Morphology, cytogenetics and classification of MDS.

Myelodysplastic syndromes are heterogeneous bone marrow diseases with a variable pathogenetic background. Cytomorphological alterations in peripheral blood films as well as bone marrow aspirates and histological findings in trephine biopsies result from cytogenetic and molecular abnormalities, epigenetic dysregulation and immune dysfunction and are key elements for setting the diagnosis of MDS. Whereas diagnosis can be made quite easily in advanced MDS this is much more difficult in early MDS, especially in cases with cytopenias or dysplasias of uncertain significance (ICUS and IDUS).

In vitro leukocyte response of three-spined sticklebacks (Gasterosteus aculeatus) to helminth parasite antigens.

Helminth parasites of teleost fish have evolved strategies to evade and manipulate the immune responses of their hosts. Responsiveness of fish host immunity to helminth antigens may therefore vary depending on the degree of host-parasite counter-adaptation. Generalist parasites, infective for a number of host species, might be unable to adapt optimally to the immune system of a certain host species, while specialist parasites might display high levels of adaptation to a particular host species.

Endless urban growth? On the mismatch of population, household and urban land area growth and its effects on the urban debate.

In European cities, the rate of population growth has declined significantly, while the number of households has increased. This increase in the number of households is associated with an increase in space for housing. To date, the effects of both a declining population and decreasing household numbers remain unclear.

Automated approximation of center of mass position in X-ray sequences of animal locomotion.

A crucial aspect of comparative biomechanical research is the center of mass (CoM) estimation in animal locomotion scenarios. Important applications include the parameter estimation of locomotion models, the discrimination of gaits, or the calculation of mechanical work during locomotion. Several methods exist to approximate the CoM position, e.

Monosomal karyotype in MDS: explaining the poor prognosis?

Monosomal karyotype (MK) is associated with an adverse prognosis in patients in acute myeloid leukemia (AML). This study analyzes the prognostic impact of MK in a cohort of primary, untreated patients with myelodysplastic syndromes (MDS). A total of 431 patients were extracted from an international database.

Dibenzosilanorbornadienyl cations and their fragmentation into silyliumylidenes.

The terphenyl-substituted dibenzosilanorbornadienyl cation 11 was synthesized and isolated in the form of its [B(C6F5)4](-) salt. The salt was characterized by NMR spectroscopy supported by quantum mechanical computations and by an XRD analysis of a corresponding acetonitrilium salt. The thermal fragmentation of 11[B(C6F5)4] in benzene results in the high-yield formation of diphenylterphenylsilylium borate 17[B(C6F5)4].

Factors affecting antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy: a cross-sectional study.

Background: Although some studies show higher antiretroviral concentrations in women compared to men, data are limited. We conducted a cross-sectional study of HIV-positive women to determine if protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) C(min) and Cmax values were significantly different than historical general population (predominantly male) averages and to evaluate correlates of higher concentrations.

Methods: HIV-positive women with virologic suppression (viral load < 50copies/mL) on their first antiretroviral regimen were enrolled.

Molecular cytogenetic monitoring from CD34+ peripheral blood cells in myelodysplastic syndromes: first results from a prospective multicenter German diagnostic study.

The gold standard of cytogenetic analysis in myelodysplastic syndromes (MDS) is conventional chromosome banding (CCB) analysis of bone marrow (BM) metaphases. Most aberrations can also be detected by fluorescence-in situ-hybridization (FISH). For this prospective multicenter German diagnostic study (www.

Structural study of helical polyfluorene under high quasihydrostatic pressure.

We report on an x-ray diffraction (XRD) study of helical poly[9,9-bis(2-ethylhexyl)fluorene] (PF2/6) under high quasihydrostatic pressure and show an effect of pressure on the torsion angle (dihedral angle) between adjunct repeat units and on the hexagonal unit cell. A model for helical backbone conformation is constructed. The theoretical position for the most prominent 00l x-ray reflection is calculated as a function of torsion angle.

Absence of major histocompatibility complex class II mediated immunity in pipefish, Syngnathus typhle: evidence from deep transcriptome sequencing.

The major histocompatibility complex (MHC)-mediated adaptive immune system is the hallmark of gnathostome immune defence. Recent work suggests that cod-like fishes (Gadidae) lack important components of the MHC class II mediated immunity. Here, we report a putative independent loss of functionality of this pathway in another species, the pipefish Syngnathus typhle, that belongs to a distantly related fish family (Syngnathidae).

Tyrosinekinase inhibition facilitates cooperation of transcription factor SALL4 and ABC transporter A3 towards intrinsic CML cell drug resistance.

Although BCR-ABL1 tyrosine kinase inhibitors reliably induce disease remission for patients with chronic myeloid leukaemia (CML), unlimited extension of therapy is necessary to prevent relapse from persistent leukaemic cells. Here, we analysed model cell lines and primary CML cells for the expression and functions of the ABC transporter A3 (ABCA3) as well as the embryonic stem cell-associated transcription factor SALL4. ABCA3 protected leukaemic cells from the cytotoxic effects of the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib.

Genetic compatibilities, outcrossing rates and fitness consequences across life stages of the trematode Diplostomum pseudospathaceum.

Many parasitic helminths exhibit mixed mating systems, and switches between self-fertilization and outcrossing may be influenced by environmental conditions and parasite demography. While inbreeding depression selects against the development of purely self-fertilizing populations, genetic compatibility may contribute to stabilizing mixed strategies. Here we study the effects of inbreeding and genetic compatibility on offspring fitness in the digenean trematode Diplostomum pseudospathaceum, a parasite with a three-host life cycle.

Iron overload impairs proliferation of erythroid progenitors cells (BFU-E) from patients with myelodysplastic syndromes.

In patients with myelodysplastic syndromes (MDS) iron overload caused by long-term red blood cell transfusions is an important factor for comorbidity especially in low-risk MDS. In this report we present the results of a comparative study based on colony formation assays of hematopoietic cells in MDS patients with and without iron overload. We demonstrate that iron overload suppresses the proliferation of erythroid progenitors cells (BFU-E), while the myeloid compartment (CFU-GM) was not found to be affected.

Results from a 1-year, open-label, single arm, multi-center trial evaluating the efficacy and safety of oral Deferasirox in patients diagnosed with low and int-1 risk myelodysplastic syndrome (MDS) and transfusion-dependent iron overload.

The majority of patients with myelodysplastic syndrome (MDS) present with anemia and will become dependent on regular transfusions of packed red blood cells (PRBC) with the risk of iron overload (IOL). Liver iron content best reflects the total body iron content, and measurement of liver iron concentration (LIC) by MRI is a validated tool for detection, but data in MDS is rather limited. Here we present the results of a multi-center trial evaluating the efficacy and safety of deferasirox (DFX) in low and intermediate-1 risk MDS patients with transfusion-dependent IOL.

Synthesis of enantiopure, trisubstituted cryptophane-A derivatives.

The efficient synthesis of enantiopure, trisubstituted cryptophane-A derivatives, organic host molecules with unusually high xenon affinity, is reported. Synthesis and chromatographic separation of (±) tri-Mosher's acid substituted cryptophane diastereomers gave ready access to the enantiopure cryptophanes, which are critical components in the design of enantiomerically pure (129)Xe biosensors. Hyperpolarized (129)Xe NMR spectroscopy identified single resonances for both trisubstituted cryptophane diastereomers that were separated by 9.

Revised international prognostic scoring system for myelodysplastic syndromes.

The International Prognostic Scoring System (IPSS) is an important standard for assessing prognosis of primary untreated adult patients with myelodysplastic syndromes (MDS). To refine the IPSS, MDS patient databases from international institutions were coalesced to assemble a much larger combined database (Revised-IPSS [IPSS-R], n = 7012, IPSS, n = 816) for analysis. Multiple statistically weighted clinical features were used to generate a prognostic categorization model.

Are we ready for the use of foxp3(+) regulatory T cells for immunodiagnosis and immunotherapy in kidney transplantation?

The existence of T-cell subsets naturally committed to perform immunoregulation has led to enthusiastic efforts to investigate their role in the immunopathogenesis of transplantation. Being able to modulate alloresponses, regulatory T cells could be used as an immunodiagnostic tool in clinical kidney transplantation. Thus, the measurement of Foxp3 transcripts, the presence of regulatory T cells in kidney biopsies, and the phenotypic characterisation of the T-cell infiltrate could aid in the diagnosis of rejection and the immune monitoring and prediction of outcomes in kidney transplantation.

HIV and hepatitis C virus coinfection in Canada: challenges and opportunities for reducing preventable morbidity and mortality.

Objectives: Hepatitis C virus (HCV) has emerged as an important health problem in the era of effective HIV treatment. However, very few data exist on the health status and disease burden of HIV/HCV-coinfected Canadians.

Methods: HIV/HCV-coinfected patients were enrolled prospectively in a multicentre cohort from 16 centres across Canada between 2003 and 2010 and followed every 6 months.

Urban land teleconnections and sustainability.

This paper introduces urban land teleconnections as a conceptual framework that explicitly links land changes to underlying urbanization dynamics. We illustrate how three key themes that are currently addressed separately in the urban sustainability and land change literatures can lead to incorrect conclusions and misleading results when they are not examined jointly: the traditional system of land classification that is based on discrete categories and reinforces the false idea of a rural-urban dichotomy; the spatial quantification of land change that is based on place-based relationships, ignoring the connections between distant places, especially between urban functions and rural land uses; and the implicit assumptions about path dependency and sequential land changes that underlie current conceptualizations of land transitions. We then examine several environmental "grand challenges" and discuss how urban land teleconnections could help research communities frame scientific inquiries.

Association of TLR3-hyporesponsiveness and functional TLR3 L412F polymorphism with recurrent herpes labialis.

HSV-1 persistently infects almost 90% of our population; however, only 30% of the infected subjects suffer from recurrent herpes lesions, most frequently herpes labialis (HL). We hypothesized that variations in toll-like receptor (TLR) functions might contribute to HL susceptibility. In our study, the TLR-2/1,-3, and -7/8 responses of immune cell subsets derived from asymptomatic HSV-1 carriers were compared with responses of subjects with HL history.

Will a peripheral blood (PB) sample yield the same diagnostic and prognostic cytogenetic data as the concomitant bone marrow (BM) in myelodysplasia?

In patients with myelodysplastic syndromes (MDS), chromosome anomalies are detected by conventional cytogenetic studies (CCS) and/or interphase fluorescence in situ hybridization (FISH) of bone marrow (BM) samples and provide prognostic and diagnostic information, which can direct therapy. Whether peripheral blood (PB) can be substituted for bone marrow in these cases and can provide the same information remains unknown. Concurrent BM and PB specimens collected from 100 patients with recently diagnosed MDS were studied using both CCS and FISH.