Spontaneous neural activity is a basic property of the developing brain, which regulates key developmental processes, including migration, neural differentiation and formation and refinement of ...connections. The mechanisms regulating spontaneous activity are not known. By using transgenic embryos that overexpress BDNF under the control of the nestin promoter, we show here that BDNF controls the emergence and robustness of spontaneous activity in embryonic hippocampal slices. Further, BDNF dramatically increases spontaneous co-active network activity, which is believed to synchronize gene expression and synaptogenesis in vast numbers of neurons. In fact, BDNF raises the spontaneous activity of E18 hippocampal neurons to levels that are typical of postnatal slices. We also show that BDNF overexpression increases the number of synapses at much earlier stages (E18) than those reported previously. Most of these synapses were GABAergic, and GABAergic interneurons showed hypertrophy and a 3-fold increase in GAD expression. Interestingly, whereas BDNF does not alter the expression of GABA and glutamate ionotropic receptors, it does raise the expression of the recently cloned K(+)/Cl(-) KCC2 co-transporter, which is responsible for the conversion of GABA responses from depolarizing to inhibitory, through the control of the Cl(-) potential. Together, results indicate that both the presynaptic and postsynaptic machineries of GABAergic circuits may be essential targets of BDNF actions to control spontaneous activity. The data indicate that BDNF is a potent regulator of spontaneous activity and co-active networks, which is a new level of regulation of neurotrophins. Given that BDNF itself is regulated by neuronal activity, we suggest that BDNF acts as a homeostatic factor controlling the emergence, complexity and networking properties of spontaneous networks.
We examined heterozygous transgenic (Tg) mice that overexpress V717F amyloid precursor protein (APP) for delay eyeblink conditioning (EBC) and hippocampal volume with magnetic resonance imaging ...(MRI). Platelet-derived APP mice were significantly impaired on EBC relative to wild type (WT) litter-mate controls. T2-weighted spin echo images (62.5 × 125 × 500 μm) of the same mice were acquired under anesthesia using a 9.4T magnet. Tg mice had hippocampal to brain volume ratios that were significantly smaller than WT controls (31% smaller in the rostral dorsal hippocampus, 13–22% smaller among equal dorsal–ventral thirds of a caudal section). These results indicate that overexpression of APP or beta amyloid profoundly affects learning and memory and hippocampal volume. The results also indicate that eyeblink conditioning and quantitative MRI in mice may be useful assays to follow the progression of disease-related changes, and to test the effectiveness of potential therapeutics against Alzheimer's disease.
Resumen: Los estudiantes de medicina necesitan adquirir una serie de conocimientos, habilidades y actitudes que les capaciten para el desempeño de la medicina. La facultad de Medicina de la ...Universidad Miguel Hernández de Elche incluyó en su plan de estudios del Grado en Medicina 4 asignaturas denominadas «talleres integrados» en las que se desarrollan diversas actividades docentes para integrar conocimientos y habilidades clínicas de varias disciplinas y fomentar la adquisición de competencias transversales. En este artículo describimos la organización y métodos didácticos empleados en la asignatura «Talleres integrados II» como un elemento de reflexión para compartir la experiencia con la comunidad educativa en medicina. Esta asignatura integra las siguientes materias: bases generales de la cirugía, farmacología clínica, patología general, inmunología y alergia, dermatología, epidemiología y demografía sanitaria, microbiología, obstetricia y oftalmología. Es una asignatura con 4,5 créditos prácticos y utiliza elementos docentes como práctica hospitalaria guiada por objetivos, participación de alumnos y talleres prácticos, simulación, prueba evaluación de competencias objetiva estructurada, y presentación clínica en formato Pecha Kucha, lo que potencia la integración de conocimientos y el aprendizaje activo con adquisición de competencias y habilidades prácticas muy pertinentes para el futuro médico. Abstract: Medical students need to acquire a range of knowledge, skills, and attitudes that will prepare them for medical clinical practice. The School of Medicine of Miguel Hernández University (Elche, Spain) includes, in its Medical Degree curriculum, 4 subjects called “Talleres integrados” (Integrated Workshops-II). Diverse teaching activities are developed to integrate knowledge and clinical skills of several disciplines, and to promote the acquisition of transversal skills. A description is presented of the organisation and didactic methods used in the Integrated Workshops-II subject as an element for reflection and to share the experience with the educational community in medicine. This subject integrates the following: general bases of surgery, clinical pharmacology, general pathology, immunology and allergy, dermatology, epidemiology and health demography, microbiology, obstetrics and ophthalmology. It is a subject with 4.5 practical credits and uses teaching elements such as hospital practice guided by objectives, student participation and practical workshops, simulation, objective structured clinical examination (OSCE), and presentation of cases in Pecha Kucha format, all of which enhances the integration of knowledge and active learning with acquisition of skills and practical skills very pertinent for the future doctor. Palabras clave: Talleres integrados, Enseñanza, Medicina, Competencias, Evolución Clínica Objetiva Estructurada, Portafolio, Keywords: Integrated workshops, Teaching, Medicine, Competencies, Objective Structured Clinical Examination, Portfolio
Background. The benefit of the combination of serum galactomannan (GM) assay and polymerase chain reaction (PCR)–based detection of serum Aspergillus DNA for the early diagnosis and therapy of ...invasive aspergillosis (IA) in high-risk hematological patients remains unclear. Methods. We performed an open-label, controlled, parallel-group randomized trial in 13 Spanish centers. Adult patients with acute myeloid leukemia and myelodysplastic syndrome on induction therapy or allogeneic hematopoietic stem cell transplant recipients were randomized (1:1 ratio) to 1 of 2 arms: "GM-PCR group" (the results of serial serum GM and PCR assays were provided to treating physicians) and "GM group" (only the results of serum GM were informed). Positivity in either assay prompted thoracic computed tomography scan and initiation of antifungal therapy. No antimold prophylaxis was permitted. Results. Overall, 219 patients underwent randomization (105 in the GM-PCR group and 114 in the GM group). The cumulative incidence of "proven" or "probable" IA (primary study outcome) was lower in the GM-PCR group (4.2% vs 13.1%; odds ratio, 0.29 95% confidence interval, .09–.91). The median interval from the start of monitoring to the diagnosis of IA was lower in the GM-PCR group (13 vs 20 days; P = .022), as well as the use of empirical antifungal therapy (16.7% vs 29.0%; P = .038). Patients in the GM-PCR group had higher proven or probable IA–free survival (P = .027). Conclusions. A combined monitoring strategy based on serum GM and Aspergillus DNA was associated with an earlier diagnosis and a lower incidence of IA in high-risk hematological patients.
Abstract
Background
Interpreting patient phenotypes is a challenge when screening for hypertrophic cardiomyopathy (HCM). Machine learning (ML) can potentially help with advanced data integration - ...combining information contained in whole-cardiac cycle echo deformation and velocity profiles with standard clinical variables. The aim is to apply an ML approach to integrate whole cardiac cycle echo data with clinical variables to explore HCM phenotypes.
Methods
The cohort consisted of 138 participants from two centres: HCM patients (n=91) and relatives (n=47). Echocardiography was performed, whereas magnetic resonance and genetic testing in 48% and 82%, respectively. Whole cardiac cycle echo data (mitral and aortic velocity profiles, and six regional left ventricular (LV) deformation curves) were combined with clinical variables (age, sex, heart rate, e' medial and e' lateral) and used as the ML input. An unsupervised ML algorithm created a representative space where participants were positioned based on integrated data, blinded to disease status. Clustering was used to determine phenogroups and estimate the average characteristics. Data on family history (FHx), genotype, arrhythmias or syncope, implantable cardioverter-defibrillators (ICD), and late gadolinium enhancement (LGE) were used to interpret the phenogroups. As the LA diameter was not available in the dataset, the HCM risk for sudden cardiac death (SCD) was not calculated, however, the Table shows relevant variables to infer clinical risk.
Results
Clustering divided the participants into 6 phenogroups (P1–6) (Figure). Average echo profiles are shown in the Figure, while the clinical data in the Table. P1/2 was defined by symptomatic patients with a high prevalence of positive genotypes, a positive FHx of SCD, and a burden of comorbidities. Echo findings showed pronounced structural/functional remodeling, and P1 was associated with severe septal hypertrophy and outflow tract obstruction. The high prevalence of ICD devices defined P1/2 as high risk groups. In comparison, patients in P3/4 were younger, with milder LV hypertrophy, but still considerable functional impairment. P3 had a higher burden of FHX and a higher prevalence of pathogenic mutations, whereas P4 a higher incidence of hypertension, high heart rate, mitral inflow fusion and findings of LGE. Finally, P5/6 consisted of younger individuals, predominantly HCM relatives, with a mild phenotype and, thus, low inferred risk. As expected, the majority of patients with the genetic variants of undetermined significance were located in P5.
Conclusion
ML can help derive clinically interpretable phenotypes in HCM based on the automated integration of whole cardiac cycle deformation and velocity data with conventional clinical parameters. The derived phenogroups correspond with established risk profiles in HCM. An expanded dataset is needed to enable further exploration of the phenotype-genotype relations and to define prognostic value.
Funding Acknowledgement
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported by the Horizon 2020 European Commission Project H2020-MSCA-ITN
Erector spinae plane block for thoracoscopy in a paediatric patient Aguado La Iglesia, I.; Granacher, P.P.; Manzano Lorefice, M.F. ...
Revista española de anestesiología y reanimación (English ed.),
December 2022, 2022-Dec, 2022-12-00, Letnik:
69, Številka:
10
Journal Article
We present the case of a 9 year old patient with a clinical history of epilepsy and various hospitalizations due to aspirative broncopneumonia among others, who was admitted to our hospital because ...of septic shock secondary to pneumonia of the lower left lobule associated with a parapneumonic pleural effusion and a complicated clinical course. During her stay, the patient undergoes surgical debridement using video assisted thoracoscopic surgery (VATS) under general anaesthesia and the hydropneumothorax is drained. For the procedure an ecoguided erector spinae plane block is performed and combined with general anaesthesia. On one hand this block permitted reduction of perioperative opioid administration and improved the patient's respiration, on the other hand it permitted avoiding the use of drugs, which can lower seizure threshold and increase the risk of convulsions. This case illustrates the importance of locoregional anaesthesia, a technique on the rise in the field of paediatric anaesthesia.
Presentamos el caso de una paciente de 9 años, con antecedentes de epilepsia y múltiples ingresos por bronconeumonía aspirativa entre otros, que ingresa en nuestro centro por shock séptico secundario a neumonía en lóbulo inferior izquierdo y derrame pleural paraneumónico, con mala evolución. Durante su ingreso, se interviene bajo anestesia combinada para desbridamiento quirúrgico por videotoracoscopia y colocación de drenaje en hidroneuomotórax izquierdo complicado. Para la intervención, se realiza un bloqueo del plano del músculo erector de la espina ecoguiado, junto a una anestesia general. Este bloqueo, permitió por un lado disminuir la dosis de opioides postoperatorios, mejorando la ventilación de la paciente; y por otro lado, evitó el uso de diversos fármacos que podían disminuir el umbral epileptógeno y aumentar el riesgo de sufrir una convulsión. Este caso, demuestra la importancia de la anestesia locorregional en el paciente pediátrico, un arma anestésica en auge.
Abstract
Currently accuracy of manufacturing machines is a must. Verification is the main way to obtain it; highlighting the volumetric verification as the best technique to improve machine tool ...position accuracy along all its workspace in the shortest time possible. In this way, different measurements based on multilateration techniques like laser tracker and laser tracer are used. This paper studies how characteristics of a new high precision telescopic system consisting in three lines, with measuring principle based on simultaneous laser affect multilateration accuracy to obtain 3D coordinates. The paper analyses instrument characterising both the design, the components and their operation. Moreover, tests carried out study how instruments behavior affect to the accuracy of data capture using analytical and optimization techniques, proving an error estimation depending on the technique used.
•CaCl2-extractable Cu was correlated with dissolved organic carbon.•CaCl2-extractable concentrations did not correlate with metal uptake.•Pinus halepensis may be used to phytostabilise metal polluted ...soils in semiarid areas.•Areas surrounding tailings were impacted by high metal(loid) concentrations.
Tailings are frequently source of pollution in mining areas due to the spread of metal(loid)s from their bare surfaces via wind, water run-off and/or leaching. For this reason, areas surrounding tailings may be affected by high concentrations of those toxic chemical elements. The aim of this study was to determine the influence of soil parameters on metal availability in a Mediterranean forest affected by mining contamination and the potential employment of Pinus halepensis as a suitable plant species for phytostabilising mining polluted sites under semiarid climates. Five tailing sites, including their surroundings were selected. At the same sampling area, additional soil samples were taken in less impacted zones (up to 1km and 3km far from tailings). The highest total concentrations occurred indistinctly at some forest samples closed to tailings (e.g. ∼12,000mgkg−1 Pb) or tailing ones (∼790mgkg−1 As). The alkaline soil pH and some carbonate minerals conditions low CaCl2-extractable metal(loid) concentrations and therefore low risk of pollutants leaching. CaCl2-extractable As and metal concentrations did not correlate with the corresponding concentrations in pine needles indicating that this procedure might not be suitable to predict metal(loid) availability in pine trees. Needles of pine trees from the less impacted areas showed lower Mn and Zn concentrations (40–100mgkg−1 Mn, 25–55mgkg−1 Zn) in relation with the ones taken from the tailings. P. halepensis Miller looks a suitable plant species to be employed in the phytostabilisation of tailings due to the higher root systems, which may provided a better soil retention, and its relative low metal accumulation.
There is limited information about clinical consequences of respiratory virus infections (RVI) in solid organ transplant recipients. No prospective epidemiological study has been published ...previously.
We selected a cohort of 152 transplant recipients (cardiac, hepatic and renal transplant recipients). Median time from transplantation was 17 months (range 1-50). They were prospectively followed-up for RVI during 7 months (October to April). Clinical and microbiological evaluation (cell culture, shell vial and polymerase chain reaction technique) of each RVI episode was made.
We detected 81 RVI (0.91 episodes/patient/year). Complications were detected in 15/81 episodes (18.5%): acute bronchitis (10 cases), pneumonia (three cases; 3.7% of RVI episodes) and bacterial sinusitis (2 cases). In 4 of 81 episodes (5%), patients needed hospitalization. A respiratory virus was isolated in 17 of 68 nasopharyngeal samples (six respiratory syncytial virus, six influenza, four picornavirus, one adenovirus). Fever presented an 83% positive predictive value for the diagnosis of influenza virus infection among those with a positive microbiological isolation. There were no episodes of acute rejection coincidentally with RVI. Only 54% of the subjects had been previously vaccinated against influenza.
Incidence of RVI among solid organ transplant recipients is similar to general population but complications are higher. A relationship between RVI and rejection was not detected. The rate of influenza vaccination was lower than expected. The presence of fever in a transplant recipient with RVI strongly suggests influenza infection.
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