GluD1, linked to schizophrenia, controls the burst firing of dopamine neurons.

Human mutations of the GRID1 gene encoding the orphan delta1 glutamate receptor-channel (GluD1) are associated with schizophrenia but the explicit role of GluD1 in brain circuits is unknown. Based on the known function of its paralog GluD2 in cerebellum, we searched for a role of GluD1 in slow glutamatergic transmission mediated by metabotropic receptor mGlu1 in midbrain dopamine neurons, whose dysfunction is a hallmark of schizophrenia. We found that an mGlu1 agonist elicits a slow depolarizing current in HEK cells co-expressing mGlu1 and GluD1, but not in cells expressing mGlu1 or GluD1 alone. This current is abolished by additional co-expression of a dominant-negative GluD1 dead pore mutant. We then characterized mGlu1-dependent currents in dopamine neurons from midbrain slices. Both the agonist-evoked and the slow postsynaptic currents are abolished by expression of the dominant-negative GluD1 mutant, pointing to the involvement of native GluD1 channels in these currents. Likewise, both mGlu1-dependent currents are suppressed in GRID1 knockout mice, which reportedly display endophenotypes relevant for schizophrenia. It is known that mGlu1 activation triggers the transition from tonic to burst firing of dopamine neurons, which signals salient stimuli and encodes reward prediction. In vivo recordings of dopamine neurons showed that their spontaneous burst firing is abolished in GRID1 knockout mice or upon targeted expression of the dominant-negative GluD1 mutant in wild-type mice. Our results de-orphanize GluD1, unravel its key role in slow glutamatergic transmission and provide insights into how GRID1 gene alterations can lead to dopaminergic dysfunctions in schizophrenia.

FDG-PET parameters predicting mediastinal malignancy in lung cancer.

BACKGROUND: Staging of mediastinal lymph nodes in non-small cell lung cancer (NSCLC) is mandatory. The maximum Standard Uptake Value (SUVmax) obtained using F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is the best non-invasive technique available for this evaluation, but its performance varies from center to center. The aim of the present study was to identify FDG-PET predictors of mediastinal malignancy that are able to minimize intercenter variability and improve the selection of subsequent staging procedures. METHOD: A multicenter study of NSCLC patients staged through FDG-PET and endobronchial ultrasonography with needle aspiration (EBUS-NA) was performed using therapeutic surgery with systematic nodal dissection as gold standard. Intercenter variability and predictive power for mediastinal malignancy of different FDG-PET measures were assessed, as well as the role of these measures for selecting additional staging procedures. RESULTS: One hundred and twenty-one NSCLC patients, of whom 94 (72%) had ≥1 hypermetabolic spots in the mediastinum, were included in the study. Mean SUVmax of the primary tumor was 12.3 (SD 6.3), and median SUVmax of the highest hypermetabolic spots in the mediastinum was 3.9 (IQR 2.4-7). Variability of FDG-PET measures between hospitals was statistically significant (p = 0.016 and p < 0.001 respectively), but lost significance when SUVmax in the mediastinum was expressed as a ratio or a subtraction from the primary tumor (SUVmax mediastinum/tumor, p = 0.083; and SUVmax mediastinum - tumor, p = 0.428 respectively). SUVmax mediastinum/tumor showed higher accuracy in the ROC analysis (AUC 0.77 CI 0.68-0.85, p < 0.001), and showed predictive power for mediastinal malignancy when using a 0.4 cutoff (OR 6.62, 95%CI 2.98-14.69). Sensitivities and negative predictive values of clinical staging through EBUS-NA attained values ranging between 57% and 92% after FDG-PET, which improved with additional techniques when the tumor had a diameter >3 cm and/or a SUVmax mediastinum/tumor ratio >0.4. CONCLUSION: The SUVmax mediastinum/tumor ratio is a good predictor of regional tumor extension in NSCLC. This measure is not influenced by intercenter variability and has an accuracy of over 70% for the identification of malignancy when using a 0.4 cutoff.

Composite anatomical-clinical-molecular prognostic model in non-small cell lung cancer.

The objective of the present study was to elaborate a survival model that integrates anatomic factors, according to the 2010 seventh edition of the tumour, node and metastasis (TNM) staging system, with clinical and molecular factors. Pathologic TNM descriptors (group A), clinical variables (group B), laboratory parameters (group C) and molecular markers (tissue microarrays; group D) were collected from 512 early-stage nonsmall cell lung cancer (NSCLC) patients with complete resection. A multivariate analysis stepped supervised learning classification algorithm was used. The prognostic performance by groups was: areas under the receiver operating characteristic curve (C-index): 0.67 (group A), 0.65 (Group B), 0.57 (group C) and 0.65 (group D). Considering all variables together selected for each of the four groups (integrated group) the C-index was 0.74 (95% CI 0.70-0.79), with statistically significant differences compared with each isolated group (from p = 0.006 to p < 0.001). Variables with the greatest prognostic discrimination were the presence of another ipsilobar nodule and tumour size > 3 cm, followed by other anatomical and clinical factors, and molecular expressions of phosphorylated mammalian target of rapamycin (phospho-mTOR), Ki67cell proliferation index and phosphorylated acetyl-coenzyme A carboxylase. This study on early-stage NSCLC shows the benefit from integrating pathological TNM, clinical and molecular factors into a composite prognostic model. The model of the integrated group classified patients with significantly higher accuracy compared to the TNM 2010 staging.

[Endoscopic techniques in bronchogenic carcinoma. Changes in recent decades]. / Técnicas endoscópicas en carcinoma broncogénico. Cambios en las últimas décadas.

A 57-year old woman with arterial hypertension under treatment. She has smoked since she was 18 years old with an accumulated index of 70 years/pack. She was studied in our Respiratory Department due to constitutional syndrome, the X-ray showing an image of focal pulmonary lesion in the right upper lobe of more than 3cm of peripheral location. The computed tomography (CT) scan confirmed the existence of a 3.3cm mass in the upper right lobe and detected paratracheal and subcarinal mediastinal abnormal lymph nodes. A subsequent Positron Emission Tomography (PET) confirmed pathological uptake of the mass and both lymph node locations. Which additional studies do you consider to be indicated for a correct diagnosis and mediastinal staging? Do bronchoscopy techniques alone establish the final diagnosis and staging of this patient?

Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus.

It has been suggested that some glutamatergic synapses lack functional AMPA receptors. We used quantitative immunogold localization to determine the number and variability of synaptic AMPA receptors in the rat hippocampus. Three classes of synapses show distinct patterns of AMPA receptor content. Mossy fiber synapses on CA3 pyramidal spines and synapses on GABAergic interneurons are all immunopositive, have less variability, and contain 4 times as many AMPA receptors as synapses made by Schaffer collaterals on CA1 pyramidal spines and by commissural/ associational (C/A) terminals on CA3 pyramidal spines. Up to 17% of synapses in the latter two connections are immunonegative. After calibrating the immunosignal (1 gold = 2.3 functional receptors) at mossy synapses of a 17-day-old rat, we estimate that the AMPA receptor content of C/A synapses on CA3 pyramidal spines ranges from <3 to 140. A similar range is found in adult Schaffer collateral and C/A synapses.

Inhibitory synaptogenesis in the rat anteroventral cochlear nucleus.

Spherical cells in the anteroventral division of the cochlear nucleus, which relay excitatory inputs from the auditory nerve, also receive both GABAergic and glycinergic inhibitory synapses. Inhibition mediated by GABA and glycine fulfils essential roles in the processing abilities of these and other auditory neurons. However, the developmental program leading to a mature complement of GABAergic and glycinergic synapses and microcircuits is largely unknown. Because of their relatively simple geometry, spherical cells provide an excellent model for unraveling basic developmental patterns of inhibitory synaptogenesis. Using a combination of high resolution immunocytochemical methods, we report that, in the rat, synapses containing GABA or glycine are deployed on spherical cell bodies over a time period extending well beyond hearing onset. Such postnatal developmental recruitment of inhibitory endings is progressive, although there are two distinct leaps in their numbers. The first occurs by the end of the first postnatal week, prior to hearing onset, and the second, during the third postnatal week, after hearing onset. This pattern suggests that adjustments in inhibition could be driven by acoustic experience. While GABAergic and glycinergic endings are maturing and growing in number and size, their neurotransmitter content also appears to be developmentally regulated. Quantitative ultrastructural immunocytochemistry with colloidal gold suggests that GABA and glycine accumulation in synaptic endings follows a staggered pattern, with labeling stabilizing at adult levels by postnatal day 21. This may account for adjustments in synaptic efficacy and strength.

Static-dynamic sequential superheated liquid extraction of phenols and fatty acids from alperujo.

Superheated liquids of different polarity have been used for sequential extraction of fatty acids and phenols from alperujo. Multivariate methodology has been used to optimise the static-dynamic extraction. Forty-two minutes are required to complete extraction (20 mg/kg of fatty acids and up to 2,200 mg/kg of hydroxytyrosol in the raw material used). The efficacy of the extraction has been demonstrated and compared with that of conventional methods (Folch and stirring-based methods for fatty acids and phenols, respectively), which needed 4.5 and 24 h for the extraction of fatty acids and phenols, respectively. The non-polar and polar extracts were injected into GC-MS and HPLC-MS-MS equipment, respectively, for individual separation-quantification of the target compounds. The simplicity of the experimental setup and the low costs of the raw material make the proposed method advisable when extraction of both fractions is required.

Liquid-liquid extraction for the enrichment of edible oils with phenols from olive leaf extracts.

A liquid-liquid extraction method to enrich edible oils--olive, sunflower, and soy oils--with phenols from olive leaf extracts is proposed. After microwave assistance to remove the phenols from three varieties of olive leaves, concentrations in the extracts between 12921 and 5173 mg/L of oleuropein, between 488 and 192 mg/L of apigenin-7-glucoside, between 444 and 219 mg/L of luteolin-7-glucoside, and between 501 and 213 mg/L of verbascoside were obtained, which clearly depended on the target variety. After optimization of the liquid-liquid extraction step, the concentrations in oils were 442, 162, and 164 mg/L of oleuropein, respectively, which were also enriched in apigenin-7-glucoside (between 8 and 15 mg/L, depending of the oil), lutelin-7-glucoside (between 11 and 12 mg/L), and verbascoside (between 11 and 13 mg/L). The oil-extract distribution factor of these compounds was also calculated for all olive leaf varieties and edible oils using different extracts concentrations and also different oil-extract volume ratios. Thus, a door is open to enrichment of any oil with olive phenols at preset concentrations using extracts preconcentrated as required and taking into account the distribution factor of the target compounds between the oil and the extracts.

Target-cell-specific facilitation and depression in neocortical circuits.

In neocortical circuits, repetitively active neurons evoke unitary postsynaptic potentials (PSPs) whose peak amplitudes either increase (facilitate) or decrease (depress) progressively. To examine the basis for these different synaptic responses, we made simultaneous recordings from three classes of neurons in cortical layer 2/3. We induced repetitive action potentials in pyramidal cells and recorded the evoked unitary excitatory (E)PSPs in two classes of GABAergic neurons. We observed facilitation of EPSPs in bitufted GABAergic interneurons, many of which expressed somatostatin immunoreactivity. EPSPs recorded from multipolar interneurons, however, showed depression. Some of these neurons were immunopositive for parvalbumin. Unitary inhibitory (I)PSPs evoked by repetitive stimulation of a bitufted neuron also showed a less pronounced but significant difference between the two target neurons. Facilitation and depression involve presynaptic mechanisms, and because a single neuron can express both behaviors simultaneously, we infer that local differences in the molecular structure of presynaptic nerve terminals are induced by retrograde signals from different classes of target neurons. Because bitufted and multipolar neurons both formed reciprocal inhibitory connections with pyramidal cells, the results imply that the balance of activation between two recurrent inhibitory pathways in the neocortex depends on the frequency of action potentials in pyramidal cells.

Molecular cloning and characterization of recombinant parasite antigens for immunodiagnosis of onchocerciasis.

Immunological cross-reactivity among nematodes has hampered the development of specific serodiagnostic assays for onchocerciasis. In the present study, an Onchocerca volvulus adult worm complementary DNA expression library was differentially screened with human sera from patients infected with O. volvulus and with an omnibus anti-nematode serum pool comprised of sera from patients infected with Brugia malayi, Loa loa, Wuchereria bancrofti, Mansonella perstans, Strongyloides stercoralis, Ancylostoma duodenale, Ascaris lumbricoides, and Dracunculus medinensis. Seven Onchocerca-specific clones were identified and screened with individual onchocerciasis patient sera. Additional studies were performed to characterize the most immunoreactive clones, OC 3.6 and OC 9.3. OC 3.6 produced a 152-kD beta-galactosidase fusion protein that was recognized in dot-immunoblots by 54 of 55 sera from onchocerciasis patients (98%). The OC 3.6 DNA insert is 996 bp long with an open reading frame of 627 bp and a 369-bp untranslated 3' end. OC 3.6 is closely related to a previously reported clone (OV 33-3), but it differs from that clone at both the 5' and 3' ends. OC 9.3 contained a novel 565-bp insert and produced a 138-kD fusion protein that was recognized by 46 of 55 sera from onchocerciasis patients (83%). Additional studies are in progress to develop and evaluate immunodiagnostic tests for onchocerciasis based on measurement of antibodies to these promising recombinant antigens.

Small branches of olive tree: a source of biophenols complementary to olive leaves.

The extraction of biophenols (BPs) from small branches (fibrous softwood) of olive tree accelerated by microwave assistance is proposed for the first time. Under optimal working conditions, no further extraction of the target analytes was achieved after 10 min, so complete removal of them within this interval was assumed (amounts ca. to 19000, 1000, 2000, 900, and 700 mg/kg of oleuropein, verbascoside, tyrosol, alpha-taxifolin, and hydroxytyrosol, respectively; the three last BPs are absent in branch-free olive leaves). The extracts required no cleanup or concentration prior to injection into a chromatograph-photodiode array detector assembly for individual separation-quantification. Extraction from this raw material was also implemented in continuous and discontinuous-continuous extractors using ultrasound assistance and superheated liquids, respectively, as auxiliary energies, and the results were compared with those obtained by microwave-assisted extraction. The simultaneous extraction of small branches and leaves from olive tree provided extracts with a higher variety of BPs, but either extracts richer in oleuropein and verbascoside without tyrosol, alpha-taxifolin, and hydroxytyrosol or rich in these three BPs can be obtained by separate extraction of leaves and branches, respectively.

Ejercicio físico y disminución del peso y el índice de masa corporal en la cirugía bariátrica: una revisión sistemática / Physical exercise and loss of weight and body mass index in bariatric surgery: a systematic review

Introducción: la cirugía bariátrica se considera exitosa cuando el porcentaje de pérdida de peso es igual o superior al 25 % o bien cuando el porcentaje de pérdida de índice de masa corporal ocurre por encima del 50 % a largo plazo. Objetivo: analizar el efecto del ejercicio físico en el peso corporal y el índice de masa corporal antes y después de la cirugía bariátrica. Metodología: se buscaron artículos registrados en las bases de datos de PudMed, Scopus y Web of Science, de artículos originales con acceso abierto en inglés y español que compararan uno o varios programas de ejercicio físico como tratamiento antes y/o después de la cirugía bariátrica, con resultados de peso e índice de masa corporal inicial y final, masa muscular y masa grasa, de enero a abril de 2021. Resultados: se obtuvieron en total 730 artículos de las diferentes bases de datos y solo 7 se seleccionaron para el análisis. El ejercicio aerobio combinado con el entrenamiento de resistencia mostró una mayor disminución del porcentaje de peso perdido (% PP) y del porcentaje perdido de índice de masa corporal (% PIMC). Conclusiones: el ejercicio físico aerobio, en combinación con el entrenamiento de resistencia, es el programa más aplicado a los sujetos con cirugia bariátrica y los efectos más importantes son el aumento del porcentaje de pérdida de peso y la disminución del índice de masa corporal (AU)

Introduction: bariatric surgery is considered successful when the percentage of weight loss is equal to or higher than 25 %, or when the percentage loss of body mass index occurs above 50 % long-term. Objective: to analyze the effect of physical exercise on body weight and body mass index before and/or after bariatric surgery. Methodology: articles registered in the PudMed, Scopus and Web of Science databases were searched for original papers with open access in English and Spanish that compared one or more physical exercise programs as treatment before and/or after bariatric surgery, with results on initial and final weight and body mass index, muscle mass, and fat mass from January to April 2021. Results: a total of 730 articles were obtained in the different databases and only 7 were selected for the analysis. Aerobic exercise combined with resistance training showed a greater decrease in the percentage of weight loss (% PP) and the percentage of loss of body mass index (% PBMI). Conclusions: aerobic physical exercise in combination with endurance training is the most applied program in subjects with bariatric surgery, and the most important effects are an increase in percentage of weight loss and a decrease in body mass index (AU)

Superheated liquid extraction of oleuropein and related biophenols from olive leaves.

Oleuropein and other healthy olive biophenols (OBPs) such as verbacoside, apigenin-7-glucoside and luteolin-7-glucoside have been extracted from olive leaves by using superheated liquids and a static-dynamic approach. Multivariate methodology has been used to carry out a detailed optimisation of the extraction. Under the optimal working conditions, complete removal without degradation of the target analytes was achieved in 13 min. The extract was injected into a chromatograph-photodiode array detector assembly for individual separation-quantification. The proposed approach - which provides more concentrated extracts than previous alternatives - is very useful to study matrix-extractant analytes partition. In addition, the efficacy of superheated liquids to extract OBPs, the simplicity of the experimental setup, its easy automation and low acquisition and maintenance costs make the industrial implementation of the proposed method advisable.

Dynamic ultrasound-assisted extraction of oleuropein and related biophenols from olive leaves.

A continuous approach for the ultrasound-assisted extraction of olive biophenols (OBPs) from olive leaves is proposed. Multivariate methodology was used to carry out a detailed optimisation of extraction. Under the optimal working conditions, complete extraction of the target analytes (namely, oleuropein, verbacoside, apigenin-7-glucoside and luteolin-7-glucoside with LODs 11.04, 2.68, 1.49 and 3.91 mg/kg, respectively) was achieved in 25 min. The extract was injected into a chromatograph-photodiode array detector assembly (HPLC-DAD) for individual separation-quantification. No clean-up or preconcentration steps were required. Gas chromatography-mass spectrometry (without derivatization of the analytes) was used to identify OBPs at concentrations below the LODs obtained by HPLC-DAD. The efficacy of ethanol-water mixtures to extract OBPs from olive leaves has been demonstrated and compared with that of a conventional method which requires 24h for complete extraction; so these mixtures can substitute toxic extractants used to date.

Discrimination and classification of olive tree varieties and cultivation zones by biophenol contents.

The peak areas from a high-performance liquid chromatography-diode array (HPLC-DAD) analysis of biophenols extracted from olive leaves have been used as chemotaxonomic markers to construct chemometric models in order to discriminate and classify (1) 13 varieties of Olea europaea olive trees, namely, Alameño, Arbequina, Azulillo, Chorna, Hojiblanca, Lechín, Manzanillo, Negrillo, Nevadillo, Ocal, Pierra, Sevillano, and Tempranillo, from the same cultivation zone and (2) Arbequina samples from six different geoghaphical origins, namely, Córdoba, Mallorca (north and south), Ciudad Real, Lleida, and Navarra. Models based on principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used for discrimination between samples as a function of the tree varieties and cultivation zone, whereas K nearest neighbors (KNN) and soft independent modeling of class analogy (SIMCA) models were generated to classify the samples used to validate the models into one of the groups previously established by PCA and HCA. KNN classified correctly 93 and 92% of the samples into the variety and cultivation zone, respectively; meanwhile, the SIMCA models predicted 85 and 92%, respectively.

Linfangioleiomiomatosis. Similitudes y diferencias entre sus dos formas clínicas / Lymphangioleiomyomatosis. Similarities and differences between its two clinical forms

La linfangioleiomiomatosis (LAM) es una enfermedad pulmonar que se caracteriza por la proliferación de células musculares lisas atípicas en el pulmón y por la destrucción del tejido en forma de quistes. Existen dos formas clínicas de LAM, la esporádica (LAM-S) y la asociada a CET (LAM-CET), esta última es cinco veces más frecuente que la LAM-S, puede tener mutación tanto en el gen TSC1 o en el TSC2, mientras que la LAM-S solo en TSC2. La LAM-S es más sintomática, agresiva, presenta mayor ocupación quística, con peores valores en FEV1 y DLCO, menor número de NP (HMNM) y menor número de AML renales que la LAM-CET. No se han descrito diferencias en cuanto a la histología, fisiopatología, tipo de tratamiento o pronóstico

Lymphangioleiomyomatosis (LAM) is a lung disease characterized by the proliferation of atypical smooth muscle cells in the lung and the destruction of tissue in the form of cysts. There are two clinical forms of LAM, sporadic (LAM-S) and associated with TSC (LAM-CET), the latter is five times more frequent than LAM-S, it may have a mutation in both the TSC1 or TSC2 gene, while LAM-S only in TSC2 while LAM-S is more symptomatic and aggressive with greater cystic occupation, worse FEV1 and DLCO values, fewer pulmonary nodules (PN) and fewer renal AML than form LAM-CET. No differences have been described in terms of histology, pathophysiology, type of treatment or prognosis

Cambios en las indicaciones en la Unidad de Endoscopia Respiratoria del Hospital Universitario 12 de Octubre en los últimos años / Changes in the type of bronchoscopies in last years in the endoscopy respiratory unit of university hospital 12 octubre

Los objetivos de este trabajo son estudiar y valorar si han existido cambios en las indicaciones de broncoscopia en la Unidad de Endoscopia Respiratoria (UER) del Hospital Universitario (H.U.) 12 de Octubre en los últimos años, puesto que se han observado cambios epidemiológicos en distintas patologías respiratorias y se han incorporado nuevas técnicas endoscópicas. Por otra parte y dado que el trasplante pulmonar se introdujo en este hospital en el año 2008, también hemos valorado las diferencias en cuanto a las indicaciones de broncoscopia entre los pacientes sometidos a trasplante frente al resto en un segundo periodo de tiempo. Para realizar el estudio se ha utilizado la base de datos de la Unidad de Endoscopia Respiratoria del H.U. 12 de Octubre. Se han comparado pacientes de dos periodos de tiempo similares de 5 años: 2003-2008 vs. 2013-2018. En este último grupo se han valorado las diferencias entre los pacientes con trasplante pulmonar frente al resto. En los últimos cinco años se ha observado un mayor requerimiento de técnicas diagnósticas más complejas, una utilización mayoritaria de la sedación y un mayor número de pacientes en régimen hospitalario. Los pacientes con trasplante pulmonar tienen mayor necesidad de exploraciones urgentes y en régimen hospitalario, con mayor requerimiento de técnicas como la biopsia transbronquial y el lavado broncoalveolar. Por tanto como conclusión podemos decir que se han producido cambios en las indicaciones con una mayor complejidad en los últimos cinco años (AU)

Since epidemiologic changes regarding bronchogenic carcinoma had been related and new endoscopic techniques are available, one of the objectives of this study is evaluate the changes in bronchoscopy indications in the Unity of Respiratory Endoscopy of the H.U. 12 de Octubre. On the other hand, since lung transplantation has been introduced in H.U. 12 de Octubre in 2008, another objective is evaluate the differences related to bronchoscopy indication between patients with lung transplantation and not. We have used the database from the Unity of Respiratory Endoscopy of the H.U. 12 de Octubre. We have compared patients from two different periods: 2003-2008 (Period 1) and 2013-2018 (Period 2). We have also evaluated the differences between lung transplantation and not during period 2. Along the last five years we have related the following changes: a larger requirement of diagnostic techniques (TBP, BAL), a main use of sedation and a larger number of patients under hospital admission. As a conclusion, the bronchoscopy has become more complex. Patients with lung transplantation have more necessity of urgent examination under hospital admission and a larger request of specific techniques such as transbronchial biopsy and bronchoalveolar lavage. Therefore, this patients had entailed changes in the complexity if the bronchoscopy techniques in the last five years (AU)

Galactomannan in bronchoalveolar lavage fluid for diagnosis of invasive aspergillosis in non-hematological patients.

BACKGROUND: The role of galactomannan (GM) in serum or bronchoalveolar lavage fluid (BALF) for the diagnosis of invasive pulmonary aspergillosis (IPA) has been extensively evaluated in hematological patients, however its performance in non-hematological patients is not well established. METHODS: We performed a multicenter retrospective study in 3 university hospitals in Madrid, Spain between 2010 and 2014. The study population comprised patients with chronic obstructive pulmonary disease (COPD) and patients with immunosuppressive conditions in whom IPA was suspected and for whom BALF GM was available. Patients with hematological disorders were excluded. RESULTS: A total of 188 patients (35 with COPD and 153 with immunosuppressive conditions) were analyzed, and 31 cases of IPA (proven or probable) were identified. The global sensitivity of BALF GM (optical density index [ODI] ≥ 1.0) was 77.4%; sensitivity was higher in patients with immunosuppressive conditions than in patients with COPD (81.8% vs 66.7%; p: 0.38). In COPD patients, the best performance was obtained for BALF GM (ODI ≥ 0.5), although sensitivity (88.9%) was similar to that of BALF fungal culture (88.9%). The sensitivity of GM in serum was very poor in both populations (36.4% and 11.6%, respectively). CONCLUSIONS: In the present series, the diagnostic performance of BALF GM was good for IPA in non-hematological patients, especially in patients with immunosuppressive conditions.

Glutamate and GABA receptor signalling in the developing brain.

Our understanding of the role played by neurotransmitter receptors in the developing brain has advanced in recent years. The major excitatory and inhibitory neurotransmitters in the brain, glutamate and GABA, activate both ionotropic (ligand-gated ion channels) and metabotropic (G protein-coupled) receptors, and are generally associated with neuronal communication in the mature brain. However, before the emergence of their role in neurotransmission in adulthood, they also act to influence earlier developmental events, some of which occur prior to synapse formation: such as proliferation, migration, differentiation or survival processes during neural development. To fulfill these actions in the constructing of the nervous system, different types of glutamate and GABA receptors need to be expressed both at the right time and at the right place. The identification by molecular cloning of 16 ionotropic glutamate receptor subunits, eight metabotropic glutamate receptor subtypes, 21 ionotropic and two metabotropic GABA receptor subunits, some of which exist in alternatively splice variants, has enriched our appreciation of how molecular diversity leads to functional diversity in the brain. It now appears that many different types of glutamate and GABA receptor subunits have prominent expression in the embryonic and/or postnatal brain, whereas others are mainly present in the adult brain. Although the significance of this differential expression of subunits is not fully understood, it appears that the change in subunit composition is essential for normal development in particular brain regions. This review focuses on emerging information relating to the expression and role of glutamatergic and GABAergic neurotransmitter receptors during prenatal and postnatal development.

Rotura traqueal iatrogénica en paciente con COVID-19 resuelta con manejo conservador / Iatrogenic tracheal rupture in COVID 19 patient solved with conservative management

El síndrome de distrés respiratorio del adulto por SARS-CoV-2 ha sido una de las causas de requerimiento de intubación orotraqueal (IOT) en pacientes con insuficiencia respiratoria grave. En los pacientes ingresados en la Unidad de Cuidados Intensivos (UCI) con dificultad para la desconexión de ventilación mecánica invasiva, se considera la traqueostomía como una opción terapéutica para la progresión respiratoria. La traqueostomía percutánea es una técnica que ofrece varias ventajas en comparación con la quirúrgica, es más rápida, más barata y tiene menos complicaciones de forma global, si bien es cierto que presenta mayor riesgo de laceración o rotura traqueal. Presentamos un caso de rotura traqueal en paciente con neumonía grave SARS-CoV-2 tras traqueostomía percutánea resuelta con manejo conservador y una revisión de la literatura

SDRA secondary due to SARS-Cov 2 infection is one of the causes of tracheal intubation. In patients with acute respiratory failure. In ICU patientes with difficcult weaning of mechanical ventilation tracheostomy is one of the therapeutic approach. Percutaneous tracheostomy have so many advantages instead of surgical tracheostomy wiht less complications rate, cheaper and quicker. One of the complications of this technique is the risk of tracheal rupture. We present a case of tracheal rupture in a patient with severe SARS- Cov-2 pneumonia secondary a percutaneous tracheostomy solved with conservative management and a literatura review