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1.
Proc Biol Sci ; 290(2004): 20230543, 2023 08 09.
Article in English | MEDLINE | ID: mdl-37528708

ABSTRACT

Medusozoa (Cnidaria) are characterized by diverse life cycles, with different semaphoronts (medusa, medusoid, fixed gonophore, polyp) representing the sexual phase and carrying the gametes. Although egg size is often considered a proxy to understand reproductive and developmental traits of medusozoans, understanding of the processes influencing egg size variation in the group under an evolutionary context is still limited. We carried out a comprehensive review of the variation of egg size in Medusozoa to test whether this variation is related to biological/sexual or environmental traits. Egg size presents a strong phylogenetic signal (λ = 0.79, K = 0.67), explaining why closely related species with different reproductive strategies and different individual sizes have similar egg sizes. However, variation in egg size is influenced by the number of eggs, depth and temperature, with larger eggs frequently present in species with few eggs (1-15), in deep-sea species and in cold-water species. Conversely, the production of small eggs among cold-water species of Staurozoa might be associated with the development of a small benthic larvae in this group. Our study reinforces that egg sizes respond to reproductive and environmental traits, although egg size is highly conserved within medusa classes.


Subject(s)
Cnidaria , Animals , Phylogeny , Reproduction , Biological Evolution , Water
2.
Article in English | MEDLINE | ID: mdl-35955037

ABSTRACT

BACKGROUND: According to the WHO, "unsafe abortion occurs when a pregnancy is terminated either by people lacking the necessary skills or in an environment that does not conform to minimal medical standards, or both". AIM: To review the legislation that ensures access to elective abortion and the main indicators of elective abortion in Spain. METHODS: A retrospective observational study was conducted across all regions of Spain from 2011 to 2020. The regulations of each region on the creation of the clinical committee and the creation of the registry of conscientious objector professionals were identified. Data were collected on rates of elective abortions per 1000 women, type of health center where the intervention was performed, interval of weeks of gestation, and cause. RESULTS: After Law 2/2010 entered into force, the Spanish regions created a clinical committee; however, very few regions have a registry of conscientious objectors. During the study period, the average annual rate in Spain was 11.10 elective abortions per 1000 women between 15 and 44 years of age, showing a decreasing trend (annual percentage change of -1.92%). Only 10.67% of abortions were performed at public centers. In 90.18% of the cases, abortions were performed at the woman's request. CONCLUSION: Spain legislated late compared to most European Union countries. The current law is similar to that of other member states, allowing abortion at the woman's request in the first fourteen weeks and thereafter for medical reasons. Most abortions are performed at private centers, although many territorial inequalities are observed.


Subject(s)
Abortion, Induced , Abortion, Legal , Female , Humans , Incidence , Population Surveillance , Pregnancy , Spain/epidemiology
3.
Rev. neuro-psiquiatr. (Impr.) ; 85(3): 206-223, jul.-sep. 2022. tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1560290

ABSTRACT

RESUMEN El Trastorno por Estrés Postraumático (TEPT) es una condición psiquiátrica que surge como respuesta a eventos traumáticos y puede afectar significativamente la funcionalidad del paciente. La sierra andina es una región cuya población ha estado expuesta a eventos altamente estresantes; sin embargo, existe escasa información sobre factores asociados a la ocurrencia de TEPT en la región. Objetivo: Determinar los factores sociodemográficos y clínicos (comorbilidad y funcionalidad) asociados al TEPT. Material y métodos: Se trata de un estudio secundario que utilizó la base de datos del adulto del Estudio Epidemiológico de Salud Mental en la Sierra - 2017. Instrumentos: Mini Entrevista Neuropsiquiátrica Internacional (MINI) en la versión en español de CIE-10, Cuestionario de Salud Mental de Colombia, Escala de Discapacidad y una ficha de datos demográficos e indicadores de pobreza. Resultados: Se encontraron asociaciones significativas entre TEPT y grupos de personas casadas y carentes de instrucción escolarizada. El episodio depresivo fue la comorbilidad más frecuente. Los principales estresores fueron la violencia política y los accidentes graves. Asimismo, hubo asociación de TEPT con pensamientos suicidas y dificultad para planificar, organizar y ejecutar diversas actividades. Conclusiones: Existe asociación relevante entre TEPT y algunos factores sociodemográficos, eventos traumáticos y trastornos clínicos. Los programas de intervención deben brindar atención inmediata a personas expuestas a eventos traumáticos y disminuir la presencia y el impacto de factores estresantes presentes en la región andina.


SUMMARY Post-traumatic stress disorder (PTSD) is a psychiatric condition that occurs in response to traumatic events and can significantly affect the patient's functional capacities. The Peruvian highlands is a region whose population has been exposed to highly stressful events; however, there is limited information on the factors associated with PTSD in the region. Objective: To determine sociodemographic and clinical factors (comorbidity and functionality) associated with PTSD. Material and methods: A secondary study was conducted using the adult database of the Epidemiological Study of Mental Health in the Peruvian Highlands - 2017. Instruments: Mini International Neuropsychiatric Interview (MINI) Spanish version ICD-10, Mental Health Questionnaire of Colombia, Disability Scale, and an intake form with demographic data and poverty indicators. Results: Significant associations were found between PTSD and groups of married people and those who had no school education. Depressive episode was the most frequent comorbidity. The main stressors were political violence and serious accidents. Likewise, there was an association of PTSD with suicidal thinking and difficulties in planning, organizing and executing a variety of activities. Conclusions: PTSD was associated with some sociodemographic factors, traumatic events and clinical disorders. Intervention programs should be aimed at providing immediate care to people exposed to traumatic events and at reducing the presence and impact of such stressors in the Andean region.

4.
Article in English | MEDLINE | ID: mdl-35055680

ABSTRACT

Respect for different sexual options and orientations prevents the occurrence of hate crimes against lesbian, gay, bisexual, trans and intersex (LGTBI) persons for this reason. Our aim was to review the legislation that protects the rights of LGTBI people and to quantify the victimization rates of hate crimes based on sexual identity and orientation. A retrospective observational study was conducted across all regions of Spain from 2011-2021. The laws on LGTBI rights in each region were identified. Hate crime victimization data on sexual identity and orientation were collected in annual rates per 100,000 inhabitants, annual percentage change and average change during the study period to assess the trend. The regulatory development of laws against discrimination against LGTBI individuals is heterogeneous across regions. Overall, in Spain there is an upward trend in the number of hate crime victimizations motivated by sexual identity or orientation. The effectiveness of data collection, thanks to better training and awareness of police forces regarding hate crimes and the processes of data cleansing and consolidation contributes to a greater visibility of hate crimes against LGTBI people.


Subject(s)
Crime Victims , Homosexuality, Female , Bisexuality , Crime , Female , Hate , Humans , Spain
5.
In. Machado Rodríguez, Fernando; Cluzet, Óscar; Liñares Divenuto, Norberto Jorge; Gorrasi Delgado, José Antonio. La pandemia por COVID-19: una mirada integral desde la emergencia del hospital universitario. Montevideo, Cuadrado, 2021. p.173-189, tab.
Monography in Spanish | LILACS, UY-BNMED, BNUY | ID: biblio-1344081
6.
Rev Alerg Mex ; 67(1): 9-18, 2020.
Article in Spanish | MEDLINE | ID: mdl-32447863

ABSTRACT

BACKGROUND: In Mexico, the economic burden of medical care for patients with atopic dermatitis is unknown. OBJECTIVE: To determine the annual direct medical costs of the treatment for patients with moderate to severe atopic dermatitis who receive medical attention at "Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado" (Institute for Social Security and Social Services for State Workers, better known as ISSSTE), as well as the main variables associated with it. METHODS: A multicenter, retrospective cohort study. Clinical records of patients with moderate to severe atopic dermatitis were reviewed and a multivariate analysis was designed by using a generalized linear model. RESULTS: 65 patients were included; 41 of them (63.07 %) had moderate atopic dermatitis, and 24 (36.92 %) had severe AD; 39 (60 %) of them were female patients. In groups with severe atopic dermatitis, statistically significant differences were observed in matters of the duration of the evolution of the disease, comorbidities, intense pruritus, and depression. The average annual cost of medical care for patients with moderate atopic dermatitis was 1527 ± 623 USD, and for patients with severe atopic dermatitis the cost was 9487 ± 8990 USD. Significant differences were observed in dermatology consultations, referrals, laboratory and diagnostic studies, and the number of drugs prescribed by physicians. With the multivariate analysis, it was identified that the highest cost was presented by severe patients (p = 0.0001) who were younger and had comorbidities, along with diagnosis of depression. CONCLUSIONS: The severity of atopic dermatitis, the age average, the presence of comorbidities, and the diagnosis of depression are the variables with the highest association and impact on the direct cost of medical care.


Antecedentes: En México se desconoce el impacto económico de la atención médica de los pacientes con dermatitis atópica. Objetivo: Determinar los costos médicos directos anuales del tratamiento de pacientes con dermatitis atópica moderada y grave que se atienden en el Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, y las principales variables asociadas. Métodos: Estudio multicéntrico de cohorte retrospectiva. Se revisaron los expedientes clínicos de pacientes con dermatitis atópica clasificada como moderada o grave y se diseñó un modelo de análisis multivariado mediante un modelo lineal generalizado. Resultados: Se incluyeron 65 pacientes, 41 (63.07 %) tuvieron dermatitis atópica moderada y 24 (36.92 %), grave; 39 (60 %) fueron del sexo femenino. En los grupos con dermatitis atópica grave se observaron diferencias estadísticamente significativas en años de evolución de la enfermedad, comorbilidades, prurito intenso y depresión. El costo promedio anual de la atención médica para dermatitis atópica moderada fue de 1527 ± 623 USD y para dermatitis atópica grave, de 9487± 8990 USD. Se obtuvieron diferencias estadísticamente significativas en consultas de dermatología, interconsultas, estudios de laboratorio y gabinete y número de medicamentos prescritos. Con el análisis multivariado se identificó que el costo mayor lo presentaban los pacientes graves (p = 0.0001), más jóvenes, con comorbilidades y diagnóstico de depresión. Conclusiones: La gravedad de la dermatitis atópica, la edad, presentar comorbilidades y contar con el diagnóstico de depresión son las variables con mayor asociación e impacto en el costo directo de la atención médica.


Subject(s)
Dermatitis, Atopic/economics , Dermatitis, Atopic/therapy , Health Care Costs , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Male , Mexico , Middle Aged , Retrospective Studies , Severity of Illness Index , Young Adult
7.
Rev. chil. anest ; 49(2): 281-283, 2020.
Article in Spanish | LILACS, UY-BNMED, BNUY | ID: biblio-1379595

ABSTRACT

Las situaciones de crisis en la sala de operaciones son eventos poco frecuentes, con personal trabajando rápido y bajo presión, intentando sobrellevar el incidente con los menores riesgos para el paciente. Se expone un caso clínico en el marco del trabajo de una unidad de anestesia para cirugía de tórax en la cual se presenta una crisis asistencial abordada por un equipo de trabajo capacitado mediante simulación en la aplicación de la herramienta de "Manejo de los Recursos en Crisis (CRM)". Planteamos que la aplicación de esta herramienta por un equipo capacitado en su utilización contribuyó al éxito y buena evolución de un paciente crítico.


Crisis situations on the operation room seldom happen, with staff working fast and under pressure, trying to overcome the incident at the same time as reducing the risks for the patient. Here we expose a clinical case on the frame of work of an anesthesia unit assembled for thorax surgery during which an asistential crisis occurs and is managed by a group of coworkers trained by means of simulation on the appliance of the tool called "Crisis Resource Management (CRM)". We support the idea that the appliance of this tool by a team of professionals trained on its use, contributed to the success and good evolution on a critical patient.


Subject(s)
Humans , Male , Aged , Postoperative Complications , Biopsy/adverse effects , Anesthesiologists , Mediastinal Neoplasms/pathology , Case Management/standards , Emergencies
8.
J Exp Child Psychol ; 186: 33-44, 2019 10.
Article in English | MEDLINE | ID: mdl-31195209

ABSTRACT

This study examined whether and how young children make spontaneous use of geometric maps for two different purposes: to determine and to represent the locations of objects. A total of 64 2.5-, 3-, 3.5-, and 4-year-old children solved a task with two phases in counterbalanced order; they needed to use a map to locate a toy hidden in a referent space (retrieval) and to indicate on the symbol with a sticker the location of the hidden toy (map making). Results show that there is a clear developmental progression, with 2.5-year-olds failing both phases, 3- and 3.5-year-olds succeeding only in the map making phase, and 4-year-olds succeeding in both the map making and retrieval phases. The differences between making use of maps to represent locations and locating objects in space allow for a closer comprehension of map reading as a progressive sequenced process and the factors at play as children develop symbolic understanding.


Subject(s)
Child Development/physiology , Comprehension/physiology , Orientation, Spatial/physiology , Child, Preschool , Female , Humans , Male
9.
Educ. med. super ; 33(1): e1514, ene.-mar. 2019. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1089883

ABSTRACT

Introducción: La reforma psiquiátrica y promulgación del Plan Nacional de Salud Mental y Psiquiatría, plantea el desafío de un cambio de actitud hacia las personas con enfermedad mental. Es debido a la estigmatización y discriminación que los pacientes sufren violaciones de derechos humanos, negándoseles la posibilidad de gozar del grado más alto de salud. Para Enfermería de la Universidad Del Desarrollo es un desafío y deber formar profesionales respetuosos de la diversidad y capaces de generar cuidados de enfermería especializados, por lo que se diseñó un curso que incorporó Aprendizaje Experiencial. Objetivo: Promover un cambio de actitud hacia la enfermedad mental en estudiantes de Enfermería de tercer año mediante la incorporación del Aprendizaje Experiencial. Métodos: Estudio de cohorte. Se analizó la existencia de diferencias estadísticamente significativas (test t, 95 por ciento confianza y 0,05 significancia) en los puntajes obtenidos por 52 estudiantes de Enfermería, luego de aplicar la Escala de medición de actitudes hacia los enfermos mentales en futuros técnicos de salud, pre y post realización del curso, previa firma de consentimiento informado. Resultados: El puntaje promedio aumentó de 59,3 (de: 10,5) a 64,5 puntos (de: 8,8). La diferencia promedio en el puntaje total del test antes y después del curso es de 5,2 puntos. Al distinguir entre ítems favorables y desfavorables los puntajes promedios aumentan post realización del curso. Conclusión: Es posible promover un cambio de actitud hacia la enfermedad mental en estudiantes de Enfermería mediante el Aprendizaje Experiencial(AU)


Introduction: The psychiatric reform and the promulgation of the National Plan of Mental Health and Psychiatry posed the challenge of a change of attitude towards people with mental illnesses. Due to stigmatization and discrimination, patients suffer human rights violations, being denied the possibility of enjoying the highest degree of health. For Nursing at Universidad del Desarrollo it is a challenge and a duty to train professionals who are respectful of diversity and capable of generating specialized nursing care, so a course was designed that incorporated experiential learning. Objective: To promote a change of attitude towards mental illnesses in third-year Nursing students through the incorporation of experiential learning. Methods: Cohort study. We analyzed the existence of statistically significant differences (t-test, 95 percent confidence interval and 0.05 significance) in the scores obtained by 52 Nursing students, after applying the Attitudes towards the Mentally Ill Measuring Scale in future health technicians, before and after the completion of the course, after signing informed consent. Results: The average score increased from 59.3 (from: 10.5) to 64.5 points (from: 8.8). The average difference in the total score of the test before and after the course is 5.2 points. Upon distinguishing between favorable and unfavorable items, the average scores increase after the completion of the course. Conclusion: It is possible to promote a change of attitude towards mental illnesses in Nursing students by means of experiential learning(AU)


Subject(s)
Humans , Psychiatry , Students, Nursing , Mental Health , Mentally Ill Persons , Nursing Care
10.
Arch. pediatr. Urug ; 90(4): 195-202, 2019. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1011177

ABSTRACT

Resumen: Se define prescripción de medicamentos off label como aquella que se realiza en condiciones distintas a las indicadas en la ficha técnica o prospecto y, por lo tanto, diferentes para las que fueron autorizados y registrados. Se desconoce el conocimiento que tienen los pediatras sobre este tema en nuestro medio. Objetivo: indagar sobre el conocimiento que tienen estudiantes de posgrado de Pediatría y pediatras sobre la prescripción off label. Material y método: encuesta anónima a posgrados de Pediatría y pediatras que desempeñan su actividad en el Centro Hospitalario Pereira Rossell, Asociación Española y Médica Uruguaya. Se indagó acerca del conocimiento del término off label, su definición y prácticas habituales de prescripción. Se seleccionaron cinco fármacos de prescripción frecuente con el fin de indagar sus usos fuera de prospecto. Resultados: se encuestaron 63 profesionales, 34 posgrados y 29 pediatras. Refirieron conocer el término off label 25 (40%), de éstos, 10 desconocían el significado del mismo. Lograron identificar los usos off label de adrenalina 18, domperidona 17, loratadina 13, omeprazol 8 y ondansetrón 8. Conclusiones: se puede observar que la mayoría de los encuestados no tiene el conocimiento suficiente acerca de esta práctica, pudiendo constituir un problema para su prescripción.


Summary: Off-label drug prescription involves prescribing drugs under different conditions from those described in packaging labels or inserts or to those under which they were originally authorized or registered. In Uruguay, we do not know the level of pediatricians' awareness about this issue. Objective: to find out the level of awareness that pediatricians and pediatrics' postgraduate students have regarding off-label prescriptions. Materials and methods: anonymous survey to pediatricians and pediatrics' postgraduate students from the Pereira Rossell Children Hospital, Médica Uruguaya and Asociación Española HMOs. We asked them about their understanding about the term off-label, its definition and habitual prescription practices. We selected five frequently prescribed drugs in order to research about their use outside the package insert. Results: we surveyed 63 professionals, 34 postgraduates and 29 pediatricians. 25 of them (40%) stated that they were aware of the term off-label, thought 10 of them did not know what the term meant. 18 respondents identified off-label use of adrenaline, 17 of domperidone, 13 of loratadine, 8 of omeprazole and 8 of ondansetron. Conclusions: most of the respondents did not have enough awareness or knowledge regarding off-label practices, which can lead to prescription problems.


Resumo: A prescrição de medicamentos off-label é aquela que é realizada em condições diferentes das indicadas na ficha técnica ou prospecto e, portanto, diferentes daquelas para as que os medicamentos foram originalmente ou autorizados e registrados. Não conhecemos o nível de conhecimento que os pediatras têm sobre o assunto em Uruguai. Objetivo: investigar o conhecimento que os pediatras e estudantes de pós-graduação em pediatria têm sobre a prescrição off-label. Materiais e métodos: pesquisa anónima realizada a pediatras e estudantes de pediatria que trabalham no CHPR, Associação Espanhola e na Médica Uruguaia. Lhes perguntamos sobre o seu conhecimento do termo off-label, sobre sua definição e práticas de prescrição habitual. Selecionamos cinco medicamentos de prescrição frequente e pesquisamos o seu uso fora do folheto informativo. Resultados: pesquisamos 63 médicos, 34 pós-graduandos e 29 pediatras. 25 (40%) referiram conhecer o termo off-label. Desses 25, 10 não sabiam o significado do mesmo. Eles conseguiram identificar usos off-label de: adrenalina 18, domperidona 17, loratadina 13, omeprazol 8 e ondansetrom 8. Conclusões: a maioria dos entrevistados não tinham suficiente conhecimento sobre esta prática, o que pode ser um problema no momento da prescrição.

11.
J Morphol ; 279(6): 841-856, 2018 06.
Article in English | MEDLINE | ID: mdl-29570829

ABSTRACT

Cubozoans (box jellyfish) are gonochoristic cnidarians with distinct reproductive strategies. This comparative histological study examines the gonad organization of Alatina alata and Copula sivickisi, two box jellyfish species that exhibit different modes of internal fertilization. A. alata reproduces via spermcasting aggregations while C. sivickisi reproduces via copulation; in both cases, internal fertilization occurs in the gastrovascular cavity. Herein, we provide the first histological description of subgastric sacs-structures unique to C. sivickisi. Although previously thought to function as sperm storage sacs, our findings reveal that subgastric sacs are nematocyst nests lacking sperm entirely. Conversely, we discovered that velarial spots in C. sivickisi females correspond to actual sperm storage structures. Histological examination of cubozoan sperm packages revealed that while sperm packages from both species have motile flagella, A. alata males produce nonencapsulated sperm bundles (i.e., "spermatozeugmata"), and C. sivickisi males produce encapsulated packages (i.e., "spermatophores"). Our findings corroborate the presence of several types of nematocysts in C. sivickisi embryo strands and spermatophores, and indicate their provenance to be both female and male gonads respectively, as well as subgastric sacs (i.e., nematocyst nests). In contrast to our findings of velarial spots as sperm storages structures in C. sivickisi females, and of nematocysts in the gonads of both sexes, we report that A. alata medusae lack both sperm storage structures and gonadal nematocysts. Finally, we discuss our findings on reproductive morphology of C. sivickisi and A. alata in light of the respective reproductive behavior of these two cubozoan species.


Subject(s)
Cubozoa/anatomy & histology , Animals , Cubozoa/physiology , Female , Male , Reproduction/physiology
13.
PLoS One ; 7(10): e46422, 2012.
Article in English | MEDLINE | ID: mdl-23071566

ABSTRACT

The control of cell death is a biological process essential for proper development, and for preventing devastating pathologies like cancer and neurodegeneration. On the other hand, autophagy regulation is essential for protein and organelle degradation, and its dysfunction is associated with overlapping pathologies like cancer and neurodegeneration, but also for microbial infection and aging. In the present report we show that two evolutionarily unrelated receptors--Neurokinin 1 Receptor (NK(1)R,) a G-protein coupled receptor, and Insulin-like Growth Factor 1 Receptor (IGF1R), a tyrosine kinase receptor--both induce non-apoptotic cell death with autophagic features and requiring the activity of the autophagic core machinery proteins PI3K-III, Beclin-1 and Atg7. Remarkably, this form of cell death occurs in apoptosis-competent cells. The signal transduction pathways engaged by these receptors both converged on the activation of the nuclear receptor NR4A1, which has previously been shown to play a critical role in some paradigms of apoptosis and in NK(1)R-induced cell death. The activity of NR4A1 was necessary for IGF1R-induced cell death, as well as for a canonical model of cell death by autophagy induced by the presence of a pan-caspase inhibitor, suggesting that NR4A1 is a general modulator of this kind of cell death. During cell death by autophagy, NR4A1 was transcriptionally competent, even though a fraction of it was present in the cytoplasm. Interestingly, NR4A1 interacts with the tumor suppressor p53 but not with Beclin-1 complex. Therefore the mechanism to promote cell death by autophagy might involve regulation of gene expression, as well as protein interactions. Understanding the molecular basis of autophagy and cell death mediation by NR4A1, should provide novel insights and targets for therapeutic intervention.


Subject(s)
Autophagy , Cell Death/physiology , Nuclear Receptor Subfamily 4, Group A, Member 1/physiology , Caspase Inhibitors/pharmacology , HEK293 Cells , Humans , Receptor, IGF Type 1/physiology
14.
Expert Opin Ther Targets ; 15(7): 847-58, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21473736

ABSTRACT

INTRODUCTION: Tropomyosin-related kinase receptor C (TrkC) is a neurotrophin receptor that belongs to the tyrosine kinase receptor family. This family primarily consists of proto-oncogenes, and TrkC has been involved in oncogenic translocations. However, its expression in tumors is often associated with good prognosis, suggesting it actually acts as a tumor suppressor. TrkC has recently been demonstrated to be a dependence receptor, which regulates neuronal survival. Dependence receptors share the ability to trigger apoptosis in the absence of their ligand, a feature that has been suggested to confer a tumor suppressor function to these receptors. A selective advantage for a tumor cell to survive in an environment with limited ligand availability would hence be either to lose the expression of the dependence receptor, or to gain expression of its ligand. AREAS COVERED: The role of neurotrophin-3 (NT-3) and its dependence receptor TrkC in neuroblastoma, and its suitability as a therapeutic target. EXPERT OPINION: Autocrine production of NT-3 represents a selective advantage for tumor growth and dissemination, in a large fraction of aggressive neuroblastoma. Disruption of the NT-3 autocrine loop in malignant neuroblasts, triggers neuroblastoma cell death, and inhibits neuroblastoma metastasis in animal models. Thus, a novel way of targeting the tyrosine kinase receptor, is via the reactivation of its intrinsic ability to trigger cell death.


Subject(s)
Antineoplastic Agents/pharmacology , Neurotrophin 3/drug effects , Receptor, trkC/metabolism , Animals , Child , Humans , Oncogenes
15.
J Biol Chem ; 286(16): 14628-38, 2011 Apr 22.
Article in English | MEDLINE | ID: mdl-21357690

ABSTRACT

RET is a tyrosine kinase receptor involved in numerous cellular mechanisms including proliferation, neuronal navigation, migration, and differentiation upon binding with glial cell derived neurotrophic factor family ligands. RET is an atypical tyrosine kinase receptor containing four cadherin domains in its extracellular part. Furthermore, it has been shown to act as a dependence receptor. Such a receptor is active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. However, different data suggest that RET is not always associated with the cell death/survival balance but rather provides positional information. We demonstrate here that caspase cleavage of RET is involved in the regulation of adhesion in sympathetic neurons. The cleavage of RET generates an N-terminal truncated fragment that functions as a cadherin accessory protein, modifying cadherin environment and potentiating cadherin-mediated cell aggregation. Thus, the caspase cleavage of RET generates two RET fragments: one intracellular domain that can trigger cell death in apoptotic permissive settings, and one membrane-anchored ectodomain with cadherin accessory activity. We propose that this latter function may notably be important for the adequate development of the superior cervical ganglion.


Subject(s)
Caspases/metabolism , Neurons/metabolism , Proto-Oncogene Proteins c-ret/metabolism , Proto-Oncogene Proteins c-ret/physiology , Animals , Animals, Newborn , Apoptosis , COS Cells , Cadherins/metabolism , Cell Adhesion , Cell Membrane/metabolism , Chlorocebus aethiops , Ganglia/metabolism , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Humans , Mice
16.
J Clin Invest ; 120(3): 850-8, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20160348

ABSTRACT

Tropomyosin-related kinase receptor C (TrkC) is a neurotrophin receptor with tyrosine kinase activity that was expected to be oncogenic. However, it has several characteristics of a tumor suppressor: its expression in tumors has often been associated with good prognosis; and it was recently demonstrated to be a dependence receptor, transducing different positive signals in the presence of ligand but inducing apoptosis in the absence of ligand. Here we show that the TrkC ligand neurotrophin-3 (NT-3) is upregulated in a large fraction of aggressive human neuroblastomas (NBs) and that it blocks TrkC-induced apoptosis of human NB cell lines, consistent with the idea that TrkC is a dependence receptor. Functionally, both siRNA knockdown of NT-3 expression and incubation with a TrkC-specific blocking antibody triggered apoptosis in human NB cell lines. Importantly, disruption of the NT-3 autocrine loop in malignant human neuroblasts triggered in vitro NB cell death and inhibited tumor growth and metastasis in both a chick and a mouse xenograft model. Thus, we believe that our data suggest that NT-3/TrkC disruption is a putative alternative targeted therapeutic strategy for the treatment of NB.


Subject(s)
Apoptosis , Autocrine Communication , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/biosynthesis , Neuroblastoma/metabolism , Neurotrophin 3/biosynthesis , Receptor, trkC/biosynthesis , Animals , Cell Line, Tumor , Cell Survival , Chickens , Gene Knockdown Techniques , Humans , Mice , Mice, Nude , Neoplasm Proteins/genetics , Neoplasm Transplantation , Neuroblastoma/genetics , Neuroblastoma/pathology , Neuroblastoma/therapy , Neurotrophin 3/genetics , Receptor, trkC/genetics , Transplantation, Heterologous , Up-Regulation/genetics
17.
Comput Methods Programs Biomed ; 96(2): 141-57, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19481289

ABSTRACT

Innovation in the fields of wireless data communications, mobile devices and biosensor technology enables the development of new types of monitoring systems that provide people with assistance anywhere and at any time. In this paper we present an architecture useful to build those kind of systems that monitor data streams generated by biological sensors attached to mobile users. We pay special attention to three aspects related to the system efficiency: selection of the optimal granularity, that is, the selection of the size of the input data stream package that has to be acquired in order to start a new processing cycle; the possible use of compression techniques to store and send the acquired input data stream and; finally, the performance of a local analysis versus a remote one. Moreover, we introduce two particular real systems to illustrate the suitability and applicability of our proposal: an anywhere and at any time monitoring system of heart arrhythmias and an apnea monitoring system.


Subject(s)
Biosensing Techniques/economics , Biosensing Techniques/instrumentation , Monitoring, Ambulatory/economics , Monitoring, Ambulatory/instrumentation , Telemedicine/economics , Telemedicine/instrumentation , Computer Communication Networks/economics , Computer Communication Networks/instrumentation , Computer Systems , Computer-Aided Design , Equipment Design , Equipment Failure Analysis , Reproducibility of Results , Sensitivity and Specificity , Spain
18.
Proc Natl Acad Sci U S A ; 104(33): 13361-6, 2007 Aug 14.
Article in English | MEDLINE | ID: mdl-17686986

ABSTRACT

The TrkC/NT-3 receptor/ligand pair is believed to be part of the classic neurotrophic theory claiming that neuronal death occurs by default when neurotrophic factors become limited, through loss of survival signals. Here, we show that TrkC is a dependence receptor and, as such, induces caspase-dependent apoptotic death in the absence of NT-3 in immortalized cells, a proapoptotic activity inhibited by the presence of NT-3. This proapoptotic activity of TrkC relies on the caspase-mediated cleavage of the intracellular domain of TrkC, which permits the release of a proapoptotic fragment. This fragment induces apoptosis through a caspase-9-dependent mechanism. Finally, we show that the death of dorsal root ganglion (DRG) neurons provoked by NT-3 withdrawal is inhibited when TrkC-proapoptotic activity is antagonized. Thus, the death of neurons upon disappearance of NT-3 is not only due to a loss of survival signals but also to the active proapoptotic activity of the unbound TrkC dependence receptor.


Subject(s)
Apoptosis/physiology , Receptor, trkC/physiology , Animals , Caspases/metabolism , Humans , Hydrolysis , Neurons/cytology , Rats
19.
IEEE Trans Inf Technol Biomed ; 9(1): 23-34, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15787004

ABSTRACT

The new advances in sensor technology, personal digital assistants (PDAs), and wireless communications favor the development of a new type of monitoring system that can provide patients with assistance anywhere and at any time. Of particular interest are the monitoring systems designed for people that suffer from heart arrhythmias, due to the increasing number of people with cardiovascular diseases. PDAs can play a very important role in these kinds of systems because they are portable devices that can execute more and more complex tasks. The main questions answered in this paper are whether PDAs can perform a complete electrocardiogram beat and rhythm classifier, if the classifier has a good accuracy, and if they can do it in real time. In order to answer these questions, in this paper, we show the steps that we have followed to build the algorithm that classifies beats and rhythms, and the obtained results, which show a competitive accuracy. Moreover, we also show the feasibility of incorporating the built algorithm into the PDA.


Subject(s)
Algorithms , Artificial Intelligence , Computers, Handheld , Diagnosis, Computer-Assisted/methods , Electrocardiography, Ambulatory/methods , Heart Rate/physiology , Pattern Recognition, Automated/methods , Computer Systems , Humans , Online Systems , Physiology , Reproducibility of Results , Sensitivity and Specificity
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