Revisiting nonclassical HLA II functions in antigen presentation: Peptide editing and its modulation

The nonclassical major histocompatibility complex of class II molecules (ncMHCII) HLA-DM (DM) and HLA-DO (DO) feature essential functions for the selection of the peptides that are displayed by classical MHCII proteins (MHCII) for CD4(+)T(h)cell surveillance. Thus, although the binding groove of classical MHCII dictates the main features of the peptides displayed, ncMHCII function defines the preferential loading of peptides from specific cellular compartments and the extent to which they are presented. DM acts as a chaperone for classical MHCII molecules facilitating peptide exchange and thereby favoring the binding of peptide-MHCII complexes of high kinetic stability mostly in late endosomal compartments. DO on the other hand binds to DM blocking its peptide-editing function in B cells and thymic epithelial cells, limiting DM activity in these cellular subsets. DM and DO distinct expression patterns therefore define specific antigen presentation profiles that select unique peptide pools for each set of antigen presenting cell. We have come a long way understanding the mechanistic underpinnings of such distinct editing profiles and start to grasp the implications for ncMHCII biological function. DM acts as filter for the selection of immunodominant, pathogen-derived epitopes while DO blocks DM activity under certain physiological conditions to promote tolerance to self. Interestingly, recent findings have shown that the unexplored and neglected ncMHCII genetic diversity modulates retroviral infection in mouse, and affects human ncMHCII function. This review aims at highlighting the importance of ncMHCII function for CD4(+)T(h)cell responses while integrating and evaluating what could be the impact of distinct editing profiles because of natural genetic variations

“Causas que generan la conducta rebelde de los estudiantes del Instituto Nacional de Educación Básica de San Lorenzo”.

Rebellion is not an issue that is considered recent, has always been present for generations, parents have had to deal with these problems, based on the experience acquired in childhood. When the child becomes an adult, he faces a period of physical and mental changes that can make this time the best or worst for both the teen and the parents. This change is called adolescence is marked by the growth and development of the body and reproductive organs. Physical growth presents teen voice changes, muscle growth and development of certain glands in the body. In men it is common to notice the voice change, broadening the shoulders and the growth of pubic hair. In the ladies breast growth occurs, hips like weight and size, also appears the first period. With the onset of first menstruation in adolescents, it sets the tone for the girl entered his sexual reproductive stage; although it is an early stage because it needs certain internal body parts come in top condition. The psychological changes are marked in the manner of conduct now teenagers, anxiety disorders can show shyness and the worst, default. It is therefore important to know what are the causes of this rebellion, to work them properly, thus achieving sensitize the future adult. It is vital to show the teenager who has the full support of parents, making them feel wanted and loved. It is also good to create that bond between parent and child. thousands of ways in which you can raise young people may exist, but depend on the method you choose

Comparative analysis of income trends and perceived value of squad of the highest turnover European football clubs (2010-2019)

The purpose was to analyse the income variation of the 13 top clubs of Deloitte Football Money League Report (2019) as well as the variation of the perceived value of their squad, obtained from the website www.transfermarkt.es during 9 seasons. Friedman's two-way analysis by ranges of selected samples and Wilcoxon W tests were used to measure the evolution and relation among the clubs’ income and perceived value of players. The income of clubs was deflected according to inflation (CPI: 2016) and market value was adjusted to a 20 players squad. Market value and income have a significant positive variation from one year to the next (p = .000). We found differences between both variables only in the last 2 years on the period analysed (2011-2019). Market value has suffered an increase higher than expected. This fact should make football managers reflect on how to control constant inflation in the transfer market

Biomechanical Loading as an Alternative Treatment for Tremor: A Review of Two Approaches

Background: Tremor is the most common movement disorder and strongly increases in incidence and prevalence with aging. Although not life threatening, upper-limb tremors hamper the independence of 65% of people suffering from them affected persons, greatly impacting their quality of life. Current treatments include pharmacotherapy and surgery (thalamotomy and deep brain stimulation). However, these options are not sufficient for approximately 25% of patients. Therefore, further research and new therapeutic options are required to effectively manage pathological tremor. Methods: This paper presents findings of two research projects in which two different wearable robots for tremor management were developed based on force loading and validated. The first consisted of a robotic exoskeleton that applied forces to tremulous limbs and consistently attenuated mild and severe tremors. The second was a neuroprosthesis based on transcutaneous neurostimulation. A total of 22 patients suffering from parkinsonian or essential tremor (ET) of different severities were recruited for experimental validation, and both systems were evaluated using standard tasks employed for neurological examination. The inclusion criterion was a postural and/or kinetic pathological upper-limb tremor resistant to medication. Results: The results demonstrate that both approaches effectively suppressed tremor in most patients, although further research is required. The work presented here is based on clinical evidence from a small number of patients (n = 10 for robotic exoskeleton and n = 12 for the neuroprosthesis), but most had a positive response to the approaches. In summary, biomechanical loading is non-invasive and painless. It may be effective in patients who are insufficiently responsive (or have adverse reactions) to drugs or in whom surgery is contraindicated. Discussion: This paper identifies and evaluates biomechanical loading approaches to tremor management and discusses their potential

Pulmonary artery mycotic aneurism owing to aspergillus in SARS-CoV-2 convalescent: a case report and literature review

Invasive aspergillosis is a severe illness described in immune-compromised and critically ill non-immuno-compromised patients. Aspergillosis and COVID-19 co-infection cases harbor multiple unfavorable prognostic factors, with a 44% mortality versus 19% without aspergillosis. We presented the case of a 61-year-old man known with hypertension, diabetes, and smoking that went through COVID-19 infection, during the convalescent period presented multiple hemoptoic events due to A. fumigatus mycotic pseudoaneurysm, successfully resolved by selective angioembolization. Selective angioembolization is an effective alternative for high surgical risk due to comorbidities in the treatment of pulmonary mycotic aneurism

Laparoscopic limited liver resection decreases morbidity irrespective of the hepatic segment resected

AbstractObjectivesThe laparoscopic approach is widely used in abdominal surgery. However, the benefits of laparoscopy in liver surgery have hitherto been insufficiently established. This study sought to investigate these benefits and, in particular, to establish whether or not the laparoscopic approach is beneficial in patients with lesions involving the posterosuperior segments of the liver.MethodsOutcomes in a cohort of patients undergoing mostly minor hepatectomy (50 laparoscopic and 52 open surgery procedures) between January 2000 and December 2010 at the University Clinic of Navarra were analysed. The two groups displayed similar clinical characteristics.ResultsPatients submitted to laparoscopic liver resection (LLR) had a lower risk for complications [odds ratio (OR) = 0.24, 95% confidence interval (CI) 0.07–0.74; P = 0.013] and shorter hospital stay (OR = 0.08, 95% CI 0.02–0.27; P < 0.001) independently of the presence of classical risk factors for complications. In the cohort of patients with lesions involving posterosuperior liver segments (20 laparoscopic, 21 open procedures), LLR was associated with significantly fewer complications (OR = 0.16, 95% CI 0.04–0.71) and a lower risk for a long hospital stay (OR = 0.1, 95% CI 0.02–0.43).ConclusionsThis study confirms that the laparoscopic approach to hepatic resection decreases the risk for post-surgical complications and lengthy hospitalization in patients undergoing minor liver resections. This beneficial effect is observed even in patients with lesions located in segments that require technically difficult resections

A Multi-Peer, Low Cost Immersive Communication System for Pandemic Times

Porceeding of: 28th IEEE Conference on Virtual Reality and 3D User Interfaces (IEEE VR 3D UI Contest), March 27-April 3, 2021, VirtualThis work has been partially supported by the Spanish Administration Agency CDTI under Project IDI-20200225 (TARDIS). This work has also received funding from the European Union (EU) Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie ETN TeamUp5G, grant agreement No. 813391

KV1.5–KV 1.3 Recycling Is PKC-Dependent

KV1.5 channel function is modified by different regulatory subunits. KVβ1.3 subunits assemble with KV1.5 channels and induce a fast and incomplete inactivation. Inhibition of PKC abolishes the KVβ1.3-induced fast inactivation, decreases the amplitude of the current KV1.5–KVβ1.3 and modifies their pharmacology likely due to changes in the traffic of KV1.5–KVβ1.3 channels in a PKC-dependent manner. In order to analyze this hypothesis, HEK293 cells were transfected with KV1.5–KVβ1.3 channels, and currents were recorded by whole-cell configuration of the patch-clamp technique. The presence of KV1.5 in the membrane was analyzed by biotinylation techniques, live cell imaging and confocal microscopy approaches. PKC inhibition resulted in a decrease of 33 ± 7% of channels in the cell surface due to reduced recycling to the plasma membrane, as was confirmed by confocal microscopy. Live cell imaging indicated that PKC inhibition almost abolished the recycling of the KV1.5–KVβ1.3 channels, generating an accumulation of channels into the cytoplasm. All these results suggest that the trafficking regulation of KV1.5–KVβ1.3 channels is dependent on phosphorylation by PKC and, therefore, they could represent a clinically relevant issue, mainly in those diseases that exhibit modifications in PKC activity.This research was funded by Ministerio de Ciencia e Innovación (MICINN) Spain SAF2016-75021-R and PID2019-104366RB-C21 (to C.V. and T.G.), the Instituto de Salud Carlos III CIBERCV program CB/11/00222 (to C.V.), and the Consejo Superior de Investigaciones Científicas grants: PIE 201820E104 and 2019AEP148 (to C.V.). The cost of this publication was paid in part by funds from the European Fund for Economic and Regional Development (FEDER). A.M. holds a postdoctoral contract at CNIC. A.d.l.C. and D.A.P. held CSIC contracts. A.d.B.-B. holds an MICINN predoctoral contract (BES-2017-080184

Diffusion tensor imaging in orthostatic tremor: a tract‐based spatial statistics study

[Abstract] Objective The pathogenesis of orthostatic tremor (OT) is unknown. We investigated OT‐related white matter changes and their correlations with scores from a neuropsychological testing battery. Methods Diffusion tensor imaging measures were compared between 14 OT patients and 14 age‐ and education‐matched healthy controls, using whole‐brain tract‐based spatial statistics analysis. Correlations between altered diffusion metrics and cognitive performance in OT group were assessed. Results In all cognitive domains (attention, executive function, visuospatial ability, verbal memory, visual memory, and language), OT patients’ cognitive performance was significantly worse than that of healthy controls. OT patients demonstrated altered diffusivity metrics not only in the posterior lobe of the cerebellum (left cerebellar lobule VI) and in its efferent cerebellar fibers (left superior cerebellar peduncle), but also in medial lemniscus bilaterally (pontine tegmentum), anterior limb of the internal capsule bilaterally, right posterior limb of the internal capsule, left anterior corona radiata, right insula, and the splenium of corpus callosum. No relationship was found between diffusion measures and disease duration in OT patients. Diffusion white matter changes, mainly those located in right anterior limb of the internal capsule, were correlated with poor performance on tests of executive function, visuospatial ability, verbal memory, and visual memory in OT patients. Interpretation White matter changes were preferentially located in the cerebellum, its efferent pathways, as well as in the pontine tegmentum and key components of the frontal–thalamic–cerebellar circuit. Further work needs to be done to understand the evolution of these white matter changes and their functional consequences.National Institutes of Health; R01 NS39422National Institutes of Health; R01 NS094607National Institutes of Health; R01 NS085136National Institutes of Health; R01 NS073872National Institutes of Health; R01 NS088257European Commission. Grant Number: ICT‐2011‐287739Ministerio de Ecnomía y Competitividad; RTC‐2015‐3967‐1Spanish Health Research Agency; FIS PI12/01602Spanish Health Research Agency; FIS PI16/00451Ministerio de Ecnomía y Competitividad; DPI‐2015‐68664‐C4‐1‐