Association of Coagulation Activation with Clinical Complications in Sickle Cell Disease

Background: The contribution of hypercoagulability to the pathophysiology of sickle cell disease (SCD) remains poorly defined. We sought to evaluate the association of markers of coagulation and platelet activation with specific clinical complications and laboratory variables in patients with SCD. Design and Methods: Plasma markers of coagulation activation (D-dimer and TAT), platelet activation (soluble CD40 ligand), microparticle-associated tissue factor (MPTF) procoagulant activity and other laboratory variables were obtained in a cohort of patients with SCD. Tricuspid regurgitant jet velocity was determined by Doppler echocardiography and the presence/history of clinical complications was ascertained at the time of evaluation, combined with a detailed review of the medical records. Results: No significant differences in the levels of D-dimer, TAT, soluble CD40 ligand, and MPTF procoagulant activity were observed between patients in the SS/SD/Sb 0 thalassemia and SC/Sb + thalassemia groups. Both TAT and D-dimer were significantly correlated with measures of hemolysis (lactate dehydrogenase, indirect bilirubin and hemoglobin) and soluble vascular cell adhesion molecule-1. In patients in the SS/SD/Sb 0 thalassemia group, D-dimer was associated with a history of stroke (p = 0.049), TAT was associated with a history of retinopathy (p = 0.0176), and CD40 ligand was associated with the frequency of pain episodes (p = 0.039). In multivariate analyses, D-dimer was associated with reticulocyte count, lactat

The value of haptic feedback in conventional and robot-assisted minimal invasive surgery and virtual reality training: a current review

BACKGROUND: Virtual reality (VR) as surgical training tool has become a state-of-the-art technique in training and teaching skills for minimally invasive surgery (MIS). Although intuitively appealing, the true benefits of haptic (VR training) platforms are unknown. Many questions about haptic feedback in the different areas of surgical skills (training) need to be answered before adding costly haptic feedback in VR simulation for MIS training. This study was designed to review the current status and value of haptic feedback in conventional and robot-assisted MIS and training by using virtual reality simulation. METHODS: A systematic review of the literature was undertaken using PubMed and MEDLINE. The following search terms were used: Haptic feedback OR Haptics OR Force feedback AND/OR Minimal Invasive Surgery AND/OR Minimal Access Surgery AND/OR Robotics AND/OR Robotic Surgery AND/OR Endoscopic Surgery AND/OR Virtual Reality AND/OR Simulation OR Surgical Training/Education. RESULTS: The results were assessed according to level of evidence as reflected by the Oxford Centre of Evidence-based Medicine Levels of Evidence. CONCLUSIONS: In the current literature, no firm consensus exists on the importance of haptic feedback in performing minimally invasive surgery. Although the majority of the results show positive assessment of the benefits of force feedback, results are ambivalent and not unanimous on the subject. Benefits are least disputed when related to surgery using robotics, because there is no haptic feedback in currently used robotics. The addition of haptics is believed to reduce surgical errors resulting from a lack of it, especially in knot tying. Little research has been performed in the area of robot-assisted endoscopic surgical training, but results seem promising. Concerning VR training, results indicate that haptic feedback is important during the early phase of psychomotor skill acquisitio

Definitions, Foundations and Associations of Physical Literacy: A Systematic Review

Background: The concept of physical literacy has stimulated increased research attention in recent years—being deployed in physical education, sport participation, and the promotion of physical activity. Independent research groups currently operationalize the construct differently. Objective The purpose of this systematic review was to conduct a systematic review of the physical literacy construct,as reflected in contemporary research literature. Methods: Five databases were searched using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines for systematic reviews. Inclusion criteria were English language, peer reviewed, published by March 2016, and seeking to conceptualize physical literacy. Articles that met these criteria were analysed in relation to three core areas: properties/attributes, philosophicalfoundations and theoretical associations with other constructs. A total of 50 published articles met the inclusion criteria and were analysed qualitatively using inductive thematic analysis.Results: The thematic analysis addressed the three core areas. Under definitions, core attributes that define physical literacy were identified, as well as areas of conflict between different approaches currently being adopted. One relatively clear philosophical approach was prominent in approximately half of the papers, based on a monist/holistic ontology and phenomenological epistemology. Finally, theanalysis identified a number of theoretical associations, including health, physical activity and academic performance.Conclusions: Current literature contains different representations of the physical literacy construct. The costs and benefits of adopting an exclusive approach versus pluralism are considered. Recommendations for both researchers and practitioners focus on identifying and clearly articulating the definitions, philosophical assumptions and expected outcomes prior to evaluating the effectiveness of this emerging concept

Cervical epidural steroid injections in the management of cervical radiculitis: interlaminar versus transforaminal. A review

There has been recent concern regarding the safety of cervical epidural steroid injections. The decision to proceed with treatment requires balancing the risk and benefits. This article is an in depth review of the efficacy, complications, and technique of both interlaminar and transforaminal cervical epidural steroid injections in the management of cervical radiculitis

In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization

Treating pain by inhibiting ATP activation of P2X3-containing receptors heralds an exciting new approach to pain management, and Afferent's program marks the vanguard in a new class of drugs poised to explore this approach to meet the significant unmet needs in pain management. P2X3 receptor subunits are expressed predominately and selectively in so-called C- and Aδ-fiber primary afferent neurons in most tissues and organ systems, including skin, joints, and hollow organs, suggesting a high degree of specificity to the pain sensing system in the human body. P2X3 antagonists block the activation of these fibers by ATP and stand to offer an alternative approach to the management of pain and discomfort. In addition, P2X3 is expressed pre-synaptically at central terminals of C-fiber afferent neurons, where ATP further sensitizes transmission of painful signals. As a result of the selectivity of the expression of P2X3, there is a lower likelihood of adverse effects in the brain, gastrointestinal, or cardiovascular tissues, effects which remain limiting factors for many existing pain therapeutics. In the periphery, ATP (the factor that triggers P2X3 receptor activation) can be released from various cells as a result of tissue inflammation, injury or stress, as well as visceral organ distension, and stimulate these local nociceptors. The P2X3 receptor rationale has aroused a formidable level of investigation producing many reports that clarify the potential role of ATP as a pain mediator, in chronic sensitized states in particular, and has piqued the interest of pharmaceutical companies. P2X receptor-mediated afferent activation has been implicated in inflammatory, visceral, and neuropathic pain states, as well as in airways hyperreactivity, migraine, itch, and cancer pain. It is well appreciated that oftentimes new mechanisms translate poorly from models into clinical efficacy and effectiveness; however, the breadth of activity seen from P2X3 inhibition in models offers a realistic chance that this novel mechanism to inhibit afferent nerve sensitization may find its place in the sun and bring some merciful relief to the torment of persistent discomfort and pain. The development philosophy at Afferent is to conduct proof of concept patient studies and best identify target patient groups that may benefit from this new intervention

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules

The use of the CR-10 scale to allow self-regulation of isometric exercise intensity in pre-hypertensive and hypertensive participants

Purpose: Isometric exercise (IE) has been shown to lower blood pressure (BP). Using equipment with force output displays, intensity is usually regulated at 30% maximal voluntary contraction (MVC); however, the cost of programmable equipment and their requirement for maximal contractions presents limitations. A simple, cost-effective alternative deserves investigation. The purpose of this study was (i) to explore the relationship between %MVC, change in systolic BP (ΔSBP), and perceived exertion (CR-10) and (ii) to assess the validity of self-regulation of intensity during isometric handgrip exercise. Methods: Fourteen pre-hypertensive and hypertensive adults completed eight, 2-minute isometric handgrip exercises at randomised intensities; participants estimated their perceived exertion at 30-second intervals (Estimation Task). Subsequently, on three separate occasions participants performed four 2-minute contractions at an exertion level that they perceived to be equivalent to CR-10 “Level-6” (Production Task). Results: There were significant linear relationships between the estimated exertion on the CR-10 scale, and ΔSBP (r=0.784) and %MVC (r=0.845). Level 6 was equivalent to an average ΔSBP of 38mmHg (95% CI; 44mmHg, 32mmHg) and a relative force of 33% MVC (95% CI; 36.2%, 30%). During the production task, %MVC was not significantly different between the estimation task and each production task. In at least the first two repetitions of each production task, ΔSBP was significantly lower than that observed in the estimation task. Conclusion: These findings show that CR-10 “level-6” is an appropriate method of self-regulating isometric handgrip intensity; its use offers an affordable and accessible alternative for isometric exercise prescription aimed at reducing BP