Shallow vs deep learning architectures for white matter lesion segmentation in the early stages of multiple sclerosis

In this work, we present a comparison of a shallow and a deep learning architecture for the automated segmentation of white matter lesions in MR images of multiple sclerosis patients. In particular, we train and test both methods on early stage disease patients, to verify their performance in challenging conditions, more similar to a clinical setting than what is typically provided in multiple sclerosis segmentation challenges. Furthermore, we evaluate a prototype naive combination of the two methods, which refines the final segmentation. All methods were trained on 32 patients, and the evaluation was performed on a pure test set of 73 cases. Results show low lesion-wise false positives (30%) for the deep learning architecture, whereas the shallow architecture yields the best Dice coefficient (63%) and volume difference (19%). Combining both shallow and deep architectures further improves the lesion-wise metrics (69% and 26% lesion-wise true and false positive rate, respectively).Comment: Accepted to the MICCAI 2018 Brain Lesion (BrainLes) worksho

CASA-Mot technology: how results are affected by the frame rate and counting chamber

For over 30 years, CASA-Mot technology has been used for kinematic analysis of sperm motility in different mammalian species, but insufficient attention has been paid to the technical limitations of commercial computer-aided sperm analysis (CASA) systems. Counting chamber type and frame rate are two of the most important aspects to be taken into account. Counting chambers can be disposable or reusable, with different depths. In human semen analysis, reusable chambers with a depth of 10 mm are the most frequently used, whereas for most farm animal species it is more common to use disposable chambers with a depth of 20 mm. The frame rate was previously limited by the hardware, although changes in the number of images collected could lead to significant variations in some kinematic parameters, mainly in curvilinear velocity (VCL). A frame rate of 60 frames s(-1) is widely considered to be the minimum necessary for satisfactory results. However, the frame rate is species specific and must be defined in each experimental condition. In conclusion, we show that the optimal combination of frame rate and counting chamber type and depth should be defined for each species and experimental condition in order to obtain reliable results

Ten years since the introduction of therapeutic hypothermia in neonates with perinatal hypoxic-ischaemic encephalopathy in Spain

More than a decade has passed since therapeutic hypothermia (TH) was introduced in Spain; this is the only neuroprotective intervention that has become standard practice in the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE). This article aims to provide a current picture of the technique and to address the controversies surrounding its use. In the last 10 years, TH has been successfully implemented in the vast majority of tertiary hospitals in Spain, and more than 85% of newborns with moderate or severe HIE currently receive the treatment. The factors that can improve the efficacy of TH include early treatment onset (first 6 hours of life) and the control of comorbid factors associated with perinatal asphyxia. In patients with moderate HIE, treatment onset after 6 hours seems to have some neuroprotective efficacy. TH duration longer than 72 hours or deeper hypothermia do not offer greater neuroprotective efficacy, but instead increase the risk of adverse effects. Unclarified aspects are the sedation of patients during TH, the application of the treatment in infants with mild HIE, and its application in other scenarios. Prognostic information and time frame are one of the most challenging aspects. TH is universal in countries with sufficient economic resources, although certain unresolved controversies remain. While the treatment is widespread in Spain, there is a need for cooling devices for the transfer of these patients and their centralisationSe cumple ahora más de una década del inicio de la hipotermia terapéutica (HT) en España, la única intervención neuroprotectora que ha venido a ser práctica estándar en el tratamiento de la encefalopatía hipóxico-isquémica perinatal (EHI). El objetivo de este artículo es ofrecer un panorama actual y presentar las controversias surgidas alrededor de la aplicación de esta terapia. En esta década se ha implantado con éxito la HT en la gran mayoría de los hospitales terciarios de España y más del 85% de los recién nacidos con EHI moderada-grave reciben esta terapia. Entre los aspectos que pueden mejorar la eficacia de la HT están su inicio precoz dentro de las primeras 6 horas de vida y el control de factores comórbidos asociados a la asfixia perinatal. En los pacientes con EHI moderada el inicio después de las 6 horas parece mantener cierta eficacia neuroprotectora. Una duración de la HT mayor de 72 horas o un enfriamiento más profundo no ofrecen mayor eficacia neuroprotectora y aumentan el riesgo de efectos adversos. Persiste la controversia acerca de la sedación durante la HT, la aplicación de esta intervención a los neonatos con EHI leve y en otros escenarios. La información pronóstica y su marco temporal es uno de los aspectos más desafiantes. La HT es universal en países con recursos económicos, aunque existen puntos de controversia no resueltos. Si bien es un tratamiento generalizado en nuestro país, falta disponer de dispositivos para el traslado de estos pacientes y su centralizació

Structural Determinants for Functional Coupling Between the β and α Subunits in the Ca2+-activated K+ (BK) Channel

High conductance, calcium- and voltage-activated potassium (BK, MaxiK) channels are widely expressed in mammals. In some tissues, the biophysical properties of BK channels are highly affected by coexpression of regulatory (β) subunits. The most remarkable effects of β1 and β2 subunits are an increase of the calcium sensitivity and the slow down of channel kinetics. However, the detailed characteristics of channels formed by α and β1 or β2 are dissimilar, the most remarkable difference being a reduction of the voltage sensitivity in the presence of β1 but not β2. Here we reveal the molecular regions in these β subunits that determine their differential functional coupling with the pore-forming α-subunit. We made chimeric constructs between β1 and β2 subunits, and BK channels formed by α and chimeric β subunits were expressed in Xenopus laevis oocytes. The electrophysiological characteristics of the resulting channels were determined using the patch clamp technique. Chimeric exchange of the different regions of the β1 and β2 subunits demonstrates that the NH3 and COOH termini are the most relevant regions in defining the behavior of either subunit. This strongly suggests that the intracellular domains are crucial for the fine tuning of the effects of these β subunits. Moreover, the intracellular domains of β1 are responsible for the reduction of the BK channel voltage dependence. This agrees with previous studies that suggested the intracellular regions of the α-subunit to be the target of the modulation by the β1-subunit

IP3 sensitizes TRPV4 channel to the mechano- and osmotransducing messenger 5′-6′-epoxyeicosatrienoic acid

Mechanical and osmotic sensitivity of the transient receptor potential vanilloid 4 (TRPV4) channel depends on phospholipase A2 (PLA2) activation and the subsequent production of the arachidonic acid metabolites, epoxyeicosatrienoic acid (EET). We show that both high viscous loading and hypotonicity stimuli in native ciliated epithelial cells use PLA2–EET as the primary pathway to activate TRPV4. Under conditions of low PLA2 activation, both also use extracellular ATP-mediated activation of phospholipase C (PLC)–inositol trisphosphate (IP3) signaling to support TRPV4 gating. IP3, without being an agonist itself, sensitizes TRPV4 to EET in epithelial ciliated cells and cells heterologously expressing TRPV4, an effect inhibited by the IP3 receptor antagonist xestospongin C. Coimmunoprecipitation assays indicated a physical interaction between TRPV4 and IP3 receptor 3. Collectively, our study suggests a functional coupling between plasma membrane TRPV4 channels and intracellular store Ca2+ channels required to initiate and maintain the oscillatory Ca2+ signal triggered by high viscosity and hypotonic stimuli that do not reach a threshold level of PLA2 activation

Impact of glucocorticoid on a cellular model of parkinson’s disease: Oxidative stress and mitochondrial function

Stress seems to contribute to the neuropathology of Parkinson’s disease (PD), possibly by dysregulation of the hypothalamic–pituitary–adrenal axis. Oxidative distress and mitochondrial dysfunction are key factors involved in the pathophysiology of PD and neuronal glucocorticoid-induced toxicity. Animal PD models have been generated to study the effects of hormonal stress, but no in vitro model has yet been developed. Our aim was to examine the impact of corticosterone (CORT) administration on a dopaminergic neuronal cell model of PD induced by the neurotoxin MPP+, as a new combined PD model based on the marker of endocrine response to stress, CORT, and oxidative-mitochondrial damage. We determined the impact of CORT, MPP+ and their co-incubation on reactive oxygen species production (O2−• ), oxidative stress cellular markers (advanced-oxidation protein products and total antioxidant status), mitochondrial function (mitochondrial membrane potential and mitochondrial oxygen consumption rate) and neurodegeneration (Fluoro-Jade staining). Accordingly, the administration of MPP+ or CORT individually led to cell damage compared to controls (p < 0.05), as determined by several methods, whereas their co-incubation produced strong cell damage (p < 0.05). The combined model described here could be appropriate for investigating neuropathological hallmarks and for evaluating potential new therapeutic tools for PD patients suffering mild to moderate emotional stress

Comments on ”A new conformal FDTD for lossy thin panels”

In the paper ”A new conformal FDTD for lossy thin panels” by M. R. Cabello et al., the appearance of spiky antiresonances in the simulation of the shielding properties of lossy thin-shell spherical cavities by FDTD, was categorised as spurious solutions. In this document, we briefly clarify this topic, and show that these solutions are not really spurious in the common interpretation of the term. Actually, they correspond to physical solutions, appearing due to lack of symmetry inherent to the staggered co-location nature of field components in FDTD

Mechanisms of Tolerance and Resistance to Chlorhexidine in Clinical Strains of Klebsiella pneumoniae Producers of Carbapenemase: Role of New Type II Toxin-Antitoxin System, PemIK

Although the failure of antibiotic treatment is normally attributed to resistance, tolerance and persistence display a significant role in the lack of response to antibiotics. Due to the fact that several nosocomial pathogens show a high level of tolerance and/or resistance to chlorhexidine, in this study we analyzed the molecular mechanisms associated with chlorhexidine adaptation in two clinical strains of Klebsiella pneumoniae by phenotypic and transcriptomic studies. These two strains belong to ST258-KPC3 (high-risk clone carrying β-lactamase KPC3) and ST846-OXA48 (low-risk clone carrying β-lactamase OXA48). Our results showed that the K. pneumoniae ST258-KPC3CA and ST846-OXA48CA strains exhibited a different behavior under chlorhexidine (CHLX) pressure, adapting to this biocide through resistance and tolerance mechanisms, respectively. Furthermore, the appearance of cross-resistance to colistin was observed in the ST846-OXA48CA strain (tolerant to CHLX), using the broth microdilution method. Interestingly, this ST846-OXA48CA isolate contained a plasmid that encodes a novel type II toxin/antitoxin (TA) system, PemI/PemK. We characterized this PemI/PemK TA system by cloning both genes into the IPTG-inducible pCA24N plasmid, and found their role in persistence and biofilm formation. Accordingly, the ST846-OXA48CA strain showed a persistence biphasic curve in the presence of a chlorhexidine-imipenem combination, and these results were confirmed by the enzymatic assay (WST-1).The State Plan for R+D+I 2013–2016 National Plan for Scientific Research, Technological Development and Innovation 2008–2011 PI16/01163 and PI19/00878ISCIII-Deputy General Directorate for Evaluation and Promotion of Research - European Regional Development Fund “A way of Making Europe” and Instituto de Salud Carlos III FEDER, Spanish Network for the Research in Infectious Diseases REIPI, RD16/0016/0001, RD16/CIII/0004/0002 and RD16/0016/0006The Study Group on Mechanisms of Action and Resistance to Antimicrobials, GEMAR

Cost-Utility Analysis of a Medication Adherence Management Service Alongside a Cluster Randomized Control Trial in Community Pharmacy.

Background: It is necessary to determine the cost utility of adherence interventions in chronic diseases due to humanistic and economic burden of non-adherence. Purpose: To evaluate, alongside a cluster-randomized controlled trial, the cost-utility of a pharmacist-led medication adherence management service (MAMS) compared with usual care in community pharmacies. Materials and Methods: The trial was conducted over six months. Patients with treatments for hypertension, asthma or chronic obstructive pulmonary disease (COPD) were included. Patients in the intervention group (IG) received a MAMS based on a brief complex intervention, whilst patients in the control group (CG) received usual care. The cost–utility analysis adopted a health system perspective. Costs related to medications, healthcare resources and adherence intervention were included. The effectiveness was estimated as quality-adjusted life years (QALYs), using a multiple imputation missing data model. The incremental cost–utility ratio (ICUR) was calculated on the total sample of patients. Results: A total of 1186 patients were enrolled (IG: 633; CG: 553). The total intervention cost was estimated to be € 27.33 ± 0.43 per patient for six months. There was no statistically significant difference in total cost of medications and healthcare resources per patient between IG and CG. The values of EQ-5D-5L at 6 months were significantly higher in the IG [IG: 0.881 ± 0.005 vs CG: 0.833 ± 0.006; p = 0.000]. In the base case, the service was more expensive and more effective than usual care, resulting in an ICUR of € 1,494.82/QALY. In the complete case, the service resulted in an ICUR of € 2,086.30/QALY, positioned between the north-east and south-east quadrants of the cost–utility plane. Using a threshold value of € 20,000/QALY gained, there is a 99% probability that the intervention is cost-effective. Conclusion: The medication adherence management service resulted in an improvement in the quality of life of the population with chronic disease, with similar costs compared to usual care. The service is cost-effective