RESUMO
Apart from amyloid ß deposition and tau neurofibrillary tangles, Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuronal loss and astrocytosis in the cerebral cortex. The goal of this study is to investigate genetic factors associated with the neuronal proportion in health and disease. To identify cell-autonomous genetic variants associated with neuronal proportion in cortical tissues, we inferred cellular population structure from bulk RNA-Seq derived from 1536 individuals. We identified the variant rs1990621 located in the TMEM106B gene region as significantly associated with neuronal proportion (p value = 6.40 × 10-07) and replicated this finding in an independent dataset (p value = 7.41 × 10-04) surpassing the genome-wide threshold in the meta-analysis (p value = 9.42 × 10-09). This variant is in high LD with the TMEM106B non-synonymous variant p.T185S (rs3173615; r2 = 0.98) which was previously identified as a protective variant for frontotemporal lobar degeneration (FTLD). We stratified the samples by disease status, and discovered that this variant modulates neuronal proportion not only in AD cases, but also several neurodegenerative diseases and in elderly cognitively healthy controls. Furthermore, we did not find a significant association in younger controls or schizophrenia patients, suggesting that this variant might increase neuronal survival or confer resilience to the neurodegenerative process. The single variant and gene-based analyses also identified an overall genetic association between neuronal proportion, AD and FTLD risk. These results suggest that common pathways are implicated in these neurodegenerative diseases, that implicate neuronal survival. In summary, we identified a protective variant in the TMEM106B gene that may have a neuronal protection effect against general aging, independent of disease status, which could help elucidate the relationship between aging and neuronal survival in the presence or absence of neurodegenerative disorders. Our findings suggest that TMEM106B could be a potential target for neuronal protection therapies to ameliorate cognitive and functional deficits.
Assuntos
Envelhecimento/genética , Encéfalo , Predisposição Genética para Doença/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Doenças Neurodegenerativas/genética , Neurônios , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Humanos , Masculino , Neurônios/metabolismo , Neurônios/patologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The Beyond Ultrasound First Forum was conceived to increase awareness that the quality of obstetric and gynecologic ultrasound can be improved, and is inconsistent throughout the country, likely due to multiple factors, including the lack of a standardized curriculum and competency assessment in ultrasound teaching. The forum brought together representatives from many professional associations; the imaging community including radiology, obstetrics and gynecology, and emergency medicine among others; in addition to government agencies, insurers, industry, and others with common interest in obstetric and gynecologic ultrasound. This group worked together in focus sessions aimed at developing solutions on how to standardize and improve ultrasound training at the resident level and beyond. A new curriculum and competency assessment program for teaching residents (obstetrics and gynecology, radiology, and any other specialty doing obstetrics and gynecology ultrasound) was presented, and performance measures of ultrasound quality in clinical practice were discussed. The aim of this forum was to increase and unify the quality of ultrasound examinations in obstetrics and gynecology with the ultimate goal of improving patient safety and quality of clinical care. This report describes the proceedings of this conference including possible approaches to resident teaching and means to improve the inconsistent quality of ultrasound examinations performed today.
Assuntos
Competência Clínica , Internato e Residência , Obstetrícia/educação , Garantia da Qualidade dos Cuidados de Saúde , Melhoria de Qualidade , Ultrassonografia Pré-Natal , Acreditação , Feminino , Humanos , Gravidez , Estados UnidosRESUMO
Ultrasound imaging has become integral to the practice of obstetrics and gynecology. With increasing educational demands and limited hours in residency programs, dedicated time for training and achieving competency in ultrasound has diminished substantially. The American Institute of Ultrasound in Medicine assembled a multisociety task force to develop a consensus-based, standardized curriculum and competency assessment tools for obstetric and gynecologic ultrasound training in residency programs. The curriculum and competency assessment tools were developed based on existing national and international guidelines for the performance of obstetric and gynecologic ultrasound examinations and thus are intended to represent the minimum requirement for such training. By expert consensus, the curriculum was developed for each year of training, criteria for each competency assessment image were generated, the pass score was established at, or close to, 75% for each, and obtaining a set of 5 ultrasound images with pass score in each was deemed necessary for attaining each competency. Given the current lack of substantial data on competency assessment in ultrasound training, the task force expects that the criteria set forth in this document will evolve with time. The task force also encourages use of ultrasound simulation in residency training and expects that simulation will play a significant part in the curriculum and the competency assessment process. Incorporating this training curriculum and the competency assessment tools may promote consistency in training and competency assessment, thus enhancing the performance and diagnostic accuracy of ultrasound examination in obstetrics and gynecology.
Assuntos
Competência Clínica/normas , Currículo , Internato e Residência , Obstetrícia/educação , Garantia da Qualidade dos Cuidados de Saúde , Ultrassonografia Pré-Natal/normas , Acreditação , Feminino , Humanos , Gravidez , Estados UnidosRESUMO
The Beyond Ultrasound First Forum was conceived to increase awareness that the quality of obstetric and gynecologic ultrasound can be improved, and is inconsistent throughout the country, likely due to multiple factors, including the lack of a standardized curriculum and competency assessment in ultrasound teaching. The forum brought together representatives from many professional associations; the imaging community including radiology, obstetrics and gynecology, and emergency medicine among others; in addition to government agencies, insurers, industry, and others with common interest in obstetric and gynecologic ultrasound. This group worked together in focus sessions aimed at developing solutions on how to standardize and improve ultrasound training at the resident level and beyond. A new curriculum and competency assessment program for teaching residents (obstetrics and gynecology, radiology, and any other specialty doing obstetrics and gynecology ultrasound) was presented, and performance measures of ultrasound quality in clinical practice were discussed. The aim of this forum was to increase and unify the quality of ultrasound examinations in obstetrics and gynecology with the ultimate goal of improving patient safety and quality of clinical care. This report describes the proceedings of this conference including possible approaches to resident teaching and means to improve the inconsistent quality of ultrasound examinations performed today.
Assuntos
Competência Clínica/normas , Ginecologia/educação , Obstetrícia/educação , Melhoria de Qualidade , Ultrassom/educação , Ultrassonografia Pré-Natal/normas , Currículo/normas , Feminino , Humanos , Gravidez , Estados UnidosRESUMO
Ultrasound imaging has become integral to the practice of obstetrics and gynecology. With increasing educational demands and limited hours in residency programs, dedicated time for training and achieving competency in ultrasound has diminished substantially. The American Institute of Ultrasound in Medicine assembled a multisociety task force to develop a consensus-based, standardized curriculum and competency assessment tools for obstetric and gynecologic ultrasound training in residency programs. The curriculum and competency assessment tools were developed based on existing national and international guidelines for the performance of obstetric and gynecologic ultrasound examinations and thus are intended to represent the minimum requirement for such training. By expert consensus, the curriculum was developed for each year of training, criteria for each competency assessment image were generated, the pass score was established at, or close to, 75% for each, and obtaining a set of 5 ultrasound images with pass score in each was deemed necessary for attaining each competency. Given the current lack of substantial data on competency assessment in ultrasound training, the task force expects that the criteria set forth in this document will evolve with time. The task force also encourages use of ultrasound simulation in residency training and expects that simulation will play a significant part in the curriculum and the competency assessment process. Incorporating this training curriculum and the competency assessment tools may promote consistency in training and competency assessment, thus enhancing the performance and diagnostic accuracy of ultrasound examination in obstetrics and gynecology.
Assuntos
Competência Clínica/normas , Currículo/normas , Internato e Residência/normas , Ultrassom/educação , Ultrassonografia Pré-Natal/normas , Feminino , Ginecologia/educação , Humanos , Obstetrícia/educação , Gravidez , Melhoria de Qualidade , Estados UnidosRESUMO
A generally applicable method for the study of phenyl radicals' reactions with neutral biomolecules in the gas phase is demonstrated. Neutral biomolecules were evaporated into a Fourier-transform ion cyclotron resonance mass spectrometer (FT-ICR) by means of laser-induced acoustic desorption (LIAD) and subsequently reacted with trapped charged phenyl radicals. The structural integrity of the evaporated alanylalanine molecules was verified by reaction with dichlorophosphenium ions. Examination of the reactions of charged phenyl radicals with alanylalanine and thymidine evaporated via LIAD revealed hydrogen atom abstraction for both alanylalanine and thymidine as well as an addition/elimination product for the reaction with thymidine. These reactions are consistent with the results obtained by others in solution. Further, a previously unstudied reaction of the nucleotide of thymine (T1) with charged phenyl radical was found to yield analogous products as the reaction with thymidine.
Assuntos
Radicais Livres/química , Peptídeos/química , Ciclotrons , Dipeptídeos/química , Análise de Fourier , Indicadores e Reagentes , Lasers , Espectrometria de Massas , Timidina/químicaRESUMO
Laser-induced acoustic desorption combined with mass spectrometry has been used to demonstrate that phenyl radicals can attack dinucleoside phosphates at both the sugar and base moieties, that purine bases are more susceptible to the attack than pyrimidine bases, and that the more electrophilic the radical, the more efficient the damage to dinucleoside phosphates.