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Introduction: Patient satisfaction with septoturbinoplasty was measured using the subjective visual analogue scale (VAS) and Nasal Obstruction Symptom Evaluation (NOSE) scale. In addition, those factors that impacted satisfaction were confirmed. Materials and Methods: We conducted an observational study of patients who underwent septoturbinoplasty. Age, sex, smoking habit, duration of improvement, postoperative complications, type of packing and surgeon were analysed. The results were compared using the VAS and NOSE scale. Results: The improvement experienced with surgery corresponded to 69.80±26.97 points on the VAS 42.65±22.9 points (p <0.01) on the NOSE scale. A strong, direct correlation between the two scales (r = 0.79; p <0.01) was achieved. Surgeon, presence of complications, smoking habit and type of packing were not associated with the improvement experienced on the VAS or NOSE scale. Patients under 30 years of age and patients with permanent improvement achieved higher levels of satisfaction on both scales (p <0.01). Women showed a stronger tendency to perceive their improvement as temporary (p <0.01). Conclusions: Patients who underwent septoturbinoplasty experienced a subjectively measured improvement in nasal obstruction. The VAS and the NOSE scale were strongly correlated with one another. Sex, age and duration of improvement (temporary versus permanent) impacted patient perception; surgeon, smoking habit and type of packing did not.
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BACKGROUND AND OBJECTIVES: Epistaxis is a common emergency for otorhinolaryngologists. Although the aetiological factors have been widely studied, they remain subject to debate. The role of meteorological variables has been discussed in recent years, but results have been inconsistent. Given a lack of prior data, the aim of our study was to identify the meteorological variables that influence the frequency of visits and hospital admission for epistaxis in a city with a cold semi-arid climate in Spain. METHODS: Case-control study. CASES: patients who attended the accident and emergency department of a secondary level hospital for epistaxis over a 9-year period (2011-2019). Controls were established by simple random sampling among emergency rooms visits in general (patients who attended the same centre over the same period of time). Sociodemographic, clinical and meteorological variables were all taken into account. RESULTS: 2749 patients in the epistaxis group and 2764 in the control group. There were significant differences in the epistaxis group, with a higher proportion of male (62.85%) and older patients. Univariate and multivariate analysis revealed that the daily minimum temperature and maximum wind speed were factors significantly associated with the onset of epistaxis. In addition, logistic regression analysis showed that decreases in minimum temperature and increases in maximum wind speed were associated with an increase in epistaxis (p < 0.01). No association was found between hospital admission and the weather conditions. CONCLUSION: Our findings suggest that low minimum temperatures and high wind speeds are associated with the number of visits to hospital accident and emergency departments for epistaxis, but not with hospital admission.
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Epistaxis , Tiempo (Meteorología) , Humanos , Masculino , Epistaxis/epidemiología , Epistaxis/etiología , Epistaxis/terapia , Estudios de Casos y Controles , España/epidemiología , HospitalesRESUMEN
ATG9A and ATG2A are essential core members of the autophagy machinery. ATG9A is a lipid scramblase that allows equilibration of lipids across a membrane bilayer, whereas ATG2A facilitates lipid flow between tethered membranes. Although both have been functionally linked during the formation of autophagosomes, the molecular details and consequences of their interaction remain unclear. By combining data from peptide arrays, crosslinking, and hydrogen-deuterium exchange mass spectrometry together with cryoelectron microscopy, we propose a molecular model of the ATG9A-2A complex. Using this integrative structure modeling approach, we identify several interfaces mediating ATG9A-2A interaction that would allow a direct transfer of lipids from ATG2A into the lipid-binding perpendicular branch of ATG9A. Mutational analyses combined with functional activity assays demonstrate their importance for autophagy, thereby shedding light on this protein complex at the heart of autophagy.
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Autofagosomas , Autofagia , Microscopía por Crioelectrón , Bioensayo , LípidosRESUMEN
Externalization of the phospholipid cardiolipin (CL) to the outer mitochondrial membrane has been proposed to act as a mitophagy trigger. CL would act as a signal for binding the LC3 macroautophagy/autophagy proteins. As yet, the behavior of the LC3-subfamily members has not been directly compared in a detailed way. In the present contribution, an analysis of LC3A, LC3B and LC3C interaction with CL-containing model membranes, and of their ability to translocate to mitochondria, is described. Binding of LC3A to CL was stronger than that of LC3B; both proteins showed a similar ability to colocalize with mitochondria upon induction of CL externalization in SH-SY5Y cells. Besides, the double silencing of LC3A and LC3B proteins was seen to decrease CCCP-induced mitophagy. Residues 14 and 18 located in the N-terminal region of LC3A were shown to be important for its recognition of damaged mitochondria during rotenone- or CCCP-induced mitophagy. Moreover, the in vitro results suggested a possible role of LC3A, but not of LC3B, in oxidized-CL recognition as a counterweight to excessive apoptosis activation. In the case of LC3C, even if this protein showed a stronger CL binding than LC3B or LC3A, the interaction was less specific, and colocalization of LC3C with mitochondria was not rotenone dependent. These results suggest that, at variance with LC3A, LC3C does not participate in cargo recognition during CL-mediated-mitophagy. The data support the notion that the various LC3-subfamily members might play different roles during autophagy initiation, identifying LC3A as a novel stakeholder in CL-mediated mitophagy. Abbreviations: ACTB/ß-actin: actin beta; Atg8: autophagy-related 8; CL: cardiolipin; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; DMSO: dimethyl sulfoxide; DOPE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; DTT: DL-dithiothreitol; FKBP8: FKBP prolyl isomerase 8; GABARAP: GABA type A receptor associated protein; GABARAPL1: GABA type A receptor associated protein like 1; GABARAPL2: GABA type A receptor associated protein like 2; GFP: green fluorescent protein; IMM: inner mitochondrial membrane; LUV/LUVs: large unilamellar vesicle/s; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAP1LC3C/LC3C: microtubule associated protein 1 light chain 3 gamma; NME4/NDPK-D/Nm23-H4: NME/NM23 nucleoside diphosphate kinase 4; O/A: oligomycin A + antimycin A; OMM: outer mitochondrial membrane; PA: phosphatidic acid; PC: phosphatidylcholine; PG: phosphatidylglycerol; PINK1: PTEN induced putative kinase 1; PtdIns4P: phosphatidylinositol-4-phosphate; Rho-PE: lissamine rhodamine phosphatidylethanolamine; SUV/SUVs: small unilamellar vesicle/s.
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Proteínas Asociadas a Microtúbulos , Mitofagia , Neuroblastoma , Humanos , Autofagia/fisiología , Carbonil Cianuro m-Clorofenil Hidrazona , Cardiolipinas/metabolismo , Ácido gamma-Aminobutírico , Proteínas Asociadas a Microtúbulos/metabolismo , Rotenona/farmacología , Liposomas UnilamelaresRESUMEN
Traditionally, earthquake impact assessments have been made via fieldwork by non-governmental organisations (NGO's) sponsored data collection; however, this approach is time-consuming, expensive and often limited. Recently, social media (SM) has become a valuable tool for quickly collecting large amounts of first-hand data after a disaster and shows great potential for decision-making. Nevertheless, extracting meaningful information from SM is an ongoing area of research. This paper tests the accuracy of the pre-trained sentiment analysis (SA) model developed by the no-code machine learning platform MonkeyLearn using the text data related to the emergency response and early recovery phase of the three major earthquakes that struck Albania on the 26th November 2019. These events caused 51 deaths, 3000 injuries and extensive damage. We obtained 695 tweets with the hashtags: #Albania #AlbanianEarthquake, and #albanianearthquake from the 26th November 2019 to the 3rd February 2020. We used these data to test the accuracy of the pre-trained SA classification model developed by MonkeyLearn to identify polarity in text data. This test explores the feasibility to automate the classification process to extract meaningful information from text data from SM in real-time in the future. We tested the no-code machine learning platform's performance using a confusion matrix. We obtained an overall accuracy (ACC) of 63% and a misclassification rate of 37%. We conclude that the ACC of the unsupervised classification is sufficient for a preliminary assessment, but further research is needed to determine if the accuracy is improved by customising the training model of the machine learning platform.
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Objetivos El objetivo de este estudio es determinar a qué tipo de patologías nos enfrentamos. Utilizamos la Clasificación Internacional de Atención Primaria para asegurar una nomenclatura objetiva y comparable. Métodos Se realizó un estudio descriptivo, observacional y retrospectivo de una muestra de 108102 consultas de atención primaria de pacientes que acudieron a Urgencias de nuestro hospital para evaluar la epidemiología de la atención pediátrica brindada entre 2011 y 2019. Utilizamos el sistema de clasificación diagnóstica ICPC-2. Resultados El número de asistencias fue mayor en enero, febrero y marzo, así como los fines de semana. Tras ser atendidos, el 6,7% de los pacientes ingresaron en nuestro hospital. Las patologías más frecuentes fueron las infecciones del tracto respiratorio superior, gastroenteritis, fiebre y traumatismos / lesiones. Las patologías que con mayor frecuencia dieron lugar a ingresos hospitalarios fueron fiebre, bronquitis, gastroenteritis y vómitos (p> 0,001). En los ingresos hospitalarios de menores de 1 año, la bronquitis fue la patología más frecuente, mientras que entre los de 1 a 6 años fue la gastroenteritis y entre los de 7 a 14 años fue la apendicitis aguda (p <0,001). Conclusiones Las patologías pediátricas suponen un porcentaje importante de las visitas a urgencias, destacando las infecciones del tracto respiratorio superior, las infecciones intestinales y la fiebre. Sería aconsejable incrementar los recursos de personal en los fines de semana. Es necesario enfatizar en la educación sanitaria de la población para ajustar la demanda de asistencia en los servicios públicos. Se requiere más investigación para adaptar mejor la terminología ICPC-2.
Objectives The aim of this study is to determine what type of pathologies we are facing. We use the International Classification of Primary Care to ensure an objective and comparable nomenclature. Methods We carried out a descriptive, observational, and retrospective study of a sample comprising 108102 primary care encounters of patients presenting at our hospital's Emergency Room to assess the epidemiology of the pediatric care provided between 2011 and 2019. We used the ICPC-2 diagnosis classification system. Results The number of attendances was higher in January, February, and March, as well as at weekends. After being seen, 6.7% of patients were admitted to our hospital. The most frequent pathologies were upper respiratory tract infections, gastroenteritis, fever and trauma/injury. Pathologies most frequently resulting in hospital admissions were fever, bronchitis, gastroenteritis and vomiting (p>0.001). In hospital admissions involving patients under 1 year of age, bronchitis was the most frequent pathology, while among those aged between 1 and 6 years, it was gastroenteritis and among those aged between 7 and 14 years it was acute appendicitis (p<0.001). Conclusions Pediatric pathologies account for a significant percentage of visits to the emergency room, highlighting infections of the upper respiratory tract, intestinal infections, and fever. It would be necessary to increase staff resources on the weekends. It is highly recommended to emphasize the health education of the population to adjust the demand for assistance in public services. More research is required to better adapt the ICPC-2 terminology.
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Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Pediatría , Medicina de Urgencia Pediátrica/estadística & datos numéricos , Hospitales Generales/estadística & datos numéricos , Infecciones del Sistema Respiratorio/epidemiología , Heridas y Lesiones/epidemiología , Estudios Retrospectivos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Fiebre/epidemiología , Gastroenteritis/epidemiologíaRESUMEN
Myofibroblastic tumors are rare lesions which can affect any part of the body. Although benign, their mass effect causes symptoms that can become life-threatening. Supraglottic laryngeal involvement is extremely rare, with only 4 cases described in the English literature. Because the pathophysiology is unknown and the incidence is so low, there is no standardized therapeutic management, although for laryngeal tumors surgery has traditionally been the preferred initial option. Another less common option is intravenous and oral corticosteroid therapy, but this is usually reserved for myofibroblastic tumors in other head and neck sites that are more difficult to access surgically, or patients who cannot undergo surgery. These lesions have a very high tendency to recur, and morbidity rates are therefore also high. We present a case of supraglottic myofibroblastic tumor in which we elected high-dose corticosteroid therapy as the only form of treatment. With this new therapeutic approach, we avoided the undesirable effects of the usual type of surgery. At the 12-month follow-up, the patient is in complete remission.
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Corticoesteroides/uso terapéutico , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias de Tejido Muscular/tratamiento farmacológico , Humanos , Neoplasias Laríngeas/patología , Laringe/patología , Neoplasias de Tejido Muscular/patología , Resultado del TratamientoRESUMEN
Autophagy is traditionally depicted as a signaling cascade that culminates in the formation of an autophagosome that degrades cellular cargo. However, recent studies have identified myriad pathways and cellular organelles underlying the autophagy process, be it as signaling platforms or through the contribution of proteins and lipids. The Golgi complex is recognized as being a central transport hub in the cell, with a critical role in endocytic trafficking and endoplasmic reticulum (ER) to plasma membrane (PM) transport. However, the Golgi is also an important site of key autophagy regulators, including the protein autophagy-related (ATG)-9A and the lipid, phosphatidylinositol-4-phosphate [PI(4)P]. In this review, we highlight the central function of this organelle in autophagy as a transport hub supplying various components of autophagosome formation.
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Autofagosomas/fisiología , Aparato de Golgi/fisiología , Autofagia , Proteínas Relacionadas con la Autofagia/fisiología , Transporte Biológico , Endosomas/metabolismo , Humanos , Metabolismo de los Lípidos , Proteínas de la Membrana/fisiología , Proteínas de Transporte Vesicular/fisiologíaRESUMEN
PURPOSE: To determine the incidence and distribution of care in relation to urgent otorhinolaryngologic pathologies by the different medical specialist units. METHODS: A descriptive, observational and retrospective study was conducted of patients seen by the Emergency Service at a secondary hospital over the course of 7 years (2011-2017). RESULTS: A total of 546,701 patients were seen during the period in question, of which 64,054 presented with otorhinolaryngologic symptoms. The attendance rate was 450/1000 inhabitants/year. The most frequent diagnoses were upper respiratory tract infection, with 13,639 cases (21.3%), tonsillopharyngitis, with 10,150 cases (15.8%) and vertigo/dizziness with 8761 cases (13.7%). Patients seen by the Hospital Emergency Service physicians and those referred to the Otorhinolaryngology or Paediatric Units were analysed both together and separately. The Hospital Emergency Service dealt with 77.1% of the cases, and referred 15.4% to the Otorhinolaryngology Unit and 7.5% to the Paediatrics Unit. Within the subgroup of patients referred to the Otorhinolaryngology Unit, the most frequent diagnoses were problems related to inflammatory ear disease (25.6%), followed by cervicofacial trauma (15.4%) and bleeding with otorhinolaryngologic symptoms (12.5%). The percentage of hospital admissions for the entire sample was 3%, while for patients referred to the Otorhinolaryngology Unit this figure was 6.8%. CONCLUSIONS: A large percentage of patients presenting at the Hospital Emergency Service do so with otorhinolaryngologic symptoms, and the vast majority are treated effectively by the physicians in that service and are referred to the specialist services on the basis of sound criteria.
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Urgencias Médicas/epidemiología , Enfermedades Otorrinolaringológicas/epidemiología , Adulto , Anciano , Niño , Preescolar , Medicina de Emergencia/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Otolaringología/estadística & datos numéricos , Faringitis/epidemiología , Estudios Retrospectivos , Centros de Atención Secundaria/estadística & datos numéricosRESUMEN
Autophagy is an important cellular process in which cell components are degraded in a controlled way and their building blocks are recycled into new macromolecules. Autophagy starts within a double-membrane container, the autophagosome, itself the result of a number of interconversions of cell membranous elements. In our recent work, we have described reconstituted model systems for the interactions of autophagy proteins with membrane lipid bilayers and for the autophagy protein-mediated vesicle tethering and fusion, with the aim of ultimately reconstituting the autophagosome formation. The present chapter describes in detail (a) the steps required for the preparation of semisynthetic lipid vesicles (liposomes), including giant unilamellar vesicles, (b) ultracentrifugation and fluorescence methods for assaying protein binding to membranes, and (c) procedures for assessing vesicle-vesicle aggregation and fusion. The latter include methods for intervesicular total lipid mixing, mixing of lipids in the vesicle inner monolayers, and aqueous contents mixing.
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Proteínas Relacionadas con la Autofagia/metabolismo , Liposomas/metabolismo , Lípidos de la Membrana/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis , Autofagia , Humanos , Liposomas/química , Fusión de Membrana , Lípidos de la Membrana/química , Modelos Moleculares , Fosfolípidos/química , Fosfolípidos/metabolismo , Unión Proteica , Espectrometría de Fluorescencia/métodos , Ultracentrifugación/métodosRESUMEN
Specific protein-lipid interactions lead to a gradual recruitment of AuTophaGy-related (ATG) proteins to the nascent membrane during autophagosome (AP) formation. ATG3, a key protein in the movement of LC3 towards the isolation membrane, has been proposed to facilitate LC3/GABARAP lipidation in highly curved membranes. In this work we have performed a biophysical study of human ATG3 interaction with membranes containing phosphatidylethanolamine, phosphatidylcholine and anionic phospholipids. We have found that ATG3 interacts more strongly with negatively-charged phospholipid vesicles or nanotubes than with electrically neutral model membranes, cone-shaped anionic phospholipids (cardiolipin and phosphatidic acid) being particularly active in promoting binding. Moreover, an increase in membrane curvature facilitates ATG3 recruitment to membranes although addition of anionic lipid molecules makes the curvature factor relatively less important. The predicted N-terminus amphipathic α-helix of ATG3 would be responsible for membrane curvature detection, the positive residues Lys 9 and 11 being essential in the recognition of phospholipid negative moieties. We have also observed membrane aggregation induced by ATG3 in vitro, which could point to a more complex function of this protein in AP biogenesis. Moreover, in vitro GABARAP lipidation assays suggest that ATG3-membrane interaction could facilitate the lipidation of ATG8 homologues.
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Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Relacionadas con la Autofagia/genética , Membrana Dobles de Lípidos/química , Lípidos/química , Proteínas Asociadas a Microtúbulos/genética , Enzimas Ubiquitina-Conjugadoras/genética , Proteínas Adaptadoras Transductoras de Señales/química , Proteínas Reguladoras de la Apoptosis , Autofagosomas/química , Autofagia/genética , Proteínas Relacionadas con la Autofagia/química , Fenómenos Biofísicos/genética , Cardiolipinas/química , Cardiolipinas/genética , Membrana Celular/química , Membrana Celular/genética , Humanos , Lípidos/genética , Proteínas Asociadas a Microtúbulos/química , Unión Proteica , Enzimas Ubiquitina-Conjugadoras/químicaRESUMEN
The use of Spatial Division Multiplexing for Microwave Photonics signal processing is proposed and experimentally demonstrated, for the first time to our knowledge, based on the selective inscription of Bragg gratings in homogeneous multicore fibers. The fabricated devices behave as sampled true time delay elements for radiofrequency signals offering a wide range of operation possibilities within the same optical fiber. The key to processing flexibility comes from the implementation of novel multi-cavity configurations by inscribing a variety of different fiber Bragg gratings along the different cores of a 7-core fiber. This entails the development of the first fabrication method to inscribe high-quality gratings characterized by arbitrary frequency spectra and located in arbitrary longitudinal positions along the individual cores of a multicore fiber. Our work opens the way towards the development of unique compact fiber-based solutions that enable the implementation of a wide variety of 2D (spatial and wavelength diversity) signal processing functionalities that will be key in future fiber-wireless communications scenarios. We envisage that Microwave Photonics systems and networks will benefit from this technology in terms of compactness, operation versatility and performance stability.
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The phospholipid cardiolipin (CL) has been proposed to play a role in selective mitochondrial autophagy, or mitophagy. CL externalization to the outer mitochondrial membrane would act as a signal for the human Atg8 ortholog subfamily, MAP1LC3 (LC3). The latter would mediate both mitochondrial recognition and autophagosome formation, ultimately leading to removal of damaged mitochondria. We have applied quantitative biophysical techniques to the study of CL interaction with various Atg8 human orthologs, namely LC3B, GABARAPL2 and GABARAP. We have found that LC3B interacts preferentially with CL over other di-anionic lipids, that CL-LC3B binding occurs with positive cooperativity, and that the CL-LC3B interaction relies only partially on electrostatic forces. CL-induced increased membrane fluidity appears also as an important factor helping LC3B to bind CL. The LC3B C terminus remains exposed to the hydrophilic environment after protein binding to CL-enriched membranes. In intact U87MG human glioblastoma cells rotenone-induced autophagy leads to LC3B translocation to mitochondria and subsequent delivery of mitochondria to lysosomes. We have also observed that GABARAP, but not GABARAPL2, interacts with CL in vitro. However neither GABARAP nor GABARAPL2 were translocated to mitochondria in rotenone-treated U87MG cells. Thus the various human Atg8 orthologs might play specific roles in different autophagic processes.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Familia de las Proteínas 8 Relacionadas con la Autofagia/metabolismo , Autofagia , Cardiolipinas/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Mitofagia , Secuencia de Aminoácidos , Proteínas Reguladoras de la Apoptosis , Autofagia/efectos de los fármacos , Familia de las Proteínas 8 Relacionadas con la Autofagia/química , Línea Celular Tumoral , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Dronabinol/farmacología , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Proteínas Asociadas a Microtúbulos/química , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Membranas Mitocondriales/efectos de los fármacos , Membranas Mitocondriales/metabolismo , Mitofagia/efectos de los fármacos , Presión , Unión Proteica/efectos de los fármacos , Rotenona/farmacología , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Homología de Secuencia de AminoácidoRESUMEN
This paper presents a Fabry-Perot fiber tip sensor based on an air-liquid filled cavity. The cavity is sealed off by a thin gold coated membrane of parylene C, between 300 and 350 nm, creating a particularly flexible diaphragm. In order to retrieve and track the cavity of interest from other cavities formed within the sensor tip, a signal processing of the feedback signal is performed by inverse fast Fourier transform. The experimental sensor has been manufactured and tested for temperature, giving cavity length sensitivities of 6.1 nm/°C and 9.6 nm/°C for temperature increase and decrease respectively. The external gas pressure response gives a sensitivity of 15 nm/kPa. The fiber sensor has also been adapted for force sensing after silicone embedment and has shown a sensitivity of about 8.7 nm/mN. Finally, the sensor has been tested on insertion into a human temporal bone, proving that it could be an interesting candidate for insertion force monitoring for robotic cochlear implantation.
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Autophagy, an important catabolic pathway involved in a broad spectrum of human diseases, implies the formation of double-membrane-bound structures called autophagosomes (AP), which engulf material to be degraded in lytic compartments. How APs form, especially how the membrane expands and eventually closes upon itself, is an area of intense research. Ubiquitin-like ATG8 has been related to both membrane expansion and membrane fusion, but the underlying molecular mechanisms are poorly understood. Here, we used two minimal reconstituted systems (enzymatic and chemical conjugation) to compare the ability of human ATG8 homologs (LC3, GABARAP, and GATE-16) to mediate membrane fusion. We found that both enzymatically and chemically lipidated forms of GATE-16 and GABARAP proteins promote extensive membrane tethering and fusion, whereas lipidated LC3 does so to a much lesser extent. Moreover, we characterize the GATE-16/GABARAP-mediated membrane fusion as a phenomenon of full membrane fusion, independently demonstrating vesicle aggregation, intervesicular lipid mixing, and intervesicular mixing of aqueous content, in the absence of vesicular content leakage. Multiple fusion events give rise to large vesicles, as seen by cryo-electron microscopy observations. We also show that both vesicle diameter and selected curvature-inducing lipids (cardiolipin, diacylglycerol, and lyso-phosphatidylcholine) can modulate the fusion process, smaller vesicle diameters and negative intrinsic curvature lipids (cardiolipin, diacylglycerol) facilitating fusion. These results strongly support the hypothesis of a highly bent structural fusion intermediate (stalk) during AP biogenesis and add to the growing body of evidence that identifies lipids as important regulators of autophagy.
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Proteínas Adaptadoras Transductoras de Señales/química , Membrana Dobles de Lípidos/química , Proteínas Asociadas a Microtúbulos/química , Fagosomas/química , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Secuencia de Aminoácidos , Proteínas Reguladoras de la Apoptosis , Autofagia , Familia de las Proteínas 8 Relacionadas con la Autofagia , Humanos , Fusión de Membrana , Proteínas de Microfilamentos/química , Proteínas de Microfilamentos/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Datos de Secuencia Molecular , Fagosomas/ultraestructuraRESUMEN
Inner ear bone malformations are one cause of profound sensorineural hearing loss. This investigation focused on those affecting the posterior labyrinth, especially enlarged vestibular aqueduct syndrome, which is associated with fluctuating and progressive hearing loss. The objectives of this study were to analyze the behavior of the electrical stimulation, auditory functionality and linguistic development in patients with inner ear malformations involving the posterior labyrinth. The study included ten patients undergoing cochlear implantation (cases: five with enlarged vestibular aqueduct, two with vestibular aqueduct stenosis/aplasia, and three with semicircular canal disorders). Post-implantation, data were gathered on the electrical stimulation threshold and maximum comfort levels and on the number of functioning electrodes. Evaluation of Auditory Responses to Speech (EARS) subtests were used to assess auditory functionality and language acquisition at 6, 12, and 24 months post-implantation. Results were compared with findings in a control group of 28 cochlear implantation patients without these malformations. No significant differences were found between case and control groups in electrical stimulation parameters; auditory functionality subtest scores were lower in cases than controls, although the difference was only statistically significant for some subtests. In conclusion, cochlear implantation patients with posterior labyrinth bone malformations and profound hearing loss, including those with enlarged vestibular aqueduct syndrome, showed no significant difference in electrical stimulation threshold with controls. Although some auditory functionality test results were lower in cases than in controls, cochlear implantation appears to be beneficial for all patients with these malformations.
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Implantación Coclear , Pérdida Auditiva Sensorineural , Acueducto Vestibular/anomalías , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Implantación Coclear/métodos , Implantación Coclear/rehabilitación , Estimulación Eléctrica/métodos , Femenino , Pérdida Auditiva Sensorineural/complicaciones , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/cirugía , Pruebas Auditivas/métodos , Humanos , Desarrollo del Lenguaje , Masculino , Periodo Posoperatorio , Canales Semicirculares/anomalías , Canales Semicirculares/fisiopatología , España , Resultado del Tratamiento , Acueducto Vestibular/fisiopatologíaRESUMEN
We present new kind of microwave phase shifters (MPS) based on dispersion of PbS colloidal quantum dots (QDs) in commercially available photoresist SU8 after a ligand exchange process. Ridge PbS-SU8 waveguides are implemented by integration of the nanocomposite in a silicon platform. When these waveguides are pumped at wavelengths below the band-gap of the PbS QDs, a phase shift in an optically conveyed (at 1550 nm) microwave signal is produced. The strong light confinement produced in the ridge waveguides allows an improvement of the phase shift as compared to the case of planar structures. Moreover, a novel ridge bilayer waveguide composed by a PbS-SU8 nanocomposite and a SU8 passive layer is proposed to decrease the propagation losses of the pump beam and in consequence to improve the microwave phase shift up to 36.5° at 25 GHz. Experimental results are reproduced by a theoretical model based on the slow light effect produced in a semiconductor waveguide due to the coherent population oscillations. The resulting device shows potential benefits respect to the current MPS technologies since it allows a fast tunability of the phase shift and a high level of integration due to its small size.
RESUMEN
OBJECTIVE: To study electrical stimulation, auditory functionality, and language development in patients with inner ear malformations involving the anterior labyrinth who underwent cochlear implantation. STUDY DESIGN: Retrospective case review. SETTING: Reference hospital for cochlear implantation. PATIENTS: Review of 14 cases of severe hearing loss with major (common cavity deformity and cochlear hypoplasia) or minor (e.g., incomplete partition and basal turn aplasia) malformations. INTERVENTIONS: After cochlear implantation, data were gathered on the threshold (THR) and maximum comfort level (MCL) of the electrical stimulation and the number of functioning electrodes. Auditory responses to speech (EARS protocol) subtests were used to evaluate auditory functionality and language acquisition at 6, 12, and 24 months post-implantation. Tests used were: LIP profile, MTP (3, 6 and 12 words), OLD (open set test) and CLD (close set test). Results were compared with findings in a control group of 28 cochlear implantation patients without these malformations and with congenital hearing loss. RESULTS: The mean THR was 11.02µC in patients with malformations versus 3.5µC in those without, a significant difference. The THR also significantly differed between groups with major and minor malformations. Fewer functioning electrodes were used in patients with malformations. Auditory functionality scores were best in controls than in patients with malformations, who scored ≤50%, finding the lowest scores in those with major malformations. CONCLUSION: Patients with inner ear malformations undergoing cochlear implantation require greater stimuli to obtain an auditory response and have worse auditory functionality outcomes; these differences are greater in those with major versus minor malformations Nevertheless, cochlear implantation appears to be beneficial for all patients with these malformations to a greater or lesser extent.
Asunto(s)
Umbral Auditivo , Implantes Cocleares , Oído Interno/anomalías , Desarrollo del Lenguaje , Percepción Auditiva , Estudios de Casos y Controles , Niño , Sordera/cirugía , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVES/HYPOTHESIS: To determine the effect of topical intranasal oxymetazoline on nasal resistance and aerobic exercise performance in patients with nasal congestion caused by inferior turbinate hypertrophy. STUDY DESIGN: Individual randomized controlled trial. METHODS: Eight patients with inferior turbinate hypertrophy performed a set of exercise tests to exhaustion 1 week apart. They were given oxymetazoline or a placebo before each of the two test sessions according to a random pattern. Changes in nasal airflow were measured as peak nasal flow and ventilatory efficiency parameters, ventilatory equivalents, end-expiratory pressure, oxygen consumption, cardiac efficiency, rate of perceived exertion, and maximal and submaximal mechanical power. RESULTS: Ten minutes after use of the drug or placebo, improvements in maximum nasal airflow were seen in the oxymetazoline group (P < 0.05). However, exercise tests showed improvements in both groups (P < 0.05). After exertion, there was no difference between the two groups in maximum nasal airflow (P > 0.05). There were no differences between groups in oxygen consumption, rate of perceived exertion, respiratory exchange ratio, ventilation, or ventilatory equivalents for oxygen. CONCLUSION: Oxymetazoline increased nasal airflow in patients with turbinate hypertrophy, but this change did not translate into gains in physical exercise parameters or perceived exertion. LEVEL OF EVIDENCE: 1b.