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1.
Eur J Intern Med ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38653633

RESUMO

Elevated blood pressure (BP) is the largest contributor to the incident cardiovascular disease worldwide. Despite explicit guideline recommendations for the diagnosis and management of hypertension, a large proportion of patients remain undiagnosed, untreated, or treated but uncontrolled. Inadequate BP control is associated with many complex factors including patient preference, physician's inertia, health systems disparities, and poor adherence to prescribed antihypertensive drug treatment. The primary driver for reduced cardiovascular morbidity and mortality is lowering of BP ''per se'' and not class effects of specific pharmacotherapies. The recent ESH guidelines recommend the use of four major classes of drugs including renin-angiotensin-aldosterone system (RAS) blockers (angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEi)), calcium channel blockers (CCB), thiazide and thiazide-like diuretics, and betablockers. Initiation of treatment for hypertension with a two-drug regimen, preferably in a single pill combination (SPC), is recommended for most patients. Preferred combinations should comprise a RAS blocker (either an ACEi or an ARB) with a CCB or thiazide/thiazide-like diuretic. These strategies are supported by robust evidence that combination therapy produces greater BP reductions than monotherapy, reduces side effects of the individual components, improves therapeutic adherence and long-term persistence on treatment, and permits achievement of earlier BP control.

2.
J Hosp Med ; 18(9): 795-802, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37553979

RESUMO

BACKGROUND: Time spent awaiting discharge after the acute need for hospitalization has resolved is an important potential contributor to hospital length of stay (LOS). OBJECTIVE: To measure the prevalence, impact, and context of patients who remain hospitalized for prolonged periods after completion of acute care needs. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional "point-in-time" survey at each of 15 academic US hospitals using a structured data collection tool with on-service acute care medicine attending physicians in fall 2022. MAIN OUTCOMES AND MEASURES: Primary outcomes were number and percentage of patients considered "medically ready for discharge" with emphasis on those who had experienced a "major barrier to discharge" (medically ready for discharge for ≥1 week). Estimated LOS attributable to major discharge barriers, contributory discharge needs, and associated hospital characteristics were measured. RESULTS: Of 1928 patients sampled, 35.0% (n = 674) were medically ready for discharge including 9.8% (n = 189) with major discharge barriers. Many patients with major discharge barriers (44.4%; 84/189) had spent a month or longer medically ready for discharge and commonly (84.1%; 159/189) required some form of skilled therapy or daily living support services for discharge. Higher proportions of patients experiencing major discharge barriers were found in public versus private, nonprofit hospitals (12.0% vs. 7.2%; p = .001) and county versus noncounty hospitals (14.5% vs. 8.8%; p = .002). CONCLUSIONS: Patients experience major discharge barriers in many US hospitals and spend prolonged time awaiting discharge, often for support needs that may be outside of clinician control.


Assuntos
Hospitalização , Alta do Paciente , Humanos , Estudos Transversais , Tempo de Internação , Hospitais
3.
Arch. Soc. Esp. Oftalmol ; 98(3): 150-154, mar. 2023. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-216822

RESUMO

Objetivo Evaluar la posibilidad de terapia génica en pacientes con enfermedades oculares hereditarias con diagnóstico genético establecido. Los objetivos secundarios son revisar la tasa de diagnóstico genético y hacer una actualización de los genes para los cuales hay estudios clínicos o preclínicos en curso que pudieran permitir la terapia génica. Métodos Estudio observacional, retrospectivo y multicéntrico de 177 pacientes con enfermedades oculares hereditarias a quienes se realizó estudio genético.Resultados De 177 pacientes con estudio genético, se incluyeron 146. Se identificaron variantes causantes de enfermedad en 117 pacientes con lo que se obtuvo una tasa de detección de variantes del 80,1%. Se encontraron variantes patogénicas en 47 genes, siendo ABCA4 el gen más común (17,9%), seguido por CRB1 (11,9%). De los pacientes con diagnóstico genético, el 64,1% tienen una variante en un gen para el cual se ha estudiado terapia génica y solo el 40,1% presentan una variante en genes con estudios para su terapia génica en fase clínica. Conclusiones El estudio genético ha abierto nuevos horizontes en el manejo de pacientes con enfermedades oculares hereditarias. Cerca de dos tercios de los pacientes presentó variantes patogénicas en genes para los cuales se ha evaluado la posibilidad de terapia génica. Sin embargo, muchos estudios se encuentran en fase preclínica. Se debe adecuar las expectativas de los pacientes sometidos a estudio genético y sus familias (AU)


Objective To evaluate the possibility of gene therapy in patients with inherited ocular conditions and established genetic diagnosis. The secondary objectives were to determine the genetic diagnostic rate and to update the list of genes for which there are ongoing clinical trials or preclinical studies that could allow for gene therapy. Methods Observational, retrospective, multicentric study of 177 patients with inherited ocular conditions that underwent genetic testing. Results Of 177 patients with genetic testing, 146 were enrolled for this study. Disease-causing variants were identified in 117 patients (variant detection rate of 80.1%). Pathogenic variants were found in 47 genes, with ABCA4 being the most common gene (17.9%), followed by CRB1 (11.9%). 64.1% of patients with a genetic diagnosis have a variant in genes for which gene therapy has been studied and only 40.1% have a variant in genes with studies for gene therapy in clinical phase. Conclusions Genetic testing has opened new horizons in the management of patients with hereditary ocular diseases. About two-thirds of the patients had pathogenic variants in genes for which gene therapy has been evaluated. However, many studies are in the pre-clinical phase. The expectations of patients undergoing genetic study and their families should be managed accordingly (AU)


Assuntos
Humanos , Terapia Genética/métodos , Doenças Retinianas/terapia , Oftalmopatias Hereditárias/terapia , Estudos Retrospectivos
4.
Arch Soc Esp Oftalmol (Engl Ed) ; 98(3): 150-154, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36577466

RESUMO

OBJECTIVE: To evaluate the possibility of gene therapy in patients with inherited ocular conditions and established genetic diagnosis. The secondary objectives were to determine the genetic diagnostic rate and to update the list of genes for which there are ongoing clinical trials or preclinical studies that could allow for gene therapy. METHODS: Observational, retrospective, multicentric study of 177 patients with inherited ocular conditions that underwent genetic testing. RESULTS: Of 177 patients with genetic testing, 146 were enrolled for this study. Disease-causing variants were identified in 117 patients (variant detection rate of 80.1%). Pathogenic variants were found in 47 genes, with ABCA4 being the most common gene (17.9%), followed by CRB1 (11.9%). 64.1% of patients with a genetic diagnosis have a variant in genes for which gene therapy has been studied and only 40.1% have a variant in genes with studies for gene therapy in clinical phase. CONCLUSIONS: Genetic testing has opened new horizons in the management of patients with hereditary ocular diseases. About two-thirds of the patients had pathogenic variants in genes for which gene therapy has been evaluated. However, many studies are in the pre-clinical phase. The expectations of patients undergoing genetic study and their families should be managed accordingly.


Assuntos
Proteínas do Olho , Doenças Retinianas , Humanos , Estudos Retrospectivos , Proteínas do Olho/genética , Retina , Terapia Genética , Transportadores de Cassetes de Ligação de ATP/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética
5.
Rev Gastroenterol Mex (Engl Ed) ; 87(2): 235-250, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35623990

RESUMO

Cow's milk protein allergy (CMPA) is the most frequent cause of food allergy in the first months of life. Despite the fact that there are different guidelines and recommendations on the management of children with CMPA, there continues to be great variability in diagnostic and therapeutic criteria in Latin America. The Food Allergy Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition summoned a group of Latin American experts to reach a consensus and formulate a document to unify diagnostic and therapeutic criteria for CMPA. Three teams were formed, each with a coordinator, and the members of each team developed a series of statements for their corresponding module: a) clinical manifestations and diagnosis; b) diagnostic tools, and c) treatment. A search of the medical literature was carried out to support the information presented in each module and 28 statements were then selected. The statements were discussed, after which they were evaluated by all the experts, utilizing the Delphi method. Their opinions on statement agreement or disagreement were anonymously issued. The final statements selected were those with above 75% agreement and their corresponding recommendations were formulated, resulting in the document presented herein.


Assuntos
Gastroenterologia , Hipersensibilidade a Leite , Animais , Bovinos , Consenso , Feminino , Humanos , América Latina , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/terapia , Proteínas do Leite/efeitos adversos
6.
Phys Rev E ; 104(5-1): 054143, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34942778

RESUMO

Lévy flight superdiffusion consists of random walks characterized by very long jumps that dominate the transport. However, the finite size of real samples introduces truncation of long jumps and modifies the transport properties. We measure typical Levy flight parameters for photon diffusion in atomic vapor characterized by a Voigt absorption profile. We observe the change of Lévy parameter as a function of truncation length. We associate this variation with size-dependent contributions from different spectral regions of the emission profile with the Doppler core dominating the transport for thin samples and Lorentz wings for thick samples. Monte Carlo simulations are implemented to support the interpretation of results.

7.
Rev. clín. esp. (Ed. impr.) ; 221(9): 547-552, nov. 2021. graf, ilus
Artigo em Espanhol | IBECS | ID: ibc-227030

RESUMO

La hipertensión arterial (HTA) es el principal factor de riesgo de enfermedad cardiovascular. Aunque es un problema global, independiente de la situación económica, región, raza o cultura, los datos disponibles con respecto a Latinoamérica no son muy abundantes. Por otra parte, las guías clínicas enfatizan la importancia de obtener lecturas fiables de la presión arterial. Por ello, se recomienda el uso de la monitorización ambulatoria de la presión arterial (MAPA), que mejora su precisión y reproducibilidad, ayudando a un mejor diagnóstico, en la toma de decisiones terapéuticas, y representa una mejor estimación pronóstica que las medidas en consulta. Lamentablemente, no existe ningún registro prospectivo global de MAPA para toda Latinoamérica que analice la prevalencia de HTA, el grado de su conocimiento, su porcentaje de tratamiento y el grado de control. En consecuencia, los autores de este artículo consideran prioritaria su puesta en marcha (AU)


Hypertension (HT) is one of the main risk factors for cardiovascular disease. Although it is a global problem, independently of economic situation, region, race or culture, the data available on Latin America are limited. Clinical guidelines emphasise the importance of obtaining reliable blood pressure readings. For this reason, the use of ambulatory blood pressure monitoring (ABPM) is recommended. This improves precision and reproducibility, resulting in better diagnosing and therapeutic decision-making, and constitutes a better estimation of prognosis than office measurements. Unfortunately, there is no global prospective ABPM registry for all of Latin America that analyses HT prevalence, the level of knowledge about it, treatment percentage and the degree of control. Consequently, the authors of this article consider its implementation a priority (AU)


Assuntos
Humanos , Monitorização Ambulatorial da Pressão Arterial , Hipertensão/epidemiologia , Hipertensão/prevenção & controle , América Latina/epidemiologia
8.
Rev Clin Esp (Barc) ; 221(9): 547-552, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34509417

RESUMO

Hypertension (HT) is one of the main risk factors for cardiovascular disease (CVD). Although it is a global problem, independently of economic situation, region, race or culture, the data available on Latin America are limited. Clinical guidelines emphasise the importance of obtaining reliable blood pressure readings. For this reason, the use of ambulatory blood pressure monitoring (ABPM) is recommended. This improves precision and reproducibility, resulting in better diagnosing and therapeutic decision-making, and constitutes a better estimation of prognosis than office measurements. Unfortunately, there is no global prospective ABPM registry for all of Latin America that analyses HT prevalence, the level of knowledge about it, treatment percentage and the degree of control. Consequently, the authors of this article consider its implementation a priority.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Hipertensão , Pressão Sanguínea , Humanos , Hipertensão/epidemiologia , Estudos Prospectivos , Sistema de Registros , Reprodutibilidade dos Testes , Estados Unidos
9.
Arch Soc Esp Oftalmol (Engl Ed) ; 96(6): 288-292, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34092282

RESUMO

OBJECTIVE: To establish the success rate of salvage intra-arterial chemotherapy (IAC), defined as the percentage of eyes that achieved tumoral remission and avoided enucleation. The second objective was the clinical characterization, catheterization results, and associated local and systemic complications. METHODS: Retrospective, interventional case series of 29 patients (35 eyes) with persistent or recurrent retinoblastoma. RESULTS: A total of 73 salvage IAC procedures with topotecan and melphalan were carried out. Success rate was 77% at a mean follow-up of 41.4 months. All patients with only one remaining eye avoided enucleation (10 cases). Catheterization was successful in 98.6% of cases. The types of catheterizations were as follows: 71.2% supraselective ophthalmic artery, 12.3% occlusion pump assisted supraselective ophthalmic artery, 16.4% selective external carotid with retrograde flow. 14% of patients suffered local adverse effects: 1 (2.8%) transitory ptosis, 1 (2.8%) transitory oculomotor nerve palsy, 2 (5.7%) aseptic cellulitis and 1 (2.8%) periorbitary pigmentation. 4.1% (3 cases) suffered neutropenia due to medullar chemosuppression. There were no cases of severe anemia or thrombocytopenia. There were no cerebral ischemic events or mortality associated to the procedure. CONCLUSION: IAC with melphalan and topotecan is a safe and effective treatment option for persistent or recurrent retinoblastoma, able to reduce enucleation rates.


Assuntos
Neoplasias da Retina , Retinoblastoma , Chile , Humanos , Infusões Intra-Arteriais , Recidiva Local de Neoplasia , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Estudos Retrospectivos
10.
Arch. Soc. Esp. Oftalmol ; 96(6): 288-292, jun. 2021.
Artigo em Espanhol | IBECS | ID: ibc-217835

RESUMO

Objetivo Establecer la tasa de éxito de la quimioterapia intraarterial (QIA) en modalidad de rescate expresada en el porcentaje de ojos que lograron remisión tumoral y evitaron la enucleación. El segundo objetivo fue analizar la caracterización clínica, resultados del cateterismo, complicaciones locales y sistémicas asociadas. Métodos Estudio retrospectivo de serie de casos intervencional de 29 pacientes (35 ojos) con retinoblastoma intraocular persistente o recidivado. Resultados Se realizaron un total de 73 procedimientos de QIA con topotecán y melfalán en modalidad de rescate. La tasa de éxito de la QIA fue del 77% en un seguimiento promedio de 41,4 meses. Todos los casos con ojo único evitaron la enucleación de su ojo residual (10 casos). El cateterismo fue exitoso en un 98,6%. Los tipos de cateterización logrados fueron los siguientes: supraselectiva por arteria oftálmica (71,2%), supraselectiva por arteria oftálmica asistida con balón de oclusión en carótida externa (12,3%), selectiva por rama de carótida externa con flujo retrógrado (16,4%). Se reportaron efectos adversos locales en el 14% de los pacientes: una (2,8%) ptosis palpebral transitoria, una (2,8%) parálisis del sexto par transitoria, 2 (5,7%) celulitis aséptica y una (2,8%) pigmentación de región periorbitaria. La frecuencia de neutropenia por quimiosupresión medular fue del 4,1% (3 casos). No hubo casos de anemia ni trombocitopenia severas. No hubo eventos isquémicos cerebrales ni mortalidad asociada al procedimiento. Conclusión La QIA con melfalán y topotecán es una alternativa segura y efectiva para el tratamiento del retinoblastoma persistente o recidivado, permitiendo reducir las tasas de enucleación (AU)


Objective To establish the success rate of salvage intra-arterial chemotherapy (IAC), defined as the percentage of eyes that achieved tumoral remission and avoided enucleation. The second objective was the clinical characterization, catheterization results, and associated local and systemic complications. Methods Retrospective, interventional case series of 29 patients (35 eyes) with persistent or recurrent retinoblastoma. Results A total of 73 salvage IAC procedures with topotecan and melphalan were carried out. Success rate was 77% at a mean follow-up of 41.4 months. All patients with only one remaining eye avoided enucleation (10 cases). Catheterization was successful in 98.6% of cases. The types of catheterizations were as follows: 71.2% supraselective ophthalmic artery, 12.3% occlusion pump assisted supraselective ophthalmic artery, 16.4% selective external carotid with retrograde flow. 14% of patients suffered local adverse effects: 1 (2.8%) transitory ptosis, 1 (2.8%) transitory oculomotor nerve palsy, 2 (5.7%) aseptic cellulitis and 1 (2.8%) periorbitary pigmentation. 4.1% (3 cases) suffered neutropenia due to medullar chemosuppression. There were no cases of severe anemia or thrombocytopenia. There were no cerebral ischemic events or mortality associated to the procedure. Conclusion IAC with melphalan and topotecan is a safe and effective treatment option for persistent or recurrent retinoblastoma, able to reduce enucleation rates (AU)


Assuntos
Humanos , Masculino , Feminino , Retinoblastoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Injeções Intra-Arteriais , Resultado do Tratamento , Estudos Retrospectivos , Recidiva Local de Neoplasia , Seguimentos , Análise de Sobrevida , Chile
11.
Arch Soc Esp Oftalmol (Engl Ed) ; 96(1): 26-31, 2021 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33067032

RESUMO

INTRODUCTION: The red reflex examination (RRE) and visual acuity testing (VA) is a mandatory part of the examination during the well-child visits (WCV) in primary health care centres of the public system of health in Chile. The eye examination is aimed at the early detection of severe eye diseases in children, such as retinoblastoma, congenital cataracts, and amblyopia. The knowledge and difficulties experienced by health workers in primary care health centres for evaluating the red reflex during WCV in Chile is unknown. MATERIAL AND METHODS: A survey was performed in primary community health centres of XXX Santiago de Chile. RESULTS: The WCV were mainly performed by physicians (45.2%) and nurses (35.8%). Only 34% of health workers performed the red reflex test, and 42.3% checked VA during the WCV. The main reasons for not doing it include the lack of direct ophthalmoscopes and VA charts (55.2% and 43.9%, respectively) at their centres, and not having the knowledge or skills (29.3% and 22%, respectively) to properly perform these clinical tests. CONCLUSION: In this series, the eye examination of children attending WCV was unfrequently performed. A better implementation of the health centres and training of the health workers are needed in order to improve the access and quality of the paediatric eye examination in primary health care institutions in Chile.

12.
Opt Lett ; 45(13): 3490-3493, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32630879

RESUMO

We report on a new, to the best of our knowledge, type of optical memory that allows for the amplification of the optical signal carrying the stored information during its reading process. The memory mechanism is demonstrated in an ensemble of cold cesium atoms and is based on the multiple parametric four-wave mixing exploring the external atomic degrees of freedom via recoil-induced resonances. We have particularly demonstrated the storage of light carrying orbital angular momentum with a fourfold amplifying factor for the retrieved signal during the reading process. Memory lifetimes of the order of hundreds of microseconds have been measured, and possible applications for this self-amplifying memory are discussed.

13.
Mol Psychiatry ; 23(10): 2050-2056, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29158579

RESUMO

Bipolar disorder (BD) is a prevalent mood disorder that tends to cluster in families. Despite high heritability estimates, few genetic susceptibility factors have been identified over decades of genetic research. One possible interpretation for the shortcomings of previous studies to detect causative genes is that BD is caused by highly penetrant rare variants in many genes. We explored this hypothesis by sequencing the exomes of affected individuals from 40 well-characterized multiplex families. We identified rare variants segregating with affected status in many interesting genes, and found an enrichment of deleterious variants in G protein-coupled receptor (GPCR) family genes, which are important drug targets. Furthermore, we showed targeted downstream GPCR dysregulation for some of the variants that may contribute to disease pathology. Particularly interesting was the finding of a rare and functionally relevant nonsense mutation in the corticotropin-releasing hormone receptor 2 (CRHR2) gene that tracked with affected status in one family. By focusing on rare variants in informative families, we identified key biochemical pathways likely implicated in this complex disorder.


Assuntos
Transtorno Bipolar/genética , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Adulto , Transtorno Bipolar/metabolismo , Estudos de Casos e Controles , Família , Feminino , Frequência do Gene/genética , Ligação Genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Receptores de Hormônio Liberador da Corticotropina/genética , Sequenciamento do Exoma
14.
Opt Lett ; 42(21): 4474-4477, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29088191

RESUMO

We report a new type of optical memory using a pure two-level system of cesium atoms cooled by the magnetically assisted Sisyphus effect. The optical information of a probe field is stored in the coherence between quantized vibrational levels of the atoms in the potential wells of a 1-D optical lattice. The retrieved pulse shows Rabi oscillations with a frequency determined by the reading beam intensity and are qualitatively understood in terms of a simple theoretical model. The exploration of the external degrees of freedom of an atom may add another capability in the design of quantum-information protocols using light.

16.
Arch Soc Esp Oftalmol ; 91(8): 379-84, 2016 Aug.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27021801

RESUMO

OBJECTIVES: To report the benefits of genetic diagnosis in patients with retinoblastoma. METHOD: Observational study. Patients with retinoblastoma and their families were included. Demographic and clinical data were recorded. Blood and tumour samples were obtained. Next generation sequencing was performed on the samples. When deletion 13 q syndrome was suspected, cytogenetics microarray was performed (Cytoscan® HD, Affymetrix, Santa Clara, CA, USA), with a high density chip of 1.9 million of non-polymorphic probes and 750 thousand SNP probes. RESULTS: Of the 7 cases were analysed 4 were male. The mean age at diagnosis was 21 months (range 5-36). Three cases had bilateral retinoblastoma, and 4 unilateral. None had family history. In all patients, blood was analysed, and a study was performed on the tissue from 2 unilateral enucleated tumours, in which 6 mutations were identified, all de novo. Just one was novel (c.164delC; case 1). One case of unilateral tumour revealed blood mosaicism, showing that his condition was inheritable, and that there is a high risk of developing retinoblastoma in the unaffected eye. The patient also has an increased risk of presenting with other primary tumours. CONCLUSION: Molecular diagnosis of RB1 in patients with retinoblastoma impacts on the decision process, costs, treatment, and prognosis of patients, as well as their families.


Assuntos
DNA de Neoplasias/genética , Neoplasias Oculares/genética , Genes do Retinoblastoma , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas de Ligação a Retinoblastoma/genética , Retinoblastoma/genética , Ubiquitina-Proteína Ligases/genética , Pré-Escolar , Chile , Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 13/genética , Análise Mutacional de DNA , DNA de Neoplasias/sangue , DNA de Neoplasias/isolamento & purificação , Neoplasias Oculares/sangue , Neoplasias Oculares/química , Neoplasias Oculares/diagnóstico , Feminino , Humanos , Lactente , Masculino , Mosaicismo , Mutação , Neoplasias Primárias Múltiplas/sangue , Neoplasias Primárias Múltiplas/química , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/genética , Polimorfismo de Nucleotídeo Único , Retinoblastoma/sangue , Retinoblastoma/química , Retinoblastoma/diagnóstico , Análise de Sequência de DNA/métodos
17.
Transl Psychiatry ; 5: e565, 2015 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-25966365

RESUMO

Genes implicated in neurodevelopmental disorders (NDDs) important in cognition and behavior may have convergent function and several cellular pathways have been implicated, including protein translational control, chromatin modification, and synapse assembly and maintenance. Here, we test the convergent effects of methyl-CpG binding domain 5 (MBD5) and special AT-rich binding protein 2 (SATB2) reduced dosage in human neural stem cells (NSCs), two genes implicated in 2q23.1 and 2q33.1 deletion syndromes, respectively, to develop a generalized model for NDDs. We used short hairpin RNA stably incorporated into healthy neural stem cells to supress MBD5 and SATB2 expression, and massively parallel RNA sequencing, DNA methylation sequencing and microRNA arrays to test the hypothesis that a primary etiology of NDDs is the disruption of the balance of NSC proliferation and differentiation. We show that reduced dosage of either gene leads to significant overlap of gene-expression patterns, microRNA patterns and DNA methylation states with control NSCs in a differentiating state, suggesting that a unifying feature of 2q23.1 and 2q33.1 deletion syndrome may be a lack of regulation between proliferation and differentiation in NSCs, as we observed previously for TCF4 and EHMT1 suppression following a similar experimental paradigm. We propose a model of NDDs whereby the balance of NSC proliferation and differentiation is affected, but where the molecules that drive this effect are largely specific to disease-causing genetic variation. NDDs are diverse, complex and unique, but the optimal balance of factors that determine when and where neural stem cells differentiate may be a major feature underlying the diverse phenotypic spectrum of NDDs.


Assuntos
Diferenciação Celular/genética , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação à Região de Interação com a Matriz/genética , Células-Tronco Neurais/metabolismo , Transtornos do Neurodesenvolvimento/genética , Neurogênese/genética , Fatores de Transcrição/genética , Células Cultivadas , Deleção Cromossômica , Cromossomos Humanos Par 2 , Metilação de DNA , Epigênese Genética , Dosagem de Genes , Regulação da Expressão Gênica no Desenvolvimento , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MicroRNAs , Modelos Moleculares , Análise de Sequência de RNA
18.
Transl Psychiatry ; 5: e511, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25689572

RESUMO

Although multiple studies have reported that peripheral glial cell line-derived neurotrophic factor (GDNF) is reduced in depression, cerebral GDNF signalling has yet to be examined in this condition. Here, we report an isoform-specific decrease in GDNF family receptor alpha 1 (GFRA1) mRNA expression, resulting in lowered GFRα1a protein levels in basolateral amygdala (BLA) samples from depressed subjects. Downregulation of GFRα1a was associated with increased expression of microRNAs, including miR-511, predicted to bind to long 3' untranslated region (3'-UTR)-containing transcripts (GFRA1-L) coding for GFRα1a. Transfection of human neural progenitor cells (NPCs) with a miR-511 mimic was sufficient to repress GFRA1-L/GFRα1a without altering GFRα1b, and resulted in pathway-specific changes in immediate early gene activity. Unexpectedly, GFRα1a knockdown did not reduce NPC responses to GDNF. Rather, it greatly enhanced mitogen-activated protein kinase signalling. This effect appeared to be mediated by GDNF/soluble GFRα1/neural cell adhesion molecule binding, and substituting the soluble GFRα1a/GFRα1b content of miR-511-transfected NPCs with that of controls rescued signalling. In light of previous reports suggesting that GFRα1b can inhibit GFRα1a-induced neuroplasticity, we also assessed the association between GFRα1 and doublecortin (DCX; a hyperplastic marker) in human BLA. Although controls displayed coordinated expression of GFRα1a and b isoforms and these correlated positively with DCX, the only significant association observed among depressed subjects was a strongly negative correlation between GFRα1b and DCX. Taken together, these results suggest that microRNA-mediated reductions of GFRα1a in depression change the quality, rather than the quantity, of GDNF signalling. They also suggest that central GDNF signalling may represent a novel target for antidepressant treatment.


Assuntos
Tonsila do Cerebelo/metabolismo , Transtorno Depressivo Maior/genética , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/genética , RNA Mensageiro/metabolismo , Adulto , Estudos de Casos e Controles , Transtorno Depressivo Maior/metabolismo , Proteínas do Domínio Duplacortina , Proteína Duplacortina , Regulação para Baixo , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Humanos , Masculino , MicroRNAs/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Moléculas de Adesão de Célula Nervosa , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/metabolismo , Transdução de Sinais/genética , Adulto Jovem
19.
Arch Soc Esp Oftalmol ; 90(1): 9-13, 2015 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-25443208

RESUMO

OBJECTIVE: To study the correlation between expert and non-expert observers in the reporting images for the diagnosis of retinopathy of prematurity (ROP) in a telemedicine setting. METHODS: A cross-sectional, multicenter study, consisting of 25 sets of images of patients screened for ROP. They were evaluated by two experts in ROP and 1 non-expert and classified according to telemedicine classification, zone, stage, plus disease and Ells referral criteria. The telemedicine classification was: no ROP, mild ROP, type 2 ROP, or ROP that requires treatment. Ells referral criteria is defined as the presence at least one of the following: ROP in zone I, Stage 3 in zone I or II, or plus+ For statistical analysis, SPSS 16.0 was used. For correlation, Kappa value was performed. RESULTS: There was a high correlation between observers for the assessment of ROP stage (0.75; 0.54-0.88) plus disease (0.85; 0.71-0.92), and Ells criteria (0.89; 0.83-1.0). However, inter-observer values were low for zone (0.41; 0.27-0.54) and telemedicine classification (0.43; 0.33-0.6). CONCLUSIONS: When evaluating telemedicine images by examiners with different levels of expertise in ROP, the Ells criteria gave the best correlation. In addition, stage of disease and plus disease have good correlation among observers. In contrast, the correlation between observers was low for zone and telemedicine classification.


Assuntos
Variações Dependentes do Observador , Oftalmologia , Oftalmoscopia , Retinopatia da Prematuridade/diagnóstico por imagem , Telemedicina , Estudos Transversais , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Internato e Residência , Oftalmologia/educação , Médicos , Hemorragia Retiniana/diagnóstico por imagem , Hemorragia Retiniana/etiologia , Retinopatia da Prematuridade/complicações , Índice de Gravidade de Doença
20.
Obes Rev ; 15(10): 781-90, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25040597

RESUMO

We performed a systematic review of the prevalence of metabolically healthy obesity (MHO). Medline, Web of Science and EMBASE were searched for original articles from inception to November 2013. Only prospective and cross-sectional studies were included. After screening 478 titles, we selected 55 publications, of which 27 were population-based studies and were used in the narrative synthesis. From the 27 studies, we identified 30 definitions of metabolic health, mainly based on four criteria: blood pressure, high-density lipoprotein cholesterol, triglycerides and plasma glucose. Body mass index ≥30 kg m(-2) was the main indicator used to define obesity (74% of the studies). Overall, MHO prevalence ranged between 6% and 75%. In the studies that stratified the analysis by sex, prevalence was higher in women (seven out of nine studies) and in younger ages (all four studies). One-third of the studies (n = 9) reported the response rate. Of these, four reported a response rate of ≥70% and they showed MHO prevalence estimates between 10% and 51%. The heterogeneity of MHO prevalence estimates described in this paper strengthens calls for the urgent need for a commonly established metabolic health definition.


Assuntos
Glicemia/fisiologia , Pressão Sanguínea/fisiologia , HDL-Colesterol/sangue , Obesidade/epidemiologia , Triglicerídeos/sangue , Biomarcadores/sangue , Composição Corporal , Índice de Massa Corporal , Estudos Transversais , Comportamentos Relacionados com a Saúde , Humanos , Obesidade/classificação , Obesidade/metabolismo , Prevalência , Estudos Prospectivos
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