Numerical Investigation of Cryopreserved Zebrafish Sperm Cell Activation in Microchannels

This aim of this research project is to probe the activation process of zebrafish spermatozoa. Zebrafish are a model species for biological engineering applications, and the cryopreservation of their reproductive cells allows for inexpensive cataloging and maintenance of valuable biological material. Evaluation of cryopreservation protocols for aquatic sperm cells is typically accomplished by motility analysis after subjecting cells to a cryopreservation treatment. In zebrafish sperm cells, motility is initiated when cells come into contact with a hypo-osmotic environment. Subsequent activation analysis is currently done manually and brings with it an inherent difficulty and error. This process is slow and not ideal for high-throughput sample processing and analysis. As such, there is a critical need for an influx of enabling technologies to improve the throughput and optimization of these procedures. Microfluidics offers an intriguing solution to this problem. These devices, the size of a single 1-inch by 3-inch glass slide, offer automated, high-throughput, highly reproducible results. Additionally they utilize small sample volumes, which is important in minimizing valuable sample loss. Cells can be input into a micromixer which can rapidly dilute the extracellular environment, and then sent to an analysis chamber that acn determine the efficacy of a cryopreservation treatment. Despite its popularity in other fields, computational modeling of sperm cell activation has been nearly non-existent in literature. In this work, we model both the macroscopic aspects of particulate flow in a microchannel, and the microscopic mass transport across the cellular membrane. By tracking cells as they move throughout a simulated microdevice, we can find a history for each particle and predict cell outcomes. We are the first to introduce this combinatory model to the problem of cryoprotectant loading, where numerical modeling has well-established presence, and to the problem of zebrafish sperm cell activation. I envision the combination of microfluidics, with their controllable and reproducible flow patterns, and computational methods capturing both macro- and micro-transport, as two examples of the very enabling technologies that cryopreservation needs. While we apply these methods primarily to sperm cell analysis, the framework can be widely applied to a variety of cells and tissues

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Implant infections: adhesion, biofilm formation and immune evasion

Medical device-associated infections account for a large proportion of hospital-acquired infections. A variety of opportunistic pathogens can cause implant infections, depending on the type of the implant and on the anatomical site of implantation. The success of these versatile pathogens depends on rapid adhesion to virtually all biomaterial surfaces and survival in the hostile host environment. Biofilm formation on implant surfaces shelters the bacteria and encourages persistence of infection. Furthermore, implant-infecting bacteria can elude innate and adaptive host defences as well as biocides and antibiotic chemotherapies. In this Review, we explore the fundamental pathogenic mechanisms underlying implant infections, highlighting orthopaedic implants and Staphylococcus aureus as a prime example, and discuss innovative targets for preventive and therapeutic strategies