Quantitative transrectal shear wave elastography undergoing salvage extraperitoneal laparoscopic radical prostatectomy following failed radiotherapy

Background: To evaluate pre-surgical quantitative transrectal shear wave elastography (SWE) in the detection and characterisation of radioresistant prostate cancer.Methods: Twelve men with recurrent prostate cancer following external beam radiotherapy were included in a prospective protocol-driven study. All underwent MR imaging and quantitative shear wave elastographic assessment of recurrent disease prior to salvage laparoscopic radical prostatectomy procedures. Images were used to construct 3D mold printing and histopathological processing of surgical specimen. Statistical analyses including ROC were generated using software programmes.Results: There were 48 cancer foci identified on final histopathology using patient-specific mold-based approach in 12 patients. Mean number of lesion was 3.4 (range 2–4). Quantitative transrectal SWE showed a sensitivity and specificity 0.77 (95% CI 0.627–0.880) and 0.82 (95% CI 0.642–0.942), respectively. The diagnostic accuracy increased with increasing size of the lesions with overall AUC of 0.89.Conclusions: In our series, quantitative transrectal SWE showed a good diagnostic accuracy in the detection and characterisation of recurrent prostate cancer following failed radiotherapy treatment. These findings may help in targeting biopsies or future focal treatment options

Криостимуляция околораневых и раневых тканей в лечении длительно не заживающих ран и язв конечностей

Представлен опыт применения разработанного автором метода криостимуляции околораневых и раневых тканей, его сочетания с атравматическим адгезивным растяжением тканей у больных с длительно не заживающими ранами и язвами конечностей. Определены критерии его безопасного применения и эффекты влияния на ткани. Получены положительные результаты в восстановлении опорных и других тканей конечностей.The experience of application of the original method of cryostimulation of wound tissue and its combination with atraumatic adhesive stretching of the tissue in patients with persisting wounds and ulcers of the extremities is presented. The criteria of its safe use and effects of influence on the tissue were determined. Positive results in restoration of supporting and other tissue of the extremities were obtained

Thermopower and magnetotransport properties of Bi100−xSbx topological insulator thin films prepared by flash evaporation

We have measured the temperature dependence of resistance R(T), thermopower S(T), magnetoresistance (MR) and the Hall effect (HE) of Bi80Sb20, Bi85Sb15 and Bi90Sb10 topological insulator thin films. Samples were prepared by sequential flash-evaporation at room temperature and annealing at T = 350 K. The R(T) of the three investigated samples show metallic-like behavior at temperatures less than T = 75 K, while at higher temperatures, R(T) curves show a semiconducting-like behavior. The thermopower S(T) of the three investigated samples is negative in the entire temperature range measured in this work, with a linear behavior from 5 K up to ≈100 K. The magnetoresistance of all samples is positive with a small temperature dependence. The highest MR(B = 7 T) was observed in Bi85Sb15 with a ≈600% and ≈125% change at 5 K and 300 K, respectively. Clear evidence of weak antilocalization contribution to the MR was observed only in sample Bi85Sb15 at temperatures T < 75 K. Quantum oscillations in the MR originating from the Fermi surface, which has a clear two-dimensional character, were observed in sample Bi85Sb15 up to ≈21 K. Carrier mobility information of sample Bi85Sb15 was extracted from low field HE data, showing a remarkably high value of μ ≈ 2.8 × 104 cm2/Vs at 5 K, with a small decrease for increasing temperature.Fil: Osmic, E.. Universitat Leipzig. Felix Bloch Institut Fur Festkorperphysik.; AlemaniaFil: Barzola Quiquia, Jose Luis. Universitat Leipzig. Felix Bloch Institut Fur Festkorperphysik.; AlemaniaFil: Böhlmann, W.. Universitat Leipzig. Felix Bloch Institut Fur Festkorperphysik.; AlemaniaFil: Bercoff, Paula Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Venosta, Lisandro Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Häussler, P.. Chemnitz University Of Technology; Alemani

Recent advances in understanding the roles of whole genome duplications in evolution

Ancient whole-genome duplications (WGDs)—paleopolyploidy events—are key to solving Darwin’s ‘abominable mystery’ of how flowering plants evolved and radiated into a rich variety of species. The vertebrates also emerged from their invertebrate ancestors via two WGDs, and genomes of diverse gymnosperm trees, unicellular eukaryotes, invertebrates, fishes, amphibians and even a rodent carry evidence of lineage-specific WGDs. Modern polyploidy is common in eukaryotes, and it can be induced, enabling mechanisms and short-term cost-benefit assessments of polyploidy to be studied experimentally. However, the ancient WGDs can be reconstructed only by comparative genomics: these studies are difficult because the DNA duplicates have been through tens or hundreds of millions of years of gene losses, mutations, and chromosomal rearrangements that culminate in resolution of the polyploid genomes back into diploid ones (rediploidisation). Intriguing asymmetries in patterns of post-WGD gene loss and retention between duplicated sets of chromosomes have been discovered recently, and elaborations of signal transduction systems are lasting legacies from several WGDs. The data imply that simpler signalling pathways in the pre-WGD ancestors were converted via WGDs into multi-stranded parallelised networks. Genetic and biochemical studies in plants, yeasts and vertebrates suggest a paradigm in which different combinations of sister paralogues in the post-WGD regulatory networks are co-regulated under different conditions. In principle, such networks can respond to a wide array of environmental, sensory and hormonal stimuli and integrate them to generate phenotypic variety in cell types and behaviours. Patterns are also being discerned in how the post-WGD signalling networks are reconfigured in human cancers and neurological conditions. It is fascinating to unpick how ancient genomic events impact on complexity, variety and disease in modern life

In Vivo Evaluation of Cervical Stiffness Evolution during Induced Ripening Using Shear Wave Elastography, Histology and 2 Photon Excitation Microscopy: Insight from an Animal Model

Prematurity affects 11% of the births and is the main cause of infant mortality. On the opposite case, the failure of induction of parturition in the case of delayed spontaneous birth is associated with fetal suffering. Both conditions are associated with precocious and/or delayed cervical ripening. Quantitative and objective information about the temporal evolution of the cervical ripening may provide a complementary method to identify cases at risk of preterm delivery and to assess the likelihood of successful induction of labour. In this study, the cervical stiffness was measured in vivo in pregnant sheep by using Shear Wave Elastography (SWE). This technique assesses the stiffness of tissue through the measurement of shear waves speed (SWS). In the present study, 9 pregnant ewes were used. Cervical ripening was induced at 127 days of pregnancy (term: 145 days) by dexamethasone injection in 5 animals, while 4 animals were used as control. Elastographic images of the cervix were obtained by two independent operators every 4 hours during 24 hours after injection to monitor the cervical maturation induced by the dexamethasone. Based on the measurements of SWS during vaginal ultrasound examination, the stiffness in the second ring of the cervix was quantified over a circular region of interest of 5 mm diameter. SWS was found to decrease significantly in the first 4–8 hours after dexamethasone compared to controls, which was associated with cervical ripening induced by dexamethasone (from 1.779 m/s ± 0.548 m/s, p < 0.0005, to 1.291 m/s ± 0.516 m/s, p < 0.000). Consequently a drop in the cervical elasticity was quantified too (from 9.5 kPa ± 0.9 kPa, p < 0.0005, to 5.0 kPa ± 0.8 kPa, p < 0.000). Moreover, SWE measurements were highly reproducible between both operators at all times. Cervical ripening induced by dexamethasone was confirmed by the significant increase in maternal plasma Prostaglandin E2 (PGE2), as evidenced by the assay of its metabolite PGEM. Histological analyses and two-photon excitation microscopy, combining both Second Harmonic Generation (SHG) and Two-photon Fluorescence microscopy (2PF) contrasts, were used to investigate, at the microscopic scale, the structure of cervical tissue. Results show that both collagen and 2PF-active fibrillar structures could be closely related to the mechanical properties of cervical tissue that are perceptible in elastography. In conclusion, SWE may be a valuable method to objectively quantify the cervical stiffness and as a complementary diagnostic tool for preterm birth and for labour induction success

Impact of the HIV-1 env Genetic Context outside HR1–HR2 on Resistance to the Fusion Inhibitor Enfuvirtide and Viral Infectivity in Clinical Isolates

Resistance mutations to the HIV-1 fusion inhibitor enfuvirtide emerge mainly within the drug's target region, HR1, and compensatory mutations have been described within HR2. The surrounding envelope (env) genetic context might also contribute to resistance, although to what extent and through which determinants remains elusive. To quantify the direct role of the env context in resistance to enfuvirtide and in viral infectivity, we compared enfuvirtide susceptibility and infectivity of recombinant viral pairs harboring the HR1–HR2 region or the full Env ectodomain of longitudinal env clones from 5 heavily treated patients failing enfuvirtide therapy. Prior to enfuvirtide treatment onset, no env carried known resistance mutations and full Env viruses were on average less susceptible than HR1–HR2 recombinants. All escape clones carried at least one of G36D, V38A, N42D and/or N43D/S in HR1, and accordingly, resistance increased 11- to 2800-fold relative to baseline. Resistance of full Env recombinant viruses was similar to resistance of their HR1–HR2 counterpart, indicating that HR1 and HR2 are the main contributors to resistance. Strictly X4 viruses were more resistant than strictly R5 viruses, while dual-tropic Envs featured similar resistance levels irrespective of the coreceptor expressed by the cell line used. Full Env recombinants from all patients gained infectivity under prolonged drug pressure; for HR1–HR2 viruses, infectivity remained steady for 3/5 patients, while for 2/5 patients, gains in infectivity paralleled those of the corresponding full Env recombinants, indicating that the env genetic context accounts mainly for infectivity adjustments. Phylogenetic analyses revealed that quasispecies selection is a step-wise process where selection of enfuvirtide resistance is a dominant factor early during therapy, while increased infectivity is the prominent driver under prolonged therapy

The Politics of Federalism in Argentina: Implications for Governance and Accountability

This paper contributes to an agenda that views the effects of policies and institutional reforms as dependent on the structure of political incentives for national and subnational political actors. The paper studies political incentive structures at the subnational level and the mechanisms whereby they affect national-level politics and policymaking at the national level in Argentina, a highly decentralized middle-income democracy, Argentina. The Argentine political system makes subnational political power structures very influential in national politics. Moreover, most Argentine provinces are local bastions of power dominated by entrenched elites, characterized by scarce political competition, weak division of powers, and clientelistic political linkages. Political dominance in the provinces and political importance at the national level reinforce each other, dragging the Argentine political and policymaking system towards the practices and features of its most politically backward regions

The CD85j+ NK Cell Subset Potently Controls HIV-1 Replication in Autologous Dendritic Cells

Natural killer (NK) cells and dendritic cells (DC) are thought to play critical roles in the first phases of HIV infection. In this study, we examined changes in the NK cell repertoire and functions occurring in response to early interaction with HIV-infected DC, using an autologous in vitro NK/DC coculture system. We show that NK cell interaction with HIV-1-infected autologous monocyte-derived DC (MDDC) modulates NK receptor expression. In particular, expression of the CD85j receptor on NK cells was strongly down-regulated upon coculture with HIV-1-infected MDDC. We demonstrate that CD85j+ NK cells exert potent control of HIV-1 replication in single-round and productively HIV-1-infected MDDC, whereas CD85j− NK cells induce a modest and transient decrease of HIV-1 replication. HIV-1 suppression in MDCC by CD85j+ NK cells required cell-to-cell contact and did not appear mediated by cytotoxicity or by soluble factors. HIV-1 inhibition was abolished when NK-MDDC interaction through the CD85j receptor was blocked with a recombinant CD85j molecule, whereas inhibition was only slightly counteracted by blocking HLA class I molecules, which are known CD85j ligands. After masking HLA class I molecules with specific antibodies, a fraction of HIV-1 infected MDDC was still strongly stained by a recombinant CD85j protein. These results suggest that CD85j+ NK cell inhibition of HIV-1 replication in MDDC is mainly mediated by CD85j interaction with an unknown ligand (distinct from HLA class I molecules) preferentially expressed on HIV-1-infected MDDC

HIV-2 Integrase Variation in Integrase Inhibitor-Naïve Adults in Senegal, West Africa

Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2-infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at "secondary" HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2-infected patients

Human TRIM Gene Expression in Response to Interferons

Tripartite motif (TRIM) proteins constitute a family of proteins that share a conserved tripartite architecture. The recent discovery of the anti-HIV activity of TRIM5α in primate cells has stimulated much interest in the potential role of TRIM proteins in antiviral activities and innate immunity.To test if TRIM genes are up-regulated during antiviral immune responses, we performed a systematic analysis of TRIM gene expression in human primary lymphocytes and monocyte-derived macrophages in response to interferons (IFNs, type I and II) or following FcγR-mediated activation of macrophages. We found that 27 of the 72 human TRIM genes are sensitive to IFN. Our analysis identifies 9 additional TRIM genes that are up-regulated by IFNs, among which only 3 have previously been found to display an antiviral activity. Also, we found 2 TRIM proteins, TRIM9 and 54, to be specifically up-regulated in FcγR-activated macrophages.Our results present the first comprehensive TRIM gene expression analysis in primary human immune cells, and suggest the involvement of additional TRIM proteins in regulating host antiviral activities