Patients awaiting surgery for neurosurgical diseases during the first wave of the COVID-19 pandemic in Spain: a multicentre cohort study.

OBJECTIVES: The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery. DESIGN: This was an observational retrospective study. SETTINGS: A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020. PARTICIPANTS: A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection. RESULTS: More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p<0.001), degenerative spine (OR=0.296, p=0.027) and expedited indications (OR=6.095, p<0.001) were independent factors for being operated on during the pandemic. CONCLUSIONS: Patients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures.

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: a nationwide study in Spain.

OBJECTIVE: To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. SETTINGS: The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. PARTICIPANTS: This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. INTERVENTIONS: An exploratory factorial analysis was performed to select the most relevant variables of the sample. PRIMARY AND SECONDARY OUTCOME MEASURES: Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. RESULTS: Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/105 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade ≥3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/105 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. CONCLUSIONS: Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/105 people/week) was a statistically independent predictor of mortality. TRIAL REGISTRATION NUMBER: CEIM 20/217.

High risk of thrombosis in patients with advanced lung cancer harboring rearrangements in ROS1.

INTRODUCTION: Based on the high incidence of thromboembolic events (TEs) observed in lung adenocarcinomas with ALK translocations and taking into account the biological proximity of ROS1 and ALK, we conducted a retrospective analysis of patients with advanced lung carcinoma carrying rearrangements in ROS1 from 23 centres in Spain and one centre in Portugal. METHODS: The main objective of the study was to analyse the incidence of TE in this population, looking for predictive risk factors, and its impact on overall survival. RESULTS: A total of 58 patients were included. The incidence of TEs throughout the disease was 46.6% (n = 27) with a median follow-up of 19 months (range: 1-78 months) and a median overall survival of 52 months in the total population and 50 months for the patients presenting TEs, with a hazards ratio of 1.12 (95% confidence interval: 0.47-2.65) p = 0.78. The majority of the events were venous (n = 24; 89%) and occurred in the ambulatory setting (n = 18; 67%). Almost half of the patients (n = 13; 48%) presented the TE in the peri-diagnostic period. CONCLUSIONS: The high incidence of thrombosis, especially during the cancer diagnosis process, requires special attention from a clinician. Despite the limitations of such a small descriptive study, its results are in accordance with previously reported data. It would be important to design prospective studies of antithrombotic prophylaxis in this population because of their possible impact in reducing the risk of TEs.

Characterization of Mycoplasma hyopneumoniae strains in vaccinated and non-vaccinated pigs from Spanish slaughterhouses.

This study aimed to describe Mycoplasma hyopneumoniae (M. hyopneumoniae) genetic variability in vaccinated (V) and non-vaccinated (NV) slaughtered pigs showing cranio-ventral pulmonary consolidation (CVPC). Ten V and 10 NV fattening farms with respiratory problems associated to M. hyopneumoniae were selected. Lung lesions of one batch per farm were scored at slaughterhouse and the enzootic pneumonia (EP)-index was calculated. Moreover, three lungs showing the most extensive CVPC per farm were sampled and tested for M. hyopneumoniae detection by real-time (rt)-PCR. Positive samples with cycle threshold ≤30 were selected to be genotyped by sequencing of four loci (P97, P146, H1 and H5). Typing profiles (TP) were assigned considering four or two (P97, P146) loci. Five commercial vaccines for M. hyopneumoniae (VS) and two reference strains (RF) were also genotyped. The EP-index (mean ± SD) in NV farms (3.8 ± 1.9) was not significantly different from V ones (2.2 ± 1.3). From the 60 selected lungs, 46 (76.7%) were M. hyopneumoniae positive by rt-PCR (25/30 and 21/30 from NV and V farms, respectively), and 43 (93.5%) of those were successfully genotyped. A total of 24 different TP(12 in V and 12 in NV farms) or 17 TP(9 in V and 9 in NV farms, being one TP in both farm types) were identified by analyzing four or two loci, respectively. One to three TP per farm were detected, being different from VS and RF. Interestingly, farms with same breeding origin had the same TP using two loci, but such link was not found using four loci. Therefore, high inter-farm and limited intra-farm M. hyopneumoniae genetic variability were detected, but variability depended on the number of studied loci.

Comparison of vaccination protocols against Mycoplasma hyopneumoniae during the gilt acclimation period.

This study evaluated different gilt vaccination protocols against Mycoplasma (M.) hyopneumoniae at acclimation and their effect on the genetic diversity. A total of 180 M. hyopneumoniae naïve gilts were selected 1 week post-entry (wpe) at the acclimation barn in a clinically affected M. hyopneumoniae farm. Gilts were distributed according to the M. hyopneumoniae antibodies levels into three different vaccination schedules: A) four doses of a M. hyopneumoniae commercial vaccine at 2, 4, 6 and 8 wpe; B) two vaccine doses at 2 and 6 wpe and PBS at 4 and 8 wpe; and C) four PBS doses at the same wpe. Detection of M. hyopneumoniae (rt-PCR) and antibodies (ELISA) were assessed in gilts at 1, 14, 27 and 34 wpe and in 6 of their piglets at weaning. Rt-PCR positive gilts were detected at 14 wpe, being the proportion significantly lower in groups A and B (3/120, 3%) than C (27/60, 45%). Seroconversion was detected at 14 wpe, showing significant differences in percentage of inhibition (PI) between groups A (median 4.9, range 3.1-19.9) and B (5.5, 3.7-13.5), and C (14.3, 3.3-53.2). Gilts remained seropositive over the study and significant differences in PI were detected between groups A and B versus C. All piglets were rt-PCR negative, but the proportion of seropositive piglets coming from vaccinated gilts was significantly higher than the non-vaccinated group. M. hyopneumoniae characterization showed high variability. Hence, gilt vaccination with 2 or 4 doses significantly decreased the pathogen infectious pressure, variability, and provided high antibody levels to gilts and their offspring.

Dextran as a Resorbable Coating Material for Flexible Neural Probes.

In the quest for chronically reliable and bio-tolerable brain interfaces there has been a steady evolution towards the use of highly flexible, polymer-based electrode arrays. The reduced mechanical mismatch between implant and brain tissue has shown to reduce the evoked immune response, which in turn has a positive effect on signal stability and noise. Unfortunately, the low stiffness of the implants also has practical repercussions, making surgical insertion extremely difficult. In this work we explore the use of dextran as a coating material that temporarily stiffens the implant, preventing buckling during insertion. The mechanical properties of dextran coated neural probes are characterized, as well as the different parameters which influence the dissolution rate. Tuning parameters, such as coating thickness and molecular weight of the used dextran, allows customization of the stiffness and dissolution time to precisely match the user's needs. Finally, the immunological response to the coated electrodes was analyzed by performing a histological examination after four months of in vivo testing. The results indicated that a very limited amount of glial scar tissue was formed. Neurons have also infiltrated the area that was initially occupied by the dissolving dextran coating. There was no noticeable drop in neuron density around the site of implantation, confirming the suitability of the coating as a temporary aid during implantation of highly flexible polymer-based neural probes.

Low frequency pulse stimulation of Schaffer collaterals in Trpm4-/- knockout rats differently affects baseline BOLD signals in target regions of the right hippocampus but not BOLD responses at the site of stimulation.

Electrical stimulation of right Schaffer collateral in Trpm4-/- knockout and wild type rats were used to study the role of Trpm4 channels for signal processing in the hippocampal formation. Stimulation induced neuronal activity was simultaneously monitored in the CA1 region by in vivo extracellular field recordings and in the entire brain by BOLD fMRI measurements. In wild type and Trpm4-/- knockout rats, consecutive 5 Hz pulse trains elicited similar neuronal responses in the CA1 region and similar BOLD responses in the stimulated right hippocampus. Stimulus-related positive BOLD responses were also found in the left dorsal hippocampus. In contrast to the right dorsal hippocampus, baseline BOLD signals in the left hippocampus significantly decreased during consecutive stimulation trains. Similarly, slowly developing significant declines in baseline BOLD signals, in absence of any positive BOLD responses, were also observed in the right entorhinal, right piriform cortex, right basolateral amygdala and right dorsal striatum whereas baseline BOLD signals remained almost stable in the corresponding left regions. Furthermore, significant declines in baseline BOLD signals were found in the prefrontal cortex and prelimbic/infralimbic cortex. Because significant baseline BOLD declines were only observed in target regions of the right dorsal hippocampus, it might reflect functional connectivity between these regions. In all observed regions the decline in baseline BOLD signals was significantly delayed and less pronounced in Trpm4-/- knockout rats when compared to wild type rats. Thus, either Trpm4 channels are involved in mediating these baseline BOLD shifts or functional connectivity of the hippocampus is impaired in Trpm4-/- knockout rats.

Un análisis de la Estrategia Curricular de Inglés de la carrera Cultura Física / An Analysis about the English Curricular Strategy for Physical Culture degree

RESUMEN La presente investigación tiene como objetivo exponer un análisis de las tendencias y regularidades de la Estrategia Curricular de Inglés en la carrera de Cultura Física, en la Universidad de Pinar del Río, con el propósito de presentar un conjunto de acciones que permitan minimizar las insuficiencias presentadas durante la implementación de dicha estrategia. Para ello se utilizaron métodos fundamentalmente a nivel empírico, tales como el análisis de documentos, la encuesta y la entrevista. Se trabajó con una muestra de 56 estudiantes de II, III y IV años (curso regular diurno) de la Facultad de Cultura Física y 10 profesores, quienes imparten las diferentes asignaturas en estos años. Como resultado trasciende un conjunto de insuficiencias, las cuales denotan que en la práctica la estrategia no ha cumplido las expectativas para que fue diseñada. El trabajo sugiere los aspectos a tenerse en cuenta para optimizar la aplicación de la Estrategia Curricular de Inglés, en el contexto de la nueva política para el perfeccionamiento de la enseñanza del inglés en la Educación Superior Cubana.

ABSTRACT This research is aimed at stating an analysis of the English Curricular Strategy tendencies and regularities in the Physical Culture degree of Pinar del Rio University, leading to introduce actions able to reduce insufficiencies in the already mentioned strategy implementation. To meet the goal, it was used mainly empirical methods such as documents `analysis, the survey and the interview. It was considered a sample of 56 students from I, II, III and IV years (Daytime Regular Course) of Physical Culture Faculty and 10 teachers who teach the different subjects in these years. As the result a group of insufficiencies transcends, which convey that in the practice, the strategy has not achieved the mission it was designed for. The work suggests some aspects that should be taken into consideration to optimize the strategy application in the context of the new policy about the English teaching improvement in the Cuban Higher Education.

Disentangling the role of TRPM4 in hippocampus-dependent plasticity and learning: an electrophysiological, behavioral and FMRI approach.

Hippocampal long-term potentiation (LTP) has been extensively studied as a cellular model of learning and memory. Recently, we described a central function of the Transient Receptor Potential M4 (TRPM4) channel in hippocampal LTP in mice in vitro. Here, we used Trpm4 knock-out (Trpm4-/-) rats to scrutinize TRPM4's role in the intact brain in vivo. After having confirmed the previous in vitro findings in mice, we studied hippocampal synaptic plasticity by chronic recordings in freely moving rats, hippocampus-dependent learning by a behavioral battery and hippocampal-cortical connectivity by fMRI. The electrophysiological investigation supports an involvement of TRPM4 in LTP depending on the induction protocol. Moreover, an exhaustive analysis of the LTP kinetics point to mechanistic changes in LTP by trpm4 deletion. General behavior as measured by open field test, light-dark box and elevated plus maze was inconspicuous in Trpm4-/- rats. However, they showed a distinct deficit in spatial working and reference memory associated to the Barnes maze and T-maze test, respectively. In contrast, performance of the Trpm4-/- in the Morris water maze was unaltered. Finally, fMRI investigation of the effects of a strong LTP induction manifested BOLD responses in the ipsilateral and contralateral hippocampus and the prefrontal cortex of both groups. Yet, the initial BOLD response in the stimulated hippocampal area of Trpm4-/- was significantly enhanced compared to WT rats. Our findings at the cellular, behavioral and system level point to a relevant role for TRPM4 in specific types of hippocampal synaptic plasticity and learning but not in hippocampal-prefrontal interaction.

Star Wars en una terapia grupal infantil / Star Wars in a child therapy group

El presente trabajo describe y reflexiona acerca de una experiencia terapéutica grupal con niños con diagnósticos dentro de las disarmonías evolutivas de tipo psicótico. Los terapeutas utilizaron el emergente grupal del universo Star Wars para facilitar la relación y mejorar la capacidad de vínculo con iguales de estos niños, así como para favorecer la evolución de su pensamiento dentro del mundo simbólico y contribuir, también así, a salir de la relación dual psicótica (AU)

The present work describes and reflects on a therapeutic group experience with children with diagnoses within the psychotic type developmental disharmonies. The therapists used the Star Wars universe proposed by the group to facilitate the relationship and enhance these children’s ability to link with peers, as well as to favor the development of their thinking within the symbolic world and contribute to abandon dual psychotic relationships (AU)

Zoledronic acid as an antimetastatic agent for different human tumor cell lines.

BACKGROUND: Zoledronic acid effectively reduces skeletal events in patients with metastatic disease. The results of pre-clinical and emerging clinical data suggest an additional activity of zoledronic acid as an antitumor agent, interfering with the growth and dissemination of malignant cells. However, the mechanisms by which zoledronic acid impairs tumor progression are practically unknown. In the present study, we aimed to investigate the impact of zoledronic acid on invasion and colony formation ability of different human tumour cell lines. MATERIALS AND METHODS: Human ovarian (SKOV3), colonic (HCT116), endometrial (HEC1A and Ishikawa) and breast cancer (MCF-7, MDA-MB-231, HCC1937, SKBR3 and T47D) cell lines were treated with different concentrations (10-100 µM) of zoledronic acid and analyzed using 3D assays to test their invasiveness and their ability to grow anchorage-independently, both hallmarks of aggressive tumor cell behavior. RESULTS: The most intense effect of the drug on tumor invasion was observed on MDA-MB-231 cells, but at high concentrations HEC1A, SKOV3 and SKBR3 cells also exhibited reduced invasion capacity. We also found a significant reduction of colony formation under zoledronic acid treatment in MCF-7, T47-D, HCT116, Ishikawa, HEC1A and SKOV3 cells. CONCLUSION: Zoledronic acid presents an interesting potential for use as anti-metastatic agent for different solid tumor types, affecting relevant steps of tumor dissemination.