Using the incremental Hole-drilling technique for measuring residual stresses in fibre-reinforce polymer composites

The Incremental hole-drilling technique (IHD) seems to be a promising technique, among the destructive (relaxation) techniques, to determine in-depth non-uniform residual stresses in fibre-reinforced polymer composites. Hence, valid theoretical approaches for IHD residual stress determination in composite laminates, based on a set of strain-depth relaxation curves, are needed. Nevertheless, the influence of the drilling process itself on the initial residual stress state, i.e. existing prior to hole drilling, must be verified first. In this work, the IHD residual stress evaluation procedures in composite laminates will be reviewed and an original hybrid experimental-numerical methodology will be used to quantify the residual strain induced by the drilling process. Thus, residual strains induced by ultra-high speed drilling processes on carbon-epoxy laminates (CFRPs) have been quantified. The results seem to show that IHD technique can be improved to be successfully applied for measuring residual stresses in CFRPs

Successful tactile based visual sensory substitution use functions independently of visual pathway integrity

Purpose: Neuronal reorganization after blindness is of critical interest because it has implications for the rational prescription of artificial vision devices. The purpose of this study was to distinguish the microstructural differences between perinatally blind (PB), acquired blind (AB), and normally sighted controls (SCs) and relate these differences to performance on functional tasks using a sensory substitution device (BrainPort). Methods: We enrolled 52 subjects (PB n = 11; AB n = 35; SC n = 6). All subjects spent 15 h undergoing BrainPort device training. Outcomes of light perception, motion, direction, temporal resolution, grating, and acuity were tested at baseline and after training. Twenty-six of the subjects were scanned with a three Tesla MRI scanner for diffusion tensor imaging (DTI), and with a positron emission tomography (PET) scanner for mapping regional brain glucose consumption during sensory substitution function. Non-parametric models were used to analyze fractional anisotropy (FA; a DTI measure of microstructural integrity) of the brain via region-of-interest (ROI) analysis and tract-based spatial statistics (TBSS). Results: At baseline, all subjects performed all tasks at chance level. After training, light perception, time resolution, location and grating acuity tasks improved significantly for all subject groups. ROI and TBSS analyses of FA maps show areas of statistically significant differences (p ≤ 0.025) in the bilateral optic radiations and some visual association connections between all three groups. No relationship was found between FA and functional performance with the BrainPort. Discussion: All subjects showed performance improvements using the BrainPort irrespective of nature and duration of blindness. Definite brain areas with significant microstructural integrity changes exist among PB, AB, and NC, and these variations are most pronounced in the visual pathways. However, the use of sensory substitution devices is feasible irrespective of microstructural integrity of the primary visual pathways between the eye and the brain. Therefore, tongue based devices devices may be usable for a broad array of non-sighted patients. © 2014 Lee, Nau, Laymon, Chan, Rosario and Fisher

Cerebrospinal fluid findings in adults with acute Lyme neuroborreliosis

Presence of BB-specific antibodies in the cerebrospinal fluid (CSF) with evidence of their intrathecal production in conjunction with the white cell count in the CSF and typical clinical symptoms is the traditional diagnostic gold standard of Lyme neuroborreliosis (LNB). Few data are available on the CSF lactate concentration in European adults with the diagnosis of acute LNB. The objective of the study was to investigate the CSF changes during acute LNB. Routine CSF parameters [leukocyte count, protein, lactate and albumin concentrations, CSF/serum quotients of albumin (QAlb), IgG, IgA and IgM, and oligoclonal IgG bands] and the Borrelia burgdorferi (BB)-specific antibody index were retrospectively studied in relation to the clinical presentation in patients diagnosed with acute LNB. A total of 118 patients with LNB were categorized into the following groups according to their symptoms at presentation; group 1: polyradiculoneuritis (Bannwarth’s syndrome), group 2: isolated facial palsy and group 3: predominantly meningitic course of the disease. In addition to the CSF of patients with acute LNB, CSF of 19 patients with viral meningitis (VM) and 3 with neurolues (NL) were analyzed. There were 97 patients classified with definite LNB, and 21 as probable LNB. Neck stiffness and fever were reported by 15.3% of patients. Most of these patients were younger than 50 years. Polyradiculoneuritis was frequently found in patients older than 50 years. Lymphopleocytosis was found in all patients. Only 5 patients had a CSF lactate ≥3.5 mmol/l, and the mean CSF lactate level was not elevated (2.1 ± 0.6 mmol/l). The patients with definite LNB had significantly higher lactate levels than patients with probable LNB. Elevated lactate levels were accompanied by fever and headache. In the Reiber nomograms, intrathecal immunoglobulin synthesis was found for IgM in 70.2% followed by IgG in 19.5%. Isoelectric focussing detected an intrathecal IgG synthesis in 83 patients (70.3%). Elevated BB AIs in the CSF were found in 97 patients (82.2%). Patients with VM showed lower CSF protein concentration and CSF/serum quotients of albumin than LNB patients. In acute LNB, all patients had elevated cerebrospinal fluid (CSF) leukocyte counts. In contrast to infections by other bacteria, CSF lactate was lower than 3.5 mmol/l in all but 5 patients. The CSF findings did not differ between polyradiculoneuritis, facial palsy, and meningitis. The CSF in LNB patients strongly differed from CSF in VM patients with respect to protein concentration and the CSF/serum albumin quotient

Fast- or Slow-inactivated State Preference of Na+ Channel Inhibitors: A Simulation and Experimental Study

Sodium channels are one of the most intensively studied drug targets. Sodium channel inhibitors (e.g., local anesthetics, anticonvulsants, antiarrhythmics and analgesics) exert their effect by stabilizing an inactivated conformation of the channels. Besides the fast-inactivated conformation, sodium channels have several distinct slow-inactivated conformational states. Stabilization of a slow-inactivated state has been proposed to be advantageous for certain therapeutic applications. Special voltage protocols are used to evoke slow inactivation of sodium channels. It is assumed that efficacy of a drug in these protocols indicates slow-inactivated state preference. We tested this assumption in simulations using four prototypical drug inhibitory mechanisms (fast or slow-inactivated state preference, with either fast or slow binding kinetics) and a kinetic model for sodium channels. Unexpectedly, we found that efficacy in these protocols (e.g., a shift of the “steady-state slow inactivation curve”), was not a reliable indicator of slow-inactivated state preference. Slowly associating fast-inactivated state-preferring drugs were indistinguishable from slow-inactivated state-preferring drugs. On the other hand, fast- and slow-inactivated state-preferring drugs tended to preferentially affect onset and recovery, respectively. The robustness of these observations was verified: i) by performing a Monte Carlo study on the effects of randomly modifying model parameters, ii) by testing the same drugs in a fundamentally different model and iii) by an analysis of the effect of systematically changing drug-specific parameters. In patch clamp electrophysiology experiments we tested five sodium channel inhibitor drugs on native sodium channels of cultured hippocampal neurons. For lidocaine, phenytoin and carbamazepine our data indicate a preference for the fast-inactivated state, while the results for fluoxetine and desipramine are inconclusive. We suggest that conclusions based on voltage protocols that are used to detect slow-inactivated state preference are unreliable and should be re-evaluated

Osteopontin Impairs Host Defense during Established Gram-Negative Sepsis Caused by Burkholderia pseudomallei (Melioidosis)

Melioidosis is a severe tropical disease caused by infection with the bacterium Burkholderia (B.) pseudomallei. In northeast Thailand infection with this bacterium is the major cause of community-acquired septicemia with a mortality rate up to 40%. Extending the knowledge on the mechanisms of host defense against B. pseudomallei infection would be helpful to improve treatment of this severe illness. Osteopontin (OPN) is a cytokine that is involved in several immune responses that occur during bacterial infection. In this study, we investigated levels of OPN in patients with melioidosis, and studied the function of OPN during experimental melioidosis in mice. We found that OPN concentrations were elevated in patients with severe melioidosis, and that high OPN concentrations are associated with poor outcome in patients with melioidosis. In experimental melioidosis in mice plasma and lung OPN levels were also increased. Moreover, mice with melioidosis that were deficient for OPN demonstrated reduced bacterial numbers in their lungs, diminished pulmonary tissue injury, and decreased neutrophil infiltration into the lungs during established melioidosis. Moreover, these mice displayed a delayed mortality as compared to control mice. In conclusion, sustained production of OPN impairs host defense during melioidosis

Sodium channel slow inactivation interferes with open channel block

Mutations in the voltage-gated sodium channel Nav1.7 are linked to inherited pain syndromes such as erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD). PEPD mutations impair Nav1.7 fast inactivation and increase persistent currents. PEPD mutations also increase resurgent currents, which involve the voltage-dependent release of an open channel blocker. In contrast, IEM mutations, whenever tested, leave resurgent currents unchanged. Accordingly, the IEM deletion mutation L955 (ΔL955) fails to produce resurgent currents despite enhanced persistent currents, which have hitherto been considered a prerequisite for resurgent currents. Additionally, ΔL955 exhibits a prominent enhancement of slow inactivation (SI). We introduced mutations into Nav1.7 and Nav1.6 that either enhance or impair SI in order to investigate their effects on resurgent currents. Our results show that enhanced SI is accompanied by impaired resurgent currents, which suggests that SI may interfere with open-channel block

Peritoneal dialysis prescription in children: bedside principles for optimal practice

There is no unique optimal peritoneal dialysis prescription for all children, although the goals of ultrafiltration and blood purification are universal. In turn, a better understanding of the physiology of the peritoneal membrane, as a dynamic dialysis membrane with an exchange surface area recruitment capacity and unique permeability characteristics, results in the transition from an empirical prescription process based on clinical experience alone to the potential for a personalized prescription with individually adapted fill volumes and dwell times. In all cases, the prescribed exchange fill volume should be scaled for body surface area (ml/m2), and volume enhancement should be conducted based on clinical tolerance and intraperitoneal pressure measurements (IPP; cmH2O). The exchange dwell times should be determined individually and adapted to the needs of the patient, with particular attention to phosphate clearance and ultrafiltration capacity. The evolution of residual kidney function and the availability of new, more physiologic, peritoneal dialysis fluids (PDFs) also influence the prescription process. An understanding of all of these principles is integral to the provision of clinically optimal PD

Strengthening insights into host responses to mastitis infection in ruminants by combining heterogeneous microarray data sources

<p>Abstract</p> <p>Background</p> <p>Gene expression profiling studies of mastitis in ruminants have provided key but fragmented knowledge for the understanding of the disease. A systematic combination of different expression profiling studies via meta-analysis techniques has the potential to test the extensibility of conclusions based on single studies. Using the program Pointillist, we performed meta-analysis of transcription-profiling data from six independent studies of infections with mammary gland pathogens, including samples from cattle challenged <it>in vivo </it>with <it>S. aureus</it>, <it>E. coli</it>, and <it>S. uberis</it>, samples from goats challenged <it>in vivo </it>with <it>S. aureus</it>, as well as cattle macrophages and ovine dendritic cells infected <it>in vitro </it>with <it>S. aureus</it>. We combined different time points from those studies, testing different responses to mastitis infection: overall (common signature), early stage, late stage, and cattle-specific.</p> <p>Results</p> <p>Ingenuity Pathway Analysis of affected genes showed that the four meta-analysis combinations share biological functions and pathways (e.g. protein ubiquitination and polyamine regulation) which are intrinsic to the general disease response. In the overall response, pathways related to immune response and inflammation, as well as biological functions related to lipid metabolism were altered. This latter observation is consistent with the milk fat content depression commonly observed during mastitis infection. Complementarities between early and late stage responses were found, with a prominence of metabolic and stress signals in the early stage and of the immune response related to the lipid metabolism in the late stage; both mechanisms apparently modulated by few genes, including <it>XBP1 </it>and <it>SREBF1</it>.</p> <p>The cattle-specific response was characterized by alteration of the immune response and by modification of lipid metabolism. Comparison of <it>E. coli </it>and <it>S. aureus </it>infections in cattle <it>in vivo </it>revealed that affected genes showing opposite regulation had the same altered biological functions and provided evidence that <it>E. coli </it>caused a stronger host response.</p> <p>Conclusions</p> <p>This meta-analysis approach reinforces previous findings but also reveals several novel themes, including the involvement of genes, biological functions, and pathways that were not identified in individual studies. As such, it provides an interesting proof of principle for future studies combining information from diverse heterogeneous sources.</p