Value of treatment by comprehensive stroke services for the reduction of critical gaps in acute stroke care in Europe.

Stroke is the second leading cause of death and dependency in Europe and costs the European Union more than €30bn, yet significant gaps in the patient pathway remain and the cost-effectiveness of comprehensive stroke care to meet these needs is unknown. The European Brain Council Value of Treatment Initiative combined patient representatives, stroke experts, neurological societies and literature review to identify unmet needs in the patient pathway according to Rotterdam methodology. The cost-effectiveness of comprehensive stroke services was determined by a Markov model, using UK cost data as an exemplar and efficacy data for prevention of death and dependency from published systematic reviews and trials, expressing effectiveness as quality-adjusted life-years (QALYs). Model outcomes included total costs, total QALYs, incremental costs, incremental QALYs and the incremental cost-effectiveness ratio (ICER). Key unmet needs in the stroke patient pathway included inadequate treatment of atrial fibrillation (AF), access to neurorehabilitation and implementation of comprehensive stroke services. In the Markov model, full implementation of comprehensive stroke services was associated with a 9.8% absolute reduction in risk of death of dependency, at an intervention cost of £9566 versus £6640 for standard care, and long-term care costs of £35 169 per 5.1251 QALYS vs. £32 347.40 per 4.5853 QALYs, resulting in an ICER of £5227.89. Results were robust in one-way and probabilistic sensitivity analyses. Implementation of comprehensive stroke services is a cost-effective approach to meet unmet needs in the stroke patient pathway, to improve acute stroke care and support better treatment of AF and access to neurorehabilitation.

Immune aging in diabetes and its implications in wound healing.

Immune systems have evolved to recognize and eliminate pathogens and damaged cells. In humans, it is estimated to recognize 109 epitopes and natural selection ensures that clonally expanded cells replace unstimulated cells and overall immune cell numbers remain stationary. But, with age, it faces continuous repertoire restriction and concomitant accumulation of primed cells. Changes shaping the aging immune system have bitter consequences because, as inflammatory responses gain intensity and duration, tissue-damaging immunity and inflammatory disease arise. During inflammation, the glycolytic flux cannot cope with increasing ATP demands, limiting the immune response's extent. In diabetes, higher glucose availability stretches the glycolytic limit, dysregulating proteostasis and increasing T-cell expansion. Long-term hyperglycemia exerts an accumulating effect, leading to higher inflammatory cytokine levels and increased cytotoxic mediator secretion upon infection, a phenomenon known as diabetic chronic inflammation. Here we review the etiology of diabetic chronic inflammation and its consequences on wound healing.

Proteostasis in epicardial versus subcutaneous adipose tissue in heart failure subjects with and without diabetes.

BACKGROUND: Cardiovascular diseases (CVDs) are leading cause of death and primary cause of morbidity and mortality in diabetic population. Epicardial adipose tissue (EAT) covers the heart's surface and is a source of biomolecules regulating heart and blood vessel physiology. The protective activation of the unfolded protein response (UPR) and autophagy allows the cardiomyocyte reticular network to restore energy and/or nutrient homeostasis and to avoid cell death. However, an excessive or prolonged UPR activation can trigger cell death. UPR activation is an early event of diabetic cardiomyopathies and deregulated autophagy is associated with CVDs. RESULTS: An upregulation of UPR markers (glucose-regulated protein 78 KDa, glucose-regulated protein 94 KDa, inositol-requiring enzyme 1α, protein kinase RNA-like ER kinase and CCAAT/-enhancer-binding protein homologous protein (CHOP) gene) in EAT compared to subcutaneous adipose tissue (SAT), was observed as well as the UPR-related apoptosis marker caspase-4/procaspase-4 ratio but not in CHOP protein levels. Additionally, levels of ubiquitin and ubiquitinated proteins were decreased in EAT. Moreover, upregulation of autophagy markers (5' adenosine monophosphate-activated protein kinase, mechanistic target of rapamycin, Beclin 1, microtubule-associated protein light chain 3-II, lysosome-associated membrane protein 2, and PTEN-induced putative kinase 1) was observed, as well as an increase in the apoptotic Bim but not the ratio between Bim and the anti-apoptotic Bcl-2 in EAT. Diabetic patients show alterations in UPR activation markers but not in autophagy or apoptosis markers. CONCLUSION: UPR and autophagy are increased in EAT compared to SAT, opening doors to the identification of early biomarkers for cardiomyopathies and novel therapeutic targets.

European Academy of Neurology and European Stroke Organization consensus statement and practical guidance for pre-hospital management of stroke.

BACKGROUND AND PURPOSE: The reduction of delay between onset and hospital arrival and adequate pre-hospital care of persons with acute stroke are important for improving the chances of a favourable outcome. The objective is to recommend evidence-based practices for the management of patients with suspected stroke in the pre-hospital setting. METHODS: The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to define the key clinical questions. An expert panel then reviewed the literature, established the quality of the evidence, and made recommendations. RESULTS: Despite very low quality of evidence educational campaigns to increase the awareness of immediately calling emergency medical services are strongly recommended. Moderate quality evidence was found to support strong recommendations for the training of emergency medical personnel in recognizing the symptoms of a stroke and in implementation of a pre-hospital 'code stroke' including highest priority dispatch, pre-hospital notification and rapid transfer to the closest 'stroke-ready' centre. Insufficient evidence was found to recommend a pre-hospital stroke scale to predict large vessel occlusion. Despite the very low quality of evidence, restoring normoxia in patients with hypoxia is recommended, and blood pressure lowering drugs and treating hyperglycaemia with insulin should be avoided. There is insufficient evidence to recommend the routine use of mobile stroke units delivering intravenous thrombolysis at the scene. Because only feasibility studies have been reported, no recommendations can be provided for pre-hospital telemedicine during ambulance transport. CONCLUSIONS: These guidelines inform on the contemporary approach to patients with suspected stroke in the pre-hospital setting. Further studies, preferably randomized controlled trials, are required to examine the impact of particular interventions on quality parameters and outcome.

Epileptic manifestations in stroke patients treated with intravenous alteplase.

BACKGROUND AND PURPOSE: Intravenous alteplase (rtPA) may be associated with seizures and epileptic activity in the electroencephalogram (EEG). The aim of this work was to compare the frequency of seizures and EEG abnormalities between stroke patients treated and not treated with rtPA. METHODS: This was a prospective study of consecutive acute anterior circulation ischaemic stroke patients, with 1-year follow-up. Patients were previously independent, had an admission National Institute of Health Stroke Scale score ≥4, an acute ischaemic lesion and no previous seizures. They received standardized diagnostic and medical care. A video-EEG was performed in 72 h (first EEG); during admission (daily until day 7 and after that if neurological worsening); at discharge and 1 year after stroke. RESULTS: In all, 151 patients (101 treated with rtPA) were included. The frequency of acute and remote symptomatic seizures was not significantly different between rtPA treated and non-treated patients (P = 0.726 and P = 0.748, respectively). Clinical paroxysmal phenomena during rtPA perfusion were observed in five (5%) patients. In the first EEG, rtPA treated patients more often had background diffuse slowing (43.6% vs. 26.0%, P = 0.036). This difference was no longer observed at discharge (24.0% vs. 19.1%, P = 0.517) nor 1 year after (11.8% vs. 10.0%, P = 0.765). No differences were found in the frequency of epileptiform (P = 0.867) or periodic discharges (P = 0.381). CONCLUSIONS: Intravenous alteplase is not associated with an increased risk of clinical or electroencephalographic epileptic phenomena.

Language improvement one week after thrombolysis in acute stroke.

OBJECTIVES: Language recovery following acute stroke is difficult to predict due to several evaluation factors and time constraints. We aimed to investigate the predictors of aphasia recovery and to identify the National Institute of Health and Stroke Scale (NIHSS) items that best reflect linguistic performance, 1 week after thrombolysis. MATERIALS AND METHODS: We retrieved data from a prospective registry of patients with aphasia secondary to left middle cerebral artery (MCA) stroke treated with intravenous thrombolysis. Complete recovery at day 7 (D7) was measured in a composite verbal score (CVS) (Σ Language+Questions+Commands NIHSS scores). Lesion size was categorized by the Alberta Stroke Program Early CT score (ASPECTS) and vascular patency by ultrasound. CVS was correlated with standardized aphasia testing if both were performed within a two-day interval. RESULTS: Of 228 patients included (age average 67.32 years, 131 men), 72% presented some language improvement that was complete in 31%. Total recovery was predicted by ASPECTS (OR=1.65; 95% CI, 1.295-2.108; P < 0.00) and baseline aphasia severity (OR=0.439; 95% CI, 0.242-0.796; P < 0.007). CVS correlated better with standardized aphasia measures (aphasia quotient, severity, comprehension) than NIHSS_Language item. CONCLUSIONS: Lesion size and initial aphasia severity are the main predictors of aphasia recovery one week after thrombolysis. A NIHSS composite verbal score seems to capture the global linguistic performance better than the language item alone.

Cryptogenic stroke.

In about a quarter of ischaemic strokes the cause is undetermined, because the investigation is incomplete or delayed, because there are multiple causes or because the stroke is truly cryptogenic. Cryptogenic stroke can be further classified as non-embolic or embolic. Embolic stroke of undetermined source can be due to paroxysmal atrial fibrillation, minor emboligenic cardiac conditions, atheroembolism, cancer associated and paradoxical embolism through a patent foramen ovale (PFO) or less often a pulmonary fistula. Currently, risk factor control, statins and antiplatelets are the main therapeutic measures to prevent recurrent stroke. There is no evidence to implement routine closure of PFO in patients with cryptogenic stroke. Direct anticoagulants are being evaluated in randomized controlled trials including embolic stroke of undetermined source patients. Advances in high resolution ultrasound or magnetic resonance imaging of extracranial and intracranial vessels and of the heart and prolonged heart rhythm monitoring will be instrumental techniques to identify arterial and cardiac hidden causes of stroke.

Effect of corn silage hybrids differing in starch and neutral detergent fiber digestibility on lactation performance and total-tract nutrient digestibility by dairy cows.

Selection for hybrids with greater starch and NDF digestibility may be beneficial for dairy producers. The objective of this study was to determine the effect of feeding a TMR containing a floury-leafy corn silage hybrid (LFY) compared with a brown midrib corn silage hybrid (BMR) for intake, lactation performance, and total-tract nutrient digestibility in dairy cows. Ninety-six multiparous Holstein cows, 105±31d in milk at trial initiation, were stratified by DIM and randomly assigned to 12 pens of 8 cows each. Pens were randomly assigned to 1 of 2 treatments, BMR or LFY, in a completely randomized design; a 2-wk covariate period with cows fed a common diet followed by a 14-wk treatment period with cows fed their assigned treatment diet. Starch digestibilities, in situ, in vitro, and in vivo, were greater for LFY compared with BMR; the opposite was observed for NDF digestibility. Cows fed BMR consumed 1.7kg/d more dry matter than LFY. Although, actual-, energy-, and solids-corrected milk yields were greater for BMR than LFY, feed conversions (kg of milk or component-corrected milk per kg of DMI) did not differ. Fat-corrected milk and milk fat yield were similar, as milk fat content was greater for cows fed LFY (4.05%) than BMR (3.83%). Cows fed BMR had lower milk urea nitrogen concentration, but greater milk protein and lactose yields compared with LFY. Body weight change and condition score were unaffected by treatment. Total-tract starch digestibility was greater for cows fed the LFY corn silage; however, dry matter intake and milk and protein yields were greater for cows fed the BMR corn silage. Although total-tract starch digestibility was greater for cows fed the LFY corn silage, feed efficiency was not affected by hybrid type due to greater dry matter intake and milk and protein yields by cows fed the BMR corn silage.

Calculation of multichannel reactions in the four-nucleon system above breakup threshold.

The exact four-body equations of Alt, Grassberger, and Sandhas are solved for neutron-3He and proton-3H scattering in the energy regime above the four-nucleon breakup threshold. Cross sections and spin observables for elastic, transfer, charge-exchange, and breakup reactions are calculated using realistic nucleon-nucleon interaction models, including the one with effective many-nucleon forces due to explicit Δ-isobar excitation. The experimental data are described reasonably well with only few exceptions such as vector analyzing powers.

Short communication: Intestinal digestibility of amino acids in fluid- and particle-associated rumen bacteria determined using a precision-fed cecectomized rooster bioassay.

Microbial protein represents the majority of metabolizable protein absorbed by ruminant animals. Enhanced understanding of the AA digestibility of rumen microbes will improve estimates of metabolizable protein. The objective of this experiment was to determine the digestibility of AA in fluid- (FAB) and particle-associated bacteria (PAB) using the precision-fed cecectomized rooster bioassay. Bacteria were isolated from 4 ruminally cannulated lactating Holstein cows by differential centrifugation, including particle suspension in 0.1% Tween-80 for increased removal of PAB from ruminal digesta. Samples of FAB and PAB were fed to 9 cecectomized roosters to determine standardized digestibility of AA. Total AA digestibility was 76.8 and 75.5% for FAB and PAB, respectively, but did not differ. Differences existed in AA digestibilities within bacterial type when compared with the mean essential AA digestibility value. Compared with previous literature estimates of AA digestibility in microbes (mean = 76%; range = 57-87%) and relative to National Research Council estimates of total AA from rumen bacteria (80%), the precision-fed cecectomized rooster assay is an acceptable in vivo model to determine AA digestibility of rumen bacteria.

PLP1 duplication at the breakpoint regions of an apparently balanced t(X;22) translocation causes Pelizaeus-Merzbacher disease in a girl.

PLP1 (proteolipid protein1 gene) mutations cause Pelizaeus-Merzbacher disease (PMD), characterized by hypomyelination of the central nervous system, and affecting almost exclusively males. We report on a girl with classical PMD who carries an apparently balanced translocation t(X;22)(q22;q13). By applying array-based comparative genomic hybridization (a-CGH), we detected duplications at 22q13 and Xq22, encompassing 487-546 kb and 543-611 kb, respectively. The additional copies were mapped by fluorescent in situ hybridization to the breakpoint regions, on the derivative X chromosome (22q13 duplicated segment) and on the derivative 22 chromosome (Xq22 duplicated segment). One of the 14 duplicated X-chromosome genes was PLP1.The normal X chromosome was the inactive one in the majority of peripheral blood leukocytes, a pattern of inactivation that makes cells functionally balanced for the translocated segments. However, a copy of the PLP1 gene on the derivative chromosome 22, in addition to those on the X and der(X) chromosomes, resulted in two active copies of the gene, irrespective of the X-inactivation pattern, thus causing PMD. This t(X;22) is the first constitutional human apparently balanced translocation with duplications from both involved chromosomes detected at the breakpoint regions.

Analyzing power Ay(θ) of n-3He elastic scattering between 1.60 and 5.54 MeV.

Comprehensive and high-accuracy n-3He elastic scattering analyzing power Ay(θ) angular distributions were obtained at five incident neutron energies between 1.60 and 5.54 MeV. The data are compared to rigorous four-nucleon calculations using high-precision nucleon-nucleon potential models; three-nucleon force effects are found to be very small. The agreement between data and calculations is fair at the lower energies and becomes less satisfactory with increasing neutron energy. Comparison to p-3He scattering over the same energy range exhibits unexpectedly large isospin effects.

First measurements of spin-dependent double-differential cross sections and the Gerasimov-Drell-Hearn Integrand from 3He(γ,n)pp at incident photon energies of 12.8 and 14.7 MeV.

The first measurement of the three-body photodisintegration of longitudinally polarized (3)He with a circularly polarized γ-ray beam was carried out at the High Intensity γ-ray Source facility located at Triangle Universities Nuclear Laboratory. The spin-dependent double-differential cross sections and the contributions from the three-body photodisintegration to the (3)He Gerasimov-Drell-Hearn integrand are presented and compared with state-of-the-art three-body calculations at the incident photon energies of 12.8 and 14.7 MeV. The data reveal the importance of including the Coulomb interaction between protons in three-body calculations.

Does anticoagulation promote mural hematoma growth or delayed occlusion in spontaneous cervical artery dissections?.

BACKGROUND: In case of spontaneous cervical artery dissection (CAD), a medical treatment with anticoagulant or antiplatelet (AP) drugs would avoid the occurrence of an ischemic stroke. Although immediate anticoagulation (AC) is advocated, evidence from randomized trials is lacking. Since CAD is characterized by a mural accumulation of blood, the dissecting hematoma may enlarge under AC, with subsequent lumen narrowing. Although direct evidence of mural hematoma enlargement is lacking in the literature, such a complication may not only be theoretical. Magnetic resonance imaging (MRI) of the mural hematoma on transverse sections through the neck is the current diagnostic gold standard. Our aim was to compare the evolution of the mural hematoma in CAD during the first week after treatment initiation (AP agent: groupAP, AC: groupAC), using dedicated cervical MRI of the arterial wall. METHODS: The study was -approved by the Ethics Committee of Ile de France III. Informed consent was waived. The manuscript was prepared in accordance with the STROBE statement. Fast spin-echo T1-weighted fat-suppressed axial sequences were performed at admission (MRI1) and during the first week after initiation of the treatment (MRI2). Two readers measured volumes, craniocaudal length of the mural hematoma and lumen patency, and searched for early recurrent CAD. They also searched for extension or recurrence of ischemic brain lesions and for hemorrhagic transformation on diffusion-weighted imaging (DWI) and gradient echo T2 (T2*) sequences, respectively. RESULTS: The population included 44 patients (31 in groupAC, 13 in groupAP) with 49 CAD (35 carotid, 14 vertebral). Recurrent CAD and reduction of the lumen did not occur in either group. We did not observe recurrent DWI lesions or occurrence of hemorrhagic transformation. Interobserver agreement [intraclass correlation coefficient (95% CI)] was excellent for volume measurement [0.98 (0.97-0.99) and 0.99 (0.98-1.0) for volume1 and volume2, respectively]. While mean volumes and length of the mural hematoma decreased after treatment in both groups (volume: groupAC -13 ± 22%, groupAP -12 ± 24%, p = 0.33; length: groupAC -10 ± 27%, groupAP -10 ± 20%, p = 0.18), approximately one third of patients in each group had some growth of the mural hematoma as well as an increase in length. CONCLUSION: Limited growth of the mural hematoma was seen with both treatments in approximately one third of patients during the first week after treatment initiation. However, neither AC nor AP agents promote reduction of the lumen or recurrent dissection.

Time course of NT-proBNP levels after acute ischemic stroke.

BACKGROUND: Studies suggest that N-terminal-pro-brain natriuretic peptide (NT-proBNP) can be a biomarker of cardioembolic stroke. However, the best time to measure it after stroke is unknown. We studied the time course of NT-proBNP in patients with ischemic stroke. METHODS: Consecutive acute ischemic stroke patients were admitted over 10 months to a Stroke Unit. Stroke type was classified according to TOAST. Blood samples were drawn within 24, 48, and 72 hours after stroke. Friedman test was used to compare NT-proBNP values across the 3 times in all, cardioembolic and non-cardioembolic stroke patients. Post hoc analysis with Wilcoxon signed-rank tests was conducted with a Bonferroni correction. Mann-Whitney test was used to compare median values of NT-proBNP between cardioembolic and non-cardioembolic stroke patients. ROC curves were drawn to determine NT-proBNP accuracy to diagnose cardioembolic stroke at 24, 48, and 72 hours after stroke onset. RESULTS: One hundred and one patients were included (29 cardioembolic) with a mean age of 64.5±12.3 years. NT-proBNP values for cardioembolic stroke were significantly higher (P < 0.001) than for non-cardioembolic stroke in the 3 time points. NT-proBNP was highest in the first 24-48 h after ischemic stroke and decreased significantly 72 h after stroke onset. The area under the curve for the three time points was similar. CONCLUSION: NT-proBNP levels were highest in the first 2 days after ischemic stroke and declined significantly thereafter. However, the area under the curve for the three time points was similar. The first 72 hours after ischemic stroke have a similar diagnostic accuracy to diagnose cardioembolic stroke.

Diagnostic difficulties in the classification of transient neurological attacks.

BACKGROUND: It is frequently difficult to distinguish transient ischaemic attacks (TIA) from other transient (<24 h) neurological attacks (TNA). We aimed to classify patients with TNA and identify the most frequent problems in establishing a diagnosis. METHODS: Analysis of a consecutive cohort of patients referred to a TIA Clinic during 5 years. TNA were classified as TIA, mimic and difficult to classify/possible TIA. Reasons limiting classification were listed and grouped. RESULTS: Four hundred and fifty-eight patients were included. Diagnoses were as follows: TIA-259 (56.6%), mimic-90 (19.7%) and difficult to classify/possible TIA-109 (23.8%). Amongst the 109 patients, main difficulties in the differential diagnosis were between TIA and seizure, psychiatric disturbance, peripheral vertigo, pre-syncope and metabolic condition. The reasons contributing for classification difficulties were as follows: atypical symptoms (49 patients), paucity of details in symptoms description (24 patients), presence of focal symptoms accompanying psychiatric symptoms (anxiety or panic) (12 patients), restraints formulated by current criteria of TIA and migraine (16 patients), previous neurological deficit (eight patients). CONCLUSION: This systematic study identified distinct groups of reasons limiting the diagnosis of TNA. Different clinical approaches should be applied according to specific reasons for classification difficulty. These strategies may help to clarify the aetiology of transient neurological symptoms and improve TIA diagnosis.

Study of Nα-benzoyl-L-argininate ethyl ester chloride, a model compound for poly(ester amide) precursors: x-ray diffraction, infrared and Raman spectroscopies, and quantum chemistry calculations.

Poly(ester amide)s (PEAs) are lacking in structural and spectroscopic information. This paper reports a structural and spectroscopic characterization of N(α)-benzoyl-L-argininate ethyl ester chloride (BAEEH(+)·Cl(-)), an important amino acid derivative and an adequate PEAs' model compound. Crystals of BAEEH(+)·Cl(-) obtained by slow evaporation in an ethanol∕water mixture were studied by different complementary techniques. X-ray analysis shows that BAEEH(+)·Cl(-) crystallizes in the chiral space group P2(1). There are two symmetry independent cations (and anions) in the unit cell. The two cations have different conformations: in one of them, the angle between the least-squares planes of the phenyl ring and the guanidyl group is 5.1(2)°, and in the other the corresponding angle is 13.3(2)°. There is an extensive network of H-bonds that assembles the ions in layers parallel to the ab plane. Experimental FT-IR and Raman spectra of BAEEH(+)·Cl(-) were recorded at room temperature in the 3750-600 cm(-1) and 3380-100 cm(-1) regions, respectively, and fully assigned. Both structural and spectroscopic analysis were supported by quantum chemistry calculations based on different models (in vacuo and solid-state DFT simulations).

Marine habitats map of "Isla del Caño", Costa Rica, comparing Quickbird and Hymap images classification results.

Isla del Caño is a marine protected area on the south Pacific coast of Costa Rica, surrounded by coral reefs and coral communities. The ecology of these coral reefs has been studied for over 20 years, but they have not been mapped. Maps are considered a great research, planning, management and monitoring tool. Medium to high resolution images (HyMap 2005 and Quickbird 2007 respectively) were processed and classified in order to test and compare their accuracy in producing a marine habitat map. Manta tow surveys were performed in the field for identification of 7 marine habitats 1. Coral community; 2. Coral reef; 3. Bed rock; 4. Sand; 5. Sand with boulders; 6. Sand with rodolyths; and 7. Deep water. The overall accuracy was slightly higher using Quickbird (87%) than using Hymap (60%), however the difference was not significant. The map produced using Quickbird was selected to represent the marine habitats of Isla del Caño. This map will help to analyze the adequate size and zoning of the marine protected area.

Innovative tailor made dextran based membranes with excellent non-inflammatory response: In vivo assessment.

In this work, dextran based membranes with potential to be used as implantable devices in Tissue Engineering and Regenerative Medicine (TERM) were prepared by a straightforward strategy. Briefly, two polymers approved by the Food and Drug Administration, viz. dextran and poly(ε-caprolactone) (PCL) were functionalized with methacrylate moieties, and subjected to photocrosslinking. Employing different weight ratios of each polymer in the formulations allowed to obtain transparent membranes with tunable physicochemical properties and low adverse host tissue response. Independently of the material, all formulations have shown to be thermally stable up to 300 °C whilst variations in the polymer ratio resulted in membranes with different glass transition temperatures (Tg) and flexibility. The swelling capacity ranged from 50% to 200%. On the other hand, in vitro hydrolytic degradation did not show to be material-dependent and all membranes maintained their structural integrity for more than 30 days, losing only 8-12% of their initial weight. Preliminary in vitro biological tests did not show any cytotoxic effect on seeded human dental pulp stem cells (hDPSCs), suggesting that, in general, all membranes are capable of supporting cell adhesion and viability. The in vivo biocompatibility of membranes implanted subcutaneously in rats' dorsum indicate that M100/0 (100%wt dextran) and M25/75 (25 %wt dextran) formulations can be classified as "slight-irritant" and "non-irritant", respectively. From the histological analysis performed on the main tissue organs it was not possible to detect any signs of fibrosis or necrosis thereby excluding the presence of toxic degradation by-products deposited or accumulated in these tissues. In combination, these results suggest that the newly developed formulations hold great potential as engineered devices for biomedical applications, where the biological response of cells and tissues are greatly dependent on the physical and chemical cues provided by the substrate.

Insights on the genetic features of endometrial pathogenic Escherichia coli strains from pyometra in companion animals: Improving the knowledge about pathogenesis.

Endometrial pathogenic E. coli (EnPEC) isolates are involved in endometrial infections in animals and humans. Besides the high aggressiveness of the endometrial infections, the EnPEC virulence profile and pathogenesis are still little known. In this study, we have sequenced and analyzed an EnPEC strain from canine pyometra (E. coli_LBV005/17), following a molecular characterization of the virulence profile and phylogenetic evolution of an EnPEC collection from canines and felines (45 strains). Most of the strains belonged to phylo-group B2, and display a high virulence profile. In particular we highlight the classification of the E. coli_LBV005/17 as sequence type 131 (ST131), in addition to other five strains, as observed by gyrB phylogenetic analysis. Also, the phylogenetic position of EnPEC strains from pyometra in companion animals suggests that their origins are from both extraintestinal and commensal E. coli strains. Accordingly to Principal Coordinates Analysis (PCoA) and phylogenetic analysis we can propose that EnPEC strains have neither the same genetic profile, nor a unique common ancestral. In summary, the present work characterize an EnPEC genome from bitch pyometra and the genetic profile of 45 EnPEC strains from companion animals pyometra, being the commonest virulence pattern: fimA, papC, hlyA, hlyE, cnf1, entB, iroN, irp1, bssS, bssR, and hmsP. These data improving the background knowledge of this E. coli pathotype related to pyometra in companion animals and may support new methods to prevent the disease evolution.