Hepatitis C Genotypes 1a, 1b: Possible Implication of Subtype-Specific Resistance Selection in Multiple Direct Acting Antivirals Drugs Combination Treatment

    Directory of Open Access Journals (Sweden)

    Sabrina Bagaglio

    2016-03-01

    Full Text Available Different HCV subtypes may naturally harbor different resistance selection to anti-NS5a inhibitors. 2761 sequences retrieved from the Los Alamos HCV database were analyzed in the NS5a domain 1, the target of NS5a inhibitors. The NS5a resistance-associated polymorphisms (RAPs were more frequently detected in HCV G1b compared to G1a. The prevalence of polymorphisms associated with cross-resistance to compounds in clinical use (daclatasvir, DCV, ledipasvir, LDV, ombitasvir, and OMV or scheduled to come into clinical use in the near future (IDX719, elbasvir, and ELV was higher in G1b compared to G1a (37/1552 (2.4% in 1b sequences and 15/1209 (1.2% in 1a isolates, p = 0.040. Interestingly, on the basis of the genotype-specific resistance pattern, 95 (6.1% G1b sequences had L31M RAP to DCV/IDX719, while 6 sequences of G1a (0.5% harbored L31M RAP, conferring resistance to DCV/LDV/IDX719/ELV (p < 0.0001. Finally, 28 (2.3% G1a and none of G1b isolates harbored M28V RAP to OMV (p < 0.0001. In conclusion, the pattern of subtype-specific resistance selection in the naturally occurring strains may guide the treatment option in association with direct acting antivirals (DAAs targeting different regions, particularly in patients that are difficult to cure, such as those with advanced liver disease or individuals who have failed previous DAAs.

  18. Robust stratification of breast cancer subtypes using differential patterns of transcript isoform expression.

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    Thomas P Stricker

    2017-03-01

    Full Text Available Breast cancer, the second leading cause of cancer death of women worldwide, is a heterogenous disease with multiple different subtypes. These subtypes carry important implications for prognosis and therapy. Interestingly, it is known that these different subtypes not only have different biological behaviors, but also have distinct gene expression profiles. However, it has not been rigorously explored whether particular transcriptional isoforms are also differentially expressed among breast cancer subtypes, or whether transcript isoforms from the same sets of genes can be used to differentiate subtypes. To address these questions, we analyzed the patterns of transcript isoform expression using a small set of RNA-sequencing data for eleven Estrogen Receptor positive (ER+ subtype and fourteen triple negative (TN subtype tumors. We identified specific sets of isoforms that distinguish these tumor subtypes with higher fidelity than standard mRNA expression profiles. We found that alternate promoter usage, alternative splicing, and alternate 3'UTR usage are differentially regulated in breast cancer subtypes. Profiling of isoform expression in a second, independent cohort of 68 tumors confirmed that expression of splice isoforms differentiates breast cancer subtypes. Furthermore, analysis of RNAseq data from 594 cases from the TCGA cohort confirmed the ability of isoform usage to distinguish breast cancer subtypes. Also using our expression data, we identified several RNA processing factors that were differentially expressed between tumor subtypes and/or regulated by estrogen receptor, including YBX1, YBX2, MAGOH, MAGOHB, and PCBP2. RNAi knock-down of these RNA processing factors in MCF7 cells altered isoform expression. These results indicate that global dysregulation of splicing in breast cancer occurs in a subtype-specific and reproducible manner and is driven by specific differentially expressed RNA processing factors.

  19. Frequent intra-subtype recombination among HIV-1 circulating in Tanzania.

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    Ireen E Kiwelu

    Full Text Available The study estimated the prevalence of HIV-1 intra-subtype recombinant variants among female bar and hotel workers in Tanzania. While intra-subtype recombination occurs in HIV-1, it is generally underestimated. HIV-1 env gp120 V1-C5 quasispecies from 45 subjects were generated by single-genome amplification and sequencing (median (IQR of 38 (28-50 sequences per subject. Recombination analysis was performed using seven methods implemented within the recombination detection program version 3, RDP3. HIV-1 sequences were considered recombinant if recombination signals were detected by at least three methods with p-values of ≤0.05 after Bonferroni correction for multiple comparisons. HIV-1 in 38 (84% subjects showed evidence for intra-subtype recombination including 22 with HIV-1 subtype A1, 13 with HIV-1 subtype C, and 3 with HIV-1 subtype D. The distribution of intra-patient recombination breakpoints suggested ongoing recombination and showed selective enrichment of recombinant variants in 23 (60% subjects. The number of subjects with evidence of intra-subtype recombination increased from 29 (69% to 36 (82% over one year of follow-up, although the increase did not reach statistical significance. Adjustment for intra-subtype recombination is important for the analysis of multiplicity of HIV infection. This is the first report of high prevalence of intra-subtype recombination in the HIV/AIDS epidemic in Tanzania, a region where multiple HIV-1 subtypes co-circulate. HIV-1 intra-subtype recombination increases viral diversity and presents additional challenges for HIV-1 vaccine design.

  20. Ultrasonographic Features of Papillary Thyroid Carcinomas According to Their Subtypes

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    Hye Jin Baek

    2018-05-01

    Full Text Available BackgroundThe ultrasonographic characteristics and difference for various subtypes of papillary thyroid carcinoma (PTC are still unclear. The aim of this study was to compare the ultrasonographic features of PTC according to its subtype in patients undergoing thyroid surgery.MethodsIn total, 140 patients who underwent preoperative thyroid ultrasonography (US and thyroid surgery between January 2016 and December 2016 were included. The ultrasonographic features and the Korean Thyroid Imaging Reporting and Data System (K-TIRADS category of each thyroid nodule were retrospectively evaluated by a single radiologist, and differences in ultrasonographic features according to the PTC subtype were assessed.ResultsAccording to histopathological analyses, there were 97 classic PTCs (62.2%, 34 follicular variants (21.8%, 5 tall cell variants (3.2%, 2 oncocytic variants (1.3%, 1 Warthin-like variant (0.6%, and 1 diffuse sclerosing variant (0.6%. Most PTCs were classified under K-TIRADS category 5. Among the ultrasonographic features, the nodule margin and the presence of calcification were significantly different among the PTC subtypes. A spiculated/microlobulated margin was the most common type of margin, regardless of the PTC subtype. In particular, all tall cell variants exhibited a spiculated/microlobulated margin. The classic PTC group exhibited the highest prevalence of intranodular calcification, with microcalcification being the most common. The prevalence of multiplicity and nodal metastasis was high in the tall cell variant group.ConclusionThe majority of PTCs in the present study belonged to K-TIRADS category 5, regardless of the subtype. Our findings suggest that ultrasonographic features are not useful for distinguishing PTC subtypes.

  1. Motor subtype changes in early Parkinson's disease.

    Science.gov (United States)

    Eisinger, Robert S; Hess, Christopher W; Martinez-Ramirez, Daniel; Almeida, Leonardo; Foote, Kelly D; Okun, Michael S; Gunduz, Aysegul

    2017-10-01

    Distinct motor subtypes of Parkinson's disease (PD) have been described through both clinical observation and through data-driven approaches. However, the extent to which motor subtypes change during disease progression remains unknown. Our objective was to determine motor subtypes of PD using an unsupervised clustering methodology and evaluate subtype changes with disease duration. The Parkinson's Progression Markers Initiative database of 423 newly diagnosed PD patients was utilized to retrospectively identify unique motor subtypes through a data-driven, hierarchical correlational clustering approach. For each patient, we assigned a subtype to each motor assessment at each follow-up visit (time points) and by using published criteria. We examined changes in PD subtype with disease duration using both qualitative and quantitative methods. Five distinct motor subtypes were identified based on the motor assessment items and these included: Tremor Dominant (TD), Axial Dominant, Appendicular Dominant, Rigidity Dominant, and Postural and Instability Gait Disorder Dominant. About half of the patients had consistent subtypes at all time points. Most patients met criteria for TD subtype soon after diagnosis. For patients with inconsistent subtypes, there was an overall trend to shift away from a TD phenotype with disease duration, as shown by chi-squared test, p motor subtypes in PD can shift with increasing disease duration. Shifting subtypes is a factor that should be accounted for in clinical practice or in clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Assessing the Differences in Public Health Impact of Salmonella Subtypes Using a Bayesian Microbial Subtyping Approach for Source Attribution

    DEFF Research Database (Denmark)

    Pires, Sara Monteiro; Hald, Tine

    2010-01-01

    Salmonella is a major cause of human gastroenteritis worldwide. To prioritize interventions and assess the effectiveness of efforts to reduce illness, it is important to attribute salmonellosis to the responsible sources. Studies have suggested that some Salmonella subtypes have a higher health...... impact than others. Likewise, some food sources appear to have a higher impact than others. Knowledge of variability in the impact of subtypes and sources may provide valuable added information for research, risk management, and public health strategies. We developed a Bayesian model that attributes...... illness to specific sources and allows for a better estimation of the differences in the ability of Salmonella subtypes and food types to result in reported salmonellosis. The model accommodates data for multiple years and is based on the Danish Salmonella surveillance. The number of sporadic cases caused...

  3. Persistence of Immunopathological and Radiological Traits in Multiple Sclerosis

    NARCIS (Netherlands)

    Koenig, Fatima B.; Wildemann, Brigitte; Nessler, Stefan; Zhou, Dun; Hemmer, Bernhard; Metz, Imke; Hartung, Hans-Peter; Kieseier, Bernd C.; Brueck, Wolfgang

    Background: Multiple sclerosis (MS) is a heterogeneous autoimmune disease of the central nervous system. The identification of 4 different immunopathological subtypes of MS raises the question of whether these subtypes represent different patient subgroups that can be distinguished according to

  4. Classification of alpha 1-adrenoceptor subtypes

    NARCIS (Netherlands)

    Michel, M. C.; Kenny, B.; Schwinn, D. A.

    1995-01-01

    Two alpha 1-adrenoceptor subtypes (alpha 1A and alpha 1B) have been detected in various tissues by pharmacological techniques, and three distinct cDNAs encoding alpha 1-adrenoceptor subtypes have been cloned. The profile of an increasing number of subtype-selective compounds at cloned and endogenous

  5. Subtypes of nonmedical prescription drug misuse

    Science.gov (United States)

    McCabe, Sean Esteban; Boyd, Carol J.; Teter, Christian J.

    2010-01-01

    This study used three characteristics (i.e., motive, route of administration, and co-ingestion with alcohol) of nonmedical prescription drug misuse across four separate classes (i.e., pain, sedative/anxiety, sleeping and stimulant medications) to examine subtypes and drug related problems. A Web survey was self-administered by a randomly selected sample of 3,639 undergraduate students attending a large Midwestern 4-year U.S. university. Self-treatment subtypes were characterized by motives consistent with the prescription drug's pharmaceutical main indication, oral only routes of administration, and no co-ingestion with alcohol. Recreational subtypes were characterized by recreational motives, oral or non-oral routes, and co-ingestion. Mixed subtypes consisted of other combinations of motives, routes, and co-ingestion. Among those who reported nonmedical prescription drug misuse, approximately 13% were classified into the recreational subtype, while 39% were in the self-treatment subtype, and 48% were in the mixed subtype. There were significant differences in the subtypes in terms of gender, race and prescription drug class. Approximately 50% of those in subtypes other than self-treatment screened positive for drug abuse. The odds of substance use and abuse were generally lower among self-treatment subtypes than other subtypes. The findings indicate subtypes should be considered when examining nonmedical prescription drug misuse, especially for pain medication. PMID:19278795

  6. Diabetes and Breast Cancer Subtypes.

    Directory of Open Access Journals (Sweden)

    Heleen K Bronsveld

    Full Text Available Women with diabetes have a worse survival after breast cancer diagnosis compared to women without diabetes. This may be due to a different etiological profile, leading to the development of more aggressive breast cancer subtypes. Our aim was to investigate whether insulin and non-insulin treated women with diabetes develop specific clinicopathological breast cancer subtypes compared to women without diabetes.This cross-sectional study included randomly selected patients with invasive breast cancer diagnosed in 2000-2010. Stratified by age at breast cancer diagnosis (≤50 and >50 years, women with diabetes were 2:1 frequency-matched on year of birth and age at breast cancer diagnosis (both in 10-year categories to women without diabetes, to select ~300 patients with tumor tissue available. Tumor MicroArrays were stained by immunohistochemistry for estrogen and progesterone receptor (ER, PR, HER2, Ki67, CK5/6, CK14, and p63. A pathologist scored all stains and revised morphology and grade. Associations between diabetes/insulin treatment and clinicopathological subtypes were analyzed using multivariable logistic regression. Morphology and grade were not significantly different between women with diabetes (n = 211 and women without diabetes (n = 101, irrespective of menopausal status. Premenopausal women with diabetes tended to have more often PR-negative (OR = 2.44(95%CI:1.07-5.55, HER2-negative (OR = 2.84(95%CI:1.11-7.22, and basal-like (OR = 3.14(95%CI:1.03-9.60 tumors than the women without diabetes, with non-significantly increased frequencies of ER-negative (OR = 2.48(95%CI:0.95-6.45 and triple negative (OR = 2.60(95%CI:0.88-7.67 tumors. After adjustment for age and BMI, the associations remained similar in size but less significant. We observed no evidence for associations of clinicopathological subtypes with diabetes in postmenopausal women, or with insulin treatment in general.We found no compelling evidence that women with diabetes

  7. Diabetes and Breast Cancer Subtypes.

    Science.gov (United States)

    Bronsveld, Heleen K; Jensen, Vibeke; Vahl, Pernille; De Bruin, Marie L; Cornelissen, Sten; Sanders, Joyce; Auvinen, Anssi; Haukka, Jari; Andersen, Morten; Vestergaard, Peter; Schmidt, Marjanka K

    2017-01-01

    Women with diabetes have a worse survival after breast cancer diagnosis compared to women without diabetes. This may be due to a different etiological profile, leading to the development of more aggressive breast cancer subtypes. Our aim was to investigate whether insulin and non-insulin treated women with diabetes develop specific clinicopathological breast cancer subtypes compared to women without diabetes. This cross-sectional study included randomly selected patients with invasive breast cancer diagnosed in 2000-2010. Stratified by age at breast cancer diagnosis (≤50 and >50 years), women with diabetes were 2:1 frequency-matched on year of birth and age at breast cancer diagnosis (both in 10-year categories) to women without diabetes, to select ~300 patients with tumor tissue available. Tumor MicroArrays were stained by immunohistochemistry for estrogen and progesterone receptor (ER, PR), HER2, Ki67, CK5/6, CK14, and p63. A pathologist scored all stains and revised morphology and grade. Associations between diabetes/insulin treatment and clinicopathological subtypes were analyzed using multivariable logistic regression. Morphology and grade were not significantly different between women with diabetes (n = 211) and women without diabetes (n = 101), irrespective of menopausal status. Premenopausal women with diabetes tended to have more often PR-negative (OR = 2.44(95%CI:1.07-5.55)), HER2-negative (OR = 2.84(95%CI:1.11-7.22)), and basal-like (OR = 3.14(95%CI:1.03-9.60) tumors than the women without diabetes, with non-significantly increased frequencies of ER-negative (OR = 2.48(95%CI:0.95-6.45)) and triple negative (OR = 2.60(95%CI:0.88-7.67) tumors. After adjustment for age and BMI, the associations remained similar in size but less significant. We observed no evidence for associations of clinicopathological subtypes with diabetes in postmenopausal women, or with insulin treatment in general. We found no compelling evidence that women with diabetes, treated

  8. Motoric subtypes of delirium in geriatric patients

    Directory of Open Access Journals (Sweden)

    Sandeep Grover

    2014-01-01

    Results: On amended DMSS, hyperactive subtype (N = 45; 45.9% was the most common motoric subtype of delirium, followed by hypoactive subtype (N = 23; 23.5%, and mixed subtype (N = 21; 21.4%. On DRS-R-98, all patients fulfilled the criteria of ′acute (temporal onset of symptoms′, ′presence of an underlying physical disorder′ and ′difficulty in attention′. In the total sample, >90% of the patients had disturbances in sleep-wake cycle, orientation and fluctuation of symptoms. The least common symptoms were delusions, visuospatial disturbances and motor retardation. When compared to hypoactive group, significantly higher proportion of patients with hyperactive subtype had delusions, perceptual disturbances, and motor agitation. Whereas, compared to hyperactive subtype, significantly higher proportion of patients with hypoactive subtype had thought process abnormality and motor retardation. When the hyperactive and mixed motoric subtype groups were compared, patients with mixed subtype group had significantly higher prevalence of thought process abnormality and motor retardation. Comparison of hypoactive and mixed subtype revealed significant differences in the frequency of perceptual disturbances, delusions and motor agitation and all these symptoms being found more commonly in patients with the mixed subtype. Severity of symptoms were found to be significantly different across the various motoric subtypes for some of the non-cognitive symptoms, but significant differences were not seen for the cognitive symptoms as assessed on DRS-R-98. Conclusion: In elderly patients, motor subtypes of delirium differ from each other on non-cognitive symptom profile in terms of frequency and severity.

  9. Hypertension Subtypes among Hypertensive Patients in Ibadan

    OpenAIRE

    Abiodun M. Adeoye; Adewole Adebiyi; Bamidele O. Tayo; Babatunde L. Salako; Adesola Ogunniyi; Richard S. Cooper

    2014-01-01

    Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% fema...

  10. The Origin and Evolutionary History of HIV-1 Subtype C in Senegal

    Science.gov (United States)

    Jung, Matthieu; Leye, Nafissatou; Vidal, Nicole; Fargette, Denis; Diop, Halimatou; Toure Kane, Coumba; Gascuel, Olivier; Peeters, Martine

    2012-01-01

    Background The classification of HIV-1 strains in subtypes and Circulating Recombinant Forms (CRFs) has helped in tracking the course of the HIV pandemic. In Senegal, which is located at the tip of West Africa, CRF02_AG predominates in the general population and Female Sex Workers (FSWs). In contrast, 40% of Men having Sex with Men (MSM) in Senegal are infected with subtype C. In this study we analyzed the geographical origins and introduction dates of HIV-1 C in Senegal in order to better understand the evolutionary history of this subtype, which predominates today in the MSM population Methodology/Principal Findings We used a combination of phylogenetic analyses and a Bayesian coalescent-based approach, to study the phylogenetic relationships in pol of 56 subtype C isolates from Senegal with 3,025 subtype C strains that were sampled worldwide. Our analysis shows a significantly well supported cluster which contains all subtype C strains that circulate among MSM in Senegal. The MSM cluster and other strains from Senegal are widely dispersed among the different subclusters of African HIV-1 C strains, suggesting multiple introductions of subtype C in Senegal from many different southern and east African countries. More detailed analyses show that HIV-1 C strains from MSM are more closely related to those from southern Africa. The estimated date of the MRCA of subtype C in the MSM population in Senegal is estimated to be in the early 80's. Conclusions/Significance Our evolutionary reconstructions suggest that multiple subtype C viruses with a common ancestor originating in the early 1970s entered Senegal. There was only one efficient spread in the MSM population, which most likely resulted from a single introduction, underlining the importance of high-risk behavior in spread of viruses. PMID:22470456

  11. Breast cancer molecular subtype classification using deep features: preliminary results

    Science.gov (United States)

    Zhu, Zhe; Albadawy, Ehab; Saha, Ashirbani; Zhang, Jun; Harowicz, Michael R.; Mazurowski, Maciej A.

    2018-02-01

    Radiogenomics is a field of investigation that attempts to examine the relationship between imaging characteris- tics of cancerous lesions and their genomic composition. This could offer a noninvasive alternative to establishing genomic characteristics of tumors and aid cancer treatment planning. While deep learning has shown its supe- riority in many detection and classification tasks, breast cancer radiogenomic data suffers from a very limited number of training examples, which renders the training of the neural network for this problem directly and with no pretraining a very difficult task. In this study, we investigated an alternative deep learning approach referred to as deep features or off-the-shelf network approach to classify breast cancer molecular subtypes using breast dynamic contrast enhanced MRIs. We used the feature maps of different convolution layers and fully connected layers as features and trained support vector machines using these features for prediction. For the feature maps that have multiple layers, max-pooling was performed along each channel. We focused on distinguishing the Luminal A subtype from other subtypes. To evaluate the models, 10 fold cross-validation was performed and the final AUC was obtained by averaging the performance of all the folds. The highest average AUC obtained was 0.64 (0.95 CI: 0.57-0.71), using the feature maps of the last fully connected layer. This indicates the promise of using this approach to predict the breast cancer molecular subtypes. Since the best performance appears in the last fully connected layer, it also implies that breast cancer molecular subtypes may relate to high level image features

  12. Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin

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    Mora Xavier

    2007-05-01

    Full Text Available Abstract Background Histone H1 is involved in the formation and maintenance of chromatin higher order structure. H1 has multiple isoforms; the subtypes differ in timing of expression, extent of phosphorylation and turnover rate. In vertebrates, the amino acid substitution rates differ among subtypes by almost one order of magnitude, suggesting that each subtype might have acquired a unique function. We have devised a competitive assay to estimate the relative binding affinities of histone H1 mammalian somatic subtypes H1a-e and H1° for long chromatin fragments (30–35 nucleosomes in physiological salt (0.14 M NaCl at constant stoichiometry. Results The H1 complement of native chromatin was perturbed by adding an additional amount of one of the subtypes. A certain amount of SAR (scaffold-associated region DNA was present in the mixture to avoid precipitation of chromatin by excess H1. SAR DNA also provided a set of reference relative affinities, which were needed to estimate the relative affinities of the subtypes for chromatin from the distribution of the subtypes between the SAR and the chromatin. The amounts of chromatin, SAR and additional H1 were adjusted so as to keep the stoichiometry of perturbed chromatin similar to that of native chromatin. H1 molecules freely exchanged between the chromatin and SAR binding sites. In conditions of free exchange, H1a was the subtype of lowest affinity, H1b and H1c had intermediate affinities and H1d, H1e and H1° the highest affinities. Subtype affinities for chromatin differed by up to 19-fold. The relative affinities of the subtypes for chromatin were equivalent to those estimated for a SAR DNA fragment and a pUC19 fragment of similar length. Avian H5 had an affinity ~12-fold higher than H1e for both DNA and chromatin. Conclusion H1 subtypes freely exchange in vitro between chromatin binding sites in physiological salt (0.14 M NaCl. The large differences in relative affinity of the H1 subtypes for

  13. Transsexual subtypes : Clinical and theoretical significance

    NARCIS (Netherlands)

    Smith, YLS; van Goozen, SHM; Kuiper, AJ; Cohen-Kettenis, PT

    2005-01-01

    The present study was designed to investigate whether transsexuals can be validly subdivided into subtypes on the basis of sexual orientation, and whether differences between subtypes of transsexuals are similar for male-to-female (ME) and female-to-male transsexuals (FMs). Within a large

  14. Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev

    2014-01-01

    expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal...

  15. Variation of types of alcoholism: review and subtypes identified in Han Chinese.

    Science.gov (United States)

    Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Lu, Ru-Band

    2014-01-03

    Alcoholism, as it has been hypothesized, is caused by a highly heterogeneous genetic load. Since 1960, many reports have used the bio-psycho-social approach to subtype alcoholism; however, no subtypes have been genetically validated. We reviewed and compared the major single-gene, multiple-gene, and gene-to-gene interaction studies on alcoholism published during the past quarter-century, including many recent studies that have made contributions to the subtyping of alcoholism. Four subtypes of alcoholism have been reported: [1] pure alcoholism, [2] anxiety/depression alcoholism, [3] antisocial alcoholism, and [4] mixed alcoholism. Most of the important studies focused on three genes: DRD2, MAOA, and ALDH2. Therefore, our review focuses on these three genes. © 2013.

  16. Molecular subtypes of Alzheimer's disease.

    Science.gov (United States)

    Di Fede, Giuseppe; Catania, Marcella; Maderna, Emanuela; Ghidoni, Roberta; Benussi, Luisa; Tonoli, Elisa; Giaccone, Giorgio; Moda, Fabio; Paterlini, Anna; Campagnani, Ilaria; Sorrentino, Stefano; Colombo, Laura; Kubis, Adriana; Bistaffa, Edoardo; Ghetti, Bernardino; Tagliavini, Fabrizio

    2018-02-19

    Protein misfolding and aggregation is a central feature of several neurodegenerative disorders including Alzheimer's disease (AD), in which assemblies of amyloid β (Aβ) peptides accumulate in the brain in the form of parenchymal and/or vascular amyloid. A widely accepted concept is that AD is characterized by distinct clinical and neuropathological phenotypes. Recent studies revealed that Aβ assemblies might have structural differences among AD brains and that such pleomorphic assemblies can correlate with distinct disease phenotypes. We found that in both sporadic and inherited forms of AD, amyloid aggregates differ in the biochemical composition of Aβ species. These differences affect the physicochemical properties of Aβ assemblies including aggregation kinetics, resistance to degradation by proteases and seeding ability. Aβ-amyloidosis can be induced and propagated in animal models by inoculation of brain extracts containing aggregated Aβ. We found that brain homogenates from AD patients with different molecular profiles of Aβ are able to induce distinct patterns of Aβ-amyloidosis when injected into mice. Overall these data suggest that the assembly of mixtures of Aβ peptides into different Aβ seeds leads to the formation of distinct subtypes of amyloid having distinctive physicochemical and biological properties which result in the generation of distinct AD molecular subgroups.

  17. Clinical investigation of set-shifting subtypes in anorexia nervosa.

    Science.gov (United States)

    Abbate-Daga, Giovanni; Buzzichelli, Sara; Marzola, Enrica; Amianto, Federico; Fassino, Secondo

    2014-11-30

    While evidence continues to accumulate on the relevance of cognitive inflexibility in anorexia nervosa (AN), its clinical correlates remain unclear. We aimed at examining the relationship between set-shifting and clinical variables (i.e., eating psychopathology, depression, and personality) in AN. Ninety-four individuals affected by AN and 59 healthy controls (HC) were recruited. All participants were assessed using: Eating Disorders Inventory-2 (EDI-2), Temperament and Character Inventory (TCI), Beck Depression Inventory (BDI), and Wisconsin Card Sorting Test (WCST). The AN group scored worse than HCs on set-shifting. According to their neuropsychological performances, AN patients were split into two groups corresponding to poor (N=30) and intact (N=64) set-shifting subtypes. Interoceptive awareness, impulse regulation, and maturity fears on the EDI-2 and depression on the BDI differed across all groups (HC, intact, and poor set-shifting subtype). Self-directedness on the TCI differed significantly among all groups. Cooperativeness and reward dependence differed instead only between HC and AN poor set-shifting subtype. After controlling for depression, only interoceptive awareness remained significant with reward dependence showing a trend towards statistical significance. These findings suggest that multiple clinical variables may be correlated with set-shifting performances in AN. The factors contributing to impaired cognitive inflexibility could be more complex than heretofore generally considered. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Hypertension Subtypes among Hypertensive Patients in Ibadan

    Directory of Open Access Journals (Sweden)

    Abiodun M. Adeoye

    2014-01-01

    Full Text Available Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% female, hypertensive, aged 18 and above were recruited into the study from two centers in Ibadan, Nigeria. Hypertension was identified using JNCVII definition and was further grouped into four subtypes: controlled hypertension (CH, isolated systolic hypertension (ISH, isolated diastolic hypertension (IDH, and systolic-diastolic hypertension (SDH. Results. Systolic-diastolic hypertension was the most prevalent. Whereas SDH (77.6% versus 73.5% and IDH (4.9% versus 4.7% were more prevalent among females, ISH (10.1% versus 6.2% was higher among males (P=0.048. Female subjects were more obese (P<0.0001 and SDH was prevalent among the obese group. Conclusion. Gender and obesity significantly influenced the distribution of the hypertension subtypes. Characterization of hypertension by subtypes in genetic association studies could lead to identification of previously unknown genetic variants involved in the etiology of hypertension. Large-scale studies among various ethnic groups may be needed to confirm these observations.

  19. Interferon α subtypes in HIV infection.

    Science.gov (United States)

    Sutter, Kathrin; Dickow, Julia; Dittmer, Ulf

    2018-02-13

    Type I interferons (IFN), which are immediately induced after most virus infections, are central for direct antiviral immunity and link innate and adaptive immune responses. However, several viruses have evolved strategies to evade the IFN response by preventing IFN induction or blocking IFN signaling pathways. Thus, therapeutic application of exogenous type I IFN or agonists inducing type I IFN responses are a considerable option for future immunotherapies against chronic viral infections. An important part of the type I IFN family are 12 IFNα subtypes, which all bind the same receptor, but significantly differ in their biological activities. Up to date only one IFNα subtype (IFNα2) is being used in clinical treatment against chronic virus infections, however its therapeutic success rate is rather limited, especially during Human Immunodeficiency Virus (HIV) infection. Recent studies addressed the important question if other IFNα subtypes would be more potent against retroviral infections in in vitro and in vivo experiments. Indeed, very potent IFNα subtypes were defined and their antiviral and immunomodulatory properties were characterized. In this review we summarize the recent findings on the role of individual IFNα subtypes during HIV and Simian Immunodeficiency Virus infection. This includes their induction during HIV/SIV infection, their antiretroviral activity and the regulation of immune response against HIV by different IFNα subtypes. The findings might facilitate novel strategies for HIV cure or functional cure studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. An evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1.

    Directory of Open Access Journals (Sweden)

    Sergei L Kosakovsky Pond

    2009-11-01

    Full Text Available Genetically diverse pathogens (such as Human Immunodeficiency virus type 1, HIV-1 are frequently stratified into phylogenetically or immunologically defined subtypes for classification purposes. Computational identification of such subtypes is helpful in surveillance, epidemiological analysis and detection of novel variants, e.g., circulating recombinant forms in HIV-1. A number of conceptually and technically different techniques have been proposed for determining the subtype of a query sequence, but there is not a universally optimal approach. We present a model-based phylogenetic method for automatically subtyping an HIV-1 (or other viral or bacterial sequence, mapping the location of breakpoints and assigning parental sequences in recombinant strains as well as computing confidence levels for the inferred quantities. Our Subtype Classification Using Evolutionary ALgorithms (SCUEAL procedure is shown to perform very well in a variety of simulation scenarios, runs in parallel when multiple sequences are being screened, and matches or exceeds the performance of existing approaches on typical empirical cases. We applied SCUEAL to all available polymerase (pol sequences from two large databases, the Stanford Drug Resistance database and the UK HIV Drug Resistance Database. Comparing with subtypes which had previously been assigned revealed that a minor but substantial (approximately 5% fraction of pure subtype sequences may in fact be within- or inter-subtype recombinants. A free implementation of SCUEAL is provided as a module for the HyPhy package and the Datamonkey web server. Our method is especially useful when an accurate automatic classification of an unknown strain is desired, and is positioned to complement and extend faster but less accurate methods. Given the increasingly frequent use of HIV subtype information in studies focusing on the effect of subtype on treatment, clinical outcome, pathogenicity and vaccine design, the importance

  1. Species-Specific Mechanisms of Neuron Subtype Specification Reveal Evolutionary Plasticity of Amniote Brain Development

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    Tadashi Nomura

    2018-03-01

    Full Text Available Summary: Highly ordered brain architectures in vertebrates consist of multiple neuron subtypes with specific neuronal connections. However, the origin of and evolutionary changes in neuron specification mechanisms remain unclear. Here, we report that regulatory mechanisms of neuron subtype specification are divergent in developing amniote brains. In the mammalian neocortex, the transcription factors (TFs Ctip2 and Satb2 are differentially expressed in layer-specific neurons. In contrast, these TFs are co-localized in reptilian and avian dorsal pallial neurons. Multi-potential progenitors that produce distinct neuronal subtypes commonly exist in the reptilian and avian dorsal pallium, whereas a cis-regulatory element of avian Ctip2 exhibits attenuated transcription suppressive activity. Furthermore, the neuronal subtypes distinguished by these TFs are not tightly associated with conserved neuronal connections among amniotes. Our findings reveal the evolutionary plasticity of regulatory gene functions that contribute to species differences in neuronal heterogeneity and connectivity in developing amniote brains. : Neuronal heterogeneity is essential for assembling intricate neuronal circuits. Nomura et al. find that species-specific transcriptional mechanisms underlie diversities of excitatory neuron subtypes in mammalian and non-mammalian brains. Species differences in neuronal subtypes and connections suggest functional plasticity of regulatory genes for neuronal specification during amniote brain evolution. Keywords: Ctip2, Satb2, multi-potential progenitors, transcriptional regulation, neuronal connectivity

  2. Isolation of Panels of Llama Single-Domain Antibody Fragments Binding All Nine Neuraminidase Subtypes of Influenza A Virus

    Directory of Open Access Journals (Sweden)

    Guus Koch

    2013-04-01

    Full Text Available Avian influenza A virus comprises sixteen hemagglutinin (HA and nine neuraminidase (NA subtypes (N1–N9. To isolate llama single-domain antibody fragments (VHHs against all N subtypes, four llamas were immunized with mixtures of influenza viruses. Selections using influenza virus yielded predominantly VHHs binding to the highly immunogenic HA and nucleoprotein. However, selection using enzymatically active recombinant NA (rNA protein enabled us to isolate NA binding VHHs. Some isolated VHHs cross-reacted to other N subtypes. These were subsequently used for the capture of N subtypes that could not be produced as recombinant protein (rN6 or were enzymatically inactive (rN1, rN5 in phage display selection, yielding novel VHHs. In total we isolated 188 NA binding VHHs, 64 of which were expressed in yeast. Most VHHs specifically recognize a single N subtype, but some VHHs cross-react with other N-subtypes. At least one VHH bound to all N subtypes, except N4, identifying a conserved antigenic site. Thus, this work (1 describes methods for isolating NA binding VHHs, (2 illustrates the suitability of llama immunization with multiple antigens for retrieving many binders against different antigens and (3 describes 64 novel NA binding VHHs, including a broadly reactive VHH, which can be used in various assays for influenza virus subtyping, detection or serology.

  3. First report of an HIV-1 triple recombinant of subtypes B, C and F in Buenos Aires, Argentina

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    Weissenbacher Mercedes

    2006-09-01

    Full Text Available Abstract We describe the genetic diversity of currently transmitted strains of HIV-1 in men who have sex with men (MSM in Buenos Aires, Argentina between 2000 and 2004. Nearly full-length sequence analysis of 10 samples showed that 6 were subtype B, 3 were BF recombinant and 1 was a triple recombinant of subtypes B, C and F. The 3 BF recombinants were 3 different unique recombinant forms. Full genome analysis of one strain that was subtype F when sequenced in pol was found to be a triple recombinant. Gag and pol were predominantly subtype F, while gp120 was subtype B; there were regions of subtype C interspersed throughout. The young man infected with this strain reported multiple sexual partners and sero-converted between May and November of 2004. This study reported for the first time the full genome analysis of a triple recombinant between subtypes B, C and F, that combines in one virus the three most common subtypes in South America.

  4. 4-[125I]iodo-(2,5-dimethoxy)phenylisopropylamine and [3H]ketanserin labeling of 5-hydroxytryptamine2 (5HT2) receptors in mammalian cells transfected with a rat 5HT2 cDNA: Evidence for multiple states and not multiple 5HT2 receptor subtypes

    International Nuclear Information System (INIS)

    Teitler, M.; Leonhardt, S.; Weisberg, E.L.; Hoffman, B.J.

    1990-01-01

    Evidence has accumulated indicating that the radioactive hallucinogens 4-bromo-[3H](2,5-dimethoxy)phenylisopropylamine ([3H]DOB) and 4-[125I]iodo-(2,5-dimethoxy)phenylisopropylamine ([125I]DOI) label an agonist high affinity state of the 5-hydroxytryptamine2 (5HT2) receptor and [3H]ketanserin labels both agonist high and low affinity states. Recently, an alternative hypothesis has been put forward proposing that the radioactive hallucinogens are labeling a 5HT2 receptor subtype distinct from the receptor labeled by [3H]ketanserin. In order to provide definitive evidence as to which of these hypotheses is correct, the rat 5HT2 receptor gene was transfected into NIH-3T3 cells and COS cells. Neither nontransfected cell type expresses 5HT2 receptors; the transfected cells expressed high affinity binding sites for both [125I] DOI (KD = 0.8 nM and Bmax = 363 fmol/mg in NIH-3T3 cells; KD = 0.2 nM and Bmax = 26 fmol/mg in COS cells) and [3H]ketanserin (KD = 0.4 nM and Bmax = 5034 fmol/mg in NIH-3T3 cells; KD = 1.0 nM and Bmax = 432 fmol/mg in COS cells). The affinities of agonists and antagonists for the [125I]DOI-labeled receptor were significantly higher than for the [3H]ketanserin-labeled receptor. The affinities of agonists and antagonists for these binding sites were essentially identical to their affinities for the sites radiolabeled by these radioligands in mammalian brain homogenates. The [125I]DOI binding was guanyl nucleotide sensitive, indicating a coupling to a GTP-binding protein. These data indicate that the 5HT2 receptor gene product contains both the guanyl nucleotide-sensitive [125I]DOI binding site and the [3H]ketanserin binding site. Therefore, these data indicate that the 5HT2 receptor gene product can produce a high affinity binding site for the phenylisopropylamine hallucinogen agonists as well as for the 5HT2 receptor antagonists

  5. Going It Alone: Comparing Subtypes of Withdrawal on Indices of Adjustment and Maladjustment in Emerging Adulthood

    Science.gov (United States)

    Nelson, Larry J.

    2013-01-01

    Scholars have distinguished conceptually between multiple forms of social withdrawal among children and adolescents, but this distinction has yet to be investigated fully during emerging adulthood. Therefore, the overarching goal of this study was to employ a person-oriented approach to examine differences between subtypes of withdrawal on…

  6. Precise subtyping for synchronous multiparty sessions

    Directory of Open Access Journals (Sweden)

    Mariangiola Dezani-Ciancaglini

    2016-02-01

    Full Text Available The notion of subtyping has gained an important role both in theoretical and applicative domains: in lambda and concurrent calculi as well as in programming languages. The soundness and the completeness, together referred to as the preciseness of subtyping, can be considered from two different points of view: operational and denotational. The former preciseness has been recently developed with respect to type safety, i.e. the safe replacement of a term of a smaller type when a term of a bigger type is expected. The latter preciseness is based on the denotation of a type which is a mathematical object that describes the meaning of the type in accordance with the denotations of other expressions from the language. The result of this paper is the operational and denotational preciseness of the subtyping for a synchronous multiparty session calculus. The novelty of this paper is the introduction of characteristic global types to prove the operational completeness.

  7. Population dynamics and rates of molecular evolution of a recently emerged paramyxovirus, avian metapneumovirus subtype C.

    Science.gov (United States)

    Padhi, Abinash; Poss, Mary

    2009-02-01

    We report the existence of two distinct sublineages of avian metapneumovirus (MPV) subtype C, a virus which has caused serious economic loss in commercial turkey farms in the United States. This subtype is closely related to human MPV, infects multiple avian species, and is globally distributed. The evolutionary rates of this virus are estimated to be 1.3 x 10(-3) to 7 x 10(-3) substitutions per site per year, and coalescent estimates place its emergence between 1991 and 1996. The four genes examined show a concordant demographic pattern which is characterized by a rapid increase in population size followed by stable population grown until the present.

  8. Rate of renal cell carcinoma subtypes in different races

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    Alexander Sankin

    2011-02-01

    Full Text Available PURPOSE: We sought to identify racial differences among histological subtypes of renal cell carcinoma (RCC between black and non-black patients in an equal-access health care system. MATERIALS AND METHODS: We established a multi-institutional, prospective database of patients undergoing partial or radical nephrectomy between January 1, 2000 and Sept 31, 2009. For the purposes of this study, data captured included age at diagnosis, race, tumor size, presence of lymphovascular invasion, presence of capsular invasion, margin status, and tumor histology. RESULTS: 204 kidney tumors were identified (Table-1. Of these, 117 (57.4% were in black patients and 87 (42.6% were in non-black patients. Age at surgery ranged from 37 to 87 with a median of 62. Tumor size ranged from 1.0 to 22.0 cm with a median of 5.0 cm. Overall, tumors were composed of clear cell RCC in 97 cases (47.5%, papillary RCC in 65 cases (31.9%, chromophobe RCC in 13 cases (6.4%, collecting duct/medullary RCC in 2 cases (1.0%, RCC with multiple histological subtypes in 8 cases (3.9%, malignant tumors of other origin in 6 cases (2.9%, and benign histology in 13 cases (6.4%. Among black patients, papillary RCC was seen in 56 cases (47.9%, compared to 9 cases (10.3% among non-black patients (p < 0.001 (Table-2. Clear cell RCC was present in 38 (32.5% of black patients and in 59 (67.8% of non-blacks (p < 0.001. CONCLUSIONS: In our study, papillary RCC had a much higher occurrence among black patients compared to non-black patients. This is the first study to document such a great racial disparity among RCC subtypes.

  9. High-resolution molecular epidemiology and evolutionary history of HIV-1 subtypes in Albania.

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    Marco Salemi

    2008-01-01

    Full Text Available HIV-1 epidemic in Western Europe is largely due to subtype B. Little is known about the HIV-1 in Eastern Europe, but a few studies have shown that non-B subtypes are quite common. In Albania, where a recent study estimated a ten-fold increase of AIDS incidence during the last six years, subtype A and B account for 90% of the know infections.We investigated the demographic history of HIV-1 subtype A and B in Albania by using a statistical framework based on coalescent theory and phylogeography. High-resolution phylogenetic and molecular clock analysis showed a limited introduction to the Balkan country of subtype A during the late 1980s followed by an epidemic outburst in the early 1990 s. In contrast, subtype B was apparently introduced multiple times between the mid-1970s and mid-1980s. Both subtypes are growing exponentially, although the HIV-1A epidemic displays a faster growth rate, and a significantly higher basic reproductive number R(0. HIV-1A gene flow occurs primarily from the capital Tirane, in the center of the country, to the periphery, while HIV-1B flow is characterized by a balanced exchange between center and periphery. Finally, we calculated that the actual number of infections in Albania is at least two orders of magnitude higher than previously thought.Our analysis demonstrates the power of recently developed computational tools to investigate molecular epidemiology of pathogens, and emphasize the complex factors involved in the establishment of HIV-1 epidemics. We suggest that a significant correlation exists between HIV-1 exponential spread and the socio-political changes occurred during the Balkan wars. The fast growth of a relatively new non-B epidemic in the Balkans may have significant consequences for the evolution of HIV-1 epidemiology in neighboring countries in Eastern and Western Europe.

  10. Classifying distinct basal cell carcinoma subtype by means of dermatoscopy and reflectance confocal microscopy.

    Science.gov (United States)

    Longo, Caterina; Lallas, Aimilios; Kyrgidis, Athanassios; Rabinovitz, Harold; Moscarella, Elvira; Ciardo, Silvana; Zalaudek, Iris; Oliviero, Margaret; Losi, Amanda; Gonzalez, Salvador; Guitera, Pascale; Piana, Simonetta; Argenziano, Giuseppe; Pellacani, Giovanni

    2014-10-01

    The current guidelines for the management of basal cell carcinoma (BCC) suggest a different therapeutic approach according to histopathologic subtype. Although dermatoscopic and confocal criteria of BCC have been investigated, no specific studies were performed to evaluate the distinct reflectance confocal microscopy (RCM) aspects of BCC subtypes. To define the specific dermatoscopic and confocal criteria for delineating different BCC subtypes. Dermatoscopic and confocal images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of predefined criteria. Frequencies of dermatoscopic and confocal parameters are provided. Univariate and adjusted odds ratios were calculated. Discriminant analyses were performed to define the independent confocal criteria for distinct BCC subtypes. Eighty-eight BCCs were included. Dermatoscopically, superficial BCCs (n=44) were primarily typified by the presence of fine telangiectasia, multiple erosions, leaf-like structures, and revealed cords connected to the epidermis and epidermal streaming upon RCM. Nodular BCCs (n=22) featured the classic dermatoscopic features and well outlined large basaloid islands upon RCM. Infiltrative BCCs (n=22) featured structureless, shiny red areas, fine telangiectasia, and arborizing vessels on dermatoscopy and dark silhouettes upon RCM. The retrospective design. Dermatoscopy and confocal microscopy can reliably classify different BCC subtypes. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  11. Genetic contributions to subtypes of aggression

    NARCIS (Netherlands)

    Ligthart, R.S.L.; Bartels, M.; Hoekstra, R.A.; Hudziak, J.; Boomsma, D.I.

    2005-01-01

    Boys and girls may display different styles of aggression. The aim of this study was to identify subtypes of aggression within the Child Behavior Checklist (CBCL) aggression scale, and determine their characteristics for both sexes. Maternal CBCL ratings of 7449 7-year-old twin pairs were analyzed

  12. Obesity and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

    Olsen, Catherine M; Nagle, Christina M; Whiteman, David C

    2013-01-01

    Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improv...

  13. Parkinson's disease motor subtypes and mood.

    Science.gov (United States)

    Burn, David J; Landau, Sabine; Hindle, John V; Samuel, Michael; Wilson, Kenneth C; Hurt, Catherine S; Brown, Richard G

    2012-03-01

    Parkinson's disease is heterogeneous, both in terms of motor symptoms and mood. Identifying associations between phenotypic variants of motor and mood subtypes may provide clues to understand mechanisms underlying mood disorder and symptoms in Parkinson's disease. A total of 513 patients were assessed using the Hospital Anxiety and Depression Scale, and separately classified into anxious, depressed, and anxious-depressed mood classes based on latent class analysis of a semistructured interview. Motor subtypes assessed related to age-of-onset, rate of progression, presence of motor fluctuations, lateralization of motor symptoms, tremor dominance, and the presence of postural instability and gait symptoms and falls. The directions of observed associations tended to support previous findings with the exception of lateralization of symptoms, for which there were no consistent or significant results. Regression models examining a range of motor subtypes together indicated increased risk of anxiety in patients with younger age-of-onset and motor fluctuations. In contrast, depression was most strongly related to axial motor symptoms. Different risk factors were observed for depressed patients with and without anxiety, suggesting heterogeneity within Parkinson's disease depression. Such association data may suggest possible underlying common risk factors for motor subtype and mood. Combined with convergent evidence from other sources, possible mechanisms may include cholinergic system damage and white matter changes contributing to non-anxious depression in Parkinson's disease, while situational factors related to threat and unpredictability may contribute to the exacerbation and maintenance of anxiety in susceptible individuals. Copyright © 2011 Movement Disorder Society.

  14. Subtyping can have a simple semantics

    NARCIS (Netherlands)

    Balsters, H.; Fokkinga, M.M.

    1991-01-01

    Consider a first order typed language, with semantics $S$ for expressions and types. Adding subtyping means that a partial order $<$; on types is defined and that the typing rules are extended to the effect that expression $e$ has type $t$ whenever $e$ has type $s$ and $s

  15. Subtypes of children with attention disabilities.

    NARCIS (Netherlands)

    Brand, E.F.J.M.; Das-Smaal, E.A.; Jong, de P.F.

    1996-01-01

    Subtypes of children with attentional problems were investigated using cluster analysis. Subjects were 9-year-old-elementary school children (N = 443). The test battery administered to these children comprised a comprehensive set of common attention tests, covering different aspects of attentional

  16. Metastatic Organotropism: An Intrinsic Property of Breast Cancer Molecular Subtypes.

    Science.gov (United States)

    Wei, Shi; Siegal, Gene P

    2017-03-01

    It has long been known that some cancers have the propensity to metastasize to certain organs thus creating a nonrandom distribution of sites for distant relapse, a phenomenon known as "metastatic organotropism." Some of these examples include ovary primary to abdominal cavity, prostate primary to bone, and pancreas primary to liver. In contrast, other tumor types, such as mammary and renal cell carcinoma, can relapse in multiple organs although approximately half of advanced breast cancers metastasize to bone. On the other hand gene expression profiling studies have identified various breast cancer classes with prognostic significance. Recent studies have revealed that breast cancer subtypes differ not only in primary tumor characteristics but also in their metastatic behavior. In particular, the luminal tumors are remarkable for their significant bone-seeking phenotype; the HER2 subtype demonstrates a significant liver-homing characteristic; whereas so-called triple-negative breast cancers predispose to lung metastases. These findings suggest that this knowledge could potentially be utilized in the development of effective disease surveillance strategies in the pursuit of precision medicine, thus necessitating further investigation.

  17. Linking social and spatial networks to viral community phylogenetics reveals subtype-specific transmission dynamics in African lions.

    Science.gov (United States)

    Fountain-Jones, Nicholas M; Packer, Craig; Troyer, Jennifer L; VanderWaal, Kimberly; Robinson, Stacie; Jacquot, Maude; Craft, Meggan E

    2017-10-01

    Heterogeneity within pathogen species can have important consequences for how pathogens transmit across landscapes; however, discerning different transmission routes is challenging. Here, we apply both phylodynamic and phylogenetic community ecology techniques to examine the consequences of pathogen heterogeneity on transmission by assessing subtype-specific transmission pathways in a social carnivore. We use comprehensive social and spatial network data to examine transmission pathways for three subtypes of feline immunodeficiency virus (FIV Ple ) in African lions (Panthera leo) at multiple scales in the Serengeti National Park, Tanzania. We used FIV Ple molecular data to examine the role of social organization and lion density in shaping transmission pathways and tested to what extent vertical (i.e., father- and/or mother-offspring relationships) or horizontal (between unrelated individuals) transmission underpinned these patterns for each subtype. Using the same data, we constructed subtype-specific FIV Ple co-occurrence networks and assessed what combination of social networks, spatial networks or co-infection best structured the FIV Ple network. While social organization (i.e., pride) was an important component of FIV Ple transmission pathways at all scales, we find that FIV Ple subtypes exhibited different transmission pathways at within- and between-pride scales. A combination of social and spatial networks, coupled with consideration of subtype co-infection, was likely to be important for FIV Ple transmission for the two major subtypes, but the relative contribution of each factor was strongly subtype-specific. Our study provides evidence that pathogen heterogeneity is important in understanding pathogen transmission, which could have consequences for how endemic pathogens are managed. Furthermore, we demonstrate that community phylogenetic ecology coupled with phylodynamic techniques can reveal insights into the differential evolutionary pressures acting

  18. Rising prevalence of non-B HIV-1 subtypes in North Carolina and evidence for local onward transmission.

    Science.gov (United States)

    Dennis, Ann M; Hué, Stephane; Learner, Emily; Sebastian, Joseph; Miller, William C; Eron, Joseph J

    2017-01-01

    HIV-1 diversity is increasing in North American and European cohorts which may have public health implications. However, little is known about non-B subtype diversity in the southern United States, despite the region being the epicenter of the nation's epidemic. We characterized HIV-1 diversity and transmission clusters to identify the extent to which non-B strains are transmitted locally. We conducted cross-sectional analyses of HIV-1 partial pol sequences collected from 1997 to 2014 from adults accessing routine clinical care in North Carolina (NC). Subtypes were evaluated using COMET and phylogenetic analysis. Putative transmission clusters were identified using maximum-likelihood trees. Clusters involving non-B strains were confirmed and their dates of origin were estimated using Bayesian phylogenetics. Data were combined with demographic information collected at the time of sample collection and country of origin for a subset of patients. Among 24,972 sequences from 15,246 persons, the non-B subtype prevalence increased from 0% to 3.46% over the study period. Of 325 persons with non-B subtypes, diversity was high with over 15 pure subtypes and recombinants; subtype C (28.9%) and CRF02_AG (24.0%) were most common. While identification of transmission clusters was lower for persons with non-B versus B subtypes, several local transmission clusters (≥3 persons) involving non-B subtypes were identified and all were presumably due to heterosexual transmission. Prevalence of non-B subtype diversity remains low in NC but a statistically significant rise was identified over time which likely reflects multiple importation. However, the combined phylogenetic clustering analysis reveals evidence for local onward transmission. Detection of these non-B clusters suggests heterosexual transmission and may guide diagnostic and prevention interventions.

  19. Muscarinic acetylcholine receptor subtypes: localization and structure/function

    DEFF Research Database (Denmark)

    Brann, M R; Ellis, J; Jørgensen, H

    1993-01-01

    Based on the sequence of the five cloned muscarinic receptor subtypes (m1-m5), subtype selective antibody and cDNA probes have been prepared. Use of these probes has demonstrated that each of the five subtypes has a markedly distinct distribution within the brain and among peripheral tissues...... are described, as well as the implied structures of these functional domains....

  20. Subtypes of depression in cancer patients : An empirically driven approach

    NARCIS (Netherlands)

    Zhu, Lei; Ranchor, Adelita V; van der Lee, Marije; Garssen, Bert; Sanderman, Robbert; Schroevers, Maya J

    PURPOSE: This study aimed to (1) identify subgroups of cancer patients with distinct subtypes of depression before the start of psychological care, (2) examine whether socio-demographic and medical characteristics distinguished these subtypes, and (3) examine whether people with distinct subtypes

  1. Subtypes of depression in cancer patients: an empirically driven approach

    NARCIS (Netherlands)

    Zhu, Lei; Ranchor, A.V.; van der Lee, Marije; Garssen, Bert; Sanderman, Robbert; Schroevers, Maya J.

    2016-01-01

    Purpose This study aimed to (1) identify subgroups of cancer patients with distinct subtypes of depression before the start of psychological care, (2) examine whether socio-demographic and medical characteristics distinguished these subtypes, and (3) examine whether people with distinct subtypes

  2. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

    DEFF Research Database (Denmark)

    Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C

    2016-01-01

    studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian...

  3. FIV diversity: FIV Ple subtype composition may influence disease outcome in African lions.

    Science.gov (United States)

    Troyer, Jennifer L; Roelke, Melody E; Jespersen, Jillian M; Baggett, Natalie; Buckley-Beason, Valerie; MacNulty, Dan; Craft, Meggan; Packer, Craig; Pecon-Slattery, Jill; O'Brien, Stephen J

    2011-10-15

    Feline immunodeficiency virus (FIV) infects domestic cats and at least 20 additional species of non-domestic felids throughout the world. Strains specific to domestic cat (FIV(Fca)) produce AIDS-like disease progression, sequelae and pathology providing an informative model for HIV infection in humans. Less is known about the immunological and pathological influence of FIV in other felid species although multiple distinct strains of FIV circulate in natural populations. As in HIV-1 and HIV-2, multiple diverse cross-species infections may have occurred. In the Serengeti National Park, Tanzania, three divergent subtypes of lion FIV (FIV(Ple)) are endemic, whereby 100% of adult lions are infected with one or more of these strains. Herein, the relative distribution of these subtypes in the population are surveyed and, combined with observed differences in lion mortality due to secondary infections based on FIV(Ple) subtypes, the data suggest that FIV(Ple) subtypes may have different patterns of pathogenicity and transmissibility among wild lion populations. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Comparison of symptoms of delirium across various motoric subtypes.

    Science.gov (United States)

    Grover, Sandeep; Sharma, Akhilesh; Aggarwal, Munish; Mattoo, Surendra K; Chakrabarti, Subho; Malhotra, Savita; Avasthi, Ajit; Kulhara, Parmanand; Basu, Debasish

    2014-04-01

    The aim of this study was to determine the correlation between delirium motor subtypes and other symptoms of delirium. Three hundred and twenty-one (n = 321) consecutive patients referred to consultation-liaison psychiatry services were evaluated on Delirium Rating scale-Revised-98 version and amended Delirium Motor Symptom Scale. Half of the patients had hyperactive subtype (n = 161; 50.15%) delirium. One-quarter of the study sample met the criteria for mixed subtype (n = 79; 24.61%), about one-fifth of the study sample met the criteria for hypoactive delirium subtype (n = 64; 19.93%), and only very few patients (n = 17; 5.29%) did not meet the required criteria for any of these three subtypes and were categorized as 'no subtype'. When the hyperactive and hypoactive subtypes were compared, significant differences were seen in the prevalence of perceptual disturbances, delusions, lability of affect, thought process abnormality, motor agitation and motor retardation. All the symptoms were more common in the hyperactive subtype except for thought process abnormality and motor retardation. Compared to hyperactive subtype, the mixed subtype had significantly higher prevalence of thought process abnormality and motor retardation. Significant differences emerged with regard to perceptual disturbances, delusions, lability of affect and motor agitation when comparing the patients with mixed subtype with those with hypoactive subtype. All these symptoms were found to be more common in the mixed subtype. No significant differences emerged for the cognitive symptoms as assessed on Delirium Rating scale-Revised-98 across the different motoric subtypes. Different motoric subtypes of delirium differ on non-cognitive symptoms. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

  5. A taxometric investigation of developmental dyslexia subtypes.

    Science.gov (United States)

    O'Brien, Beth A; Wolf, Maryanne; Lovett, Maureen W

    2012-02-01

    Long-standing issues with the conceptualization, identification and subtyping of developmental dyslexia persist. This study takes an alternative approach to examine the heterogeneity of developmental dyslexia using taxometric classification techniques. These methods were used with a large sample of 671 children ages 6-8 who were diagnosed with severe reading disorders. Latent characteristics of the sample are assessed in regard to posited subtypes with phonological deficits and naming speed deficits, thus extending prior work by addressing whether these deficits embody separate classes of individuals. Findings support separate taxa of dyslexia with and without phonological deficits. Different latent structure for naming speed deficits was found depending on the definitional criterion used to define dyslexia. Non-phonologically based forms of dyslexia showed particular difficulty with naming speed and reading fluency. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Proteomic maps of breast cancer subtypes

    DEFF Research Database (Denmark)

    Tyanova, Stefka; Albrechtsen, Reidar; Kronqvist, Pauliina

    2016-01-01

    Systems-wide profiling of breast cancer has almost always entailed RNA and DNA analysis by microarray and sequencing techniques. Marked developments in proteomic technologies now enable very deep profiling of clinical samples, with high identification and quantification accuracy. We analysed 40...... oestrogen receptor positive (luminal), Her2 positive and triple negative breast tumours and reached a quantitative depth of >10,000 proteins. These proteomic profiles identified functional differences between breast cancer subtypes, related to energy metabolism, cell growth, mRNA translation and cell......-cell communication. Furthermore, we derived a signature of 19 proteins, which differ between the breast cancer subtypes, through support vector machine (SVM)-based classification and feature selection. Remarkably, only three proteins of the signature were associated with gene copy number variations and eleven were...

  7. Agonist discrimination between AMPA receptor subtypes

    DEFF Research Database (Denmark)

    Coquelle, T; Christensen, J K; Banke, T G

    2000-01-01

    The lack of subtype-selective compounds for AMPA receptors (AMPA-R) led us to search for compounds with such selectivity. Homoibotenic acid analogues were investigated at recombinant GluR1o, GluR2o(R), GluR3o and GluR1o + 3o receptors expressed in Sf9 insect cells and affinities determined in [3H...

  8. Global DNA methylation of ischemic stroke subtypes.

    Directory of Open Access Journals (Sweden)

    Carolina Soriano-Tárraga

    Full Text Available Ischemic stroke (IS, a heterogeneous multifactorial disorder, is among the leading causes of mortality and long-term disability in the western world. Epidemiological data provides evidence for a genetic component to the disease, but its epigenetic involvement is still largely unknown. Epigenetic mechanisms, such as DNA methylation, change over time and may be associated with aging processes and with modulation of the risk of various pathologies, such as cardiovascular disease and stroke. We analyzed 2 independent cohorts of IS patients. Global DNA methylation was measured by luminometric methylation assay (LUMA of DNA blood samples. Univariate and multivariate regression analyses were used to assess the methylation differences between the 3 most common IS subtypes, large-artery atherosclerosis (LAA, small-artery disease (SAD, and cardio-aortic embolism (CE. A total of 485 IS patients from 2 independent hospital cohorts (n = 281 and n = 204 were included, distributed across 3 IS subtypes: LAA (78/281, 59/204, SAD (97/281, 53/204, and CE (106/281, 89/204. In univariate analyses, no statistical differences in LUMA levels were observed between the 3 etiologies in either cohort. Multivariate analysis, adjusted by age, sex, hyperlipidemia, and smoking habit, confirmed the lack of differences in methylation levels between the analyzed IS subtypes in both cohorts. Despite differences in pathogenesis, our results showed no global methylation differences between LAA, SAD, and CE subtypes of IS. Further work is required to establish whether the epigenetic mechanism of methylation might play a role in this complex disease.

  9. Subtyping borderline personality disorder by suicidal behavior.

    Science.gov (United States)

    Soloff, Paul H; Chiappetta, Laurel

    2012-06-01

    Course and outcome of Borderline Personality Disorder (BPD) are favorable for the vast majority of patients; however, up to 10% die by suicide. This discrepancy begs the question of whether there is a high lethality subtype in BPD, defined by recurrent suicidal behavior and increasing attempt lethality over time. In a prospective, longitudinal study, we sought predictors of high lethality among repeat attempters, and defined clinical subtypes by applying trajectory analysis to consecutive lethality scores. Criteria-defined subjects with BPD were assessed using standardized instruments and followed longitudinally. Suicidal behavior was assessed on the Columbia Suicide History, Lethality Rating Scale, and Suicide Intent Scale. Variables discriminating single and repeat attempters were entered into logistic regression models to define predictors of high and low lethality attempts. Trajectory analysis using three attempt and five attempt models identified discrete patterns of Lethality Rating Scale scores. A high lethality trajectory was associated with inpatient recruitment, and poor psychosocial function, a low lethality trajectory with greater Negativism, Substance Use Disorders, Histrionic and/or Narcissistic PD co-morbidity. Illness severity, older age, and poor psychosocial function are characteristics of a poor prognosis subtype related to suicidal behavior.

  10. Transcriptome classification reveals molecular subtypes in psoriasis

    Directory of Open Access Journals (Sweden)

    Ainali Chrysanthi

    2012-09-01

    Full Text Available Abstract Background Psoriasis is an immune-mediated disease characterised by chronically elevated pro-inflammatory cytokine levels, leading to aberrant keratinocyte proliferation and differentiation. Although certain clinical phenotypes, such as plaque psoriasis, are well defined, it is currently unclear whether there are molecular subtypes that might impact on prognosis or treatment outcomes. Results We present a pipeline for patient stratification through a comprehensive analysis of gene expression in paired lesional and non-lesional psoriatic tissue samples, compared with controls, to establish differences in RNA expression patterns across all tissue types. Ensembles of decision tree predictors were employed to cluster psoriatic samples on the basis of gene expression patterns and reveal gene expression signatures that best discriminate molecular disease subtypes. This multi-stage procedure was applied to several published psoriasis studies and a comparison of gene expression patterns across datasets was performed. Conclusion Overall, classification of psoriasis gene expression patterns revealed distinct molecular sub-groups within the clinical phenotype of plaque psoriasis. Enrichment for TGFb and ErbB signaling pathways, noted in one of the two psoriasis subgroups, suggested that this group may be more amenable to therapies targeting these pathways. Our study highlights the potential biological relevance of using ensemble decision tree predictors to determine molecular disease subtypes, in what may initially appear to be a homogenous clinical group. The R code used in this paper is available upon request.

  11. An Elementary Semantics for Cardelli's System of Multiple Inheritance

    NARCIS (Netherlands)

    Fokkinga, M.M.

    1987-01-01

    In [Cardelli 84] Luca Cardelli gave a formal definition of a typed object-oriented language incorporating a sub-type relation used to describe multiple inheritance. Cardelli's fundamental result was a semantics for his system that enabled sub-typing to be modelled as straightforward set-inclusion.

  12. Molecular subtypes and imaging phenotypes of breast cancer

    International Nuclear Information System (INIS)

    Cho, Nariya

    2016-01-01

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics

  13. Molecular subtypes and imaging phenotypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Nariya Cho

    2016-10-01

    Full Text Available During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2, and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  14. Molecular subtypes and imaging phenotypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nariya [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-08-15

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  15. The differences between NAD-ME and NADP-ME subtypes of C4 photosynthesis: more than decarboxylating enzymes

    Directory of Open Access Journals (Sweden)

    Xiaolan Rao

    2016-10-01

    Full Text Available As an adaptation to changing climatic conditions that caused high rates of photorespiration, C4 plants have evolved to display higher photosynthetic efficiency than C3 plants under elevated temperature, high light intensities and drought. The C4 plants independently evolved more than 60 times in 19 families of angiosperms to establish similar but not uniform C4 mechanisms to concentrate CO2 around the carboxylating enzyme Rubisco. C4 photosynthesis is divided into at least two basic biochemical subtypes based on the primary decarboxylating enzymes, NAD-dependent malic enzyme (NAD-ME and NADP-dependent malic enzyme (NADP-ME. The multiple polygenetic origins of these subtypes raise questions about the association of C4 variation between biochemical subtypes and diverse lineages. This review addresses the differences in evolutionary scenario, leaf anatomy, and especially C4 metabolic flow, C4 transporters and cell-specific function deduced from recently reported cell-specific transcriptomic, proteomic and metabolic analyses of NAD-ME and NADP-ME subtypes. Current omic analysis has revealed the extent to which component abundances differ between the two biochemical subtypes, leading to a better understanding of C4 photosynthetic mechanisms in NAD-ME and NADP-ME subtypes.

  16. Burnout syndrome among dental students: a short version of the "Burnout Clinical Subtype Questionnaire" adapted for students (BCSQ-12-SS).

    Science.gov (United States)

    Montero-Marin, Jesus; Monticelli, Francesca; Casas, Marina; Roman, Amparo; Tomas, Inmaculada; Gili, Margarita; Garcia-Campayo, Javier

    2011-12-12

    Burnout has been traditionally defined in relation to the dimensions of "exhaustion", "cynicism", and "inefficiency". More recently, the Burnout Clinical Subtype Questionnaire (BCSQ-12) further established three different subtypes of burnout: the "frenetic" subtype (related to "overload"), the "under-challenged" subtype (related to "lack of development"), and the "worn-out" subtype (related to "neglect"). However, to date, these definitions have not been applied to students. The aims of this research were (1) to adapt a Spanish version of the BCSQ-12 for use with students, (2) to test its factorial validity, internal consistency, convergent and discriminant validity, and (3) to assess potential socio-demographic and occupational risk factors associated with the development of the subtypes. We used a cross-sectional design on a sample of dental students (n = 314) from Santiago and Huesca universities (Spain). Participants completed the Burnout Clinical Subtype Questionnaire Student Survey (BCSQ-12-SS), the Maslach Burnout Inventory Student Survey (MBI-SS), and a series of socio-demographic and occupational questions formulated for the specific purpose of this study. Data were subjected to exploratory factor analysis (EFA) using the principal component method with varimax orthogonal rotation. To assess the relations with the criterion, we calculated the Pearson correlation coefficient (r), multiple correlation coefficient (R(y.123)), and the coefficient of determination (R(2)(y.123)). To assess the association between the subtypes and the socio-demographic variables, we examined the adjusted odds ratio (OR) obtained from multivariate logistic regression models. Factorial analyses supported the theoretical proposition of the BCSQ-12-SS, with α-values exceeding 0.80 for all dimensions. The "overload-exhaustion" relation was r = 0.59 (p burnout as established by the BCSQ-12-SS. As such, the BCSQ-12-SS can be used for the recognition of clinical profiles and for the

  17. Subtype distribution of Blastocystis isolates from synanthropic and zoo animals and identification of a new subtype

    DEFF Research Database (Denmark)

    Stensvold, C. R.; Alfellani, M. A.; Nørskov-Lauritsen, S.

    2009-01-01

    Blastocystis isolates from 56 Danish synanthropic and zoo animals, 62 primates primarily from United Kingdom (UK) collections and 16 UK primate handlers were subtyped by PCR, sequencing and phylogenetic analysis. A new subtype (ST) from primates and artiodactyls was identified and designated...... infections from primates by their handlers had occurred in these cases. Data from published studies of non-human primates, other mammals and birds were collected and interpreted to generate a comprehensive overview on the ST distribution in such animals. On the basis of information on 438 samples...

  18. Tracing the HIV-1 subtype B mobility in Europe: a phylogeographic approach

    Energy Technology Data Exchange (ETDEWEB)

    Leitner, Thomas [Los Alamos National Laboratory; Paraskevis, D [KATHOLIEKE UNIV; Pybus, O [UNIV OF OXFORD; Magiorkinis, G [KATHOLIEKE UNIV; Hatzakis, A [KATHOLIEKE UNIV

    2008-01-01

    The prevalence and the origin of HIV-1 subtype B, the most prevalent circulating clade among the long-term residents in Europe, have been studied extensively. However the spatial diffusion of the epidemic from the perspective of the virus has not previously been traced. In the current study we inferred the migration history of HIV-1 subtype B by way of a phylogeography of viral sequences sampled from 16 European countries and Israel. Migration events were inferred from viral phylogenies by character reconstruction using parsimony. With regard to the spatial dispersal of the HIV subtype B sequences across viral phylogenies, in most of the countries in Europe the epidemic was introduced by multiple sources and subsequently spread within local networks. Poland provides an exception where most of the infections were the result of a single point introduction. According to the significant migratory pathways, we show that there are considerable differences across Europe. Specifically, Greece, Portugal, Serbia and Spain, provide sources shedding HIV-1; Austria, Belgium and Luxembourg, on the other hand, are migratory targets, while for Denmark, Germany, Italy, Israel, Norway, the Netherlands, Sweden, Switzerland and the UK we inferred significant bidirectional migration. For Poland no significant migratory pathways were inferred. Subtype B phylogeographies provide a new insight about the geographical distribution of viral lineages, as well as the significant pathways of virus dispersal across Europe, suggesting that intervention strategies should also address tourists, travellers and migrants.

  19. The Integrative Method Based on the Module-Network for Identifying Driver Genes in Cancer Subtypes

    Directory of Open Access Journals (Sweden)

    Xinguo Lu

    2018-01-01

    Full Text Available With advances in next-generation sequencing(NGS technologies, a large number of multiple types of high-throughput genomics data are available. A great challenge in exploring cancer progression is to identify the driver genes from the variant genes by analyzing and integrating multi-types genomics data. Breast cancer is known as a heterogeneous disease. The identification of subtype-specific driver genes is critical to guide the diagnosis, assessment of prognosis and treatment of breast cancer. We developed an integrated frame based on gene expression profiles and copy number variation (CNV data to identify breast cancer subtype-specific driver genes. In this frame, we employed statistical machine-learning method to select gene subsets and utilized an module-network analysis method to identify potential candidate driver genes. The final subtype-specific driver genes were acquired by paired-wise comparison in subtypes. To validate specificity of the driver genes, the gene expression data of these genes were applied to classify the patient samples with 10-fold cross validation and the enrichment analysis were also conducted on the identified driver genes. The experimental results show that the proposed integrative method can identify the potential driver genes and the classifier with these genes acquired better performance than with genes identified by other methods.

  20. Tracing the HIV-1 subtype B mobility in Europe: a phylogeographic approach

    Directory of Open Access Journals (Sweden)

    Perrin Luc

    2009-05-01

    Full Text Available Abstract Background The prevalence and the origin of HIV-1 subtype B, the most prevalent circulating clade among the long-term residents in Europe, have been studied extensively. However the spatial diffusion of the epidemic from the perspective of the virus has not previously been traced. Results In the current study we inferred the migration history of HIV-1 subtype B by way of a phylogeography of viral sequences sampled from 16 European countries and Israel. Migration events were inferred from viral phylogenies by character reconstruction using parsimony. With regard to the spatial dispersal of the HIV subtype B sequences across viral phylogenies, in most of the countries in Europe the epidemic was introduced by multiple sources and subsequently spread within local networks. Poland provides an exception where most of the infections were the result of a single point introduction. According to the significant migratory pathways, we show that there are considerable differences across Europe. Specifically, Greece, Portugal, Serbia and Spain, provide sources shedding HIV-1; Austria, Belgium and Luxembourg, on the other hand, are migratory targets, while for Denmark, Germany, Italy, Israel, Norway, the Netherlands, Sweden, Switzerland and the UK we inferred significant bidirectional migration. For Poland no significant migratory pathways were inferred. Conclusion Subtype B phylogeographies provide a new insight about the geographical distribution of viral lineages, as well as the significant pathways of virus dispersal across Europe, suggesting that intervention strategies should also address tourists, travellers and migrants.

  1. Different neuraminidase inhibitor susceptibilities of human H1N1, H1N2, and H3N2 influenza A viruses isolated in Germany from 2001 to 2005/2006.

    Science.gov (United States)

    Bauer, Katja; Richter, Martina; Wutzler, Peter; Schmidtke, Michaela

    2009-04-01

    In the flu season 2005/2006 amantadine-resistant human influenza A viruses (FLUAV) of subtype H3N2 circulated in Germany. This raises questions on the neuraminidase inhibitor (NAI) susceptibility of FLUAV. To get an answer, chemiluminescence-based neuraminidase inhibition assays were performed with 51 H1N1, H1N2, and H3N2 FLUAV isolated in Germany from 2001 to 2005/2006. According to the mean IC(50) values (0.38-0.91 nM for oseltamivir and 0.76-1.13 nM for zanamivir) most H1N1 and H3N2 FLUAV were NAI-susceptible. But, about four times higher zanamivir concentrations were necessary to inhibit neuraminidase activity of H1N2 viruses. Two H1N1 isolates were less susceptible to both drugs in NA inhibition as well as virus yield reduction assays. Results from sequence analysis of viral hemagglutinin and neuraminidase genes and evolutionary analysis of N2 gene revealed (i) different subclades for N2 in H1N2 and H3N2 FLUAV that could explain the differences in zanamivir susceptibility among these viruses and (ii) specific amino acid substitutions in the neuraminidase segment of the two less NAI-susceptible H1N1 isolates. One H3N2 was isolate proved to be a mixture of a NA deletion mutant and full-length NA viruses.

  2. Immunohistochemical visualization of mouse interneuron subtypes

    DEFF Research Database (Denmark)

    Jensen, Simon Mølgaard; Ulrichsen, Maj; Boggild, Simon

    2014-01-01

    , and calretinin are also commonly used as markers to narrow down the specific interneuron subtype. Here, we describe a journey to find the necessary immunological reagents for studying GABAergic interneurons of the mouse hippocampus. Based on web searches there are several hundreds of different antibodies...... of the hippocampus where they have previously been described. Additionally, the antibodies were also tested on sections from mouse spinal cord with similar criteria for specificity of the antibodies. Using the antibodies with a high rating on pAbmAbs, stainings with high signal-to-noise ratios and location...

  3. Avian metapneumovirus subtype A in China and subtypes A and B in Nigeria.

    Science.gov (United States)

    Owoade, A A; Ducatez, M F; Hübschen, J M; Sausy, A; Chen, H; Guan, Y; Muller, C P

    2008-09-01

    In order to detect and characterize avian metapneumovirus, organs or swabs were collected from 697 chicken and 110 turkeys from commercial farms in Southwestern Nigeria and from 107 chickens from live bird markets in Southeastern China. In Nigeria, 15% and 6% of the chicken and turkey samples, respectively, and 39% of the chicken samples from China, were positive for aMPV genome by PCR. The sequence of a 400 nt fragment of the attachment protein gene (G gene) revealed the presence of aMPV subtype A in both Nigeria and Southeastern China. Essentially identical subtype A viruses were found in both countries and were also previously reported from Brazil and the United Kingdom, suggesting a link between these countries or a common source of this subtype. In Nigeria, subtype B was also found, which may be a reflection of chicken importations from most major poultry-producing countries in Europe and Asia. In order to justify countermeasures, further studies are warranted to better understand the metapneumoviruses and their impact on poultry production.

  4. Liposarcoma : MR findings in the histologic subtypes

    International Nuclear Information System (INIS)

    Lee, Jeong Hoon; Sohn, Jeong Eun; Chung, Soo Jeong; Kim, Kie Hwan; Chin, Soo Yil

    1999-01-01

    To evaluate the MR imaging findings of liposarcomas of different histologic subtypes. We evaluated MR images of 21 patients (5 men and 16 women, mean age, 55 years) with liposarcoma and correlated the findings with the results of histopathology. In the study group seven liposarcomas were well-differentiated, seven were myxoid, three were mixed, two were pleomorphic, and one was round cell. On T1-and T2-weighted images, six of seven well-differentiated liposarcomas showed signal intensity equal to the fat and hypointense septa, while the other showed low signal intensity on a T1-weighted image, heterogeneous high signal intensity on a T2-weighted image, heterogeneous enhancement after the administration of contrast media and was dedifferentiate. Nine masses in seven patients with myxoid liposarcoma showed low signal intensity on T1-weighted images, six of the nine showed lace-like foci of high signal intensity. On T2-weighted images, all masses showed homogeneous high signal intensity. After administration of contrast media, five of seven masses showed heterogeneous enhancement. Two of three mixed form were well-differentiated and myxoid types, and two subtypes were separable on MR. Pleomorphic, round cell, mixed type myxoid and pleomorphic and unclassified cases showed low signal intensity on T1-weighted images, heterogeneous high signal intensity on T2-weighted and heterogeneous enhancement. Using MR imaging, well-differentiated and myxoid liposcarcomas may be differentiated from other types

  5. Cigarette smoking and risk of Hodgkin lymphoma and its subtypes

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Rostgaard, K; Glaser, S L

    2013-01-01

    The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes....

  6. Salmonella source attribution based on microbial subtyping

    DEFF Research Database (Denmark)

    Barco, Lisa; Barrucci, Federica; Olsen, John Elmerdahl

    2013-01-01

    Source attribution of cases of food-borne disease represents a valuable tool for identifying and prioritizing effective food-safety interventions. Microbial subtyping is one of the most common methods to infer potential sources of human food-borne infections. So far, Salmonella microbial subtyping...... source attribution through microbial subtyping approach. It summarizes the available microbial subtyping attribution models and discusses the use of conventional phenotypic typing methods, as well as of the most commonly applied molecular typing methods in the European Union (EU) laboratories...

  7. Spatiotemporal dynamics of the HIV-1 subtype G epidemic in West and Central Africa.

    Science.gov (United States)

    Delatorre, Edson; Mir, Daiana; Bello, Gonzalo

    2014-01-01

    The human immunodeficiency virus type 1 (HIV-1) subtype G is the second most prevalent HIV-1 clade in West Africa, accounting for nearly 30% of infections in the region. There is no information about the spatiotemporal dynamics of dissemination of this HIV-1 clade in Africa. To this end, we analyzed a total of 305 HIV-1 subtype G pol sequences isolated from 11 different countries from West and Central Africa over a period of 20 years (1992 to 2011). Evolutionary, phylogeographic and demographic parameters were jointly estimated from sequence data using a Bayesian coalescent-based method. Our analyses indicate that subtype G most probably emerged in Central Africa in 1968 (1956-1976). From Central Africa, the virus was disseminated to West and West Central Africa at multiple times from the middle 1970s onwards. Two subtype G strains probably introduced into Nigeria and Togo between the middle and the late 1970s were disseminated locally and to neighboring countries, leading to the origin of two major western African clades (G WA-I and G WA-II). Subtype G clades circulating in western and central African regions displayed an initial phase of exponential growth followed by a decline in growth rate since the early/middle 1990 s; but the mean epidemic growth rate of G WA-I (0.75 year-1) and G WA-II (0.95 year-1) clades was about two times higher than that estimated for central African lineages (0.47 year-1). Notably, the overall evolutionary and demographic history of G WA-I and G WA-II clades was very similar to that estimated for the CRF06_cpx clade circulating in the same region. These results support the notion that the spatiotemporal dissemination dynamics of major HIV-1 clades circulating in western Africa have probably been shaped by the same ecological factors.

  8. Population Dynamics and Rates of Molecular Evolution of a Recently Emerged Paramyxovirus, Avian Metapneumovirus Subtype C▿ †

    OpenAIRE

    Padhi, Abinash; Poss, Mary

    2008-01-01

    We report the existence of two distinct sublineages of avian metapneumovirus (MPV) subtype C, a virus which has caused serious economic loss in commercial turkey farms in the United States. This subtype is closely related to human MPV, infects multiple avian species, and is globally distributed. The evolutionary rates of this virus are estimated to be 1.3 × 10−3 to 7 × 10−3 substitutions per site per year, and coalescent estimates place its emergence between 1991 and 1996. The four genes exam...

  9. Population Dynamics and Rates of Molecular Evolution of a Recently Emerged Paramyxovirus, Avian Metapneumovirus Subtype C▿ †

    Science.gov (United States)

    Padhi, Abinash; Poss, Mary

    2009-01-01

    We report the existence of two distinct sublineages of avian metapneumovirus (MPV) subtype C, a virus which has caused serious economic loss in commercial turkey farms in the United States. This subtype is closely related to human MPV, infects multiple avian species, and is globally distributed. The evolutionary rates of this virus are estimated to be 1.3 × 10−3 to 7 × 10−3 substitutions per site per year, and coalescent estimates place its emergence between 1991 and 1996. The four genes examined show a concordant demographic pattern which is characterized by a rapid increase in population size followed by stable population grown until the present. PMID:19052092

  10. Prevalence of Plasmodium vivax VK210 and VK247 subtype in Myanmar

    Directory of Open Access Journals (Sweden)

    Kang Yoon-Joong

    2010-07-01

    Full Text Available Abstract Background Plasmodium vivax is divided into two subtypes, a dominant form, VK210 and a variant form, VK247. This division is dependent on the amino acid composition of the circumsporozoite (CS protein. In this study, the prevalence of the VK247 variant form of P. vivax was investigated in Myanmar. Methods The existence of malaria parasites in blood samples was determined by microscopic examination, polymerase chain reaction (PCR and DNA hybridization assays. To test for antibodies against P. vivax and Plasmodium falciparum in blood samples, an indirect immunofluorescence antibody test (IFAT was performed using asexual blood antigens. An enzyme-linked immunosorbent assay with synthetic VK210 and VK247 antigens was carried out to discriminate between the P. vivax subtypes. Results By thick smear examination, 73 (n = 100 patients were single infected with P. vivax, one with P. falciparum and 13 with both species. By thin smear, 53 patients were single infected with P. vivax, eight with only P. falciparum and 16 with both. Most of the collected blood samples were shown to be P. vivax positive (n = 95 by PCR. All cases that were positive for P. falciparum by PCR (n = 43 were also positive for P. vivax. However, 52 cases were single infected with P. vivax. IFAT showed antibody titres from 1:32 to 1:4,096. Additionally, using specific antibodies for VK210 and VK247, ELISA showed that 12 patients had antibodies for only the VK210 subtype, 4 patients had only VK247 subtype antibodies and 21 patients had antibodies for both subtypes. Using a DNA hybridization test, 47 patients were infected with the VK210 type, one patient was infected with VK247 and 23 patients were infected with both subtypes. Conclusions The proportion of the VK247 subtype in Myanmar was 43.1% (n = 25 among 58 positive cases by serodiagnosis and 25.6% (n = 24 among 94 positive cases by genetic diagnosis. In both diagnostic methods, the infection status of malaria patients is

  11. Subtype differentiation of renal tumors using voxel-based histogram analysis of intravoxel incoherent motion parameters.

    Science.gov (United States)

    Gaing, Byron; Sigmund, Eric E; Huang, William C; Babb, James S; Parikh, Nainesh S; Stoffel, David; Chandarana, Hersh

    2015-03-01

    The aim of this study was to determine if voxel-based histogram analysis of intravoxel incoherent motion imaging (IVIM) parameters can differentiate various subtypes of renal tumors, including benign and malignant lesions. A total of 44 patients with renal tumors who underwent surgery and had histopathology available were included in this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved, single-institution prospective study. In addition to routine renal magnetic resonance imaging examination performed on a 1.5-T system, all patients were imaged with axial diffusion-weighted imaging using 8 b values (range, 0-800 s/mm). A biexponential model was fitted to the diffusion signal data using a segmented algorithm to extract the IVIM parameters perfusion fraction (fp), tissue diffusivity (Dt), and pseudodiffusivity (Dp) for each voxel. Mean and histogram measures of heterogeneity (standard deviation, skewness, and kurtosis) of IVIM parameters were correlated with pathology results of tumor subtype using unequal variance t tests to compare subtypes in terms of each measure. Correction for multiple comparisons was accomplished using the Tukey honestly significant difference procedure. A total of 44 renal tumors including 23 clear cell (ccRCC), 4 papillary (pRCC), 5 chromophobe, and 5 cystic renal cell carcinomas, as well as benign lesions, 4 oncocytomas (Onc) and 3 angiomyolipomas (AMLs), were included in our analysis. Mean IVIM parameters fp and Dt differentiated 8 of 15 pairs of renal tumors. Histogram analysis of IVIM parameters differentiated 9 of 15 subtype pairs. One subtype pair (ccRCC vs pRCC) was differentiated by mean analysis but not by histogram analysis. However, 2 other subtype pairs (AML vs Onc and ccRCC vs Onc) were differentiated by histogram distribution parameters exclusively. The standard deviation of Dt [σ(Dt)] differentiated ccRCC (0.362 ± 0.136 × 10 mm/s) from AML (0.199 ± 0.043 × 10 mm/s) (P = 0

  12. Molecular Subtyping of Treponema pallidum subsp. pallidum in Lisbon, Portugal▿

    Science.gov (United States)

    Castro, R.; Prieto, E.; Águas, M. J.; Manata, M. J.; Botas, J.; Martins Pereira, F.

    2009-01-01

    The objectives of this study were to evaluate the reproducibility of a molecular method for the subtyping of Treponema pallidum subsp. pallidum and to discriminate strains of this microorganism from strains from patients with syphilis. We studied 212 specimens from a total of 82 patients with different stages of syphilis (14 primary, 7 secondary and 61 latent syphilis). The specimens were distributed as follows: genital ulcers (n = 9), skin and mucosal lesions (n = 7), blood (n = 82), plasma (n = 82), and ear lobe scrapings (n = 32). The samples were assayed by a PCR technique to amplify a segment of the polymerase gene I (polA). Positive samples were typed on the basis of the analysis of two variable genes, tpr and arp. Sixty-two of the 90 samples positive for polA yielded typeable Treponema pallidum DNA. All skin lesions in which T. pallidum was identified (six of six [100%]) were found to contain enough DNA for typing of the organism. It was also possible to type DNA from 7/9 (77.7%) genital ulcer samples, 13/22 (59.1%) blood samples, 20/32 (62.5%) plasma samples, and 16/21 (76.2%) ear lobe scrapings. The same subtype was identified in all samples from the same patient. Five molecular subtypes (subtypes 10a, 14a, 14c, 14f, and 14g) were identified, with the most frequently found subtype being subtype 14a and the least frequently found subtype being subtype 10a. In conclusion, the subtyping technique used in this study seems to have good reproducibility. To our knowledge, subtype 10a was identified for the first time. Further studies are needed to explain the presence of this subtype in Portugal, namely, its relationship to the Treponema pallidum strains circulating in the African countries where Portuguese is spoken. PMID:19494073

  13. Difference of achalasia subtypes based on clinical symptoms, radiographic findings, and stasis scores

    Directory of Open Access Journals (Sweden)

    A. Meillier

    2018-01-01

    Conclusions: Achalasia subtypes had similar clinical symptoms, except for increased vomiting severity in subtype i. The maximum esophageal diameter in subtype ii was significantly greater than in subtype iii. Esophageal stasis scores were similar. Thus, high-resolution esophageal manometry remains essential in assessing achalasia subtypes.

  14. Subtype selective kainic acid receptor agonists

    DEFF Research Database (Denmark)

    Bunch, Lennart; Krogsgaard-Larsen, Povl

    2009-01-01

    (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

  15. The validity and utility of subtyping bulimia nervosa

    NARCIS (Netherlands)

    van Hoeken, Daphne; Veling, Wim; Sinke, Sjoukje; Mitchell, James E.; Hoek, Hans W.

    Objective: To review the evidence for the validity and utility of subtyping bulimia nervosa (BN) into a purging (BN-P) and a nonpurging subtype (BN-NP), and of distinguishing BN-NP from binge eating disorder (BED), by comparing course, complications, and treatment. Method: A literature search of

  16. The validity and utility of subtyping bulimia nervosa

    NARCIS (Netherlands)

    van Hoeken, Daphne; Veling, Wim; Sinke, Sjoukje; Mitchell, James E.; Hoek, Hans W.

    2009-01-01

    Objective: To review the evidence for the validity and utility of subtyping bulimia nervosa (BN) into a purging (BN-P) and a nonpurging subtype (BN-NP), and of distinguishing BN-NP from binge eating disorder (BED), by comparing course, complications, and treatment. Method: A literature search of

  17. ADHD subtype differences in reinforcement sensitivity and visuospatial working memory

    NARCIS (Netherlands)

    Dovis, S.; van der Oord, S.; Wiers, R.W.; Prins, P.J.M.

    2015-01-01

    Both cognitive and motivational deficits are thought to give rise to the problems in the combined (ADHD-C) and inattentive subtype (ADHD-I) of attention-deficit hyperactivity disorder (ADHD). In both subtypes one of the most prominent cognitive weaknesses appears to be in visuospatial working memory

  18. The Association between Physical Morbidity and Subtypes of Severe Depression

    DEFF Research Database (Denmark)

    Østergaard, Søren Dinesen; Petrides, Georgio; Dinesen, Peter Thisted

    2013-01-01

    Physical illness and depression are related, but the association between specific physical diseases and diagnostic subtypes of depression remains poorly understood. This study aimed to clarify the relationship between a number of physical diseases and the nonpsychotic and psychotic subtype...... of severe depression....

  19. Stroke subtypes and factors associated with ischemic stroke in ...

    African Journals Online (AJOL)

    Stroke subtypes assessed four OCSP (Oxfordshire Communi-. African Health Sciences Vol 15 Issue 1, March 2015. 68. 69 ty Stroke Project Classification) subtypes classification. 13 was used with lacunar circulation infarct (LACI) and total anterior (TACI), partial anterior (PACI), posterior. (POCI) circulation infarcts as non ...

  20. Ethnic variation of the histological subtypes of renal cell carcinoma ...

    African Journals Online (AJOL)

    E.V. Ezenwa

    The content of the data obtained included the ethnicity categorized as Chinese, Malays, Indians and others (Indonesians, Vietnamese and other minor groups). Other data collected included age, gender and the histological subtype categorized as clear cell, papillary, chromophobe, collecting duct and unclassified subtypes.

  1. Tubal ligation and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

    Sieh, Weiva; Salvador, Shannon; McGuire, Valerie

    2013-01-01

    Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes....

  2. Integrative subtype discovery in glioblastoma using iCluster.

    Directory of Open Access Journals (Sweden)

    Ronglai Shen

    Full Text Available Large-scale cancer genome projects, such as the Cancer Genome Atlas (TCGA project, are comprehensive molecular characterization efforts to accelerate our understanding of cancer biology and the discovery of new therapeutic targets. The accumulating wealth of multidimensional data provides a new paradigm for important research problems including cancer subtype discovery. The current standard approach relies on separate clustering analyses followed by manual integration. Results can be highly data type dependent, restricting the ability to discover new insights from multidimensional data. In this study, we present an integrative subtype analysis of the TCGA glioblastoma (GBM data set. Our analysis revealed new insights through integrated subtype characterization. We found three distinct integrated tumor subtypes. Subtype 1 lacks the classical GBM events of chr 7 gain and chr 10 loss. This subclass is enriched for the G-CIMP phenotype and shows hypermethylation of genes involved in brain development and neuronal differentiation. The tumors in this subclass display a Proneural expression profile. Subtype 2 is characterized by a near complete association with EGFR amplification, overrepresentation of promoter methylation of homeobox and G-protein signaling genes, and a Classical expression profile. Subtype 3 is characterized by NF1 and PTEN alterations and exhibits a Mesenchymal-like expression profile. The data analysis workflow we propose provides a unified and computationally scalable framework to harness the full potential of large-scale integrated cancer genomic data for integrative subtype discovery.

  3. Identification of neural transcription factors required for the differentiation of three neuronal subtypes in the sea urchin embryo.

    Science.gov (United States)

    Slota, Leslie A; McClay, David R

    2018-03-15

    Correct patterning of the nervous system is essential for an organism's survival and complex behavior. Embryologists have used the sea urchin as a model for decades, but our understanding of sea urchin nervous system patterning is incomplete. Previous histochemical studies identified multiple neurotransmitters in the pluteus larvae of several sea urchin species. However, little is known about how, where and when neural subtypes are differentially specified during development. Here, we examine the molecular mechanisms of neuronal subtype specification in 3 distinct neural subtypes in the Lytechinus variegatus larva. We show that these subtypes are specified through Delta/Notch signaling and identify a different transcription factor required for the development of each neural subtype. Our results show achaete-scute and neurogenin are proneural for the serotonergic neurons of the apical organ and cholinergic neurons of the ciliary band, respectively. We also show that orthopedia is not proneural but is necessary for the differentiation of the cholinergic/catecholaminergic postoral neurons. Interestingly, these transcription factors are used similarly during vertebrate neurogenesis. We believe this study is a starting point for building a neural gene regulatory network in the sea urchin and for finding conserved deuterostome neurogenic mechanisms. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Toward Precision Medicine: A Cancer Molecular Subtyping Nano-Strategy for RNA Biomarkers in Tumor and Urine.

    Science.gov (United States)

    Koo, Kevin M; Wee, Eugene J H; Mainwaring, Paul N; Wang, Yuling; Trau, Matt

    2016-12-01

    Cancer is a heterogeneous disease which manifests as different molecular subtypes due to the complex nature of tumor initiation, progression, and metastasis. The concept of precision medicine aims to exploit this cancer heterogeneity by incorporating diagnostic technology to characterize each cancer patient's molecular subtype for tailored treatments. To characterize cancer molecular subtypes accurately, a suite of multiplexed bioassays have currently been developed to detect multiple oncogenic biomarkers. Despite the reliability of current multiplexed detection techniques, novel strategies are still needed to resolve limitations such as long assay time, complex protocols, and difficulty in interpreting broad overlapping spectral peaks of conventional fluorescence readouts. Herein a rapid (80 min) multiplexed platform strategy for subtyping prostate cancer tumor and urine samples based on their RNA biomarker profiles is presented. This is achieved by combining rapid multiplexed isothermal reverse transcription-recombinase polymerase amplification (RT-RPA) of target RNA biomarkers with surface-enhanced Raman spectroscopy (SERS) nanotags for "one-pot" readout. This is the first translational application of a RT-RPA/SERS-based platform for multiplexed cancer biomarker detection to address a clinical need. With excellent sensitivity of 200 zmol (100 copies) and specificity, we believed that this platform methodology could be a useful tool for rapid multiplexed subtyping of cancers. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Osteoclastic finger arthrosis - a subtype of polyarthrosis of the hand; Osteoklastische Fingerarthrose - Subtyp der Handpolyarthrose

    Energy Technology Data Exchange (ETDEWEB)

    Dihlmann, W. [Radiologische Praxis, Hamburg-Barmbek (Germany); Dihlmann, A. [Berufsgenossenschaftliches Unfallkrankenhaus Hamburg (Germany)

    1998-02-01

    Aim: Description of a subtype of arthrosis deformans of the hand which is characterised as osteoclastic arthrosis. Patients and methods: Retrospective analysis of radiographs of the hands of 150 women and 100 men with radiological findings of arthrosis deformans. Results: 5% of women and 2% of men showed at least one digital joint with subchondral osteolysis of one or both articulating bones involving at least a third of the phalanx. This subchondral osteolysis far exceeds the cysts which are situated in the epiphyseal part of the articular region. It may develop within a year. Conclusion: Osteoclastic arthrosis of the finger is a subtype of polyarthrosis of the hand. Serial observations suggest that an osteoclast stimulating substance is produced by the cysts or arises directly from the synovial fluid; this enters the subchondral part of the bone through clefts which may or may not be visible radiologically and that this produces osteoclastic activity. The most important differential diagnoses are chronic tophacious gout and a benign tumor. (orig.) [Deutsch] Ziel: Beschreibung eines Subtyps der Arthrosis deformans an der Hand, der als osteoklastische Arthrose bezeichnet wird. Patienten und Methode: Retrospektive Analyse der Handroentgenaufnahmen von 150 Frauen und 100 Maennern mit Roentgenbefunden der Arthrosis deformans. Ergebnisse: 5% der Frauen und 2% der maennlichen Patienten des durchgesehenen Krankenguts zeigten an mindestens einem Fingergelenk eine Arthrose mit subchondralen Osteolysen an einem oder beiden artikulierenden Knochen, die mindestens ein Drittel der Phalanxlaenge erfasst hatten. Diese subchondralen Osteolysen gehen ueber die Groesse und Form der arthrotischen Geroellzysten, die lediglich im knoechernen (epiphysaeren) Gelenksockel sitzen, weit hinaus. Sie koennen innerhalb eines Jahres entstehen. Schlussfolgerung: Die osteoklastische Arthrose der Finger ist ein Subtyp der Handpolyarthrose. Nach Verlaufsbeobachtungen wird vermutet, dass eine

  6. Salmonella Source Attribution in Japan by a Microbiological Subtyping Approach

    DEFF Research Database (Denmark)

    Toyofuku, Hajime; Pires, Sara Monteiro; Hald, Tine

    2011-01-01

    In order to estimate the number of human Salmonella infections attributable to each of major animal-food source, and help identifying the best Salmonella intervention strategies, a microbial subtyping approach for source attribution was applied. We adapted a Bayesian model that attributes illnesses......-food sources, subtype-related factors, and source-related factors. National-surveillance serotyping data from 1998 to 2007 were applied to the model. Results suggested that the relative contribution of the sources to salmonellosis varied during the 10 year period, and that eggs are the most important source...... to specific sources and allows for the estimation of the differences in the ability of Salmonella subtypes and food types to result in reported salmonellosis. The number of human cases caused by different Salmonella subtypes is estimated as a function of the prevalence of these subtypes in the animal...

  7. Sensory Subtypes in Preschool Aged Children with Autism Spectrum Disorder.

    Science.gov (United States)

    Tomchek, Scott D; Little, Lauren M; Myers, John; Dunn, Winnie

    2018-06-01

    Given the heterogeneity of autism spectrum disorder (ASD), research has investigated how sensory features elucidate subtypes that enhance our understanding of etiology and tailored treatment approaches. Previous studies, however, have not integrated core developmental behaviors with sensory features in investigations of subtypes in ASD. Therefore, we used latent profile analysis to examine subtypes in a preschool aged sample considering sensory processing patterns in combination with social-communication skill, motor performance, and adaptive behavior. Results showed four subtypes that differed by degree and quality of sensory features, age and differential presentation of developmental skills. Findings partially align with previous literature on sensory subtypes and extends our understanding of how sensory processing aligns with other developmental domains in young children with ASD.

  8. Molecular Subtyping of Tumors from Patients with Familial Glioma.

    Science.gov (United States)

    Ruiz, Vanessa Y; Praska, Corinne E; Armstrong, Georgina; Kollmeyer, Thomas M; Yamada, Seiji; Decker, Paul A; Kosel, Matthew L; Eckel-Passow, Jeanette E; Consortium, The Gliogene; Lachance, Daniel H; Bainbridge, Matthew N; Melin, Beatrice S; Bondy, Melissa L; Jenkins, Robert B

    2017-10-10

    Single-gene mutation syndromes account for some familial glioma (FG); however, they make up only a small fraction of glioma families. Gliomas can be classified into 3 major molecular subtypes based on IDH mutation and 1p/19q co-deletion. We hypothesized that the prevalence of molecular subtypes might differ in familial versus sporadic gliomas, and that tumors in the same family should have the same molecular subtype. Participants in the FG study (Gliogene) provided samples for germline DNA analysis. Formalin-fixed, paraffin-embedded (FFPE) tumor was obtained for a subset of FG cases, and DNA was extracted. We analyzed tissue from 75 families, including 10 families containing a second affected family member. Copy number variation (CNV) data was obtained using a first-generation Affymetrix molecular inversion probe (MIP) array. Samples from 62 of 75 (83%) FG cases could be classified into the 3 subtypes. The prevalence of the molecular subtypes was: 30 (48%) IDH-wild type, 21 (34%) IDH-mutant non-codeleted, and 11 (19%) IDH-mutant and 1p/19q-codeleted. This distribution of molecular subtypes was not statistically different from that of sporadic gliomas (p=0.54). Of 10 paired FG samples, molecular subtypes were concordant for 7 (κ=0.59): 3 IDH-mutant non-codeleted, 2 IDH-wild type, and 2 IDH-mutant and 1p/19q-codeleted gliomas. Our data suggest that within individual families, patients develop gliomas of the same molecular subtype. However, we did not observe differences in the prevalence of the molecular subtypes in FG compared with sporadic gliomas. These observations provide further insight about the distribution of molecular subtypes in FG. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  9. Appreciating HIV-1 diversity: subtypic differences in ENV

    Energy Technology Data Exchange (ETDEWEB)

    Gnanakaran, S [Los Alamos National Laboratory; Shen, Tongye [Los Alamos National Laboratory; Lynch, Rebecca M [NON LANL; Derdeyn, Cynthia A [NON LANL

    2008-01-01

    Human immunodeficiency virus type 1 (HIV-1) group M is responsible for the current AIDS pandemic and exhibits exceedingly high levels of viral genetic diversity around the world, necessitating categorization of viruses into distinct lineages, or subtypes. These subtypes can differ by around 35% in the envelope (Env) glycoproteins of the virus, which are displayed on the surface of the virion and are targets for both neutralizing antibody and cell-mediated immune responses. This diversity reflects the remarkable ability of the virus to adapt to selective pressures, the bulk of which is applied by the host immune response, and represents a serious obstacle for developing an effective vaccine with broad coverage. Thus, it is important to understand the underlying biological consequences of inter-subtype diversity. Recent studies have revealed that the HIV-1 subtypes exhibit phenotypic differences that result from subtle differences in Env structure, particularly within the highly immunogenic V3 domain, which participates directly in viral entry. This review will therefore explore current research that describes subtypic differences in Env at the genetic and phenotypic level, focusing in particular on V3, and highlighting recent discoveries about the unique features of subtype C Env, which is the most prevalent subtype globally.

  10. Racial difference in histologic subtype of renal cell carcinoma

    International Nuclear Information System (INIS)

    Olshan, Andrew F; Kuo, Tzy-Mey; Meyer, Anne-Marie; Nielsen, Matthew E; Purdue, Mark P; Rathmell, W Kimryn

    2013-01-01

    In the United States, renal cell carcinoma (RCC) has rapidly increased in incidence for over two decades. The most common histologic subtypes of RCC, clear cell, papillary, and chromophobe have distinct genetic and clinical characteristics; however, epidemiologic features of these subtypes have not been well characterized, particularly regarding any associations between race, disease subtypes, and recent incidence trends. Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we examined differences in the age-adjusted incidence rates and trends of RCC subtypes, including analysis focusing on racial differences. Incidence rates increased over time (2001–2009) for all three subtypes. However, the proportion of white cases with clear cell histology was higher than among blacks (50% vs. 31%, respectively), whereas black cases were more likely than white cases to have papillary RCC (23% vs. 9%, respectively). Moreover, papillary RCC incidence increased more rapidly for blacks than whites (P < 0.01) over this period. We also observed that increased incidence of papillary histology among blacks is not limited to the smallest size strata. We observed racial differences in proportionate incidence of RCC subtypes, which appear to be increasing over time; this novel finding motivates further etiologic, clinical, molecular, and genetic studies. Using national data, we observed a higher proportion of black renal cell carcinoma (RCC) cases with papillary histology compared to Caucasian cases. We also observed time trends in black-white incidence differences in histologic RCC subtypes, with rapid increases in the disproportionate share of black cases with papillary histology

  11. Racial Disparities in the Pathogenesis of Type 2 Diabetes and its Subtypes in the African Diaspora: A New Paradigm.

    Science.gov (United States)

    Gaillard, Trudy R; Osei, Kwame

    2016-03-01

    The global epidemic of diabetes has extended to the developing countries including Sub-Sahara Africa. In this context, blacks with type 2 diabetes in the African Diaspora continue to manifest 1.5-2 times higher prevalent rates than in their white counterparts. Previous studies have demonstrated that blacks with and without type 2 diabetes have alterations in hepatic and peripheral insulin sensitivity, beta-cell function, and hepatic insulin clearance as well as hepatic glucose dysregulation when compared to whites. In addition, non-diabetic blacks in the African Diaspora manifest multiple metabolic mediators that predict type 2 diabetes and its subtypes. These pathogenic modifiers include differences in subclinical inflammation, oxidative stress burden, and adipocytokines in blacks in the African Diaspora prior to clinical diagnosis. Consequently, blacks in the African Diaspora manifest subtypes of type 2 diabetes, including ketosis-prone diabetes and J type diabetes. Given the diversity of type 2 diabetes in blacks in the African Diaspora, we hypothesize that blacks manifest multiple early pathogenic defects prior to the diagnosis of type 2 diabetes and its subtypes. These metabolic alterations have strong genetic component, which appears to play pivotal and primary role in the pathogenesis of type 2 diabetes and its subtypes in blacks in the African Diaspora. However, environmental factors must also be considered as major contributors to the higher prevalence of type 2 diabetes and its subtypes in blacks in the African Diaspora. These multiple alterations should be targets for early prevention of type 2 diabetes in blacks in the African Diaspora.

  12. HIV-1 subtype A gag variability and epitope evolution.

    Science.gov (United States)

    Abidi, Syed Hani; Kalish, Marcia L; Abbas, Farhat; Rowland-Jones, Sarah; Ali, Syed

    2014-01-01

    The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes. We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G → A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined. The most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956 ± 1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2-3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005-2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005-2010. It appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences.

  13. HIV-1 subtype A gag variability and epitope evolution.

    Directory of Open Access Journals (Sweden)

    Syed Hani Abidi

    Full Text Available OBJECTIVE: The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes. METHODS: We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G → A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined. RESULTS: The most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956 ± 1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2-3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005-2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005-2010. CONCLUSION: It appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences.

  14. An Overview of Achalasia and Its Subtypes

    Science.gov (United States)

    Patel, Dhyanesh A.; Lappas, Brian M.

    2017-01-01

    Achalasia is one of the most studied esophageal motility disorders. However, the pathophysiology and reasons that patients develop achalasia are still unclear. Patients often present with dysphagia to solids and liquids, regurgitation, and varying degrees of weight loss. There is significant latency prior to diagnosis, which can have nutritional implications. The diagnosis is suspected based on clinical history and confirmed by esophageal high-resolution manometry testing. Esophagogastroduodenoscopy is necessary to rule out potential malignancy that can mimic achalasia. Recent data presented in abstract form suggest that patients with type II achalasia may be most likely, and patients with type III achalasia may be least likely, to report weight loss compared to patients with type I achalasia. Although achalasia cannot be permanently cured, palliation of symptoms is possible in over 90% of patients with the treatment modalities currently available (pneumatic dilation, Heller myotomy, or peroral endoscopic myotomy). This article reviews the clinical presentation, diagnosis, and management options in patients with achalasia, as well as potential insights into histopathologic differences and nutritional implications of the subtypes of achalasia. PMID:28867969

  15. (Re-)programming of subtype specific cardiomyocytes.

    Science.gov (United States)

    Hausburg, Frauke; Jung, Julia Jeannine; Hoch, Matti; Wolfien, Markus; Yavari, Arash; Rimmbach, Christian; David, Robert

    2017-10-01

    Adult cardiomyocytes (CMs) possess a highly restricted intrinsic regenerative potential - a major barrier to the effective treatment of a range of chronic degenerative cardiac disorders characterized by cellular loss and/or irreversible dysfunction and which underlies the majority of deaths in developed countries. Both stem cell programming and direct cell reprogramming hold promise as novel, potentially curative approaches to address this therapeutic challenge. The advent of induced pluripotent stem cells (iPSCs) has introduced a second pluripotent stem cell source besides embryonic stem cells (ESCs), enabling even autologous cardiomyocyte production. In addition, the recent achievement of directly reprogramming somatic cells into cardiomyocytes is likely to become of great importance. In either case, different clinical scenarios will require the generation of highly pure, specific cardiac cellular-subtypes. In this review, we discuss these themes as related to the cardiovascular stem cell and programming field, including a focus on the emergent topic of pacemaker cell generation for the development of biological pacemakers and in vitro drug testing. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Microdroplet sandwich real-time rt-PCR for detection of pandemic and seasonal influenza subtypes.

    Directory of Open Access Journals (Sweden)

    Stephanie L Angione

    Full Text Available As demonstrated by the recent 2012/2013 flu epidemic, the continual emergence of new viral strains highlights the need for accurate medical diagnostics in multiple community settings. If rapid, robust, and sensitive diagnostics for influenza subtyping were available, it would help identify epidemics, facilitate appropriate antiviral usage, decrease inappropriate antibiotic usage, and eliminate the extra cost of unnecessary laboratory testing and treatment. Here, we describe a droplet sandwich platform that can detect influenza subtypes using real-time reverse-transcription polymerase chain reaction (rtRT-PCR. Using clinical samples collected during the 2010/11 season, we effectively differentiate between H1N1p (swine pandemic, H1N1s (seasonal, and H3N2 with an overall assay sensitivity was 96%, with 100% specificity for each subtype. Additionally, we demonstrate the ability to detect viral loads as low as 10(4 copies/mL, which is two orders of magnitude lower than viral loads in typical infected patients. This platform performs diagnostics in a miniaturized format without sacrificing any sensitivity, and can thus be easily developed into devices which are ideal for small clinics and pharmacies.

  17. Ischemic stroke subtype is associated with outcome in thrombolyzed patients

    DEFF Research Database (Denmark)

    Schmitz, Marie Louise; Simonsen, Claus Ziegler; Svendsen, M L

    2017-01-01

    OBJECTIVES: The impact of ischemic stroke subtype on clinical outcome in patients treated with intravenous tissue-type plasminogen activator (IV-tPA) is sparsely examined. We studied the association between stroke subtype and clinical outcome in magnetic resonance imaging (MRI)-evaluated patients...... patients were more likely to achieve early neurological improvement and favorable outcome compared with LVD stroke following MRI-based IV-tPA treatment. This finding may reflect a difference in the effect of IV-tPA among stroke subtypes....

  18. CRISPR-cas subtype I-Fb in Acinetobacter baumannii: evolution and utilization for strain subtyping.

    Science.gov (United States)

    Karah, Nabil; Samuelsen, Ørjan; Zarrilli, Raffaele; Sahl, Jason W; Wai, Sun Nyunt; Uhlin, Bernt Eric

    2015-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) are polymorphic elements found in the genome of some or all strains of particular bacterial species, providing them with a system of acquired immunity against invading bacteriophages and plasmids. Two CRISPR-Cas systems have been identified in Acinetobacter baumannii, an opportunistic pathogen with a remarkable capacity for clonal dissemination. In this study, we investigated the mode of evolution and diversity of spacers of the CRISPR-cas subtype I-Fb locus in a global collection of 76 isolates of A. baumannii obtained from 14 countries and 4 continents. The locus has basically evolved from a common ancestor following two main lineages and several pathways of vertical descent. However, this vertical passage has been interrupted by occasional events of horizontal transfer of the whole locus between distinct isolates. The isolates were assigned into 40 CRISPR-based sequence types (CST). CST1 and CST23-24 comprised 18 and 9 isolates, representing two main sub-clones of international clones CC1 and CC25, respectively. Epidemiological data showed that some of the CST1 isolates were acquired or imported from Iraq, where it has probably been endemic for more than one decade and occasionally been able to spread to USA, Canada, and Europe. CST23-24 has shown a remarkable ability to cause national outbreaks of infections in Sweden, Argentina, UAE, and USA. The three isolates of CST19 were independently imported from Thailand to Sweden and Norway, raising a concern about the prevalence of CST19 in Thailand. Our study highlights the dynamic nature of the CRISPR-cas subtype I-Fb locus in A. baumannii, and demonstrates the possibility of using a CRISPR-based approach for subtyping a significant part of the global population of A. baumannii.

  19. CRISPR-cas Subtype I-Fb in Acinetobacter baumannii: Evolution and Utilization for Strain Subtyping

    Science.gov (United States)

    Karah, Nabil; Samuelsen, Ørjan; Zarrilli, Raffaele; Sahl, Jason W.; Wai, Sun Nyunt; Uhlin, Bernt Eric

    2015-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) are polymorphic elements found in the genome of some or all strains of particular bacterial species, providing them with a system of acquired immunity against invading bacteriophages and plasmids. Two CRISPR-Cas systems have been identified in Acinetobacter baumannii, an opportunistic pathogen with a remarkable capacity for clonal dissemination. In this study, we investigated the mode of evolution and diversity of spacers of the CRISPR-cas subtype I-Fb locus in a global collection of 76 isolates of A. baumannii obtained from 14 countries and 4 continents. The locus has basically evolved from a common ancestor following two main lineages and several pathways of vertical descent. However, this vertical passage has been interrupted by occasional events of horizontal transfer of the whole locus between distinct isolates. The isolates were assigned into 40 CRISPR-based sequence types (CST). CST1 and CST23-24 comprised 18 and 9 isolates, representing two main sub-clones of international clones CC1 and CC25, respectively. Epidemiological data showed that some of the CST1 isolates were acquired or imported from Iraq, where it has probably been endemic for more than one decade and occasionally been able to spread to USA, Canada, and Europe. CST23-24 has shown a remarkable ability to cause national outbreaks of infections in Sweden, Argentina, UAE, and USA. The three isolates of CST19 were independently imported from Thailand to Sweden and Norway, raising a concern about the prevalence of CST19 in Thailand. Our study highlights the dynamic nature of the CRISPR-cas subtype I-Fb locus in A. baumannii, and demonstrates the possibility of using a CRISPR-based approach for subtyping a significant part of the global population of A. baumannii. PMID:25706932

  20. α1A-Subtype adrenergic agonist therapy for the failing right ventricle.

    Science.gov (United States)

    Cowley, Patrick M; Wang, Guanying; Joshi, Sunil; Swigart, Philip M; Lovett, David H; Simpson, Paul C; Baker, Anthony J

    2017-12-01

    Failure of the right ventricle (RV) is a serious disease with a poor prognosis and limited treatment options. Signaling by α 1 -adrenergic receptors (α 1 -ARs), in particular the α 1A -subtype, mediate cardioprotective effects in multiple heart failure models. Recent studies have shown that chronic treatment with the α 1A -subtype agonist A61603 improves function and survival in a model of left ventricular failure. The goal of the present study was to determine if chronic A61603 treatment is beneficial in a RV failure model. We used tracheal instillation of the fibrogenic antibiotic bleomycin in mice to induce pulmonary fibrosis, pulmonary hypertension, and RV failure within 2 wk. Some mice were chronically treated with a low dose of A61603 (10 ng·kg -1 ·day -1 ). In the bleomycin model of RV failure, chronic A61603 treatment was associated with improved RV fractional shortening and greater in vitro force development by RV muscle preparations. Cell injury markers were reduced with A61603 treatment (serum cardiac troponin I, RV fibrosis, and expression of matrix metalloproteinase-2). RV oxidative stress was reduced (using the probes dihydroethidium and 4-hydroxynonenal). Consistent with lowered RV oxidative stress, A61603 was associated with an increased level of the cellular antioxidant superoxide dismutase 1 and a lower level of the prooxidant NAD(P)H oxidase isoform NOX4. In summary, in the bleomycin model of RV failure, chronic A61603 treatment reduced RV oxidative stress, RV myocyte necrosis, and RV fibrosis and increased both RV function and in vitro force development. These findings suggest that in the context of pulmonary fibrosis, the α 1A -subtype is a potential therapeutic target to treat the failing RV. NEW & NOTEWORTHY Right ventricular (RV) failure is a serious disease with a poor prognosis and no effective treatments. In the mouse bleomycin model of RV failure, we tested the efficacy of a treatment using the α 1A -adrenergic receptor subtype

  1. Burnout Subtypes and Absence of Self-Compassion in Primary Healthcare Professionals: A Cross-Sectional Study.

    Science.gov (United States)

    Montero-Marin, Jesus; Zubiaga, Fernando; Cereceda, Maria; Piva Demarzo, Marcelo Marcos; Trenc, Patricia; Garcia-Campayo, Javier

    2016-01-01

    Primary healthcare professionals report high levels of distress and burnout. A new model of burnout has been developed to differentiate three clinical subtypes: 'frenetic', 'underchallenged' and 'worn-out'. The aim of this study was to confirm the validity and reliability of the burnout subtype model in Spanish primary healthcare professionals, and to assess the explanatory power of the self-compassion construct as a possible protective factor. The study employed a cross-sectional design. A sample of n = 440 Spanish primary healthcare professionals (214 general practitioners, 184 nurses, 42 medical residents) completed the Burnout Clinical Subtype Questionnaire (BCSQ-36), the Maslach Burnout Inventory General Survey (MBI-GS), the Self-Compassion Scale (SCS), the Utrecht Work Engagement Scale (UWES) and the Positive and Negative Affect Schedule (PANAS). The factor structure of the BCSQ-36 was estimated using confirmatory factor analysis (CFA) by the unweighted least squares method from polychoric correlations. Internal consistency (R) was assessed by squaring the correlation between the latent true variable and the observed variables. The relationships between the BCSQ-36 and the other constructs were analysed using Spearman's r and multiple linear regression models. The structure of the BCSQ-36 fit the data well, with adequate CFA indices for all the burnout subtypes. Reliability was adequate for all the scales and sub-scales (R≥0.75). Self-judgement was the self-compassion factor that explained the frenetic subtype (Beta = 0.36; pUWES and PANAS. The typological definition of burnout through the BCSQ-36 showed good structure and appropriate internal consistence in Spanish primary healthcare professionals. The negative self-compassion dimensions seem to play a relevant role in explaining the burnout profiles in this population, and they should be considered when designing specific treatments and interventions tailored to the specific vulnerability of each subtype.

  2. Interpersonal subtypes in social phobia: diagnostic and treatment implications.

    Science.gov (United States)

    Cain, Nicole M; Pincus, Aaron L; Grosse Holtforth, Martin

    2010-11-01

    Interpersonal assessment may provide a clinically useful way to identify subtypes of social phobia. In this study, we examined evidence for interpersonal subtypes in a sample of 77 socially phobic outpatients. A cluster analysis based on the dimensions of dominance and love on the Inventory of Interpersonal Problems-Circumplex Scales (Alden, Wiggins, & Pincus, 1990) found 2 interpersonal subtypes of socially phobic patients. These subtypes did not differ on pretreatment global symptom severity as measured by the Brief Symptom Inventory (Derogatis, 1993) or diagnostic comorbidity but did exhibit differential responses to outpatient psychotherapy. Overall, friendly-submissive social phobia patients had significantly lower scores on measures of social anxiety and significantly higher scores on measures of well-being and satisfaction at posttreatment than cold-submissive social phobia patients. We discuss the results in terms of interpersonal theory and the clinical relevance of assessment of interpersonal functioning prior to beginning psychotherapy with socially phobic patients.

  3. New paradigms for Salmonella source attribution based on microbial subtyping.

    NARCIS (Netherlands)

    Mughini-Gras, Lapo; Franz, Eelco; van Pelt, Wilfrid

    Microbial subtyping is the most common approach for Salmonella source attribution. Typically, attributions are computed using frequency-matching models like the Dutch and Danish models based on phenotyping data (serotyping, phage-typing, and antimicrobial resistance profiling). Herewith, we

  4. Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Chaisaingmongkol, Jittiporn; Budhu, Anuradha; Dang, Hien

    2017-01-01

    Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integratio...

  5. Acquired Demyelinating Syndromes: Focus on Neuromyelitis Optica and childhood-onset Multiple Sclerosis

    NARCIS (Netherlands)

    E.D. van Pelt - Gravesteijn (Daniëlle)

    2016-01-01

    markdownabstractAcquired demyelinating syndromes (ADS) cover a broad spectrum of central nervous system (CNS) inflammatory demyelinating syndromes, of which multiple sclerosis (MS) is the most common subtype. This thesis focuses on two relatively rare clinical subtypes of ADS: neuromyelitis optica

  6. Anxiety After Stroke: The Importance of Subtyping.

    Science.gov (United States)

    Chun, Ho-Yan Yvonne; Whiteley, William N; Dennis, Martin S; Mead, Gillian E; Carson, Alan J

    2018-03-01

    Anxiety after stroke is common and disabling. Stroke trialists have treated anxiety as a homogenous condition, and intervention studies have followed suit, neglecting the different treatment approaches for phobic and generalized anxiety. Using diagnostic psychiatric interviews, we aimed to report the frequency of phobic and generalized anxiety, phobic avoidance, predictors of anxiety, and patient outcomes at 3 months poststroke/transient ischemic attack. We followed prospectively a cohort of new diagnosis of stroke/transient ischemic attack at 3 months with a telephone semistructured psychiatric interview, Fear Questionnaire, modified Rankin Scale, EuroQol-5D5L, and Work and Social Adjustment Scale. Anxiety disorder was common (any anxiety disorder, 38 of 175 [22%]). Phobic disorder was the predominant anxiety subtype: phobic disorder only, 18 of 175 (10%); phobic and generalized anxiety disorder, 13 of 175 (7%); and generalized anxiety disorder only, 7 of 175 (4%). Participants with anxiety disorder reported higher level of phobic avoidance across all situations on the Fear Questionnaire. Younger age (per decade increase in odds ratio, 0.64; 95% confidence interval, 0.45-0.91) and having previous anxiety/depression (odds ratio, 4.38; 95% confidence interval, 1.94-9.89) were predictors for anxiety poststroke/transient ischemic attack. Participants with anxiety disorder were more dependent (modified Rankin Scale score 3-5, [anxiety] 55% versus [no anxiety] 29%; P anxiety] 19.5, 10-27 versus [no anxiety] 0, 0-5; P Anxiety after stroke/transient ischemic attack is predominantly phobic and is associated with poorer patient outcomes. Trials of anxiety intervention in stroke should consider the different treatment approaches needed for phobic and generalized anxiety. © 2018 The Authors.

  7. Molecular subtypes of glioblastoma are relevant to lower grade glioma.

    Directory of Open Access Journals (Sweden)

    Xiaowei Guan

    Full Text Available Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas.Gene expression array, single nucleotide polymorphism (SNP array and clinical data were obtained for 228 GBMs and 176 grade II/II gliomas (GII/III from the publically available Rembrandt dataset. Two additional datasets with IDH1 mutation status were utilized as validation datasets (one publicly available dataset and one newly generated dataset from MD Anderson. Unsupervised clustering was performed and compared to gene expression subtypes assigned using the Verhaak et al 840-gene classifier. The glioma-CpG Island Methylator Phenotype (G-CIMP was assigned using prediction models by Fine et al.Unsupervised clustering by gene expression aligned with the Verhaak 840-gene subtype group assignments. GII/IIIs were preferentially assigned to the proneural subtype with IDH1 mutation and G-CIMP. GBMs were evenly distributed among the four subtypes. Proneural, IDH1 mutant, G-CIMP GII/III s had significantly better survival than other molecular subtypes. Only 6% of GBMs were proneural and had either IDH1 mutation or G-CIMP but these tumors had significantly better survival than other GBMs. Copy number changes in chromosomes 1p and 19q were associated with GII/IIIs, while these changes in CDKN2A, PTEN and EGFR were more commonly associated with GBMs.GBM gene-expression and methylation based subtypes are relevant for GII/III s and associate with overall survival differences. A better understanding of the association between these subtypes and GII/IIIs could further knowledge regarding prognosis and mechanisms of glioma progression.

  8. Progranulin expression in breast cancer with different intrinsic subtypes.

    Science.gov (United States)

    Li, Li Qin; Min, Li Shan; Jiang, Qun; Ping, Jin Liang; Li, Jing; Dai, Li Cheng

    2012-04-15

    Progranulin is a newly discovered 88-kDa glycoprotein originally purified from the highly tumorigenic mouse teratoma-derived cell line PC. We found that high progranulin expression was associated with higher breast carcinoma angiogenesis, reflected by increased vascular endothelial growth factor expression and higher microvessel density. However, no immunohistochemical evidence currently exists to correlate progranulin expression with clinicopathological features in different intrinsic subtypes of breast carcinoma biopsies. The aim of this study was to investigate the progranulin expression profiles in the intrinsic subtypes of breast carcinomas and their relevance to histopathological and clinicopathological features. Tissue blocks containing 264 cases of breast carcinomas from 2006 to 2009 were classified as different intrinsic subtypes. Tissues of four intrinsic subtypes were immunostained for progranulin, vascular endothelial growth factor and CD105. Their relevance to histopathological and clinicopathological features was also analyzed. Twenty tissue samples from breast fibroadenomas were included in this study. Progranulin expression showed no significant differences in different intrinsic subtypes, although an increasing tendency could be found in the triple-negative breast cancer (TNBC) subgroup (χ(2)=5.00, df=3, p=0.17). However, differences were significant when pathologically node metastasis-positive (pN(+)) TNBC were excluded (χ(2)=17.84, df=3, pprogranulin in pathologically node metastasis-negative (pN(-)) TNBC. It was noted that the EGFR expression level of the pN(-) TNBC subtype was significantly higher in cases with strong progranulin expression than in cases with weak progranulin expression (χ(2)=11.26, df=1, pprogranulin in pN(-) TNBC suggests that progranulin is a promising new target for pN(-) TNBC treatment. Strong expression of progranulin correlates with positive EGFR expression in the pN(-) TNBC subtype. The close relationship between

  9. Epidemic dynamics of two coexisting hepatitis C virus subtypes.

    Science.gov (United States)

    Jiménez-Hernández, Nuria; Torres-Puente, Manuela; Bracho, Maria Alma; García-Robles, Inmaculada; Ortega, Enrique; del Olmo, Juan; Carnicer, Fernando; González-Candelas, Fernando; Moya, Andrés

    2007-01-01

    Hepatitis C virus (HCV) infection affects about 3% of the human population. Phylogenetic analyses have grouped its variants into six major genotypes, which have a star-like distribution and several minor subtypes. The most abundant genotype in Europe is the so-called genotype 1, with two prevalent subtypes, 1a and 1b. In order to explain the higher prevalence of subtype 1b over 1a, a large-scale sequence analysis (100 virus clones) has been carried out over 25 patients of both subtypes in two regions of the HCV genome: one comprising hypervariable region 1 and another including the interferon sensitivity-determining region. Neither polymorphism analysis nor molecular variance analysis (attending to intra- and intersubtype differences, age, sex and previous history of antiviral treatment) was able to show any particular difference between subtypes that might account for their different prevalence. Only the demographic history of the populations carrying both subtypes and analysis of molecular variance (AMOVA) for risk practice suggested that the route of transmission may be the most important factor to explain the observed difference.

  10. [Human immunodeficiency virus type 1 subtypes in Djibouti].

    Science.gov (United States)

    Abar, A Elmi; Jlizi, A; Darar, H Youssouf; Ben Nasr, M; Abid, S; Kacem, M Ali Ben Hadj; Slim, A

    2012-01-01

    The authors had for aim to study the distribution of HIV-1 subtypes in a cohort of HIV positive patients in the hospital General Peltier of Djibouti. An epidemiological study was made on 40 HIV-1 positive patients followed up in the Infectious Diseases Department over three months. All patients sample were subtyped by genotyping. Thirty-five patients (15 men and 20 women) were found infected by an HIV-1 strain belonging to the M group. Genotyping revealed that - 66% of samples were infected with subtype C, 20% with CRF02_AG, 8.5% with B, 2.9% with CRF02_AG/C and 2.9% with K/C. In fact, Subtype C prevalence has been described in the Horn of Africa and a similar prevalence was previously reported in Djibouti. However our study describes the subtype B in Djibouti for the first time. It is the predominant subtype in the Western world. The detection of CRF02_AG strains indicates that they are still circulating in Djibouti, the only country in East Africa in which this recombinant virus was found. CRF02_AG recombinant isolates were primarily described in West and Central Africa. The presence of this viral heterogeneity, probably coming from the mixing of populations in Djibouti, which is an essential economic and geographical crossroads, incites us to vigilance in the surveillance of this infection.

  11. Subtyping pathological gamblers based on impulsivity, depression, and anxiety.

    Science.gov (United States)

    Ledgerwood, David M; Petry, Nancy M

    2010-12-01

    This study examined putative subtypes of pathological gamblers (PGs) based on the Pathways model, and it also evaluated whether the subtypes would benefit differentially from treatment. Treatment-seeking PGs (N = 229) were categorized into Pathways subtypes based on scores from questionnaires assessing anxiety, depression, and impulsivity. The Addiction Severity Index-Gambling assessed severity of gambling problems at baseline, posttreatment, and 12-month follow-up. Compared with behaviorally conditioned (BC) gamblers, emotionally vulnerable (EV) gamblers had higher psychiatric and gambling severity, and were more likely to have a parent with a psychiatric history. Antisocial impulsive (AI) gamblers also had elevated gambling and psychiatric severity relative to BC gamblers. They were more likely to have antisocial personality disorder and had the highest legal and family/social severity scores. They were also most likely to have a history of substance abuse treatment, history of inpatient psychiatric treatment, and a parent with a substance use or gambling problem. AI and EV gamblers experienced greater gambling severity throughout treatment than BC gamblers, but all three subtypes demonstrated similar patterns of treatment response. Thus, the three Pathways subtypes differ on some baseline characteristics, but subtyping did not predict treatment outcomes beyond a simple association with problem gambling severity. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  12. Heterogeneity of muscarinic receptor subtypes in cerebral blood vessels

    International Nuclear Information System (INIS)

    Garcia-Villalon, A.L.; Krause, D.N.; Ehlert, F.J.; Duckles, S.P.

    1991-01-01

    The identity and distribution of muscarinic cholinergic receptor subtypes and associated signal transduction mechanisms was characterized for the cerebral circulation using correlated functional and biochemical investigations. Subtypes were distinguished by the relative affinities of a panel of muscarinic antagonists, pirenzepine, AF-DX 116 [11-2-[[2-[diethylaminomethyl]- 1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one], hexahydrosiladifenidol, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methobromide, dicyclomine, para-fluoro-hexahydrosiladifenidol and atropine. Muscarinic receptors characterized by inhibition of [3H]quinuclidinylbenzilate binding in membranes of bovine pial arteries were of the M2 subtype. In contrast pharmacological analysis of [3H]-quinuclidinylbenzilate binding in bovine intracerebral microvessels suggests the presence of an M4 subtype. Receptors mediating endothelium-dependent vasodilation in rabbit pial arteries were of the M3 subtype, whereas muscarinic receptors stimulating endothelium-independent phosphoinositide hydrolysis in bovine pial arteries were of the M1 subtype. These findings suggest that characteristics of muscarinic receptors in cerebral blood vessels vary depending on the type of vessel, cellular location and function mediated

  13. Substance Use Disorders and Suicide Attempts in Bipolar Subtypes

    Science.gov (United States)

    Sublette, M. Elizabeth; Carballo, Juan J.; Moreno, Carmen; Galfalvy, Hanga C.; Brent, David A.; Birmaher, Boris; Mann, J. John; Oquendo, Maria A.

    2009-01-01

    1. Abstract Bipolar disorder (BD) is associated with high rates of suicide attempt and completion. Substance use disorders (SUD) have been identified as potent risk factors for suicidal behavior in BD. However, little is known concerning differences between BD subtypes with regard to SUD as a risk factor for suicidal behavior. We studied previous suicidal behavior in adults with a major depressive episode in context of BD type I (BD-I; N=96) or BD type II (BD-II; N=42), with and without history of SUD. Logistic regressions assessed the association between SUD and suicide attempt history by BD type, and exploratory analyses examined the effects of other clinical characteristics on these relationships. SUD were associated with suicide attempt in BD-I but not BD-II, an effect not attributable to sample size differences. The higher suicide attempt rate associated with alcoholism in BD-I was mostly explained by higher aggression scores, and earlier age of BD onset increased the likelihood that alcohol use disorder would be associated with suicide attempt(s). The higher suicide attempt rate associated with other drug use disorders in BD-I was collectively explained by higher impulsivity, hostility, and aggression scores. The presence of both alcohol and drug use disorders increased odds of a history of suicide attempt in a multiplicative fashion: 97% of BD-I who had both comorbid drug and alcohol use disorders had made a suicide attempt. A critical next question is how to target SUD and aggressive traits for prevention of suicidal behavior in BD-I. PMID:18590916

  14. Burnout syndrome among dental students: a short version of the "Burnout Clinical Subtype Questionnaire" adapted for students (BCSQ-12-SS

    Directory of Open Access Journals (Sweden)

    Montero-Marin Jesus

    2011-12-01

    Full Text Available Abstract Background Burnout has been traditionally defined in relation to the dimensions of "exhaustion", "cynicism", and "inefficiency". More recently, the Burnout Clinical Subtype Questionnaire (BCSQ-12 further established three different subtypes of burnout: the "frenetic" subtype (related to "overload", the "under-challenged" subtype (related to "lack of development", and the "worn-out" subtype (related to "neglect". However, to date, these definitions have not been applied to students. The aims of this research were (1 to adapt a Spanish version of the BCSQ-12 for use with students, (2 to test its factorial validity, internal consistency, convergent and discriminant validity, and (3 to assess potential socio-demographic and occupational risk factors associated with the development of the subtypes. Method We used a cross-sectional design on a sample of dental students (n = 314 from Santiago and Huesca universities (Spain. Participants completed the Burnout Clinical Subtype Questionnaire Student Survey (BCSQ-12-SS, the Maslach Burnout Inventory Student Survey (MBI-SS, and a series of socio-demographic and occupational questions formulated for the specific purpose of this study. Data were subjected to exploratory factor analysis (EFA using the principal component method with varimax orthogonal rotation. To assess the relations with the criterion, we calculated the Pearson correlation coefficient (r, multiple correlation coefficient (Ry.123, and the coefficient of determination (R2y.123. To assess the association between the subtypes and the socio-demographic variables, we examined the adjusted odds ratio (OR obtained from multivariate logistic regression models. Results Factorial analyses supported the theoretical proposition of the BCSQ-12-SS, with α-values exceeding 0.80 for all dimensions. The "overload-exhaustion" relation was r = 0.59 (p y.123 = 0.62, 30.25% in "cynicism" (Ry.123 = 0.55, and 26.01% in "inefficiency" (Ry.123 = 0

  15. Pulmonary emphysema subtypes on computed tomography: the MESA COPD study.

    Science.gov (United States)

    Smith, Benjamin M; Austin, John H M; Newell, John D; D'Souza, Belinda M; Rozenshtein, Anna; Hoffman, Eric A; Ahmed, Firas; Barr, R Graham

    2014-01-01

    Pulmonary emphysema is divided into 3 major subtypes at autopsy: centrilobular, paraseptal, and panlobular emphysema. These subtypes can be defined by visual assessment on computed tomography (CT); however, clinical characteristics of emphysema subtypes on CT are not well defined. We developed a reliable approach to visual assessment of emphysema subtypes on CT and examined if emphysema subtypes have distinct characteristics. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with chronic obstructive pulmonary disease (COPD) and controls ages 50-79 years with ≥ 10 pack-years. Participants underwent CT following a standardized protocol. Definitions of centrilobular, paraseptal, and panlobular emphysema were obtained by literature review. Six-minute walk distance and pulmonary function were performed following guidelines. Twenty-seven percent of 318 smokers had emphysema on CT. Interrater reliability of emphysema subtype was substantial (K: 0.70). Compared with participants without emphysema, individuals with centrilobular or panlobular emphysema had greater dyspnea, reduced walk distance, greater hyperinflation, and lower diffusing capacity. In contrast, individuals with paraseptal emphysema were similar to controls, except for male predominance. Centrilobular, but not panlobular or paraseptal, emphysema was associated with greater smoking history (+21 pack-years P emphysema, was associated with reduced body mass index (-5 kg/m(2); P = .01). Other than for dyspnea, these findings were independent of the forced expiratory volume in 1 second. Seventeen percent of smokers without COPD on spirometry had emphysema, which was independently associated with reduced walk distance. Emphysema subtypes on CT are common in smokers with and without COPD. Centrilobular and panlobular emphysema, but not paraseptal emphysema, have considerable symptomatic and physiological consequences. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Is PIGD a legitimate motor subtype in Parkinson disease?

    Science.gov (United States)

    Kotagal, Vikas

    2016-06-01

    Parkinson disease is a chronic progressive syndrome with a broad array of clinical features. Different investigators have suggested the heterogeneous motor manifestations of early Parkinson disease can be conceptualized through a taxonomy of clinical subtypes including tremor-predominant and postural instability and gait difficulty-predominant subtypes. Although it is theoretically valuable to distinguish subtypes of Parkinson disease, the reality is that few patients fit these discrete categories well and many transition from exhibiting elements of one subtype to elements of another. In the time since the initial description of the postural instability and gait difficulty-predominant subtype, Parkinson disease clinical research has blossomed in many ways - including an increased emphasis on the role of medical comorbidities and extranigral pathologies in Parkinson disease as markers of prognostic significance. By conceptualizing the pathogenesis of an expansive disease process in the limited terms of categorical motor subtypes, we run the risk of overlooking or misclassifying clinically significant pathogenic risk factors that lead to the development of motor milestones such as falls and related axial motor disability. Given its critical influence on quality of life and overall prognosis, we are in need of a model of postural instability and gait difficulty-predominant features in Parkinson disease that emphasizes the overlooked pathological influence of aging and medical comorbidities on the development of axial motor burden and postural instability and gait difficulty-predominant features. This Point of View proposes thinking of postural instability and gait difficulties in Parkinson disease not as a discrete subtype, but rather as multidimensional continuum influenced by several overlapping age-related pathologies.

  17. Pulmonary Emphysema Subtypes on Computed Tomography in Smokers

    Science.gov (United States)

    Smith, Benjamin M.; Austin, John H.M.; Newell, John D.; D’Souza, Belinda M.; Rozenshtein, Anna; Hoffman, Eric A.; Ahmed, Firas; Barr, R. Graham

    2013-01-01

    Background Pulmonary emphysema is divided into three major subtypes at autopsy: centrilobular, paraseptal and panlobular emphysema. These subtypes can be defined by visual assessment on computed tomography (CT); however, clinical characteristics of emphysema subtypes on CT are not well-defined. We developed a reliable approach to visual assessment of emphysema subtypes on CT and examined if emphysema subtypes have distinct characteristics. Methods The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years with ≥10 pack-years. Participants underwent CT following a standardized protocol. Definitions of centrilobular, paraseptal and panlobular emphysema were obtained by literature review. Six-minute walk distance and pulmonary function were performed following guidelines. Results Twenty-seven percent of 318 smokers had emphysema on CT. Inter-rater reliability of emphysema subtype was substantial (K:0.70). Compared to participants without emphysema, individuals with centrilobular or panlobular emphysema had greater dyspnea, reduced walk distance, greater hyperinflation, and lower diffusing capacity. In contrast, individuals with PSE were similar to controls, except for male predominance. Centrilobular but not panlobular or paraseptal emphysema was associated with greater smoking history (+21 pack-years Pemphysema was associated with reduced body mass index (−5 kg/m2;P=0.01). Other than for dyspnea, these findings were independent of the forced expiratory volume in one second. Seventeen percent of smokers without COPD on spirometry had emphysema, which was independently associated with reduced walk distance. Conclusions Emphysema subtypes on CT are common in smokers with and without COPD. Centrilobular and panlobular emphysema but not paraseptal emphysema have considerable symptomatic and physiological consequences. PMID:24384106

  18. The natural history of primary progressive multiple sclerosis

    NARCIS (Netherlands)

    Koch, Marcus; Kingwell, Elaine; Rieckmann, Peter; Tremlett, Helen

    2009-01-01

    Background: Primary progressive multiple sclerosis (PPMS) carries the worst prognosis of the multiple sclerosis (MS) subtypes and is currently untreatable. A previous analysis of the British Columbia MS database challenged the view that disability progression is rapid in PPMS, but identified few

  19. Diagnosis and subtypes of adolescent antisocial personality disorder.

    Science.gov (United States)

    Jones, Meredith; Westen, Drew

    2010-04-01

    The present study examined the application of the Antisocial Personality Disorder (APD) diagnosis to adolescents and investigated the possibility of subtypes of APD adolescents. As part of a broader study of adolescent personality in clinically-referred patients, experienced clinicians provided personality data on a randomly selected patient in their care using the SWAP-II-A personality pathology instrument. Three hundred thirteen adolescents met adult DSM-IV diagnostic criteria for APD. To characterize adolescents with the disorder, we aggregated the data to identify the items most descriptive and distinctive of APD adolescents relative to other teenagers in the sample (N = 950). Q-factor analysis identified five personality subtypes: psychopathic-like, socially withdrawn, impulsive-histrionic, emotionally dysregulated, and attentionally dysregulated. The five subtypes differed in predictable ways on a set of external criteria related to global adaptive functioning, childhood family environment, and family history of psychiatric illness. Both the APD diagnosis and the empirically derived APD subtypes provided incremental validity over and above the DSM-IV disruptive behavior disorders in predicting global adaptive functioning, number of arrests, early-onset severe externalizing pathology, and quality of peer relationships. Although preliminary, these results provide support for the use of both APD and personality-based subtyping systems in adolescents.

  20. Clinically-inspired automatic classification of ovarian carcinoma subtypes

    Directory of Open Access Journals (Sweden)

    Aicha BenTaieb

    2016-01-01

    Full Text Available Context: It has been shown that ovarian carcinoma subtypes are distinct pathologic entities with differing prognostic and therapeutic implications. Histotyping by pathologists has good reproducibility, but occasional cases are challenging and require immunohistochemistry and subspecialty consultation. Motivated by the need for more accurate and reproducible diagnoses and to facilitate pathologists′ workflow, we propose an automatic framework for ovarian carcinoma classification. Materials and Methods: Our method is inspired by pathologists′ workflow. We analyse imaged tissues at two magnification levels and extract clinically-inspired color, texture, and segmentation-based shape descriptors using image-processing methods. We propose a carefully designed machine learning technique composed of four modules: A dissimilarity matrix, dimensionality reduction, feature selection and a support vector machine classifier to separate the five ovarian carcinoma subtypes using the extracted features. Results: This paper presents the details of our implementation and its validation on a clinically derived dataset of eighty high-resolution histopathology images. The proposed system achieved a multiclass classification accuracy of 95.0% when classifying unseen tissues. Assessment of the classifier′s confusion (confusion matrix between the five different ovarian carcinoma subtypes agrees with clinician′s confusion and reflects the difficulty in diagnosing endometrioid and serous carcinomas. Conclusions: Our results from this first study highlight the difficulty of ovarian carcinoma diagnosis which originate from the intrinsic class-imbalance observed among subtypes and suggest that the automatic analysis of ovarian carcinoma subtypes could be valuable to clinician′s diagnostic procedure by providing a second opinion.

  1. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

    2010-01-01

    Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

  2. Origin, imports and exports of HIV-1 subtype C in South Africa: A historical perspective.

    Science.gov (United States)

    Wilkinson, Eduan; Rasmussen, David; Ratmann, Oliver; Stadler, Tanja; Engelbrecht, Susan; de Oliveira, Tulio

    2016-12-01

    While the HIV epidemic in South Africa had a later onset than epidemics in other southern African countries, prevalence grew rapidly during the 1990's when the country was going through socio-political changes with the end of Apartheid. South Africa currently has the largest number of people living with HIV in the world and the epidemic is dominated by a unique subtype, HIV-1 subtype C. This large epidemic is also characterized by high level of genetic diversity. We hypothesize that this diversity is due to multiple introductions of the virus during the period of change. In this paper, we apply novel phylogeographic methods to estimate the number of viral imports and exports from the start of the epidemic to the present. We assembled 11,289 unique subtype C pol sequences from southern Africa. These represent one of the largest sequence datasets ever analyzed in the region. Sequences were stratified based on country of sampling and levels of genetic diversity were estimated for each country. Sequences were aligned and a maximum-likelihood evolutionary tree was inferred. Least-Squares Dating was then used to obtain a dated phylogeny from which we estimated the number of introductions into and exports out of South Africa using parsimony-based ancestral location reconstructions. Our results identified 189 viral introductions into South Africa with the largest number of introductions attributed to Zambia (n=109), Botswana (n=32), Malawi (n=26) and Zimbabwe (n=13). South Africa also exported many viral lineages to its neighbours. The bulk viral imports and exports appear to have occurred between 1985 and 2000, coincident with the period of socio-political transition. The high level of subtype C genetic diversity in South Africa is related to multiple introductions of the virus to the country. While the number of viral imports and exports we identified was highly sensitive to the number of samples included from each country, they mostly clustered around the period of

  3. The spectrum of aphasia subtypes and etiology in subacute stroke.

    Science.gov (United States)

    Hoffmann, Michael; Chen, Ren

    2013-11-01

    Aphasia is one of the most common stroke syndrome presentations, yet little is known about the spectrum of different subtypes or their stroke mechanisms. Yet, subtypes and etiology are known to influence the prognosis and recovery. Our aim is to analyze aphasia subtypes and etiology in a large subacute stroke population. Consecutive patients from a dedicated cognitive stroke registry were accrued. A validated cognitive screening examination was administered during the first month of stroke presentation, which enabled a diagnosis of 14 different aphasic subtypes. The evolution from one subtype to another in the acute and subacute period, at times, resulted in more than 1 subtype being diagnosed. Etiology of stroke was determined by the modified Trial of Org 10172 in Acute Stroke Treatment criteria that included intracerebral hemorrhage. Exclusions included dementia, chronic medical illness, substance abuse, and severe depression. Of 2389 stroke patients, after exclusions (n=593), aphasias numbered 625 (625 of 1796; 34.8%), and the subtype frequencies included Broca aphasia (n=170; 27.2%), anomic aphasia (n=165; 26.4%), global aphasia (n=119; 19.04%), and subcortical aphasia (n=57; 9.12%). Less frequent subtypes (total n=40; 6.7%) included transcortical aphasia (n=11), Wernicke aphasia (n=10), conduction aphasia (n=7), aphemia (n=3), semantic aphasia (n=3), crossed aphasia (n=3), pure word deafness (n=2), and foreign accent syndrome (n=1). Aphasia subtypes and etiologies had some significant associations (chi-square: 855.8, P valueaphasia had a significant association with small-vessel disease (SVD) (odds ratio [OR]=2.0254, 95% confidence interval [CI]: 1.3820-2.9681), and global aphasia patients mostly had cardioembolic (CE) causes (OR=2.3589, 95% CI: 1.5506-3.5885) and less likely SVD (OR=.2583, 95% CI: .1444-.4654). Other notable inferences were included. Wernicke aphasia was caused by either CE (6 of 12; 50%) or hemorrhage (4 of 12; 33.3%) in a combined 83% of

  4. Parkinson's disease severity and motor subtype influence physical capacity components

    Directory of Open Access Journals (Sweden)

    Marcelo Pinto Pereira

    2013-09-01

    Full Text Available The severity of Parkinson's disease (PD and PD's motor subtypes influence the components of physical capacity. The aim of this study was to investigate the impact of both PD severity and motor subtype in the performance of these components. Thirty-six PD patients were assigned into four groups: Tremor (TD initial and TD mild, akinetic-rigid (AR initial, and AR mild. Patients' strength, balance, coordination, mobility and aerobic capacity were evaluated and groups were compared using a two-way ANOVA (severity and subtype as factors. AR presents a poorer performance than TD in almost all tests. Also this performance was worsened with the advance of the disease in AR, contrary to TD. We conclude that AR and TD subgroups are different about their performance on physical capacity components, moreover, this performance worsens with the advance of the disease of the AR group, but not for TD.

  5. HLA-B27 subtypes among the Chukotka native groups

    International Nuclear Information System (INIS)

    Krylov, M.Y.; Alexeeva, L.I.; Erdesz, S.; Benevolenskaya, L.I.; Reveille, J.D.; Arnett, F.C.

    1995-01-01

    The purpose of this study was to assess the relative frequency of the known HLA-B27 subtypes in HLA-B27 positive Chukotka natives, which have higher frequencies of HLA-B27 (to 40%) and spondylarthropathies (to 2%) than the Russian Caucasian population. Using oligotyping of the polymerase-chain reaction amplified second and third exons of the HLA-B27 gene in 86 DNA samples from HLA-B27 positive individuals were successfully typed. All had HLA-B*2705, including 4 patients with Reiter's syndrome and 5 with ankylosing spondyloarthritis, except one Eskimo who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. With respect to HLA-B27 subtypes the indigenous populations from the eastern part of the Chukotka Peninsula are genetically more closely related to Caucasians than to Orientals. (author). 18 refs, 1 fig., 2 tabs

  6. Fixation Characteristics of Severe Amblyopia Subtypes: Which One is Worse?

    Science.gov (United States)

    Koylu, Mehmet Talay; Ozge, Gokhan; Kucukevcilioglu, Murat; Mutlu, Fatih Mehmet; Ceylan, Osman Melih; Akıncıoglu, Dorukcan; Ayyıldız, Onder

    2017-01-01

    To determine differences in macular sensitivity and fixation patterns in different subtypes of severe amblyopia. This case-control study enrolled a total of 73 male adults, including 18 with pure strabismic severe amblyopia, 19 with pure anisometropic severe amblyopia, 18 with mixed (strabismic plus anizometropic) severe amblyopia, and 18 healthy controls. MP-1 microperimetry was used to evaluate macular sensitivity, location of fixation, and stability of fixation. Mean macular sensitivity, stability of fixation, and location of fixation were significantly worse in all amblyopia subtypes when compared with healthy controls. Intergroup comparisons between amblyopia subtypes revealed that mean macular sensitivity, stability of fixation, and location of fixation were significantly worse in pure strabismic and mixed amblyopic eyes when compared with pure anisometropic amblyopic eyes. Strabismus seems to be a worse prognostic factor in severe amblyopia than anisometropia in terms of fixation characteristics and retinal sensitivity.

  7. HLA-B27 subtypes among the Chukotka native groups

    Energy Technology Data Exchange (ETDEWEB)

    Krylov, M.Y.; Alexeeva, L.I.; Erdesz, S.; Benevolenskaya, L.I. [Akademiya Meditsinskikh Nauk SSSR, Moscow (Russian Federation). Inst. Revmatizma; Reveille, J.D.; Arnett, F.C. [Texas Univ., Houston, TX (United States). Health Science Center

    1995-12-31

    The purpose of this study was to assess the relative frequency of the known HLA-B27 subtypes in HLA-B27 positive Chukotka natives, which have higher frequencies of HLA-B27 (to 40%) and spondylarthropathies (to 2%) than the Russian Caucasian population. Using oligotyping of the polymerase-chain reaction amplified second and third exons of the HLA-B27 gene in 86 DNA samples from HLA-B27 positive individuals were successfully typed. All had HLA-B*2705, including 4 patients with Reiter`s syndrome and 5 with ankylosing spondyloarthritis, except one Eskimo who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. With respect to HLA-B27 subtypes the indigenous populations from the eastern part of the Chukotka Peninsula are genetically more closely related to Caucasians than to Orientals. (author). 18 refs, 1 fig., 2 tabs.

  8. BCDForest: a boosting cascade deep forest model towards the classification of cancer subtypes based on gene expression data.

    Science.gov (United States)

    Guo, Yang; Liu, Shuhui; Li, Zhanhuai; Shang, Xuequn

    2018-04-11

    The classification of cancer subtypes is of great importance to cancer disease diagnosis and therapy. Many supervised learning approaches have been applied to cancer subtype classification in the past few years, especially of deep learning based approaches. Recently, the deep forest model has been proposed as an alternative of deep neural networks to learn hyper-representations by using cascade ensemble decision trees. It has been proved that the deep forest model has competitive or even better performance than deep neural networks in some extent. However, the standard deep forest model may face overfitting and ensemble diversity challenges when dealing with small sample size and high-dimensional biology data. In this paper, we propose a deep learning model, so-called BCDForest, to address cancer subtype classification on small-scale biology datasets, which can be viewed as a modification of the standard deep forest model. The BCDForest distinguishes from the standard deep forest model with the following two main contributions: First, a named multi-class-grained scanning method is proposed to train multiple binary classifiers to encourage diversity of ensemble. Meanwhile, the fitting quality of each classifier is considered in representation learning. Second, we propose a boosting strategy to emphasize more important features in cascade forests, thus to propagate the benefits of discriminative features among cascade layers to improve the classification performance. Systematic comparison experiments on both microarray and RNA-Seq gene expression datasets demonstrate that our method consistently outperforms the state-of-the-art methods in application of cancer subtype classification. The multi-class-grained scanning and boosting strategy in our model provide an effective solution to ease the overfitting challenge and improve the robustness of deep forest model working on small-scale data. Our model provides a useful approach to the classification of cancer subtypes

  9. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

    2010-01-01

    Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis.......Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

  10. Therapeutic response to benzodiazepine in panic disorder subtypes

    Directory of Open Access Journals (Sweden)

    Alexandre Martins Valença

    Full Text Available CONTEXT: This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam, a benzodiazepine. OBJECTIVES: To evaluate the clinical efficacy of clonazepam in a fixed dosage (2 mg/day, compared to placebo, in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes. TYPE OF STUDY: Randomized study with clonazepam and placebo. SETTING: Outpatient Anxiety and Depression Unit of the Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. PARTICIPANTS: 34 patients with a diagnosis of panic disorder with agoraphobia, between 18 and 55 years old. PROCEDURES: Administration of clonazepam or placebo for 6 weeks, in panic disorder patients, after they were classified within two subtypes of panic disorder: respiratory and non-respiratory. MAIN MEASUREMENTS: Changes in the number of panic attacks in comparison with the period before the beginning of the study; Hamilton Anxiety Scale; Global Clinical Impression Scale; and Patient's Global Impression scale. RESULTS: In the group that received clonazepam, by the end of the 6th week there was a statistically significant clinical improvement, shown by the remission of panic attacks (p < 0.001 and decrease in anxiety (p = 0.024. In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder, regarding the therapeutic response to clonazepam. CONCLUSION: Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder, suggesting there is no difference in the therapeutic response between the two subtypes.

  11. Competing endogenous RNA network analysis identifies critical genes among the different breast cancer subtypes.

    Science.gov (United States)

    Chen, Juan; Xu, Juan; Li, Yongsheng; Zhang, Jinwen; Chen, Hong; Lu, Jianping; Wang, Zishan; Zhao, Xueying; Xu, Kang; Li, Yixue; Li, Xia; Zhang, Yan

    2017-02-07

    Although competing endogenous RNAs (ceRNAs) have been implicated in many solid tumors, their roles in breast cancer subtypes are not well understood. We therefore generated a ceRNA network for each subtype based on the significance of both, positive co-expression and the shared miRNAs, in the corresponding subtype miRNA dys-regulatory network, which was constructed based on negative regulations between differentially expressed miRNAs and targets. All four subtype ceRNA networks exhibited scale-free architecture and showed that the common ceRNAs were at the core of the networks. Furthermore, the common ceRNA hubs had greater connectivity than the subtype-specific hubs. Functional analysis of the common subtype ceRNA hubs highlighted factors involved in proliferation, MAPK signaling pathways and tube morphogenesis. Subtype-specific ceRNA hubs highlighted unique subtype-specific pathways, like the estrogen response and inflammatory pathways in the luminal subtypes or the factors involved in the coagulation process that participates in the basal-like subtype. Ultimately, we identified 29 critical subtype-specific ceRNA hubs that characterized the different breast cancer subtypes. Our study thus provides new insight into the common and specific subtype ceRNA interactions that define the different categories of breast cancer and enhances our understanding of the pathology underlying the different breast cancer subtypes, which can have prognostic and therapeutic implications in the future.

  12. Value of subtyping in studies of irradiation and human leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Darby, S C

    1985-01-01

    The two largest studies of the effects of irradiation on humans in postnatal life are described. These are 1) the Ankylosing Spondylitis Study(ASS) carried out on patients given X-ray therapy as treatment for spondylitis in the UK and 2) the Life Span Study(LSS) carried out on the survivors of the atomic bombings of Hiroshima and Nagasaki. From these studies, a limited degree of subtyping of leukemias is indicated. Chronic lymphatic leukemia is much less readily induced by radiation than the other major subtypes. The inducibility of acute myeloid leukemia increases with age at exposure.

  13. Parent stress across molecular subtypes of children with Angelman syndrome.

    Science.gov (United States)

    Miodrag, N; Peters, S

    2015-09-01

    Parenting stress has been consistently reported among parents of children with developmental disabilities. However, to date, no studies have investigated the impact of a molecular subtype of Angelman syndrome (AS) on parent stress, despite distinct phenotypic differences among subtypes. Data for 124 families of children with three subtypes of AS: class I and II deletions (n = 99), imprinting centre defects (IC defects; n = 11) and paternal uniparental disomy (UPD; n = 14) were drawn from the AS Rare Diseases Clinical Research Network (RDCRN) database and collected from five research sites across the Unites States. The AS study at the RDCRN gathered health information to understand how the syndrome develops and how to treat it. Parents completed questionnaires on their perceived psychological stress, the severity of children's aberrant behaviour and children's sleep patterns. Children's adaptive functioning and developmental levels were clinically evaluated. Child-related stress reached clinical levels for 40% of parents of children with deletions, 100% for IC defects and 64.3% for UPD. Sleep difficulties were similar and elevated across subtypes. There were no differences between molecular subtypes for overall child and parent-related stress. However, results showed greater isolation and lack of perceived parenting skills for parents of children with UPD compared with deletions. Better overall cognition for children with deletions was significantly related to more child-related stress while their poorer adaptive functioning was associated with more child-related stress. For all three groups, the severity of children's inappropriate behaviour was positively related to different aspects of stress. How parents react to stress depends, in part, on children's AS molecular subtype. Despite falling under the larger umbrella term of AS, it is important to acknowledge the unique aspects associated with children's molecular subtype. Identifying these factors can

  14. The whole-genome landscape of medulloblastoma subtypes

    DEFF Research Database (Denmark)

    Northcott, Paul A.; Buchhalter, Ivo; Morrissy, A. Sorana

    2017-01-01

    actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target...... KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive...

  15. Burnout Subtypes and Absence of Self-Compassion in Primary Healthcare Professionals: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Jesus Montero-Marin

    Full Text Available Primary healthcare professionals report high levels of distress and burnout. A new model of burnout has been developed to differentiate three clinical subtypes: 'frenetic', 'underchallenged' and 'worn-out'. The aim of this study was to confirm the validity and reliability of the burnout subtype model in Spanish primary healthcare professionals, and to assess the explanatory power of the self-compassion construct as a possible protective factor.The study employed a cross-sectional design. A sample of n = 440 Spanish primary healthcare professionals (214 general practitioners, 184 nurses, 42 medical residents completed the Burnout Clinical Subtype Questionnaire (BCSQ-36, the Maslach Burnout Inventory General Survey (MBI-GS, the Self-Compassion Scale (SCS, the Utrecht Work Engagement Scale (UWES and the Positive and Negative Affect Schedule (PANAS. The factor structure of the BCSQ-36 was estimated using confirmatory factor analysis (CFA by the unweighted least squares method from polychoric correlations. Internal consistency (R was assessed by squaring the correlation between the latent true variable and the observed variables. The relationships between the BCSQ-36 and the other constructs were analysed using Spearman's r and multiple linear regression models.The structure of the BCSQ-36 fit the data well, with adequate CFA indices for all the burnout subtypes. Reliability was adequate for all the scales and sub-scales (R≥0.75. Self-judgement was the self-compassion factor that explained the frenetic subtype (Beta = 0.36; p<0.001; isolation explained the underchallenged (Beta = 0.16; p = 0.010; and over-identification the worn-out (Beta = 0.25; p = 0.001. Other significant associations were observed between the different burnout subtypes and the dimensions of the MBI-GS, UWES and PANAS.The typological definition of burnout through the BCSQ-36 showed good structure and appropriate internal consistence in Spanish primary healthcare professionals

  16. Subtypes of borderline personality disorder patients: a cluster-analytic approach.

    Science.gov (United States)

    Smits, Maaike L; Feenstra, Dine J; Bales, Dawn L; de Vos, Jasmijn; Lucas, Zwaan; Verheul, Roel; Luyten, Patrick

    2017-01-01

    The borderline personality disorder (BPD) population is notably heterogeneous, and this has potentially important implications for intervention. Identifying distinct subtypes of patients may represent a first step in identifying which treatments work best for which individuals. A cluster-analysis on dimensional personality disorder (PD) features, as assessed with the SCID-II, was performed on a sample of carefully screened BPD patients ( N  = 187) referred for mentalization-based treatment. The optimal cluster solution was determined using multiple indices of fit. The validity of the clusters was explored by investigating their relationship with borderline pathology, symptom severity, interpersonal problems, quality of life, personality functioning, attachment, and trauma history, in addition to demographic and clinical features. A three-cluster solution was retained, which identified three clusters of BPD patients with distinct profiles. The largest cluster ( n  = 145) consisted of patients characterized by "core BPD" features, without marked elevations on other PD dimensions. A second "Extravert/externalizing" cluster of patients ( n  = 27) was characterized by high levels of histrionic, narcissistic, and antisocial features. A third, smaller "Schizotypal/paranoid" cluster ( n  = 15) consisted of patients with marked schizotypal and paranoid features. Patients in these clusters showed theoretically meaningful differences in terms of demographic and clinical features. Three meaningful subtypes of BPD patients were identified with distinct profiles. Differences were small, even when controlling for severity of PD pathology, suggesting a strong common factor underlying BPD. These results may represent a stepping stone toward research with larger samples aimed at replicating the findings and investigating differential trajectories of change, treatment outcomes, and treatment approaches for these subtypes. The study was retrospectively registered 16 April 2010

  17. Isolation and characterization of a subtype C avian metapneumovirus circulating in Muscovy ducks in China.

    Science.gov (United States)

    Sun, Shikai; Chen, Feng; Cao, Sheng; Liu, Jiajia; Lei, Wen; Li, Guangwei; Song, Yongfeng; Lu, Junpeng; Liu, Chuang; Qin, Jianping; Li, Haiyan

    2014-07-25

    Subtype C avian metapneumovirus (aMPV-C), is an important pathogen that can cause egg-drop and acute respiratory diseases in poultry. To date, aMPV-C infection has not been documented in Muscovy ducks in China. Here, we isolated and characterized an aMPV-C, designated S-01, which has caused severe respiratory disease and noticeable egg drop in Muscovy duck flocks in south China since 2010. Electron microscopy showed that the isolate was an enveloped virus exhibiting multiple morphologies with a diameter of 20-500 nm. The S-01 strain was able to produce a typical cytopathic effect (CPE) on Vero cells and cause death in 10- to 11-day-old Muscovy duck embryos. In vivo infection of layer Muscovy ducks with the isolate resulted in typical clinical signs and pathological lesions similar to those seen in the original infected cases. We report the first complete genomic sequence of aMPV-C from Muscovy ducks. A phylogenetic analysis strongly suggested that the S-01 virus belongs to the aMPV-C family, sharing 92.3%-94.3% of nucleotide identity with that of aMPV-C, and was most closely related to the aMPV-C strains isolated from Muscovy ducks in France. The deduced eight main proteins (N, P, M, F, M2, SH, G and L) of the novel isolate shared higher identity with hMPV than with other aMPV (subtypes A, B and D). S-01 could bind a monoclonal antibody against the F protein of hMPV. Together, our results indicate that subtype-C aMPV has been circulating in Muscovy duck flocks in South China, and it is urgent for companies to develop new vaccines to control the spread of the virus in China.

  18. Bulimia nervosa-nonpurging subtype: closer to the bulimia nervosa-purging subtype or to binge eating disorder?

    Science.gov (United States)

    Jordan, Jennifer; McIntosh, Virginia V W; Carter, Janet D; Rowe, Sarah; Taylor, Kathryn; Frampton, Christopher M A; McKenzie, Janice M; Latner, Janet; Joyce, Peter R

    2014-04-01

    DSM-5 has dropped subtyping of bulimia nervosa (BN), opting to continue inclusion of the somewhat contentious diagnosis of BN-nonpurging subtype (BN-NP) within a broad BN category. Some contend however that BN-NP is more like binge eating disorder (BED) than BN-P. This study examines clinical characteristics, eating disorder symptomatology, and Axis I comorbidity in BN-NP, BN-P, and BED groups to establish whether BN-NP more closely resembles BN-P or BED. Women with BN-P (n = 29), BN-NP (n = 29), and BED (n = 54) were assessed at baseline in an outpatient psychotherapy trial for those with binge eating. Measures included the Structured Clinical Interviews for DSM-IV, Eating Disorder Examination, and Eating Disorder Inventory-2. The BN-NP subtype had BMIs between those with BN-P and BED. Both BN subtypes had higher Restraint and Drive for Thinness scores than BED. Body Dissatisfaction was highest in BN-NP and predicted BN-NP compared to BN-P. Higher Restraint and lower BMI predicted BN-NP relative to BED. BN-NP resembled BED with higher lifetime BMIs; and weight-loss clinic than eating disorder clinic attendances relative to the BN-P subtype. Psychiatric comorbidity was comparable except for higher lifetime cannabis use disorder in the BN-NP than BN-P subtype These results suggest that BN-NP sits between BN-P and BED however the high distress driving inappropriate compensatory behaviors in BN-P requires specialist eating disorder treatment. These results support retaining the BN-NP group within the BN category. Further research is needed to determine whether there are meaningful differences in outcome over follow-up. Copyright © 2013 Wiley Periodicals, Inc.

  19. Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

    Science.gov (United States)

    Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

    2016-08-15

    A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and

  20. Brain neurodevelopmental markers related to the deficit subtype of schizophrenia.

    Science.gov (United States)

    Takahashi, Tsutomu; Takayanagi, Yoichiro; Nishikawa, Yumiko; Nakamura, Mihoko; Komori, Yuko; Furuichi, Atsushi; Kido, Mikio; Sasabayashi, Daiki; Noguchi, Kyo; Suzuki, Michio

    2017-08-30

    Deficit schizophrenia is a homogeneous subtype characterized by a trait-like feature of primary and prominent negative symptoms, but the etiologic factors related to this specific subtype remain largely unknown. This magnetic resonance imaging study aimed to examine gross brain morphology that probably reflects early neurodevelopment in 38 patients with deficit schizophrenia, 37 patients with non-deficit schizophrenia, and 59 healthy controls. Potential brain neurodevelopmental markers investigated in this study were the adhesio interthalamica (AI), cavum septi pellucidi (CSP), and surface morphology (i.e., olfactory sulcus depth, sulcogyral pattern, and number of orbital sulci) of the orbitofrontal cortex (OFC). The subtype classification of schizophrenia patients was based on the score of Proxy for the Deficit Syndrome. The deficit schizophrenia group had a significantly shorter AI compared with the non-deficit group and controls. The deficit group, but not the non-deficit group, was also characterized by an altered distribution of the OFC sulcogyral pattern, as well as fewer posterior orbital sulcus compared with controls. Other neurodevelopmental markers did not differentiate the deficit and non-deficit subgroups. These results suggest that the deficit subtype of schizophrenia and its clinical manifestation may be at least partly related to prominent neurodevelopmental pathology. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  1. Outcomes of treatment for achalasia depend on manometric subtype

    NARCIS (Netherlands)

    Rohof, Wout O.; Salvador, Renato; Annese, Vito; Bruley des Varannes, Stanislas; Chaussade, Stanislas; Costantini, Mario; Elizalde, J. Ignasi; Gaudric, Marianne; Smout, Andre J.; Tack, Jan; Busch, Olivier R.; Zaninotto, Giovanni; Boeckxstaens, Guy E.

    2013-01-01

    Patients with achalasia are treated with either pneumatic dilation (PD) or laparoscopic Heller myotomy (LHM), which have comparable rates of success. We evaluated whether manometric subtype was associated with response to treatment in a large population of patients treated with either PD or LHM (the

  2. Social Withdrawal Subtypes during Early Adolescence in India

    Science.gov (United States)

    Bowker, Julie C.; Raja, Radhi

    2011-01-01

    The overarching goal of this study was to examine the associations between three social withdrawal subtypes (shyness, unsociability, avoidance), peer isolation, peer difficulties (victimization, rejection, exclusion, low acceptance), and loneliness in India during early adolescence. Participants were 194 adolescents in Surat, India (M age=13.35…

  3. Effects of tamsulosin metabolites at alpha-1 adrenoceptor subtypes

    NARCIS (Netherlands)

    Taguchi, K.; Saitoh, M.; Sato, S.; Asano, M.; Michel, M. C.

    1997-01-01

    We have investigated the affinity and selectivity of tamsulosin and its metabolites, M1, M2, M3, M4 and AM1, at the tissue and the cloned alpha-1 adrenoceptor subtypes in the radioligand binding and the functional studies. In the radioligand binding studies, the compounds competed for [3H]prazosin

  4. Psychosocial and Adaptive Deficits Associated with Learning Disability Subtypes

    Science.gov (United States)

    Backenson, Erica M.; Holland, Sara C.; Kubas, Hanna A.; Fitzer, Kim R.; Wilcox, Gabrielle; Carmichael, Jessica A.; Fraccaro, Rebecca L.; Smith, Amanda D.; Macoun, Sarah J.; Harrison, Gina L.; Hale, James B.

    2015-01-01

    Children with specific learning disabilities (SLD) have deficits in the basic psychological processes that interfere with learning and academic achievement, and for some SLD subtypes, these deficits can also lead to emotional and/or behavior problems. This study examined psychosocial functioning in 123 students, aged 6 to 11, who underwent…

  5. The global spread of HIV-1 subtype B epidemic

    NARCIS (Netherlands)

    Magiorkinis, Gkikas; Angelis, Konstantinos; Mamais, Ioannis; Katzourakis, Aris; Hatzakis, Angelos; Albert, Jan; Lawyer, Glenn; Hamouda, Osamah; Struck, Daniel; Vercauteren, Jurgen; Wensing, Annemarie; Alexiev, Ivailo; Åsjö, Birgitta; Balotta, Claudia; Gomes, Perpétua; Camacho, Ricardo J.; Coughlan, Suzie; Griskevicius, Algirdas; Grossman, Zehava; Horban, Anders; Kostrikis, Leondios G.; Lepej, Snjezana J.; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elizabeth; Schmit, Jean Claude; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Stylianou, Dora C.; Boucher, Charles A B; Nikolopoulos, Georgios; Vasylyeva, Tetyana; Friedman, Samuel R.; van de Vijver, David; Angarano, Gioacchino; Chaix, Marie Laure; de Luca, Andrea; Korn, Klaus; Loveday, Clive; Soriano, Vincent; Yerly, Sabine; Zazzi, Mauricio; Vandamme, Anne Mieke; Paraskevis, Dimitrios

    2016-01-01

    Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti

  6. Cognitive Profiling and Preliminary Subtyping in Chinese Developmental Dyslexia

    Science.gov (United States)

    Ho, Connie Suk-Han; Chan, David Wai-Ock; Lee, Suk-Han; Tsang, Suk-Man; Luan, Vivian Hui

    2004-01-01

    The present study examined the cognitive profile and subtypes of developmental dyslexia in a nonalphabetic script, Chinese. One hundred and forty-seven Chinese primary school children with developmental dyslexia were tested on a number of literacy and cognitive tasks. The results showed that rapid naming deficit and orthographic deficit were the…

  7. Longitudinal Stability of Phonological and Surface Subtypes of Developmental Dyslexia

    Science.gov (United States)

    Peterson, Robin L.; Pennington, Bruce F.; Olson, Richard K.; Wadsworth, Sally J.

    2014-01-01

    Limited evidence supports the external validity of the distinction between developmental phonological and surface dyslexia. We previously identified children ages 8 to 13 meeting criteria for these subtypes (Peterson, Pennington, & Olson, 2013) and now report on their reading and related skills approximately 5 years later. Longitudinal…

  8. Brief Report: Further Evidence of Sensory Subtypes in Autism

    Science.gov (United States)

    Lane, Alison E.; Dennis, Simon J.; Geraghty, Maureen E.

    2011-01-01

    Distinct sensory processing (SP) subtypes in autism have been reported previously. This study sought to replicate the previous findings in an independent sample of thirty children diagnosed with an Autism Spectrum Disorder. Model-based cluster analysis of parent-reported sensory functioning (measured using the Short Sensory Profile) confirmed the…

  9. Sensory Processing Subtypes in Autism: Association with Adaptive Behavior

    Science.gov (United States)

    Lane, Alison E.; Young, Robyn L.; Baker, Amy E. Z.; Angley, Manya T.

    2010-01-01

    Children with autism are frequently observed to experience difficulties in sensory processing. This study examined specific patterns of sensory processing in 54 children with autistic disorder and their association with adaptive behavior. Model-based cluster analysis revealed three distinct sensory processing subtypes in autism. These subtypes…

  10. Distinct Response Time Distributions in Attention Deficit Hyperactivity Disorder Subtypes

    Science.gov (United States)

    Querne, Laurent; Berquin, Patrick

    2009-01-01

    Objective: To address the issue of response time (RT) profiles in hyperactive-impulsive (ADHD-HI), inattentive (ADHD-IA), and combined (ADHD-C) subtypes of ADHD. We hypothesized that children with ADHD-HI should respond more rapidly than children without ADHD and children with ADHD-IA and ADHD-C should respond more slowly than children without…

  11. Breast cancer molecular subtype classifier that incorporates MRI features.

    Science.gov (United States)

    Sutton, Elizabeth J; Dashevsky, Brittany Z; Oh, Jung Hun; Veeraraghavan, Harini; Apte, Aditya P; Thakur, Sunitha B; Morris, Elizabeth A; Deasy, Joseph O

    2016-07-01

    To use features extracted from magnetic resonance (MR) images and a machine-learning method to assist in differentiating breast cancer molecular subtypes. This retrospective Health Insurance Portability and Accountability Act (HIPAA)-compliant study received Institutional Review Board (IRB) approval. We identified 178 breast cancer patients between 2006-2011 with: 1) ERPR + (n = 95, 53.4%), ERPR-/HER2 + (n = 35, 19.6%), or triple negative (TN, n = 48, 27.0%) invasive ductal carcinoma (IDC), and 2) preoperative breast MRI at 1.5T or 3.0T. Shape, texture, and histogram-based features were extracted from each tumor contoured on pre- and three postcontrast MR images using in-house software. Clinical and pathologic features were also collected. Machine-learning-based (support vector machines) models were used to identify significant imaging features and to build models that predict IDC subtype. Leave-one-out cross-validation (LOOCV) was used to avoid model overfitting. Statistical significance was determined using the Kruskal-Wallis test. Each support vector machine fit in the LOOCV process generated a model with varying features. Eleven out of the top 20 ranked features were significantly different between IDC subtypes with P machine-learning-based predictive model using features extracted from MRI that can distinguish IDC subtypes with significant predictive power. J. Magn. Reson. Imaging 2016;44:122-129. © 2016 Wiley Periodicals, Inc.

  12. Molecular Subtypes and Clinical Outcomes of Breast Cancer

    African Journals Online (AJOL)

    2010-01-04

    Jan 4, 2010 ... Some early work has started in earnest at both the. AKUH(N) and Kijabe Hospitals to try and stratify our breast cancer patients to those mentioned subtypes to help in both diagnosis and treatment. The limiting fac- tors are small numbers of patients expense to undertake the tests and lack of both internal ...

  13. [Distorted cognition of bodily sensations in subtypes of social anxiety].

    Science.gov (United States)

    Kanai, Yoshihiro; Sasaki, Shoko; Iwanaga, Makoto; Seiwa, Hidetoshi

    2010-02-01

    The purpose of this study was to investigate the relationship between subtypes of social anxiety and distorted cognition of bodily sensations. The package of questionnaires including the Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS) was administered to 582 undergraduate students. To identify subtypes of social anxiety, cluster analysis was conducted using scores of the SPS and SIAS. Five clusters were identified and labeled as follows: Generalized type characterized by intense anxiety in most social situations, Non-anxious type characterized by low anxiety levels in social situations, Averaged type whose anxiety levels are averaged, Interaction anxiety type who feels anxiety mainly in social interaction situations, and Performance anxiety type who feels anxiety mainly in performance situations. Results of an ANOVA indicated that individuals with interaction type fear the negative evaluation from others regarding their bodily sensations whereas individuals with performance type overestimate the visibility of their bodily sensations to others. Differences in salient aspects of cognitive distortion among social anxiety subtypes may show necessity to select intervention techniques in consideration of subtypes.

  14. A study of symptom profile and clinical subtypes of delirium

    OpenAIRE

    Meagher, David

    2012-01-01

    Delineating delirium phenomenology facilitates detection, understanding neuroanatomical endophenotypes, and patient management. This compendium reflects an integrated research plan executed over a five year period, employing detailed, standardized phenomenological assessments cross-sectionally and longitudinally. Motor activity studies were controlled and included both subjective and objective measures, aimed at identifying a new approach to defining this clinical subtype as a more pure motor...

  15. Central Timing Deficits in Subtypes of Primary Speech Disorders

    Science.gov (United States)

    Peter, Beate; Stoel-Gammon, Carol

    2008-01-01

    Childhood apraxia of speech (CAS) is a proposed speech disorder subtype that interferes with motor planning and/or programming, affecting prosody in many cases. Pilot data (Peter & Stoel-Gammon, 2005) were consistent with the notion that deficits in timing accuracy in speech and music-related tasks may be associated with CAS. This study…

  16. Preoperative subtyping of meningiomas by perfusion MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hao [University Medical Center Groningen, University of Groningen (Netherlands); Shanghai Jiaotong University affiliated First People' s Hospital, Department of Radiology, Shanghai (China); Department of Radiology, University of Groningen (Netherlands); Roediger, Lars A.; Oudkerk, Matthijs [University Medical Center Groningen, University of Groningen (Netherlands); Department of Radiology, University of Groningen (Netherlands); Shen, Tianzhen [Fudan University Huashan Hospital, Department of Radiology, Shanghai (China); Miao, Jingtao [Shanghai Jiaotong University affiliated First People' s Hospital, Department of Radiology, Shanghai (China)

    2008-10-15

    This paper aims to evaluate the value of perfusion magnetic resonance (MR) imaging in the preoperative subtyping of meningiomas by analyzing the relative cerebral blood volume (rCBV) of three benign subtypes and anaplastic meningiomas separately. Thirty-seven meningiomas with peritumoral edema (15 meningothelial, ten fibrous, four angiomatous, and eight anaplastic) underwent perfusion MR imaging by using a gradient echo echo-planar sequence. The maximal rCBV (compared with contralateral normal white matter) in both tumoral parenchyma and peritumoral edema of each tumor was measured. The mean rCBVs of each two histological subtypes were compared using one-way analysis of variance and least significant difference tests. A p value less than 0.05 indicated a statistically significant difference. The mean rCBV of meningothelial, fibrous, angiomatous, and anaplastic meningiomas in tumoral parenchyma were 6.93{+-}3.75, 5.61{+-}4.03, 11.86{+-}1.93, and 5.89{+-}3.85, respectively, and in the peritumoral edema 0.87{+-}0.62, 1.38{+-}1.44, 0.87{+-}0.30, and 3.28{+-}1.39, respectively. The mean rCBV in tumoral parenchyma of angiomatous meningiomas and in the peritumoral edema of anaplastic meningiomas were statistically different (p<0.05) from the other types of meningiomas. Perfusion MR imaging can provide useful functional information on meningiomas and help in the preoperative diagnosis of some subtypes of meningiomas. (orig.)

  17. Detection and subtyping avian metapneumovirus from turkeys in Iran.

    Science.gov (United States)

    Mayahi, Mansour; Momtaz, Hassan; Jafari, Ramezan Ali; Zamani, Pejman

    2017-01-01

    Avian metapneumovirus (aMPV) causes diseases like rhinotracheitis in turkeys, swollen head syndrome in chickens and avian rhinotracheitis in other birds. Causing respiratory problems, aMPV adversely affects production and inflicts immense economic losses and mortalities, especially in turkey flocks. In recent years, several serological and molecular studies have been conducted on this virus, especially in poultry in Asia and Iran. The purpose of the present study was detecting and subtyping aMPV by reverse transcriptase polymerase chain reaction (RT-PCR) from non-vaccinated, commercial turkey flocks in Iran for the first time. Sixty three meat-type unvaccinated turkey flocks from several provinces of Iran were sampled in major turkey abattoirs. Samples were tested by RT-PCR for detecting and subtyping aMPV. The results showed that 26 samples from three flocks (4.10%) were positive for viral RNA and all of the viruses were found to be subtype B of aMPV. As a result, vaccination especially against subtype B of aMPV should be considered in turkey flocks in Iran to control aMPV infections.

  18. Racial Differences by Ischemic Stroke Subtype: A Comprehensive Diagnostic Approach

    Directory of Open Access Journals (Sweden)

    Sarah Song

    2012-01-01

    Full Text Available Background. Previous studies have suggested that black populations have more small-vessel and fewer cardioembolic strokes. We sought to analyze racial differences in ischemic stroke subtype employing a comprehensive diagnostic workup with magnetic resonance-imaging-(MRI- based evaluation including diffusion-weighted imaging (DWI. Methods. 350 acute ischemic stroke patients admitted to an urban hospital with standardized comprehensive diagnostic evaluations were retrospectively analyzed. Ischemic stroke subtype was determined by three Trial of Org 10172 in Acute Stroke Treatment (TOAST classification systems. Results. We found similar proportions of cardioembolic and lacunar strokes in the black and white cohort. The only subtype category with a significant difference by race was “stroke of other etiology,” more common in whites. Black stroke patients were more likely to have an incomplete evaluation, but this did not reach significance. Conclusions. We found similar proportions by race of cardioembolic and lacunar strokes when employing a full diagnostic evaluation including DWI MRI. The relatively high rate of cardioembolism may have been underappreciated in black stroke patients when employing a CT approach to stroke subtype diagnosis. Further research is required to better understand the racial differences in frequency of “stroke of other etiology” and explore disparities in the extent of diagnostic evaluations.

  19. The global spread of HIV-1 subtype B epidemic

    NARCIS (Netherlands)

    G. Magiorkinis (Gkikas); K. Angelis (Konstantinos); I. Mamais (Ioannis); Katzourakis, A. (Aris); A. Hatzakis (Angelos); J. Albert (Jan); Lawyer, G. (Glenn); O. Hamouda (Osamah); D. Struck (Daniel); J. Vercauteren (Jurgen); A. Wensing (Amj); I. Alexiev (Ivailo); B. Åsjö (Birgitta); C. Balotta (Claudia); Gomes, P. (Perpétua); R.J. Camacho (Ricardo Jorge); S. Coughlan (Suzie); A. Griskevicius (Algirdas); Z. Grossman (Zehava); Horban, A. (Anders); L.G. Kostrikis (Leondios); Lepej, S.J. (Snjezana J.); K. Liitsola (Kirsi); M. Linka (Marek); C. Nielsen; D. Otelea (Dan); R. Paredes (Roger); M. Poljak (Mario); E. Puchhammer-Stöckl (Elisabeth); J.C. Schmit; A. Sonnerborg (Anders); D. Stanekova (Danica); M. Stanojevic (Maja); Stylianou, D.C. (Dora C.); C.A.B. Boucher (Charles); Nikolopoulos, G. (Georgios); Vasylyeva, T. (Tetyana); Friedman, S.R. (Samuel R.); D.A.M.C. van de Vijver (David); G. Angarano (Guiseppe); M.L. Chaix (Marie Laure); A. de Luca (Andrea); K. Korn (Klaus); Loveday, C. (Clive); V. Soriano (Virtudes); S. Yerly (Sabine); M. Zazzi; A.M. Vandamme (Anne Mieke); D. Paraskevis (Dimitrios)

    2016-01-01

    textabstractHuman immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa

  20. The subtype of VSD and the angiographic differentiation

    International Nuclear Information System (INIS)

    Choe, Kyu Ok; Sul, Jun Hee; Lee, Sung Kyu; Cho, Bum Koo; Hong, Sung Nok

    1985-01-01

    VSD is the most common congenital cardiac malformation and the natural history depends not only on the age of patients and the size of defect but the subtype of VSD as well, important factor in clinical management of those patients. In 110 patients, with surgically repaired VSD in Yonsei Medical Center in 1984, the subtype of VSDs evaluated by surgical observation were correlated with LV angiogram findings to verify the incidence of subtype in Korean and the diagnostic accuracy to predict the subtype by angiogram. 1. 110 patients included 64 boys and 46 girls, the age ranged from 3 months to 14 years (average 4.6 years old). 2. Angiographic findings were interpreted as follows; a. Perimembranous defects were profiled in LAO 60 .deg. LV angiogram and located below the aortic valve. In inlet excavation the shunted blood opacified the recess between septal leaflet of tricuspid valve and interventricular septum in early phase, in infundibular excavation opacified the recess between anterior leaflet of TV and anterior free wall of RV and in trabecular excavation the shunted blood traversed anterior portion of TV ring, opacified trabecular portion of RV cavity. b. Subarterial types were profiled in RAO 30 .deg. LV angiogram, just below aortic valve as well as pulmonic valve. Total infundibular defects were profiled in RAO 30 .deg. and LAO 60 .deg. LV angiogram subaortic in location in both views. c. In muscular VSD the profiled angle was varied according to the subtype but the defects were separated from the aortic valve as muscular septum interposed between the aortic valve and the defect. 3. The incidence of subtype of VSDs evaluated by surgical observation were as follows. Subarterial type : 32 cases (29.1%) Total infundibular defect : 5 cases (4.5%) Perimembranous type : 73 cases (66.3%) Infundibular excavation : 32 cases (29.2%) Trabecular excavation : 28 cases (25.5%) Inlet excavation : 10 cases (9.1%) Mixed : 3 cases (2.7%) Muscular type : 1 cases (0.9%) Total 63

  1. Clinical neurological characteristics of ischemic stroke subtypes in acute phase

    Directory of Open Access Journals (Sweden)

    S. I. Shkrobot

    2018-02-01

    Full Text Available Objectives. The aim of the present study was to clarify clinical neurological characteristics and different ischemic stroke subtypes unfavorable course predictors in acute phase. Material and Methods. 482 patients with different ischemic stroke subtypes were observed. Among them there were 125 (25.9 % with cardioembolic infarct (CEI, 119 (24.7 % with large artery atherosclerosis (LAAS infarct, 122 (25.3 % with lacunar stroke (LAC, 116 (24.1 % with stroke of undetermined etiology (UDE. The comparative analysis of clinical picture was performed. The predictors of unfavorable course of acute phase were established. Results. We have found out that severe neurological deficit, high mortality and the worst functional outcome during the first 14 days were observed in patients with CEI and LAAS. The highest frequency of early neurological deterioration (END was detected at LAC (in 22.7 % of patients. There was a relationship between END and presence of transient ischemic attack (TIA in past medical history, the level of systolic blood pressure (SBP at the beginning of the disease and the degree of carotid arteries stenosis on the side of lesion. The patients with LAC had mild neurological deficit and better prognosis compared with other ischemic stroke subtypes. Among the clinical factors that have impact on the CEI, LAAS and UDE acute phase course were: the size of lesion, the level of consciousness on the 1st day, the baseline SBP, patient’s age. At LAAS, the presence of transient ischemic attack (TIA in past medical history and low SBP in the onset of the disease (less than140 mm Hg has an additional prognostic value for an unfavorable functional outcome. The severity of LAC in acute period depended on its localization and size. Localization of LAC in the internal capsule, thalamus and pons were characterized by the highest severity. Conclusions. Clinical neurological features of ischemic stroke depend on its subtype and have some prognostic value

  2. Gene specific actions of thyroid hormone receptor subtypes.

    Directory of Open Access Journals (Sweden)

    Jean Z Lin

    Full Text Available There are two homologous thyroid hormone (TH receptors (TRs α and β, which are members of the nuclear hormone receptor (NR family. While TRs regulate different processes in vivo and other highly related NRs regulate distinct gene sets, initial studies of TR action revealed near complete overlaps in their actions at the level of individual genes. Here, we assessed the extent that TRα and TRβ differ in target gene regulation by comparing effects of equal levels of stably expressed exogenous TRs +/- T(3 in two cell backgrounds (HepG2 and HeLa. We find that hundreds of genes respond to T(3 or to unliganded TRs in both cell types, but were not able to detect verifiable examples of completely TR subtype-specific gene regulation. TR actions are, however, far from identical and we detect TR subtype-specific effects on global T(3 response kinetics in HepG2 cells and many examples of TR subtype specificity at the level of individual genes, including effects on magnitude of response to TR +/- T(3, TR regulation patterns and T(3 dose response. Cycloheximide (CHX treatment confirms that at least some differential effects involve verifiable direct TR target genes. TR subtype/gene-specific effects emerge in the context of widespread variation in target gene response and we suggest that gene-selective effects on mechanism of TR action highlight differences in TR subtype function that emerge in the environment of specific genes. We propose that differential TR actions could influence physiologic and pharmacologic responses to THs and selective TR modulators (STRMs.

  3. Molecular subtype classification of urothelial carcinoma in Lynch syndrome.

    Science.gov (United States)

    Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias; Jönsson, Mats; Sjödahl, Gottfrid; Nilbert, Mef; Liedberg, Fredrik

    2018-05-23

    Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as Urothelial-like tumors with only 20% being Genomically Unstable, Basal/SCC-like or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger data sets revealed that Lynch syndrome-associated UC share molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the Urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset. This article is protected by copyright. All rights reserved. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  4. Nicotine Receptor Subtype-Specific Effects on Auditory Evoked Oscillations and Potentials

    Science.gov (United States)

    Featherstone, Robert E.; Phillips, Jennifer M.; Thieu, Tony; Ehrlichman, Richard S.; Halene, Tobias B.; Leiser, Steven C.; Christian, Edward; Johnson, Edwin; Lerman, Caryn; Siegel, Steven J.

    2012-01-01

    receptors. Event-related gamma is strongly influenced by activation of α4β2, but not α7, receptor subtypes, while disruption of N40 amplitude requires the activation of multiple receptor subtypes. PMID:22911690

  5. Comparing two basic subtypes in OCD across three large community samples: a pure compulsive versus a mixed obsessive-compulsive subtype.

    Science.gov (United States)

    Rodgers, Stephanie; Ajdacic-Gross, Vladeta; Kawohl, Wolfram; Müller, Mario; Rössler, Wulf; Hengartner, Michael P; Castelao, Enrique; Vandeleur, Caroline; Angst, Jules; Preisig, Martin

    2015-12-01

    Due to its heterogeneous phenomenology, obsessive-compulsive disorder (OCD) has been subtyped. However, these subtypes are not mutually exclusive. This study presents an alternative subtyping approach by deriving non-overlapping OCD subtypes. A pure compulsive and a mixed obsessive-compulsive subtype (including subjects manifesting obsessions with/without compulsions) were analyzed with respect to a broad pattern of psychosocial risk factors and comorbid syndromes/diagnoses in three representative Swiss community samples: the Zurich Study (n = 591), the ZInEP sample (n = 1500), and the PsyCoLaus sample (n = 3720). A selection of comorbidities was examined in a pooled database. Odds ratios were derived from logistic regressions and, in the analysis of pooled data, multilevel models. The pure compulsive subtype showed a lower age of onset and was characterized by few associations with psychosocial risk factors. The higher social popularity of the pure compulsive subjects and their families was remarkable. Comorbidities within the pure compulsive subtype were mainly restricted to phobias. In contrast, the mixed obsessive-compulsive subtype had a higher prevalence and was associated with various childhood adversities, more familial burden, and numerous comorbid disorders, including disorders characterized by high impulsivity. The current comparison study across three representative community surveys presented two basic, distinct OCD subtypes associated with differing psychosocial impairment. Such highly specific subtypes offer the opportunity to learn about pathophysiological mechanisms specifically involved in OCD.

  6. Association between endometriosis and risk of histological subtypes of ovarian cancer

    DEFF Research Database (Denmark)

    Pearce, Celeste Leigh; Templeman, Claire; Rossing, Mary Anne

    2012-01-01

    Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes...

  7. Neurocognitive Impairments Are More Severe in the Binge-Eating/Purging Anorexia Nervosa Subtype Than in the Restricting Subtype.

    Science.gov (United States)

    Tamiya, Hiroko; Ouchi, Atushi; Chen, Runshu; Miyazawa, Shiho; Akimoto, Yoritaka; Kaneda, Yasuhiro; Sora, Ichiro

    2018-01-01

    Objective: To evaluate cognitive function impairment in patients with anorexia nervosa (AN) of either the restricting (ANR) or binge-eating/purging (ANBP) subtype. Method: We administered the Japanese version of the MATRICS Consensus Cognitive Battery to 22 patients with ANR, 18 patients with ANBP, and 69 healthy control subjects. Our participants were selected from among the patients at the Kobe University Hospital and community residents. Results: Compared to the healthy controls, the ANR group had significantly lower visual learning and social cognition scores, and the ANBP group had significantly lower processing speed, attention/vigilance, visual learning, reasoning/problem-solving, and social cognition scores. Compared to the ANR group, the ANBP group had significantly lower attention/vigilance scores. Discussion: The AN subtypes differed in cognitive function impairments. Participants with ANBP, which is associated with higher mortality rates than ANR, exhibited greater impairment severities, especially in the attention/vigilance domain, confirming the presence of impairments in continuous concentration. This may relate to the impulsivity, an ANBP characteristic reported in the personality research. Future studies can further clarify the cognitive impairments of each subtype by addressing the subtype cognitive functions and personality characteristics.

  8. Multiple Perspectives / Multiple Readings

    Directory of Open Access Journals (Sweden)

    Simon Biggs

    2005-01-01

    Full Text Available People experience things from their own physical point of view. What they see is usually a function of where they are and what physical attitude they adopt relative to the subject. With augmented vision (periscopes, mirrors, remote cameras, etc we are able to see things from places where we are not present. With time-shifting technologies, such as the video recorder, we can also see things from the past; a time and a place we may never have visited.In recent artistic work I have been exploring the implications of digital technology, interactivity and internet connectivity that allow people to not so much space/time-shift their visual experience of things but rather see what happens when everybody is simultaneously able to see what everybody else can see. This is extrapolated through the remote networking of sites that are actual installation spaces; where the physical movements of viewers in the space generate multiple perspectives, linked to other similar sites at remote locations or to other viewers entering the shared data-space through a web based version of the work.This text explores the processes involved in such a practice and reflects on related questions regarding the non-singularity of being and the sense of self as linked to time and place.

  9. The Shifting Subtypes of ADHD: Classification Depends on How Symptom Reports Are Combined

    Science.gov (United States)

    Rowland, Andrew S.; Skipper, Betty; Rabiner, David L.; Umbach, David M.; Stallone, Lil; Campbell, Richard A.; Hough, Richard L.; Naftel, A. J.; Sandler, Dale P.

    2008-01-01

    Research on the correlates of ADHD subtypes has yielded inconsistent findings, perhaps because the procedures used to define subtypes vary across studies. We examined this possibility by investigating whether the ADHD subtype distribution in a community sample was sensitive to different methods for combining informant data. We conducted a study to…

  10. Empirically Derived Learning Disability Subtypes: A Replication Attempt and Longitudinal Patterns over 15 Years.

    Science.gov (United States)

    Spreen, Otfried; Haaf, Robert G.

    1986-01-01

    Test scores of two groups of learning disabled children (N=63 and N=96) were submitted to cluster analysis in an attempt to replicate previously described subtypes. All three subtypes (visuo-perceptual, linguistic, and articulo-graphomotor types) were identified along with minimally and severely impaired subtypes. Similar clusters in the same…

  11. 1 original article diverse genetic subtypes of hiv-1 among female sex

    African Journals Online (AJOL)

    boaz

    Keywords: Diverse, HIV, subtypes, Female Sex workers and Vaccine ... significant probability that infection with this subtype occurred with a short incubation period (p< 0.05). Conclusion: This study .... regression was used to adjust for potential cofounders. .... TABLE 2: DISTRIBUTION OF HIV-1 SUBTYPES AMONG FSWS.

  12. Subtypes of dissociative (conversion) disorder in two tertiary hospitals in Bangladesh.

    Science.gov (United States)

    Ahsan, M S; Mullick, S I; Sobhan, M A; Khanam, M; Nahar, J S; Salam, M A; Ali, R; Islam, M; Kabir, M S

    2010-01-01

    Dissociative (conversion) disorders are common among the patients attending in and out patients of Psychiatry Department of tertiary hospitals in Bangladesh. This study was done to see the subtypes of dissociative (conversion) disorder according to International Classification of Diseases, Tenth Revision (ICD-10). This is a descriptive, cross sectional study done on 100 consecutive patients from the Departments of Psychiatry, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka and Dhaka Medical College Hospital (DMCH). Study period was July 2005 to June 2006. Among the patients of dissociative (conversion) disorder, mixed dissociative (conversion) disorder was found highest 34%, followed by dissociative convulsion 33%, dissociative motor disorders 19%, dissociative anaesthesia and sensory loss 5%, dissociative amnesia 4%, dissociative fugue 3%. However, the researcher did not find any multiple personality disorder which is relatively common in North America. This finding reflected that there are differences in prevalence of sub types of dissociative disorders in Bangladesh and Western countries.

  13. Effect of HIV type 1 subtype on virological and immunological response to combination antiretroviral therapy: evidence for a more rapid viral suppression for subtype A than subtype B-infected Greek individuals.

    Science.gov (United States)

    Paraskevis, Dimirios; Touloumi, Giota; Bakoyannis, Giorgos; Paparizos, Vassilios; Lazanas, Marios; Gargalianos, Panagiotis; Chryssos, Georgios; Antoniadou, Anastasia; Psichogiou, Mina; Panos, Georgios; Katsarou, Olga; Sambatakou, Helen; Kordossis, Theodoros; Hatzakis, Angelos

    2013-03-01

    Whether response to combination antiretroviral therapy (cART) differs between those infected with HIV-1 subtype A or B remains unclear. We compared virological and immunological response to cART in individuals infected with subtype A or B in an ethnically homogeneous population. Data derived from the Athens Multicenter AIDS Cohort Study (AMACS) and analysis were restricted to those of Greek origin. Time to virological response (confirmed HIV-RNA 500 copies/ml at any time or no response by month 6) were analyzed using survival models and CD4 changes after cART initiation using piecewise linear mixed effects models. Of the 571 subjects included in the analysis, 412 (72.2%) were infected with subtype B and 159 (27.8%) with subtype A. After adjusting for various prognostic factors, the rate of virological response was higher for those infected with subtype A versus B (adjusted HR: 1.35; 95% CI: 1.08-1.68; p=0.009). Subtype A was also marginally associated with a lower hazard of virological failure compared to subtype B (HR=0.73; 95% CI: 0.53-1.02; p=0.062). Further adjustment for treatment adherence did not substantially changed the main results. No significant differences were observed in the rates of CD4 increases by subtype. The overall median (95% CI) CD4 increase at 2 years of cART was 193 (175, 212) cells/μl. Our study, based on one of the largest homogeneous groups of subtype A and B infections in Europe, showed that individuals infected with subtype A had an improved virological but similar immunological response to cART compared to those infected with subtype B.

  14. Severe pulmonary hypertension associated with the acute motor sensory axonal neuropathy subtype of Guillain-Barré syndrome.

    Science.gov (United States)

    Rooney, Kris A; Thomas, Neal J

    2010-01-01

    To evaluate pulmonary hypertension associated with acute motor sensory axonal neuropathy subtype of Guillain-Barré syndrome. Guillain-Barré syndrome consists of a group of autoimmune disorders that generally manifest as symmetric, progressive, ascending paralysis. There are five subtypes of Guillain-Barré syndrome, and autonomic involvement has been described in all subtypes, including cardiovascular, vasomotor, or pseudomotor dysfunction of both the sympathetic and parasympathetic systems. Case report. Tertiary care pediatric intensive care unit. Three-yr-old female patient. None. Serial measurements of pulmonary artery pressure. We report the case of a young girl with acute motor sensory axonal neuropathy who presented with severe cardiovascular collapse secondary to severe pulmonary hypertension. In this patient, multiple factors may have played a role in the development of pulmonary hypertension including autonomic dysfunction, hypoventilation, and immobility as a risk for thrombosis and pulmonary emboli. It is possible that many other individuals suffering from severe forms of Guillain-Barré syndrome, especially those with significant autonomic dysfunction, may actually have undiagnosed and therefore untreated pulmonary hypertension. Therefore, it is recommended that clinicians caring for critically ill children with Guillain-Barré syndrome have a high index of suspicion for pulmonary hypertension and consider echocardiography if there are clinical signs of this potentially fatal process.

  15. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

    Energy Technology Data Exchange (ETDEWEB)

    Hashem, Anwar M. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah (Saudi Arabia); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada); Van Domselaar, Gary [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Li, Changgui; Wang, Junzhi [National Institute for the Control of Pharmaceutical and Biological Products, Beijing (China); She, Yi-Min; Cyr, Terry D. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Sui, Jianhua [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); He, Runtao [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Marasco, Wayne A. [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Li, Xuguang, E-mail: Sean.Li@hc-sc.gc.ca [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada)

    2010-12-10

    Research highlights: {yields} The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. {yields} Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. {yields} The universal antibodies cross-neutralize different influenza A subtypes. {yields} The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

  16. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

    International Nuclear Information System (INIS)

    Hashem, Anwar M.; Van Domselaar, Gary; Li, Changgui; Wang, Junzhi; She, Yi-Min; Cyr, Terry D.; Sui, Jianhua; He, Runtao; Marasco, Wayne A.; Li, Xuguang

    2010-01-01

    Research highlights: → The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. → Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. → The universal antibodies cross-neutralize different influenza A subtypes. → The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

  17. HIV subtype, epidemiological and mutational correlations in patients from Paraná, Brazil.

    Science.gov (United States)

    Silva, Monica Maria Gomes da; Telles, Flavio Queiroz; da Cunha, Clovis Arns; Rhame, Frank S

    2010-01-01

    Analyze patients with HIV infection from Curitiba, Paraná, their epidemiological characteristics and HIV RAM. Patients regularly followed in an ID Clinic had their medical data evaluated and cases of virological failure were analyzed with genotypic report. Patients with complete medical charts were selected (n = 191). Demographic and clinical characteristics were compared. One hundred thirty two patients presented with subtype B infection (69.1%), 41 subtype C (21.5%), 10 subtype F (5.2%), 7 BF (3.7%) and 1 CF (0.5%). Patients with subtype B infection had been diagnosed earlier than patients with subtype non-B. Also, subtype B infection was more frequent in men who have sex with men, while non-B subtypes occurred more frequently in heterosexuals and women. Patients with previous history of three classes of ARVs (n = 161) intake were selected to evaluate resistance. For RT inhibitors, 41L and 210W were more frequently observed in subtype B than in non-B strains. No differences between subtypes and mutations were observed to NNTRIs. Mutations at 10, 32 and 63 position of protease were more observed in subtype B viruses than non-B, while positions 20 and 36 of showed more amino acid substitutions in subtype non-B viruses. Patients with history of NFV intake were evaluated to resistance pathway. The 90M pathway was more frequent in subtypes B and non-B. Mutations previously reported as common in non-B viruses, such as 65R and 106M, were uncommon in our study. Mutations 63P and 36I, previously reported as common in HIV-1 subtypes B and C from Brazil, respectively, were common. There is a significant frequency of HIV-1 non-B infections in Paraná state, with isolates classified as subtypes C, F, BF and BC. Patients with subtype C infection were more frequently female, heterosexual and had a longer average time of HIV diagnosis.

  18. Lynx1 and Aβ1-42 bind competitively to multiple nicotinic acetylcholine receptor subtypes

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Arvaniti, Maria; Jensen, Majbrit M

    2016-01-01

    Lynx1 regulates synaptic plasticity in the brain by regulating nicotinic acetylcholine receptors (nAChRs). It is not known to which extent Lynx1 can bind to endogenous nAChR subunits in the brain or how this interaction is affected by Alzheimer's disease pathology. We apply affinity purification....... Incubation with Ws-Lynx1 decreases nicotine-mediated extracellular signal-regulated kinase phosphorylation in PC12 cells and striatal neurons, indicating that binding of Ws-Lynx1 is sufficient to inhibit signaling downstream of nAChRs. The effect of nicotine in PC12 cells is independent of α7 or α4β2 n...

  19. Multiple distinct subtypes of GABAergic neurons in mouse visual cortex identified by triple immunostaining

    Directory of Open Access Journals (Sweden)

    Yuri Gonchar

    2008-03-01

    Full Text Available The majority of cortical interneurons use GABA (gamma amino butyric acid as inhibitory neurotransmitter. GABAergic neurons are morphologically, connectionally, electrically and chemically heterogeneous. In rat cerebral cortex three distinct groups of GABAergic interneurons have been identifi ed by the expression of parvalbumin (PV, calretinin (CR and somatostatin (SOM. Recent studies in mouse cerebral cortex have revealed a different organization in which the CR and SOM populations are partially overlapping. Because CR and SOM neurons derive from different progenitors located in different embryonic structures, the coexpression of CR + SOM suggests that the chemical differentiation of interneurons is regulated postmitotically. Here, we have taken an important fi rst step towards understanding this process by triple immunostaining mouse visual cortex with a panel of antibodies, which has been used extensively for classifying developing interneurons. We have found at least 13 distinct groups of GABAergic neurons which include PV, CR, SOM, CCK (cholecystokinin, CR + SOM, CR + NPY (neuropeptide Y, CR + VIP (vasointestinal polypeptide, SOM + NPY, SOM + VIP, VIP + ChAT (choline acetyltransferase, CCK + NPY, CR + SOM + NPY and CR + SOM + VIP expressing cells. Triple immunostaining with PV, CR and SOM antibodies during postnatal development further showed that PV is never colocalized with CR and SOM. Importantly, expression of SOM and CR + SOM developed after the percentage of CR cells that do not express SOM has reached the mature level, suggesting that the chemical differentiation of SOM and CR + SOM neurons is a postnatal event, which may be controlled by transcriptional regulation.

  20. Multiple endocrine neoplasia similar to human subtype 2A in a dog ...

    African Journals Online (AJOL)

    Primary hyperparathyroidism was diagnosed by biochemical testing. Histopathology report was consistent with diagnosis of bilateral pheochromocytoma and parathyroid adenoma. Immunohistochemical staining was positive for calcitonin and synaptophysin, and negative for thyroglobulin, which confirmed medullary thyroid ...

  1. Structural features of subtype-selective EP receptor modulators.

    Science.gov (United States)

    Markovič, Tijana; Jakopin, Žiga; Dolenc, Marija Sollner; Mlinarič-Raščan, Irena

    2017-01-01

    Prostaglandin E2 is a potent endogenous molecule that binds to four different G-protein-coupled receptors: EP1-4. Each of these receptors is a valuable drug target, with distinct tissue localisation and signalling pathways. We review the structural features of EP modulators required for subtype-selective activity, as well as the structural requirements for improved pharmacokinetic parameters. Novel EP receptor subtype selective agonists and antagonists appear to be valuable drug candidates in the therapy of many pathophysiological states, including ulcerative colitis, glaucoma, bone healing, B cell lymphoma, neurological diseases, among others, which have been studied in vitro, in vivo and in early phase clinical trials. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Unique Migraine Subtypes, Rare Headache Disorders, and Other Disturbances.

    Science.gov (United States)

    Goadsby, Peter J

    2015-08-01

    The medical aphorism that common things happen commonly makes unique (and less common) migraine subtypes especially appropriate to review for the general neurologist. This article also identifies some rare headache disorders and other disturbances, and offers strategies to manage them. This article discusses migraine with brainstem aura, which is troublesome clinically and has had a change in terminology in the International Classification of Headache Disorders, Third Edition, beta version (ICHD-3 beta), and hemiplegic migraine, which is also troublesome in practice. The rare headache disorder hypnic headache and the exploding head syndrome are also discussed. When hypnic headache is recognized, it is eminently treatable, while exploding head syndrome is a benign condition with no reported consequences. Unique migraine subtypes, rare headache disorders, and other disturbances present to neurologists. When recognized, they can often be managed very well, which offers significant benefits to patients and practice satisfaction to neurologists.

  3. Etiologic stroke subtypes: updated definition and efficient workup strategies.

    Science.gov (United States)

    Mehndiratta, Prachi; Chapman Smith, Sherita; Worrall, Bradford B

    2015-01-01

    Stroke affects approximately 16.9 million individuals per year worldwide and is the second leading cause of death. Stroke represents a family of related, but distinct subtypes. Classifying stroke subtypes must take into account various aspects of a standardized stroke workup to allow optimization of treatment and prevention strategies. Secondary prevention and pharmacologic treatment is tailored based on stroke mechanism. Additionally prognostication and recurrent risk also depends on stroke etiology. Efficient workup of stroke relies on a thorough history, clinical examination, imaging studies, and putative mechanism of stroke that lead the treating physician to a particular etiological path. Here , we provide the reader with updated definitions of etiologic ischemic stroke types as well as efficient workup strategies.

  4. Reproductive profiles and risk of breast cancer subtypes

    DEFF Research Database (Denmark)

    Brouckaert, Olivier; Rudolph, Anja; Laenen, Annouschka

    2017-01-01

    Background: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis. Methods: We used...... pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer...... the risk for TNBC (OR = 0.78, CI 0.70-0.88, p diagnosis, whereas the association with luminal HER2-like BC was present only for early onset BC....

  5. The whole-genome landscape of medulloblastoma subtypes

    Science.gov (United States)

    Northcott, Paul A.; Buchhalter, Ivo; Morrissy, A. Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Groebner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H.; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M.; Erkek, Serap; Jones, David T.W.; Worst, Barbara C.; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D.; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D.; Wolf, Stephan; Robinson, Giles W.; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M.G.; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L.; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M.; Mora, Jaume; McLendon, Roger E.; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J.M.; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O.; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A.; Pfister, Stefan M.; Taylor, Michael D.; Lichter, Peter

    2018-01-01

    Summary Current therapies for medulloblastoma (MB), a highly malignant childhood brain tumor, impose debilitating effects on the developing child, warranting deployment of molecularly targeted treatments with reduced toxicities. Prior studies failed to disclose the full spectrum of driver genes and molecular processes operative in MB subgroups. Herein, we detail the somatic landscape across 491 sequenced MBs and molecular heterogeneity amongst 1,256 epigenetically analyzed cases, identifying subgroup-specific driver alterations including previously unappreciated actionable targets. Driver mutations explained the majority of Group 3 and Group 4 patients, remarkably enhancing previous knowledge. Novel molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions targeting KBTBD4 and ‘enhancer hijacking’ driving PRDM6 activation. Thus, application of integrative genomics to an unprecedented cohort of clinical samples derived from a single childhood cancer entity disclosed a series of new cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for treating MB patients. PMID:28726821

  6. Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

    Directory of Open Access Journals (Sweden)

    Michael W. Peck

    2017-01-01

    Full Text Available Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future.

  7. Osteosarcoma subtypes: Magnetic resonance and quantitative diffusion weighted imaging criteria.

    Science.gov (United States)

    Zeitoun, Rania; Shokry, Ahmed M; Ahmed Khaleel, Sahar; Mogahed, Shaimaa M

    2018-03-01

    Osteosarcoma (OS) is a primary bone malignancy, characterized by spindle cells producing osteoid. The objective of this study is to describe the magnetic resonance imaging (MRI) features of different OS subtypes, record their attenuation diffusion coefficient (ADC) values and to point to the relation of their pathologic base and their corresponding ADC value. We performed a retrospective observational lesion-based analysis for 31 pathologically proven osteosarcoma subtypes: osteoblastic (n = 9), fibroblastic (n = 8), chondroblastic (n = 6), para-osteal (n = 3), periosteal (n = 1), telangiectatic (n = 2), small cell (n = 1) and extra-skeletal (n = 1). On conventional images we recorded: bone of origin, epicenter, intra-articular extension, and invasion of articulating bones, skip lesions, distant metastases, pathological fractures, ossified matrix, hemorrhage and necrosis. We measured the mean ADC value for each lesion. Among the included OS lesions, 51.6% originated at the femur, 29% showed intra-articular extension, 16% invaded neighboring bone, 9% were associated with pathological fracture and 25.8% were associated with distant metastases. On MRI, all lesions showed ossified matrix, 35.5% showed hemorrhage and 58% showed necrosis. The mean ADC values for OS lesions ranged from 0.74 × 10 -3  mm 2 /s (recorded for conventional osteoblastic OS) to 1.50 × 10 -3  mm 2 /s (recorded for telangiectatic OS) with an average value of 1.16 ± 0.18 × 10 -3  mm 2 /s. Conventional chondroblastic OS recorded higher values compared to the other two conventional subtypes. Osteosarcoma has different pathologic subtypes which correspondingly vary in their imaging criteria and their ADC values. Copyright © 2018. Production and hosting by Elsevier B.V.

  8. Maltreatment and psychopathy subtypes in high-risk adolescent females

    OpenAIRE

    Coupland, Ruth Louise

    2011-01-01

    Psychopathy is often viewed as a unitary construct, however, research with adults and adolescent males has revealed two heterogeneous subtypes. Primary psychopathy is presumed to have biological underpinnings and is associated with low levels of anxiety and psychological distress. In contrast, secondary psychopathy is believed to result from exposure to adversity, including childhood maltreatment, and is associated with emotional reactivity, impulsivity, and comorbid psychological problems. T...

  9. Somatostatin receptor subtype expression in human thyroid tumours.

    Science.gov (United States)

    Klagge, A; Krause, K; Schierle, K; Steinert, F; Dralle, H; Fuhrer, D

    2010-04-01

    Somatostatin receptors (SSTR) are expressed in various endocrine tumours. The expression of SSTR at the tumour cell surface confers the possibility for diagnostic imaging and therapy of tumours using radiolabeled somatostatin analogues. The majority of currently available somatostatin analogues show a higher binding affinity for the SSTR2 subtype. To date, the precise expression pattern of the SSTR subtypes 1-5 in thyroid epithelial tumours remains to be determined. We investigated the mRNA expression of SSTR1-5 in benign and malignant epithelial thyroid tumours [20 cold thyroid nodules (CTNs), 20 toxic thyroid nodules (TTNs), 20 papillary, 20 follicular, and 5 anaplastic carcinomas (PTCs, FTCs, ATCs, respectively)] and compared them to normal surrounding thyroid tissues. Four out of five SSTR subtypes were detected in malignant thyroid tumours, benign neoplasia, and normal surrounding tissue with a predominant expression of SSTR2 and SSTR5, and a weak expression of SSTR1 and SSTR3. Weak SSTR4 mRNA expression was detected in some PTCs. Compared to normal thyroid tissue, SSTR2 was significantly upregulated in PTC and ATC. In addition significant upregulation of SSTR3 was found in PTC. SSTR5 mRNA expression was increased in PTC and FTC and significantly decreased in CTN and TTN compared to normal thyroid tissue. SSTR2 is the predominant subtype in thyroid epithelial tumours with a high expression pattern, in particular, in PTC . Perspectively, the expression of distinct SSTR in thyroid epithelial tumours might represent a promising avenue for diagnostics and therapy of advanced thyroid cancer with somatostatin analogues. Georg Thieme Verlag KG Stuttgart New York.

  10. Major depressive disorder subtypes to predict long-term course

    Science.gov (United States)

    van Loo, Hanna M.; Cai, Tianxi; Gruber, Michael J.; Li, Junlong; de Jonge, Peter; Petukhova, Maria; Rose, Sherri; Sampson, Nancy A.; Schoevers, Robert A.; Wardenaar, Klaas J.; Wilcox, Marsha A.; Al-Hamzawi, Ali Obaid; Andrade, Laura Helena; Bromet, Evelyn J.; Bunting, Brendan; Fayyad, John; Florescu, Silvia E.; Gureje, Oye; Hu, Chiyi; Huang, Yueqin; Levinson, Daphna; Medina-Mora, Maria Elena; Nakane, Yoshibumi; Posada-Villa, Jose; Scott, Kate M.; Xavier, Miguel; Zarkov, Zahari; Kessler, Ronald C.

    2016-01-01

    Background Variation in course of major depressive disorder (MDD) is not strongly predicted by existing subtype distinctions. A new subtyping approach is considered here. Methods Two data mining techniques, ensemble recursive partitioning and Lasso generalized linear models (GLMs) followed by k-means cluster analysis, are used to search for subtypes based on index episode symptoms predicting subsequent MDD course in the World Mental Health (WMH) Surveys. The WMH surveys are community surveys in 16 countries. Lifetime DSM-IV MDD was reported by 8,261 respondents. Retrospectively reported outcomes included measures of persistence (number of years with an episode; number of with an episode lasting most of the year) and severity (hospitalization for MDD; disability due to MDD). Results Recursive partitioning found significant clusters defined by the conjunctions of early onset, suicidality, and anxiety (irritability, panic, nervousness-worry-anxiety) during the index episode. GLMs found additional associations involving a number of individual symptoms. Predicted values of the four outcomes were strongly correlated. Cluster analysis of these predicted values found three clusters having consistently high, intermediate, or low predicted scores across all outcomes. The high-risk cluster (30.0% of respondents) accounted for 52.9-69.7% of high persistence and severity and was most strongly predicted by index episode severe dysphoria, suicidality, anxiety, and early onset. A total symptom count, in comparison, was not a significant predictor. Conclusions Despite being based on retrospective reports, results suggest that useful MDD subtyping distinctions can be made using data mining methods. Further studies are needed to test and expand these results with prospective data. PMID:24425049

  11. Refining developmental coordination disorder subtyping with multivariate statistical methods

    Directory of Open Access Journals (Sweden)

    Lalanne Christophe

    2012-07-01

    Full Text Available Abstract Background With a large number of potentially relevant clinical indicators penalization and ensemble learning methods are thought to provide better predictive performance than usual linear predictors. However, little is known about how they perform in clinical studies where few cases are available. We used Random Forests and Partial Least Squares Discriminant Analysis to select the most salient impairments in Developmental Coordination Disorder (DCD and assess patients similarity. Methods We considered a wide-range testing battery for various neuropsychological and visuo-motor impairments which aimed at characterizing subtypes of DCD in a sample of 63 children. Classifiers were optimized on a training sample, and they were used subsequently to rank the 49 items according to a permuted measure of variable importance. In addition, subtyping consistency was assessed with cluster analysis on the training sample. Clustering fitness and predictive accuracy were evaluated on the validation sample. Results Both classifiers yielded a relevant subset of items impairments that altogether accounted for a sharp discrimination between three DCD subtypes: ideomotor, visual-spatial and constructional, and mixt dyspraxia. The main impairments that were found to characterize the three subtypes were: digital perception, imitations of gestures, digital praxia, lego blocks, visual spatial structuration, visual motor integration, coordination between upper and lower limbs. Classification accuracy was above 90% for all classifiers, and clustering fitness was found to be satisfactory. Conclusions Random Forests and Partial Least Squares Discriminant Analysis are useful tools to extract salient features from a large pool of correlated binary predictors, but also provide a way to assess individuals proximities in a reduced factor space. Less than 15 neuro-visual, neuro-psychomotor and neuro-psychological tests might be required to provide a sensitive and

  12. Memory Processes in Learning Disability Subtypes of Children Born Preterm

    OpenAIRE

    McCoy, Thomasin E.; Conrad, Amy L.; Richman, Lynn C.; Nopoulos, Peg C.; Bell, Edward F.

    2012-01-01

    The purpose of this study was to evaluate immediate auditory and visual memory processes in learning disability subtypes of 40 children born preterm. Three subgroups of children were examined: (a) primary language disability group (n = 13), (b) perceptual-motor disability group (n = 14), and (c) no learning disability diagnosis group without identified language or perceptual-motor learning disability (n = 13). Between-group comparisons indicate no significant differences in immediate auditory...

  13. Anatomic mapping of molecular subtypes in diffuse glioma.

    Science.gov (United States)

    Tang, Qisheng; Lian, Yuxi; Yu, Jinhua; Wang, Yuanyuan; Shi, Zhifeng; Chen, Liang

    2017-09-15

    Tumor location served as an important prognostic factor in glioma patients was considered to postulate molecular features according to cell origin theory. However, anatomic distribution of unique molecular subtypes was not widely investigated. The relationship between molecular phenotype and histological subgroup were also vague based on tumor location. Our group focuses on the study of glioma anatomic location of distinctive molecular subgroups and histology subtypes, and explores the possibility of their consistency based on clinical background. We retrospectively reviewed 143 cases with both molecular information (IDH1/TERT/1p19q) and MRI images diagnosed as cerebral diffuse gliomas. The anatomic distribution was analyzed between distinctive molecular subgroups and its relationship with histological subtypes. The influence of tumor location, molecular stratification and histology diagnosis on survival outcome was investigated as well. Anatomic locations of cerebral diffuse glioma indicate varied clinical outcome. Based on that, it can be stratified into five principal molecular subgroups according to IDH1/TERT/1p19q status. Triple-positive (IDH1 and TERT mutation with 1p19q codeletion) glioma tended to be oligodendroglioma present with much better clinical outcome compared to TERT mutation only group who is glioblastoma inclined (median overall survival 39 months VS 18 months). Five molecular subgroups were demonstrated with distinctive locational distribution. This kind of anatomic feature is consistent with its corresponding histological subtypes. Each molecular subgroup in glioma has unique anatomic location which indicates distinctive clinical outcome. Molecular diagnosis can be served as perfect complementary tool for the precise diagnosis. Integration of histomolecular diagnosis will be much more helpful in routine clinical practice in the future.

  14. Functional characteristics of HIV-1 subtype C compatible with increased heterosexual transmissibility

    DEFF Research Database (Denmark)

    Walter, Brandon L; Armitage, Andrew E; Graham, Stephen C

    2009-01-01

    BACKGROUND: Despite the existence of over 50 subtypes and circulating recombinant forms of HIV-1, subtype C dominates the heterosexual pandemic causing approximately 56% of all infections. OBJECTIVE: To evaluate whether viral genetic factors may contribute to the observed subtype-C predominance. ....... CONCLUSION: As CD4-CCR5-T cells are key targets for genital HIV infection and cervical selection can favor compact V1-V2 loops and 316T, which increase viral infectivity, we propose that these conserved subtype-C motifs may contribute to transmission and spread of this subtype....

  15. Association of Blastocystis subtypes with diarrhea in children

    Science.gov (United States)

    Zulfa, F.; Sari, I. P.; Kurniawan, A.

    2017-08-01

    Blastocystis hominis is an intestinal zoonotic protozoa that epidemiological surveys have shown, is highly prevalent among children and may cause chronic diarrhea. This study aimed to identify Blastocystis subtypes among children and associate those subtypes to pathology. The study’s population was children aged 6-12 years old divided into asymptomatic and symptomatic (diarrhea) groups. The asymptomatic samples were obtained from primary school students in the Bukit Duri area of South Jakarta, while the symptomatic samples were obtained from patients who visited nearby primary health centers (Puskesmas). Symptomatic stool samples were examined inParasitology Laboratory FKUI. Microscopic examination of the stool samples was performed to screen for single Blastocystic infection, followed by culture, PCR of 18S rRNA, and sequencing. In the study, 53.2% of children (n = 156) harbored intestinal parasites, Blastocysts sp. A single infection of Blastocystis sp. was present in 69 (44.23%) samples, comprised of 36 symptomatic and 33 asymptomatic participants. The Blastocystis subtypes (STs) identified in this study were STs 1-4 ST3 was the most dominant and was observed with statistically significant higher frequency in the symptomatic group. ST4 was only found in one sample in the symptomatic group. While ST1 and ST2 were found more frequently in the asymptomatic group, no statistical association was observed. ST3 is more likely to be associated with clinical symptoms than ST1 and ST2.

  16. Somatoform disorders and the subtypes: do differences exist?

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2015-07-01

    Full Text Available Background: Psychiatric diagnoses, especially somatoform disorders, are based on phenomenology, i.e. the subjective experience of the symptoms by the patient. The concept of “medically unexplained symptoms” (MUS is now getting away with much focus on the symptoms per se rather than its explanation by some medical illness. Aim of the study: To study the symptom profile of somatoform disorders and to see its variability in relation to different subtypes of the disorder. Materials and methods: Hundred consecutive patients of somatoform disorders, diagnosed clinically based on the tenth revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10 criteria, were chosen after applying various inclusion and exclusion criteria.The Post Graduate Institute of Medical Education and Research (PGI Health Questionnaire N-2 was used to evaluate symptoms of the patients. Data was analysed with chi-square test. Result: Patients of somatization disorder (SD have significantly higher prevalence of symptoms related to eyes (p=.0412 and higher complaints of hot sensation in the body (p=.0007as compared to undifferentiated somatoform (UD disorder and other somatoform disorders. Hypochondriacal ideas are significantly less in UD and SD. Conclusion: Although traditionally, subtypes of somatoform disorders are supposed to have differences in the phenomenology, there is considerable overlap between them in clinical practice. It may mean that all somatoform disorders are virtually same and there may be no need to have many subtypes.

  17. Ruminative subtypes and impulsivity in risk for suicidal behavior.

    Science.gov (United States)

    Valderrama, Jorge; Miranda, Regina; Jeglic, Elizabeth

    2016-02-28

    Rumination has been previously linked to negative psychological outcomes, including depression and suicidal behavior. However, there has been conflicting research on whether or not two different subtypes of rumination - brooding and reflection - are more or less maladaptive. The present research sought to (1) examine whether individuals high in brooding but lower in reflection would show higher trait and behavioral impulsivity, relative to individuals low in brooding and low in reflection; and (2) examine impulsivity as a mediator of the relation between ruminative subtypes and suicidal ideation. In Study 1, participants (N=78) were recruited based on high, average, and low scores on a measure of brooding and reflective rumination. Individuals who scored high in brooding and average in reflection scored significantly higher in negative urgency, that is, in the tendency to act rashly in an attempt to reduce negative affect, than did those who scored low in brooding and low in reflection. Study 2 (N=1638) examined the relationship between ruminative subtypes, impulsivity, and suicide risk. We found an indirect relationship between brooding and suicide risk through lack of premeditation and lack of perseverance, independently of reflection. These findings are discussed in relation to cognitive risk for suicide. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. The global spread of HIV-1 subtype B epidemic.

    Science.gov (United States)

    Magiorkinis, Gkikas; Angelis, Konstantinos; Mamais, Ioannis; Katzourakis, Aris; Hatzakis, Angelos; Albert, Jan; Lawyer, Glenn; Hamouda, Osamah; Struck, Daniel; Vercauteren, Jurgen; Wensing, Annemarie; Alexiev, Ivailo; Åsjö, Birgitta; Balotta, Claudia; Gomes, Perpétua; Camacho, Ricardo J; Coughlan, Suzie; Griskevicius, Algirdas; Grossman, Zehava; Horban, Anders; Kostrikis, Leondios G; Lepej, Snjezana J; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elizabeth; Schmit, Jean Claude; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Stylianou, Dora C; Boucher, Charles A B; Nikolopoulos, Georgios; Vasylyeva, Tetyana; Friedman, Samuel R; van de Vijver, David; Angarano, Gioacchino; Chaix, Marie-Laure; de Luca, Andrea; Korn, Klaus; Loveday, Clive; Soriano, Vincent; Yerly, Sabine; Zazzi, Mauricio; Vandamme, Anne-Mieke; Paraskevis, Dimitrios

    2016-12-01

    Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Stroke subtype classification by geometrical descriptors of lesion shape.

    Directory of Open Access Journals (Sweden)

    Bastian Cheng

    Full Text Available Inference of etiology from lesion pattern in acute magnetic resonance imaging is valuable for management and prognosis of acute stroke patients. This study aims to assess the value of three-dimensional geometrical lesion-shape descriptors for stroke-subtype classification, specifically regarding stroke of cardioembolic origin.Stroke Etiology was classified according to ASCOD in retrospectively selected patients with acute stroke. Lesions were segmented on diffusion-weighed datasets, and descriptors of lesion shape quantified: surface area, sphericity, bounding box volume, and ratio between bounding box and lesion volume. Morphological measures were compared between stroke subtypes classified by ASCOD and between patients with embolic stroke of cardiac and non-cardiac source.150 patients (mean age 77 years; 95% CI, 65-80 years; median NIHSS 6, range 0-22 were included. Group comparison of lesion shape measures demonstrated that lesions caused by small-vessel disease were smaller and more spherical compared to other stroke subtypes. No significant differences of morphological measures were detected between patients with cardioembolic and non-cardioembolic stroke.Stroke lesions caused by small vessel disease can be distinguished from other stroke lesions based on distinctive morphological properties. However, within the group of embolic strokes, etiology could not be inferred from the morphology measures studied in our analysis.

  20. Association of human herpesvirus 6 subtypes with symptomatic apical periodontitis.

    Science.gov (United States)

    Hernádi, Katinka; Csoma, Eszter; Adám, Balázs; Szalmás, Anita; Gyöngyösi, Eszter; Veress, György; Ildikó-Márton; Kónya, József

    2011-09-01

    The occurrence of human herpesvirus (HHV) 6 subtypes A and B in apical periodontitis was determined. The relationship of HHV-6 subtypes to other disease associated herpesviruses, i.e., Epstein-Barr virus (EBV) and human cytomegalovirus, was also investigated. Forty apical periodontitis samples (17 symptomatic and 23 asymptomatic) and 40 healthy pulp control samples were collected. Nested polymerase chain reaction was used to detect HHV-6 DNA. HHV-6 DNA was observed in significantly higher frequencies in apical periodontitis samples than in control samples (20% vs. 2.5%; P = .03). Further classification of apical lesions revealed that subtype B of HHV-6 was significantly associated with large-sized and symptomatic lesions (P apical lesions (77%) harbored ≥1 of the tested herpesviruses: EBV was the most frequent herpesvirus (72.5%) in apical periodontitis, followed by HHV-6 (20%). Our findings suggest that EBV and HHV-6B infections can be associated with symptomatic apical periodontitis. Copyright © 2011 Mosby, Inc. All rights reserved.

  1. Multiple sclerosis

    Science.gov (United States)

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  2. Strategies for subtyping influenza viruses circulating in the Danish pig population

    DEFF Research Database (Denmark)

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona

    2010-01-01

    in the Danish pig population functional and rapid subtyping assays are required. The conventional RT-PCR influenza subtyping assays developed by Chiapponi et al. (2003) have been implemented and used for typing of influenza viruses found positive in a pan influenza A real time RT-PCR assay. The H1 and N1 assays......Influenza viruses are endemic in the Danish pig population and the dominant circulating subtypes are H1N1, a Danish H1N2 reassortant, and H3N2. Here we present our current and future strategies for influenza virus subtyping. For diagnostic and surveillance of influenza subtypes circulating...... were specific when applied on Danish influenza positive samples, whereas the N2 assay consistently showed several unspecific PCR products. A subset of positive influenza samples detected by the real time RT-PCR screening assay could not be subtyped using these assays. Therefore, new influenza subtyping...

  3. Distribution of human immunodeficiency virus type 1 subtypes in the State of Amazonas, Brazil, and subtype C identification

    International Nuclear Information System (INIS)

    Cunha, L.K.H.; Kashima, S.; Amarante, M.F.C.; Haddad, R.; Rodrigues, E.S.; Silva, K.L.T.; Lima, T.A.; Castro, D.B.; Brito, F.C.; Almeida, E.G.; Covas, D.T.; Malheiro, A.

    2012-01-01

    Few studies have reported the molecular epidemiological characterization of HIV-1 in the Northern region of Brazil. The present study reports the molecular and epidemiological characterization of 31 HIV-1 isolates from blood donors from the State of Amazonas who donated blood between April 2006 and March 2007. Serum/plasma samples from all donors were screened for HIV antibodies by ELISA and the results confirmed by Western blot analysis. Genomic DNA was extracted from the buffy coat using the Super Quik-Gene-DNA Isolation kit. Nested PCR was performed on the env, gag, and pol regions of HIV-1 using the Gene Amp PCR System 9700. Sequencing reactions were performed using the inner PCR primers and the DYEnamic™ ET Dye Terminator Kit, and phylogenetic analysis was performed using the gag, pol, and env gene sequences. We collected samples from 31 blood donors who tested positive for HIV-1 in confirmatory experiments. The male:female ratio of blood donors was 3.4:1, and the mean age was 32.4 years (range: 19 to 61 years). Phylogenetic analysis showed that subtype B is the most prevalent among Northern Brazilian HIV-1-seropositive blood donors. One HIV-1 subtype C and one circulating recombinant form (CRF-BF) of HIV-1 were identified in the State of Amazonas. This is the first study showing the occurrence of a possible “homogenous” subtype C in this region of Brazil. This finding could contribute to a better characterization of the HIV-1 strains that circulate in the country. Key words: HIV-1; Subtypes; Phylogenetic analysis; Blood donors; Molecular and epidemiological characterization

  4. Gene expression profiling, pathway analysis and subtype classification reveal molecular heterogeneity in hepatocellular carcinoma and suggest subtype specific therapeutic targets.

    Science.gov (United States)

    Agarwal, Rahul; Narayan, Jitendra; Bhattacharyya, Amitava; Saraswat, Mayank; Tomar, Anil Kumar

    2017-10-01

    A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis. The differential gene expression analysis using non-parametric Wilcoxon test revealed a total of 479 up-regulated and 91 down-regulated genes in HCC compared to controls. The list of top differentially expressed genes mainly consists of tumor/cancer associated genes, such as AFP, THBS4, LCN2, GPC3, NUF2, etc. The genes over-expressed in HCC were mainly associated with cell cycle pathways. In total, 59 kinases associated genes were found over-expressed in HCC, including TTK, MELK, BUB1, NEK2, BUB1B, AURKB, PLK1, CDK1, PKMYT1, PBK, etc. Overall four distinct HCC subtypes were predicted using consensus clustering method. Each subtype was unique in terms of gene expression, pathway enrichment and median survival. Conclusively, this study has exposed a number of interesting genes which can be exploited in future as potential markers of HCC, diagnostic as well as prognostic and subtype classification may guide for improved and specific therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Distribution of human immunodeficiency virus type 1 subtypes in the State of Amazonas, Brazil, and subtype C identification

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, L.K.H. [Departamento de Parasitologia, Universidade Federal do Amazonas, Manaus, AM (Brazil); Kashima, S.; Amarante, M.F.C.; Haddad, R.; Rodrigues, E.S. [Laboratório de Biologia Molecular, Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, K.L.T.; Lima, T.A.; Castro, D.B.; Brito, F.C.; Almeida, E.G. [Diretoria de Ensino e Pesquisa,Fundação de Hematologia e Hemoterapia do Amazonas, Manaus, AM (Brazil); Covas, D.T. [Laboratório de Biologia Molecular, Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Malheiro, A. [Departamento de Parasitologia, Universidade Federal do Amazonas, Manaus, AM (Brazil); Diretoria de Ensino e Pesquisa,Fundação de Hematologia e Hemoterapia do Amazonas, Manaus, AM (Brazil)

    2012-01-20

    Few studies have reported the molecular epidemiological characterization of HIV-1 in the Northern region of Brazil. The present study reports the molecular and epidemiological characterization of 31 HIV-1 isolates from blood donors from the State of Amazonas who donated blood between April 2006 and March 2007. Serum/plasma samples from all donors were screened for HIV antibodies by ELISA and the results confirmed by Western blot analysis. Genomic DNA was extracted from the buffy coat using the Super Quik-Gene-DNA Isolation kit. Nested PCR was performed on the env, gag, and pol regions of HIV-1 using the Gene Amp PCR System 9700. Sequencing reactions were performed using the inner PCR primers and the DYEnamic™ ET Dye Terminator Kit, and phylogenetic analysis was performed using the gag, pol, and env gene sequences. We collected samples from 31 blood donors who tested positive for HIV-1 in confirmatory experiments. The male:female ratio of blood donors was 3.4:1, and the mean age was 32.4 years (range: 19 to 61 years). Phylogenetic analysis showed that subtype B is the most prevalent among Northern Brazilian HIV-1-seropositive blood donors. One HIV-1 subtype C and one circulating recombinant form (CRF-BF) of HIV-1 were identified in the State of Amazonas. This is the first study showing the occurrence of a possible “homogenous” subtype C in this region of Brazil. This finding could contribute to a better characterization of the HIV-1 strains that circulate in the country. Key words: HIV-1; Subtypes; Phylogenetic analysis; Blood donors; Molecular and epidemiological characterization.

  6. MULTIPLE OBJECTS

    Directory of Open Access Journals (Sweden)

    A. A. Bosov

    2015-04-01

    Full Text Available Purpose. The development of complicated techniques of production and management processes, information systems, computer science, applied objects of systems theory and others requires improvement of mathematical methods, new approaches for researches of application systems. And the variety and diversity of subject systems makes necessary the development of a model that generalizes the classical sets and their development – sets of sets. Multiple objects unlike sets are constructed by multiple structures and represented by the structure and content. The aim of the work is the analysis of multiple structures, generating multiple objects, the further development of operations on these objects in application systems. Methodology. To achieve the objectives of the researches, the structure of multiple objects represents as constructive trio, consisting of media, signatures and axiomatic. Multiple object is determined by the structure and content, as well as represented by hybrid superposition, composed of sets, multi-sets, ordered sets (lists and heterogeneous sets (sequences, corteges. Findings. In this paper we study the properties and characteristics of the components of hybrid multiple objects of complex systems, proposed assessments of their complexity, shown the rules of internal and external operations on objects of implementation. We introduce the relation of arbitrary order over multiple objects, we define the description of functions and display on objects of multiple structures. Originality.In this paper we consider the development of multiple structures, generating multiple objects.Practical value. The transition from the abstract to the subject of multiple structures requires the transformation of the system and multiple objects. Transformation involves three successive stages: specification (binding to the domain, interpretation (multiple sites and particularization (goals. The proposed describe systems approach based on hybrid sets

  7. Superficial basal cell carcinoma: A comparison of superficial only subtype with superficial combined with other subtypes by age, sex and anatomic site in 3150 cases.

    Science.gov (United States)

    Pyne, John H; Myint, Esther; Barr, Elizabeth M; Clark, Simon P; David, Michael; Na, Renua; Hou, Ruihang

    2017-08-01

    Basal cell carcinoma (BCC) may present as superficial subtype alone (sBCC) or superficial combined with other subtypes. The objective of this study was to compare sBCC without or with other BCC subtypes by age, sex and anatomic site. We retrospectively collected superficial BCC with the above characteristics from an Australian center during 2009 to 2014. We recorded 1528 sBCC and 1622 superficial BCC combined with other BCC subtype cases. Males numbered 2007 and females 1140. On males, head sites (forehead, cheek, nose and ear combined) compared to limb plus trunk sites displayed a higher incidence of superficial BCC combined with either nodular and or aggressive BCC subtypes (OR 13.15 CI 95% 8.9-19.5 P < .0001). On females a similar comparison also found a higher incidence of superficial BCC combined with solid subtype BCC on head sites compared to trunk and limb sites (OR 9.66 CI 95% 5.8-16.1 P < .0001). Superficial BCC alone is more likely on younger females on trunk and limb sites. Small partial biopsies reported as sBCC may miss other BCC subtypes present with higher risk on facial sites for males and females. Males had smaller proportions of superficial only subtype BCC on facial and ear sites compared to females. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. The Region of Difference Four is a Robust Genetic Marker for Subtyping Mycobacterium caprae Isolates and is Linked to Spatial Distribution of Three Subtypes.

    Science.gov (United States)

    Rettinger, A; Broeckl, S; Fink, M; Prodinger, W M; Blum, H; Krebs, S; Domogalla, J; Just, F; Gellert, S; Straubinger, R K; Büttner, M

    2017-06-01

    Alpine Mycobacterium caprae isolates found in cattle and red deer display at least three genetic variations in the region of difference four (RD4) that can be used for further differentiation of the isolates into the subtypes 'Allgäu', 'Karwendel' and 'Lechtal'. Each genomic subtype is thereby characterized by a specific nucleotide deletion pattern in the 12.7-kb RD4 region. Even though M. caprae infections are frequently documented in cattle and red deer, little is known about the transmission routes. Hence, robust markers for M. caprae subtyping are needed to gain insight into the molecular epidemiology. For this reason, a rapid and robust multiplex PCR was developed for the simultaneous detection of three M. caprae RD4 subtypes and was used to subtype a total number of 241 M. caprae isolates from animals (145 cattle, 95 red deer and one fox) from Bavaria and Austria. All three subtypes occur spatially distributed and are found in cattle and in red deer suggesting transmission between the two species. As subtypes are genetically stable in both species it is hypothesized that the described genetic variations developed within the host due to 'within-host replication'. The results of this study recommend the genomic RD4 region as a reliable diagnostic marker for M. caprae subtype differentiation. © 2015 Blackwell Verlag GmbH.

  9. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

    Directory of Open Access Journals (Sweden)

    Hsu Hui-Chi

    2011-04-01

    Full Text Available Abstract Background Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Methods Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. Results We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was

  10. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

    International Nuclear Information System (INIS)

    Kao, Kuo-Jang; Chang, Kai-Ming; Hsu, Hui-Chi; Huang, Andrew T

    2011-01-01

    Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was consistent with a unique subset of luminal A intrinsic

  11. The Genetic Diversity and Evolution of HIV-1 Subtype B Epidemic in Puerto Rico

    Directory of Open Access Journals (Sweden)

    Pablo López

    2015-12-01

    Full Text Available HIV-1 epidemics in Caribbean countries, including Puerto Rico, have been reported to be almost exclusively associated with the subtype B virus (HIV-1B. However, while HIV infections associated with other clades have been only sporadically reported, no organized data exist to accurately assess the prevalence of non-subtype B HIV-1 infection. We analyzed the nucleotide sequence data of the HIV pol gene associated with HIV isolates from Puerto Rican patients. The sequences (n = 945 were obtained from our “HIV Genotyping” test file, which has been generated over a period of 14 years (2001–2014. REGA subtyping tool found the following subtypes: B (90%, B-like (3%, B/D recombinant (6%, and D/B recombinant (0.6%. Though there were fewer cases, the following subtypes were also found (in the given proportions: A1B (0.3%, BF1 (0.2%, subtype A (01-AE (0.1%, subtype A (A2 (0.1%, subtype F (12BF (0.1%, CRF-39 BF-like (0.1%, and others (0.1%. Some of the recombinants were identified as early as 2001. Although the HIV epidemic in Puerto Rico is primarily associated with HIV-1B virus, our analysis uncovered the presence of other subtypes. There was no indication of subtype C, which has been predominantly associated with heterosexual transmission in other parts of the world.

  12. The Genetic Diversity and Evolution of HIV-1 Subtype B Epidemic in Puerto Rico.

    Science.gov (United States)

    López, Pablo; Rivera-Amill, Vanessa; Rodríguez, Nayra; Vargas, Freddie; Yamamura, Yasuhiro

    2015-12-23

    HIV-1 epidemics in Caribbean countries, including Puerto Rico, have been reported to be almost exclusively associated with the subtype B virus (HIV-1B). However, while HIV infections associated with other clades have been only sporadically reported, no organized data exist to accurately assess the prevalence of non-subtype B HIV-1 infection. We analyzed the nucleotide sequence data of the HIV pol gene associated with HIV isolates from Puerto Rican patients. The sequences (n = 945) were obtained from our "HIV Genotyping" test file, which has been generated over a period of 14 years (2001-2014). REGA subtyping tool found the following subtypes: B (90%), B-like (3%), B/D recombinant (6%), and D/B recombinant (0.6%). Though there were fewer cases, the following subtypes were also found (in the given proportions): A1B (0.3%), BF1 (0.2%), subtype A (01-AE) (0.1%), subtype A (A2) (0.1%), subtype F (12BF) (0.1%), CRF-39 BF-like (0.1%), and others (0.1%). Some of the recombinants were identified as early as 2001. Although the HIV epidemic in Puerto Rico is primarily associated with HIV-1B virus, our analysis uncovered the presence of other subtypes. There was no indication of subtype C, which has been predominantly associated with heterosexual transmission in other parts of the world.

  13. Brn3a regulates neuronal subtype specification in the trigeminal ganglion by promoting Runx expression during sensory differentiation

    Directory of Open Access Journals (Sweden)

    Raisa Eng S

    2010-01-01

    Full Text Available Abstract The transcription factor Brn3a, product of the pou4f1 gene, is expressed in most sensory neurons throughout embryogenesis. Prior work has demonstrated a role for Brn3a in the repression of early neurogenic genes; here we describe a second major role for Brn3a in the specification of sensory subtypes in the trigeminal ganglion (TG. Sensory neurons initially co-express multiple Trk-family neurotrophin receptors, but are later marked by the unique expression of TrkA, TrkB or TrkC. Maturation of these sensory subtypes is known to depend on the expression of Runx transcription factors. Newborn Brn3a knockout mice fail to express TrkC, which is associated in the TG with mechanoreceptors, plus a set of functional genes associated with nociceptor subtypes. In embryonic Brn3a-/- ganglia, the normal expression of Runx3 is never initiated in TrkC+ neurons, and Runx1 expression is greatly attenuated in TrkA+ nociceptors. These changes are accompanied by expanded expression of TrkB in neurons that abnormally express multiple Trks, followed by the loss of TrkC and TrkA expression. In transgenic embryos expressing a Brn3a-VP16 dominant transactivator, Runx3 mRNA expression is increased, suggesting that it is a direct regulatory target of Brn3a. Chromatin immunoprecipitation confirms that Brn3a binds in vivo to a conserved upstream enhancer element within histone H3-acetylated chromatin in the Runx3 locus. Together these data show that Brn3a acts upstream of the Runx factors, which then repress TrkB expression to allow establishment of the non-overlapping Trk receptor profiles and correct terminally differentiated phenotypes.

  14. Clinical Features Associated with Delirium Motor Subtypes in Older Inpatients: Results of a Multicenter Study.

    Science.gov (United States)

    Morandi, Alessandro; Di Santo, Simona G; Cherubini, Antonio; Mossello, Enrico; Meagher, David; Mazzone, Andrea; Bianchetti, Angelo; Ferrara, Nicola; Ferrari, Alberto; Musicco, Massimo; Trabucchi, Marco; Bellelli, Giuseppe

    2017-10-01

    To date motor subtypes of delirium have been evaluated in single-center studies with a limited examination of the relationship between predisposing factors and motor profile of delirium. We sought to report the prevalence and clinical profile of subtypes of delirium in a multicenter study. This is a point prevalence study nested in the "Delirium Day 2015", which included 108 acute and 12 rehabilitation wards in Italy. Delirium was detected using the 4-AT and motor subtypes were measured with the Delirium Motor Subtype Scale (DMSS). A multinomial logistic regression was used to determine the factors associated with delirium subtypes. Of 429 patients with delirium, the DMSS was completed in 275 (64%), classifying 21.5% of the patients with hyperactive delirium, 38.5% with hypoactive, 27.3% with mixed and 12.7% with the non-motor subtype. The 4-AT score was higher in the hyperactive subtype, similar in the hypoactive, mixed subtypes, while it was lowest in the non-motor subtype. Dementia was associated with all three delirium motor subtypes (hyperactive, OR 3.3, 95% CI: 1.2-8.7; hypoactive, OR 2.8, 95% CI: 1.2-6.5; mixed OR 2.6, 95% CI: 1.1-6.2). Atypical antipsychotics were associated with hypoactive delirium (OR 0.23, 95% CI: 0.1-0.7), while intravenous lines were associated with mixed delirium (OR 2.9, 95% CI: 1.2-6.9). The study shows that hypoactive delirium is the most common subtype among hospitalized older patients. Specific clinical features were associated with different delirium subtypes. The use of standardized instruments can help to characterize the phenomenology of different motor subtypes of delirium. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus.

    Science.gov (United States)

    Male, Christoph; Foulon, Denise; Hoogendoorn, Hugh; Vegh, Patricia; Silverman, Earl; David, Michèle; Mitchell, Lesley

    2005-12-15

    Study objectives were to determine, in children with systemic lupus erythematosus (SLE), (1) the association of antiphosholipid antibody (APLA) subtypes with thrombotic events (TEs) and (2) the predictive value of persistent versus transient antibodies for TEs. This is a cohort study of 58 SLE children in whom lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), anti-beta2-glycoprotein-I (anti-beta2-GPI), and antiprothrombin (anti-PT) were assessed on at least 2 occasions (more than 3 months apart). Antibodies were classified as persistent (positive on at least 2 occasions) or transient (positive once). Outcomes were symptomatic TEs confirmed by objective radiographic tests identified retrospectively and prospectively. Seven of the 58 patients (12%) had 10 TEs; 5 patients had TEs during prospective follow-up. Persistent LAs showed the strongest association with TEs (P < .001). Persistent ACLAs (P = .003) and anti-beta2-GPI (P = .002) were significantly associated with TEs; anti-PT (P = .063) showed a trend. Persistent or transient LAs and anti-beta2-GPI showed similar strength of association, while ACLAs and anti-PT were no longer associated with TEs. Positivity for multiple APLA subtypes showed stronger associations with TEs than for individual APLA subtypes because of improved specificity. Lupus anticoagulant is the strongest predictor of the risk of TEs; other APLA subtypes provide no additional diagnostic value. Anticardiolipin antibodies and anti-PT require serial testing because only persistent antibodies are associated with TEs.

  16. Diabetes, obesity, and recommended fruit and vegetable consumption in relation to food environment sub-types: a cross-sectional analysis of Behavioral Risk Factor Surveillance System, United States Census, and food establishment data.

    Science.gov (United States)

    Frankenfeld, Cara L; Leslie, Timothy F; Makara, Matthew A

    2015-05-14

    Social and spatial factors are an important part of individual and community health. The objectives were to identify food establishment sub-types and evaluate prevalence of diabetes, obesity, and recommended fruit and vegetable consumption in relation to these sub-types in the Washington DC metropolitan area. A cross-sectional study design was used. A measure of retail food environment was calculated as the ratio of number of sources of unhealthier food options (fast food, convenience stores, and pharmacies) to healthier food options (grocery stores and specialty food stores). Two categories were created: ≤ 1.0 (healthier options) and > 1.0 (unhealthier options). k-means clustering was used to identify clusters based on proportions of grocery stores, restaurants, specialty food, fast food, convenience stores, and pharmacies. Prevalence data for county-level diabetes, obesity, and consumption of five or more fruits or vegetables per day (FV5) was obtained from the Behavioral Risk Factor Surveillance System. Multiple imputation was used to predict block-group level health outcomes with US Census demographic and economic variables as the inputs. The healthier options category clustered into three sub-types: 1) specialty food, 2) grocery stores, and 3) restaurants. The unhealthier options category clustered into two sub-types: 1) convenience stores, and 2) restaurants and fast food. Within the healthier options category, diabetes prevalence in the sub-types with high restaurants (5.9 %, p = 0.002) and high specialty food (6.1 %, p = 0.002) was lower than the grocery stores sub-type (7.1 %). The high restaurants sub-type compared to the high grocery stores sub-type had significantly lower obesity prevalence (28.6 % vs. 31.2 %, p restaurants (including fast food) sub-type was significantly associated with lower diabetes and obesity, and higher FV prevalence compared to grocery store sub-type. These results suggest that there are sub-types within larger categories of

  17. Changes in insomnia subtypes in early Parkinson disease.

    Science.gov (United States)

    Tholfsen, Lena K; Larsen, Jan P; Schulz, Jörn; Tysnes, Ole-Bjørn; Gjerstad, Michaela D

    2017-01-24

    To examine the development of factors associated with insomnia in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis. One hundred eighty-two drug-naive patients with PD derived from a population-based incident cohort and 202 control participants were assessed for insomnia before treatment initiation and were repeatedly examined after 1, 3, and 5 years. Insomnia was diagnosed according to the Stavanger Sleepiness Questionnaire. The Parkinson's Disease Sleep Scale was used to differentiate sleep initiation problems from problems of sleep maintenance. Generalized estimating equation models were applied for statistical measures. The prevalence of insomnia in general was not higher in patients with PD compared to controls at the 5-year follow-up. There were changes in the prevalence of the different insomnia subtypes over the 5-year follow-up. The prevalence of solitary problems in sleep maintenance increased from 31% (n = 18) in the drug-naive patients at baseline to 49% (n = 29) after 1 year and were associated with the use of dopamine agonists and higher Montgomery-Åsberg Depression Rating Scale scores. The prevalence of solitary sleep initiation problems decreased continuously from 21% (n = 12) at baseline to 7.4% (n = 4) after 5 years; these were associated with less daytime sleepiness. The prevalence rates of the different insomnia subtypes changed notably in patients with early PD. The frequency of sleep maintenance problems increased, and these problems were associated with dopamine agonist use and depressive symptoms, while the total number of patients with insomnia remained stable. Our findings reflect the need for early individual assessments of insomnia subtypes and raise the possibility of intervention to reduce these symptoms in patients with early PD. © 2016 American Academy of Neurology.

  18. OCD with comorbid OCPD: a subtype of OCD?

    Science.gov (United States)

    Coles, Meredith E; Pinto, Anthony; Mancebo, Maria C; Rasmussen, Steven A; Eisen, Jane L

    2008-03-01

    The current study examined the validity of using comorbid obsessive-compulsive personality disorder (OCPD) to identify a subtype of individuals with obsessive-compulsive disorder (OCD). Data for the current study were drawn from an ongoing, longitudinal study of the course of OCD and include intake assessments for 238 subjects with primary and current DSM-IV OCD who were treatment seeking. More than one fourth of the subjects (N=65, 27%) met criteria for comorbid OCPD. As compared to OCD-OCPD subjects, the OCD+OCPD subjects had a significantly younger age at onset of first OC symptoms (p=0.013), and a higher rate of symmetry and hoarding obsessions, and cleaning, ordering, repeating, and hoarding compulsions (all p'sOCPD had higher rates of comorbid anxiety disorders (p=0.007) and avoidant personality disorder (p=0.006). The OCD+OCPD subjects also had significantly lower ratings of global functioning (p=0.001) and more impaired social functioning (p=0.004), despite a lack of significant differences on overall severity of OCD symptoms. Our findings indicate that individuals with both OCD and OCPD have distinct clinical characteristics in terms of age at onset of initial OC symptoms, the types of obsessions and compulsions they experience, and psychiatric comorbidity. Our findings, coupled with data from family studies showing a higher than expected frequency of OCPD in first degree relatives of OCD probands, suggest that OCD associated with OCPD may represent a specific subtype of OCD. Additional research is warranted to further establish the validity of this subtype.

  19. Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.

    Directory of Open Access Journals (Sweden)

    Yen T Duong

    Full Text Available Mean duration of recent infection (MDRI and misclassification of long-term HIV-1 infections, as proportion false recent (PFR, are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus.A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs.Using different statistical methods, MDRI values ranged from 88-94 days at cutoff ODn = 1.0 to 177-183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing for misclassification among long-term infections indicated that overall PFRs were 0.6% to 2.5% at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0% suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D to 152 days (subtype C.Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118-142. Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use.

  20. Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.

    Science.gov (United States)

    Duong, Yen T; Kassanjee, Reshma; Welte, Alex; Morgan, Meade; De, Anindya; Dobbs, Trudy; Rottinghaus, Erin; Nkengasong, John; Curlin, Marcel E; Kittinunvorakoon, Chonticha; Raengsakulrach, Boonyos; Martin, Michael; Choopanya, Kachit; Vanichseni, Suphak; Jiang, Yan; Qiu, Maofeng; Yu, Haiying; Hao, Yan; Shah, Neha; Le, Linh-Vi; Kim, Andrea A; Nguyen, Tuan Anh; Ampofo, William; Parekh, Bharat S

    2015-01-01

    Mean duration of recent infection (MDRI) and misclassification of long-term HIV-1 infections, as proportion false recent (PFR), are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus. A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs. Using different statistical methods, MDRI values ranged from 88-94 days at cutoff ODn = 1.0 to 177-183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing for misclassification among long-term infections indicated that overall PFRs were 0.6% to 2.5% at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0%) suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D) to 152 days (subtype C). Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118-142). Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use.

  1. Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

    Science.gov (United States)

    2016-08-26

    Each neurotoxin subtype within a serotype cleaves its target substrate at the same single conserved peptide bond, except for BoNT/F5 (Table 2) [55...common for strains of C. botulinum Group III to form a chimeric or hybrid protein that combines elements of BoNT/C and BoNT/D neurotoxin, rather than a...Approved for public release; distribution is unlimited. UNCLASSIFIED 15 reported as BoNT/CD or BoNT/DC chimeric toxins [22]. Two exotoxins

  2. Multiple sclerosis

    International Nuclear Information System (INIS)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

  3. Efficacy of zolpidem for dystonia: a study among different subtypes

    Directory of Open Access Journals (Sweden)

    Yoshimichi eMiyazaki

    2012-04-01

    Full Text Available Although there are some newly-developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1(ω1 , was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5-20mg in 34 patients suffering from miscellaneous types of dystonia using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS. Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous 2 successive visits. After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2±7.9 to 5.5±5.0 (P=0.042. Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8%, 17.8% and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome and hand dystonia including musician’s. Drowsiness was the dose-limiting factor.

  4. CT assessment of subtypes of pulmonary emphysema in females

    International Nuclear Information System (INIS)

    Togami, Taro; Yamamoto, Yuka; Kameyama, Reiko; Murota, Makiko; Kimura, Naruhide; Nishiyama, Yoshihiro; Satoh, Katashi

    2011-01-01

    We performed a retrospective study examining the prevalence and subtypes of pulmonary emphysema (PE) identified by computed tomography (CT) in females. We reviewed the records of 1,687 female subjects who had undergone CT. They were divided into the following 2 age groups: group A (<50 years) and group B (≥50 years). PE was diagnosed by the presence of low-attenuation areas using visual assessment (grades 0-3) on CT images. Two subtypes of PE were observed: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). PE was divided into the following 3 categories: I (CLE or CLE-predominant); II (CLE and PSE of equal extent); and III (PSE or PSE-predominant). PE was found in 64 of 274 smokers (23.3%) and 54 of 1,413 non-smokers (3.8%). In smoking subjects, when grades 1 and 2 were grouped together as mild PE, the mean age for CT grade 3 (severe PE) was significantly higher than that for mild PE. In group A, category III predominated, whereas category I was more prevalent in group B, in both smoking and non-smoking subjects. A high incidence of PE was found in smoking subjects as compared with non-smoking subjects. PSE predominated in younger subjects, whereas CLE predominated in older subjects. (author)

  5. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-03

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  6. posttraumatic stress disorder: a theoretical model of the hyperarousal subtype

    Directory of Open Access Journals (Sweden)

    Charles Stewart Weston

    2014-04-01

    Full Text Available Posttraumatic stress disorder (PTSD is a frequent and distressing mental disorder, about which much remains to be learned. It is a heterogeneous disorder; the hyperarousal subtype (about 70% of occurrences and simply termed PTSD in this paper is the topic of this article, but the dissociative subtype (about 30% of occurrences and likely involving quite different brain mechanisms is outside its scope. A theoretical model is presented that integrates neuroscience data on diverse brain regions known to be involved in PTSD, and extensive psychiatric findings on the disorder. Specifically, the amygdala is a multifunctional brain region that is crucial to PTSD, and processes peritraumatic hyperarousal on grounded cognition principles to produce hyperarousal symptoms. Amygdala activity also modulates hippocampal function, which is supported by a large body of evidence, and likewise amygdala activity modulates several brainstem regions, visual cortex, rostral anterior cingulate cortex (rACC, and medial orbitofrontal cortex (mOFC, to produce diverse startle, visual, memory, numbing, anger, and recklessness symptoms. Additional brain regions process other aspects of peritraumatic responses to produce further symptoms. These contentions are supported by neuroimaging, neuropsychological, neuroanatomical, physiological, cognitive, and behavioral evidence. Collectively, the model offers an account of how responses at the time of trauma are transformed into an extensive array of the 20 PTSD symptoms that are specified in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. It elucidates the neural mechanisms of a specific form of psychopathology, and accords with the Research Domain Criteria framework

  7. Cognitive process-based subtypes of developmental coordination disorder (DCD).

    Science.gov (United States)

    Asonitou, Katerina; Koutsouki, Dimitra

    2016-06-01

    The purpose of the study was to identify the cognitive subtypes demonstrated by children with developmental coordination disorder (DCD) using the Planning-Attention-Simultaneous-Successive Processing (PASS) theory and the Cognitive Assessment System (D-N CAS). Participants were 108 children aged 5- and 6-years old, 54 with DCD and 54 without DCD, all attending typical kindergartens. They were examined on 31 cognitive-motor variables. Hierarchical-agglomerative and iterative partitioning cluster analyses including 9 motor and 7 cognitive variables revealed the following six subtypes: o C1 = children at risk (having considerable difficulty with jumping and minor difficulty with manual dexterity and simultaneous coding); o C2 = children on the mean (all cognitive-motor scores close to the mean); o C3 = free from cognitive-motor problems (all scores above average); o C4 = manual dexterity, planning and simultaneous coding difficulties; o C5 = manual dexterity, dynamic balance, and planning difficulties; o C6 = generalized cognitive-motor dysfunction (all scores considerably below average). It is well known that DCD is a heterogeneous condition. However, whenever cognitive processes were lower than average, cognitive-motor relationship was evident in subgroups C1, C4, C5 and C6. Early identification of task-specific cognitive-motor difficulties may be essential for early educational intervention practices in order to anticipate and improve learning, academic and performing difficulties. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Efficacy of Zolpidem for Dystonia: A Study Among Different Subtypes

    Science.gov (United States)

    Miyazaki, Yoshimichi; Sako, Wataru; Asanuma, Kotaro; Izumi, Yuishin; Miki, Tetsuro; Kaji, Ryuji

    2012-01-01

    Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5–20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician’s. Drowsiness was the dose-limiting factor. PMID:22529836

  9. Osteoclastic finger arthrosis - a subtype of polyarthrosis of the hand

    International Nuclear Information System (INIS)

    Dihlmann, W.; Dihlmann, A.

    1998-01-01

    Aim: Description of a subtype of arthrosis deformans of the hand which is characterised as osteoclastic arthrosis. Patients and methods: Retrospective analysis of radiographs of the hands of 150 women and 100 men with radiological findings of arthrosis deformans. Results: 5% of women and 2% of men showed at least one digital joint with subchondral osteolysis of one or both articulating bones involving at least a third of the phalanx. This subchondral osteolysis far exceeds the cysts which are situated in the epiphyseal part of the articular region. It may develop within a year. Conclusion: Osteoclastic arthrosis of the finger is a subtype of polyarthrosis of the hand. Serial observations suggest that an osteoclast stimulating substance is produced by the cysts or arises directly from the synovial fluid; this enters the subchondral part of the bone through clefts which may or may not be visible radiologically and that this produces osteoclastic activity. The most important differential diagnoses are chronic tophacious gout and a benign tumor. (orig.) [de

  10. Relationship between EDNOS and its subtypes and borderline personality disorder.

    Science.gov (United States)

    Marino, M F; Zanarini, M C

    2001-04-01

    The purpose of this study was to assess the prevalence of eating disorder not otherwise specified (EDNOS) and four well-defined subtypes of this disorder found in a sample of female borderline patients. The lifetime prevalence of EDNOS and its various subtypes among 233 female borderline patients and 46 female Axis II comparison subjects was assessed using the Structured Clinical Interview for DSM-III-R Axis I disorders. Thirty-three percent of female borderline patients met DSM-III-R criteria for EDNOS at some point in their lives. Of these 76 women, 20% reported a pattern of restricting without low weight, 37% reported a pattern of binging without purging, 37% reported a pattern of purging without binging, and 33% reported a pattern of low weight without loss of menses. However, less than 25% of these 76 borderline women had ever met criteria for anorexia nervosa or bulimia nervosa. The results of this study suggest that EDNOS is a separate cluster of eating disorders among borderline women, rather than a prodromal or residual form of a more clear-cut case of anorexia or bulimia nervosa. Copyright 2001 by John Wiley & Sons, Inc.

  11. [Neuropsychological subtypes of the inattention and hyperactivity syndrome].

    Science.gov (United States)

    Etchepareborda, M C

    1999-02-01

    One of the commonest neurological development disorders is the syndrome of inattention with hyperactivity, ADHD. The complex neurobiological network which intervenes in paying attention permits us to maintain a basal state of alertness, to focalize and maintain attention for long periods, select the stimulus-signal required and analyze its components, and also to simultaneously carry out processes of input-output and performance (tutorial, controlling). Damage to the various systems participating in 'paying attention' leads to a syndrome of inattention, with or without hyperactivity. The distinction into clinical sub-types (combined, mainly lacking attention or mainly hyperactive and impulsive) gives a primary differentiation of the syndrome. However, from the neuropsychological point of view, some degree of heterogeneity within the groups which defines academic behaviour and conduct may also be recognized. This type of study permits a more specific neuro-cognitive and pharmacological approach. Some clinical characteristics of the syndrome of inattention improve with different drugs, such as the state of alterness (methylphenidate), impulsivity (pipamperone) and selective attention (tiapride). However, this treatment is symptomatic and in most cases is useful to accompany the ultimate biological development of the neocortical control mechanisms. A neuro-cognitive approach which permits acquisition of habits of control, functional strategies, sequential planning of activities and per- and post-functional surveillance is fundamental. The EFE programme for training executive functions is directed towards working with the damaged processing mechanisms in each neuropsychological subtype.

  12. Complete nucleotide sequences of avian metapneumovirus subtype B genome.

    Science.gov (United States)

    Sugiyama, Miki; Ito, Hiroshi; Hata, Yusuke; Ono, Eriko; Ito, Toshihiro

    2010-12-01

    Complete nucleotide sequences were determined for subtype B avian metapneumovirus (aMPV), the attenuated vaccine strain VCO3/50 and its parental pathogenic strain VCO3/60616. The genomes of both strains comprised 13,508 nucleotides (nt), with a 42-nt leader at the 3'-end and a 46-nt trailer at the 5'-end. The genome contains eight genes in the order 3'-N-P-M-F-M2-SH-G-L-5', which is the same order shown in the other metapneumoviruses. The genes are flanked on either side by conserved transcriptional start and stop signals and have intergenic sequences varying in length from 1 to 88 nt. Comparison of nt and predicted amino acid (aa) sequences of VCO3/60616 with those of other metapneumoviruses revealed higher homology with aMPV subtype A virus than with other metapneumoviruses. A total of 18 nt and 10 deduced aa differences were seen between the strains, and one or a combination of several differences could be associated with attenuation of VCO3/50.

  13. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability.

    Science.gov (United States)

    Frielink, N; Schuengel, C; Embregts, P

    2017-07-01

    According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and integrated motivation. Although it has been argued theoretically that the different types of motivation are universally applicable, Reid et al. () proposed a dichotomy of broad subtypes of extrinsic motivation for people with intellectual disability (ID) due to their cognitive limitations. The current study challenges this proposal by testing whether the four subtypes of extrinsic motivation can be differentiated among people with ID as well. The subtypes of extrinsic motivation were measured using two adapted versions of the Self-Regulation Questionnaire, one regarding exercise and one regarding support. In total, 186 adults with mild to borderline ID participated in the study. Results supported the distinction between the four subtypes of extrinsic motivation regarding both exercise and support. In addition, the correlation coefficients supported a quasi-simplex pattern of correlations among the subtypes, indicating that adjacent subtypes were more closely related than non-adjacent subtypes. Moreover, the study showed sufficient Cronbach's alphas and test-retest reliabilities for early stage research. Overall, the results of the current study provide initial evidence for the universality of the four subtypes of extrinsic motivation across populations with and without ID. © 2017 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disibilities and John Wiley & Sons Ltd.

  14. The dissociative subtype of posttraumatic stress disorder: rationale, clinical and neurobiological evidence, and implications.

    Science.gov (United States)

    Lanius, Ruth A; Brand, Bethany; Vermetten, Eric; Frewen, Paul A; Spiegel, David

    2012-08-01

    Clinical and neurobiological evidence for a dissociative subtype of posttraumatic stress disorder (PTSD) has recently been documented. A dissociative subtype of PTSD is being considered for inclusion in the forthcoming Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) to address the symptoms of depersonalization and derealization found among a subset of patients with PTSD. This article reviews research related to the dissociative subtype including antecedent, concurrent, and predictive validators as well as the rationale for recommending the dissociative subtype. The relevant literature pertaining to the dissociative subtype of PTSD was reviewed. Latent class analyses point toward a specific subtype of PTSD consisting of symptoms of depersonalization and derealization in both veteran and civilian samples of PTSD. Compared to individuals with PTSD, those with the dissociative subtype of PTSD also exhibit a different pattern of neurobiological response to symptom provocation as well as a differential response to current cognitive behavioral treatment designed for PTSD. We recommend that consideration be given to adding a dissociative subtype of PTSD in the revision of the DSM. This facilitates more accurate analysis of different phenotypes of PTSD, assist in treatment planning that is informed by considering the degree of patients' dissociativity, will improve treatment outcome, and will lead to much-needed research about the prevalence, symptomatology, neurobiology, and treatment of individuals with the dissociative subtype of PTSD. © 2012 Wiley Periodicals, Inc.

  15. Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers

    Directory of Open Access Journals (Sweden)

    Xinxin Peng

    2018-04-01

    Full Text Available Summary: Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes—modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility. : Peng et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to characterize tumor subtypes based on the expression of seven metabolic pathways. They find metabolic expression subtypes are associated with patient survivals and suggest the therapeutic and predictive relevance of subtype-related master regulators. Keywords: The Cancer Genome Atlas, tumor subtypes, prognostic markers, somatic drivers, master regulator, therapeutic targets, drug sensitivity, carbohydrate metabolism

  16. Complete genome of a European hepatitis C virus subtype 1g isolate: phylogenetic and genetic analyses.

    Science.gov (United States)

    Bracho, Maria A; Saludes, Verónica; Martró, Elisa; Bargalló, Ana; González-Candelas, Fernando; Ausina, Vicent

    2008-06-05

    Hepatitis C virus isolates have been classified into six main genotypes and a variable number of subtypes within each genotype, mainly based on phylogenetic analysis. Analyses of the genetic relationship among genotypes and subtypes are more reliable when complete genome sequences (or at least the full coding region) are used; however, so far 31 of 80 confirmed or proposed subtypes have at least one complete genome available. Of these, 20 correspond to confirmed subtypes of epidemic interest. We present and analyse the first complete genome sequence of a HCV subtype 1g isolate. Phylogenetic and genetic distance analyses reveal that HCV-1g is the most divergent subtype among the HCV-1 confirmed subtypes. Potential genomic recombination events between genotypes or subtype 1 genomes were ruled out. We demonstrate phylogenetic congruence of previously deposited partial sequences of HCV-1g with respect to our sequence. In light of this, we propose changing the current status of its subtype-specific designation from provisional to confirmed.

  17. Complete genome of a European hepatitis C virus subtype 1g isolate: phylogenetic and genetic analyses

    Directory of Open Access Journals (Sweden)

    Bargalló Ana

    2008-06-01

    Full Text Available Abstract Background Hepatitis C virus isolates have been classified into six main genotypes and a variable number of subtypes within each genotype, mainly based on phylogenetic analysis. Analyses of the genetic relationship among genotypes and subtypes are more reliable when complete genome sequences (or at least the full coding region are used; however, so far 31 of 80 confirmed or proposed subtypes have at least one complete genome available. Of these, 20 correspond to confirmed subtypes of epidemic interest. Results We present and analyse the first complete genome sequence of a HCV subtype 1g isolate. Phylogenetic and genetic distance analyses reveal that HCV-1g is the most divergent subtype among the HCV-1 confirmed subtypes. Potential genomic recombination events between genotypes or subtype 1 genomes were ruled out. We demonstrate phylogenetic congruence of previously deposited partial sequences of HCV-1g with respect to our sequence. Conclusion In light of this, we propose changing the current status of its subtype-specific designation from provisional to confirmed.

  18. Clinical Manifestations of Cryptosporidiosis and Identification of a New Cryptosporidium Subtype in Patients From Sonora, Mexico.

    Science.gov (United States)

    Urrea-Quezada, Alejandro; González-Díaz, Mariana; Villegas-Gómez, Isaac; Durazo, María; Hernández, Jesús; Xiao, Lihua; Valenzuela, Olivia

    2018-05-01

    The aim of this study was to identify the clinical manifestations of cryptosporidiosis and the distribution of Cryptosporidium spp. and subtypes in children in Sonora, Mexico. Two subtypes of C. parvum, including IIaA15G2R1 and IIcA5G3a, and 6 subtypes of Cryptosporidium hominis, including IaA14R3, IaA15R3, IbA12G3, IdA23, IeA11G3T3, and a new subtype IaA14R11, were identified. Cryptosporidium as an etiologic agent for acute gastroenteritis is discussed.

  19. Subtype and pathway specific responses to anticancer compounds in breast cancer.

    Science.gov (United States)

    Heiser, Laura M; Sadanandam, Anguraj; Kuo, Wen-Lin; Benz, Stephen C; Goldstein, Theodore C; Ng, Sam; Gibb, William J; Wang, Nicholas J; Ziyad, Safiyyah; Tong, Frances; Bayani, Nora; Hu, Zhi; Billig, Jessica I; Dueregger, Andrea; Lewis, Sophia; Jakkula, Lakshmi; Korkola, James E; Durinck, Steffen; Pepin, François; Guan, Yinghui; Purdom, Elizabeth; Neuvial, Pierre; Bengtsson, Henrik; Wood, Kenneth W; Smith, Peter G; Vassilev, Lyubomir T; Hennessy, Bryan T; Greshock, Joel; Bachman, Kurtis E; Hardwicke, Mary Ann; Park, John W; Marton, Laurence J; Wolf, Denise M; Collisson, Eric A; Neve, Richard M; Mills, Gordon B; Speed, Terence P; Feiler, Heidi S; Wooster, Richard F; Haussler, David; Stuart, Joshua M; Gray, Joe W; Spellman, Paul T

    2012-02-21

    Breast cancers are comprised of molecularly distinct subtypes that may respond differently to pathway-targeted therapies now under development. Collections of breast cancer cell lines mirror many of the molecular subtypes and pathways found in tumors, suggesting that treatment of cell lines with candidate therapeutic compounds can guide identification of associations between molecular subtypes, pathways, and drug response. In a test of 77 therapeutic compounds, nearly all drugs showed differential responses across these cell lines, and approximately one third showed subtype-, pathway-, and/or genomic aberration-specific responses. These observations suggest mechanisms of response and resistance and may inform efforts to develop molecular assays that predict clinical response.

  20. Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data.

    Science.gov (United States)

    Ren, Zhonglu; Wang, Wenhui; Li, Jinming

    2016-02-01

    Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristics of each subtype. Clustering analysis and discriminant analysis were utilized to discover the subtypes in two different molecular levels on 153 colon cancer samples from The Cancer Genome Atlas (TCGA) Data Portal. At gene expression level, we identified two major subtypes, ECL1 (expression cluster 1) and ECL2 (expression cluster 2) and a list of signature genes. Due to the heterogeneity of colon cancer, the subtype ECL1 can be further subdivided into three nested subclasses, and HOTAIR were found upregulated in subclass 2. At DNA methylation level, we uncovered three major subtypes, MCL1 (methylation cluster 1), MCL2 (methylation cluster 2) and MCL3 (methylation cluster 3). We found only three subtypes of CpG island methylator phenotype (CIMP) in colon cancer instead of the four subtypes in the previous reports, and we found no sufficient evidence to subdivide MCL3 into two distinct subgroups.

  1. Multiple homicides.

    Science.gov (United States)

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  2. Multiple Sclerosis

    Science.gov (United States)

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

  3. Multiple myeloma.

    LENUS (Irish Health Repository)

    Collins, Conor D

    2012-02-01

    Advances in the imaging and treatment of multiple myeloma have occurred over the past decade. This article summarises the current status and highlights how an understanding of both is necessary for optimum management.

  4. Multiple mononeuropathy

    Science.gov (United States)

    ... with multiple mononeuropathy are prone to new nerve injuries at pressure points such as the knees and elbows. They should avoid putting pressure on these areas, for example, by not leaning on the elbows, crossing the knees, ...

  5. Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration.

    Directory of Open Access Journals (Sweden)

    Rami Kantor

    2005-04-01

    Full Text Available The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate.To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80% of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates.Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.

  6. Breast Conservation Therapy: The Influence of Molecular Subtype and Margins

    International Nuclear Information System (INIS)

    Demirci, Senem; Broadwater, Gloria; Marks, Lawrence B.; Clough, Robert; Prosnitz, Leonard R.

    2012-01-01

    Purpose: To evaluate treatment results and prognostic factors, especially margin status and molecular subtype, in early-stage breast cancer patients treated with breast conservation therapy (BCT). Methods and Materials: The records of 1,058 Stage I or II breast cancer patients treated with BCT (surgical excision plus radiotherapy) at Duke University Medical Center, Durham, North Carolina, from 1985–2005 were retrospectively reviewed. Conventional receptor analyses were used as surrogate markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal like). Actuarial estimates of overall survival (OS), cause-specific survival (CSS), failure-free survival, and locoregional control (LRC) were computed by use of Kaplan-Meier plots. We analyzed prognostic variables for significance using Cox proportional hazards univariate and multivariate analysis. The study was approved by the Duke University Medical Center Institutional Review Board. Results: The median age of the patients was 56 years (range, 18–89 years). Of the patients, 80% had T1 disease and 66% N0 disease pathologically. With a median follow-up of 9.8 years, an in-breast recurrence developed in 53 patients and 10 patients had nodal failure. For all patients, the 10-year CSS rate was 94%; LRC rate, 94%; and failure-free survival rate, 88%. Luminal A patients had a CSS rate of 95% and LRC rate of 99%. Basal-type patients appeared to do worse, with regard to both CSS rate (74%) and LRC rate (76%), but the numbers were small and the difference was not statistically significant. LRC rates of patients with negative margins (widely negative, close, and extent of margin not known) were virtually identical (93%, 96%, and 94%, respectively). Those with positive margins appeared to fare slightly worse based on LRC rate (88%), but again, the numbers were small and the difference was not statistically significant. Conclusions: BCT remains the treatment of choice for early-stage breast cancer

  7. Breast Conservation Therapy: The Influence of Molecular Subtype and Margins

    Energy Technology Data Exchange (ETDEWEB)

    Demirci, Senem, E-mail: senem.demirci@ege.edu.tr [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir (Turkey); Broadwater, Gloria [Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Durham, NC (United States); Cancer and Leukemia Group B Statistical Center, Duke Cancer Institute, Durham, NC (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC (United States); Clough, Robert; Prosnitz, Leonard R. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

    2012-07-01

    Purpose: To evaluate treatment results and prognostic factors, especially margin status and molecular subtype, in early-stage breast cancer patients treated with breast conservation therapy (BCT). Methods and Materials: The records of 1,058 Stage I or II breast cancer patients treated with BCT (surgical excision plus radiotherapy) at Duke University Medical Center, Durham, North Carolina, from 1985-2005 were retrospectively reviewed. Conventional receptor analyses were used as surrogate markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal like). Actuarial estimates of overall survival (OS), cause-specific survival (CSS), failure-free survival, and locoregional control (LRC) were computed by use of Kaplan-Meier plots. We analyzed prognostic variables for significance using Cox proportional hazards univariate and multivariate analysis. The study was approved by the Duke University Medical Center Institutional Review Board. Results: The median age of the patients was 56 years (range, 18-89 years). Of the patients, 80% had T1 disease and 66% N0 disease pathologically. With a median follow-up of 9.8 years, an in-breast recurrence developed in 53 patients and 10 patients had nodal failure. For all patients, the 10-year CSS rate was 94%; LRC rate, 94%; and failure-free survival rate, 88%. Luminal A patients had a CSS rate of 95% and LRC rate of 99%. Basal-type patients appeared to do worse, with regard to both CSS rate (74%) and LRC rate (76%), but the numbers were small and the difference was not statistically significant. LRC rates of patients with negative margins (widely negative, close, and extent of margin not known) were virtually identical (93%, 96%, and 94%, respectively). Those with positive margins appeared to fare slightly worse based on LRC rate (88%), but again, the numbers were small and the difference was not statistically significant. Conclusions: BCT remains the treatment of choice for early-stage breast cancer

  8. HIV subtype, epidemiological and mutational correlations in patients from Paraná, Brazil

    Directory of Open Access Journals (Sweden)

    Monica Maria Gomes da Silva

    Full Text Available OBJECTIVE: Analyze patients with HIV infection from Curitiba, Paraná, their epidemiological characteristics and HIV RAM. METHODS: Patients regularly followed in an ID Clinic had their medical data evaluated and cases of virological failure were analyzed with genotypic report. RESULTS: Patients with complete medical charts were selected (n = 191. Demographic and clinical characteristics were compared. One hundred thirty two patients presented with subtype B infection (69.1%, 41 subtype C (21.5%, 10 subtype F (5.2%, 7 BF (3.7% and 1 CF (0.5%. Patients with subtype B infection had been diagnosed earlier than patients with subtype non-B. Also, subtype B infection was more frequent in men who have sex with men, while non-B subtypes occurred more frequently in heterosexuals and women. Patients with previous history of three classes of ARVs (n = 161 intake were selected to evaluate resistance. For RT inhibitors, 41L and 210W were more frequently observed in subtype B than in non-B strains. No differences between subtypes and mutations were observed to NNTRIs. Mutations at 10, 32 and 63 position of protease were more observed in subtype B viruses than non-B, while positions 20 and 36 of showed more amino acid substitutions in subtype non-B viruses. Patients with history of NFV intake were evaluated to resistance pathway. The 90M pathway was more frequent in subtypes B and non-B. Mutations previously reported as common in non-B viruses, such as 65R and 106M, were uncommon in our study. Mutations 63P and 36I, previously reported as common in HIV-1 subtypes B and C from Brazil, respectively, were common. CONCLUSION: There is a significant frequency of HIV-1 non-B infections in Paraná state, with isolates classified as subtypes C, F, BF and BC. Patients with subtype C infection were more frequently female, heterosexual and had a longer average time of HIV diagnosis

  9. Preparation of quadri-subtype influenza virus-like particles using bovine immunodeficiency virus gag protein

    Energy Technology Data Exchange (ETDEWEB)

    Tretyakova, Irina; Hidajat, Rachmat; Hamilton, Garrett; Horn, Noah; Nickols, Brian; Prather, Raphael O. [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD (United States); Tumpey, Terrence M. [Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., Atlanta, GA (United States); Pushko, Peter, E-mail: ppushko@medigen-usa.com [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD (United States)

    2016-01-15

    Influenza VLPs comprised of hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins have been previously used for immunological and virological studies. Here we demonstrated that influenza VLPs can be made in Sf9 cells by using the bovine immunodeficiency virus gag (Bgag) protein in place of M1. We showed that Bgag can be used to prepare VLPs for several influenza subtypes including H1N1 and H10N8. Furthermore, by using Bgag, we prepared quadri-subtype VLPs, which co-expressed within the VLP the four HA subtypes derived from avian-origin H5N1, H7N9, H9N2 and H10N8 viruses. VLPs showed hemagglutination and neuraminidase activities and reacted with specific antisera. The content and co-localization of each HA subtype within the quadri-subtype VLP were evaluated. Electron microscopy showed that Bgag-based VLPs resembled influenza virions with the diameter of 150–200 nm. This is the first report of quadri-subtype design for influenza VLP and the use of Bgag for influenza VLP preparation. - Highlights: • BIV gag protein was configured as influenza VLP core component. • Recombinant influenza VLPs were prepared in Sf9 cells using baculovirus expression system. • Single- and quadri-subtype VLPs were prepared by using BIV gag as a VLP core. • Co-localization of H5, H7, H9, and H10 HA was confirmed within quadri-subtype VLP. • Content of HA subtypes within quadri-subtype VLP was determined. • Potential advantages of quadri-subtype VLPs as influenza vaccine are discussed.

  10. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.

    Science.gov (United States)

    Tothill, Richard W; Tinker, Anna V; George, Joshy; Brown, Robert; Fox, Stephen B; Lade, Stephen; Johnson, Daryl S; Trivett, Melanie K; Etemadmoghadam, Dariush; Locandro, Bianca; Traficante, Nadia; Fereday, Sian; Hung, Jillian A; Chiew, Yoke-Eng; Haviv, Izhak; Gertig, Dorota; DeFazio, Anna; Bowtell, David D L

    2008-08-15

    The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features. Microarray gene expression profiling was done on 285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results. Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends. Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance.

  11. Preparation of quadri-subtype influenza virus-like particles using bovine immunodeficiency virus gag protein

    International Nuclear Information System (INIS)

    Tretyakova, Irina; Hidajat, Rachmat; Hamilton, Garrett; Horn, Noah; Nickols, Brian; Prather, Raphael O.; Tumpey, Terrence M.; Pushko, Peter

    2016-01-01

    Influenza VLPs comprised of hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins have been previously used for immunological and virological studies. Here we demonstrated that influenza VLPs can be made in Sf9 cells by using the bovine immunodeficiency virus gag (Bgag) protein in place of M1. We showed that Bgag can be used to prepare VLPs for several influenza subtypes including H1N1 and H10N8. Furthermore, by using Bgag, we prepared quadri-subtype VLPs, which co-expressed within the VLP the four HA subtypes derived from avian-origin H5N1, H7N9, H9N2 and H10N8 viruses. VLPs showed hemagglutination and neuraminidase activities and reacted with specific antisera. The content and co-localization of each HA subtype within the quadri-subtype VLP were evaluated. Electron microscopy showed that Bgag-based VLPs resembled influenza virions with the diameter of 150–200 nm. This is the first report of quadri-subtype design for influenza VLP and the use of Bgag for influenza VLP preparation. - Highlights: • BIV gag protein was configured as influenza VLP core component. • Recombinant influenza VLPs were prepared in Sf9 cells using baculovirus expression system. • Single- and quadri-subtype VLPs were prepared by using BIV gag as a VLP core. • Co-localization of H5, H7, H9, and H10 HA was confirmed within quadri-subtype VLP. • Content of HA subtypes within quadri-subtype VLP was determined. • Potential advantages of quadri-subtype VLPs as influenza vaccine are discussed.

  12. Different frequencies of drug resistance mutations among HIV-1 subtypes circulating in China: a comprehensive study.

    Directory of Open Access Journals (Sweden)

    Hongshuai Sui

    Full Text Available The rapid spreading of HIV drug resistance is threatening the overall success of free HAART in China. Much work has been done on drug-resistant mutations, however, most of which were based on subtype B. Due to different genetic background, subtypes difference would have an effect on the development of drug-resistant mutations, which has already been proved by more and more studies. In China, the main epidemic subtypes are CRF07_BC, CRF08_BC, Thai B and CRF01_AE. The depiction of drug resistance mutations in those subtypes will be helpful for the selection of regimens for Chinese. In this study, the distributions difference of amino acids at sites related to HIV drug resistance were compared among subtype B, CRF01_AE, CRF07_BC and CRF08_BC strains prevalent in China. The amino acid composition of sequences belonging to different subtypes, which were obtained from untreated and treated individuals separately, were also compared. The amino acids proportions of 19 sites in RT among subtype B, CRF01_AE and CRF08_BC have significant difference in drug resistance groups (chi-square test, p<0.05. Genetic barriers analysis revealed that sites 69, 138, 181, 215 and 238 were significantly different among subtypes (Kruskal Wallis test, p<0.05. All subtypes shared three highest prevalent drug resistance sites 103, 181 and 184 in common. Many drug resistant sites in protease show surprising high proportions in almost all subtypes in drug-naïve patients. This is the first comprehensive study in China on different development of drug resistance among different subtypes. The detailed data will lay a foundation for HIV treatment regimens design and improve HIV therapy in China.

  13. Percutaneous Cryoablation of Solitary, Sporadic Renal Cell Carcinoma: Outcome Analysis Based on Clear-Cell versus Papillary Subtypes.

    Science.gov (United States)

    Haddad, Mustafa M; Schmit, Grant D; Kurup, A Nicholas; Schmitz, John J; Boorjian, Stephen A; Geske, Jennifer; Thompson, R Houston; Callstrom, Matthew R; Atwell, Thomas D

    2018-06-07

    To evaluate treatment outcomes with percutaneous cryoablation (PCA) based on renal cell carcinoma (RCC) histology. Patients treated with PCA for a solitary, sporadic stage T1a RCC from 2003 to 2016 were identified from a single institution's renal ablation registry. Patients with multiple tumors, history of RCC, or genetic syndromes associated with RCC (n = 60); no specific RCC subtype determined from core biopsy (n = 66); RCC subtype other than clear-cell or papillary (n = 7); or less than 3 mo of follow-up imaging (n = 5) were excluded. In total, 173 patients met study inclusion criteria. Oncologic outcomes, clinical outcomes, and complications were evaluated based on tumor subtype. Of the 173 patients who underwent PCA for a stage T1a RCC, 130 (75%) had clear-cell RCC (ccRCC) and 43 (25%) had papillary RCC (pRCC). Median tumor size was 2.9 cm (range, 1.3-4.0 cm). Technically successful cryoablation was achieved in all 173 patients. Local tumor recurrence developed in 6 patients with ccRCC (4.6%), new renal tumors developed in 1 patient (0.8%), and metastatic RCC developed in 1 patient (0.8%) who also had local tumor recurrence. No patients with pRCC showed local tumor recurrence, new renal tumors, or metastatic disease. The 5-year disease-free survival rate in patients with ccRCC was 88%, compared with 100% in patients with pRCC (P = .48). Nine patients (5.2%), all with ccRCC, experienced major complications (P = .11). Percutaneous ablation is a viable treatment option for patients with clinical stage T1a pRCC and ccRCC. Percutaneous ablation may be a very favorable treatment strategy particularly for pRCC. Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.

  14. Evidence of avian metapneumovirus subtype C infection of wild birds in Georgia, South Carolina, Arkansas and Ohio, USA.

    Science.gov (United States)

    Turpin, E A; Stallknecht, D E; Slemons, R D; Zsak, L; Swayne, D E

    2008-06-01

    Metapneumoviruses (MPVs) were first reported in avian species (aMPVs) in the late 1970s and in humans in 2001. Although aMPVs have been reported in Europe and Asia for over 20 years, the virus first appeared in the United States in 1996, leaving many to question the origin of the virus and why it proved to be a different subtype from those found elsewhere. To examine the potential role of migratory waterfowl and other wild birds in aMPV spread, our study focused on determining whether populations of wild birds have evidence of aMPV infection. Serum samples from multiple species were initially screened using a blocking enzyme-linked immunosorbent assay. Antibodies to aMPVs were identified in five of the 15 species tested: American coots, American crows, Canada geese, cattle egrets, and rock pigeons. The presence of aMPV-specific antibodies was confirmed with virus neutralization and western blot assays. Oral swabs were collected from wild bird species with the highest percentage of aMPV-seropositive serum samples: the American coots and Canada geese. From these swabs, 17 aMPV-positive samples were identified, 11 from coots and six from geese. Sequence analysis of the matrix, attachment gene and short hydrophobic genes revealed that these viruses belong to subtype C aMPV. The detection of aMPV antibodies and the presence of virus in wild birds in Georgia, South Carolina, Arkansas and Ohio demonstrates that wild birds can serve as a reservoir of subtype C aMPV, and may provide a potential mechanism to spread aMPVs to poultry in other regions of the United States and possibly to other countries in Central and South America.

  15. Analysis on risk factors of short-term poor outcome among different subtypes of acute cerebral infarction

    International Nuclear Information System (INIS)

    Zhang Xiaolong; Ju Zhong; Xu Tan; Zhang Yonghong; Zhang Jintao; Peng Ying

    2012-01-01

    Objective: to investigate the risk factors of short-term poor outcome among patients suffering from acute cerebral infarction who had different subtypes of cerebral infarction. Methods: A total of 3231 acute cerebral infarction patients were included in the present study. Data on demographic characteristics, life style, risk factors, history of cardiovascular disease, admission blood pressure, and clinical outcome at discharge were collected for all participants. Poor outcome was defined as NIHSS ≥10 at discharge or death occurring during hospitalization. The association between poor outcome of cerebral infarction and risk factors was analyzed by using multiple logistic models. Results: Incidence rate of poor outcome is the highest in the patients with cerebral embolism, next in patients with cerebral thrombosis and the lowest in patients with lacunar infarction. Cerebral thrombosis was positively associated with smoking (OR: 1.228; 95% CI: 1.013∼1.637), dyslipidemia (OR: 1.264; 95% CI: 1.081∼1.478), and a history of diabetes mellitus (OR: 1.371; 95% CI: 1.075∼1.747); cerebral embolism was positively associated with a history of atrial fibrillation (OR: 3.131; 95% CI: 1.206∼8.128) and a history of rheumatic heart disease (OR: 5.601; 95% CI: 1.561∼20.091); lacunar infarction is positively associated with alcohol consumption, (OR: 1.428; 95% CI: 1.063∼1.919). Conclusion: The incidence rate of poor outcome is the highest in the patients with cerebral embolism among three subtypes of cerebral infarction, there are different risk factors of poor outcome for three subtypes of cerebral infarction. (authors)

  16. Analysis on risk factors of short-term poor outcome among different subtypes of acute cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Xiaolong, Zhang; Zhong, Ju; Tan, Xu; Yonghong, Zhang [Dept of Epidemiology, School of Public Health, Medical College, Soochow University, Suzhou (China); Jintao, Zhang [Dept of Neurology, the 88th Hospital of PLA, Shandong (China); Ying, Peng [Dept of Epidemiology, School of Public Health, Medical College, Soochow University, Suzhou (China); Antituberculosis Station, Center for Disease Prevention and Control of Zhejiang (China)

    2012-01-15

    Objective: to investigate the risk factors of short-term poor outcome among patients suffering from acute cerebral infarction who had different subtypes of cerebral infarction. Methods: A total of 3231 acute cerebral infarction patients were included in the present study. Data on demographic characteristics, life style, risk factors, history of cardiovascular disease, admission blood pressure, and clinical outcome at discharge were collected for all participants. Poor outcome was defined as NIHSS ≥10 at discharge or death occurring during hospitalization. The association between poor outcome of cerebral infarction and risk factors was analyzed by using multiple logistic models. Results: Incidence rate of poor outcome is the highest in the patients with cerebral embolism, next in patients with cerebral thrombosis and the lowest in patients with lacunar infarction. Cerebral thrombosis was positively associated with smoking (OR: 1.228; 95% CI: 1.013∼1.637), dyslipidemia (OR: 1.264; 95% CI: 1.081∼1.478), and a history of diabetes mellitus (OR: 1.371; 95% CI: 1.075∼1.747); cerebral embolism was positively associated with a history of atrial fibrillation (OR: 3.131; 95% CI: 1.206∼8.128) and a history of rheumatic heart disease (OR: 5.601; 95% CI: 1.561∼20.091); lacunar infarction is positively associated with alcohol consumption, (OR: 1.428; 95% CI: 1.063∼1.919). Conclusion: The incidence rate of poor outcome is the highest in the patients with cerebral embolism among three subtypes of cerebral infarction, there are different risk factors of poor outcome for three subtypes of cerebral infarction. (authors)

  17. The effects of co-morbidity in defining major depression subtypes associated with long-term course and severity.

    Science.gov (United States)

    Wardenaar, K J; van Loo, H M; Cai, T; Fava, M; Gruber, M J; Li, J; de Jonge, P; Nierenberg, A A; Petukhova, M V; Rose, S; Sampson, N A; Schoevers, R A; Wilcox, M A; Alonso, J; Bromet, E J; Bunting, B; Florescu, S E; Fukao, A; Gureje, O; Hu, C; Huang, Y Q; Karam, A N; Levinson, D; Medina Mora, M E; Posada-Villa, J; Scott, K M; Taib, N I; Viana, M C; Xavier, M; Zarkov, Z; Kessler, R C

    2014-11-01

    Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. However, it is not known whether these distinctions can be refined by added information about co-morbid conditions. The current report presents results on this question. Data came from 8261 respondents with lifetime DSM-IV MDD in the World Health Organization (WHO) World Mental Health (WMH) Surveys. Outcomes included four retrospectively reported measures of persistence/severity of course (years in episode; years in chronic episodes; hospitalization for MDD; disability due to MDD). Machine learning methods (regression tree analysis; lasso, ridge and elastic net penalized regression) followed by k-means cluster analysis were used to augment previously detected subtypes with information about prior co-morbidity to predict these outcomes. Predicted values were strongly correlated across outcomes. Cluster analysis of predicted values found three clusters with consistently high, intermediate or low values. The high-risk cluster (32.4% of cases) accounted for 56.6-72.9% of high persistence, high chronicity, hospitalization and disability. This high-risk cluster had both higher sensitivity and likelihood ratio positive (LR+; relative proportions of cases in the high-risk cluster versus other clusters having the adverse outcomes) than in a parallel analysis that excluded measures of co-morbidity as predictors. Although the results using the retrospective data reported here suggest that useful MDD subtyping distinctions can be made with machine learning and clustering across multiple indicators of illness persistence/severity, replication with prospective data is needed to confirm this preliminary conclusion.

  18. Proliferative activity (MIB-1 index) is an independent prognostic parameter in patients with high-grade soft tissue sarcomas of subtypes other than malignant fibrous histiocytomas

    DEFF Research Database (Denmark)

    Jensen, V; Sørensen, Flemming Brandt; Bentzen, S M

    1998-01-01

    . The proliferative activity was assessed by use of the monoclonal antibody MIB-1 and evaluated in multiple, random systematic sampled fields of vision. The percentage of proliferating cells (the MIB-1 index) ranged between 1% and 85% (median 12%). A significant increase in mean MIB-1 index was seen with increasing...... histological malignancy grade. Variation in the incidence of p53 accumulation and bcl-2 positivity among different histological subtypes was observed. p53 accumulation was frequent in synovial sarcomas and leiomyo- and rhabdomyosarcomas, whereas bcl-2 preferentially was expressed in synovial sarcomas....... Univariate analysis identified patient age, tumour size, histological grade of malignancy, MIB-1 index and p53 accumulation as significant prognostic parameters. Multivariate Cox analysis, including tests for interaction terms between histological subtypes and MIB-1 index, showed independent prognostic...

  19. Expression and distribution patterns of Mas-related gene receptor subtypes A-H in the mouse intestine: inflammation-induced changes.

    Science.gov (United States)

    Avula, Leela Rani; Buckinx, Roeland; Favoreel, Herman; Cox, Eric; Adriaensen, Dirk; Van Nassauw, Luc; Timmermans, Jean-Pierre

    2013-05-01

    Mas-related gene (Mrg) receptors constitute a subfamily of G protein-coupled receptors that are implicated in nociception, and are as such considered potential targets for pain therapies. Furthermore, some Mrgs have been suggested to play roles in the regulation of inflammatory responses to non-immunological activation of mast cells and in mast cell-neuron communication. Except for MrgD, E and F, whose changed expression has been revealed during inflammation in the mouse intestine in our earlier studies, information concerning the remaining cloned mouse Mrg subtypes in the gastrointestinal tract during (patho) physiological conditions is lacking. Therefore, the present study aimed at identifying the presence and putative function of these remaining cloned Mrg subtypes (n = 19) in the (inflamed) mouse intestine. Using reverse transcriptase-PCR, quantitative-PCR and multiple immunofluorescence staining with commercial and newly custom-developed antibodies, we compared the ileum and the related dorsal root ganglia (DRG) of non-inflamed mice with those of two models of intestinal inflammation, i.e., intestinal schistosomiasis and 2,4,6-trinitrobenzene sulfonic acid-induced ileitis. In the non-inflamed ileum and DRG, the majority of the Mrg subtypes examined were sparsely expressed, showing a neuron-specific expression pattern. However, significant changes in the expression patterns of multiple Mrg subtypes were observed in the inflamed ileum; for instance, MrgA4, MrgB2and MrgB8 were expressed in a clearly increased number of enteric sensory neurons and in nerve fibers in the lamina propria, while de novo expression of MrgB10 was observed in enteric sensory neurons and in newly recruited mucosal mast cells (MMCs). The MrgB10 expressing MMCs were found to be in close contact with nerve fibers in the lamina propria. This is the first report on the expression of all cloned Mrg receptor subtypes in the (inflamed) mouse intestine. The observed changes in the expression and

  20. Characterization of muscarinic receptor subtypes in human tissues

    International Nuclear Information System (INIS)

    Giraldo, E.; Martos, F.; Gomez, A.; Garcia, A.; Vigano, M.A.; Ladinsky, H.; Sanchez de La Cuesta, F.

    1988-01-01

    The affinities of selective, pirenzepine and AF-DX 116, and classical, N-methylscopolamine and atropine, muscarinic cholinergic receptor antagonists were investigated in displacement binding experiments with [ 3 H]Pirenzepine and [ 3 H]N-methylscopolamine in membranes from human autoptic tissues (forebrain, cerebellum, atria, ventricle and submaxillary salivary glands). Affinity estimates of N-methylscopolamine and atropine indicated a non-selective profile. Pirenzepine showed differentiation between the M 1 neuronal receptor of the forebrain and the receptors in other tissues while AF-DX 116 clearly discriminated between muscarinic receptors of heart and glands. The results in human tissues confirm the previously described selectivity profiles of pirenzepine and AF-DX 116 in rat tissues. These findings thus reveal the presence also in man of three distinct muscarinic receptor subtypes: the neuronal M 1 , the cardiac M 2 and the glandular M 3

  1. Groin hernia subtypes are associated in patients with bilateral hernias

    DEFF Research Database (Denmark)

    Burcharth, Jakob; Andresen, Kristoffer; Pommergaard, Hans-Christian

    2015-01-01

    repair (89.9% males) were registered, and of those were 12,041 persons operated bilaterally (94.9% males). Females and males operated for a unilaterally direct inguinal hernia (DIH) had increased Hazard Ratios (HR) of 3.85 (CI 95% 2.14-6.19) and 4.46 (CI 95% 2.57-7.88) of being contralaterally operated...... for a DIH. Females and males operated for a unilaterally indirect inguinal hernia (IIH) had HRs of 6.93 (CI 95% 3.66-13.11) and 1.89 (CI95% 1.24-2.88) for being contralaterally operated for an IIH. The same tendency was seen for femoral hernias. CONCLUSIONS: All hernia subtypes were bilaterally associated...

  2. Diagnostic subtypes of bipolar disorder in older versus younger adults

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel

    2006-01-01

    OBJECTIVE: To investigate differences in diagnostic subtypes of bipolar disorder as according to ICD-10 between patients whose first contact with psychiatric health care occurs late in life (over 50 years of age) and patients who have first contact earlier in life (50 years of age or below......). METHODS: From 1994 to 2002 all patients who received a diagnosis of a manic episode or bipolar disorder at initial contact with the mental healthcare system, whether outpatient or inpatient, were identified in Denmark's nationwide register. RESULTS: A total of 852 (49.6%) patients, who were over age 50......, and 867 patients, who were 50 or below, received a diagnosis of a manic episode or bipolar disorder at the first contact ever. Older inpatients presented with psychotic symptoms (35.4%) significantly less than younger inpatients (42.6%) due specifically to a lower prevalence of manic episodes...

  3. Do neurocognitive deficits in decision making differentiate conduct disorder subtypes?

    Science.gov (United States)

    Fanti, Kostas A; Kimonis, Eva R; Hadjicharalambous, Maria-Zoe; Steinberg, Laurence

    2016-09-01

    The present study aimed to test whether neurocognitive deficits involved in decision making underlie subtypes of conduct-disorder (CD) differentiated on the basis of callous-unemotional (CU) traits. Eighty-five participants (M age = 10.94 years) were selected from a sample of 1200 children based on repeated assessment of CD and CU traits. Participants completed a multi-method battery of well-validated measures of risky decision making and associated constructs of selective attention and future orientation (Stroop, Stoplight, and Delay-Discounting Tasks). Findings indicated that impaired decision making, selective attention, and future orientation contribute to the antisocial presentations displayed by children with CD, irrespective of level of CU traits. Youth high on CU traits without CD showed less risky decision making, as indicated by their performance on the Stoplight laboratory task, than those high on both CD and CU traits, suggesting a potential protective factor against the development of antisocial behavior.

  4. Diversity of Blastocystis subtypes in dogs in different geographical settings

    DEFF Research Database (Denmark)

    Wang, Wenqi; Cuttell, Leigh; Bielefeldt-Ohmann, Helle

    2013-01-01

    Background: Blastocystis is a ubiquitous, globally distributed intestinal protist infecting humans and a wide range of animals. Several studies have shown that Blastocystis is a potentially zoonotic parasite. A 1996 study reported a 70% Blastocystis prevalence in Brisbane pound dogs while another...... study found that pet dogs/cats of 11 symptomatic Blastocystis infected patients harboured at least one Blastocystis subtype (ST) in common with the patient. These results raised the possibility that dogs might be natural hosts of Blastocystis. In this study, we aimed to investigate this hypothesis...... by estimating the prevalence of Blastocystis carriage and characterising the diversity of STs in dogs from three different environmental settings and comparing these STs with the range that humans harbour. Methods: Two hundred and forty faecal samples from dogs from three different geographical regions...

  5. Incidence of dementia and major subtypes in Europe

    DEFF Research Database (Denmark)

    Fratiglioni, L; Launer, L J; Andersen, K

    2000-01-01

    The authors examined the association of incident dementia and subtypes with age, sex, and geographic area in Europe. Incidence data from eight population-based studies carried out in seven European countries were compared and pooled. The pooled data included 835 mild to severe dementia cases and 42......,996 person-years of follow-up. In all studies a higher proportion of cases were diagnosed with AD (60 to 70% of all demented cases) than vascular dementia (VaD). The incidence of dementia and AD continued to increase with age up to age 85 years, after which rates increased in women but not men....... There was a large variation in VaD incidence across studies. In the pooled analysis, the incidence rates increased with age without any substantial difference between men and women. Surprisingly, higher incidence rates of dementia and AD were found in the very old in northwest countries than in southern countries...

  6. Subtyping Ageism: Policy Issues in Succession and Consumption.

    Science.gov (United States)

    North, Michael S; Fiske, Susan T

    2013-01-01

    Ageism research tends to lump "older people" together as one group, as do policy matters that conceptualize everyone over-65 as "senior." This approach is problematic primarily because it often fails to represent accurately a rapidly growing, diverse, and healthy older population. In light of this, we review the ageism literature, emphasizing the importance of distinguishing between the still-active "young-old" and the potentially more impaired "old-old" (Neugarten, 1974). We argue that ageism theory has disproportionately focused on the old-old and differentiate the forms of age discrimination that apparently target each elder subgroup. In particular, we highlight the young-old's plights predominantly in the workplace and tensions concerning succession of desirable resources; by contrast, old-old predicaments likely center on consumption of shared resources outside of the workplace. For both social psychological researchers and policymakers, accurately subtyping ageism will help society best accommodate a burgeoning, diverse older population.

  7. [Cognitive performance in schizophrenia (paranoid vs residual subtype)].

    Science.gov (United States)

    Dillon, Carol; Taragano, Fernando; Sarasola, Diego; Iturry, Mónica; Serrano, Cecilia; Raczkowski, Amalia; Allegri, Ricardo

    2007-01-01

    Several studies refer to the relationship between schizophrenia and cognitive dysfunctions. The most frequent disturbances accepted are the deficits in the executive, memory and verbal tests. However, there are few comparative data about the cognitive functioning of the different subtypes of schizophrenia. Analyze and compare the neuropsychological disturbances present in patients with paranoid and residual schizophrenia. Eleven patients with paranoid schizophrenia, eleven patients with residual schizophrenia (DSM-IV criteria), and thirty one normal subjects matched by age, educational level, and general cognitive level (Mini Mental State Examination (Folstein, 1975), were assessed with a semistructured psychiatric examination and an extensive neuropsychological battery. Significant differences were found in memory, language, and executive functions when schizophrenics were compared with normal subjects. Differences in similarities were found between paranoid and residual schizophrenics. Residual schizophrenics had more disturbances in neuropsychological tests in comparison with paranoid schizophrenics. Schizophrenics demonstrated disturbances in memory, language, executive functions and attention. Residual schizophrenics had more impairment in neuropsychological tests than paranoid schizophrenics.

  8. Granulomatous slack skin: a rare subtype of mycosis fungoides.

    Science.gov (United States)

    Motta, Letícia Marra da; Soares, Cleverson Teixeira; Nakandakari, Sadamitsu; Silva, Gardênia Viana da; Nigro, Maria Helena Mazzi Freire; Brandão, Leticia Stella Gardini

    2017-01-01

    We report a case of granulomatous slack skin, a rare and indolent subtype of mycosis fungoides. It affects mainly men between the third and fourth decades. It is characterized by hardened and erithematous plaques that mainly affect flexural areas and become pedunculated after some years. Histological examination shows a dense infiltrate of small atypical lymphocytes involving the dermis (and sometimes the subcutaneous tissue) associated with histiocytic and multinucleated giant cells containing lymphocytes and elastic fibers (lymphophagocytosis and elastophagocytosis, respectively). Patients affected by this entity can develop secondary lymphomas. There are several but little effective therapeutic modalities described. Despite the indolent behavior of granulomatous slack skin, its early recognition and continuous monitoring by a dermatologist becomes essential for its management and prevention of an unfavorable outcome.

  9. Molecular subtype classification of urothelial carcinoma in Lynch syndrome

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias

    2018-01-01

    Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome......-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial...... carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed...

  10. Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

    Directory of Open Access Journals (Sweden)

    Rosa Dolz-Marco

    2014-01-01

    Full Text Available Purpose: To report corneal findings in a familial case of the crystalline subtype of pre- Descemetic corneal dystrophy. Case Report: A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion: To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti΄s dystrophy and monoclonal gammopathy.

  11. Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

    Science.gov (United States)

    Dolz-Marco, Rosa; Gallego-Pinazo, Roberto; Pinazo-Durán, María Dolores; Díaz-Llopis, Manuel

    2014-01-01

    Purpose To report corneal findings in a familial case of the crystalline subtype of pre-Descemetic corneal dystrophy. Case Report A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti´s dystrophy and monoclonal gammopathy. PMID:25279130

  12. Subtypes of depressive episodes according to ICD-10

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel

    2003-01-01

    a period from 1994 to 1999 were identified. The risk of relapse leading to readmission and the risk of committing suicide were compared for patients discharged with an ICD-10 diagnosis of a single depressive episode with and without melancholic syndrome and for patients with and without psychotic symptoms......BACKGROUND: The long-term predictive ability of the ICD-10 subtypes of depression with melancholic syndrome and depression with psychosis has not been investigated. SAMPLING AND METHODS: All patients in Denmark who had a diagnosis of a single depressive episode at their first ever discharge during......, respectively. RESULTS: In all, 1,639 patients had a diagnosis of depressive episode without psychotic symptoms, 1,275 patients a diagnosis with psychotic symptoms, 293 a diagnosis without melancholic syndrome, and 248 a diagnosis with melancholic symptoms at first discharge. The risk of relapse leading...

  13. Antisocial personality disorder--stable and unstable subtypes.

    Science.gov (United States)

    Ullrich, Simone; Coid, Jeremy

    2010-04-01

    There have been criticisms that the criteria for antisocial personality disorder (ASPD) are over-dependent on criminal behavior. This study aimed to identify unrelated criteria of social and behavioral problems and instability, and to investigate their associations in a representative household sample of adults in the UK. Approximately one third of adults with ASPD did not fulfill any of the criteria for instability. They were less aggressive and involved in illegal activities but expressed less remorse for their behaviors. Instability in ASPD was mediated primarily through comorbid anxiety disorders and borderline personality disorder. The concept of Secondary Psychopathy, which has not generally been applied to ASPD, demonstrated many similarities to the unstable subtype.

  14. [Multiple meningiomas].

    Science.gov (United States)

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Neurocognitive impairment in the deficit subtype of schizophrenia.

    Science.gov (United States)

    Fervaha, Gagan; Agid, Ofer; Foussias, George; Siddiqui, Ishraq; Takeuchi, Hiroyoshi; Remington, Gary

    2016-08-01

    Schizophrenia is a heterogeneous disorder characterized by numerous diverse signs and symptoms. Individuals with prominent, persistent, and idiopathic negative symptoms are thought to encompass a distinct subtype of schizophrenia. Previous work, including studies involving neuropsychological evaluations, has supported this position. The present study sought to further examine whether deficit patients are cognitively distinct from non-deficit patients with schizophrenia. A comprehensive neurocognitive battery including tests of verbal memory, vigilance, processing speed, reasoning, and working memory was administered to 657 patients with schizophrenia. Of these, 144 (22 %) patients were classified as deficit patients using a proxy identification method based on severity, persistence over time, and possible secondary sources (e.g., depression) of negative symptoms. Deficit patients with schizophrenia performed worse on all tests of cognition relative to non-deficit patients. These patients were characterized by a generalized cognitive impairment on the order of about 0.4 standard deviations below that of non-deficit patients. However, when comparing deficit patients to non-deficit patients who also present with negative symptoms, albeit not enduring or primary, no group differences in cognitive performance were found. Furthermore, a discriminant function analysis classifying patients into deficit/non-deficit groups based on cognitive scores demonstrated only 62.3 % accuracy, meaning over one-third of individuals were misclassified. The deficit subtype of schizophrenia is not markedly distinct from non-deficit schizophrenia in terms of neurocognitive performance. While deficit patients tend to have poorer performance on cognitive tests, the magnitude of this effect is relatively modest, translating to over 70 % overlap in scores between groups.

  16. Analysis of HIV subtypes and the phylogenetic tree in HIV-positive samples from Saudi Arabia

    International Nuclear Information System (INIS)

    Al-Zahrani, Alhusain J.

    2008-01-01

    Objective was to assess the prevalence of HIV-1 genetic subtypes in Saudi Arabia in samples that are serologically positive for HIV-1 and compare the HIV-1 genetic subtypes prevalent in Saudi Arabia with the subtypes prevalent in other countries. Thirty-nine HIV-1 positive samples were analyzed for HIV-1 subtypes using molecular techniques. The study is retrospective study that was conducted in Dammam, Kingdom of Saudi Arabia and in Abbott laboratories (United States of America) from2004 to 2007. All samples were seropositive for HIV-1 group M. Of the 39 seropositive samples, only 12 were polymerase chain reaction positive. Subtype C is the most common virus strain as it occurred in 58% of these samples; subtype B occurred in 17%; subtypes A, D and G were found in 8% each. The phylogenetic tree was also identified for the isolates. Detection of HIV subtypes is important for epidemiological purposes and may help in tracing the source of HIV infections in the Kingdom of Saudi Arabia. (author)

  17. The Complex Subtype-Dependent Role of Connexin 43 (GJA1 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mélanie Busby

    2018-02-01

    Full Text Available Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43 in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression.

  18. Classification and Validation of Behavioral Subtypes of Learning-Disabled Children.

    Science.gov (United States)

    Speece, Deborah L.; And Others

    1985-01-01

    Using the Classroom Behavior Inventory, teachers rated the behaviors of 63 school-identified, learning-disabled first and second graders. Hierarchical cluster analysis techniques identified seven distinct behavioral subtypes. Internal validation techniques indicated that the subtypes were replicable and had profile patterns different from a sample…

  19. Relationship between Self-Typicality and the In-Group Subtypes Effect.

    Science.gov (United States)

    Wallace, David S.; And Others

    1995-01-01

    Examined whether group members differ in the number of in-group subtype distinctions that they draw. Drawing on results of two studies, found that members of groups whose primary function is intragroup interaction (fraternities, sororities, athletic teams) draw more subtype distinctions within their own group than within other groups. (RJM)

  20. Genetic recombination and Cryptosporidium hominis virulent subtype IbA10G2.

    Science.gov (United States)

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

    2013-10-01

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

  1. Folic acid supplementation influences the distribution of neural tube defect subtypes : A registry-based study

    NARCIS (Netherlands)

    Bergman, J. E. H.; Otten, E.; Verheij, J. B. G. M.; de Walle, H. E. K.

    Periconceptional folic acid (FA) reduces neural tube defect (NTD) risk, but seems to have a varying effect per NTD subtype. We aimed to study the effect of FA supplementation on NTD subtype distribution using data from EUROCAT Northern Netherlands. We included all birth types with non-syndromal NTDs

  2. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability

    OpenAIRE

    Frielink, N.; Schuengel, C.; Embregts, P.J.C.M.

    2017-01-01

    Background: According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and integrated motivation. Although it has been argued theoretically that the different types of motivation are universally applicable, Reid et al. () proposed a dichotomy of broad subtypes of extrinsic ...

  3. Distribution And Clinicopathological Features Of Breast Cancer Histological Subtypes In Latvia

    Directory of Open Access Journals (Sweden)

    Srebnijs Andrejs

    2015-04-01

    Full Text Available Breast cancer is a heterogenous disease. It consists of several histological subtypes that can be separated by morphology and immunohistochemistry. The aim of our study was to determine the distribution of breast cancer histological and molecular subtypes, and their relationship with clinical and pathological characteristics. A total of 561 patients who underwent breast carcinoma surgical treatment from January 2003 till December 2012 were enrolled in the study. In total, invasive ductal carcinomas not otherwise specified (IDC-NOS plus invasive ductal carcinomas no special type (IDC-NST were observed in 430 patients (76.65% of cases, medullar carcinoma in 14 patients (2.45%, other rare ductal carcinoma subtypes in 13 patients (2.31%, lobular carcinoma in 81 patients (14.4% and tubulolobular carcinoma in 23 patients (4.19%. Ductal carcinoma, lobular and tubulolobular carcinoma had predominantly luminal A and B subtype, whereas medullar carcinoma had HER2-positive and triple-negative (TN subtype. Tubular, cribriform, mucinous, papillary, and apocrine carcinomas had predominantly luminal A subtype. Significant differences between breast cancer histological subtypes and clinicopathological characteristics were observed. Our study for the first time reported the distribution and characteristics of breast cancer histological subtypes in Latvian women and relationship to clinical and tumour histopathological characteristics.

  4. Clinical subtypes of delirium and their relevance for daily clinical practice: a systematic review

    NARCIS (Netherlands)

    de Rooij, S. E.; Schuurmans, M. J.; van der Mast, R. C.; Levi, M. [=Marcel M.

    2005-01-01

    Background Delirium is a disorder that besides four essential features consists of different combinations of symptoms. We reviewed the clinical classification of clusters of symptoms in two or three delirium subtypes. The possible implications of this subtype classification may be several. The

  5. Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test

    Directory of Open Access Journals (Sweden)

    A.M. Valença

    2002-07-01

    Full Text Available The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2 challenge test of panic disorder (PD patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in a double-blind manner using two mixtures: 1 35% CO2 and 65% O2, and 2 100% atmospheric compressed air, 20 min apart. The tests were repeated after 2 weeks during which the participants in the study did not receive any psychotropic drugs. At least 15 of 16 (93.7% respiratory PD subtype patients and 5 of 11 (43.4% nonrespiratory PD patients had a panic attack during one of two CO2 challenges (P = 0.009, Fisher exact test. Respiratory PD subtype patients were more sensitive to the CO2 challenge test. There was agreement between the severity of PD measured by the Clinical Global Impression (CGI Scale and the subtype of PD. Higher CGI scores in the respiratory PD subtype could reflect a greater sensitivity to the CO2 challenge due to a greater severity of PD. Carbon dioxide challenges in PD may define PD subtypes and their underlying mechanisms.

  6. Distinct molecular subtypes of uterine leiomyosarcoma respond differently to chemotherapy treatment.

    Science.gov (United States)

    An, Yang; Wang, Shuzhen; Li, Songlin; Zhang, Lulu; Wang, Dayong; Wang, Haojie; Zhu, Shibai; Zhu, Wan; Li, Yongqiang; Chen, Wenwu; Ji, Shaoping; Guo, Xiangqian

    2017-09-11

    Uterine leiomyosarcoma (ULMS) is an aggressive form of soft tissue tumors. The molecular heterogeneity and pathogenesis of ULMS are not well understood. Expression profiling data were used to determine the possibility and optimal number of ULMS molecular subtypes. Next, clinicopathological characters and molecular pathways were analyzed in each subtype to prospect the clinical applications and progression mechanisms of ULMS. Two distinct molecular subtypes of ULMS were defined based on different gene expression signatures. Subtype I ULMS recapitulated low-grade ULMS, the gene expression pattern of which resembled normal smooth muscle cells, characterized by overexpression of smooth muscle function genes such as LMOD1, SLMAP, MYLK, MYH11. In contrast, subtype II ULMS recapitulated high-grade ULMS with higher tumor weight and invasion rate, and was characterized by overexpression of genes involved in the pathway of epithelial to mesenchymal transition and tumorigenesis, such as CDK6, MAPK13 and HOXA1. We identified two distinct molecular subtypes of ULMS responding differently to chemotherapy treatment. Our findings provide a better understanding of ULMS intrinsic molecular subtypes, and will potentially facilitate the development of subtype-specific diagnosis biomarkers and therapy strategies for these tumors.

  7. Avian metapneumovirus subtypes circulating in Brazilian vaccinated and nonvaccinated chicken and turkey farms.

    Science.gov (United States)

    Chacón, Jorge Luis; Mizuma, Matheus; Vejarano, Maria P; Toquín, Didier; Eterradossi, Nicolas; Patnayak, Devi P; Goyal, Sagar M; Ferreira, Antonio J Piantino

    2011-03-01

    Avian metapneumovirus (AMPV) causes turkey rhinotracheitis and is associated with swollen head syndrome in chickens, which is usually accompanied by secondary infections that increase mortality. AMPVs circulating in Brazilian vaccinated and nonvaccinated commercial chicken and turkey farms were detected using a universal reverse transcriptase (RT)-PCR assay that can detect the four recognized subtypes of AMPV. The AMPV status of 228 farms with respiratory and reproductive disturbances was investigated. AMPV was detected in broiler, hen, breeder, and turkey farms from six different geographic regions of Brazil. The detected viruses were subtyped using a nested RT-PCR assay and sequence analysis of the G gene. Only subtypes A and B were detected in both vaccinated and nonvaccinated farms. AMPV-A and AMPV-B were detected in 15 and 23 farms, respectively, while both subtypes were simultaneously found in one hen farm. Both vaccine and field viruses were detected in nonvaccinated farms. In five cases, the detected subtype was different than the vaccine subtype. Field subtype B virus was detected mainly during the final years of the survey period. These viruses showed high molecular similarity (more than 96% nucleotide similarity) among themselves and formed a unique phylogenetic group, suggesting that they may have originated from a common strain. These results demonstrate the cocirculation of subtypes A and B in Brazilian commercial farms.

  8. The Complex Subtype-Dependent Role of Connexin 43 (GJA1) in Breast Cancer

    Science.gov (United States)

    Busby, Mélanie; Hallett, Michael T.; Plante, Isabelle

    2018-01-01

    Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression. PMID:29495625

  9. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Feng-Yang, E-mail: fyzheng16@fudan.edu.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Lu, Qing, E-mail: lu.qing@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Huang, Bei-Jian, E-mail: huang.beijian@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Xia, Han-Sheng, E-mail: zs12036@126.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Yan, Li-Xia, E-mail: dndyanlixia@163.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Wang, Xi, E-mail: wang.xi@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Yuan, Wei, E-mail: yuan.wei@zs-hospital.sh.cn [Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Wang, Wen-Ping, E-mail: wang.wenping@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China)

    2017-01-15

    Highlights: • ABVS imaging features have a strong correlation with breast cancer molecular subtypes. • Retraction phenomenon on the coronal planes was the most important predictor for Luminal A and Triple Negative subtypes. • ABVS expand the scope of ultrasound in identifying breast cancer molecular subtypes. - Abstract: Objectives: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. Methods: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. Results: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n = 128) were retraction phenomenon (odds ratio [OR] = 10.188), post-acoustic shadowing (OR = 5.112), and echogenic halo (OR = 3.263, P < 0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n = 39) were calcifications (OR = 6.210), absence of retraction phenomenon (OR = 4.375), non-mass lesions (OR = 4.286, P < 0.001), absence of echogenic halo (OR = 3.851, P = 0.035), and post-acoustic enhancement (OR = 3.641, P = 0.008). The predictors for the Triple-Negative subtype (n = 47) were absence of retraction phenomenon (OR = 5.884), post-acoustic enhancement (OR = 5.255, P < 0.001), absence of echogenic halo (OR = 4.138, P = 0.002), and absence of calcifications (OR = 3.363, P = 0.001). Predictors for the Luminal-B subtype (n = 89) had a relatively lower association (OR ≤ 2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for

  10. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer

    International Nuclear Information System (INIS)

    Zheng, Feng-Yang; Lu, Qing; Huang, Bei-Jian; Xia, Han-Sheng; Yan, Li-Xia; Wang, Xi; Yuan, Wei; Wang, Wen-Ping

    2017-01-01

    Highlights: • ABVS imaging features have a strong correlation with breast cancer molecular subtypes. • Retraction phenomenon on the coronal planes was the most important predictor for Luminal A and Triple Negative subtypes. • ABVS expand the scope of ultrasound in identifying breast cancer molecular subtypes. - Abstract: Objectives: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. Methods: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. Results: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n = 128) were retraction phenomenon (odds ratio [OR] = 10.188), post-acoustic shadowing (OR = 5.112), and echogenic halo (OR = 3.263, P < 0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n = 39) were calcifications (OR = 6.210), absence of retraction phenomenon (OR = 4.375), non-mass lesions (OR = 4.286, P < 0.001), absence of echogenic halo (OR = 3.851, P = 0.035), and post-acoustic enhancement (OR = 3.641, P = 0.008). The predictors for the Triple-Negative subtype (n = 47) were absence of retraction phenomenon (OR = 5.884), post-acoustic enhancement (OR = 5.255, P < 0.001), absence of echogenic halo (OR = 4.138, P = 0.002), and absence of calcifications (OR = 3.363, P = 0.001). Predictors for the Luminal-B subtype (n = 89) had a relatively lower association (OR ≤ 2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for

  11. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, Egon; Stenager, E N; Knudsen, Lone

    1994-01-01

    In a cross-sectional study of 117 randomly selected patients (52 men, 65 women) with definite multiple sclerosis, it was found that 76 percent were married or cohabitant, 8 percent divorced. Social contacts remained unchanged for 70 percent, but outgoing social contacts were reduced for 45 percent......, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap...

  12. CRISPR typing and subtyping for improved laboratory surveillance of Salmonella infections.

    Directory of Open Access Journals (Sweden)

    Laëtitia Fabre

    Full Text Available Laboratory surveillance systems for salmonellosis should ideally be based on the rapid serotyping and subtyping of isolates. However, current typing methods are limited in both speed and precision. Using 783 strains and isolates belonging to 130 serotypes, we show here that a new family of DNA repeats named CRISPR (clustered regularly interspaced short palindromic repeats is highly polymorphic in Salmonella. We found that CRISPR polymorphism was strongly correlated with both serotype and multilocus sequence type. Furthermore, spacer microevolution discriminated between subtypes within prevalent serotypes, making it possible to carry out typing and subtyping in a single step. We developed a high-throughput subtyping assay for the most prevalent serotype, Typhimurium. An open web-accessible database was set up, providing a serotype/spacer dictionary and an international tool for strain tracking based on this innovative, powerful typing and subtyping tool.

  13. Association between maternal comorbidity and preterm birth by severity and clinical subtype: retrospective cohort study.

    Science.gov (United States)

    Auger, Nathalie; Le, Thi Uyen Nhi; Park, Alison L; Luo, Zhong-Cheng

    2011-10-04

    Preterm birth (PTB) is a major cause of infant morbidity and mortality, but the relationship between comorbidity and PTB by clinical subtype and severity of gestational age remains poorly understood. We evaluated associations between maternal comorbidities and PTB by clinical subtype and gestational age. We conducted a retrospective cohort study of 1,329,737 singleton births delivered in hospitals in the province of Québec, Canada, 1989-2006. PTB was classified by clinical subtype (medically indicated, preterm premature rupture of membranes (PPROM), spontaneous preterm labour) and gestational age (PTBs across all gestational ages (OR > 2.0). At the population level, several major comorbidities (placental abruption, chorioamnionitis, oliogohydramnios, structural abnormality, cervical incompetence) were key contributors to all clinical subtypes of PTB, especially at PTBs. The relationship between comorbidity and clinical subtypes of PTB depends on gestational age. Prevention of PPROM and spontaneous PTB may benefit from greater attention to preeclampsia, anemia and comorbidities localized to the reproductive system.

  14. Specific trauma subtypes improve the predictive validity of the Harvard Trauma Questionnaire in Iraqi refugees.

    Science.gov (United States)

    Arnetz, Bengt B; Broadbridge, Carissa L; Jamil, Hikmet; Lumley, Mark A; Pole, Nnamdi; Barkho, Evone; Fakhouri, Monty; Talia, Yousif Rofa; Arnetz, Judith E

    2014-12-01

    Trauma exposure contributes to poor mental health among refugees, and exposure often is measured using a cumulative index of items from the Harvard Trauma Questionnaire (HTQ). Few studies, however, have asked whether trauma subtypes derived from the HTQ could be superior to this cumulative index in predicting mental health outcomes. A community sample of recently arrived Iraqi refugees (N = 298) completed the HTQ and measures of posttraumatic stress disorder (PTSD) and depression symptoms. Principal components analysis of HTQ items revealed a 5-component subtype model of trauma that accounted for more item variance than a 1-component solution. These trauma subtypes also accounted for more variance in PTSD and depression symptoms (12 and 10%, respectively) than did the cumulative trauma index (7 and 3%, respectively). Trauma subtypes provided more information than cumulative trauma in the prediction of negative mental health outcomes. Therefore, use of these subtypes may enhance the utility of the HTQ when assessing at-risk populations.

  15. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtype...... stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.......Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes...... were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations...

  16. Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Karch, André; Hermann, Peter; Ponto, Claudia; Schmitz, Matthias; Arora, Amandeep; Zafar, Saima; Llorens, Franc; Müller-Heine, Annika; Zerr, Inga

    2015-05-01

    The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an important prognostic marker for patient survival. However, subtype determination is not possible during lifetime. Because the rate of disease progression is associated with the molecular subtype, this study aimed at investigating if total tau, a marker of neuronal death, allows premortem diagnosis of molecular subtype when codon 129 genotype is known. Two hundred ninety-six sCJD patients were tested for their cerebrospinal fluid total tau level at the time of diagnosis and were investigated for their sCJD subtype postmortem. There was a significant association between tau levels and the prion protein type in patients with codon 129 MM (p disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Breast cancer subtypes: two decades of journey from cell culture to patients.

    Science.gov (United States)

    Zhao, Xiangshan; Gurumurthy, Channabasavaiah Basavaraju; Malhotra, Gautam; Mirza, Sameer; Mohibi, Shakur; Bele, Aditya; Quinn, Meghan G; Band, Hamid; Band, Vimla

    2011-01-01

    Recent molecular profiling has identified six major subtypes of breast cancers that exhibit different survival outcomes for patients. To address the origin of different subtypes of breast cancers, we have now identified, isolated, and immortalized (using hTERT) mammary stem/progenitor cells which maintain their stem/progenitor properties even after immortalization. Our decade long research has shown that these stem/progenitor cells are highly susceptible to oncogenesis. Given the emerging evidence that stem/progenitor cells are precursors of cancers and that distinct subtypes of breast cancer have different survival outcome, these cellular models provide novel tools to understand the oncogenic process leading to various subtypes of breast cancers and for future development of novel therapeutic strategies to treat different subtypes of breast cancers.

  18. Subtypes of suicide attempters based on longitudinal childhood profiles of co-occurring depressive, anxious and aggressive behavior symptoms.

    Science.gov (United States)

    Hart, Shelley R; Van Eck, Kathryn; Ballard, Elizabeth D; Musci, Rashelle J; Newcomer, Alison; Wilcox, Holly C

    2017-11-01

    Because suicide attempts are multi-determined events, multiple pathways to suicidal behaviors exist. However, as a low-frequency behavior, within group differences in trajectories to attempts may not emerge when examined in samples including non-attempters. We used longitudinal latent profile analysis to identify subtypes specific for suicide attempters based on longitudinal trajectories of childhood clinical symptoms (i.e., depression, anxiety, and aggression measured in 2nd, 4th-7th grades) for 161 young adults (35.6% male; 58.6% African American) who attempted suicide between ages 13-30 from a large, urban community-based, longitudinal prevention trial (n = 2311). Differences in psychiatric diagnoses, suicide attempt characteristics, criminal history and traumatic stress history were studied. Three subtypes emerged: those with all low (n = 32%), all high (n = 16%), and high depressive/anxious, but low aggressive (n = 52%) symptoms. Those with the highest levels of all symptoms were significantly more likely to report a younger age of suicide attempt, and demonstrate more substance abuse disorders and violent criminal histories. Prior studies have found that childhood symptoms of depression, anxiety and aggression are malleable targets; interventions directed at each reduce future risk for suicidal behaviors. Our findings highlight the link of childhood aggression with future suicidal behaviors extending this research by examining childhood symptoms of aggression in the context of depression and anxiety. Copyright © 2017. Published by Elsevier B.V.

  19. Sleep and daytime function in adults with attention-deficit/hyperactivity disorder: subtype differences.

    Science.gov (United States)

    Yoon, Sun Young Rosalia; Jain, Umesh Ravi; Shapiro, Colin Michael

    2013-07-01

    Although sleep disorders have been reported to affect more than half of adults with attention-deficit/hyperactivity disorder (ADHD), the association between sleep and ADHD is poorly understood. The aims of our study were to investigate sleep-related variables in adults with ADHD and to assess if any differences exist between ADHD of the predominantly inattentive (ADHD-I) and combined (ADHD-C) subtypes. We used the Epworth sleepiness scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and the fatigue severity scale (FSS) to collect data on daytime sleepiness, sleep quality, and fatigue in 126 subjects (45 ADHD-I and 81 ADHD-C subjects). Approximately 85% of subjects reported excessive daytime sleepiness or poor sleep quality. The most common sleep concerns were initial insomnia, interrupted sleep, and feeling too hot. When examining ADHD subtype differences, ADHD-I subtypes reported poorer sleep quality and more fatigue than ADHD-C subtypes. Partial correlation analyses revealed that interrelationships between sleep quality, daytime sleepiness, and fatigue differ between ADHD subtypes; in ADHD-I subtypes fatigue was associated with sleep quality, while in the ADHD-C subtypes fatigue was associated with both sleep quality and daytime sleepiness. There also appears to be a subtype×gender interaction that affects the perception of fatigue, as subjective fatigue was markedly higher in ADHD-I women than in ADHD-C women. Altogether our data indicate that the interplay of variables associated with daytime function and sleep varies between ADHD subtypes. This finding may have considerable relevance in the management and pathophysiologic understanding of ADHD, and thus lead to tailored treatments for ADHD subtypes. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  20. Origin and dynamics of HIV-1 subtype C infection in India.

    Directory of Open Access Journals (Sweden)

    Chengli Shen

    Full Text Available To investigate the geographical origin and evolution dynamics of HIV-1 subtype C infection in India.Ninety HIV-1 subtype C env gp120 subtype C sequences from India were compared with 312 env gp120 reference subtype C sequences from 27 different countries obtained from Los Alamos HIV database. All the HIV-1 subtype C env gp120 sequences from India were used for the geographical origin analysis and 61 subtype C env gp120 sequences with known sampling year (from 1991 to 2008 were employed to determine the origin of HIV infection in India.Phylogenetic analysis of HIV-1 env sequences was used to investigate the geographical origin and tMRCA of Indian HIV-1 subtype C. Evolutionary parameters including origin date and demographic growth patterns of Indian subtype C were estimated using a Bayesian coalescent-based approach under relaxed molecular clock models.The majority of the analyzed Indian and South African HIV-1 subtype C sequences formed a single monophyletic cluster. The most recent common ancestor date was calculated to be 1975.56 (95% HPD, 1968.78-1981.52. Reconstruction of the effective population size revealed three phases of epidemic growth: an initial slow growth, followed by exponential growth, and then a plateau phase approaching present time. Stabilization of the epidemic growth phase correlated with the foundation of National AIDS Control Organization in India.Indian subtype C originated from a single South African lineage in the middle of 1970s. The current study emphasizes not only the utility of HIV-1 sequence data for epidemiological studies but more notably highlights the effectiveness of community or government intervention strategies in controlling the trend of the epidemic.

  1. Multiple myeloma

    International Nuclear Information System (INIS)

    Sohn, Jeong Ick; Ha, Choon Ho; Choi, Karp Shik

    1994-01-01

    Multiple myeloma is a malignant plasma cell tumor that is thought to originate proliferation of a single clone of abnormal plasma cell resulting production of a whole monoclonal paraprotein. The authors experienced a case of multiple myeloma with severe mandibular osteolytic lesions in 46-year-old female. As a result of careful analysis of clinical, radiological, histopathological features, and laboratory findings, we diagnosed it as multiple myeloma, and the following results were obtained. 1. Main clinical symptoms were intermittent dull pain on the mandibular body area, abnormal sensation of lip and pain due to the fracture on the right clavicle. 2. Laboratory findings revealed M-spike, reversed serum albumin-globulin ratio, markedly elevated ESR and hypercalcemia. 3. Radiographically, multiple osteolytic punched-out radiolucencies were evident on the skull, zygoma, jaw bones, ribs, clavicle and upper extremities. Enlarged liver and increased uptakes on the lesional sites in RN scan were also observed. 4. Histopathologically, markedly hypercellular marrow with sheets of plasmoblasts and megakaryocytes were also observed.

  2. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K

    1988-01-01

    Forty-two (12%) of a total of 366 patients with multiple sclerosis (MS) had psychiatric admissions. Of these, 34 (81%) had their first psychiatric admission in conjunction with or after the onset of MS. Classification by psychiatric diagnosis showed that there was a significant positive correlation...

  3. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1991-01-01

    In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activities of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled...

  4. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K

    1990-01-01

    An investigation on the correlation between ability to read TV subtitles and the duration of visual evoked potential (VEP) latency in 14 patients with definite multiple sclerosis (MS), indicated that VEP latency in patients unable to read the TV subtitles was significantly delayed in comparison...

  5. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1994-01-01

    In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

  6. Multiple Sclerosis.

    Science.gov (United States)

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  7. Parenting Multiples

    Science.gov (United States)

    ... when your babies do. Though it can be hard to let go of the thousand other things you need to do, remember that your well-being is key to your ability to take care of your babies. What Problems Can Happen? It may be hard to tell multiple babies apart when they first ...

  8. Genomic characterization of H14 subtype Influenza A viruses in new world waterfowl and experimental infectivity in mallards (Anas platyrhynchos.

    Directory of Open Access Journals (Sweden)

    Andrew M Ramey

    Full Text Available Recent repeated isolation of H14 hemagglutinin subtype influenza A viruses (IAVs in the New World waterfowl provides evidence to suggest that host and/or geographic ranges for viruses of this subtype may be expanding. In this study, we used genomic analyses to gain inference on the origin and evolution of H14 viruses in New World waterfowl and conducted an experimental challenge study in mallards (Anas platyrhynchos to evaluate pathogenicity, viral replication, and transmissibility of a representative viral strain in a natural host species. Genomic characterization of H14 subtype IAVs isolated from New World waterfowl, including three isolates sequenced specifically for this study, revealed high nucleotide identity among individual gene segments (e.g. ≥95% shared identity among H14 HA gene segments. In contrast, lower shared identity was observed among internal gene segments. Furthermore, multiple neuraminidase subtypes were observed for H14 IAVs isolated in the New World. Gene segments of H14 viruses isolated after 2010 shared ancestral genetic lineages with IAVs isolated from wild birds throughout North America. Thus, genomic characterization provided evidence for viral evolution in New World waterfowl through genetic drift and genetic shift since purported introduction from Eurasia. In the challenge study, no clinical disease or lesions were observed among mallards experimentally inoculated with A/blue-winged teal/Texas/AI13-1028/2013(H14N5 or exposed via contact with infected birds. Titers of viral shedding for mallards challenged with the H14N5 IAV were highest at two days post-inoculation (DPI; however shedding was detected up to nine DPI using cloacal swabs. The distribution of viral antigen among mallards infected with H14N5 IAV was largely restricted to enterocytes lining the villi in the lower intestinal tract and in the epithelium of the bursa of Fabricius. Characterization of the infectivity of A/blue-winged teal/Texas/AI13

  9. Genomic characterization of H14 subtype influenza A viruses in New World waterfowl and experimental infectivity in mallards Anas platyrhynchos

    Science.gov (United States)

    Ramey, Andy M.; Poulson, Rebecca L.; Gonzalez-Reiche, Ana S.; Perez, Daniel R.; Stalknecht, David E.; Brown, Justin D.

    2014-01-01

    Recent repeated isolation of H14 hemagglutinin subtype influenza A viruses (IAVs) in the New World waterfowl provides evidence to suggest that host and/or geographic ranges for viruses of this subtype may be expanding. In this study, we used genomic analyses to gain inference on the origin and evolution of H14 viruses in New World waterfowl and conducted an experimental challenge study in mallards (Anas platyrhynchos) to evaluate pathogenicity, viral replication, and transmissibility of a representative viral strain in a natural host species. Genomic characterization of H14 subtype IAVs isolated from New World waterfowl, including three isolates sequenced specifically for this study, revealed high nucleotide identity among individual gene segments (e.g. ≥95% shared identity among H14 HA gene segments). In contrast, lower shared identity was observed among internal gene segments. Furthermore, multiple neuraminidase subtypes were observed for H14 IAVs isolated in the New World. Gene segments of H14 viruses isolated after 2010 shared ancestral genetic lineages with IAVs isolated from wild birds throughout North America. Thus, genomic characterization provided evidence for viral evolution in New World waterfowl through genetic drift and genetic shift since purported introduction from Eurasia. In the challenge study, no clinical disease or lesions were observed among mallards experimentally inoculated with A/blue-winged teal/Texas/AI13-1028/2013(H14N5) or exposed via contact with infected birds. Titers of viral shedding for mallards challenged with the H14N5 IAV were highest at two days post-inoculation (DPI); however shedding was detected up to nine DPI using cloacal swabs. The distribution of viral antigen among mallards infected with H14N5 IAV was largely restricted to enterocytes lining the villi in the lower intestinal tract and in the epithelium of the bursa of Fabricius. Characterization of the infectivity of A/blue-winged teal/Texas/AI13-1028/2013(H14N5) in

  10. MULTI-K: accurate classification of microarray subtypes using ensemble k-means clustering

    Directory of Open Access Journals (Sweden)

    Ashlock Daniel

    2009-08-01

    Full Text Available Abstract Background Uncovering subtypes of disease from microarray samples has important clinical implications such as survival time and sensitivity of individual patients to specific therapies. Unsupervised clustering methods have been used to classify this type of data. However, most existing methods focus on clusters with compact shapes and do not reflect the geometric complexity of the high dimensional microarray clusters, which limits their performance. Results We present a cluster-number-based ensemble clustering algorithm, called MULTI-K, for microarray sample classification, which demonstrates remarkable accuracy. The method amalgamates multiple k-means runs by varying the number of clusters and identifies clusters that manifest the most robust co-memberships of elements. In addition to the original algorithm, we newly devised the entropy-plot to control the separation of singletons or small clusters. MULTI-K, unlike the simple k-means or other widely used methods, was able to capture clusters with complex and high-dimensional structures accurately. MULTI-K outperformed other methods including a recently developed ensemble clustering algorithm in tests with five simulated and eight real gene-expression data sets. Conclusion The geometric complexity of clusters should be taken into account for accurate classification of microarray data, and ensemble clustering applied to the number of clusters tackles the problem very well. The C++ code and the data sets tested are available from the authors.

  11. MULTI-K: accurate classification of microarray subtypes using ensemble k-means clustering.

    Science.gov (United States)

    Kim, Eun-Youn; Kim, Seon-Young; Ashlock, Daniel; Nam, Dougu

    2009-08-22

    Uncovering subtypes of disease from microarray samples has important clinical implications such as survival time and sensitivity of individual patients to specific therapies. Unsupervised clustering methods have been used to classify this type of data. However, most existing methods focus on clusters with compact shapes and do not reflect the geometric complexity of the high dimensional microarray clusters, which limits their performance. We present a cluster-number-based ensemble clustering algorithm, called MULTI-K, for microarray sample classification, which demonstrates remarkable accuracy. The method amalgamates multiple k-means runs by varying the number of clusters and identifies clusters that manifest the most robust co-memberships of elements. In addition to the original algorithm, we newly devised the entropy-plot to control the separation of singletons or small clusters. MULTI-K, unlike the simple k-means or other widely used methods, was able to capture clusters with complex and high-dimensional structures accurately. MULTI-K outperformed other methods including a recently developed ensemble clustering algorithm in tests with five simulated and eight real gene-expression data sets. The geometric complexity of clusters should be taken into account for accurate classification of microarray data, and ensemble clustering applied to the number of clusters tackles the problem very well. The C++ code and the data sets tested are available from the authors.

  12. Identifying subtypes among offenders with antisocial personality disorder: a cluster-analytic study.

    Science.gov (United States)

    Poythress, Norman G; Edens, John F; Skeem, Jennifer L; Lilienfeld, Scott O; Douglas, Kevin S; Frick, Paul J; Patrick, Christopher J; Epstein, Monica; Wang, Tao

    2010-05-01

    The question of whether antisocial personality disorder (ASPD) and psychopathy are largely similar or fundamentally different constructs remains unresolved. In the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994), many of the personality features of psychopathy are cast as associated features of ASPD, although the DSM-IV offers no guidance as to how, or the extent to which, these features relate to ASPD. In a sample of 691 offenders who met DSM-IV criteria for ASPD, we used model-based clustering to identify subgroups of individuals with relatively homogeneous profiles on measures of associated features (psychopathic personality traits) and other constructs with potential etiological significance for subtypes of ASPD. Two emergent groups displayed profiles that conformed broadly to theoretical descriptions of primary psychopathy and Karpman's (1941) variant of secondary psychopathy. As expected, a third group (nonpsychopathic ASPD) lacked substantial associated features. A fourth group exhibited elevated psychopathic features as well as a highly fearful temperament, a profile not clearly predicted by extant models. Planned comparisons revealed theoretically informative differences between primary and secondary groups in multiple domains, including self-report measures, passive avoidance learning, clinical ratings, and official records. Our results inform ongoing debates about the overlap between psychopathy and ASPD and raise questions about the wisdom of placing most individuals who habitually violate social norms and laws into a single diagnostic category.

  13. Cognitive subtypes in non-affected siblings of schizophrenia patients: characteristics and profile congruency with affected family members

    NARCIS (Netherlands)

    Quee, P.J.; Alizadeh, BZ; Aleman, A.; van den Heuvel, E.R.; Bruggeman, R.; Cahn, W.; de Haan, L.; Kahn, R.; Krabbendam, L.; Linzen, D.; Myin-Germeys, I.; van Os, J; Wiersma, D.

    2013-01-01

    Background. Although cognitive subtypes have been suggested in schizophrenia patients, similar analyses have not been carried out in their non-affected siblings. Subtype classification may provide more insight into genetically driven variation in cognitive function. We investigated cognitive

  14. Marinesco-Sjögren syndrome protein SIL1 regulates motor neuron subtype-selective ER stress in ALS

    NARCIS (Netherlands)

    Filézac de L'Etang, Audrey; Maharjan, Niran; Cordeiro Braña, Marisa; Ruegsegger, Céline; Rehmann, Ruth; Goswami, Anand; Roos, Andreas; Troost, Dirk; Schneider, Bernard L.; Weis, Joachim; Saxena, Smita

    2015-01-01

    Mechanisms underlying motor neuron subtype-selective endoplasmic reticulum (ER) stress and associated axonal pathology in amyotrophic lateral sclerosis (ALS) remain unclear. Here we show that the molecular environment of the ER between motor neuron subtypes is distinct, with characteristic

  15. Seroprevalence of antibodies to Venezuelan equine encephalitis complex (subtypes IAB and VI in humans from General Belgrano Island, Formosa, Argentina

    Directory of Open Access Journals (Sweden)

    Cámara Alicia

    2003-01-01

    Full Text Available This work presents the results of the detection of antibodies (immunoglobulin G for subtypes I and VI of VEE viruses complex (Togaviridae family in people from the General Belgrano island, Formosa province (Argentina. The prevalence of neutralizing (NT antibodies for subtype VI was from 30% to 70% and the prevalence of antibodies inhibitory of hemagglutination (HI was of 0% in the first and second inquiry respectively. For the subtype IAB the prevalence of NT antibodies was from 13% to 3.6%, similar to the prevalence total for both subtypes. HI antibodies were not detected in any inquiries for any subtype. It was observed that both subtypes circulate simultaneously, while subtype VI remains constant with some peaks, subtype I was found in low level.

  16. Hepatitis C virus sequences from different patients confirm the existence and transmissibility of subtype 2q, a rare subtype circulating in the metropolitan area of Barcelona, Spain.

    Science.gov (United States)

    Martró, Elisa; Valero, Ana; Jordana-Lluch, Elena; Saludes, Verónica; Planas, Ramón; González-Candelas, Fernando; Ausina, Vicente; Bracho, Maria Alma

    2011-05-01

    The hepatitis C virus (HCV) has been classified into six genotypes and more than 70 subtypes with distinct geographical and epidemiological distributions. While 18 genotype 2 subtypes have been proposed, only 5 have had their complete sequence determined. The aim of this study was to characterize HCV isolates from three patients from the Barcelona metropolitan area of Spain for whom commercial genotyping methods provided discordant results. Full-length genome sequencing was carried out for 2 of the 3 patients; for the third patient only partial NS5B sequences could be obtained. The generated sequences were subjected to phylogenetic, recombination, and identity analyses. Sequences covering most of the HCV genome (9398 and 9566  nt in length) were obtained and showed a 90.3% identity to each other at the nucleotide level, while both sequences differed by 17.5-22.6% from the other fully sequenced genotype 2 subtypes. No evidence of recombination was found. The NS5B phylogenetic tree showed that sequences from the three patients cluster together with the only representative sequence of the provisionally designed 2q subtype, which also corresponds to a patient from Barcelona. Phylogenetic analysis of the full coding sequence showed that subtype 2q was more closely related to subtype 2k. The results obtained in this study suggest that subtype 2q now meets the requirements for confirmed designation status according to consensus criteria for HCV classification and nomenclature, and its epidemiological value is ensured as it has spread among several patients in the Barcelona metropolitan area. Copyright © 2011 Wiley-Liss, Inc.

  17. Oppositional defiant disorder dimensions and subtypes among detained male adolescent offenders.

    Science.gov (United States)

    Aebi, Marcel; Barra, Steffen; Bessler, Cornelia; Steinhausen, Hans-Christoph; Walitza, Susanne; Plattner, Belinda

    2016-06-01

    In adolescent offenders, oppositional defiant disorder (ODD) and its dimensions/subtypes have been frequently ignored due to the stronger focus on criminal behaviours. The revised criteria of the DSM-5 now allow diagnosing ODD in older youths independent of conduct disorder (CD). This study aimed at analysing ODD dimensions/subtypes and their relation to suicidality, comorbid psychiatric disorders, and criminal behaviours after release from detention in a sample of detained male adolescents. Suicidality and psychiatric disorders (including ODD symptoms) were assessed in a consecutive sample of 158 male adolescents (Mage  = 16.89 years) from the Zurich Juvenile Detention Centre. Based on previous research findings, an irritable ODD dimension and a defiant/vindictive ODD dimension based on ODD symptoms were defined. Latent Class Analysis (LCA) was used to identify distinct subtypes of adolescent offenders according to their ODD symptom profiles. Logistic regression and Cox regression were used to analyse the relations of ODD dimensions/ODD subtypes to comorbid psychopathology and criminal reoffenses from official data. The ODD-irritable dimension, but not the ODD defiant/vindictive dimension predicted comorbid anxiety, suicidality and violent reoffending. LCA identified four subtypes, namely, a no-ODD subtype, a severe ODD subtype and two moderate ODD subtypes with either defiant or irritable symptoms. The irritable ODD subtype and the severe ODD subtype were related to suicidality and comorbid affective/anxiety disorders. The irritable ODD subtype was the strongest predictor of criminal (violent) reoffending even when controlling for CD. The present findings confirm the presence of ODD dimensions/subtypes in a highly disturbed adolescent offender sample. Irritable youths were at risk of suicide and persistent criminal behaviours. Due to the severe consequences of irritability, a standardized assessment approach and a specific treatment is needed in prison to

  18. Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

    Directory of Open Access Journals (Sweden)

    Kenichi Konda

    Full Text Available Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs.We evaluated both genetic (mutations of KRAS, BRAF, TP53, and PIK3CA, and microsatellite instability [MSI] and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers alterations in 158 CRNs including 56 polypoid neoplasms (PNs, 25 granular type laterally spreading tumors (LST-Gs, 48 non-granular type LSTs (LST-NGs, 19 depressed neoplasms (DNs and 10 small flat-elevated neoplasms (S-FNs on the basis of macroscopic appearance.S-FNs showed few molecular changes except SFRP1 methylation. Significant differences in the frequency of KRAS mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs (P<0.001. By contrast, the frequency of TP53 mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively (P<0.007. We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively (P<0.005. Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05. PIK3CA mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41.We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal tumorigenesis.

  19. Avian metapneumovirus subtype C in Wild Waterfowl in Ontario, Canada.

    Science.gov (United States)

    Jardine, C M; Parmley, E J; Buchanan, T; Nituch, L; Ojkic, D

    2018-02-18

    Avian metapneumovirus (aMPV) is an emerging poultry pathogen that has a significant economic impact on poultry production worldwide. The geographic range of the virus continues to expand, and wild birds have been implicated as reservoirs of aMPV that have the potential to spread the virus over long distances. Our objective was to determine the apparent prevalence of aMPV subtype C in wild waterfowl in Ontario, Canada. Wild waterfowl were captured in August and September, 2016 as part of routine migratory waterfowl population monitoring by the Ontario Ministry of Natural Resources and Forestry. Oropharyngeal and cloacal swabs were collected from each bird and placed together for aMPV testing using real-time RT-PCR. A total of 374 live wild birds from 23 lakes were sampled and tested for aMPV. Among all ducks tested, 84 (22%) were positive for aMPV. The proportion of samples that tested positive ranged from 0% in ring-necked ducks (Aythya collaris) and green-winged teal (Anas carolinensis) to 44% (8 of 18) in American black ducks (A. rubripes). Waterfowl positive for aMPV were found at 14 of 23 lakes in the study area and the percent positive at these 14 lakes ranged between 5% and 84%. Although subtype C aMPV has been detected in a variety of wild birds in North America, this is the first report of aMPV in wild ducks in Ontario, Canada. The high apparent prevalence, particularly in mallards and American black ducks (37 and 44%, respectively), suggests that these species may be important reservoirs of aMPV. Given the potential impact of aMPV on domestic poultry and the potential role of wild birds as reservoirs of the virus, further investigation of the geographic distribution, risk factors associated with aMPV carriage in wild waterfowl and potential role of other birds in the epidemiology of aMPV in Canada is warranted. © 2018 Blackwell Verlag GmbH.

  20. Integrative clustering reveals a novel split in the luminal A subtype of breast cancer with impact on outcome

    DEFF Research Database (Denmark)

    Aure, Miriam Ragle; Vitelli, Valeria; Jernström, Sandra

    2017-01-01

    subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between...

  1. 75 FR 69046 - Notice of Determination of the High Pathogenic Avian Influenza Subtype H5N1 Status of Czech...

    Science.gov (United States)

    2010-11-10

    ... Avian Influenza Subtype H5N1 Status of Czech Republic and Sweden AGENCY: Animal and Plant Health... the highly pathogenic avian influenza (HPAI) subtype H5N1 status of the Czech Republic and Sweden... status of the Czech Republic and Sweden relative to highly pathogenic avian influenza (HPAI) subtype H5N1...

  2. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls.

    NARCIS (Netherlands)

    R.A.M. Fouchier (Ron); V.J. Munster (Vincent); A. Wallensten (Anders); T.M. Bestebroer (Theo); S. Herfst (Sander); D.J. Smith (Derek James); G.F. Rimmelzwaan (Guus); B. Olsen (Björn); A.D.M.E. Osterhaus (Albert)

    2005-01-01

    textabstractIn wild aquatic birds and poultry around the world, influenza A viruses carrying 15 antigenic subtypes of hemagglutinin (HA) and 9 antigenic subtypes of neuraminidase (NA) have been described. Here we describe a previously unidentified antigenic subtype of HA (H16), detected in viruses

  3. Multiple sclerosis

    International Nuclear Information System (INIS)

    Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

    1986-01-01

    Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

  4. Peculiarities of diagnostics and clinical course of different immunohistochemical subtypes of breast cancer

    Directory of Open Access Journals (Sweden)

    El Khazhzh M.Kh.

    2014-09-01

    Full Text Available Modern global guidelines in oncology consider treatment of various forms of breast cancer according to molecular tumor subtype. Steroid receptors, epidermal growth factor receptors, p53, Ki67 proliferative activity index and others are the key indicators of aggressiveness of malignant breast tumors. The material for this study was the retrospective study of the standard set of breast cancer immuno¬histochemical markers (estrogen receptors, progesterone, epidermal growth factor type 2 in 8171 patients. 4 groups of patients - luminal A, luminal B, triple negative and HER2-neu positive subtypes of tumors were identified according to immunohistochemical status. We analyzed overall survival without relapse in 491 patients with breast cancer, clinical data and data of immunohistochemical studies were matched. Based on the investigation it was determined that in the early stages of the disease (1-2 luminal A subtype of cancer is often diagnosed. In the late stages the most common subtype is HER2-neu positive breast cancer. Herewith, patients with luminal A subtype of cancer have the best performance of the overall survival (OS (32,91±2,33 months, and the worst results were found in patients with HER2 - neu positive breast cancer (22,58±1,28 months. The data obtained determine HER2 - neu positive subtype as the most aggressive type of breast cancer, and the luminal A subtype – as the least aggressive one.

  5. Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer

    Directory of Open Access Journals (Sweden)

    Park Hyung Seok

    2012-01-01

    Full Text Available Abstract Background Distant recurrence is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer. Methods In an investigation of 313 women with breast cancer who underwent surgery from 1994 and 2000, the expressions of estrogen and progestrone receptor (ER/PR, and human epithelial receptor-2 (HER2 were evaluated. The subtypes were defined as luminal-A, luminal-HER2, HER2-enriched, and triple negative breast cancer (TNBC according to ER, PR, and HER2 status. Results Bone was the most common site of distant recurrence. The incidence of first distant recurrence site was significantly different among the subtypes. Brain metastasis was more frequent in the luminal-HER2 and TNBC subtypes. In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was significantly different among the subtypes. Conclusions Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.

  6. Geographic distribution of hepatitis C virus genotype 6 subtypes in Thailand.

    Science.gov (United States)

    Akkarathamrongsin, Srunthron; Praianantathavorn, Kesmanee; Hacharoen, Nisachol; Theamboonlers, Apiradee; Tangkijvanich, Pisit; Tanaka, Yasuhito; Mizokami, Masashi; Poovorawan, Yong

    2010-02-01

    The nucleotide sequence of hepatitis C virus (HCV) genotype 6 found mostly in south China and south-east Asia, displays profound genetic diversity. The aim of this study to determine the genetic variability of HCV genotype 6 (HCV-6) in Thailand and locate the subtype distribution of genotype 6 in various geographic areas. Four hundred nineteen anti-HCV positive serum samples were collected from patients residing in - the central part of the country. HCV RNA positive samples based on reverse transcriptase- polymerase chain reaction (RT-PCR) of the 5'UTR were amplified with primers specific for the core and NS5B regions. Nucleotide sequences of both regions were analyzed for the genotype by phylogenetic analysis. To determine geographic distribution of HCV-6 subtypes, a search of the international database on subtype distribution in the respective countries was conducted. Among 375 HCV RNA positive samples, 71 had HCV-6 based on phylogenetic analysis of partial core and NS5B regions. The subtype distribution in order of predominance was 6f (56%), 6n (22%), 6i (11%), 6j (10%), and 6e (1%). Among the 13 countries with different subtypes of HCV-6, most sequences have been reported from Vietnam. Subtype 6f was found exclusively in Thailand where five distinct HCV-6 subtypes are circulating. HCV-6, which is endemic in south China and south-east Asia, displays profound genetic diversity and may have evolved over a considerable period of time. (c) 2009 Wiley-Liss, Inc.

  7. The Dissociative Subtype of Post-traumatic Stress Disorder: Research Update on Clinical and Neurobiological Features.

    Science.gov (United States)

    van Huijstee, Jytte; Vermetten, Eric

    2017-10-21

    Recently, a dissociative subtype of post-traumatic stress disorder (PTSD) has been included in the DSM-5. This review focuses on the clinical and neurobiological features that distinguish the dissociative subtype of PTSD from non-dissociative PTSD. Clinically, the dissociative subtype of PTSD is associated with high PTSD severity, predominance of derealization and depersonalization symptoms, a more significant history of early life trauma, and higher levels of comorbid psychiatric disorders. Furthermore, PTSD patients with dissociative symptoms exhibit different psychophysiological and neural responses to the recall of traumatic memories. While individuals with non-dissociative PTSD exhibit an increased heart rate, decreased activation of prefrontal regions, and increased activation of the amygdala in response to traumatic reminders, individuals with the dissociative subtype of PTSD show an opposite pattern. It has been proposed that dissociation is a regulatory strategy to restrain extreme arousal in PTSD through hyperinhibition of limbic regions. In this research update, promises and pitfalls in current research studies on the dissociative subtype of PTSD are listed. Inclusion of the dissociative subtype of PTSD in the DSM-5 stimulates research on the prevalence, symptomatology, and neurobiology of the dissociative subtype of PTSD and poses a challenge to improve treatment outcome in PTSD patients with dissociative symptoms.

  8. Comparison of two motor subtype classifications in de novo Parkinson's disease.

    Science.gov (United States)

    Choi, Seong-Min; Kim, Byeong C; Cho, Bang-Hoon; Kang, Kyung Wook; Choi, Kang-Ho; Kim, Joon-Tae; Lee, Seung-Han; Park, Man-Seok; Kim, Myeong-Kyu; Cho, Ki-Hyun

    2018-04-18

    Clinical subtypes of Parkinson's disease (PD) have been empirically defined based on the prominent motor symptoms. The aim of this study was to compare the prevalence of non-motor symptoms across PD motor subtypes in patients with PD. A total of 192 patients with de novo PD were included. The patients were classified into the tremor-dominant/mixed/akinetic-rigid (TD/mixed/AR) and tremor-dominant/mixed/postural instability and gait disturbance (TD/mixed/PIGD) subtypes, according to previous reports. In the TD/mixed/AR classification, scores for scales related to motor symptoms and activities of daily living (ADL) were significantly different among the groups, and patients with the AR subtype demonstrated more severe scores than patients with the TD subtype. In the TD/mixed/PIGD classification, age, age at symptom onset, scores on motor-related scales, ADL, and non-motor symptoms were significantly different among the groups. Scores including the modified Hoehn and Yahr stages, the motor and ADL subscores of the Unified Parkinson's Disease Rating Scale, the Beck Depression Inventory, and the Non-Motor Symptom Assessment Scale were significantly different after adjustments for age and age at symptom onset, and patients with the PIGD subtype obtained more severe scores than patients with the TD subtype. The TD/mixed/PIGD classification seems to be more suitable for identifying non-motor abnormalities than the TD/mixed/AR classification. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. High prevalence of luminal B breast cancer intrinsic subtype in Colombian women.

    Science.gov (United States)

    Serrano-Gomez, Silvia Juliana; Sanabria-Salas, Maria Carolina; Hernández-Suarez, Gustavo; García, Oscar; Silva, Camilo; Romero, Alejandro; Mejía, Juan Carlos; Miele, Lucio; Fejerman, Laura; Zabaleta, Jovanny

    2016-07-01

    Breast cancer is the most frequent malignancy in women worldwide. Distinct intrinsic subtypes of breast cancer have different prognoses, and their relative prevalence varies significantly among ethnic groups. Little is known about the prevalence of breast cancer intrinsic subtypes and their association with clinicopathological data and genetic ancestry in Latin Americans. Immunohistochemistry surrogates from the 2013 St. Gallen International Expert Consensus were used to classify breast cancers in 301 patients from Colombia into intrinsic subtypes. We analyzed the distribution of subtypes by clinicopathological variables. Genetic ancestry was estimated from a panel of 80 ancestry informative markers. Luminal B breast cancer subtype was the most prevalent in our population (37.2%) followed by luminal A (26.3%), non-basal triple negative (NBTN) (11.6%), basal like (9%), human epidermal growth factor receptor 2 (HER2) enriched (8.6%) and unknown (7.3%). We found statistical significant differences in distribution between Colombian region (P = 0.007), age at diagnosis (P = 0.0139), grade (P studies analyzing the molecular profiles of breast cancer in Colombian women will help us understand the molecular basis of this subtype distribution and compare the molecular characteristics of the different intrinsic subtypes in Colombian patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. HIV-1 epidemiology and circulating subtypes in the countryside of South Brazil

    Directory of Open Access Journals (Sweden)

    Carina Sperotto Librelotto

    2015-06-01

    Full Text Available INTRODUCTION: Human immunodeficiency virus type 1 (HIV-1 has spread worldwide, with several subtypes and circulating recombinant forms. Brazil has an incidence of 20.5 HIV-1/acquired immunodeficiency syndrome (AIDS patients per 100,000 inhabitants; however, the Southernmost State of Rio Grande do Sul (RS has more than twice the number of HIV-1-infected people (41.3/100,000 inhabitants and a different pattern of subtype frequencies, as previously reported in studies conducted in the capital (Porto Alegre and its metropolitan region. This study examined HIV-1/AIDS epidemiological and molecular aspects in the countryside of Rio Grande do Sul. METHODS: Socio-demographic, clinical and risk behavioral characteristics were obtained from HIV-1-positive adult patients using a structured questionnaire. HIV-1 subtypes were determined by nested-polymerase chain reaction (PCR and sequencing of the pol and env genes. RESULTS: The study sample included 149 (55% women patients with a mean age of 41.8 ± 11.9 years. Most (73.8% patients had a low education level and reported heterosexual practices as the most (91.9% probable transmission route. HIV-1 subtypes were detected in 26 patients: 18 (69.2% infected with subtype C, six (23.1% infected with subtype B and two (7.7% infected with BC recombinant forms. CONCLUSIONS: These data highlight the increasing number of HIV-1 subtype C infections in the countryside of South Brazil.

  11. Magnetic resonance imaging study of corpus callosum abnormalities in patients with different subtypes of schizophrenia

    Directory of Open Access Journals (Sweden)

    Ebru Unlu

    2014-11-01

    Full Text Available Background. Reductions in the size of the corpus callosum (CC have been described for schizophrenia patients, but little is known about the possible regional differences in schizophrenia subtypes (paranoid, disorganised, undifferentiated, residual.  Methods. We recruited 58 chronically schizophrenic patients with different subtypes, and 31 age-and-gender matched healthy controls. The callosum was extracted from a midsagittal slice from T1 weighted magnetic resonance images, and areas of the total CC, its five subregions, CC length and total brain volume were compared between schizophrenia subtypes and controls. Five subregions were approximately matched to fibre pathways from cortical regions.  Results. Schizophrenia patients had reduced CC total area and length when compared with controls. Disorganised and undifferentiated schizophrenics had a smaller prefrontal area, while there was no significant difference for the paranoid and residual groups. The premotor/supplementary motor area was smaller in all schizophrenia subtypes. The motor area was smaller only in the disorganised group. A smaller sensory area was found in all subtypes except the residual group. Parietal, temporal and occipital areas were smaller in the paranoid and undifferentiated groups. Total brain volume was smaller in all schizophrenia subtypes compared with controls, but did not reach statistical significance.  Conclusion. These findings suggest that the heterogeneity of symptoms may lead to the different CC morphological characteristics in schizophrenia subtypes.

  12. HLA-Driven Convergence of HIV-1 Viral Subtypes B and F Toward the Adaptation to Immune Responses in Human Populations

    Science.gov (United States)

    Dilernia, Dario Alberto; Jones, Leandro; Rodriguez, Sabrina; Turk, Gabriela; Rubio, Andrea E.; Pampuro, Sandra; Gomez-Carrillo, Manuel; Bautista, Christian; Deluchi, Gabriel; Benetucci, Jorge; Lasala, María Beatriz; Lourtau, Leonardo; Losso, Marcelo Horacio; Perez, Héctor; Cahn, Pedro; Salomón, Horacio

    2008-01-01

    Background Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. Methodology/Principal Findings We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naïve HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. Conclusions Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate. PMID:18941505

  13. Structure of the Unbound Form of HIV-1 Subtype A Protease: Comparison with Unbound Forms of Proteases from other HIV Subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Robbins, Arthur H.; Coman, Roxana M.; Bracho-Sanchez, Edith; Fernandez, Marty A.; Gilliland, C.Taylor; Li, Mi; Agbandje-McKenna, Mavis; Wlodawer, Alexander; Dunn, Ben M.; McKenna, Robert (NCI); (Florida)

    2010-03-12

    The crystal structure of the unbound form of HIV-1 subtype A protease (PR) has been determined to 1.7 {angstrom} resolution and refined as a homodimer in the hexagonal space group P6{sub 1} to an R{sub cryst} of 20.5%. The structure is similar in overall shape and fold to the previously determined subtype B, C and F PRs. The major differences lie in the conformation of the flap region. The flaps in the crystal structures of the unbound subtype B and C PRs, which were crystallized in tetragonal space groups, are either semi-open or wide open. In the present structure of subtype A PR the flaps are found in the closed position, a conformation that would be more anticipated in the structure of HIV protease complexed with an inhibitor. The amino-acid differences between the subtypes and their respective crystal space groups are discussed in terms of the differences in the flap conformations.

  14. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection.

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    Brian D Lehmann

    Full Text Available Triple-negative breast cancer (TNBC is a heterogeneous disease that can be classified into distinct molecular subtypes by gene expression profiling. Considered a difficult-to-treat cancer, a fraction of TNBC patients benefit significantly from neoadjuvant chemotherapy and have far better overall survival. Outside of BRCA1/2 mutation status, biomarkers do not exist to identify patients most likely to respond to current chemotherapy; and, to date, no FDA-approved targeted therapies are available for TNBC patients. Previously, we developed an approach to identify six molecular subtypes TNBC (TNBCtype, with each subtype displaying unique ontologies and differential response to standard-of-care chemotherapy. Given the complexity of the varying histological landscape of tumor specimens, we used histopathological quantification and laser-capture microdissection to determine that transcripts in the previously described immunomodulatory (IM and mesenchymal stem-like (MSL subtypes were contributed from infiltrating lymphocytes and tumor-associated stromal cells, respectively. Therefore, we refined TNBC molecular subtypes from six (TNBCtype into four (TNBCtype-4 tumor-specific subtypes (BL1, BL2, M and LAR and demonstrate differences in diagnosis age, grade, local and distant disease progression and histopathology. Using five publicly available, neoadjuvant chemotherapy breast cancer gene expression datasets, we retrospectively evaluated chemotherapy response of over 300 TNBC patients from pretreatment biopsies subtyped using either the intrinsic (PAM50 or TNBCtype approaches. Combined analysis of TNBC patients demonstrated that TNBC subtypes significantly differ in response to similar neoadjuvant chemotherapy with 41% of BL1 patients achieving a pathological complete response compared to 18% for BL2 and 29% for LAR with 95% confidence intervals (CIs; [33, 51], [9, 28], [17, 41], respectively. Collectively, we provide pre-clinical data that could inform

  15. Genetic Alterations in the Molecular Subtypes of Bladder Cancer: Illustration in the Cancer Genome Atlas Dataset.

    Science.gov (United States)

    Choi, Woonyoung; Ochoa, Andrea; McConkey, David J; Aine, Mattias; Höglund, Mattias; Kim, William Y; Real, Francisco X; Kiltie, Anne E; Milsom, Ian; Dyrskjøt, Lars; Lerner, Seth P

    2017-09-01

    Recent whole genome mRNA expression profiling studies revealed that bladder cancers can be grouped into molecular subtypes, some of which share clinical properties and gene expression patterns with the intrinsic subtypes of breast cancer and the molecular subtypes found in other solid tumors. The molecular subtypes in other solid tumors are enriched with specific mutations and copy number aberrations that are thought to underlie their distinct progression patterns, and biological and clinical properties. The availability of comprehensive genomic data from The Cancer Genome Atlas (TCGA) and other large projects made it possible to correlate the presence of DNA alterations with tumor molecular subtype membership. Our overall goal was to determine whether specific DNA mutations and/or copy number variations are enriched in specific molecular subtypes. We used the complete TCGA RNA-seq dataset and three different published classifiers developed by our groups to assign TCGA's bladder cancers to molecular subtypes, and examined the prevalence of the most common DNA alterations within them. We interpreted the results against the background of what was known from the published literature about the prevalence of these alterations in nonmuscle-invasive and muscle-invasive bladder cancers. The results confirmed that alterations involving RB1 and NFE2L2 were enriched in basal cancers, whereas alterations involving FGFR3 and KDM6A were enriched in luminal tumors. The results further reinforce the conclusion that the molecular subtypes of bladder cancer are distinct disease entities with specific genetic alterations. Our observation showed that some of subtype-enriched mutations and copy number aberrations are clinically actionable, which has direct implications for the clinical management of patients with bladder cancer. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  16. New paradigms for Salmonella source attribution based on microbial subtyping.

    Science.gov (United States)

    Mughini-Gras, Lapo; Franz, Eelco; van Pelt, Wilfrid

    2018-05-01

    Microbial subtyping is the most common approach for Salmonella source attribution. Typically, attributions are computed using frequency-matching models like the Dutch and Danish models based on phenotyping data (serotyping, phage-typing, and antimicrobial resistance profiling). Herewith, we critically review three major paradigms facing Salmonella source attribution today: (i) the use of genotyping data, particularly Multi-Locus Variable Number of Tandem Repeats Analysis (MLVA), which is replacing traditional Salmonella phenotyping beyond serotyping; (ii) the integration of case-control data into source attribution to improve risk factor identification/characterization; (iii) the investigation of non-food sources, as attributions tend to focus on foods of animal origin only. Population genetics models or simplified MLVA schemes may provide feasible options for source attribution, although there is a strong need to explore novel modelling options as we move towards whole-genome sequencing as the standard. Classical case-control studies are enhanced by incorporating source attribution results, as individuals acquiring salmonellosis from different sources have different associated risk factors. Thus, the more such analyses are performed the better Salmonella epidemiology will be understood. Reparametrizing current models allows for inclusion of sources like reptiles, the study of which improves our understanding of Salmonella epidemiology beyond food to tackle the pathogen in a more holistic way. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Amygdala enlargement: Temporal lobe epilepsy subtype or nonspecific finding?

    Science.gov (United States)

    Reyes, Anny; Thesen, Thomas; Kuzniecky, Ruben; Devinsky, Orrin; McDonald, Carrie R; Jackson, Graeme D; Vaughan, David N; Blackmon, Karen

    2017-05-01

    Amygdala enlargement (AE) is observed in patients with temporal lobe epilepsy (TLE), which has led to the suggestion that it represents a distinct TLE subtype; however, it is unclear whether AE is found at similar rates in other epilepsy syndromes or in healthy controls, which would limit its value as a marker for focal epileptogenicity. We compared rates of AE, defined quantitatively from high-resolution T1-weighted MRI, in a large multi-site sample of 136 patients with nonlesional localization related epilepsy (LRE), including TLE and extratemporal (exTLE) focal epilepsy, 34 patients with idiopathic generalized epilepsy (IGE), and 233 healthy controls (HCs). AE was found in all groups including HCs; however, the rate of AE was higher in LRE (18.4%) than in IGE (5.9%) and HCs (6.4%). Patients with unilateral LRE were further evaluated to compare rates of concordant ipsilateral AE in TLE and exTLE, with the hypothesis that rates of ipsilateral AE would be higher in TLE. Although ipsilateral AE was higher in TLE (19.4%) than exTLE (10.5%), this difference was not significant. Furthermore, among the 25 patients with unilateral LRE and AE, 13 (52%) had either bilateral AE or AE contralateral to seizure onset. Results suggest that AE, as defined with MRI volumetry, may represent an associated feature of nonlesional localization related epilepsy with limited seizure onset localization value. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Optimizing prophylactic treatment of migraine: Subtypes and patient matching

    Directory of Open Access Journals (Sweden)

    Michel Dib

    2008-09-01

    Full Text Available Michel DibFédération du système nerveux central, Hôpital de la Salpêtrière, Assistance Publique- Hôpitaux de Paris, FranceAbstract: Advances in our understanding of the pathophysiology of migraine have resulted in important breakthroughs in treatment. For example, understanding of the role of serotonin in the cerebrovascular circulation has led to the development of triptans for the acute relief of migraine headaches, and the identification of cortical spreading depression as an early central event associated wih migraine has brought renewed interest in antiepileptic drugs for migraine prophylaxis. However, migraine still remains inadequately treated. Indeed, it is apparent that migraine is not a single disease but rather a syndrome that can manifest itself in a variety of pathological conditions. The consequences of this may be that treatment needs to be matched to particular patients. Clinical research needs to be devoted to identifying which sort of patients benefit best from which treatments, particularly in the field of prophylaxis. We propose four patterns of precipitating factors (adrenergic, serotoninergic, menstrual, and muscular which may be used to structure migraine prophylaxis. Finally, little is known about long-term outcome in treated migraine. It is possible that appropriate early prophylaxis may modify the long-term course of the disease and avoid late complications.Keywords: migraine, diagnosis, treatment, prophylaxis, subtypes

  19. Subtypes of Ovarian Cancer and Ovarian Cancer Screening

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    Masafumi Koshiyama

    2017-03-01

    Full Text Available Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed.

  20. Subtypes of Ovarian Cancer and Ovarian Cancer Screening.

    Science.gov (United States)

    Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

    2017-03-02

    Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC) and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS) did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed.

  1. Substance misuse subtypes among women convicted of homicide.

    Science.gov (United States)

    de Melo Nunes, Adriana; Baltieri, Danilo Antonio

    2013-01-01

    The proportion of women incarcerated is growing at a faster pace than that for men. The reasons for this important increase have been mainly attributed to drug-using lifestyle and drug-related offenses. About half of female inmates have history of substance misuse and one third demonstrate high impulsiveness levels. The objectives of this study were to (a) identify subtypes of alcohol and drug problems and impulsiveness among women convicted of homicide, and (b) examine the association between psychosocial and criminological features and the resulting clusters. Data come from 158 female inmates serving a sentence for homicide in the Penitentiary of Sant'Ana in São Paulo State, Brazil. Latent class analysis was used to group participants into substance misuse and impulsiveness classes. Two classes were identified: nonproblematic (cluster 1: 54.53%, n = 86) and problematic (cluster 2: 45.57%, n = 72) ones. After controlling for several psychosocial and criminological variables, cluster 2 inmates showed an earlier beginning of criminal activities and a lower educational level than their counterparts. To recognize the necessities of specific groups of female offenders is crucial for the development of an adequate system of health politics and for the decrease of criminal recidivism among those offenders who have shown higher risk.

  2. Subtypes of GABAergic neurons project axons in the neocortex

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    Shigeyoshi Higo

    2009-11-01

    Full Text Available γ-aminobutyric acid (GABAergic neurons in the neocortex have been regarded as interneurons and speculated to modulate the activity of neurons locally. Recently, however, several experiments revealed that neuronal nitric oxide synthase (nNOS-positive GABAergic neurons project cortico-cortically with long axons. In this study, we illustrate Golgi-like images of the nNOS-positive GABAergic neurons using a nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d reaction and follow the emanating axon branches in cat brain sections. These axon branches projected cortico-cortically with other non-labeled arcuate fibers, contra-laterally via the corpus callosum and anterior commissure. The labeled fibers were not limited to the neocortex but found also in the fimbria of the hippocampus. In order to have additional information on these GABAergic neuron projections, we investigated green fluorescent protein (GFP-labeled GABAergic neurons in GAD67-Cre knock-in / GFP Cre-reporter mice. GFP-labeled axons emanate densely, especially in the fimbria, a small number in the anterior commissure, and very sparsely in the corpus callosum. These two different approaches confirm that not only nNOS-positive GABAergic neurons but also other subtypes of GABAergic neurons project long axons in the cerebral cortex and are in a position to be involved in information processing.

  3. Oxidatively Modified Proteins in the Serous Subtype of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Sharifeh Mehrabi

    2014-01-01

    Full Text Available Serous subtype of ovarian cancer is considered to originate from fallopian epithelium mucosa that has been exposed to physiological changes resulting from ovulation. Ovulation influences an increased in inflammation of epithelial ovarian cells as results of constant exposure of cells to ROS. The imbalance between ROS and antioxidant capacities, as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids. This study applied spectrophotometric, dinitrophenylhydrazone (DNPH assay, two-dimensional gel electrophoresis, and Western blot analyses to assess the levels of oxidatively modified proteins in 100 primary serous epithelial ovarian carcinoma and normal/surrounding tissues. These samples were obtained from 56 Caucasian and 44 African-American patients within the age range of 61±10 years. Analyses showed that the levels of reactive protein carbonyl groups increased as stages progressed to malignancy. Additionally, the levels of protein carbonyls in serous ovarian carcinoma among African Americans are 40% (P<0.05 higher relative to Caucasian at similar advanced stages. Results suggest that oxidative stress is involved in the modification of carbonyl protein groups, leading to increased aggressiveness of epithelial ovarian tumors and may contribute to the disease's invasiveness among African Americans.

  4. Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals.

    Science.gov (United States)

    Ngcapu, Sinaye; Theys, Kristof; Libin, Pieter; Marconi, Vincent C; Sunpath, Henry; Ndung'u, Thumbi; Gordon, Michelle L

    2017-11-08

    The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. Here, we investigated the prevalence and association of RNase H mutations with NRTI resistance in sequences from HIV-1 subtype C infected individuals. RNase H sequences from 112 NRTI treated but virologically failing individuals and 28 antiretroviral therapy (ART)-naive individuals were generated and analysed. In addition, sequences from 359 subtype C ART-naive sequences were downloaded from Los Alamos database to give a total of 387 sequences from ART-naive individuals for the analysis. Fisher's exact test was used to identify mutations and Bayesian network learning was applied to identify novel NRTI resistance mutation pathways in RNase H domain. The mutations A435L, S468A, T470S, L484I, A508S, Q509L, L517I, Q524E and E529D were more prevalent in sequences from treatment-experienced compared to antiretroviral treatment naive individuals, however, only the E529D mutation remained significant after correction for multiple comparison. Our findings suggest a potential interaction between E529D and NRTI-treatment; however, site-directed mutagenesis is needed to understand the impact of this RNase H mutation.

  5. Identifying the receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics.

    Science.gov (United States)

    Tsuji, Motonori; Shudo, Koichi; Kagechika, Hiroyuki

    2017-03-01

    Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands.

  6. CCR 20th Anniversary Commentary: Divide and Conquer-Breast Cancer Subtypes and Response to Therapy.

    Science.gov (United States)

    Pusztai, Lajos; Rouzier, Roman; Symmans, W Fraser

    2015-08-15

    The article by Rouzier and colleagues, published in the August 15, 2005, issue of Clinical Cancer Research, demonstrated that different molecular subtypes of breast cancer have different degrees of sensitivity to chemotherapy, but the extent of response to neoadjuvant therapy has a different meaning by subtype. Several molecular subtype-specific clinical trials are under way to maximize pathologic complete response rates in triple-negative breast cancer and HER2-positive cancers, and to provide adjuvant treatment options for patients with residual invasive disease. See related article by Rouzier et al., Clin Cancer Res 2005;11(16) Aug 15, 2005;5678-85. ©2015 American Association for Cancer Research.

  7. Molecular and epidemiological characterization of HIV-1 subtypes among Libyan patients.

    Science.gov (United States)

    Daw, Mohamed A; El-Bouzedi, Abdallah; Ahmed, Mohamed O; Dau, Aghnyia A

    2017-04-28

    The epidemiological and clinical aspects of human immunodeficiency virus subtypes are of great interest worldwide. These subtypes are rarely studied in North African countries. Libya is a large country with the longest coast on the Mediterranean Sea, facing the Southern European countries. Studies on the characterization of HIV-1 subtypes are limited in Libya. This study aimed to determine the magnitude of the HIV problem among the Libyan population and to better understand the genetic diversity and the epidemiologic dynamics of HIV 1, as well as to correlate that with the risk factors involved. A total of 159 HIV-1 strains were collected from 814 HIV positive patients from the four Libyan regions during a 16-year period (1995-2010). To determine the HIV-1 subtypes, genetic analysis and molecular sequencing were carried out using provirus polygene. Epidemiologic and demographic information was obtained from each participant and correlated with HIV-1 subtypes using logistic regression. The overall prevalence of HIV among Libyans ranged from 5 to 10 per 100,000 during the study period. It was higher among intravenous drug users (IVDUs) (53.9%), blood recipients (25.9%) and heterosexuals (17.6%) than by vertical transmission (2.6%). Prevalence was higher among males aged 20-40 years (M:F 1:6, P > 0.001). Among the 159 strains of HIV-1 available for typing, 117 strains (73.6%) were subtype B, 29 (18.2%) were CRF02_AG, and 13 (8.2%) were subtype A. HIV-1 subtype B was the most prevalent all over the country, and it was more prevalent in the Northern region, particularly among IVDUs (P HIV-1 infection is emerging in Libya with a shifting prevalence of subtypes associated with the changing epidemiology of HIV-1 among risk groups. A genetic analysis of HIV-1 strains demonstrated low subtype heterogeneity with the evolution of subtype B, and CRF_20 AG, as well as HIV-1 subtype A. Our study highlights the importance of expanded surveillance programs to control HIV

  8. Identifying Cancer Subtypes from miRNA-TF-mRNA Regulatory Networks and Expression Data.

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    Taosheng Xu

    Full Text Available Identifying cancer subtypes is an important component of the personalised medicine framework. An increasing number of computational methods have been developed to identify cancer subtypes. However, existing methods rarely use information from gene regulatory networks to facilitate the subtype identification. It is widely accepted that gene regulatory networks play crucial roles in understanding the mechanisms of diseases. Different cancer subtypes are likely caused by different regulatory mechanisms. Therefore, there are great opportunities for developing methods that can utilise network information in identifying cancer subtypes.In this paper, we propose a method, weighted similarity network fusion (WSNF, to utilise the information in the complex miRNA-TF-mRNA regulatory network in identifying cancer subtypes. We firstly build the regulatory network where the nodes represent the features, i.e. the microRNAs (miRNAs, transcription factors (TFs and messenger RNAs (mRNAs and the edges indicate the interactions between the features. The interactions are retrieved from various interatomic databases. We then use the network information and the expression data of the miRNAs, TFs and mRNAs to calculate the weight of the features, representing the level of importance of the features. The feature weight is then integrated into a network fusion approach to cluster the samples (patients and thus to identify cancer subtypes. We applied our method to the TCGA breast invasive carcinoma (BRCA and glioblastoma multiforme (GBM datasets. The experimental results show that WSNF performs better than the other commonly used computational methods, and the information from miRNA-TF-mRNA regulatory network contributes to the performance improvement. The WSNF method successfully identified five breast cancer subtypes and three GBM subtypes which show significantly different survival patterns. We observed that the expression patterns of the features in some mi

  9. Human embryonic stem cell derived cardiomyocytes self-arrange with areas of different subtypes during differentiation

    DEFF Research Database (Denmark)

    Vestergaard, Maj Linea; Grubb, Søren; Rasmussen, Karen Koefoed

    2017-01-01

    to determine action potentials (AP) further revealed spatial organization of intra-clustal CM subtypes (i.e complex clusters). Nodal-, atrial- and ventricular-like APs morphologies were detected within distinct regions of complex clusters. The ability of different CM subtypes to self-organize was documented....... Finally, the β-III tubulin specific localised expression is suggested to represent a new marker for nodal CMs. This study expands our understanding of CM specialization and intra-clustal CM subtype organization, improving the foundation for studying regulatory pathways for spatial and temporal CM...

  10. Towards a brief definition of burnout syndrome by subtypes: Development of the "Burnout Clinical Subtypes Questionnaire" (BCSQ-12

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    Gili Margarita

    2011-09-01

    Full Text Available Abstract Background Burnout has traditionally been described by means of the dimensions of exhaustion, cynicism and lack of eficacy from the "Maslach Burnout Inventory-General Survey" (MBI-GS. The "Burnout Clinical Subtype Questionnaire" (BCSQ-12, comprising the dimensions of overload, lack of development and neglect, is proposed as a brief means of identifying the different ways this disorder is manifested. The aim of the study is to test the construct and criterial validity of the BCSQ-12. Method A cross-sectional design was used on a multi-occupational sample of randomly selected university employees (n = 826. An exploratory factor analysis (EFA was performed on half of the sample using the maximum likelihood (ML method with varimax orthogonal rotation, while confirmatory factor analysis (CFA was performed on the other half by means of the ML method. ROC curve analysis was preformed in order to assess the discriminatory capacity of BCSQ-12 when compared to MBI-GS. Cut-off points were proposed for the BCSQ-12 that optimized sensitivity and specificity. Multivariate binary logistic regression models were used to estimate effect size as an odds ratio (OR adjusted for sociodemographic and occupational variables. Contrasts for sex and occupation were made using Mann-Whitney U and Kruskall-Wallis tests on the dimensions of both models. Results EFA offered a solution containing 3 factors with eigenvalues > 1, explaining 73.22% of variance. CFA presented the following indices: χ2 = 112.04 (p 2/gl = 2.44, GFI = 0.958, AGFI = 0.929, RMSEA = 0.059, SRMR = 0.057, NFI = 0.958, NNFI = 0.963, IFI = 0.975, CFI = 0.974. The area under the ROC curve for 'overload' with respect to the 'exhaustion' was = 0.75 (95% CI = 0.71-0.79; it was = 0.80 (95% CI = 0.76-0.86 for 'lack of development' with respect to 'cynicism' and = 0.74 (95% CI = 0.70-0.78 for 'neglect' with respect to 'inefficacy'. The presence of 'overload' increased the likelihood of suffering from

  11. Susceptibility of Ae. aegypti (Diptera: Culicidae) to infection with epidemic (subtype IC) and enzootic (subtypes ID, IIIC, IIID) Venezuelan equine encephalitis complex alphaviruses.

    Science.gov (United States)

    Ortiz, Diana I; Kang, Wenli; Weaver, Scoti C

    2008-11-01

    To test the hypothesis that enzootic and epidemic Venezuelan equine encephalitis (VEE) complex alphaviruses can infect and be transmitted by Ae. aegypti, we conducted a series of experimental infection studies. One set of experiments tested the susceptibility of geographic strains of Ae. aegypti from Peru and Texas (U.S.A.) for epidemic (subtype IC) and enzootic (subtype ID) strains from Colombia/Venezuela, whereas the second set of experiments tested the susceptibility of Ae. aegypti from Iquitos, Peru, to enzootic VEE complex strains (subtypes ID, IIIC, and IIID) isolated in the same region, at different infectious doses. Experimental infections using artificial bloodmeals suggested that Ae. aegypti mosquitoes, particularly the strain from Iquitos, Peru, is moderately to highly susceptible to all of these VEE complex alphaviruses. The occurrence of enzootic VEE complex viruses circulating endemically in Iquitos suggests the possibility of a dengue-like transmission cycle among humans in tropical cities.

  12. Multiple inflation

    International Nuclear Information System (INIS)

    Murphy, P.J.

    1987-01-01

    The Theory of Inflation, namely, that at some point the entropy content of the universe was greatly increased, has much promise. It may solve the puzzles of homogeneity and the creation of structure. However, no particle physics model has yet been found that can successfully drive inflation. The difficulty in satisfying the constraint that the isotropy of the microwave background places on the effective potential of prospective models is immense. In this work we have codified the requirements of such models in a most general form. We have carefully calculated the amounts of inflation the various problems of the Standard Model need for their solution. We have derived a completely model independent upper bond on the inflationary Hubble parameter. We have developed a general notation with which to probe the possibilities of Multiple Inflation. We have shown that only in very unlikely circumstances will any evidence of an earlier inflation, survive the de Sitter period of its successor. In particular, it is demonstrated that it is most unlikely that two bouts of inflation will yield high amplitudes of density perturbations on small scales and low amplitudes on large. We conclude that, while multiple inflation will be of great theoretical interest, it is unlikely to have any observational impact

  13. Subtypes of attention deficit-hyperactivity disorder (ADHD) and cannabis use.

    Science.gov (United States)

    Loflin, Mallory; Earleywine, Mitch; De Leo, Joseph; Hobkirk, Andrea

    2014-03-01

    The current study examined the association between subtypes of attention-deficit/hyperactivity disorder (ADHD) and cannabis use within a sample of 2811 current users. Data were collected in 2012 from a national U.S. survey of cannabis users. A series of logistic regression equations and chi-squares were assessed for proportional differences between users. When asked about the ADHD symptoms they have experienced when not using cannabis, a higher proportion of daily users met symptom criteria for an ADHD diagnoses of the subtypes that include hyperactive-impulsive symptoms than the inattentive subtype. For nondaily users, the proportions of users meeting symptom criteria did not differ by subtype. These results have implications for identifying which individuals with ADHD might be more likely to self-medicate using cannabis. Furthermore, these findings indirectly support research linking relevant cannabinoid receptors to regulatory control.

  14. Lumbee Native American ancestry and the incidence of aggressive histologic subtypes of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Chelsea Zhang

    2015-08-01

    Conclusion: In this retrospective cohort analysis, Lumbee Native American ancestry was not a significant independent predictor of rates of high-risk histological subtypes of endometrial cancer or poor survival outcomes.

  15. GDE2 regulates subtype-specific motor neuron generation through inhibition of Notch signaling.

    Science.gov (United States)

    Sabharwal, Priyanka; Lee, Changhee; Park, Sungjin; Rao, Meenakshi; Sockanathan, Shanthini

    2011-09-22

    The specification of spinal interneuron and motor neuron identities initiates within progenitor cells, while motor neuron subtype diversification is regulated by hierarchical transcriptional programs implemented postmitotically. Here we find that mice lacking GDE2, a six-transmembrane protein that triggers motor neuron generation, exhibit selective losses of distinct motor neuron subtypes, specifically in defined subsets of limb-innervating motor pools that correlate with the loss of force-generating alpha motor neurons. Mechanistically, GDE2 is expressed by postmitotic motor neurons but utilizes extracellular glycerophosphodiester phosphodiesterase activity to induce motor neuron generation by inhibiting Notch signaling in neighboring motor neuron progenitors. Thus, neuronal GDE2 controls motor neuron subtype diversity through a non-cell-autonomous feedback mechanism that directly regulates progenitor cell differentiation, implying that subtype specification initiates within motor neuron progenitor populations prior to their differentiation into postmitotic motor neurons. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. A comparison of the vending environment among three rural subtypes of secondary schools.

    Science.gov (United States)

    Kehm, Rebecca; Davey, Cynthia S; Kubik, Martha Y; Nanney, Marilyn S

    2018-01-01

    The purpose of this study was to further explore the rural school food environment. This study assessed trends in prevalence of vending machines and vending items within and between Minnesota schools located in 3 rural subtypes: town/rural fringe, town/rural distant, and remote rural. Generalized estimating equation models were employed to analyze data from the 2006 through 2012 School Health Profiles Principal's Surveys (Profiles). All 3 rural subtypes had a statistically significant decrease in the prevalence of low nutrient energy dense (LNED) vending items between 2006 and 2012, with the exception of sports drinks. However, different vending practices were observed between rural subtypes, with town/rural fringe schools providing more LNED vending options and experiencing less positive change over time compared to town/rural distant and remote rural schools. Differences in vending machine practices emerge when rural schools are subtyped.

  17. Racial Variations in Prostate Cancer Molecular Subtypes and Androgen Receptor Signaling Reflect Anatomic Tumor Location.

    Science.gov (United States)

    Faisal, Farzana A; Sundi, Debasish; Tosoian, Jeffrey J; Choeurng, Voleak; Alshalalfa, Mohammed; Ross, Ashley E; Klein, Eric; Den, Robert; Dicker, Adam; Erho, Nicholas; Davicioni, Elai; Lotan, Tamara L; Schaeffer, Edward M

    2016-07-01

    Prostate cancer (PCa) subtypes based on ETS gene expression have been described. Recent studies suggest there are racial differences in tumor location, with PCa located anteriorly more often among African-American (AA) compared to Caucasian-American (CA) men. In this retrospective analysis of a multi-institutional cohort treated by radical prostatectomy (179 CA, 121 AA), we evaluated associations among molecular subtype, race, anatomic tumor location, and androgen receptor (AR) signaling. Subtype (m-ERG(+), m-ETS(+), m-SPINK1(+), or triple-negative) was determined using distribution-based outlier analysis. AR signaling was investigated using gene expression profiling of canonical AR targets. m-ERG(+) was more common in CA than AA men (47% vs 22%, pprostate cancer molecular subtypes, and tumor location. Location-specific differences in androgen regulation may further underlie these relationships. Copyright © 2015. Published by Elsevier B.V.

  18. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability

    NARCIS (Netherlands)

    Frielink, N.; Schuengel, C.; Embregts, P.J.C.M.

    Background According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and

  19. Most Campylobacter subtypes from sporadic infections can be found in retail poultry products and food animals

    DEFF Research Database (Denmark)

    Nielsen, Eva M.; Fussing, V.; Engberg, J.

    2006-01-01

    subtypes that were also found in food as opposed to 31% of travel-associated infections. The results showed differences in the various Campylobacter populations, e.g. the Danish population as reflected in the domestically acquired infections and the Danish-produced food was more uniform than the isolates......The subtypes of Campylobacter isolates from human infections in two Danish counties were compared to isolates from retail food samples and faecal samples from chickens, pigs and cattle. During a 1-year period, 1285 Campylobacter isolates from these sources were typed by two methods: 'Penner' heat......-stable serotyping and automated ribotyping (RiboPrinting). C. jejuni was the dominating species, but C. coli was more prevalent among food and chicken isolates (16%) compared to human isolates (4%). In total, 356 different combined sero-ribotypes (subtypes) were found. A large subtype overlap was seen between human...

  20. Highly sensitive radioimmunoassay technique for subtyping the antibody to hepatitis B surface antigen

    Energy Technology Data Exchange (ETDEWEB)

    Fang, C T; Nath, N; Berberian, H; Dodd, R Y [American Red Cross, Blood Research Laboratory, Bethesda, MD, USA

    1978-12-01

    A highly sensitive technique for determining the subtype specificity of antibody to hepatitis B surface antigen (anti-HBs) is described. Immunoadsorbent consisting of controlled pore glass coated with subtype specific HBsAg was used to remove homologous antibody from the test samples before testing them for residual antibody by a commercially available radioimmunoassay (RIA). A total of 73 anti-HBs-positive samples from asymptomatic blood donors were tested. In nearly 80% of these samples the subtype reactivity could be determined by this technique. Only 67% could be typed by conventional liquid phase absorption RIA and 22% by passive hemagglutination inhibition techniques. Among the samples with low anti-HBs titer, ad and ay subtypes were found with equal frequency; however, with the increase in anti-HBs titer, considerably higher proportion of ad specificity was detected.

  1. Rapid detection of the avian influenza virus H5N1 subtype in Egypt ...

    African Journals Online (AJOL)

    The unprecedented spread of highly pathogenic avian influenza virus subtype H5N1 in Egypt ... Effective diagnosis and control management are needed to control the disease. ... Reconstituted clinical samples consisting of H5 AIVs mixed with ...

  2. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability

    NARCIS (Netherlands)

    Frielink, N.; Schuengel, C.; Embregts, P.J.C.M.

    2017-01-01

    Background: According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and

  3. A highly sensitive radioimmunoassay technique for subtyping the antibody to hepatitis B surface antigen

    International Nuclear Information System (INIS)

    Fang, C.T.; Nath, N.; Berberian, H.; Dodd, R.Y.

    1978-01-01

    A highly sensitive technique for determining the subtype specificity of antibody to hepatitis B surface antigen (anti-HBs) is described. Immunoadsorbent consisting of controlled pore glass coated with subtype specific HBsAg was used to remove homologous antibody from the test samples before testing them for residual antibody by a commercially available radioimmunoassay (RIA). A total of 73 anti-HBs-positive samples from asymptomatic blood donors were tested. In nearly 80% of these samples the subtype reactivity could be determined by this technique. Only 67% could be typed by conventional liquid phase absorption RIA and 22% by passive hemagglutination inhibition techniques. Among the samples with low anti-HBs titer, ad and ay subtypes were found with equal frequency; however, with the increase in anti-HBs titer, considerably higher proportion of ad specificity was detected. (Auth.)

  4. HIV subtype and drug resistance patterns among drug naïve ...

    African Journals Online (AJOL)

    SERVER

    2007-08-20

    Aug 20, 2007 ... 1Institute of Human Virology, University of Maryland, Baltimore, USA. 2PSSH, Jos ... INTRODUCTION. Many genetic subtypes of HIV-1 have been characterized ..... A comprehensive panel of near-full- length clones and ...

  5. Rapid detection of the avian influenza virus H5N1 subtype in Egypt

    African Journals Online (AJOL)

    Dr

    highly pathogenic avian influenza virus subtype H5N1 in Egypt is threatening poultry and ... Key words: Avian influenza virus, H5N1, fluorescent antibody enzyme-linked immunosorbent assay (ELISA) ..... poultry and is potentially zoonotic.

  6. Achalasia symptom response after Heller myotomy segregated by high-resolution manometry subtypes.

    Science.gov (United States)

    Patel, Amit; Patel, Ami; Mirza, Faiz A; Soudagar, Samad; Sayuk, Gregory S; Gyawali, C Prakash

    2016-02-01

    Achalasia is classified into three HRM subtypes that predict outcomes from diverse management strategies. We assessed if symptomatic response varied when a single management strategy-Heller myotomy (HM)-is employed. Treatment-naive subjects with achalasia referred for HM were followed in this observational cohort study. Chicago criteria designated achalasia subtypes (subtype I: no esophageal pressurization; subtype II: panesophageal pressurization in ≥20 % swallows; subtype III: premature contractions in ≥20 % swallows). Symptom questionnaires assessed symptom burden before and after HM on five-point Likert scales (0 = no symptoms, 4 = severe symptoms) and on 10-cm visual analog scales (global symptom severity, GSS); satisfaction with HM was recorded similarly. Data were analyzed to determine predictors of GSS change across subtypes. Sixty achalasia subjects (56.1 ± 2.4 years, 55 % female) fulfilled inclusion criteria, 15 % with subtype I, 58 % with subtype II, and 27 % with subtype III achalasia. Baseline symptoms included dysphagia (solids: 85 %, liquids: 73 %), regurgitation (84 %), and chest pain (35 %); mean GSS was 7.1 ± 0.3. Upon follow-up 2.1 ± 0.2 years after HM, GSS declined to 1.9 ± 0.4 (p < 0.001), with surgical satisfaction score of 8.7 ± 0.3 out of 10; these were similar across achalasia subtypes. On univariate analysis, female gender, Eckardt score, severity of transit symptoms, and maximal IRP predicted linear GSS improvement; female gender (p = 0.003) and dysphagia for liquids (p = 0.043) remained predictive on multivariate analysis. When a uniform surgical approach is utilized, symptomatic outcome and satisfaction with therapy are similar across achalasia subtypes. Female gender and severity of dysphagia for solids may predict better HM outcome.

  7. Clustering gene expression regulators: new approach to disease subtyping.

    Directory of Open Access Journals (Sweden)

    Mikhail Pyatnitskiy

    Full Text Available One of the main challenges in modern medicine is to stratify different patient groups in terms of underlying disease molecular mechanisms as to develop more personalized approach to therapy. Here we propose novel method for disease subtyping based on analysis of activated expression regulators on a sample-by-sample basis. Our approach relies on Sub-Network Enrichment Analysis algorithm (SNEA which identifies gene subnetworks with significant concordant changes in expression between two conditions. Subnetwork consists of central regulator and downstream genes connected by relations extracted from global literature-extracted regulation database. Regulators found in each patient separately are clustered together and assigned activity scores which are used for final patients grouping. We show that our approach performs well compared to other related methods and at the same time provides researchers with complementary level of understanding of pathway-level biology behind a disease by identification of significant expression regulators. We have observed the reasonable grouping of neuromuscular disorders (triggered by structural damage vs triggered by unknown mechanisms, that was not revealed using standard expression profile clustering. For another experiment we were able to suggest the clusters of regulators, responsible for colorectal carcinoma vs adenoma discrimination and identify frequently genetically changed regulators that could be of specific importance for the individual characteristics of cancer development. Proposed approach can be regarded as biologically meaningful feature selection, reducing tens of thousands of genes down to dozens of clusters of regulators. Obtained clusters of regulators make possible to generate valuable biological hypotheses about molecular mechanisms related to a clinical outcome for individual patient.

  8. Ocular disorders in children with spastic subtype of cerebral palsy.

    Science.gov (United States)

    Ozturk, A Taylan; Berk, A Tulin; Yaman, Aylin

    2013-01-01

    To document common ocular abnormalities in children with spastic subtype of cerebral palsy (CP) and to find out whether any correlation exists between their occurance and etiologic factors. Totally 194 patients with the diagnosis of spastic type CP were enrolled in this retrospective study. Detailed ophthalmic examinations were performed. Demographic data and neuroradiological findings were documented. Kruskal-Wallis, Mann Whitney U, Pearson Chi-square tests and Student's t tests were used in the statistical analysis. The mean age was 64.7±44.2 months on the first ophthalmic examination. Prevalences of diplegia (47.4%) and tetraplegia (36.1%) were found to be higher than the frequency of hemiplegia (16.5%) in our study population. Etiologic factor was asphyxia in 60.8% of the patients. Abnormal ocular findings were present in 78.9% of the patients. Statistically significant poor vision was detected in tetraplegia group among all the spastic ubtypes of CP (P=0.000). Anisometropia and significant refractive error were found in 14.4% and 70.1% of the patients, respectively. Thirty-six children (18.6%) had nystagmus and 107 children (55.2%) had strabismus. Lower gestational age and birth weight were statistically higher in patients with esotropia than exotropia (P=0.009 and P=0.024, respectively). Abnormal morphology of the optic disc was present in 152 eyes (39.2%). Severe periventricular leukomalacia (PVL) was found in 48 patients and statistically significant poor vision was detected in the presence of PVL (P=0.000). Spastic diplegic or tetraplegic CP patients with positive neuroradiological symptoms, younger gestational age and lower birth weight ought to have detailed ophthalmic examinations as early as possible to provide best visual rehabilitation.

  9. Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype

    Science.gov (United States)

    Kanth, Priyanka; Bronner, Mary P.; Boucher, Kenneth M.; Burt, Randall W.; Neklason, Deborah W.; Hagedorn, Curt H.; Delker, Don A.

    2016-01-01

    Sessile serrated colon adenoma/polyps (SSA/Ps) are found during routine screening colonoscopy and may account for 20–30% of colon cancers. However, differentiating SSA/Ps from hyperplastic polyps (HP) with little risk of cancer is challenging and complementary molecular markers are needed. Additionally, the molecular mechanisms of colon cancer development from SSA/Ps are poorly understood. RNA sequencing was performed on 21 SSA/Ps, 10 HPs, 10 adenomas, 21 uninvolved colon and 20 control colon specimens. Differential expression and leave-one-out cross validation methods were used to define a unique gene signature of SSA/Ps. Our SSA/P gene signature was evaluated in colon cancer RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify a subtype of colon cancers that may develop from SSA/Ps. A total of 1422 differentially expressed genes were found in SSA/Ps relative to controls. Serrated polyposis syndrome (n=12) and sporadic SSA/Ps (n=9) exhibited almost complete (96%) gene overlap. A 51-gene panel in SSA/P showed similar expression in a subset of TCGA colon cancers with high microsatellite instability (MSI-H). A smaller seven-gene panel showed high sensitivity and specificity in identifying BRAF mutant, CpG island methylator phenotype high (CIMP-H) and MLH1 silenced colon cancers. We describe a unique gene signature in SSA/Ps that identifies a subset of colon cancers likely to develop through the serrated pathway. These gene panels may be utilized for improved differentiation of SSA/Ps from HPs and provide insights into novel molecular pathways altered in colon cancer arising from the serrated pathway. PMID:27026680

  10. Ocular disorders in children with spastic subtype of cerebral palsy

    Directory of Open Access Journals (Sweden)

    Aylin Yaman

    2013-04-01

    Full Text Available AIM: To document common ocular abnormalities in children with spastic subtype of cerebral palsy (CP and to find out whether any correlation exists between their occurance and etiologic factors. METHODS: Totally 194 patients with the diagnosis of spastic type CP were enrolled in this retrospective study. Detailed ophthalmic examinations were performed. Demographic data and neuroradiological findings were documented. Kruskal-Wallis, Mann Whitney U, Pearson Chi-square tests and Student’s t tests were used in the statistical analysis. RESULTS: The mean age was 64.7±44.2 months on the first ophthalmic examination. Prevalences of diplegia (47.4% and tetraplegia (36.1% were found to be higher than the frequency of hemiplegia (16.5% in our study population. Etiologic factor was asphyxia in 60.8% of the patients. Abnormal ocular findings were present in 78.9% of the patients. Statistically significant poor vision was detected in tetraplegia group among all the spastic ubtypes of CP (P=0.000. Anisometropia and significant refractive error were found in 14.4% and 70.1% of the patients, respectively. Thirty-six children (18.6% had nystagmus and 107 children (55.2% had strabismus. Lower gestational age and birth weight were statistically higher in patients with esotropia than exotropia (P=0.009 and P=0.024, respectively. Abnormal morphology of the optic disc was present in 152 eyes (39.2%. Severe periventricular leukomalacia (PVL was found in 48 patients and statistically significant poor vision was detected in the presence of PVL (P=0.000. CONCLUSION: Spastic diplegic or tetraplegic CP patients with positive neuroradiological symptoms, younger gestational age and lower birth weight ought to have detailed ophthalmic examinations as early as possible to provide best visual rehabilitation.

  11. Using Cluster Ensemble and Validation to Identify Subtypes of Pervasive Developmental Disorders

    OpenAIRE

    Shen, Jess J.; Lee, Phil Hyoun; Holden, Jeanette J.A.; Shatkay, Hagit

    2007-01-01

    Pervasive Developmental Disorders (PDD) are neurodevelopmental disorders characterized by impairments in social interaction, communication and behavior.1 Given the diversity and varying severity of PDD, diagnostic tools attempt to identify homogeneous subtypes within PDD. Identifying subtypes can lead to targeted etiology studies and to effective type-specific intervention. Cluster analysis can suggest coherent subsets in data; however, different methods and assumptions lead to different resu...

  12. Ethnic variation of the histological subtypes of renal cell carcinoma in Singapore

    Directory of Open Access Journals (Sweden)

    E.V. Ezenwa

    2014-12-01

    Conclusion: The commonest histological subtype of RCC in each of the studied ethnic groups in Singapore is clear cell carcinoma. However, most of the cancer deaths in Chinese (16.9% and Malays (66.7% were associated with the papillary cell type, while in Indians the sarcomatoid component prevailed (9.7%. Thus, the usual prognostic trend for RCC subtypes cannot be applied to all Singaporean ethnicities, necessitating individualization of prognosis for each group.

  13. Longitudinal white matter change in frontotemporal dementia subtypes and sporadic late onset Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Fanny M. Elahi

    2017-01-01

    Conclusions: All three of the canonical subtypes of FTD are associated with significant change in white matter integrity over one year. These changes are consistent enough that drug effects in future clinical trials could be detected with relatively small numbers of participants. While there are some differences in regions of change across groups, the genu of the corpus callosum is a region that could be used to track progression in studies that include all subtypes.

  14. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability

    OpenAIRE

    Frielink, N.; Schuengel, C.; Embregts, P.J.C.M.

    2017-01-01

    Background According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and integrated motivation. Although it has been argued theoretically that the different types of motivation are universally applicable, Reid et al. (2009) proposed a dichotomy of broad subtypes of extrins...

  15. Empirically derived personality subtyping for predicting clinical symptoms and treatment response in bulimia nervosa.

    Science.gov (United States)

    Haynos, Ann F; Pearson, Carolyn M; Utzinger, Linsey M; Wonderlich, Stephen A; Crosby, Ross D; Mitchell, James E; Crow, Scott J; Peterson, Carol B

    2017-05-01

    Evidence suggests that eating disorder subtypes reflecting under-controlled, over-controlled, and low psychopathology personality traits constitute reliable phenotypes that differentiate treatment response. This study is the first to use statistical analyses to identify these subtypes within treatment-seeking individuals with bulimia nervosa (BN) and to use these statistically derived clusters to predict clinical outcomes. Using variables from the Dimensional Assessment of Personality Pathology-Basic Questionnaire, K-means cluster analyses identified under-controlled, over-controlled, and low psychopathology subtypes within BN patients (n = 80) enrolled in a treatment trial. Generalized linear models examined the impact of personality subtypes on Eating Disorder Examination global score, binge eating frequency, and purging frequency cross-sectionally at baseline and longitudinally at end of treatment (EOT) and follow-up. In the longitudinal models, secondary analyses were conducted to examine personality subtype as a potential moderator of response to Cognitive Behavioral Therapy-Enhanced (CBT-E) or Integrative Cognitive-Affective Therapy for BN (ICAT-BN). There were no baseline clinical differences between groups. In the longitudinal models, personality subtype predicted binge eating (p = 0.03) and purging (p = 0.01) frequency at EOT and binge eating frequency at follow-up (p = 0.045). The over-controlled group demonstrated the best outcomes on these variables. In secondary analyses, there was a treatment by subtype interaction for purging at follow-up (p = 0.04), which indicated a superiority of CBT-E over ICAT-BN for reducing purging among the over-controlled group. Empirically derived personality subtyping appears to be a valid classification system with potential to guide eating disorder treatment decisions. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:506-514). © 2016 Wiley Periodicals, Inc.

  16. Working memory deficits in adults with ADHD: is there evidence for subtype differences?

    OpenAIRE

    Schweitzer, Julie B; Hanford, Russell B; Medoff, Deborah R

    2006-01-01

    Abstract Background Working memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD). There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, ...

  17. Emergence of canine parvovirus subtype 2b (CPV-2b) infections in Australian dogs.

    Science.gov (United States)

    Clark, Nicholas J; Seddon, Jennifer M; Kyaw-Tanner, Myat; Al-Alawneh, John; Harper, Gavin; McDonagh, Phillip; Meers, Joanne

    2018-03-01

    Tracing the temporal dynamics of pathogens is crucial for developing strategies to detect and limit disease emergence. Canine parvovirus (CPV-2) is an enteric virus causing morbidity and mortality in dogs around the globe. Previous work in Australia reported that the majority of cases were associated with the CPV-2a subtype, an unexpected finding since CPV-2a was rapidly replaced by another subtype (CPV-2b) in many countries. Using a nine-year dataset of CPV-2 infections from 396 dogs sampled across Australia, we assessed the population dynamics and molecular epidemiology of circulating CPV-2 subtypes. Bayesian phylogenetic Skygrid models and logistic regressions were used to trace the temporal dynamics of CPV-2 infections in dogs sampled from 2007 to 2016. Phylogenetic models indicated that CPV-2a likely emerged in Australia between 1973 and 1988, while CPV-2b likely emerged between 1985 and 1998. Sequences from both subtypes were found in dogs across continental Australia and Tasmania, with no apparent effect of climate variability on subtype occurrence. Both variant subtypes exhibited a classical disease emergence pattern of relatively high rates of evolution during early emergence followed by subsequent decreases in evolutionary rates over time. However, the CPV-2b subtype maintained higher mutation rates than CPV-2a and continued to expand, resulting in an increase in the probability that dogs will carry this subtype over time. Ongoing monitoring programs that provide molecular epidemiology surveillance will be necessary to detect emergence of new variants and make informed recommendations to develop reliable detection and vaccine methods. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Subtype-specific, bi-component inhibition of SK channels by low internal pH

    DEFF Research Database (Denmark)

    Peitersen, Torben; Jespersen, Thomas; Jorgensen, Nanna K

    2006-01-01

    The effects of low intracellular pH (pH(i) 6.4) on cloned small-conductance Ca2+-activated K+ channel currents of all three subtypes (SK1, SK2, and SK3) were investigated in HEK293 cells using the patch-clamp technique. In 400 nM internal Ca2+ [Ca2+]i, all subtypes were inhibited by pH(i) 6...

  19. Eating disorder subtypes differ in their rates of psychosocial improvement over treatment

    OpenAIRE

    Kelly, Allison C; Carter, Jacqueline C

    2014-01-01

    Background Individuals with Anorexia Nervosa (AN) are renowned for their poor short- and long-term treatment outcomes. To gain more insight into the reasons for these poor outcomes, the present study compared patients with AN-R (restrictive subtype), AN-BP (binge-purge subtype), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS) over 12 weeks of specialized eating disorders treatment. Eighty-nine patients completed the Eating Disorder Examination- Questionnaire (EDE-Q) ...

  20. HIV-1 subtype A infection in a community of intravenous drug users in Pakistan

    Directory of Open Access Journals (Sweden)

    Khan Muhammad N

    2006-11-01

    Full Text Available Abstract Background Data on the subtypes of HIV in a population help in predicting the potential foci of epidemic, tracking the routes of infection and following the patterns of the virus' genetic divergence. Globally, the most prevalent HIV infection is the HIV-1 subtype C. In Asia, predominant subtypes of HIV-1 are B, C, and CRF-01AE. During the last few years, HIV prevalence in Pakistan has taken the form of a concentrated epidemic in at least two high risk groups, namely, Intravenous Drug Users (IDUs and Male Sex Workers (MSWs. Factors that have facilitated the proliferation of HIV infection include transmission through a large number of repatriates and needle-sharing intravenous drug users, unscreened blood transfusions, and sexual illiteracy. The HIV subtypes infecting Pakistani populations have not been explored to date. In this study, we analyzed HIV-1 subtypes from in a high-risk community of IDUs in Karachi, the largest city of Pakistan. Methods Samples were collected from 34 IDUs after their informed consent. In addition, the study subjects were administered a questionnaire regarding their sexual behavior and travel history. For HIV analysis, DNA was extracted from the samples and analyzed for HIV types and subtypes using subtype-specific primers in a nested polymerase chain reaction (PCR. The results from this PCR were further confirmed using the Heteroduplex Mobility Assay (HMA. Results We found HIV-1 subtype A in all the 34 samples analyzed. A few of the study subjects were found to have a history of travel and stay in the United Arab Emirates. The same subjects also admitted to having contact with commercial sex workers during their stay abroad. Conclusion Our study therefore shows clade A HIV-1 to be prevalent among the IDUs in Karachi. As the prevalence of HIV in Pakistan continues to rise, more work needs to be done to track the infection, and to analyze the strains of HIV spreading through the country.

  1. SEROMONITORING OF AVIAN INFLUENZA H9 SUBTYPE IN BREEDERS AND COMMERCIAL LAYER FLOCKS

    Directory of Open Access Journals (Sweden)

    M. Numan, M. Siddique and M. S. Yousaf1

    2005-07-01

    Full Text Available A serological survey for detection of antibodies against avian influenza virus (AIV subtype H9 in vaccinated layer flocks was carried out. Serum samples were divided into age groups A, B, C, D (commercial layers and E, F, G, H (layer breeders. Haemagglutination inhibition (HI test was performed to determine serum antibodies against AIV-H9 subtype. Geometric mean titer (GMT values were calculated. Results showed the level of protection of vaccinated birds was satisfactory.

  2. Zebrafish Mnx proteins specify one motoneuron subtype and suppress acquisition of interneuron characteristics

    Directory of Open Access Journals (Sweden)

    Seredick Steve D

    2012-11-01

    Full Text Available Abstract Background Precise matching between motoneuron subtypes and the muscles they innervate is a prerequisite for normal behavior. Motoneuron subtype identity is specified by the combination of transcription factors expressed by the cell during its differentiation. Here we investigate the roles of Mnx family transcription factors in specifying the subtypes of individually identified zebrafish primary motoneurons. Results Zebrafish has three Mnx family members. We show that each of them has a distinct and temporally dynamic expression pattern in each primary motoneuron subtype. We also show that two Mnx family members are expressed in identified VeLD interneurons derived from the same progenitor domain that generates primary motoneurons. Surprisingly, we found that Mnx proteins appear unnecessary for differentiation of VeLD interneurons or the CaP motoneuron subtype. Mnx proteins are, however, required for differentiation of the MiP motoneuron subtype. We previously showed that MiPs require two temporally-distinct phases of Islet1 expression for normal development. Here we show that in the absence of Mnx proteins, the later phase of Islet1 expression is initiated but not sustained, and MiPs become hybrids that co-express morphological and molecular features of motoneurons and V2a interneurons. Unexpectedly, these hybrid MiPs often extend CaP-like axons, and some MiPs appear to be entirely transformed to a CaP morphology. Conclusions Our results suggest that Mnx proteins promote MiP subtype identity by suppressing both interneuron development and CaP axon pathfinding. This is, to our knowledge, the first report of transcription factors that act to distinguish CaP and MiP subtype identities. Our results also suggest that MiP motoneurons are more similar to V2 interneurons than are CaP motoneurons.

  3. Hormonal modulation of breast cancer gene expression: implications for intrinsic subtyping in pre-menopausal women

    OpenAIRE

    Sarah M Bernhardt; Pallave Dasari; David Walsh; Amanda R Townsend; Amanda R Townsend; Timothy J Price; Timothy J Price; Wendy V Ingman

    2016-01-01

    Clinics are increasingly adopting gene expression profiling to diagnose breast cancer subtype, providing an intrinsic, molecular portrait of the tumour. For example, the PAM50-based Prosigna test quantifies expression of 50 key genes to classify breast cancer subtype, and this method of classification has been demonstrated to be superior over traditional immunohistochemical methods that detect proteins, to predict risk of disease recurrence. However, these tests were largely developed and val...

  4. Hormonal Modulation of Breast Cancer Gene Expression: Implications for Intrinsic Subtyping in Premenopausal Women

    OpenAIRE

    Bernhardt, Sarah M.; Dasari, Pallave; Walsh, David; Townsend, Amanda R.; Price, Timothy J.; Ingman, Wendy V.

    2016-01-01

    Clinics are increasingly adopting gene-expression profiling to diagnose breast cancer subtype, providing an intrinsic, molecular portrait of the tumor. For example, the PAM50-based Prosigna test quantifies expression of 50 key genes to classify breast cancer subtype, and this method of classification has been demonstrated to be superior over traditional immunohistochemical methods that detect proteins, to predict risk of disease recurrence. However, these tests were largely developed and vali...

  5. Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data

    OpenAIRE

    REN, ZHONGLU; WANG, WENHUI; LI, JINMING

    2015-01-01

    Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristi...

  6. Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

    Directory of Open Access Journals (Sweden)

    Ravi Goyal

    Full Text Available In response to hypoxia and other stress, the sympathetic (adrenergic nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1 - adrenergic receptor (AR subtypes (α1A-, α1B-, and α1D-AR. Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH, contractility of middle cerebral arteries (MCA is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m and those exposed to LTH (110 days at 3801 m. Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05 in the maximum tension achieved by 10-5 M phenylephrine (PHE. LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05 inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05 α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

  7. lncRNA Gene Signatures for Prediction of Breast Cancer Intrinsic Subtypes and Prognosis

    Directory of Open Access Journals (Sweden)

    Silu Zhang

    2018-01-01

    Full Text Available Background: Breast cancer is intrinsically heterogeneous and is commonly classified into four main subtypes associated with distinct biological features and clinical outcomes. However, currently available data resources and methods are limited in identifying molecular subtyping on protein-coding genes, and little is known about the roles of long non-coding RNAs (lncRNAs, which occupies 98% of the whole genome. lncRNAs may also play important roles in subgrouping cancer patients and are associated with clinical phenotypes. Methods: The purpose of this project was to identify lncRNA gene signatures that are associated with breast cancer subtypes and clinical outcomes. We identified lncRNA gene signatures from The Cancer Genome Atlas (TCGA RNAseq data that are associated with breast cancer subtypes by an optimized 1-Norm SVM feature selection algorithm. We evaluated the prognostic performance of these gene signatures with a semi-supervised principal component (superPC method. Results: Although lncRNAs can independently predict breast cancer subtypes with satisfactory accuracy, a combined gene signature including both coding and non-coding genes will give the best clinically relevant prediction performance. We highlighted eight potential biomarkers (three from coding genes and five from non-coding genes that are significantly associated with survival outcomes. Conclusion: Our proposed methods are a novel means of identifying subtype-specific coding and non-coding potential biomarkers that are both clinically relevant and biologically significant.

  8. Admixture analysis of the diagnostic subtypes of social anxiety disorder: implications for the DSM-V.

    Science.gov (United States)

    Aderka, Idan M; Nickerson, Angela; Hofmann, Stefan G

    2012-06-01

    Much controversy exists regarding diagnostic subtypes of social anxiety disorder (SAD). The present study used admixture analysis to examine whether individuals with generalized and nongeneralized SAD belong to the same or different populations of origin. This can inform diagnostic subtyping of SAD in the forthcoming DSM-V. Treatment-seeking individuals with generalized SAD (n = 154) and nongeneralized SAD (n = 48) completed a battery of questionnaires. Based on participants' responses to the Liebowitz Social Anxiety Scale (LSAS), we estimated log likelihood and chi-square goodness-of-fit for models with 1, 2, 3, or 4 populations of origin, and compared models using forward stepwise estimation and maximum likelihood ratio tests. Admixture analyses suggested that the two diagnostic subtypes of SAD belong to the same underlying population of origin. In addition, observable differences in depression, general anxiety, and comorbidity were no longer significant when controlling for social anxiety severity. Our sample was recruited in the U.S. and was a treatment-seeking sample. Future studies should examine whether our results generalize to different cultures, and community samples. Support for qualitative differences between SAD subtypes was not found. Rather, our findings support the notion that the diagnostic subtypes of SAD differ quantitatively, and that SAD exists on a continuum of severity. This finding informs diagnostic subtyping of SAD in the forthcoming DSM-V. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Association Between Imaging Characteristics and Different Molecular Subtypes of Breast Cancer.

    Science.gov (United States)

    Wu, Mingxiang; Ma, Jie

    2017-04-01

    Breast cancer can be divided into four major molecular subtypes based on the expression of hormone receptor (estrogen receptor and progesterone receptor), human epidermal growth factor receptor 2, HER2 status, and molecular proliferation rate (Ki67). In this study, we sought to investigate the association between breast cancer subtype and radiological findings in the Chinese population. Medical records of 300 consecutive invasive breast cancer patients were reviewed from the database: the Breast Imaging Reporting and Data System. The imaging characteristics of the lesions were evaluated. The molecular subtypes of breast cancer were classified into four types: luminal A, luminal B, HER2 overexpressed (HER2), and basal-like breast cancer (BLBC). Univariate and multivariate logistic regression analyses were performed to assess the association between the subtype (dependent variable) and mammography or 15 magnetic resonance imaging (MRI) indicators (independent variables). Luminal A and B subtypes were commonly associated with "clustered calcification distribution," "nipple invasion," or "skin invasion" (P cancers showed association with persistent enhancement in the delayed phase on MRI and "clustered calcification distribution" on mammography (P breast tumor, which are potentially useful tools in the diagnosis and subtyping of breast cancer. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  10. Dissociative subtype of DSM-5 posttraumatic stress disorder in U.S. veterans.

    Science.gov (United States)

    Tsai, Jack; Armour, Cherie; Southwick, Steven M; Pietrzak, Robert H

    2015-01-01

    The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) formally introduced a dissociative subtype of posttraumatic stress disorder (PTSD). This study examined the proportion of U.S. veterans with DSM-5 PTSD that report dissociative symptoms; and compared veterans with PTSD with and without the dissociative subtype and trauma-exposed controls on sociodemographics, clinical characteristics, and quality of life. Multivariable analyses were conducted on a nationally representative sample of 1484 veterans from the National Health and Resilience in Veterans Study (second baseline survey conducted September-October, 2013). Of the 12.0% and 5.2% of veterans who screened positive for lifetime and past-month DSM-5 PTSD, 19.2% and 16.1% screened positive for the dissociative subtype, respectively. Among veterans with PTSD, those with the dissociative subtype reported more severe PTSD symptoms, comorbid depressive and anxiety symptoms, alcohol use problems, and hostility than those without the dissociative subtype. Adjusting for PTSD symptom severity, those with the dissociative subtype continued to report more depression and alcohol use problems. These results underscore the importance of assessing, monitoring, and treating the considerable proportion of veterans with PTSD and dissociative symptoms. Published by Elsevier Ltd.

  11. The Prion Protein Preference of Sporadic Creutzfeldt-Jakob Disease Subtypes*

    Science.gov (United States)

    Klemm, Helen M. J.; Welton, Jeremy M.; Masters, Colin L.; Klug, Genevieve M.; Boyd, Alison; Hill, Andrew F.; Collins, Steven J.; Lawson, Victoria A.

    2012-01-01

    Sporadic Creutzfeldt-Jakob disease (CJD) is the most prevalent manifestation of the transmissible spongiform encephalopathies or prion diseases affecting humans. The disease encompasses a spectrum of clinical phenotypes that have been correlated with molecular subtypes that are characterized by the molecular mass of the protease-resistant fragment of the disease-related conformation of the prion protein and a polymorphism at codon 129 of the gene encoding the prion protein. A cell-free assay of prion protein misfolding was used to investigate the ability of these sporadic CJD molecular subtypes to propagate using brain-derived sources of the cellular prion protein (PrPC). This study confirmed the presence of three distinct sporadic CJD molecular subtypes with PrPC substrate requirements that reflected their codon 129 associations in vivo. However, the ability of a sporadic CJD molecular subtype to use a specific PrPC substrate was not determined solely by codon 129 as the efficiency of prion propagation was also influenced by the composition of the brain tissue from which the PrPC substrate was sourced, thus indicating that nuances in PrPC or additional factors may determine sporadic CJD subtype. The results of this study will aid in the design of diagnostic assays that can detect prion disease across the diversity of sporadic CJD subtypes. PMID:22930754

  12. Latent constructs underlying sensory subtypes in children with autism: A preliminary study.

    Science.gov (United States)

    Hand, Brittany N; Dennis, Simon; Lane, Alison E

    2017-08-01

    Recent reports identify sensory subtypes in ASD based on shared patterns of responses to daily sensory stimuli [Ausderau et al., 2014; Lane, Molloy, & Bishop, 2014]. Lane et al. propose that two broad sensory dimensions, sensory reactivity and multisensory integration, best explain the differences between subtypes, however this has yet to be tested. The present study tests this hypothesis by examining the latent constructs underlying Lane's sensory subtypes. Participants for this study were caregivers of children with autism spectrum disorder (ASD) aged 2-12 years. Caregiver responses on the Short Sensory Profile (SSP), used to establish Lane's sensory subtypes, were extracted from two existing datasets (total n = 287). Independent component analyses were conducted to test the fit and interpretability of a two-construct structure underlying the SSP, and therefore, the sensory subtypes. The first construct was largely comprised of the taste/smell sensitivity domain, which describes hyper-reactivity to taste and smell stimuli. The second construct had a significant contribution from the low energy/weak domain, which describes behaviors that may be indicative of difficulties with multisensory integration. Findings provide initial support for our hypothesis that sensory reactivity and multisensory integration underlie Lane's sensory subtypes in ASD. Autism Res 2017, 10: 1364-1371. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

  13. Distinct subtype distribution and somatic mutation spectrum of lymphomas in East Asia.

    Science.gov (United States)

    Ren, Weicheng; Li, Wei; Ye, Xiaofei; Liu, Hui; Pan-Hammarström, Qiang

    2017-07-01

    Here, we give an updated overview of the subtype distribution of lymphomas in East Asia and also present the genome sequencing data on two major subtypes of these tumors. The distribution of lymphoma types/subtypes among East Asian countries is very similar, with a lower proportion of B-cell malignancies and a higher proportion of T/natural killer (NK)-cell lymphomas as compared to Western populations. Extranodal NK/T-cell lymphoma is more frequently observed in East Asia, whereas follicular lymphoma and chronic lymphocytic leukemia, are proportionally lower. The incidence rate of lymphoma subtypes in Asians living in the US was generally intermediate to the general rate in US and Asia, suggesting that both genetic and environmental factors may underlie the geographical variations observed.Key cancer driver mutations have been identified in Asian patients with diffuse large B-cell lymphoma or extranodal NK/T-cell lymphoma through genome sequencing. A distinct somatic mutation profile has also been observed in Chinese diffuse large B-cell lymphoma patients. The incidence and distribution of lymphoma subtypes differed significantly between patients from East Asia and Western countries, suggesting subtype-specific etiologic mechanisms. Further studies on the mechanism underlying these geographical variations may give new insights into our understanding of lymphomagenesis.

  14. [Attention characteristics of children with different clinical subtypes of attention deficit hyperactivity disorder].

    Science.gov (United States)

    Liu, Wen-Long; Zhao, Xu; Tan, Jian-Hui; Wang, Juan

    2014-09-01

    To explore the attention characteristics of children with different clinical subtypes of attention deficit hyperactivity disorder (ADHD) and to provide a basis for clinical intervention. A total of 345 children diagnosed with ADHD were selected and the subtypes were identified. Attention assessment was performed by the intermediate visual and auditory continuous performance test at diagnosis, and the visual and auditory attention characteristics were compared between children with different subtypes. A total of 122 normal children were recruited in the control group and their attention characteristics were compared with those of children with ADHD. The scores of full scale attention quotient (AQ) and full scale response control quotient (RCQ) of children with all three subtypes of ADHD were significantly lower than those of normal children (Phyperactive/impulsive subtype (Pattention function of children with ADHD is worse than that of normal children, and the impairment of visual attention function is severer than that of auditory attention function. The degree of functional impairment of visual or auditory attention shows no significant differences between three subtypes of ADHD.

  15. SUBTYPE COASTLINE DETERMINATION IN URBAN COAST BASED ON MULTISCALE FEATURES: A CASE STUDY IN TIANJIN, CHINA

    Directory of Open Access Journals (Sweden)

    Y. Song

    2018-04-01

    Full Text Available In urban coast, coastline is a direct factor to reflect human activities. It is of crucial importance to the understanding of urban growth, resource development and ecological environment. Due to complexity and uncertainty in this type of coast, it is difficult to detect accurate coastline position and determine the subtypes of the coastline. In this paper, we present a multiscale feature-based subtype coastline determination (MFBSCD method to extract coastline and determine the subtypes. In this method, uncertainty-considering coastline detection (UCCD method is proposed to separate water and land for more accurate coastline position. The MFBSCD method can well integrate scale-invariant features of coastline in geometry and spatial structure to determine coastline in subtype scale, and can make subtypes verify with each other during processing to ensure the accuracy of final results. It was applied to Landsat Thematic Mapper (TM and Operational Land Imager (OLI images of Tianjin, China, and the accuracy of the extracted coastlines was assessed with the manually delineated coastline. The mean ME (misclassification error and mean LM (Line Matching are 0.0012 and 24.54 m respectively. The method provides an inexpensive and automated means of coastline mapping with subtype scale in coastal city sectors with intense human interference, which can be significant for coast resource management and evaluation of urban development.

  16. Subtype Coastline Determination in Urban Coast Based on Multiscale Features: a Case Study in Tianjin, China

    Science.gov (United States)

    Song, Y.; Ai, Y.; Zhu, H.

    2018-04-01

    In urban coast, coastline is a direct factor to reflect human activities. It is of crucial importance to the understanding of urban growth, resource development and ecological environment. Due to complexity and uncertainty in this type of coast, it is difficult to detect accurate coastline position and determine the subtypes of the coastline. In this paper, we present a multiscale feature-based subtype coastline determination (MFBSCD) method to extract coastline and determine the subtypes. In this method, uncertainty-considering coastline detection (UCCD) method is proposed to separate water and land for more accurate coastline position. The MFBSCD method can well integrate scale-invariant features of coastline in geometry and spatial structure to determine coastline in subtype scale, and can make subtypes verify with each other during processing to ensure the accuracy of final results. It was applied to Landsat Thematic Mapper (TM) and Operational Land Imager (OLI) images of Tianjin, China, and the accuracy of the extracted coastlines was assessed with the manually delineated coastline. The mean ME (misclassification error) and mean LM (Line Matching) are 0.0012 and 24.54 m respectively. The method provides an inexpensive and automated means of coastline mapping with subtype scale in coastal city sectors with intense human interference, which can be significant for coast resource management and evaluation of urban development.

  17. Comparative functional expression of nAChR subtypes in rodent DRG neurons.

    Science.gov (United States)

    Smith, Nathan J; Hone, Arik J; Memon, Tosifa; Bossi, Simon; Smith, Thomas E; McIntosh, J Michael; Olivera, Baldomero M; Teichert, Russell W

    2013-01-01

    We investigated the functional expression of nicotinic acetylcholine receptors (nAChRs) in heterogeneous populations of dissociated rat and mouse lumbar dorsal root ganglion (DRG) neurons by calcium imaging. By this experimental approach, it is possible to investigate the functional expression of multiple receptor and ion-channel subtypes across more than 100 neuronal and glial cells simultaneously. Based on nAChR expression, DRG neurons could be divided into four subclasses: (1) neurons that express predominantly α3β4 and α6β4 nAChRs; (2) neurons that express predominantly α7 nAChRs; (3) neurons that express a combination of α3β4/α6β4 and α7 nAChRs; and (4) neurons that do not express nAChRs. In this comparative study, the same four neuronal subclasses were observed in mouse and rat DRG. However, the expression frequency differed between species: substantially more rat DRG neurons were in the first three subclasses than mouse DRG neurons, at all developmental time points tested in our study. Approximately 70-80% of rat DRG neurons expressed functional nAChRs, in contrast to only ~15-30% of mouse DRG neurons. Our study also demonstrated functional coupling between nAChRs, voltage-gated calcium channels, and mitochondrial Ca(2) (+) transport in discrete subsets of DRG neurons. In contrast to the expression of nAChRs in DRG neurons, we demonstrated that a subset of non-neuronal DRG cells expressed muscarinic acetylcholine receptors and not nAChRs. The general approach to comparative cellular neurobiology outlined in this paper has the potential to better integrate molecular and systems neuroscience by uncovering the spectrum of neuronal subclasses present in a given cell population and the functionally integrated signaling components expressed in each subclass.

  18. Parkinson's Disease Subtypes in the Oxford Parkinson Disease Centre (OPDC) Discovery Cohort.

    Science.gov (United States)

    Lawton, Michael; Baig, Fahd; Rolinski, Michal; Ruffman, Claudio; Nithi, Kannan; May, Margaret T; Ben-Shlomo, Yoav; Hu, Michele T M

    2015-01-01

    Within Parkinson's there is a spectrum of clinical features at presentation which may represent sub-types of the disease. However there is no widely accepted consensus of how best to group patients. Use a data-driven approach to unravel any heterogeneity in the Parkinson's phenotype in a well-characterised, population-based incidence cohort. 769 consecutive patients, with mean disease duration of 1.3 years, were assessed using a broad range of motor, cognitive and non-motor metrics. Multiple imputation was carried out using the chained equations approach to deal with missing data. We used an exploratory and then a confirmatory factor analysis to determine suitable domains to include within our cluster analysis. K-means cluster analysis of the factor scores and all the variables not loading into a factor was used to determine phenotypic subgroups. Our factor analysis found three important factors that were characterised by: psychological well-being features; non-tremor motor features, such as posture and rigidity; and cognitive features. Our subsequent five cluster model identified groups characterised by (1) mild motor and non-motor disease (25.4%), (2) poor posture and cognition (23.3%), (3) severe tremor (20.8%), (4) poor psychological well-being, RBD and sleep (18.9%), and (5) severe motor and non-motor disease with poor psychological well-being (11.7%). Our approach identified several Parkinson's phenotypic sub-groups driven by largely dopaminergic-resistant features (RBD, impaired cognition and posture, poor psychological well-being) that, in addition to dopaminergic-responsive motor features may be important for studying the aetiology, progression, and medication response of early Parkinson's.

  19. Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIRaben-1 subtype B and non-subtype B receiving a salvage regimen

    NARCIS (Netherlands)

    De Luca, Andrea; Flandre, Philippe; Dunn, David; Zazzi, Maurizio; Wensing, Annemarie; Santoro, Maria Mercedes; Günthard, Huldrych F.; Wittkop, Linda; Kordossis, Theodoros; Garcia, Federico; Castagna, Antonella; Cozzi-Lepri, Alessandro; Churchill, Duncan; De Wit, Stéphane; Brockmeyer, Norbert H.; Imaz, Arkaitz; Mussini, Cristina; Obel, Niels; Perno, Carlo Federico; Roca, Bernardino; Reiss, Peter; Schülter, Eugen; Torti, Carlo; van Sighem, Ard; Zangerle, Robert; Descamps, Diane; Mocroft, Amanda; Kirk, Ole; Sabin, Caroline; De Wit, Stéphane; Casabona, Jordi; Miró, Jose M.; Touloumi, Giota; Garrido, Myriam; Teira, Ramon; Wit, Ferdinand; Warszawski, Josiane; Meyer, Laurence; Dabis, François; Krause, Murielle Mary; Ghosn, Jade; Leport, Catherine; Prins, Maria; Bucher, Heiner; Gibb, Diana; Fätkenheuer, Gerd; del Amo, Julia; Thorne, Claire; Stephan, Christoph; Pérez-Hoyos, Santiago; Hamouda, Osamah; Bartmeyer, Barbara; Chkhartishvili, Nikoloz; Noguera-Julian, Antoni; Antinori, Andrea; d'Arminio Monforte, Antonella; Prieto, Luis; Conejo, Pablo Rojo; Soriano-Arandes, Antoni; Battegay, Manuel; Kouyos, Roger; Tookey, Pat; Konopnick, Deborah; Goetghebuer, Tessa; Sönnerborg, Anders; Haerry, David; de Wit, Stéphane; Costagliola, Dominique; Raben, Dorthe; Chêne, Geneviève; Ceccherini-Silberstein, Francesca; Günthard, Huldrych; Judd, Ali; Barger, Diana; Schwimmer, Christine; Termote, Monique; Campbell, Maria; Frederiksen, Casper M.; Friis-Møller, Nina; Kjaer, Jesper; Brandt, Rikke Salbøl; Berenguer, Juan; Bohlius, Julia; Bouteloup, Vincent; Davies, Mary Anne; Dorrucci, Maria; Egger, Matthias; Furrer, Hansjakob; Guiguet, Marguerite; Grabar, Sophie; Lambotte, Olivier; Leroy, Valériane; Lodi, Sara; Matheron, Sophie; Monge, Susana; Nakagawa, Fumiyo; Paredes, Roger; Phillips, Andrew; Puoti, Massimo; Schomaker, Michael; Smit, Colette; Sterne, Jonathan; Thiebaut, Rodolphe; van der Valk, Marc; Wyss, Natasha; Aubert, V.; Battegay, M.; Bernasconi, E.; Böni, J.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Dollenmaier, G.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Fux, C. A.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H. H.; Hoffmann, M.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kouyos, R.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Nicca, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schöni-Affolter, F.; Schmid, P.; Schüpbach, J.; Speck, R.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.

    2016-01-01

    Objectives: The objective of this studywas to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. Methods: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from large

  20. The impact of immigration on env HIV-1 subtype distribution among heterosexuals in the Netherlands: influx of subtype B and non-B strains

    NARCIS (Netherlands)

    Op de Coul, E. L.; Coutinho, R. A.; van der Schoot, A.; van Doornum, G. J.; Lukashov, V. V.; Goudsmit, J.; Cornelissen, M.

    2001-01-01

    OBJECTIVE: To examine the epidemiological factors influencing the distribution and spread of HIV-1 subtypes among heterosexuals in the Netherlands. METHOD: A nationwide serosurveillance in 21 HIV/AIDS centres from 1997 to 1999 involved 200 individuals for whom the mode of HIV transmission was

  1. Genetically Diverse Low Pathogenicity Avian Influenza A Virus Subtypes Co-Circulate among Poultry in Bangladesh.

    Science.gov (United States)

    Gerloff, Nancy A; Khan, Salah Uddin; Zanders, Natosha; Balish, Amanda; Haider, Najmul; Islam, Ausraful; Chowdhury, Sukanta; Rahman, Mahmudur Ziaur; Haque, Ainul; Hosseini, Parviez; Gurley, Emily S; Luby, Stephen P; Wentworth, David E; Donis, Ruben O; Sturm-Ramirez, Katharine; Davis, C Todd

    2016-01-01

    Influenza virus surveillance, poultry outbreak investigations and genomic sequencing were assessed to understand the ecology and evolution of low pathogenicity avian influenza (LPAI) A viruses in Bangladesh from 2007 to 2013. We analyzed 506 avian specimens collected from poultry in live bird markets and backyard flocks to identify influenza A viruses. Virus isolation-positive specimens (n = 50) were subtyped and their coding-complete genomes were sequenced. The most frequently identified subtypes among LPAI isolates were H9N2, H11N3, H4N6, and H1N1. Less frequently detected subtypes included H1N3, H2N4, H3N2, H3N6, H3N8, H4N2, H5N2, H6N1, H6N7, and H7N9. Gene sequences were compared to publicly available sequences using phylogenetic inference approaches. Among the 14 subtypes identified, the majority of viral gene segments were most closely related to poultry or wild bird viruses commonly found in Southeast Asia, Europe, and/or northern Africa. LPAI subtypes were distributed over several geographic locations in Bangladesh, and surface and internal protein gene segments clustered phylogenetically with a diverse number of viral subtypes suggesting extensive reassortment among these LPAI viruses. H9N2 subtype viruses differed from other LPAI subtypes because genes from these viruses consistently clustered together, indicating this subtype is enzootic in Bangladesh. The H9N2 strains identified in Bangladesh were phylogenetically and antigenically related to previous human-derived H9N2 viruses detected in Bangladesh representing a potential source for human infection. In contrast, the circulating LPAI H5N2 and H7N9 viruses were both phylogenetically and antigenically unrelated to H5 viruses identified previously in humans in Bangladesh and H7N9 strains isolated from humans in China. In Bangladesh, domestic poultry sold in live bird markets carried a wide range of LPAI virus subtypes and a high diversity of genotypes. These findings, combined with the seven year

  2. Prediction consistency and clinical presentations of breast cancer molecular subtypes for Han Chinese population

    Directory of Open Access Journals (Sweden)

    Huang Chi-Cheng

    2012-09-01

    Full Text Available Abstract Background Breast cancer is a heterogeneous disease in terms of transcriptional aberrations; moreover, microarray gene expression profiles had defined 5 molecular subtypes based on certain intrinsic genes. This study aimed to evaluate the prediction consistency of breast cancer molecular subtypes from 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 as well as clinical presentations of each molecualr subtype in Han Chinese population. Methods In all, 169 breast cancer samples (44 from Taiwan and 125 from China of Han Chinese population were gathered, and the gene expression features corresponding to 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 were retrieved for molecular subtype prediction. Results For Sørlie 500 and Hu 306 intrinsic gene set, mean-centring of genes and distance-weighted discrimination (DWD remarkably reduced the number of unclassified cases. Regarding pairwise agreement, the highest predictive consistency was found between Hu 306 and PAM50. In all, 150 and 126 samples were assigned into identical subtypes by both Hu 306 and PAM50 genes, under mean-centring and DWD. Luminal B tended to show a higher nuclear grade and have more HER2 over-expression status than luminal A did. No basal-like breast tumours were ER positive, and most HER2-enriched breast tumours showed HER2 over-expression, whereas, only two-thirds of ER negativity/HER2 over-expression tumros were predicted as HER2-enriched molecular subtype. For 44 Taiwanese breast cancers with survival data, a better prognosis of luminal A than luminal B subtype in ER-postive breast cancers and a better prognosis of basal-like than HER2-enriched subtype in ER-negative breast cancers was observed. Conclusions We suggest that the intrinsic signature Hu 306 or PAM50 be used for breast cancers in the Han Chinese population during molecular subtyping. For the prognostic value and decision making based on intrinsic subtypes, further prospective

  3. Genetically Diverse Low Pathogenicity Avian Influenza A Virus Subtypes Co-Circulate among Poultry in Bangladesh

    Science.gov (United States)

    Gerloff, Nancy A.; Khan, Salah Uddin; Zanders, Natosha; Balish, Amanda; Haider, Najmul; Islam, Ausraful; Chowdhury, Sukanta; Rahman, Mahmudur Ziaur; Haque, Ainul; Hosseini, Parviez; Gurley, Emily S.; Luby, Stephen P.; Wentworth, David E.; Donis, Ruben O.; Sturm-Ramirez, Katharine; Davis, C. Todd

    2016-01-01

    Influenza virus surveillance, poultry outbreak investigations and genomic sequencing were assessed to understand the ecology and evolution of low pathogenicity avian influenza (LPAI) A viruses in Bangladesh from 2007 to 2013. We analyzed 506 avian specimens collected from poultry in live bird markets and backyard flocks to identify influenza A viruses. Virus isolation-positive specimens (n = 50) were subtyped and their coding-complete genomes were sequenced. The most frequently identified subtypes among LPAI isolates were H9N2, H11N3, H4N6, and H1N1. Less frequently detected subtypes included H1N3, H2N4, H3N2, H3N6, H3N8, H4N2, H5N2, H6N1, H6N7, and H7N9. Gene sequences were compared to publicly available sequences using phylogenetic inference approaches. Among the 14 subtypes identified, the majority of viral gene segments were most closely related to poultry or wild bird viruses commonly found in Southeast Asia, Europe, and/or northern Africa. LPAI subtypes were distributed over several geographic locations in Bangladesh, and surface and internal protein gene segments clustered phylogenetically with a diverse number of viral subtypes suggesting extensive reassortment among these LPAI viruses. H9N2 subtype viruses differed from other LPAI subtypes because genes from these viruses consistently clustered together, indicating this subtype is enzootic in Bangladesh. The H9N2 strains identified in Bangladesh were phylogenetically and antigenically related to previous human-derived H9N2 viruses detected in Bangladesh representing a potential source for human infection. In contrast, the circulating LPAI H5N2 and H7N9 viruses were both phylogenetically and antigenically unrelated to H5 viruses identified previously in humans in Bangladesh and H7N9 strains isolated from humans in China. In Bangladesh, domestic poultry sold in live bird markets carried a wide range of LPAI virus subtypes and a high diversity of genotypes. These findings, combined with the seven year

  4. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.

    Directory of Open Access Journals (Sweden)

    Laetitia Marisa

    Full Text Available Colon cancer (CC pathological staging fails to accurately predict recurrence, and to date, no gene expression signature has proven reliable for prognosis stratification in clinical practice, perhaps because CC is a heterogeneous disease. The aim of this study was to establish a comprehensive molecular classification of CC based on mRNA expression profile analyses.Fresh-frozen primary tumor samples from a large multicenter cohort of 750 patients with stage I to IV CC who underwent surgery between 1987 and 2007 in seven centers were characterized for common DNA alterations, including BRAF, KRAS, and TP53 mutations, CpG island methylator phenotype, mismatch repair status, and chromosomal instability status, and were screened with whole genome and transcriptome arrays. 566 samples fulfilled RNA quality requirements. Unsupervised consensus hierarchical clustering applied to gene expression data from a discovery subset of 443 CC samples identified six molecular subtypes. These subtypes were associated with distinct clinicopathological characteristics, molecular alterations, specific enrichments of supervised gene expression signatures (stem cell phenotype-like, normal-like, serrated CC phenotype-like, and deregulated signaling pathways. Based on their main biological characteristics, we distinguished a deficient mismatch repair subtype, a KRAS mutant subtype, a cancer stem cell subtype, and three chromosomal instability subtypes, including one associated with down-regulated immune pathways, one with up-regulation of the Wnt pathway, and one displaying a normal-like gene expression profile. The classification was validated in the remaining 123 samples plus an independent set of 1,058 CC samples, including eight public datasets. Furthermore, prognosis was analyzed in the subset of stage II-III CC samples. The subtypes C4 and C6, but not the subtypes C1, C2, C3, and C5, were independently associated with shorter relapse-free survival, even after

  5. New hepatitis C virus genotype 1 subtype naturally harbouring resistance-associated mutations to NS5A inhibitors.

    Science.gov (United States)

    Ordeig, Laura; Garcia-Cehic, Damir; Gregori, Josep; Soria, Maria Eugenia; Nieto-Aponte, Leonardo; Perales, Celia; Llorens, Meritxell; Chen, Qian; Riveiro-Barciela, Mar; Buti, Maria; Esteban, Rafael; Esteban, Juan Ignacio; Rodriguez-Frias, Francisco; Quer, Josep

    2018-01-01

    Hepatitis C virus (HCV) is a highly divergent virus currently classified into seven major genotypes and 86 subtypes (ICTV, June 2017), which can have differing responses to therapy. Accurate genotyping/subtyping using high-resolution HCV subtyping enables confident subtype identification, identifies mixed infections and allows detection of new subtypes. During routine genotyping/subtyping, one sample from an Equatorial Guinea patient could not be classified into any of the subtypes. The complete genomic sequence was compared to reference sequences by phylogenetic and sliding window analysis. Resistance-associated substitutions (RASs) were assessed by deep sequencing. The unclassified HCV genome did not belong to any of the existing genotype 1 (G1) subtypes. Sliding window analysis along the complete genome ruled out recombination phenomena suggesting that it belongs to a new HCV G1 subtype. Two NS5A RASs (L31V+Y93H) were found to be naturally combined in the genome which could limit treatment possibilities in patients infected with this subtype.

  6. Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes

    Directory of Open Access Journals (Sweden)

    Kent Imaizumi

    2015-12-01

    Full Text Available The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of neuronal subtype specificity of disease phenotypes remains elusive. Although in vitro disease models employing human pluripotent stem cells (PSCs have great potential to clarify the association of neuronal subtypes with disease, it is currently difficult to compare various PSC-derived subtypes. This is due to the limited number of subtypes whose induction is established, and different cultivation protocols for each subtype. Here, we report a culture system to control the regional identity of PSC-derived neurons along the anteroposterior (A-P and dorsoventral (D-V axes. This system was successfully used to obtain various neuronal subtypes based on the same protocol. Furthermore, we reproduced subtype-specific phenotypes of amyotrophic lateral sclerosis (ALS and Alzheimer’s disease (AD by comparing the obtained subtypes. Therefore, our culture system provides new opportunities for modeling neurological diseases with PSCs.

  7. Functional Impairment and Changes in Depression Subtypes for Women in STAR*D: A Latent Transition Analysis

    Science.gov (United States)

    Rothschild, Anthony J.; Lapane, Kate L.

    2016-01-01

    Abstract Objective: To characterize the association between functional impairment and major depression subtypes at baseline and to characterize changes in subtypes by functional impairment level in women receiving citalopram in level 1 of the Sequenced Treatment Alternatives to Relieve Depression trial. Method: Women who completed baseline and week 12 study visits were included. Items from the self-reported Quick Inventory of Depressive Symptomatology were used to define the latent depression subtypes. The Work and Social Adjustment Scale was used to classify baseline functional impairment. A latent transition analysis model provided estimates of the prevalence of subtype membership and transition probabilities by functional impairment level. Results: Of the 755 women included, 69% had major functional impairment at baseline. Regardless of functional impairment level, the subtypes were differentiated by depression severity, appetite changes, psychomotor disturbances, and insomnia. Sixty-seven percent of women with normal/significant functional impairment and 60% of women with major impairment were likely to transition to a symptom resolution subtype at week 12. Women with baseline major impairment who were in the severe with psychomotor agitation subtype at the beginning of the study were least likely to transition to the symptom resolution subtype (4% chance). Conclusions: Functional impairment level was related to both the baseline depression subtype and the likelihood of moving to a different subtype. These results underscore the need to incorporate not only depression symptoms but also functioning in the assessment and treatment of depression. PMID:26488110

  8. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties.

    Science.gov (United States)

    Casale, Amanda E; Foust, Amanda J; Bal, Thierry; McCormick, David A

    2015-11-25

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca(2+)-activated K(+) channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main

  9. HIV-1 subtype F1 epidemiological networks among Italian heterosexual males are associated with introduction events from South America.

    Science.gov (United States)

    Lai, Alessia; Simonetti, Francesco R; Zehender, Gianguglielmo; De Luca, Andrea; Micheli, Valeria; Meraviglia, Paola; Corsi, Paola; Bagnarelli, Patrizia; Almi, Paolo; Zoncada, Alessia; Paolucci, Stefania; Gonnelli, Angela; Colao, Grazia; Tacconi, Danilo; Franzetti, Marco; Ciccozzi, Massimo; Zazzi, Maurizio; Balotta, Claudia

    2012-01-01

    About 40% of the Italian HIV-1 epidemic due to non-B variants is sustained by F1 clade, which circulates at high prevalence in South America and Eastern Europe. Aim of this study was to define clade F1 origin, population dynamics and epidemiological networks through phylogenetic approaches. We analyzed pol sequences of 343 patients carrying F1 subtype stored in the ARCA database from 1998 to 2009. Citizenship of patients was as follows: 72.6% Italians, 9.3% South Americans and 7.3% Rumanians. Heterosexuals, Homo-bisexuals, Intravenous Drug Users accounted for 58.1%, 24.0% and 8.8% of patients, respectively. Phylogenetic analysis indicated that 70% of sequences clustered in 27 transmission networks. Two distinct groups were identified; the first clade, encompassing 56 sequences, included all Rumanian patients. The second group involved the remaining clusters and included 10 South American Homo-bisexuals in 9 distinct clusters. Heterosexual modality of infection was significantly associated with the probability to be detected in transmission networks. Heterosexuals were prevalent either among Italians (67.2%) or Rumanians (50%); by contrast, Homo-bisexuals accounted for 71.4% of South Americans. Among patients with resistant strains the proportion of clustering sequences was 57.1%, involving 14 clusters (51.8%). Resistance in clusters tended to be higher in South Americans (28.6%) compared to Italian (17.7%) and Rumanian patients (14.3%). A striking proportion of epidemiological networks could be identified in heterosexuals carrying F1 subtype residing in Italy. Italian Heterosexual males predominated within epidemiological clusters while foreign patients were mainly Heterosexual Rumanians, both males and females, and South American Homo-bisexuals. Tree topology suggested that F1 variant from South America gave rise to the Italian F1 epidemic through multiple introduction events. The contact tracing also revealed an unexpected burden of resistance in epidemiological

  10. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil.

    Science.gov (United States)

    Lei, Zhengdeng; Tan, Iain Beehuat; Das, Kakoli; Deng, Niantao; Zouridis, Hermioni; Pattison, Sharon; Chua, Clarinda; Feng, Zhu; Guan, Yeoh Khay; Ooi, Chia Huey; Ivanova, Tatiana; Zhang, Shenli; Lee, Minghui; Wu, Jeanie; Ngo, Anna; Manesh, Sravanthy; Tan, Elisabeth; Teh, Bin Tean; So, Jimmy Bok Yan; Goh, Liang Kee; Boussioutas, Alex; Lim, Tony Kiat Hon; Flotow, Horst; Tan, Patrick; Rozen, Steven G

    2013-09-01

    Almost all gastric cancers are adenocarcinomas, which have considerable heterogeneity among patients. We sought to identify subtypes of gastric adenocarcinomas with particular biological properties and responses to chemotherapy and targeted agents. We compared gene expression patterns among 248 gastric tumors; using a robust method of unsupervised clustering, consensus hierarchical clustering with iterative feature selection, we identified 3 major subtypes. We developed a classifier for these subtypes and validated it in 70 tumors from a different population. We identified distinct genomic and epigenomic properties of the subtypes. We determined drug sensitivities of the subtypes in primary tumors using clinical survival data, and in cell lines through high-throughput drug screening. We identified 3 subtypes of gastric adenocarcinoma: proliferative, metabolic, and mesenchymal. Tumors of the proliferative subtype had high levels of genomic instability, TP53 mutations, and DNA hypomethylation. Cancer cells of the metabolic subtype were more sensitive to 5-fluorouracil than the other subtypes. Furthermore, in 2 independent groups of patients, those with tumors of the metabolic subtype appeared to have greater benefits with 5-fluorouracil treatment. Tumors of the mesenchymal subtype contain cells with features of cancer stem cells, and cell lines of this subtype are particularly sensitive to phosphatidylinositol 3-kinase-AKT-mTOR inhibitors in vitro. Based on gene expression patterns, we classified gastric cancers into 3 subtypes, and validated these in an independent set of tumors. The subgroups have differences in molecular and genetic features and response to therapy; this information might be used to select specific treatment approaches for patients with gastric cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Leukocyte subtype counts and its association with vascular structure and function in adults with intermediate cardiovascular risk. MARK study.

    Directory of Open Access Journals (Sweden)

    Leticia Gomez-Sanchez

    Full Text Available We investigated the relationship between leukocyte subtype counts and vascular structure and function based on carotid intima-media thickness, pulse wave velocity, central augmentation index and cardio-ankle vascular index by gender in intermediate cardiovascular risk patients.This study analyzed 500 subjects who were included in the MARK study, aged 35 to 74 years (mean: 60.3±8.4, 45.6% women.Brachial ankle Pulse Wave Velocity (ba-PWV estimate by equation, Cardio-AnkleVascular Index (CAVI using the VaSera device and Carotid ultrasound was used to measure carotid Intima Media Thickness (IMT. The Mobil-O-Graph was used to measure the Central Augmentation Index (CAIx.Total leukocyte, neutrophil and monocyte counts were positively correlated with IMT (p < 0.01 in men. Monocyte count was positively correlated with CAIx in women (p < 0.01. In a multiple linear regression analysis, the IMT mean maintained a positive association with the neutrophil count (β = 1.500, p = 0.007 in men. CAIx maintained a positive association with the monocyte count (β = 2.445, p = 0.022 in women.The results of this study suggest that the relationship between subtype circulating leukocyte counts and vascular structure and function, although small, may be different by gender. In men, the neutrophil count was positively correlated with IMT and in women, the monocyte count with CAIx, in a large sample of intermediate-risk patients. These association were maintained after adjusting for age and other confounders.ClinicalTrials.gov NCT01428934.

  12. Predicting Subtype Selectivity for Adenosine Receptor Ligands with Three-Dimensional Biologically Relevant Spectrum (BRS-3D)

    Science.gov (United States)

    He, Song-Bing; Ben Hu; Kuang, Zheng-Kun; Wang, Dong; Kong, De-Xin

    2016-11-01

    Adenosine receptors (ARs) are potential therapeutic targets for Parkinson’s disease, diabetes, pain, stroke and cancers. Prediction of subtype selectivity is therefore important from both therapeutic and mechanistic perspectives. In this paper, we introduced a shape similarity profile as molecular descriptor, namely three-dimensional biologically relevant spectrum (BRS-3D), for AR selectivity prediction. Pairwise regression and discrimination models were built with the support vector machine methods. The average determination coefficient (r2) of the regression models was 0.664 (for test sets). The 2B-3 (A2B vs A3) model performed best with q2 = 0.769 for training sets (10-fold cross-validation), and r2 = 0.766, RMSE = 0.828 for test sets. The models’ robustness and stability were validated with 100 times resampling and 500 times Y-randomization. We compared the performance of BRS-3D with 3D descriptors calculated by MOE. BRS-3D performed as good as, or better than, MOE 3D descriptors. The performances of the discrimination models were also encouraging, with average accuracy (ACC) 0.912 and MCC 0.792 (test set). The 2A-3 (A2A vs A3) selectivity discrimination model (ACC = 0.882 and MCC = 0.715 for test set) outperformed an earlier reported one (ACC = 0.784). These results demonstrated that, through multiple conformation encoding, BRS-3D can be used as an effective molecular descriptor for AR subtype selectivity prediction.

  13. HIV-1 subtypes D and F are prevalent in Guinea Conakry.

    Science.gov (United States)

    Freimanis, G L; Loua, A; Allain, J P

    2012-04-01

    Limited data is available upon the distribution of different HIV-1/2 genotypes in the blood donor population from Guinea Conakry. To investigate the prevalence of HIV-1/2 subtypes in asymptomatic blood donors in Guinea Conakry, in order to update knowledge of HIV-1/2 epidemiology within this country. Samples from 104 blood donors seropositive for HIV-1/2 were tested for HIV-1 by real-time RT-PCR. Those negative for HIV-1 were tested with HIV-2 nested RT-PCR. Positive samples were further amplified in the HIV-1 gag and pol regions and sequenced. Subtypes were determined by phylogenetic analysis on amplicon sequences. 61 samples were positive by HIV-1 real-time RT-PCR. Of the 43 negative, 2 (4.6%) were positive for HIV-2. 52/61 (85.3%) samples were positive by nested RT-PCR. Of the 52, 43 (70.5%) and 31(59.6%) sequences were obtained in the gag and pol regions, respectively; 23 for both regions. HIV-1 subtype distribution was 1 B (2.1%), 8 F (17%), 8 D (17%) and 28 CRF02_AG (59.6%) with 2 unclassified recombinants (4.3%). Unique clusters for subtype D and F distinguished Guinea from HIV-1 subtype distribution in neighboring countries. Subtype F and subtype D strains, uncommon in West Africa, are a substantial part of HIV-1 epidemiology in Guinea. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung

    International Nuclear Information System (INIS)

    Mak, J.C.; Barnes, P.J.

    1990-01-01

    Muscarinic receptor subtypes have been localized in human and guinea pig lung sections by an autoradiographic technique, using [3H](-)quinuclidinyl benzilate [( 3H]QNB) and selective muscarinic antagonists. [3H]QNB was incubated with tissue sections for 90 min at 25 degrees C, and nonspecific binding was determined by incubating adjacent serial sections in the presence of 1 microM atropine. Binding to lung sections had the characterization expected for muscarinic receptors. Autoradiography revealed that muscarinic receptors were widely distributed in human lung, with dense labeling over submucosal glands and airway ganglia, and moderate labeling over nerves in intrapulmonary bronchi and of airway smooth muscle of large and small airways. In addition, alveolar walls were uniformly labeled. In guinea pig lung, labeling of airway smooth muscle was similar, but in contrast to human airways, epithelium was labeled but alveolar walls were not. The muscarinic receptors of human airway smooth muscle from large to small airways were entirely of the M3-subtype, whereas in guinea pig airway smooth muscle, the majority were the M3-subtype with a very small population of the M2-subtype present. In human bronchial submucosal glands, M1- and M3-subtypes appeared to coexist in the proportions of 36 and 64%, respectively. In human alveolar walls the muscarinic receptors were entirely of the M1-subtype, which is absent from the guinea pig lung. No M2-receptors were demonstrated in human lung. The localization of M1-receptors was confirmed by direct labeling with [3H]pirenzepine. With the exception of the alveolar walls in human lung, the localization of muscarinic receptor subtypes on structures in the lung is consistent with known functional studies

  15. Genetic and phylogenetic evolution of HIV-1 in a low subtype heterogeneity epidemic: the Italian example

    Directory of Open Access Journals (Sweden)

    Tornesello Maria

    2007-05-01

    Full Text Available Abstract The Human Immunodeficiency Virus type 1 (HIV-1 is classified into genetic groups, subtypes and sub-subtypes which show a specific geographic distribution pattern. The HIV-1 epidemic in Italy, as in most of the Western Countries, has traditionally affected the Intra-venous drug user (IDU and Homosexual (Homo risk groups and has been sustained by the genetic B subtype. In the last years, however, the HIV-1 transmission rate among heterosexuals has dramatically increased, becoming the prevalent transmission route. In fact, while the traditional risk groups have high levels of knowledge and avoid high-risk practices, the heterosexuals do not sufficiently perceive the risk of HIV-1 infection. This misperception, linked to the growing number of immigrants from non-Western Countries, where non-B clades and circulating recombinant forms (CRFs are prevalent, is progressively introducing HIV-1 variants of non-B subtype in the Italian epidemic. This is in agreement with reports from other Western European Countries. In this context, the Italian HIV-1 epidemic is still characterized by low subtype heterogeneity and represents a paradigmatic example of the European situation. The continuous molecular evolution of the B subtype HIV-1 isolates, characteristic of a long-lasting epidemic, together with the introduction of new subtypes as well as recombinant forms may have significant implications for diagnostic, treatment, and vaccine development. The study and monitoring of the genetic evolution of the HIV-1 represent, therefore, an essential strategy for controlling the local as well as global HIV-1 epidemic and for developing efficient preventive and therapeutic strategies.

  16. Validity of DSM-IV attention deficit/hyperactivity disorder symptom dimensions and subtypes.

    Science.gov (United States)

    Willcutt, Erik G; Nigg, Joel T; Pennington, Bruce F; Solanto, Mary V; Rohde, Luis A; Tannock, Rosemary; Loo, Sandra K; Carlson, Caryn L; McBurnett, Keith; Lahey, Benjamin B

    2012-11-01

    Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for attention deficit/hyperactivity disorder (ADHD) specify two dimensions of inattention and hyperactivity-impulsivity symptoms that are used to define three nominal subtypes: predominantly hyperactive-impulsive type (ADHD-H), predominantly inattentive type (ADHD-I), and combined type (ADHD-C). To aid decision making for DSM-5 and other future diagnostic systems, a comprehensive literature review and meta-analysis of 546 studies was completed to evaluate the validity of the DSM-IV model of ADHD. Results indicated that DSM-IV criteria identify individuals with significant and persistent impairment in social, academic, occupational, and adaptive functioning when intelligence, demographic factors, and concurrent psychopathology are controlled. Available data overwhelmingly support the concurrent, predictive, and discriminant validity of the distinction between inattention and hyperactivity-impulsivity symptoms, and indicate that nearly all differences among the nominal subtypes are consistent with the relative levels of inattention and hyperactivity-impulsivity symptoms that define the subtypes. In contrast, the DSM-IV subtype model is compromised by weak evidence for the validity of ADHD-H after first grade, minimal support for the distinction between ADHD-I and ADHD-C in studies of etiological influences, academic and cognitive functioning, and treatment response, and the marked longitudinal instability of all three subtypes. Overall, we conclude that the DSM-IV ADHD subtypes provide a convenient clinical shorthand to describe the functional and behavioral correlates of current levels of inattention and hyperactivity-impulsivity symptoms, but do not identify discrete subgroups with sufficient long-term stability to justify the classification of distinct forms of the disorder. Empirical support is stronger for an alternative model that would replace the subtypes with dimensional

  17. Angiogenic Gene Signature Derived from Subtype Specific Cell Models Segregate Proneural and Mesenchymal Glioblastoma

    Directory of Open Access Journals (Sweden)

    Aman Sharma

    2017-07-01

    Full Text Available Intertumoral molecular heterogeneity in glioblastoma identifies four major subtypes based on expression of molecular markers. Among them, the two clinically interrelated subtypes, proneural and mesenchymal, are the most aggressive with proneural liable for conversion to mesenchymal upon therapy. Using two patient-derived novel primary cell culture models (MTA10 and KW10, we developed a minimal but unique four-gene signature comprising genes vascular endothelial growth factor A (VEGF-A, vascular endothelial growth factor B (VEGF-B and angiopoietin 1 (ANG1, angiopoietin 2 (ANG2 that effectively segregated the proneural (MTA10 and mesenchymal (KW10 glioblastoma subtypes. The cell culture preclassified as mesenchymal showed elevated expression of genes VEGF-A, VEGF-B and ANG1, ANG2 as compared to the other cell culture model that mimicked the proneural subtype. The differentially expressed genes in these two cell culture models were confirmed by us using TCGA and Verhaak databases and we refer to it as a minimal multigene signature (MMS. We validated this MMS on human glioblastoma tissue sections with the use of immunohistochemistry on preclassified (YKL-40 high or mesenchymal glioblastoma and OLIG2 high or proneural glioblastoma tumor samples (n = 30. MMS segregated mesenchymal and proneural subtypes with 83% efficiency using a simple histopathology scoring approach (p = 0.008 for ANG2 and p = 0.01 for ANG1. Furthermore, MMS expression negatively correlated with patient survival. Importantly, MMS staining demonstrated spatiotemporal heterogeneity within each subclass, adding further complexity to subtype identification in glioblastoma. In conclusion, we report a novel and simple sequencing-independent histopathology-based biomarker signature comprising genes VEGF-A, VEGF-B and ANG1, ANG2 for subtyping of proneural and mesenchymal glioblastoma.

  18. A DNA methylation-based definition of biologically distinct breast cancer subtypes.

    Science.gov (United States)

    Stefansson, Olafur A; Moran, Sebastian; Gomez, Antonio; Sayols, Sergi; Arribas-Jorba, Carlos; Sandoval, Juan; Hilmarsdottir, Holmfridur; Olafsdottir, Elinborg; Tryggvadottir, Laufey; Jonasson, Jon G; Eyfjord, Jorunn; Esteller, Manel

    2015-03-01

    In cancer, epigenetic states are deregulated and thought to be of significance in cancer development and progression. We explored DNA methylation-based signatures in association with breast cancer subtypes to assess their impact on clinical presentation and patient prognosis. DNA methylation was analyzed using Infinium 450K arrays in 40 tumors and 17 normal breast samples, together with DNA copy number changes and subtype-specific markers by tissue microarrays. The identified methylation signatures were validated against a cohort of 212 tumors annotated for breast cancer subtypes by the PAM50 method (The Cancer Genome Atlas). Selected markers were pyrosequenced in an independent validation cohort of 310 tumors and analyzed with respect to survival, clinical stage and grade. The results demonstrate that DNA methylation patterns linked to the luminal-B subtype are characterized by CpG island promoter methylation events. In contrast, a large fraction of basal-like tumors are characterized by hypomethylation events occurring within the gene body. Based on these hallmark signatures, we defined two DNA methylation-based subtypes, Epi-LumB and Epi-Basal, and show that they are associated with unfavorable clinical parameters and reduced survival. Our data show that distinct mechanisms leading to changes in CpG methylation states are operative in different breast cancer subtypes. Importantly, we show that a few selected proxy markers can be used to detect the distinct DNA methylation-based subtypes thereby providing valuable information on disease prognosis. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  19. ANALYSIS OF HIV SUBTYPES AND CLINICAL STAGING OF HIV DISEASE/AIDS IN EAST JAVA

    Directory of Open Access Journals (Sweden)

    Yulia Ismail

    2012-04-01

    Full Text Available Human Immunodeficiency Virus type 1 (HIV-1 known to cause Acquired Immune Deficiency Syndrome (AIDS disease are divided into several subtypes (A, B, C, D, F, G, H, J, K and Circulating Recombinant Form (CRF. Different characteristics of subtype of the virus and its interaction with the host can affect the severity of the disease. This study was to analyze HIV-1 subtypes circulating in HIV/AIDS patients from the East Java region descriptively and to analyze its relationship with clinical stadiums of HIV/AIDS. Information from this research was expected to complement the data of mocular epidemiology of HIV in Indonesia. This study utilited blood plasma from patients who had been tested to be HIV positive who sected treatment to or were reffered to the Intermediate Care Unit of Infectious Disease (UPIPI Dr. Soetomo Hospital Surabaya from various area representing the East Java regions. Plasma was separated from blood samples by centrifugation for use in the the molecular biology examination including RNA extraction, nested PCR using specific primer for HIV gp120 env gene region, DNA purifying, DNA sequencing, and homology and phylogenetic analysis. Based on the nucleotide sequence of the HIV gp120 env gene, it was found that the most dominant subtypes in East Java were in one group of Circulating Recombinant Form (CRF that is CRF01_AE, CRF33_01B and CRF34_01B which was also found in Southeast Asia. In the phylogenetic tree, most of HIV samples (30 samples are in the same branch with CRF01_AE, CRF33_01B and CRF34_01B, except for one sample (HIV40 which is in the same branch with subtype B. HIV subtypes are associated with clinical stadiums (disease severity since samples from different stages of HIV disease have the same subtype.

  20. Association of Diabetes and Prognosis of Minor Stroke and Its Subtypes: A Prospective Observational Study.

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    Yuesong Pan

    Full Text Available The association between diabetes mellitus (DM and prognosis of minor stroke is unclear. The aim of this study is to investigate whether DM contributes to the prognosis of minor stroke or its specific subtype.All minor ischemic stroke patients were derived from the China National Stroke Registry and classified into 5 subtypes according to the TOAST (Trial of Org 10172 in Acute Stroke Treatment criteria. DM was defined as either self-reported physician diagnosis of diabetes or use of hypoglycemic medications during hospitalization or at discharge. Patients were followed up for 1 year for clinical outcomes of recurrent stroke, death and functional outcome. Poor functional outcomes were defined as a score of 2-6 for modified Rankin Score. Associations between DM and prognosis of minor stroke and its subtypes were analyzed by univariable and multivariable logistic regression.Of 4,548 patients with minor stroke, 1,230(27.0% patients had DM, 1,038(22.8% had poor outcomes and 570(13.0% of 4,401 patients had recurrent stroke at 1 year. In multivariable analyses, DM were significantly associated with 1-year stroke recurrence (Odds Ratio [OR], 1.31; 95% confidence interval [CI]: 1.08-1.59 and poor outcome (OR, 1.51; 95%CI: 1.28-1.77. Among the subtypes of minor stroke, DM was only significantly associated with 1-year stroke recurrence (OR, 1.63; 95%CI: 1.07-2.50 and poor outcome (OR, 1.73; 95%CI: 1.22-2.45 in the small-artery occlusion subtype.DM significantly increased the risk of stroke recurrence and poor outcome in the small-artery occlusion subtype, but not in other subtypes of minor stroke.

  1. Validity of DSM-IV attention–deficit/hyperactivity disorder symptom dimensions and subtypes

    Science.gov (United States)

    Willcutt, Erik G.; Nigg, Joel T.; Pennington, Bruce F.; Solanto, Mary V.; Rohde, Luis A.; Tannock, Rosemary; Loo, Sandra K.; Carlson, Caryn L.; McBurnett, Keith; Lahey, Benjamin B.

    2013-01-01

    DSM-IV criteria for ADHD specify two dimensions of inattention and hyperactivity-impulsivity symptoms that are used to define three nominal subtypes: predominantly hyperactive-impulsive type (ADHD-H), predominantly inattentive type (ADHD-I), and combined type (ADHD-C). To aid decision-making for DSM-5 and other future diagnostic systems, a comprehensive literature review and meta-analysis of 546 studies was completed to evaluate the validity of the DSM-IV model of ADHD. Results indicated that DSM-IV criteria identify individuals with significant and persistent impairment in social, academic, occupational, and adaptive functioning when intelligence, demographic factors, and concurrent psychopathology are controlled. Available data overwhelmingly support the concurrent, predictive, and discriminant validity of the distinction between inattention and hyperactivity-impulsivity symptoms, and indicate that nearly all differences among the nominal subtypes are consistent with the relative levels of inattention and hyperactivity-impulsivity symptoms that define the subtypes. In contrast, the validity of the DSM-IV subtype model is compromised by weak evidence for the validity of ADHD-H after first grade, minimal support for the distinction between ADHD-I and ADHD-C in studies of etiological influences, academic and cognitive functioning, and treatment response, and the marked longitudinal instability of all three subtypes. Overall, it is concluded that the DSM-IV ADHD subtypes provide a convenient clinical shorthand to describe the functional and behavioral correlates of current levels of inattention and hyperactivity-impulsivity symptoms, but do not identify discrete subgroups with sufficient long-term stability to justify the classification of distinct forms of the disorder. Empirical support is stronger for an alternative model that would replace the subtypes with dimensional modifiers that reflect the number of inattention and hyperactivity-impulsivity symptoms at the

  2. A human monoclonal antibody with neutralizing activity against highly divergent influenza subtypes.

    Directory of Open Access Journals (Sweden)

    Nicola Clementi

    Full Text Available The interest in broad-range anti-influenza A monoclonal antibodies (mAbs has recently been strengthened by the identification of anti-hemagglutinin (HA mAbs endowed with heterosubtypic neutralizing activity to be used in the design of "universal" prophylactic or therapeutic tools. However, the majority of the single mAbs described to date do not bind and neutralize viral isolates belonging to highly divergent subtypes clustering into the two different HA-based influenza phylogenetic groups: the group 1 including, among others, subtypes H1, H2, H5 and H9 and the group 2 including, among others, H3 subtype. Here, we describe a human mAb, named PN-SIA28, capable of binding and neutralizing all tested isolates belonging to phylogenetic group 1, including H1N1, H2N2, H5N1 and H9N2 subtypes and several isolates belonging to group 2, including H3N2 isolates from the first period of the 1968 pandemic. Therefore, PN-SIA28 is capable of neutralizing isolates belonging to subtypes responsible of all the reported pandemics, as well as other subtypes with pandemic potential. The region recognized by PN-SIA28 has been identified on the stem region of HA and includes residues highly conserved among the different influenza subtypes. A deep characterization of PN-SIA28 features may represent a useful help in the improvement of available anti-influenza therapeutic strategies and can provide new tools for the development of universal vaccinal strategies.

  3. Combining miRNA and mRNA Expression Profiles in Wilms Tumor Subtypes

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    Nicole Ludwig

    2016-03-01

    Full Text Available Wilms tumor (WT is the most common childhood renal cancer. Recent findings of mutations in microRNA (miRNA processing proteins suggest a pivotal role of miRNAs in WT genesis. We performed miRNA expression profiling of 36 WTs of different subtypes and four normal kidney tissues using microarrays. Additionally, w