High-density speckle contrast optical tomography of cerebral blood flow response to functional stimuli in the rodent brain

Noninvasive, three-dimensional, and longitudinal imaging of cerebral blood flow (CBF) in small animal models and ultimately in humans has implications for fundamental research and clinical applications. It enables the study of phenomena such as brain development and learning and the effects of pathologies, with a clear vision for translation to humans. Speckle contrast optical tomography (SCOT) is an emerging optical method that aims to achieve this goal by directly measuring three-dimensional blood flow maps in deep tissue with a relatively inexpensive and simple system. High-density SCOT is developed to follow CBF changes in response to somatosensory cortex stimulation. Measurements are carried out through the intact skull on the rat brain. SCOT is able to follow individual trials in each brain hemisphere, where signal averaging resulted in comparable, cortical images to those of functional magnetic resonance images in spatial extent, location, and depth. Sham stimuli are utilized to demonstrate that the observed response is indeed due to local changes in the brain induced by forepaw stimulation. In developing and demonstrating the method, algorithms and analysis methods are developed. The results pave the way for longitudinal, nondestructive imaging in preclinical rodent models that can readily be translated to the human brain

Enfermería : fármacos más utilizados en urgencias hospitalarias

El Servicio de Urgencias del C.H.G.U.V. cuenta con una plantilla de 84 Enfermeros/as. Una parte considerable de ellos es personal de nueva incorporación, de ahí que sea prioritaria la elaboración de protocolos de actuación. La administración de medicación intravenosa es sin duda una de las técnicas de mayor aplicación en los pacientes que acuden a Urgencias, que en nuestro Hospital oscila entre 550-600 atenciones diarias. Por ello nos planteamos, mediante la realización de reuniones de grupo, la elaboración del presente trabajo con el objetivo de elaborar un manual informativo sobre la medicación más habitual utilizada en nuestro Servicio de Urgencias; indicaciones, contraindicaciones, diluciones, cuidados y recomendaciones sobre la administración que nos ayude a visionar la practica en nuestro trabajo y la calidad del Servicio que prestamos a nuestros pacientes, y sirva de consulta sobre todo al personal de nueva incorporación.The First aid service of the C.H.G.U.V. Nurse is provided with a staff of 84, a considerable part of them is new staff, and therefore there is a priority of making of performance protocols. The administration of intravenous medication is undoubtedly one of the most used techniques in patients who come to the emergency room, which in our Hospital ranges between 550-600 daily attentions. For this reason, we considered that carrying out group meetings in order to elaborate the present essay. Our main objective is to prepare an informative guidebook about the most common used medicines in our first aid service: indications, contraindications, dilutions, care, and recommendations on the use. In this sense it will contribute to see the practice in our work and the service quality that we give to our patients. And what is more, it will serve as a reference particularly to the new [email protected]

The relationship between performance in a theory of mind task and intrinsic functional connectivity in youth with early onset psychosis

Psychotic disorders are characterized by theory of mind (ToM) impairment. Although ToM undergoes maturational changes throughout adolescence, there is a lack of studies examining ToM performance and its brain functional correlates in individuals with an early onset of psychosis (EOP; onset prior to age 18), and its relationship with age. Twenty-seven individuals with EOP were compared with 41 healthy volunteers using the "Reading-the-Mind-in-the-Eyes" Test, as a measure of ToM performance. A resting-state functional MRI scan was also acquired, in which the default mode network was used to identify areas relevant to ToM processing employing independent component analysis. Group effects revealed worse ToM performance and less intrinsic functional connectivity in the medial prefrontal cortex in EOP relative to healthy volunteers. Group by age interaction revealed age-positive associations in ToM task performance and in intrinsic connectivity in the medial prefrontal cortex in healthy volunteers, which were not present in EOP. Differences in ToM performance were partially mediated by intrinsic functional connectivity in the medial prefrontal cortex. Poorer ToM performance in EOP, coupled with less medial prefrontal cortex connectivity, could be associated with the impact of psychosis during a critical period of development of the social brain, limiting normative age-related maturation

Physiological lentiviral vectors for the generation of improved CAR-T cells

Anti-CD19 chimeric antigen receptor (CAR)-T cells have achieved impressive outcomes for the treatment of relapsed and refractory B-lineage neoplasms. However, important limitations still remain due to severe adverse events (i.e., cytokine release syndrome and neuroinflammation) and relapse of 40%-50% of the treated patients. Most CAR-T cells are generated using retroviral vectors with strong promoters that lead to high CAR expression levels, tonic signaling, premature exhaustion, and overstimulation, reducing efficacy and increasing side effects. Here, we show that lentiviral vectors (LVs) expressing the transgene through a WAS gene promoter (AW-LVs) closely mimic the T cell receptor (TCR)/CD3 expression kinetic upon stimulation. These AW-LVs can generate improved CAR-T cells as a consequence of their moderate and TCR-like expression profile. Compared with CAR-T cells generated with human elongation factor alpha (EF1 alpha)-driven-LVs, AW-CAR-T cells exhibited lower tonic signaling, higher proportion of naive and stem cell memory T cells, less exhausted phenotype, and milder secretion of tumor necrosis factor alpha (TNF-alpha) and interferon (IFN)-gamma after efficient destruction of CD19(+) lymphoma cells, both in vitro and in vivo. Moreover, we also showed their improved efficiency using an in vitro CD19(+) pancreatic tumor model. We finally demonstrated the feasibility of large-scale manufacturing of AW-CAR-T cells in guanosine monophosphate (GMP)-like conditions. Based on these data, we propose the use of AWLVs for the generation of improved CAR-T products

Brain structural trajectories in youth at familial risk for schizophrenia or bipolar disorder according to development of psychosis spectrum symptoms

Background: The evaluation of child and adolescent offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) may help understand changes taking place in the brain in individuals at heightened risk for disease during a key developmental period. Methods: One hundred twenty-eight individuals (33 SzO and 46 BpO, considered jointly as 'Familial High Risk' (FHR), and 49 controls) aged 6-17 years underwent clinical, cognitive and neuroimaging assessment at baseline, 2- and 4-year follow-up. Twenty FHR participants (11 SzO and 9 BpO) developed psychotic spectrum symptoms during follow-up, while 59 FHR participants did not. Magnetic resonance imaging was performed on a 3Tesla scanner; cortical surface reconstruction was applied to measure cortical thickness, surface area and grey matter volume. Results: FHR participants who developed psychotic spectrum symptoms over time showed greater time-related mean cortical thinning than those who did not and than controls. By subgroups, this effect was present in both BpO and SzO in the occipital cortex. At baseline, FHR participants who developed psychotic spectrum symptoms over time had smaller total surface area and grey matter volume than those who did not and than controls. Over time, all FHR participants showed less longitudinal decrease in surface area than controls. In those who developed psychotic spectrum symptoms over time, this effect was driven by BpO, while in those who did not, this was due to SzO, who also showed less grey matter volume reduction. Conclusion: The emergence of psychotic spectrum symptoms in FHR was indexed by smaller cross-sectional surface area and progressive cortical thinning. Relative preservation of surface area over time may signal different processes according to familial risk. These findings lay the foundation for future studies aimed at stratification of FHR youth

Salivary epidermal growth factor correlates with hospitalization length in rotavirus infection

The IFI27 interferon gene expression has been found to be largely increased in rotavirus (RV)-infected patients. IFI27 gene encodes for a protein of unknown function, very recently linked to epidermal proliferation and related to the epidermal growth factor (EGF) protein. The EGF is a low-molecular-weight polypeptide that is mainly produced by submandibular and parotid glands, and it plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. Our aim was to determine salivary EGF levels in RV-infected patients in order to establish its potential relationship with IFI27 increased expression and EGF-mediated mucosal protection in RV infection. We conducted a prospective comparative study using saliva samples from 27 infants infected with RV (sampled at recruitment during hospital admission and at convalescence, i.e. at least 3 months after recovery) and from 36 healthy control children. Median (SD) EGF salivary concentration was 777 (529) pg/ml in RV-infected group at acute phase and 356 (242) pg/m at convalescence, while it was 337 (119) pg/ml in the healthy control group. A significant association was found between EGF levels and hospitalization length of stay (P-value = 0.022; r(2) = -0.63). The salivary levels of EGF are significantly increased during the acute phase of natural RV infection, and relate to length of hospitalization. Further assessment of this non-invasive biomarker in RV disease is warranted.Instituto de Salud Carlos IIIXunta de Galicia. Consellería de Sanidad

Rapid serial naming: Developmental trajectory and relationship with the Bangor Dyslexia Test in Spanish students

This study aimed to analyse the developmental trajectory of the accuracy and speed of naming among dyslexics and developing readers from 1st to 6th grade of primary education. It examined how familiarity with the stimulus influences the performance of different naming tasks in both groups and evaluated the link between naming speed and the Bangor Dyslexia Test. With a descriptive and correlational design, eight naming tasks and the Bangor Dyslexia Test (Miles, 1982; Outón & Suárez, 2010) were administered to a sample of 198 dyslexics and 245 developing readers. The results showed that the dyslexics were slower and more inaccurate in all the naming tasks, compared with the developing readers of the same age. Greater difficulty was observed with the less familiar stimuli. It became evident that naming performance improved with age among both groups of subjects. Finally, a greater number of significant and positive correlations were found between the naming tasks and the Bangor Dyslexia Test in the dyslexic group; the strongest relationship was obtained by naming lettersS

Executive functioning and emotion recognition in youth with oppositional defiant disorder and/or conduct disorder

Objectives: Executive functioning and emotion recognition may be impaired in disruptive youth, yet findings in oppositional defiant disorder (ODD) and conduct disorder (CD) are inconsistent. We examined these functions related to ODD and CD, accounting for comorbid attention-deficit/hyperactivity disorder (ADHD) and internalising symptoms.Methods: We compared executive functioning (visual working memory, visual attention, inhibitory control) and emotion recognition between youth (8-18 years old, 123 boys, 55 girls) with ODD (n = 44) or CD (with/without ODD, n = 48), and healthy controls (n = 86). We also related ODD, CD, and ADHD symptom counts and internalising symptomatology to all outcome measures, as well as executive functioning to emotion recognition.Results: Visual working memory and inhibitory control were impaired in the ODD and CD groups versus healthy controls. Anger, disgust, fear, happiness, and sadness recognition were impaired in the CD group; only anger recognition was impaired in the ODD group. Deficits were not explained by comorbid ADHD or internalising symptoms. Visual working memory was associated with recognition of all basic emotions.Conclusions: Our findings challenge the view that neuropsychological impairments in youth with ODD/CD are driven by comorbid ADHD and suggest possible distinct neurocognitive mechanisms in CD versus ODD

Respiratory Syncytial Virus Seasonality:A Global Overview

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children. By the age of 1 year, 60-70% of children have been infected by RSV. In addition, early-life RSV infection is associated with the development of recurrent wheezing and asthma in infancy and childhood. The need for precise epidemiologic data regarding RSV as a worldwide pathogen has been growing steadily as novel RSV therapeutics are reaching the final stages of development. To optimize the prevention, diagnosis and treatment of RSV infection in a timely manner, knowledge about the differences in the timing of the RSV epidemics worldwide is needed. Previous analyses, based on literature reviews of individual reports obtained from medical databases, have fail to provide global country seasonality patterns. Until recently, only certain countries have been recording RSV incidence through their own surveillance systems. This analysis was based on national RSV surveillance reports and medical databases from 27 countries worldwide. This is the first study using original source high-quality surveillance data to establish a global, robust and homogeneous report on global country-specific RSV seasonality