Kidins220 sets the threshold for survival of neural stem cells and progenitors to sustain adult neurogenesis

In the adult mammalian brain, neural stem cells (NSCs) located in highly restricted niches sustain the generation of new neurons that integrate into existing circuits. A reduction in adult neurogenesis is linked to ageing and neurodegeneration, whereas dysregulation of proliferation and survival of NSCs have been hypothesized to be at the origin of glioma. Thus, unravelling the molecular underpinnings of the regulated activation that NSCs must undergo to proliferate and generate new progeny is of considerable relevance. Current research has identified cues promoting or restraining NSCs activation. Yet, whether NSCs depend on external signals to survive or if intrinsic factors establish a threshold for sustaining their viability remains elusive, even if this knowledge could involve potential for devising novel therapeutic strategies. Kidins220 (Kinase D-interacting substrate of 220 kDa) is an essential effector of crucial pathways for neuronal survival and differentiation. It is dramatically altered in cancer and in neurological and neurodegenerative disorders, emerging as a regulatory molecule with important functions in human disease. Herein, we discover severe neurogenic deficits and hippocampal-based spatial memory defects accompanied by increased neuroblast death and high loss of newly formed neurons in Kidins220 deficient mice. Mechanistically, we demonstrate that Kidins220-dependent activation of AKT in response to EGF restraints GSK3 activity preventing NSCs apoptosis. We also show that NSCs with Kidins220 can survive with lower concentrations of EGF than the ones lacking this molecule. Hence, Kidins220 levels set a molecular threshold for survival in response to mitogens, allowing adult NSCs growth and expansion. Our study identifies Kidins220 as a key player for sensing the availability of growth factors to sustain adult neurogenesis, uncovering a molecular link that may help paving the way towards neurorepair

Viruses and Mycoplasma pneumoniae are the main etiological agents of community-acquired pneumonia in hospitalized pediatric patients in Spain

[Objectives]: To describe the etiology of community-acquired pneumonia (CAP) in hospitalized children in Spain and analyze the predictors of the etiology.[Hypothesis]: The different etiological groups of pediatric CAP are associated with different clinical, radiographic, and analytical data.[Design]: Observational, multicenter, and prospective study.[Patient selection]: This study included children aged 1 month to 17 years with CAP, who were hospitalized between April 2012 and May 2019.[Methods]: An extensive microbiological workup was performed. The clinical, radiographic, and analytical parameters were analyzed for three etiological groups.[Results]: Among the 495 children included, at least one causative pathogen was identified in 262 (52.9%): pathogenic viruses in 155/262 (59.2%); atypical bacteria (AB), mainly Mycoplasma pneumonia, in 84/262 (32.1%); and typical bacteria (TyB) in 40/262 (15.3%). Consolidation was observed in 89/138 (64.5%) patients with viral CAP, 74/84 (88.1%) with CAP caused by AB, and 40/40 (100%) with CAP caused by TyB. Para-pneumonic pleural effusion (PPE) was observed in 112/495 (22.6%) patients, of which 61/112 (54.5%) presented a likely causative pathogen: viruses in 12/61 (19.7%); AB in 23/61 (37.7%); and TyB in 26/61 (42.6%). Viral etiology was significantly frequent in young patients and in those with low oxygen saturation, wheezing, no consolidation, and high lymphocyte counts. CAP patients with AB as the etiological agent had a significantly longer and less serious course as compared to those with other causative pathogens.[Conclusions]: Viruses and M. pneumoniae are the main causes of pediatric CAP in Spain. Wheezing, young age, and no consolidation on radiographs are indicative of viral etiology. Viruses and AB can also cause PPE. Since only a few cases can be directly attributed to TyB, the indications for antibiotics must be carefully considered in each patient.Instituto de Investigación Hospital 12 de Octubre (i+12), Grant/Award Number: AY191212‐1; Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and co‐funded by the European Regional Development Funds, Grant/Award Number: Project PI17/01458; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Grant/Award Number: PCAPE 2011_0025 Register 320/11; Research Project of Universidad Europea de Madrid, Grant/Award Number: 2017/UEM03Peer reviewe

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

La organización y atención a la diversidad en centros de educación secundaria de Iberoamérica. Reflexiones y experiencias

La organización y atención a la diversidad en centros de educación secundaria de Iberoamérica. Reflexiones y experiencias" es el nuevo título de la Serie Informes de RedAGE. La misma recoge la visión de 41 especialistas de 13 países iberoamericanos sobre la realidad y perspectivas de la atencion a la diversidad en centros de educación secundaria. La focalización, en esta etapa educativa, tiene que ver con la consideración de que, actualmente, es el momento de la escolarización donde se producen más abandonos y donde se abren o limitan posibilidades para el posible acceso a estudios superiores de los más capacitados. La orientación de los escritos tiene que ver con las finalidades y objetivos de la Red de Apoyo a la Gestion Educativa (RedAGE); también con el convencimiento, por parte de los que escriben, de que el contexto organizativo actúa como un amplificador o limitador de las actuaciones dirigidas a la formación de los escolares

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Kidins220 sets the threshold for survival of neural stem cells and progenitors to sustain adult neurogenesis

Abstract In the adult mammalian brain, neural stem cells (NSCs) located in highly restricted niches sustain the generation of new neurons that integrate into existing circuits. A reduction in adult neurogenesis is linked to ageing and neurodegeneration, whereas dysregulation of proliferation and survival of NSCs have been hypothesized to be at the origin of glioma. Thus, unravelling the molecular underpinnings of the regulated activation that NSCs must undergo to proliferate and generate new progeny is of considerable relevance. Current research has identified cues promoting or restraining NSCs activation. Yet, whether NSCs depend on external signals to survive or if intrinsic factors establish a threshold for sustaining their viability remains elusive, even if this knowledge could involve potential for devising novel therapeutic strategies. Kidins220 (Kinase D-interacting substrate of 220 kDa) is an essential effector of crucial pathways for neuronal survival and differentiation. It is dramatically altered in cancer and in neurological and neurodegenerative disorders, emerging as a regulatory molecule with important functions in human disease. Herein, we discover severe neurogenic deficits and hippocampal-based spatial memory defects accompanied by increased neuroblast death and high loss of newly formed neurons in Kidins220 deficient mice. Mechanistically, we demonstrate that Kidins220-dependent activation of AKT in response to EGF restraints GSK3 activity preventing NSCs apoptosis. We also show that NSCs with Kidins220 can survive with lower concentrations of EGF than the ones lacking this molecule. Hence, Kidins220 levels set a molecular threshold for survival in response to mitogens, allowing adult NSCs growth and expansion. Our study identifies Kidins220 as a key player for sensing the availability of growth factors to sustain adult neurogenesis, uncovering a molecular link that may help paving the way towards neurorepair

Anales de Edafología y Agrobiología Tomo 42 Número 1-2

Suelos. Influencia de los factores formadores en la génesis de suelos de montaña en la provincia de Teruel, V., por A. Hoyos, Ma. L. Palomar, A.Ma. Moreno y C. Fernández.-- Características petroquímicas y. micromorfológicas de los Xerumbrepts de la Sierra de Guadarrama, por P. Arévalo t, J. Benayas y J. Gallardo.-- Predicción de parámetros climáticos de interés ecológico en Galicia. II., por A.M. MolIna, J. Juste, F. Ucieda, R. Retuerto y A. Carballeira.-- Naturaleza y utilidad de las relaciones suelo-relieve en una zona granodiorftica de la parte central del Valle de los Pedroches (Córdoba), por J. Torrent, M. A. Parra, L. Montealegre y J. Barrios.-- La fracción arcilla de suelos de alta montaña sobre rocas carbonatadas. IV Xerolls, por L. J. Alias y J. Fernández Bastida.-- La fracción arcilla de suelos de alta montaña sobre rocas carbonatadas. V. Borolls, por L. J. Alias Pérez y J. Hernández Bastida.-- Aspectos qufmico-agrfcolas de suelos representativos del marco Montilla-Moriles, I., por l. Sánchez, J. Gil, L. Corral, M. Medina y G. Paneque.-- Aspectos químico-agrícolas de suelos representativos del marco Montilla-Moriles. II., por l. Sánchez, J. Gil, M. Medina, L. Corral y G. Paneque.-- Aspectos químico-agrícolas de suelos representativos del marco Montilla-Moriles. Ill., por, l. Sánchez, J. Gil, L. Corral, M. Medina y G. Paneque.-- Aspectos químico-agrícolas de suelos representativos del marco Montilla-Moriles. IV., por, l. Sánchez, J. Gil, L. Corral, M. Medina y G. Paneque.-- Caracterización de la población microbiana de un purin de vacuno, por M. J. Acea y T. Carballas.-- Efecto de la humedad ambiental en la adsorción-desorción en fase gaseosa de Heptacloro· por suelos de la cuenca del Guadalquivir, por Eduardo Peris, Juan Cornejo y Pablo de Arambarri.-- Fertilidad de Suelos. Respuesta del maíz a las aplicaciones de fósforo en un suelo pardo con tendencia fersialftica, por P. Díaz Luis, Benigna Eleizalde, V. García y Amalia Díaz.-- Effect of different composts on yield and composition of chilli, por K. R. Maurya and N. R. Dhar.-- Effect of potassium on salt tolerance plants irrigated with saline waters, por Benigna Eleizalde and S. Larsen.-- Evolución del fruto de la Vitis Vinífera "Pedro Ximenez" durante la maduración, en la zona Montilla-Moriles, I., por J. J. Moreno Vigara, M. Medina Carnicer, L. Corral Mora y G. Paneque Guerrero.--Evolución del fruto de la Vitis Vinífera "Pedro Ximenez" durante la maduración en la zona Montilla-Moriles, II., por J. J. Moreno Vigara, M. Medina Carnicer, L. Corral Mora y G. Paneque Guerrero.-- Evolución del fruto de la Vitis Vinífera "Pedro Ximenez" durante la maduración en la zona Montilla Moriles, III, por J. J. Moreno Vigara, M. Medina Carnicer, L. Corral Mora y G. Paneque Guerrero.-- Adición de residuos vegetales a suelos calizos. II., por J. Cegarra, M. T. Hernández, A. Lax y F. Costa.-- Adición de residuos vegetales a suelos calizos. III., por M. T. Hernández, J. Cegarra y F. Costa.-- Phosphorus uptake by abadia variety wheat grown in soils of Ebro Valley, by Benigna Eleizalde, V. Garcza, Amalia Dzaz and C. E. Alvarez.—Fisiología Vegetal y Nutrición. Estudio de algunos aspectos eccifisiológicos en el análisis de la Producción de grano en los cultivos de cebada. III., por L. F. Garcza del Moral, J. M. Ramos y L. Recalde Manrique.-- Actividad piruvato quinasa, contenido en potasio y azúcaresreductores en yemasde arboles vegetativos y productivos de olea europea L., por C. Mazuelos, R. Romero, V. Valpuesta, R. Sarmiento y L. Catalina.-- Inducción de callos en plántulas de Pinus Canariensis, por J. F. Pérez Francés, C., Martinez y A. C. Blesa.-- Principales propiedades de la porfibilinogenasa en semillas. de Pinus Pinea en germina· ción, por M. Sanz Muñoz, M. T. Méndez Marco y M. Méndez Marco.-- Inhibidores de porfibilinogenasa de semillas de Pinus.Pinea en germinación, por M. T. Méndez Marco, M. Méndez Marco y M. Sanz Muñoz.-- Influencia de altas concentraciones de cadmio sobre el crecimiento, desarrollo y contenido de pigmentos fotosintéticos de "Phaseolus Vulgaris", por Ch. Poschenrieder, C. Cabot y J. Barceló.-- Efecto del amitrol sobre los niveles de pigmentos cloroplásticos en Qlantas de Nicotiana rústica y Triticum Vulgare, por Carlos Codina Mahrer y Carmen Morales Pujol.-- Cultivosl redecesores de ajo colorado en plan de rotaciones cortas, por J. C. Silenzi, J. C. Lucero, A. M. Moreno y V. Larreguy.-- Notas.-- BibliografíaPeer reviewed2019-08.- CopyBook.- Libnova.- Biblioteca IC