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Alternative water disinfectants to chlorination need to be identified because its effectiveness is limited by water pH and potentially carcinogen by−products resulted from chlorination and organic compound reaction. The first study aimed to evaluate the effect of different drinking water chemical disinfection treatments on water quality, its potential hazard effects on animal health, water and feed consumption, and apparent total tract digestibility in dairy beef bulls fed high-concentrate diets. For 224 days, 24 Holstein bulls (176 ± 16.3 kg BW, and 149 ± 5.8 days of age) were individually assigned to one of four treatments with different drinking water chemical disinfectants: without disinfection (CTR); acidification and chlorination (ACCHL; 0.65 mL/L H3PO4 and 0.14 mL/L NaClO 15%); hydrogen peroxide (PER; 0.15 mL/L); and chlorine dioxide (DIO; 2.50 mL/L). Data were analysed with a mixed-effects model. Treatments affected the chemical characteristics of the water: in ACCHL, pH was 6.60 and free residual chlorine was 0.75 mg/L; in PER, H2O2 was 10.6 mg/L; and in DIO, ClO2 was 0.52 mg/L. Water physicochemical quality parameters in all treatments were below maximal thresholds established for safe water consumption by the Water Safety Royal Decree (RD 140/2003). In addition, the total coliform count of treated waters was reduced (P = 0.01) compared with CTR; moreover, ACCHL and DIO treatments were more effective in reducing total coliform count than PER. Dry matter intake tended (P = 0.07) to increase in DIO compared with CTR. Treatments did not affect blood parameters nor apparent total tract digestibility. The second study aimed to evaluate the potential benefit on animal performance of two drinking water disinfectants under commercial conditions in dairy beef crossbred Holstein bulls fed high-concentrate diets. Ninety-six animals (307 ± 4.4 kg BW, and 224 ± 1.8 days of age) were allocated to six pens for 140 days and assigned to one of two treatments: ACCHL, most common water disinfectant, and DIO. Data were analysed with a mixed-effects model. Water total coliform count and water consumption were similar between treatments. Concentrate intake was greater (P = 0.02) in ACCHL for the last 14 study days. Growth performance and carcass quality were similar between treatments. In summary, acidification and chlorination, H2O2, and ClO2 as drinking water disinfectants in dairy beef bulls had good disinfecting activity without detrimental effects on health and nutrient digestibility, and performance.

Resumen: MPOX es una enfermedad zoonótica emergente que se ha propagado rápidamente por todo el mundo y que ha sido declarada por la OMS como una emergencia de salud pública de interés internacional. Esta es una revisión no sistemática de los aspectos clínicos, epidemiológicos, diagnósticos y terapéuticos más relevantes para el dermatólogo. En el brote actual, la transmisión durante las relaciones sexuales es la principal forma de contagio como resultado del contacto físico cercano. Si bien los casos iniciales se informaron en hombres que tienen sexo con hombres, cualquier persona en contacto cercano con personas o fómites infectados está en riesgo. El pródromo clásico puede ser subclínico y la erupción puede ser sutil. Las complicaciones son frecuentes, pero el requerimiento de hospitalización es infrecuente. El diagnóstico definitivo se realiza mediante PCR de las lesiones mucocutáneas. Actualmente no existen tratamientos específicos, y el tratamiento sintomático es el pilar terapéutico. Abstract: Mpox is an emerging zoonotic disease that has spread rapidly around the world. It has been declared a public health emergency of international concern by the World Health Organization. This review is an update for dermatologists on the epidemiology, clinical presentation, diagnosis, and treatment of Mpox. The primary mode of transmission in the current outbreak is close physical contact during sexual activity. Although most of the initial cases were reported in men who have sex with men, anyone who has close contact with an infected person or contaminated fomites is at risk. Classic prodromal features of Mpox include subclinical manifestations and a mild rash. Complications are common but rarely require hospitalization. Polymerase chain reaction analysis of mucocutaneous lesions is the test of choice for a definitive diagnosis. In the absence of specific treatments, management focuses on symptomatic relief.

Mpox is an emerging zoonotic disease that has spread rapidly around the world. It has been declared a public health emergency of international concern by the World Health Organization. This review is an update for dermatologists on the epidemiology, clinical presentation, diagnosis, and treatment of Mpox. The primary mode of transmission in the current outbreak is close physical contact during sexual activity. Although most of the initial cases were reported in men who have sex with men, anyone who has close contact with an infected person or contaminated fomites is at risk. Classic prodromal features of Mpox include subclinical manifestations and a mild rash. Complications are common but rarely require hospitalization. Polymerase chain reaction analysis of mucocutaneous lesions is the test of choice for a definitive diagnosis. In the absence of specific treatments, management focuses on symptomatic relief. Resumen: MPOX es una enfermedad zoonótica emergente que se ha propagado rápidamente por todo el mundo y que ha sido declarada por la OMS como una emergencia de salud pública de interés internacional. Esta es una revisión no sistemática de los aspectos clínicos, epidemiológicos, diagnósticos y terapéuticos más relevantes para el dermatólogo. En el brote actual, la transmisión durante las relaciones sexuales es la principal forma de contagio como resultado del contacto físico cercano. Si bien los casos iniciales se informaron en hombres que tienen sexo con hombres, cualquier persona en contacto cercano con personas o fómites infectados está en riesgo. El pródromo clásico puede ser subclínico y la erupción puede ser sutil. Las complicaciones son frecuentes, pero el requerimiento de hospitalización es infrecuente. El diagnóstico definitivo se realiza mediante PCR de las lesiones mucocutáneas. Actualmente no existen tratamientos específicos, y el tratamiento sintomático es el pilar terapéutico.

Resumen: El comienzo de la psoriasis en la edad pediátrica, aunque generalmente leve, puede requerir tratamiento sistémico en las formas moderadas o graves de la enfermedad. El objetivo de este trabajo es analizar la frecuencia relativa, las características de los pacientes, el tratamiento empleado y los eventos adversos (EA) observados a partir del registro BIOBADADERM en niños y jóvenes con psoriasis moderada-grave. Del total de 3.946 pacientes del registro, se incluyen 24 pacientes menores de 21 años, con una edad media al inicio del tratamiento en BIOBADADERM de 16,1 años y un PASI medio de 9,4. El 67% de los pacientes estaba en tratamiento sistémico clásico al inicio del registro. Catorce pacientes (58%) suspendieron el tratamiento por pérdida o falta de eficacia o por EA. En conclusión, los datos del registro BIOBADADERM muestran que los menores representan un grupo muy pequeño dentro de los pacientes con psoriasis que reciben tratamiento sistémico y son manejados más frecuentemente con tratamientos clásicos. Abstract: Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.

The first study aimed to evaluate the effect of drinking water disinfection (chlorination: NaClO 15%) and conditioning (acidification: H3PO4 diluted 1:5 in water) on water quality, water and feed consumption, apparent total tract digestibility, and its potential hazardous effects on Holstein bulls fed high-concentrate diets. Twenty-four animals (221 ± 20.9 kg of BW, and 184 ± 9.9 days of age) were individually assigned to one of four treatments according to a 2 × 2 factorial arrangement: conditioning (with or without acidification) and disinfection (with or without chlorination). The entire study lasted 210 days. Physicochemical and microbiological water quality, water and feed consumption, haematological and biochemical blood parameters, and apparent total tract digestibility were measured; data were analysed via a mixed-effects model. Chlorination and acidification increased (P = 0.02) free residual chlorine in water, and chlorination reduced (P = 0.01) total coliform and Clostridium perfringens counts in water. Treatment did not affect water consumption, total DM intake, or blood parameters. At the beginning of the study, NDF digestibility decreased (P = 0.04) with acidification, however, this was restored at the end of the study. The second study evaluated the potential benefit of drinking water chlorination and acidification on the performance of crossbred Holstein bulls fed high-concentrate diets under commercial conditions. Ninety-six animals (322 ± 35.0 kg of BW, and 220 ± 14.2 days of age) were allocated into six pens assigned to one of the two treatments: untreated drinking water or drinking water treated with chlorination and acidification for a total of 112 days. Physicochemical and microbiological water quality, water and concentrate consumption, eating behaviour, growth performance, and carcass quality were analysed via a mixed-effects model. Water conditioning and disinfection increased (P = 0.01) free residual chlorine concentration and reduced (P = 0.04) total coliform count in water. Although water consumption and eating behaviour were similar between treatments, water conditioning and disinfection increased average daily weight gain (P = 0.03), BW before slaughter (P = 0.01), and hot carcass weight (P = 0.01). In conclusion, drinking water chlorination and acidification in fattening dairy beef bulls is recommended as it improves growth performance without any detrimental side effects on health or nutrient digestibility.

Abstract Background Childhood obesity represents a global public health crisis: the number of obese children and adolescents (aged 5–19 years) worldwide has risen tenfold in the past four decades. The vast majority of overweight and obese children live in high-income countries, and low socio-economic status (SES) is a significant risk factor. Family Based Interventions (FBI) have demonstrated positive results in preventing obesity, although these results are strongly influenced by SES. Moreover, we still poorly understand how FBI can determine a positive trend in weight status in low-income communities. Therefore, there is an urgent need to define and evaluate innovative and multi-target projects to reduce obesity risk behaviors and health inequalities and the present study aims to present the study protocol of FIVALIN a FBI that pretends to achieve this goal. Methods We will conduct a quasi-experimental design within 60 Community Child Centers (CCC) in Barcelona metropolitan area. Each cluster (CCC) will be assigned by convenience to the intervention and control groups. For the whole study, a total of 810 children aged 8–12 years and 600 parents will be recruited during 3 consecutive editions (1st – 2019/2020; 2nd – 2020/2021; 3rd – 2021/2022) of 10 months each. The action is a regular multicomponent health-promotion intervention targeting children, families, and CCC. All activities are based on the Motivational Interviewing (MI) approach and will focus on promoting good dietary habits, physical activity, appropriate screen time and sleep duration, and psychological well-being. The control group participate in a unique workshop on general awareness of healthy lifestyles for families. We will perform a comparative analysis of the evolution of weight status, healthy lifestyles, and socioeconomic variables, between the intervention and control groups. Discussion There is a need for more evidence on how to target and evaluate holistic interventions in low SES families. Our multi-targeting intervention for obesity prevention tackles risky behaviors that go beyond diet and physical activity (PA). Therefore, future interventions can effectively promote all the behavioral domains that determine trends in the weight status. Trial registration ISRCTN Registry: ISRCRN12682870 . Registered 9 July 2020. Retrospectively registered. Protocol version: 30 April 2021, version 5.

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. The mean age of this group when they started treatment upon registration on Biobadaderm was 16.1 years and the mean Psoriasis Area and Severity Index was 9.4. In 67% the first treatment recorded was with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs. Resumen: El comienzo de la psoriasis en la edad pediátrica, aunque generalmente leve, puede requerir tratamiento sistémico en las formas moderadas o graves de la enfermedad. El objetivo de este trabajo es analizar la frecuencia relativa, las características de los pacientes, el tratamiento empleado y los eventos adversos observados a partir del registro BIOBADADERM en niños y jóvenes con psoriasis moderada-grave. Del total de 3.946 pacientes del registro, se incluyen 24 pacientes menores de 21 años, con una edad media al inicio del tratamiento en BIOBADADERM de 16,1 años y un PASI medio de 9,4. El 67% de los pacientes estaban en tratamiento sistémico clásico al inicio del registro. Catorce pacientes (58%) suspendieron el tratamiento por pérdida o falta de eficacia o por eventos adversos. En conclusión, los datos del registro BIOBADADERM muestran que los menores representan un grupo muy pequeño dentro de los pacientes con psoriasis que reciben tratamiento sistémico y son manejados más frecuentemente con tratamientos clásicos.

Dietary strategies can potentially help to reduce nitrogen (N) emissions and decrease the environmental impact of beef production. This study aimed to evaluate the effects of dietary crude protein (CP) concentration on animal performance, N excretion, and manure N volatilisation of finishing Holstein animals. In a first study, 105 Holstein bulls (BW 344 ± 2.6 kg; age 252 ± 0.9 days) were allocated to eight pens to evaluate the effect of two treatments (medium (M) and low (L), which contained CP 14.5% and 12% on a DM basis, respectively) on performance, and results confirmed that dietary CP decrease did not impair animal growth. In a second study, N excretion study, 24 Holstein heifers (BW 310 ± 5.3 kg; age 251 ± 1.4 days) were distributed randomly depending on the initial BW to three treatments (high (H), M, and L, which contained CP 17%, 14.5% and 12% on a DM basis, respectively). Based on N excretion, urinary N excretion was greater (P

Objective: analysis and evaluation of a multidisciplinary approach, postoperative results and survival of a group of patients with resected pancreatic cancer after a multimodal therapy. Design: descriptive, prospective and observational study. Patients: between January 2004 and December 2004, 124 patients with pancreatic cancer were evaluated. In 30 patients pancreatic resection was performed, and they are the object of this study. Results of preoperative evaluation, postoperative morbidity and mortality, and long term survival were studied. Results: diagnostic evaluation was completed in ambulatory basis in 20% of the patients. In 63% of cases, admission was done in the same day of surgery. In 3 patients (9%), tumor resection was not achieved, therefore, concordance between radiological and surgical resectability rate was 91%. Resectability rate was 24.1%. Surgical Mortality was 3.3%, with a global morbidity rate of 56.6%. Survival at one, two, three and, four years was 76.2%, 56.3%, 43%, y 27.3% respectively. Conclusions: technological development and coordination of efforts in multidisciplinary teams offer an accurate evaluation of tumor involvement, and may reduce the number of laparotomies without tumor resection. The application of a systematic and generalized multimodal treatment in pancreatic cancer is progressively showing a tendency of progressive increase in resectability and survival rates in pancreatic cancer.Objetivo: analizar la evaluación del abordaje multidisciplinario de un grupo de pacientes con cáncer de páncreas resecado, los resultados postoperatorios y la supervivencia tras la aplicación de un tratamiento multimodal. Diseño: estudio descriptivo prospectivo observacional. Pacientes: entre enero de 2004 y diciembre 2009 se evaluaron 124 pacientes con cáncer de páncreas. De ellos, se realizó la resección pancreática con intención curativa en 30 casos que constituyen el objeto del estudio. Se analizaron los resultados del estudio preoperatorio de extensión tumoral, la morbi-mortalidad postoperatoria, y la supervivencia. Resultados: la evaluación diagnóstica se hizo en régimen ambulatorio en el 20% de los pacientes. En el 63% de los casos, el ingreso fue el mismo día de la intervención. En 3 pacientes intervenidos no se consiguió realizar la resección del tumor (9%), por lo que la tasa de concordancia entre la resecabilidad radiológica y la quirúrgica fue del 91%. La tasa de resecabilidad quirúrgica fue del 24,1%. La mortalidad quirúrgica de la serie fue de un 3,3%, con una morbilidad global del 56,6%. La supervivencia al año, dos, tres y cuatro años fue del 76,2%, 56,3%, 43%, y 27,3% respectivamente. Conclusiones: el desarrollo tecnológico y la evaluación multidisciplinar coordinada, permite realizar una evaluación precisa de la extensión tumoral, y puede reducir el número de laparotomías sin resección del tumor. Con la aplicación de una terapia multimodal sistemática combinada, la resecabilidad quirúrgica y la supervivencia a medio y largo plazo parece que están aumentando de forma progresiva.

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Current clinical practice in focal epilepsy involves brain source imaging (BSI) to localize brain areas where from interictal epileptiform discharges (IEDs) emerge. These areas, named irritative zones, have been useful to define candidate seizures-onset zones during pre-surgical workup. Since human histological data are mostly available from final resected zones, systematic studies characterizing pathophysiological mechanisms and abnormal molecular/cellular substrates in irritative zones--independent of them being epileptogenic--are challenging. Combining BSI and histological analysis from all types of irritative zones is only possible through the use of preclinical animal models. Here, we recorded 32-channel spontaneous electroencephalographic data from rats that have focal cortical dysplasia (FCD) and chronic seizures. BSI for different IED subtypes was performed using the methodology presented in Bae et al. (2015). Post-mortem brain sections containing irritative zones were stained to quantify anatomical, functional, and inflammatory biomarkers specific for epileptogenesis, and the results were compared with those obtained using the contralateral healthy brain tissue. We found abnormal anatomical structures in all irritative zones (i.e., larger neuronal processes, glioreactivity, and vascular cuffing) and larger expressions for neurotransmission (i.e., NR2B) and inflammation (i.e., ILb1, TNFa and HMGB1). We conclude that irritative zones in this rat preclinical model of FCD comprise abnormal tissues disregarding whether they are actually involved in icto-genesis or not. We hypothesize that seizure perpetuation happens gradually; hence, our results could support the use of IED-based BSI for the early diagnosis and preventive treatment of potential epileptic foci. Further verifications in humans are yet needed. [ABSTRACT FROM AUTHOR]

Abstract. Objective: This study evaluates the poly inosinic acid (poly I)-induced activation in the murine monocytemacrophage cell line RAW 264.7, which led to an inflammatory phenotype. [ABSTRACT FROM AUTHOR]

La sostenibilidad global es cada vez más un tema de sostenibilidad urbana. Por este motivo, es necesario un marco de trabajo que pueda ayudar en el proceso de diseño y rediseño (rehabilitación) de nuestras ciudades. El objetivo de este trabajo es presentar y describir la metodología de ecodiseño adaptada a los entornos urbanos, la cual se caracteriza por la incorporación sistemática de las consideraciones ambientales a lo largo de su ciclo de vida. El documento presenta un caso de estudio de ecodiseño del barrio de Vallbona (Barcelona). Esta experiencia demuestra que la inclusión de criterios de sostenibilidad en las etapas iniciales de diseño y planificación de los sistemas urbanos es la mejor estrategia para la prevención ambiental. Además, se presenta un marco metodológico con el fin de proporcionar a los planificadores una forma estructurada de diseño de los asentamientos urbanos que les permita avanzar hacia entornos urbanos más sostenibles.

The error-related negativity and an N2-component recorded over medial frontal cortex index core functions of cognitive control. While they are known to originate from agranular frontal areas, the underlying microcircuit mechanisms remain elusive. Most insights about microcircuit function have been derived from variations of the so-called canonical microcircuit model. These microcircuit architectures are based extensively on studies from granular sensory cortical areas in monkeys, cats, and rodents. However, evidence has shown striking cytoarchitectonic differences across species and differences in the functional relationships across cortical layers in agranular compared to granular sensory areas. In this minireview, we outline a tentative microcircuit model underlying cognitive control in the agranular frontal cortex of primates. The model incorporates the main GABAergic interneuron subclasses with specific laminar arrangements and target regions on pyramidal cells. We emphasize the role of layer 5 pyramidal cells in error and conflict detection. We offer several specific questions necessary for creating a specific intrinsic microcircuit model of the agranular frontal cortex.

In this work we propose using phase diagrams to explain the dynamical behaviour of simple mechanical systems. First the motion of the system is experimentally measured, and then the derivatives, and are obtained from it and the motion equation is represented graphically. This idea is applied to the study of a system with linear viscous drag, explaining the evolution of the system towards the dynamical equilibrium point corresponding to the limit velocity. The phase diagrams of the viscous drag are compared with those of the Coulomb drag, which is not continuous and does not necessarily lead to a uniformly accelerated motion. The method is illustrated by an experiment in a dynamic track with magnetic damping. The use of phase diagrams allows for the checking the linearity of this damping. Moreover it allows for the identification of the existence of a small Coulomb drag between the track and the cart that appears as a small discontinuity of the function when the direction of the movement changes. [ABSTRACT FROM AUTHOR]

Alongside positive blood oxygenation level–dependent (BOLD) responses associated with interictal epileptic discharges, a variety of negative BOLD responses (NBRs) are typically found in epileptic patients. Previous studies suggest that, in general, up to four mechanisms might underlie the genesis of NBRs in the brain: (i) neuronal disruption of network activity, (ii) altered balance of neurometabolic/vascular couplings, (iii) arterial blood stealing, and (iv) enhanced cortical inhibition. Detecting and classifying these mechanisms from BOLD signals are pivotal for the improvement of the specificity of the electroencephalography–functional magnetic resonance imaging (EEG-fMRI) image modality to identify the seizure-onset zones in refractory local epilepsy. This requires models with physiological interpretation that furnish the understanding of how these mechanisms are fingerprinted by their BOLD responses. Here, we used a Windkessel model with viscoelastic compliance/inductance in combination with dynamic models of both neuronal population activity and tissue/blood O2 to classify the hemodynamic response functions (HRFs) linked to the above mechanisms in the irritative zones of epileptic patients. First, we evaluated the most relevant imprints on the BOLD response caused by variations of key model parameters. Second, we demonstrated that a general linear model is enough to accurately represent the four different types of NBRs. Third, we tested the ability of a machine learning classifier, built from a simulated ensemble of HRFs, to predict the mechanism underlying the BOLD signal from irritative zones. Cross-validation indicates that these four mechanisms can be classified from realistic fMRI BOLD signals. To demonstrate proof of concept, we applied our methodology to EEG-fMRI data from five epileptic patients undergoing neurosurgery, suggesting the presence of some of these mechanisms. We concluded that a proper identification and interpretation of NBR mechanisms in epilepsy can be performed by combining general linear models and biophysically inspired models.

AIM: To develop a critical pathway for primary open angle glaucoma (POAG) diagnosis intended to be efficient, to unify criteria, reduce resource use and minimize costs to the health system. METHODS: We performed a systematic search on PubMed, Cochrane, Embase and ClinicalTrials.org databases and classified the quality of evidence from level I through III. RESULTS: A critical pathway was designed by setting a key-decision step by step model on the basis of the best current evidence. CONCLUSION: A critical pathway, evidence-based guideline, may be a useful tool intended to reduce costs while maintaining or even improving the quality of care for diagnosing a highly prevalent pathology such as open angle glaucoma.

Complete removal of epileptogenic cortex while preserving eloquent areas is crucial in patients undergoing epilepsy surgery. In this manuscript, the feasibility was explored of developing a new methodology based on dynamic intrinsic optical signal imaging (DIOSI) to intraoperatively detect and differentiate epileptogenic from eloquent cortices in pediatric patients with focal epilepsy. From 11 pediatric patients undergoing epilepsy surgery, negatively-correlated hemodynamic low-frequency oscillations (LFOs, ~0.02–0.1 Hz) were observed from the exposed epileptogenic and eloquent cortical areas, as defined by electrocorticography (ECoG), using a DIOSI system. These LFOs were classified into multiple groups in accordance with their unique temporal profiles. Causal relationships within these groups were investigated using the Granger causality method, and 83% of the ECoG-defined epileptogenic cortical areas were found to have a directed influence on one or more cortical areas showing LFOs within the field of view of the imaging system. To understand the physiological origins of LFOs, blood vessel density was compared between epileptogenic and normal cortical areas and a statistically-significant difference (p

Current clinical practice in focal epilepsy involves brain source imaging (BSI) to localize brain areas where from interictal epileptiform discharges (IEDs) emerge. These areas, named irritative zones, have been useful to define candidate seizures-onset zones during pre-surgical workup. Since human histological data are mostly available from final resected zones, systematic studies characterizing pathophysiological mechanisms and abnormal molecular/cellular substrates in irritative zones—independent of them being epileptogenic—are challenging. Combining BSI and histological analysis from all types of irritative zones is only possible through the use of preclinical animal models. Here, we recorded 32-channel spontaneous electroencephalographic data from rats that have focal cortical dysplasia (FCD) and chronic seizures. BSI for different IED subtypes was performed using the methodology presented in Bae et al. (2015). Post-mortem brain sections containing irritative zones were stained to quantify anatomical, functional, and inflammatory biomarkers specific for epileptogenesis, and the results were compared with those obtained using the contralateral healthy brain tissue. We found abnormal anatomical structures in all irritative zones (i.e., larger neuronal processes, glioreactivity, and vascular cuffing) and larger expressions for neurotransmission (i.e., NR2B) and inflammation (i.e., ILβ1, TNFα and HMGB1). We conclude that irritative zones in this rat preclinical model of FCD comprise abnormal tissues disregarding whether they are actually involved in icto-genesis or not. We hypothesize that seizure perpetuation happens gradually; hence, our results could support the use of IED-based BSI for the early diagnosis and preventive treatment of potential epileptic foci. Further verifications in humans are yet needed.

Survival after lung transplantation (LT) is hampered by the development of chronic lung allograft dysfunction (CLAD). There is no treatment available to reverse CLAD once diagnosed, but early intervention could modify the progressive lung function decline. Thus, biomarkers are need for early detection of CLAD. High levels of donor derived cell-free DNA (ddcfDNA) have been described to precede acute cellar rejection and antibody mediated rejection diagnosis. The aim of this study is to assess if there is any association between ddcfDNA and chronic lung allograft dysfunction (CLAD). This is a longitudinal study in which ddcfDNA levels were determined in 100 LT recipients at the 3rd, 6th, 9th, 12th, 24th and 36th month after LT. Firstly, real-time PCR was performed to detect an informative INDEL polymorphism for each donor/recipient pair. Secondly, levels of ddcfDNA were determined by quantifying the informative INDEL by digital PCR in the plasma of the recipient. Clinical data was collected during a three years follow-up to determine infections, antibody mediated and acute cellular rejection, and CLAD. Globally, we noted an upward trend of ddcfDNA levels at 1, 2 and 3 years of follow-up when referred to 3 months. Levels of ddcfDNA were compared between CLAD and no CLAD patients at different time points, and a cut-off value of 1.86% at 12 months could identify those patients with higher probability of developing CLAD (Figure 1). Determine ddcfDNA levels in plasma could be a useful non-invasive biomarker for CLAD prediction. This study was partially funded by ISCIII ("PI17/01485"), co-funded by ERDF and SEPAR (552/2017). [ABSTRACT FROM AUTHOR]

Alterations in the connectivity patterns of the fMRI-based resting-state networks (RSNs) have been reported in several types of epilepsies. Evidence pointed out these alterations might be associated with the genesis and propagation of interictal epileptiform discharges (IEDs). IEDs also evoke blood-oxygen-level dependent (BOLD) responses, which have been used to delineate irritative zones during preoperative work-up. Therefore, one may expect a relationship between the topology of the IED-evoked BOLD response network and the altered spatial patterns of the RSNs. In this study, we used EEG recordings and fMRI data obtained simultaneously from a chronic model of focal epilepsy in Wistar rats to verify our hypothesis. We found that IED-evoked BOLD response networks comprise both cortical and subcortical structures with a rat-dependent topology. In all rats, IEDs evoke both activation and deactivation types of BOLD responses. Using a Granger causality method, we found that in many cases areas with BOLD deactivation have directed influences on areas with activation (p

Here we propose a methodology to analyze volumetric electrical activity of neuronal masses in the Wistar somatosensory barrel field. The key elements of the proposed methodology are a three-dimensional microelectrode array, which was customized by our group to observe extracellular recordings from an extended area of the barrel field, and a novel method for the current source density analysis. By means of this methodology, we were able to localize single barrels from their event-related responses to single whisker deflection. It was also possible to assess the spatiotemporal dynamics of neuronal aggregates in several barrels at the same time with the resolution of single neurons. We used simulations to study the robustness of our methodology to unavoidable physiological noise and electrode configuration. We compared the accuracy to reconstruct neocortical current sources with that obtained with a previous method. This constitutes a type of electrophysiological microscopy with high spatial and temporal resolution, which could change the way we analyze the activity of cortical neurons in the future.

After severe spinal cord injury, spontaneous functional recovery is limited. Numerous studies have demonstrated cell transplantation as a reliable therapeutic approach. However, it remains unknown whether grafted neuronal cells could replace lost neurons and reconstruct neuronal networks in the injured spinal cord. To address this issue, we transplanted bone marrow stromal cell-derived neural progenitor cells (BM-NPCs) in a rat model of complete spinal cord transection 9 days after the injury. BM-NPCs were induced from bone marrow stromal cells (BMSCs) by gene transfer of the Notch-1 intracellular domain followed by culturing in the neurosphere method. As reported previously, BM-NPCs differentiated into neuronal cells in a highly selective manner in vitro. We assessed hind limb movements of the animals weekly for 7 weeks to monitor functional recovery after local injection of BM-NPCs to the transected site. To test the sensory recovery, we performed functional magnetic resonance imaging (fMRI) using electrical stimulation of the hind limbs. In the injured spinal cord, transplanted BM-NPCs were confirmed to express neuronal markers 7 weeks following the transplantation. Grafted cells successfully extended neurites beyond the transected portion of the spinal cord. Adjacent localization of synaptophysin and PSD-95 in the transplanted cells suggested synaptic formations. These results indicated survival and successful differentiation of BM-NPCs in the severely injured spinal cord. Importantly, rats that received BM-NPCs demonstrated significant motor recovery when compared to the vehicle injection group. Volumes of the fMRI signals in somatosensory cortex were larger in the BM-NPC-grafted animals. However, neuronal activity was diverse and not confined to the original hind limb territory in the somatosensory cortex. Therefore, reconstruction of neuronal networks was not clearly confirmed. Our results indicated BM-NPCs as an effective method to deliver neuronal lineage cells in a severely injured spinal cord. However, reestablishment of neuronal networks in completed transected spinal cord was still a challenging task.

Over the last decade, several papers have focused on the construction of highly detailed mouse high field MRI templates via nonlinear registration to unbiased reference spaces, allowing for a variety of neuroimaging applications such as robust morphometric analyses. However, work in rats has only provided medium field MRI averages based on linear registration to biased spaces with the sole purpose of approximate fMRI localization. This precludes any morphometric analysis in spite of the need of exploring in detail the neuroanatomical substrates of diseases in a recent advent of rat models. In this paper we present a new in vivo rat T2 MRI template set, comprising average images of both intensity and shape, obtained via nonlinear registration. Also, unlike previous rat template sets, we include white and gray matter probabilistic segmentations, expanding its use to those applications demanding prior-based tissue segmentation, e.g. SPM voxel-based morphometry. We also provide a preliminary digitalization of latest Paxinos & Watson atlas for anatomical and functional interpretations within the cerebral cortex. We confirmed that, like with previous templates, forepaw and hindpaw fMRI activations can be correctly localized in the expected atlas structure. To exemplify the use of our new MRI template set, we reported the volumes of brain tissues and cortical structures and probed their relationships with ontogenetic development. Other in vivo applications in the near future can be tensor-, deformation- or voxel-based morphometry, morphological connectivity and diffusion tensor-based anatomical connectivity. Our template set, freely available through the SPM extension website, could be an important tool for future longitudinal and/or functional extensive preclinical studies.