Therapeutic implications of recombinant human erythropoietin in anaemic related clinical manifestations

The introduction of recombinant human erythropoietin (RHUEPO) has revolutionised the treatment strategies for patients suffering with anaemia of chronic renal disease and chronic heart failure. Clinicalstudies and several observational evidences have demonstrated that RHUEPO is also useful in various non-uraemic conditions including haematological and oncological disorders, prematurity, HIV infectionand preoperative therapies. The successful treatment of all the anaemic related malfunctions with recombinant human erythropoietin (RHUEPO) has become a standard treatment tool for dialysis patients and as an interesting therapeutic option for several forms of non-renal anaemia. As a conesquence of both, RHUEPO has achieved the highest annual sales worldwide and the potential of it increases its scope in the future prospective also

Epstein-Barr virus (EBV) deletions as biomarkers of response to treatment of chronic active EBV

Chronic active Epstein–Barr virus (CAEBV) disease is a rare condition characterised by persistent EBV infection in previously healthy individuals. Defective EBV genomes were found in East Asian patients with CAEBV. In the present study, we sequenced 14 blood EBV samples from three UK patients with CAEBV, comparing the results with saliva CAEBV samples and other conditions. We observed EBV deletions in blood, some of which may disrupt viral replication, but not saliva in CAEBV. Deletions were lost overtime after successful treatment. These findings are compatible with CAEBV being associated with the evolution and persistence of EBV+ haematological clones that are lost on successful treatment

Genome-Wide Association Study of Human Immunodeficiency Virus (HIV)-1 Coreceptor Usage in Treatment-Naive Patients from An AIDS Clinical Trials Group Study

OBJECTIVES: We conducted a genome-wide association study to explore whether common host genetic variants (>5% frequency) were associated with presence of virus able to use CXCR4 for entry. METHODS: Phenotypic determination of human immunodeficiency virus (HIV)-1 coreceptor usage was performed on pretreatment plasma HIV-1 samples from treatment-naive participants in AIDS Clinical Trials Group A5095, a study of initial antiretroviral regimens. Associations between genome-wide single-nucleotide polymorphisms (SNPs), CCR5 Δ32 genotype, and human leukocyte antigen (HLA) class I alleles and viral coreceptor usage were explored. RESULTS: Viral phenotypes were obtained from 593 patients with available genome-wide SNP data. Forty-four percent of subjects had virus capable of using CXCR4 for entry as determined by phenotyping. Overall, no associations, including those between polymorphisms in genes encoding viral coreceptors and their promoter regions or in HLA genes previously associated with HIV-1 disease progression, passed the statistical threshold for genome-wide significance (P < 5.0 × 10(-8)) in any comparison. However, the presence of viruses able to use CXCR4 for entry was marginally associated with the CCR5 Δ32 genotype in the nongenome-wide analysis. CONCLUSIONS: No human genetic variants were significantly associated with virus able to use CXCR4 for entry at the genome-wide level. Although the sample size had limited power to definitively exclude genetic associations, these results suggest that host genetic factors, including those that influence coreceptor expression or the immune pressures leading to viral envelope diversity, are either rare or have only modest effects in determining HIV-1 coreceptor usage

Hemorrhagic Shock Caused by Rupture of an Intra-Abdominal Leydig Cell Tumour: Case Report

The rupture of an intra-abdominal testicular neoplasm is a rare cause of acute abdomen and massive intra-abdominal haemorrhage. We report the case of a 70-year-old male presenting a massive intra-abdominal bleeding caused by a Leydig cell tumour in an undescended testis. The clinical details and pathology of this rare testicular tumour are discussed

Measuring organisational readiness for patient engagement (MORE) : an international online Delphi consensus study

Date of Acceptance: 28/01/2015. © 2015 Oostendorp et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedWidespread implementation of patient engagement by organisations and clinical teams is not a reality yet. The aim of this study is to develop a measure of organisational readiness for patient engagement designed to monitor and facilitate a healthcare organisation’s willingness and ability to effectively implement patient engagement in healthcarePeer reviewedFinal Published versio

Two-dimensional amine and hydroxy functionalized fused aromatic covalent organic framework

Ordered two-dimensional covalent organic frameworks (COFs) have generally been synthesized using reversible reactions. It has been difficult to synthesize a similar degree of ordered COFs using irreversible reactions. Developing COFs with a fused aromatic ring system via an irreversible reaction is highly desirable but has remained a significant challenge. Here we demonstrate a COF that can be synthesized from organic building blocks via irreversible condensation (aromatization). The as-synthesized robust fused aromatic COF (F-COF) exhibits high crystallinity. Its lattice structure is characterized by scanning tunneling microscopy and X-ray diffraction pattern. Because of its fused aromatic ring system, the F-COF structure possesses high physiochemical stability, due to the absence of hydrolysable weak covalent bonds

SALL4 Expression in Gonocytes and Spermatogonial Clones of Postnatal Mouse Testes

The spermatogenic lineage is established after birth when gonocytes migrate to the basement membrane of seminiferous tubules and give rise to spermatogonial stem cells (SSC). In adults, SSCs reside within the population of undifferentiated spermatogonia (Aundiff) that expands clonally from single cells (Asingle) to form pairs (Apaired) and chains of 4, 8 and 16 Aaligned spermatogonia. Although stem cell activity is thought to reside in the population of Asingle spermatogonia, new research suggests that clone size alone does not define the stem cell pool. The mechanisms that regulate self-renewal and differentiation fate decisions are poorly understood due to limited availability of experimental tools that distinguish the products of those fate decisions. The pluripotency factor SALL4 (sal-like protein 4) is implicated in stem cell maintenance and patterning in many organs during embryonic development, but expression becomes restricted to the gonads after birth. We analyzed the expression of SALL4 in the mouse testis during the first weeks after birth and in adult seminiferous tubules. In newborn mice, the isoform SALL4B is expressed in quiescent gonocytes at postnatal day 0 (PND0) and SALL4A is upregulated at PND7 when gonocytes have colonized the basement membrane and given rise to spermatogonia. During steady-state spermatogenesis in adult testes, SALL4 expression overlapped substantially with PLZF and LIN28 in Asingle, Apaired and Aaligned spermatogonia and therefore appears to be a marker of undifferentiated spermatogonia in mice. In contrast, co-expression of SALL4 with GFRα1 and cKIT identified distinct subpopulations of Aundiff in all clone sizes that might provide clues about SSC regulation. Collectively, these results indicate that 1) SALL4 isoforms are differentially expressed at the initiation of spermatogenesis, 2) SALL4 is expressed in undifferentiated spermatogonia in adult testes and 3) SALL4 co-staining with GFRα1 and cKIT reveals distinct subpopulations of Aundiff spermatogonia that merit further investigation. © 2013 Gassei, Orwig

Exploring the Free Energy Landscape: From Dynamics to Networks and Back

The knowledge of the Free Energy Landscape topology is the essential key to understand many biochemical processes. The determination of the conformers of a protein and their basins of attraction takes a central role for studying molecular isomerization reactions. In this work, we present a novel framework to unveil the features of a Free Energy Landscape answering questions such as how many meta-stable conformers are, how the hierarchical relationship among them is, or what the structure and kinetics of the transition paths are. Exploring the landscape by molecular dynamics simulations, the microscopic data of the trajectory are encoded into a Conformational Markov Network. The structure of this graph reveals the regions of the conformational space corresponding to the basins of attraction. In addition, handling the Conformational Markov Network, relevant kinetic magnitudes as dwell times or rate constants, and the hierarchical relationship among basins, complete the global picture of the landscape. We show the power of the analysis studying a toy model of a funnel-like potential and computing efficiently the conformers of a short peptide, the dialanine, paving the way to a systematic study of the Free Energy Landscape in large peptides.Comment: PLoS Computational Biology (in press

Prediction of post-operative necrosis after mastectomy: A pilot study utilizing optical diffusion imaging spectroscopy

<p>Abstract</p> <p>Introduction</p> <p>Flap necrosis and epidermolysis occurs in 18-30% of all mastectomies. Complications may be prevented by intra-operative detection of ischemia. Currently, no technique enables quantitative valuation of mastectomy skin perfusion. Optical Diffusion Imaging Spectroscopy (ViOptix T.Ox Tissue Oximeter) measures the ratio of oxyhemoglobin to deoxyhemoglobin over a 1 × 1 cm area to obtain a non-invasive measurement of perfusion (StO₂).</p> <p>Methods</p> <p>This study evaluates the ability of ViOptix T.Ox Tissue Oximeter to predict mastectomy flap necrosis. StO₂measurements were taken at five points before and at completion of dissection in 10 patients. Data collected included: demographics, tumor size, flap length/thickness, co-morbidities, procedure length, and wound complications.</p> <p>Results</p> <p>One patient experienced mastectomy skin flap necrosis. Five patients underwent immediate reconstruction, including the patient with necrosis. Statistically significant factors contributing to necrosis included reduction in medial flap StO₂(p = 0.0189), reduction in inferior flap StO₂(p = 0.003), and flap length (p = 0.009).</p> <p>Conclusion</p> <p>StO₂reductions may be utilized to identify impaired perfusion in mastectomy skin flaps.</p