“Human Babesiosis”: An Emerging Transfusion Dilemma

Babesiosis, a common disease of animals, can infect humans via vector “tick bite”, particularly in endemic areas. The recent reports of fatal cases in Hepatitis C and postliver transplant patients resulting from transfusion of contaminated blood should alert the medical profession regarding this emerging dilemma in endemic as well as nonendemic areas and the need for accurate blood screening for transfusion. Here, we illustrate different stages of the parasite lifecycle, progression of babesiosis in animal model, some aspects of pathologic outcomes, ongoing therapeutic modalities, and a feasible Acridine Orange fluorescent methodology for the diagnostic evaluation of blood samples

Exploring the logic of mobile search

After more than a decade of development work and hopes, the usage of mobile Internet has finally taken off. Now, we are witnessing the first signs of evidence of what might become the explosion of mobile content and applications that will be shaping the (mobile) Internet of the future. Similar to the wired Internet, search will become very relevant for the usage of mobile Internet. Current research on mobile search has applied a limited set of methodologies and has also generated a narrow outcome of meaningful results. This article covers new ground, exploring the use and visions of mobile search with a users' interview-based qualitative study. Its main conclusion builds upon the hypothesis that mobile search is sensitive to a mobile logic different than today's one. First, (advanced) users ask for accessing with their mobile devices the entire Internet, rather than subsections of it. Second, success is based on new added-value applications that exploit unique mobile functionalities. The authors interpret that such mobile logic involves fundamentally the use of personalised and context-based services

Histone Deacetylase Inhibitors Prevent Persistent Hypersensitivity in an Orofacial Neuropathic Pain Model

Chronic orofacial pain is a significant health problem requiring identification of regulating processes. Involvement of epigenetic modifications that is reported for hindlimb neuropathic pain experimental models, however, is less well studied in cranial nerve pain models. Three independent observations reported here are the (1) epigenetic profile in mouse trigeminal ganglia (TG) after trigeminal inflammatory compression (TIC) nerve injury mouse model determined by gene expression microarray, (2) H3K9 acetylation pattern in TG by immunohistochemistry, and (3) efficacy of histone deacetylase (HDAC) inhibitors to attenuate development of hypersensitivity. After TIC injury, ipsilateral whisker pad mechanical sensitization develops by day 3 and persists well beyond day 21 in contrast to sham surgery. Global acetylation of H3K9 decreases at day 21 in ipsilateral TG. Thirty-four genes are significantly (p \u3c 0.05) overexpressed in the ipsilateral TG by at least two-fold at either 3 or 21 days post-trigeminal inflammatory compression injury. The three genes most overexpressed three days post-trigeminal inflammatory compression nerve injury are nerve regeneration-associated gene ATF3, up 6.8-fold, and two of its regeneration-associated gene effector genes, Sprr1a and Gal, up 174- and 25-fold, respectively. Although transcription levels of 25 of 32 genes significantly overexpressed three days post-trigeminal inflammatory compression return to constitutive levels by day 21, these three regeneration-associated genes remain significantly overexpressed at the later time point. On day 21, when tissues are healed, other differentially expressed genes include 39 of the top 50 upregulated and downregulated genes. Remarkably, preemptive manipulation of gene expression with two HDAC inhibitors (HDACi\u27s), suberanilohydroxamic acid (SAHA) and MS-275, reduces the magnitude and duration of whisker pad mechanical hypersensitivity and prevents the development of a persistent pain state. These findings suggest that trigeminal nerve injury leads to epigenetic modifications favoring overexpression of genes involved in nerve regeneration and that maintaining transcriptional homeostasis with epigenetic modifying drugs could help prevent the development of persistent pain

Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat

Reduced catechol-O-methyltransferase (COMT) activity resulting from genetic variation or pharmacological depletion results in enhanced pain perception in humans and nociceptive behaviors in animals. Using phasic mechanical and thermal reflex tests (e.g. von Frey, Hargreaves), recent studies show that acute COMT-dependent pain in rats is mediated by β-adrenergic receptors (βARs). In order to more closely mimic the characteristics of human chronic pain conditions associated with prolonged reductions in COMT, the present study sought to determine volitional pain-related and anxiety-like behavioral responses following sustained as well as acute COMT inhibition using an operant 10–45°C thermal place preference task and a light/dark preference test. In addition, we sought to evaluate the effects of sustained COMT inhibition on generalized body pain by measuring tactile sensory thresholds of the abdominal region. Results demonstrated that acute and sustained administration of the COMT inhibitor OR486 increased pain behavior in response to thermal heat. Further, sustained administration of OR486 increased anxiety behavior in response to bright light, as well as abdominal mechanosensation. Finally, all pain-related behaviors were blocked by the non-selective βAR antagonist propranolol. Collectively, these findings provide the first evidence that stimulation of ARs following acute or chronic COMT inhibition drives cognitive-affective behaviors associated with heightened pain that affects multiple body sites

Social Capital, Network Governance and Social Innovation: Towards a New Paradigm?

Limited knowledge and empirical evidence exist so far on how governance is related to social capital, and to comprehensively evaluate the effects of collaborative public-private partnerships in rural development actions, and whether these elements foster socially innovative actions. The book chapter begins to address these knowledge gaps. It highlights the conceptual framework linking social capital and network governance and identifies specific approaches to analysing governance. Moreover, it conceptually identifies the key elements for assessing governance mechanisms in the LEADER approach and explains its adoption in the evaluation method proposed in the book. The chapter concludes by outlining how social capital and governance may support social innovation, a topic which is developed more comprehensively in relation to LEADER's specific contribution in the final chapter of the same book

MAO-B Elevation in Mouse Brain Astrocytes Results in Parkinson's Pathology

Age-related increases in monoamine oxidase B (MAO-B) may contribute to neurodegeneration associated with Parkinson's disease (PD). The MAO-B inhibitor deprenyl, a long-standing antiparkinsonian therapy, is currently used clinically in concert with the dopamine precursor L-DOPA. Clinical studies suggesting that deprenyl treatment alone is not protective against PD associated mortality were targeted to symptomatic patients. However, dopamine loss is at least 60% by the time PD is symptomatically detectable, therefore lack of effect of MAO-B inhibition in these patients does not negate a role for MAO-B in pre-symptomatic dopaminergic loss. In order to directly evaluate the role of age-related elevations in astroglial MAO-B in the early initiation or progression of PD, we created genetically engineered transgenic mice in which MAO-B levels could be specifically induced within astroglia in adult animals. Elevated astrocytic MAO-B mimicking age related increase resulted in specific, selective and progressive loss of dopaminergic neurons in the substantia nigra (SN), the same subset of neurons primarily impacted in the human condition. This was accompanied by other PD-related alterations including selective decreases in mitochondrial complex I activity and increased mitochondrial oxidative stress. Along with a global astrogliosis, we observed local microglial activation within the SN. These pathologies correlated with decreased locomotor activity. Importantly, these events occurred even in the absence of the PD-inducing neurotoxin MPTP. Our data demonstrates that elevation of murine astrocytic MAO-B by itself can induce several phenotypes of PD, signifying that MAO-B could be directly involved in multiple aspects of disease neuropathology. Mechanistically this may involve increases in membrane permeant H2O2 which can oxidize dopamine within dopaminergic neurons to dopaminochrome which, via interaction with mitochondrial complex I, can result in increased mitochondrial superoxide. Our inducible astrocytic MAO-B transgenic provides a novel model for exploring pathways involved in initiation and progression of several key features associated with PD pathology and for therapeutic drug testing

Pressure and Flow Properties of Cannulae for Extracorporeal Membrane Oxygenation I: Return (Arterial) Cannulae

Adequate extracorporeal membrane oxygenation support in the adult requires cannulae permitting blood flows up to 6-8 L/minute. In accordance with Poiseuille's law, flow is proportional to the fourth power of cannula inner diameter and inversely proportional to its length. Poiseuille's law can be applied to obtain the pressure drop of an incompressible, Newtonian fluid (such as water) flowing in a cylindrical tube. However, as blood is a pseudoplastic non-Newtonian fluid, the validity of Poiseuille's law is questionable for prediction of cannula properties in clinical practice. Pressure-flow charts with non-Newtonian fluids, such as blood, are typically not provided by the manufacturers. A standardized laboratory test of return (arterial) cannulae for extracorporeal membrane oxygenation was performed. The aim was to determine pressure-flow data with human whole blood in addition to manufacturers' water tests to facilitate an appropriate choice of cannula for the desired flow range. In total, 14 cannulae from three manufacturers were tested. Data concerning design, characteristics, and performance were graphically presented for each tested cannula. Measured blood flows were in most cases 3-21% lower than those provided by manufacturers. This was most pronounced in the narrow cannulae (15-17 Fr) where the reduction ranged from 27% to 40% at low flows and 5-15% in the upper flow range. These differences were less apparent with increasing cannula diameter. There was a marked disparity between manufacturers. Based on the measured results, testing of cannulae including whole blood flows in a standardized bench test would be recommended.info:eu-repo/semantics/publishedVersio