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Brain damage is the major cause of permanent disability and it is particularly relevant in the elderly. While most studies focused on the immediate phase of neuronal loss upon injury, much less is known about the process of axonal regeneration after damage. The development of new refined preclinical models to investigate neuronal regeneration and the recovery of brain tissue upon injury is a major unmet challenge. Here, we present a novel experimental paradigm in mice that entails the (i) tracing of cortico-callosal connections, (ii) a mechanical lesion of the motor cortex, (iii) the stereological and histological analysis of the damaged tissue, and (iv) the functional characterization of motor deficits. By combining conventional microscopy with semi-automated 3D reconstruction, this approach allows the analysis of fine subcellular structures, such as axonal terminals, with the tridimensional overview of the connectivity and tissue integrity around the lesioned area. Since this 3D reconstruction is performed in serial sections, multiple labeling can be performed by combining diverse histological markers. We provide an example of how this methodology can be used to study cellular interactions. Namely, we show the correlation between active microglial cells and the perineuronal nets that envelop parvalbumin interneurons. In conclusion, this novel experimental paradigm will contribute to a better understanding of the molecular and cellular interactions underpinning the process of cortical regeneration upon brain damage.

Brain Imaging Data Structure (BIDS) provides a valuable tool to organise brain imaging data into a clear and easy standard directory structure. Moreover, BIDS is widely supported by the scientific community and has been established as a powerful standard for medical imaging management. Nonetheless, the original BIDS is restricted to magnetic resonance imaging (MRI) of the brain, limiting its implantation to other techniques and anatomical regions. We developed Medical Imaging Data Structure (MIDS), conceived to extend BIDS methodology to other anatomical regions and multiple imaging systems in these areas. The MIDS standard was developed to store and manage medical images as an extension of BIDS. It allows the user to handily save studies of multiple anatomical regions and imaging techniques. Besides, MIDS improves the classification of multiple images within the structure, allowing the possibility to unify them in a single study to apply on them preprocessing or artificial intelligence algorithms. Finally, the results generated are saved in the derivatives folder.

Multifunctional hydrogels are a class of materials offering new opportunities for interfacing living organisms with machines due to their mechanical compliance, biocompatibility, and capacity to be triggered by external stimuli. Here, we report a dual magnetic- and electric-stimuli-responsive hydrogel with the capacity to be disassembled and reassembled up to three times through reversible cross-links. This allows its use as an electronic device (e.g., temperature sensor) in the cross-linked state and spatiotemporal control through narrow channels in the disassembled state via the application of magnetic fields, followed by reassembly. The hydrogel consists of an interpenetrated polymer network of alginate (Alg) and poly(3,4-ethylenedioxythiophene) (PEDOT), which imparts mechanical and electrical properties, respectively. In addition, the incorporation of magnetite nanoparticles (Fe(3)O(4) NPs) endows the hydrogel with magnetic properties. After structural, (electro)chemical, and physical characterization, we successfully performed dynamic and continuous transport of the hydrogel through disassembly, transporting the polymer-Fe(3)O(4) NP aggregates toward a target using magnetic fields and its final reassembly to recover the multifunctional hydrogel in the cross-linked state. We also successfully tested the PEDOT/Alg/Fe(3)O(4) NP hydrogel for temperature sensing and magnetic hyperthermia after various disassembly/re-cross-linking cycles. The present methodology can pave the way to a new generation of soft electronic devices with the capacity to be remotely transported.

A conducting nanocomposite hydrogel is developed for the detection of L-lactate. The hydrogel is based on a mixture of alginate (Alg) and poly(3,4-ethylenedioxythiophene) (PEDOT), which is loaded with gold nanoparticles (GNP). In this novel hydrogel, Alg provides 3D structural support and flexibility, PEDOT confers conductivity and sensing capacity, and GNP provides signal amplification with respect to simple voltammetric and chronoamperometric response. The synergistic combination of the properties provided by each component results in a new flexible nanocomposite with outstanding capacity to detect hydrogen peroxide, which has been used to detect the oxidation of L-lactate. The hydrogel detects hydrogen peroxide with linear response and limits of detection of 0.91 µM and 0.02 µM by cyclic voltammetry and chronoamperometry, respectively. The hydrogel is functionalized with lactate oxidase, which catalyzes the oxidation of L-lactate to pyruvate, forming hydrogen peroxide. For L-lactate detection, the functionalized biosensor works in two linear regimes, one for concentrations lower than 5 mM with a limit of detection of 0.4 mM, and the other for concentrations up to 100 mM with a limit of detection of 3.5 mM. Because of its linear range interval, the developed biosensor could be suitable for a wide number of biological fluids.

Objective: To investigate the relationship between length of hospitalisation (LOH) and post-discharge outcomes in acute heart failure (AHF) patients and to ascertain whether there are different patterns according to department of initial hospitalisation. Methods: Consecutive AHF patients hospitalised in 41 Spanish centres were grouped based on the LOH (< 6/6-10/11-15/ > 15 days). Outcomes were defined as 90-day post-discharge all-cause mortality, AHF readmissions, and the combination of both. Hazard ratios (HRs), adjusted by chronic conditions and severity of decompensation, were calculated for groups with LOH > 6 days vs. LOH < 6 days (reference), and stratified by hospitalisation in cardiology, internal medicine, geriatrics, or short-stay units. Results: We included 8563 patients (mean age: 80 (SD = 10) years, 55.5% women), with a median LOH of 7 days (IQR 4-11): 2934 (34.3%) had a LOH < 6 days, 3184 (37.2%) 6-10 days, 1287 (15.0%) 11-15 days, and 1158 (13.5%) > 15 days. The 90-day post-discharge mortality was 11.4%, readmission 32.2%, and combined end-point 37.4%. Mortality was increased by 36.5% (95%CI = 13.0-64.9) when LOH was 11-15 days, and by 72.0% (95%CI = 42.6-107.5) when > 15 days. Conversely, no differences were found in readmission risk, and the combined end-point only increased 21.6% (95%CI = 8.4-36.4) for LOH > 15 days. Stratified analysis by hospitalisation departments rendered similar post-discharge outcomes, with all exhibiting increased mortality for LOH > 15 days and no significant increments in readmission risk. Conclusions: Short hospitalisations are not associated with worse outcomes. While post-discharge readmissions are not affected by LOH, mortality risk increases as the LOH lengthens. These findings were similar across hospitalisation departments.

Study objective: The Multiple Estimation of Risk Based on the Emergency Department Spanish Score in Patients With Acute Heart Failure (MEESSI-AHF) is a validated clinical decision tool that characterizes risk of mortality in emergency department (ED) acute heart failure patients. The objective of this study is to compare the distribution of risk categories between hospitalized and discharged ED patients with acute heart failure. Methods: We included consecutive acute heart failure patients from 34 Spanish EDs. Patients were retrospectively classified according to MEESSI-AHF risk categories. We calculated the odds of hospitalization (versus direct discharge from the ED) across MEESSI-AHF risk categories. Next, we assessed the following 30-day postdischarge outcomes: ED revisit, hospitalization, death, and their combination. We used Cox hazards models to determine the adjusted association between ED disposition decision and the outcomes among patients who were stratified into low-and increased-risk categories. Results: We included 7,930 patients (80.5 years [SD 10.1 years]; women 54.7%; hospitalized 75.3%). Compared with that for low-risk MEESSI-AHF patients, odds ratios for hospitalization of patients in intermediate-, high-, and very-high-risk categories were 1.83 (95% confidence interval [CI] 1.64 to 2.05), 3.05 (95% CI 2.48 to 3.76), and 3.98 (95% CI 3.13 to 5.05), respectively. However, almost half (47.6%) of all discharged patients were categorized as being at increased risk by MEESSI-AHF, and 19.0% of all the increased-risk patients were discharged from the ED. Among the low-risk MEESSI-AHF patients, the 30-day postdischarge mortality did not differ by ED disposition (hazard ratio [HR] for discharged patients with respect to hospitalized ones 0.65; 95% CI 0.70 to 1.11), nor did it differ in the increased-risk group (HR 0.88; 95% CI 0.63 to 1.23). The discharged low-risk MEESSI-AHF patients had higher risks of 30-day ED revisit and hospitalization (HR 1.86, 95% CI 1.57 to 2.20; and HR 1.92, 95% CI 1.54 to 2.40, respectively) compared with the admitted patients, as did the discharged patients in the increased-risk group (HR 1.62, 95% CI 1.39 to 1.89; and HR 1.40, 95% CI 1.16 to 1.68, respectively), with similar results for the combined endpoint. Conclusion: The disposition decisions made in current clinical practice for ED acute heart failure patients calibrate with MEESSI-AHF risk categories, but nearly half of the patients currently discharged from the ED fall into increased-risk MEESSI-AHF categories.

Objective. To determine whether chest radiographs can contribute to prognosis in patients with acute heart failure (AHF). Methods. Consecutive patients with AHF were enrolled by the participating emergency departments. Radiographic variables assessed were the presence or absence of evidence of cardiomegaly and pleural effusion and the pulmonary parenchymal pattern observed (vascular redistribution, interstitial edema, and/or alveolar edema). We gathered variables for the AHF episode and the patient's baseline state. Outcomes were in-hospital and 1-year mortality; hospital stay longer than 7 days, and a composite of events within 30 days of discharge (revisit, rehospitalization, and/or death). Crude and adjusted hazard ratios were calculated for the 3 categories of radiographic variables. The variables were also studied in combination. Results. A total of 2703 patients with a mean (SD) age of 81 (19) years were enrolled; 54.5% were women. Cardiomegaly was observed in 1711 cases (76.8%) and pleural effusion in 992 (36.7%). A pulmonary parenchymal pattern was observed in all cases, as follows: vascular redistribution in 1672 (61.9%), interstitial edema in 629 (23.3%) and alveolar edema in 402 (14.9%). The adjusted hazard ratios showed that cardiomegaly lacked prognostic value. However, the presence of pleural effusion was associated with a 23% (95% CI, 2%-49%) higher rate of the 30day composite outcome; in-hospital mortality was 89% (30%-177%) higher in the presence of alveolar edema, and 1-year mortality was 38% (14%-67%) higher in association with vascular redistribution. The results for the variables in combination were consistent with the results for individual variables. Conclusions. A diagnostic chest radiograph can also contribute to the prediction of adverse events. Pleural effusion is associated with a higher rate of events after discharge, and alveolar edema is associated with higher mortality.

Study objective: We assess the value of the Barthel Index (BI) in predicting 30-day mortality risk among patients with acute heart failure who are attending the emergency department (ED). Methods: We selected 9,098 acute heart failure patients from the Acute Heart Failure in Emergency Departments registry who had BI score available both at baseline and the ED visit. Patients' data were collected from 41 Spanish hospitals during four 1- to 2-month periods between 2009 and 2016. Unadjusted and adjusted logistic regression models were used to assess the association between 30-day mortality and BI score. c Statistics were used to estimate their prognostic value. Results: The mean baseline BI score was 79.4 (SD 24.6) and the mean ED BI score was 65.3 (SD 29.1). Acute functional decline (>= 5-point decrease between baseline BI and ED BI score) was observed in 5,771 patients (53.4%). Within 30 days of the ED visit, 905 patients (9.9%) died. There was a steep inverse gradient in 30-day mortality risk for baseline BI and ED BI score. For instance, compared with BI score=100, a BI score of 50 to 55 doubled the mortality risk both at baseline and the ED visit. At the ED visit, a BI score of 0 to 5 carried a 5-fold increase in risk after adjustment for other risk predictors. In comparison with baseline BI score, ED BI score consistently provided greater discrimination. Neither baseline BI score nor the change in BI score from baseline to the ED visit added further prognostic value to the ED BI score. Conclusion: Functional status assessed by the BI score at the ED visit is a strong predictor of 30-day mortality in acute heart failure patients, with higher predictive value than baseline BI score and acute functional decline. Routine recording of BI score at the ED visit may help in decisionmaking and health care planning.

Objective: To study the outcomes of patients with acute heart failure (AHF) presenting renal dysfunction (RD) or hyperkalaemia (Hk) alone or in combination. Method: We analysed the data of the EAHFE registry, a multicentre, non interventionist cohort with prospective follow-up of patients with AHF. Four groups were defined based on the presence or not of RD or Hk alone or in combination. The primary endpoint was 30-day all-cause mortality. Results: A total of 11,935 of the 13,791 patients included in the EAHFE registry were analysed. Of these, 5088 (42.6%) did not have RD or Hk (NoRD-NoHk), 150 (1.3%) had no RD but had Hk (NoRD-Hk), 6012 (50.4%) had RD but not Hk (RD-NoHk) and 685 (5.7%) had both RD and Hk (RD-Hk). Thirty-day all-cause mortality was greatest in the RD-Hk group with an adjusted Hazard Ratio (HR) of 2.44 (confidence interval 95% [C195%] 1.67-3.55; p < 0.001) and in the RD-NoHk group with an adjusted HR of 1.34 (CI95% 1.04-1.71; p = 0.022). There were no significant differences in in-hospital mortality and reconsultation at 30 days for HF. For the combined endpoint of 30-day all-cause mortality the adjusted HR was 1.33 (CI95% 1.04-1.70); (p = 0.021) for the RD-Hk group. Conclusions: The association of 30-day all-cause mortality with the presence of RD and Hk in patients presenting AHF at admission is greater than in those without this combination.

Objective To compare the clinical characteristics and outcomes of patients with acute heart failure (AHF) according to clinical profiles based on congestion and perfusion determined in the emergency department (ED). Methods and results Overall, 11 261 unselected AHF patients from 41 Spanish EDs were classified according to perfusion (normoperfusion = warm; hypoperfusion = cold) and congestion (not = dry; yes = wet). Baseline and decompensation characteristics were recorded as were the main wards to which patients were admitted. The primary outcome was 1-year all-cause mortality; secondary outcomes were need for hospitalisation during the index AHF event, in-hospital all-cause mortality, prolonged hospitalisation, 7-day post-discharge ED revisit for AHF and 30-day post-discharge rehospitalisation for AHF. A total of 8558 patients (76.0%) were warm+ wet, 1929 (17.1%) cold+ wet, 675 (6.0%) warm+ dry, and 99 (0.9%) cold+ dry; hypoperfused (cold) patients were more frequently admitted to intensive care units and geriatrics departments, and warm+ wet patients were discharged home without admission. The four phenotypes differed in most of the baseline and decompensation characteristics. The 1-year mortality was 30.8%, and compared to warm+ dry, the adjusted hazard ratios were significantly increased for cold+ wet (1.660; 95% confidence interval 1.400-1.968) and cold+ dry (1.672; 95% confidence interval 1.189-2.351). Hypoperfused (cold) phenotypes also showed higher rates of index episode hospitalisation and in-hospital mortality, while congestive (wet) phenotypes had a higher risk of prolonged hospitalisation but decreased risk of rehospitalisation. No differences were observed among phenotypes in ED revisit risk. Conclusions Bedside clinical evaluation of congestion and perfusion of AHF patients upon ED arrival and classification according to phenotypic profiles proposed by the latest European Society of Cardiology guidelines provide useful complementary information and help to rapidly predict patient outcomes shortly after ED patient arrival.

Objectives We investigated the natural history of patients after a first episode of acute heart failure (FEAHF) requiring emergency department (ED) consultation, focusing on: the frequency of ED visits and hospitalisations, departments admitting patients during the first and subsequent hospitalisations, and factors associated with difficult disease control. Methods and results We included consecutive patients diagnosed with FEAHF (either with or without previous heart failure diagnosis) in four EDs during 5 months in three different time periods (2009, 2011, 2014). Diagnosis was adjudicated by local principal investigators. The clinical characteristics of the index event were prospectively recorded, and all post-discharge ED visits and hospitalisations [related/unrelated to acute heart failure (AHF)], as well as departments involved in subsequent hospitalisations were retrospectively ascertained. 'Uncontrolled disease' during the first year after FEAHF was considered if patients were attended at ED (>= 3 times) or hospitalised (>= 2 times) for AHF or died. Overall, 505 patients with FEAHF were included and followed for a mean of 2.4 years. In-hospital mortality was 7.5%. Among 467 patients discharged alive, 288 died [median survival 3.9 years, 95% confidence interval (CI) 3.5-4.4], 421 (90%) revisited the ED (2342 ED visits; 42.4% requiring hospitalisation, 34.0% AHF-related) and 357 (77%) were hospitalised (1054 hospitalisations; 94.1% through ED, 51.4% AHF-related). AHF-related hospitalisations were mainly in internal medicine (28.0%), short-stay unit (26.3%), cardiology (20.8%), and geriatrics (14.1%). Only 47.4% of AHF-related hospitalisations were in the same department as the FEAHF, and internal medicine involvement significantly increased with subsequent hospitalisations (P = 0.01). Uncontrolled disease was observed in 31% of patients, which was independently related to age > 80 years [odds ratio (OR) 1.80, 95% CI 1.17-2.77], systolic blood pressure < 110 mmHg at ED arrival (OR 2.61, 95% CI 1.26-5.38) and anaemia (OR 2.39, 95% CI 1.51-3.78). Conclusion In the present aged cohort of AHF patients from Barcelona, Spain, the natural history after FEAHF showed different patterns of hospital department involvement. Advanced age, low systolic blood pressure and anaemia were factors related to uncontrolled disease during the year after debut.

Objectives. To describe the pattern of care usually given to patients with acute heart failure (AHF) who are taking sacubitril/valsartan (SV) and to explore the effects of care characteristics on clinical outcomes. Methods. Exploratory study of AHF cases in patients taking SV who were included in the register for the Epidemiology of Acute Heart Failure in Emergency Departments during the sixth period of data collection (EAHFE-6). We extracted baseline and episode variables and information related to SV treatment. We also analyzed associations between the discontinuation of SV therapy and adverse events within 180 days (all-cause mortality) and after discharge (emergency revisits, admission for AHF, death from any cause, or a composite event). Results. Fifty patients on SV were included. The median time on SV therapy was 81 days (interquartile range, 43-284 days). SV was discontinued in 19 cases (38%; 5 in the emergency department and 14 on the ward). Sixteen records specified the reason for discontinuing SV: renal insufficiency, 4 cases; arterial hypotension, 3; weakness/dizziness, 3; and exacerbated AHF, 3. SV discontinuation was associated with older age, absence of treatment with a betablocker, and hyperkalemia. The EAHFE-6 cases did not reveal significant differences related to SV discontinuation with respect to the rates of adverse events within 180 days or on discharge after the index event. Conclusions. Long-term SV therapy is discontinued in over a third of patients who present with exacerbated AHF even though no association with clinical outcomes could be identified.

El objetivo de este trabajo, auspiciado y financiado mediante el proyecto europeo TREASURE, ha sido analizar el efecto sobre el crecimiento, la composición de la canal y los caracteres de calidad de la carne de dos dietas basadas en suboproductos de la industria aceitera (alperujo), preparados en forma seca y húmeda, suministradas durante el período de crecimiento de cerdos ibéricos de montanera. Conclusión: La batería de resultados obtenidos en este trabajo apuntan a una utilización de dietas basadas en alperujo suministrado como ensilado, con un complemento diario en forma de pienso, como una posible alternativa para reducir el estrés alimentario de los cerdos Ibéricos durante el largo periodo previo a la montanera. No se han encontrado efectos negativos de este tipo de dieta en crecimiento, composición de la canal o en los caracteres de calidad de grasa y carne aquí considerados. Antes bien, aparecen efectos favorables en crecimiento y en composición lipídica. Sin embargo, sería deseable abordar estas alternativas también desde el punto de vista económico.

Studies of monogenic heritable pain disorders provide valuable insights into human pain mechanisms. Habib et al. show that a point mutation in the gene ZFHX2 causes an autosomal dominant form of pain insensitivity. Modulating ZFHX2 and/or downstream genes may present a new strategy for the treatment of chronic pain., Chronic pain is a major global public health issue causing a severe impact on both the quality of life for sufferers and the wider economy. Despite the significant clinical burden, little progress has been made in terms of therapeutic development. A unique approach to identifying new human-validated analgesic drug targets is to study rare families with inherited pain insensitivity. Here we have analysed an otherwise normal family where six affected individuals display a pain insensitive phenotype that is characterized by hyposensitivity to noxious heat and painless bone fractures. This autosomal dominant disorder is found in three generations and is not associated with a peripheral neuropathy. A novel point mutation in ZFHX2, encoding a putative transcription factor expressed in small diameter sensory neurons, was identified by whole exome sequencing that segregates with the pain insensitivity. The mutation is predicted to change an evolutionarily highly conserved arginine residue 1913 to a lysine within a homeodomain. Bacterial artificial chromosome (BAC) transgenic mice bearing the orthologous murine p.R1907K mutation, as well as Zfhx2 null mutant mice, have significant deficits in pain sensitivity. Gene expression analyses in dorsal root ganglia from mutant and wild-type mice show altered expression of genes implicated in peripheral pain mechanisms. The ZFHX2 variant and downstream regulated genes associated with a human pain-insensitive phenotype are therefore potential novel targets for the development of new analgesic drugs.

Background The main problem for ideal anesthetic managment of composite tissue transplantation CTT is the little experience and limited literature Methods We report our experience in bilateral hand transplants face transplant and bilateral leg transplant performed during the period men and woman aged years In the first case bilateral hands rapid sequence induction and anesthesia maintenance with propofol remifentanil and rocuronium was performed The rest of cases were protocolized to balanced anesthesia with sevofluorane remifentanyl and cisatracurium Results The mean duration per intervention was h SD h Only the first hand transplant required dopamine Fluid replacement and blood derivatives per intervention was SD mL of crystalloids SD mL of colloids SD CH SD FFP SD of platelet pool and SD g of fibrinogen Only the first case had bleeding and coagulopathy with a Hb of g dL requiring repeat surgery Mean extubation time was h SD h including the hand transplant patient that had been tracheotomized Postoperative analgesia was controlled with NSAIDs and PCA morphine Discharge to the ward was performed at h except for discharge at h Conclusion CTT involves complex techniques with blood loss hypovolemia and coagulopathy We recommend a balanced anesthetic technique with invasive hemodynamic monitoring placement of a high flow central line frequent serial laboratory tests ABG TEG and maintenance of adequate graft flow

We want to make in this article, a deep review of our experience in kidney transplantation since the moment we started the technique in 1986 to the end of the year 2000. We also want to make a compilation of the most important points of the surgical technique, patients selection criteria, and the most common and uncommon complications that can appear in kidney transplantation, analizing our results all along this time.

International audience

International audience

International audience

International audience

Paget disease (PD) is defined as the presence of neoplastic cells of glandular differentiation, interspersed between keratinocytes of nipple epidermis, and constitutes approximately 1% of breast cancer cases. More than 90% of cases are associated with an underlying in situ or invasive breast carcinoma. The most accepted explanation for the development of PD is that it results from the migration of cells from the underlying tumor via the duct system into the epidermis, the so-called epidermotropic theory. Migration may be mediated by keratinocyte-secreted heregulin-α through its binding to HER3 or HER4 receptors, dimerized to highly overexpressed HER2. The approximately 10% of cases of PD not associated with an underlying breast cancer may result from neoplastic transformation of Toker cells, benign cells with glandular phenotype frequently located in the normal nipple epidermis. The differential diagnosis of PD includes other eczematous conditions of the nipple, but any unilateral nipple abnormality in an adult woman should be considered malignant until proven otherwise. Pathologically, the differential diagnosis includes other neoplastic entities associated with atypical cells in the epidermis, as well as benign mimics. Up to two-thirds of patients presenting with PD without a palpable breast mass have a normal mammogram. Magnetic resonance imaging is recommended in cases with no findings on clinical examination, mammogram, or ultrasound. Despite data suggesting that breast conserving surgery plus radiotherapy is effective in treating PD, mastectomy continues to be the most popular treatment. Review of published data suggests a significant bias to perform mastectomy in PD, even in the presence of tumors that would likely be managed with breast conservation had they not presented with PD. Sentinel lymph node surgery is appropriate in PD patients with a clinically negative axilla and should be used in accordance with guidelines established for usual breast cancer.

Se evaluo la reactividad de un antigeno metabolico « crudo » y de un extracto metabolico « purificado » de P. brasiliensis, mediante inmunoelectroforesis, frente a 10 sueros de paracoccidioidomicosis y 6 de histoplasmosis.Ambos antigenos dieron origen al sistema precipitante especifico en 9 de los 10 sueros de paracoccidioidomicosis. El antigeno « crudo » revelo anticuerpos precipitantes en todas las muestras estudiadas, aunque el numero de arcos formados fue mayor en los inmunosueros homologos. El antigeno « purificado », por el contrario, solo reacciono con los sueros de paracoccidioidomicosis.Se postula que el uso del antigeno « purificado » puede reducir significativamente el riesgo de inespecificidad en pruebas como la doble difusion en gel, que presentan reacciones cruzadas con sueros de otras micosis, especialmente con la histoplasmosis.

SummaryAgar gel electrophoresis of soluble extracts obtained from 9 cultures of Paracoccidioides brasiliensis, in alkaline pH, revealed 8 protein fractions, 5 aniodic and 3 cathiodic. Electrophoregrams revealed 15 enzymes, only 6 of which were further identified on immunoelectrophoregrams.Immunoelectrophoretic analysis of the extracts with hyperimmune serum prepared in rabbits confirmed that P. brasiliensis has a minimum of 25 antigenic fractions. One of them of cathodic mobility with alkaline phosphatase activity, reacted with all immune sera employed and thereby produced a characteristic antigen antibody system. An antibody corresponding to this fraction was formed early during the experimental infection of rabbits. This suggested that the antigen involved in the formation of arc E, was specific in human paracoccidioidomycosis. The existence of various antigenic fractions common to P. brasiliensis and species of Emmonsia was verified.

Traditional Iberian pig production is characterized for having a fattening period with a feeding based on acorn and pastures. During the previous growing period, the feeding is restricted to avoid undesirable weight gains. However, this procedure could cause feeding stress. The use of ad libitum diets based on olive by-products during the growing period may be an alternative to avoid this stress. Two diets based on olive by-products, one incorporating dry olive pulp in the feed (DD) and the other one incorporating olive cake in wet form (WD) were compared with a control standard diet group (CD). CD and DD diets were supplied once a day and WD diet was supplied ad libitum and supplemented with a specific feed given once a day. Comparisons were performed using ANOVA for: growth, backfat fatty acid profile, carcass composition, percentage of intramuscular fat (%IMF) and other quality meat traits (thaw, cook and centrifuge force losses, shear force, marbling, Minolta colours and myoglobin concentration). No significant differences between the treatment groups were observed for most of the traits. Although animals fed with DD and WD diets grew slower than those fed with CD during the growing period, no differences in the total average daily gain were observed. DD animals showed a higher carcass yield and less %IMF in loin. Olive-cake diets caused higher levels of unsaturation than CD one after the growing period. Lower centrifuge force losses were observed in WD than in CD. DD samples were paler and less red-coloured and has lower myoglobin content than CD and WD ones. Results (of this study within project TREASURE) suggest that WD diet could be a suitable feeding for growing period in traditional Iberian pig production since negative effects on growth, carcass and quality traits were not observed in the current study. Funded by European Union’s H2020 RIA program (Grant agreement no. 634476).

Traditional Iberian pig production is characterized for having a fattening period with a feeding based on acorn and pastures. During the previous growing period, the feeding is restricted to avoid undesirable weight gains. However, this procedure could cause feeding stress. The use of ad libitum diets based on olive by-products during the growing period may be an alternative to avoid this stress. Two diets based on olive by-products, one incorporating dry olive pulp in the feed (DD) and the other one incorporating olive cake in wet form (WD) were compared with a control standard diet group (CD). CD and DD diets were supplied once a day and WD diet was supplied ad libitum and supplemented with a specific feed given once a day. Comparisons were performed using ANOVA for: growth, backfat fatty acid profile, carcass composition, percentage of intramuscular fat (%IMF) and other quality meat traits (thaw, cook and centrifuge force losses, shear force, marbling, Minolta colours and myoglobin concentration). No significant differences between the treatment groups were observed for most of the traits. Although animals fed with DD and WD diets grew slower than those fed with CD during the growing period, no differences in the total average daily gain were observed. DD animals showed a higher carcass yield and less %IMF in loin. Olive-cake diets caused higher levels of unsaturation than CD one after the growing period. Lower centrifuge force losses were observed in WD than in CD. DD samples were paler and less red-coloured and has lower myoglobin content than CD and WD ones. Results (of this study within project TREASURE) suggest that WD diet could be a suitable feeding for growing period in traditional Iberian pig production since negative effects on growth, carcass and quality traits were not observed in the current study. Funded by European Union’s H2020 RIA program (Grant agreement no. 634476).

Both TRPA1 and purinergic P2X receptors have been proposed as potential targets for the treatment of visceral pain. We found that the intracolonic administration of a low dose mustard oil (0.5%), a well-known TRPA1 agonist, produced nociceptive responses and abdominal wall referred mechanical hyperalgesia, without inducing apparent tissue damage. Both nociceptive responses and referred hyperalgesia were abolished by the ablation of TRPV1-expressing neurons (and the consequent ablation of TRPA1+ nociceptors) by resiniferatoxin (RTX) treatment, and by the TRPA1 antagonist AP18. However, a higher dose of mustard oil (2.5%) damaged the colonic epithelium and induced pERK activation in the spinal cord, and these processes were clearly independent of TRPV1-expressing neurons ablated by RTX. This higher dose of mustard oil induced nociceptive responses and referred mechanical hyperalgesia which were insensitive or only slightly sensitive to resiniferatoxin or AP18, but were markedly reduced by the P2X antagonist TNP-ATP, which is known to inhibit nociceptive actions induced by ATP released from injured tissues. In conclusion, whereas a low dose of intracolonic mustard oil induces visceral pain in a manner fully dependent on TRPA1 actions, when a high dose of this chemical irritant is used, visceral pain becomes mostly independent of TRPA1 activation but clearly enhanced by ATP purportedly released by the damaged colonic epithelium. Therefore, TRPA1 inhibition is not sufficient to substantially decrease visceral pain during tissue injury, whereas purinergic antagonism appears to be a more effective strategy., Spanish State Research Agency under MINECO PID2019-108691RB-I00, Junta de Andalucia CTS-109