Acquired thrombotic thrombocytopenic purpura: puzzles,curiosities and conundrums

We report a case of acquired thrombotic thrombocytopenic purpura (TTP) in a 34-year old patient with a prior diagnosis of systemic lupus erythematosis (SLE) who was recently started on hydroxychloroquine. Presenting symptoms included fevers, sore throat and productive cough with progressive weakness, dyspnea on exertion, hemoptysis and dark urine. Initial laboratory abnormalities were consistent with an acute microangiopathic hemolytic anemia and severe thrombocytopenia. At the time of admission, the patient’s lupus was highly active as evident by his high SLE Disease Activity Index (SLEDAI) score. He was later also found to have severely reduced ADAMTS-13 levels and a positive antibody assay. This case highlights the occasional difficulty in pinpointing the exact etiology of TTP as well as establishes a possible novel drug association between hydroxychloroquine and TTP development.     

Innovation at the Intersection of Alcohol and HIV Research

Working in an interdisciplinary manner at the crossroads of alcohol and HIV research is a challenge. This paper presents six novel approaches that could be applied to activities at the intersection of alcohol and HIV. These approaches are (i) address the fact that the availability of new technology is unevenly distributed around the world, (ii) use technology to move beyond both paper and digital surveys, (iii) introduce a focus on advocacy and partnerships with large technology companies, (iv) harness technological innovation to utilise digital counselling, (v) explore the use of virtual reality in both research and delivering interventions, and (vi) consider alternative funding models to those currently in existence to improve efficiencies and innovations. Aiming to understand the interplay of alcohol and HIV will require creativity. The six approaches outlines in this paper provide possible directions from which new approaches may emerge.     

Visualization of endothelial cell cycle dynamics in mouse using the Flt-1/eGFP-anillin system

Endothelial cell proliferation is a key process during vascular growth but its kinetics could only be assessed in vitro or ex vivo so far. To enable the monitoring and quantification of cell cycle kinetics in vivo, we have generated transgenic mice expressing an eGFP-anillin construct under control of the endothelial-specific Flt-1 promoter. This construct labels the nuclei of endothelial cells in late G1, S and G2 phase and changes its localization during the different stages of M phase, thereby enabling the monitoring of EC proliferation and cytokinesis. In Flt-1/eGFP-anillin mice, we found eGFP⁺ signals specifically in Ki67⁺/PECAM⁺ endothelial cells during vascular development. Quantification using this cell cycle reporter in embryos revealed a decline in endothelial cell proliferation between E9.5 to E12.5. By time-lapse microscopy, we determined the length of different cell cycle phases in embryonic endothelial cells in vivo and found a M phase duration of about 80 min with 2/3 covering karyokinesis and 1/3 cytokinesis. Thus, we have generated a versatile transgenic system for the accurate assessment of endothelial cell cycle dynamics in vitro and in vivo.     

Breast cancer classification and prognostication through diverse systems along with recent emerging findings in this respect; the dawn of new perspectives in the clinical applications

Breast cancer is the most common malignancy among women and the second leading cause of mortality due to cancer worldwide. The complexity of breast cancer resembles an intricate ecosystem comprising various cleverly designed interaction levels of internal and external factors to generate a pliable context in the clonal evolution of breast cancer cells. Principally, the complex entity can become evident toward delineating a number of significant variations in the specific fields of breast cancer analyses, including the molecular, physiological, and morphological characteristics, clinical presentations, risk factors, the histopathological conditions, and response to systemic therapy regarding the maintenance of tumor as a whole. In hindsight, various classification systems developing based on specific inclusion criteria have indisputably changed both our appreciation of the biological demeanor of breast cancer and the main strategies for designing tailored therapy regimens through the proper evaluation of diagnosis and prognostication of given specimens. Here, we endeavor to provide a general overview of different types of breast cancer classification as well as the clinical acceptance of their applications along with the latest findings in this area. Taken together, the major significance of breast cancer management that can be ascertained by operational convergent points of its stratification areas is owing to the fact that the achievement of individualized and targeted therapy may denounce new horizons of surveillance and treatment strategies in which they may function as a rheostat of specific therapy regimens toward reducing the detected distances between experimental data and operating options in clinical practice.