Platelet Biorheology and Mechanobiology in Thrombosis and Hemostasis: Perspectives from Multiscale Computation.

Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s-1) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s-1) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modeling informed by biology can provide new pathophysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to the better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine.

Origin of congenital coronary arterio-ventricular fistulae from anomalous epicardial and myocardial development.

Coronary Artery Fistulae (CAFs) are cardiac congenital anomalies consisting of an abnormal communication of a coronary artery with either a cardiac chamber or another cardiac vessel. In humans, these congenital anomalies can lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation, and failure. Unfortunately, despite their clinical relevance, the aetiology of CAFs remains unknown. In this work, we have used two different species (mouse and avian embryos) to experimentally model CAFs morphogenesis. Both conditional Itga4 (alpha 4 integrin) epicardial deletion in mice and cryocauterisation of chick embryonic hearts disrupted epicardial development and ventricular wall growth, two essential events in coronary embryogenesis. Our results suggest that myocardial discontinuities in the embryonic ventricular wall promote the early contact of the endocardium with epicardial-derived coronary progenitors at the cardiac surface, leading to ventricular endocardial extrusion, precocious differentiation of coronary smooth muscle cells, and the formation of pouch-like aberrant coronary-like structures in direct connection with the ventricular lumen. The structure of these CAF-like anomalies was compared with histopathological data from a human CAF. Our results provide relevant information for the early diagnosis of these congenital anomalies and the molecular mechanisms that regulate their embryogenesis.

Interaction with touchscreen smartphones in patients with essential tremor and healthy individuals.

INTRODUCTION: Smartphone use in biomedical research is becoming more prevalent in different clinical settings. We performed a pilot study to obtain information on smartphone use by patients with essential tremor (ET) and healthy controls, with a view to determining whether performance of touchscreen tasks is different between these groups and describing touchscreen interaction factors. METHOD: A total of 31 patients with ET and 40 sex- and age-matched healthy controls completed a descriptive questionnaire about the use of smartphones. Participants subsequently interacted with an under-development Android application, and performed 4 tests evaluating typical touchscreen interaction gestures; each test was performed 5 times. RESULT: The type of smartphone use and touchscreen interaction were not significantly different between patients and controls. Age and frequency of smartphone use are key factors in touchscreen interaction. CONCLUSION: Our results support the use of smartphone touchscreens for research into ET, although further studies are required.

Interaction with touchscreen smartphones in patients with essential tremor and healthy individuals. / Interacción con pantalla táctil de smartphone en pacientes con temblor esencial y sujetos sanos.

INTRODUCTION: Smartphones use in biomedical research is becoming more prevalent in different clinical settings. We performed a pilot study to obtain information on smartphone use by patients with essential tremor (ET) and healthy controls, with a view to determining whether performance of touchscreen tasks is different between these groups and describing touchscreen interaction factors. METHOD: A total of 31 patients with ET and 40 sex- and age-matched healthy controls completed a descriptive questionnaire about the use of smartphones. Participants subsequently interacted with an under-development Android application, and performed 4 tests evaluating typical touchscreen interaction gestures; each test was performed 5 times. RESULT: The type of smartphone use and touchscreen interaction were not significantly different between patients and controls. Age and frequency of smartphone use are key factors in touchscreen interaction. CONCLUSION: Our results support the use of smartphone touchscreens for research into ET, although further studies are required.

Task independent identification of sensor location on upper limb from orientation data.

In this paper we describe a novel method for sensor placement identification, and demonstrate the effectiveness of this method on an upper limb neuroprothesis for tremor suppression under a variety of tasks. Our objective is to facilitate long-term tremor monitoring; tremor is the most prevalent movement disorder. Two assumptions are made: 1) movement and tremor demonstrate an additive effect further down the kinematic chain; 2) most applications have chained or fixed sensor locations. These assumptions justify obtaining absolute location through identifying relative location and thus to allow us to simplify the classification algorithm. Seventeen tasks were performed by patients suffering from essential tremor or Parkinson's disease. Ten features were found that resulted in 98.30% average accuracy (min: 92.31%; max: 100%) for the best configuration, irrespective of the task being performed. The method presented here is an important step towards more user-friendly and context-aware neuroprostheses for tremor suppression and monitoring, and facilitates the use of wearable sensors by non-trained personnel.