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PURPOSE: To evaluate the incidence of mosaicism in de novo neurofibromatosis 2 (NF2). METHODS: Patients fulfilling NF2 criteria, but with no known affected family member from a previous generation (n = 1055), were tested for NF2 variants in lymphocyte DNA and where available tumor DNA. The proportion of individuals with a proven or presumed mosaic NF2 variant was assessed and allele frequencies of identified variants evaluated using next-generation sequencing. RESULTS: The rate of proven/presumed mosaicism was 232/1055 (22.0%). However, nonmosaic heterozygous pathogenic variants were only identified in 387/1055 (36.7%). When variant detection rates in second generation nonmosaics were applied to de novo cases, we assessed the overall probable mosaicism rate to be 59.7%. This rate differed by age from 21.7% in those presenting with bilateral vestibular schwannoma <20 years to 80.7% in those aged ≥60 years. A mosaic variant was detected in all parents of affected children with a single-nucleotide pathogenic NF2 variant. CONCLUSION: This study has identified a very high probable mosaicism rate in de novo NF2, probably making NF2 the condition with the highest expressed rate of mosaicism in de novo dominant disease that is nonlethal in heterozygote form. Risks to offspring are small and probably correlate with variant allele frequency detected in blood.
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Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mosaicismo , Neurofibromatosis 2/genética , Neurofibromina 2/genética , Adulto , Femenino , Frecuencia de los Genes , Mutación de Línea Germinal , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Tasa de Mutación , Linaje , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
PURPOSE: We have evaluated deficiencies in existing diagnostic criteria for neurofibromatosis 2 (NF2). METHODS: Two large databases of individuals fulfilling NF2 criteria (n = 1361) and those tested for NF2 variants with criteria short of diagnosis (n = 1416) were interrogated. We assessed the proportions meeting each diagnostic criterion with constitutional or mosaic NF2 variants and the positive predictive value (PPV) with regard to definite diagnosis. RESULTS: There was no evidence for usefulness of old criteria "glioma" or "neurofibroma." "Ependymoma" had 100% PPV and high levels of confirmed NF2 diagnosis (67.7%). Those with bilateral vestibular schwannoma (VS) alone aged ≥60 years had the lowest confirmation rate (6.6%) and reduced PPV (80%). Siblings as a first-degree relative, without an affected parent, had 0% PPV. All three individuals with unilateral VS and an affected sibling were proven not to have NF2. The biggest overlap was with LZTR1-associated schwannomatosis. In this category, seven individuals with unilateral VS plus ≥2 nondermal schwannomas reduced PPV to 67%. CONCLUSIONS: The present study confirms important deficiencies in NF2 diagnostic criteria. The term "glioma" should be dropped and replaced by "ependymoma." Similarly "neurofibroma" should be removed. Dropping "sibling" from first-degree relatives should be considered and testing of LZTR1 should be recommended for unilateral VS.
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Bases de Datos Factuales , Neurofibromatosis 2/diagnóstico , Adolescente , Adulto , Niño , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Técnicas de Diagnóstico Molecular , Neurofibromatosis 2/fisiopatología , Terminología como Asunto , Adulto JovenRESUMEN
BACKGROUND Intervertebral disc (IVD) degeneration is a common cause of lower back pain, which carries substantial morbidity and economic cost. Omega-3 fatty acids (n-3 FA) are known to reduce inflammatory processes with a relatively benign side effect profile. This study aimed to investigate the effect of n-3 FA supplementation on IVD degeneration. MATERIAL AND METHODS Two non-contiguous lumbar discs of 12 Sprague Dawley rats were needle-punctured to induce disc degeneration. Post-surgery, rats were randomly assigned to either a daily n-3 FA diet (530 mg/kg/day of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in a 2: 1 ratio, administered in sucrose solution) or control diet (sucrose solution only), which was given for the duration of the study. After 1 month, blood serum arachidonic acid/eicosapentaenoic acid (AA/EPA) ratios were analyzed. After 2 months, micro-MRI (magnetic resonance imaging) analysis and histological staining of disc explants were performed to analyze the IVD. RESULTS A reduction of blood AA/EPA ratios from 40 to 20 was demonstrated after 1 month of daily supplementation with n-3 FA. Micro-MRI analysis showed an injury-induced reduction of IVD hydration, which was attenuated in rats receiving n-3 FA. Histological evaluation demonstrated the destruction of nucleus pulposus tissue in response to needle puncture injury, which was less severe in the n-3 FA diet group. CONCLUSIONS The results of this study suggest that n-3 FA dietary supplementation reduces systemic inflammation by lowering AA/EPA ratios in blood serum and has potential protective effects on the progression of spinal disc degeneration, as demonstrated by reduced needle injury-induced dehydration of intervertebral discs and reduced histological signs of IVD degeneration.
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Ácidos Grasos Omega-3/farmacología , Degeneración del Disco Intervertebral/tratamiento farmacológico , Animales , Suplementos Dietéticos , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Ácidos Grasos Omega-3/metabolismo , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/patología , Dolor de la Región Lumbar/patología , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/veterinaria , Masculino , Núcleo Pulposo/citología , Ratas , Ratas Sprague-DawleyRESUMEN
Insulin resistance is a multi-faceted disruption of the communication between insulin and the interior of a target cell. The underlying cause of insulin appears to be inflammation that can either be increased or decreased by the fatty acid composition of the diet. However, the molecular basis for insulin resistance can be quite different in various organs. This review deals with various types of inflammatory inputs mediated by fatty acids, which affect the extent of insulin resistance in various organs.
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Dieta , Grasas de la Dieta/metabolismo , Ácidos Grasos/metabolismo , Resistencia a la Insulina , Obesidad/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Grasas de la Dieta/administración & dosificación , Ácidos Grasos/administración & dosificación , Regulación de la Expresión Génica , Humanos , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Hipotálamo/patología , Quinasa I-kappa B/genética , Quinasa I-kappa B/metabolismo , Inflamación , Insulina/genética , Insulina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , MAP Quinasa Quinasa 4/genética , MAP Quinasa Quinasa 4/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Obesidad/genética , Obesidad/patología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Exercise-induced angiogenesis is a key determinant of skeletal muscle function. Here, we investigated whether the E3 ubiquitin ligase murine double minute-2 (Mdm2) exerts a proangiogenic function in exercised skeletal muscle. Mdm2 hypomorphic (Mdm2(Puro/Δ7-9)) mice have a 60% reduction in Mdm2 expression compared with that in wild-type animals. Capillary staining on muscle sections from Mdm2(Puro/Δ7-9) sedentary mice with a wild-type or knockout background for p53 revealed that deficiency in Mdm2 resulted in 20% capillary regression independently of p53 status. In response to one bout of exercise, protein expression of the proangiogenic vascular endothelial growth factor-A (VEGF-A) was increased by 64% in muscle from wild-type animals, and endothelial cell outgrowth from exercised muscle biopsy samples cultured in a 3-dimensional collagen gel was enhanced by 37%. These proangiogenic responses to exercise were impaired in exercised Mdm2(Puro/Δ7-9) mice. Prolonged exercise training resulted in increased Mdm2 protein expression (+49%) and capillarization (+24%) in wild-type muscles. However, exercise training-induced angiogenesis was abolished in Mdm2(Puro/Δ7-9) mice. Finally, exercise training restored Mdm2, VEGF-A, and capillarization levels in skeletal muscles from obese Zucker diabetic fatty rats compared with those in healthy animals. Our results define Mdm2 as a crucial regulator of capillary maintenance and exercise-induced angiogenesis in skeletal muscle.
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Regulación de la Expresión Génica/fisiología , Músculo Esquelético/irrigación sanguínea , Neovascularización Fisiológica/fisiología , Condicionamiento Físico Animal/fisiología , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Animales , Capilares , Femenino , Masculino , Ratones , Músculo Esquelético/metabolismo , Neovascularización Fisiológica/genética , Obesidad/fisiopatología , Proteínas Proto-Oncogénicas c-mdm2/genética , Ratas , Ratas Sprague-Dawley , Ratas Zucker , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The ability to estimate mean particle size using simple, low-power optical instruments promises to greatly expand coverage of particle size measurements in the ocean and advance understanding of myriad processes from sediment transport to biological carbon sequestration. Here we present a method for estimating the mean diameter of particles in suspension from high-resolution time series of simple optical measurements, such as beam attenuation or optical backscattering. Validation results from a laboratory clay aggregation experiment show a good fit with independent mean particle diameter estimates in the 10-80 µm diameter range, with relative biases of 17%-38% and relative root mean square errors of 10%-24%. In the 80-200 µm range, quantitative validation data were not available, but our mean diameter estimates correlated strongly with particle settling rates.
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Background: Obesity is complicated by low-grade chronic inflammation characterised by increases in inflammatory proteins and cells in peripheral blood. It has been known that omega-3 fatty acids (FA) like eicosapentaenoic (EPA) and docosahexaenoic (DHA) could modulate the inflammatory process and improve metabolic markers. Objective: This study aimed to determine the effect of high-dose omega-3 FA on metabolic and inflammatory markers among patients with obesity and healthy volunteers. Methods: This prospective study included 12 women with obesity (body mass index [BMI] ≥ 35.0 kg/m2) and 12 healthy women (BMI < 24.0 kg/m2) who were supplemented with a dose of 4.8 g/day (3.2 g EPA plus 1.6 g DHA) for 3 months followed by no treatment for 1 month. Plasma metabolic and inflammatory markers and levels of mRNA transcripts of CD4+ T lymphocyte subsets were determined monthly. Results: None of the participants exhibited changes in weight or body composition after study completion. EPA and DHA supplementation improved metabolic (insulin, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR], triglyceride [TG]/ high-density lipoprotein [HDL] ratio, TG, and arachidonic acid [AA]/EPA ratio) and tumor necrosis factor-alpha (TNF-α). Moreover, the levels of mRNA transcripts of T CD4+ lymphocyte subsets (TBX21, IFNG, GATA-3, interleukin [IL]-4, FOXP3, IL-10 IL-6, and TNF-α), were down-regulated during the intervention phase. After 1 month without supplementation, only insulin, HOMA-IR and the mRNA transcripts remained low, whereas all other markers returned to their levels before supplementation. Conclusion: Supplementation with high-dose omega-3 FAs could modulate metabolism and inflammation in patients with obesity without weight loss or changes in body composition. However, these modulatory effects were ephemeral and with clear differential effects: short-duration on metabolism and long-lasting on inflammation.
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The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Diabetes Mellitus , Endocrinología , Insuficiencia Renal Crónica , Humanos , Nivel de Atención , Diabetes Mellitus/terapia , Insuficiencia Renal Crónica/terapia , Sociedades Médicas , Estándares de ReferenciaRESUMEN
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Endocrinología , Humanos , Diabetes Mellitus Tipo 2/prevención & control , Nivel de Atención , Comorbilidad , Diabetes Mellitus/terapia , Sociedades Médicas , Estándares de ReferenciaRESUMEN
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Diabetes Mellitus , Endocrinología , Humanos , Nivel de Atención , Diabetes Mellitus/terapia , Sociedades Médicas , Estándares de ReferenciaRESUMEN
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Endocrinología , Humanos , Enfermedades Cardiovasculares/terapia , Nivel de Atención , Diabetes Mellitus/terapia , Sociedades Médicas , Estándares de ReferenciaRESUMEN
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Diabetes Mellitus , Endocrinología , Enfermedades del Sistema Nervioso Periférico , Enfermedades de la Retina , Humanos , Nivel de Atención , Diabetes Mellitus/terapia , Sociedades Médicas , Estándares de ReferenciaRESUMEN
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Diabetes Mellitus , Endocrinología , Humanos , Nivel de Atención , Mejoramiento de la Calidad , Diabetes Mellitus/terapia , Sociedades Médicas , Estándares de ReferenciaRESUMEN
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Endocrinología , Humanos , Diabetes Mellitus Tipo 2/prevención & control , Nivel de Atención , Obesidad/prevención & control , Diabetes Mellitus/terapia , Sociedades Médicas , Estándares de ReferenciaRESUMEN
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Diabetes Mellitus , Endocrinología , Humanos , Anciano , Nivel de Atención , Diabetes Mellitus/terapia , Sociedades Médicas , Estándares de ReferenciaRESUMEN
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Diabetes Mellitus , Endocrinología , Humanos , Nivel de Atención , Diabetes Mellitus/terapia , Sociedades Médicas , Estándares de ReferenciaRESUMEN
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Diabetes Mellitus , Endocrinología , Humanos , Nivel de Atención , Diabetes Mellitus/terapia , Hospitales , Sociedades Médicas , Estándares de ReferenciaRESUMEN
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Diabetes Mellitus , Endocrinología , Niño , Adolescente , Humanos , Nivel de Atención , Diabetes Mellitus/terapia , Sociedades Médicas , Estándares de ReferenciaRESUMEN
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.