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1.
Langmuir ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934899

RESUMO

DNA-templated nanofabrication presents an innovative approach to creating self-assembled nanoscale metal-semiconductor-based Schottky contacts, which can advance nanoelectronics. Herein, we report the successful fabrication of metal-semiconductor Schottky contacts using a DNA origami scaffold. The scaffold, consisting of DNA strands organized into a specific linear architecture, facilitates the competitive arrangement of Au and CdS nanorods, forming heterojunctions, and addresses previous limitations in low electrical conductance making DNA-templated electronics with semiconductor nanomaterials. Electroless gold plating extends the Au nanorods and makes the necessary electrical contacts. Tungsten electrical connection lines are further created by electron beam-induced deposition. Electrical characterization reveals nonlinear Schottky barrier behavior, with electrical conductance ranging from 0.5 × 10-4 to 1.7 × 10-4 S. The conductance of these DNA-templated junctions is several million times higher than with our prior Schottky contacts. Our research establishes an innovative self-assembly approach with applicable metal and semiconductor materials for making highly conductive nanoscale Schottky contacts, paving the way for the future development of DNA-based nanoscale electronics.

2.
Public Health Rep ; 139(1_suppl): 62S-70S, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779994

RESUMO

OBJECTIVES: People with disabilities, people experiencing homelessness, and people who have substance use disorders face unique health challenges. Gaps in public health surveillance data limit the identification of public health needs of these groups and data-driven action. This study aimed to identify current practices, challenges, and opportunities for collecting and reporting COVID-19 surveillance data for these populations. METHODS: We used a rapid qualitative assessment to explore COVID-19 surveillance capacities. From July through October 2021, we virtually interviewed key informants from the Centers for Disease Control and Prevention, state and local health departments, and health care providers across the United States. We thematically analyzed and contextualized interview notes, peer-reviewed articles, and participant documents using a literature review. RESULTS: We identified themes centered on foundational structural and systems issues that hinder actionable surveillance data for these and other populations that are disproportionately affected by multiple health conditions. Qualitative data analysis of 61 interviews elucidated 4 primary challenges: definitions and policies, resources, data systems, and articulation of the purpose of data collection to these groups. Participants noted the use of multisector partnerships, automated data collection and integration, and data scorecards to circumvent challenges. CONCLUSIONS: This study highlights the need for multisector, systematic improvements in surveillance data collection and reporting to advance health equity. Improvements must be buttressed with adequate investment in data infrastructure and promoted through clear communication of how data are used to protect health.


Assuntos
COVID-19 , Pessoas com Deficiência , Equidade em Saúde , Pessoas Mal Alojadas , Transtornos Relacionados ao Uso de Substâncias , Humanos , Estados Unidos/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Pessoas com Deficiência/estatística & dados numéricos , COVID-19/epidemiologia , Vigilância em Saúde Pública/métodos , Pesquisa Qualitativa , SARS-CoV-2 , Vigilância da População/métodos
3.
Fam Med ; 52(10): 745-751, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33151536

RESUMO

BACKGROUND AND OBJECTIVES: Increasing human papillomavirus vaccination (HPVV) uptake is critical to the prevention of cervical cancer. Effective physician communication and clinical workflow policies have a significant impact on vaccination rates. However, resident training programs vary in the inclusion of training in effective HPVV practices. At Dell Medical School in Austin, Texas, HPVV rates at primary care residents' clinic sites vary. We examined HPVV-related knowledge, training, barriers, and practices among residents in pediatrics (Peds), family medicine (FM), obstetrics and gynecology (Ob/Gyn), and internal medicine (IM) with the aim of identifying interventional targets to improve vaccination rates. METHODS: This was a mixed-method study including qualitative interviews and a survey. We interviewed a sample of residents from each specialty to assess their training experiences and how they discuss HPVV. We recorded, transcribed, and coded interviews for thematic analysis. All residents were offered the opportunity to complete an electronic survey to quantitatively evaluate knowledge and vaccine practices. We performed χ2 and Fisher exact analysis to compare results between disciplines. RESULTS: HPVV-related knowledge was similar across all four specialties and between resident year. Peds residents reported always recommending the HPVV significantly more than FM and Ob/Gyn residents for 11-17-year-old females. Only Peds residents reported receiving evidence-based vaccine communication training. Among all residents, the primary HPVV barriers included forgetting to offer the vaccine and time constraints. When discussing the vaccine, many interviewed residents were not offering a confident recommendation to all eligible patients, and instead were using a risk-based approach to vaccination. CONCLUSIONS: There were inconsistencies across programs related to how and where residents receive HPVV training. This may impact the frequency and strength of resident vaccine recommendations. To increase HPVV rates, residency programs should prioritize implementation of multimodal interventions, including opt-out workflows and education on how to give confident vaccine recommendations.


Assuntos
Ginecologia , Internato e Residência , Obstetrícia , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Criança , Feminino , Ginecologia/educação , Humanos , Obstetrícia/educação , Infecções por Papillomavirus/prevenção & controle , Gravidez , Vacinação
4.
J Adolesc Health ; 65(1): 94-100, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30819581

RESUMO

PURPOSE: Rates of suicide are increasing rapidly among youth. Social media messages and online games promoting suicide are a concern for parents and clinicians. We examined the timing and location of social media posts about one alleged youth suicide game to better understand the degree to which social media data can provide earlier public health awareness. METHODS: We conducted a search of all public social media posts and news articles on the Blue Whale Challenge (BWC), an alleged suicide game, from January 1, 2013, through June 30, 2017. Data were retrieved through multiple keyword search; sources included social media platforms Twitter, YouTube, Reddit, Tumblr, as well as blogs, forums, and news articles. Posts were classified into three categories: individual "pro"-BWC posts (support for game), individual "anti"-BWC posts (opposition to game), and media reports. Timing and location of posts were assessed. RESULTS: Overall, 95,555 social media posts and articles about the BWC were collected. In total, over one-quarter (28.3%) were "pro"-BWC. The first U.S. news article related to the BWC was published approximately 4 months after the first English language U.S. social media post about the BWC and 9 months after the first U.S. social media post in any language. By the close of the study period, "pro"-BWC posts had spread to 127 countries. CONCLUSIONS: Novel online risks to mental health, such as prosuicide games or messages, can spread rapidly and globally. Better understanding social media and Web data may allow for detection of such threats earlier than is currently possible.


Assuntos
Jogos Recreativos/psicologia , Mídias Sociais/estatística & dados numéricos , Suicídio/psicologia , Adolescente , Humanos , Comportamento Autodestrutivo/psicologia , Mídias Sociais/tendências
5.
Clin Diabetes ; 37(1): 50-56, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30705497

RESUMO

IN BRIEF Diabetes management is challenging for youth. We developed a theoretical framework for the facilitators and barriers to diabetes management in youth from the perspective of parents.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30588150

RESUMO

INTRODUCTION: Our study objective was to determine the health care provider liver enzyme screening testing (LEST) rates in obese pediatric patients at risk for nonalcoholic fatty liver disease (NAFLD), with the goal of improving NAFLD LEST after specific system-wide provider intervention. METHODS: We conducted a bi-phased retrospective electronic medical record review of health care practitioner encounters to determine LEST in overweight/obese (body mass index≥25) patients between ages 2 and 18 years in our outpatient clinics. Intervention activities included lectures to staff and residents, fliers distributed to providers, monthly email reminders, and computer stickers placed on all terminals. From both phases, samples of simple random samples were drawn from the selected electronic medical records and reviewed for LEST screening; after intervention from this pool of patients, a random sample was chosen for LEST rate analysis. LEST rates were calculated per 100 patient encounters. RESULTS: We screened 2,979 and 2,634 pre and postintervention pediatric encounters from which we obtained a simple random sample of patients for LEST analysis. Overall of the 264 preintervention patients, 65 (24.4%) patients received LEST translating to 24/100 encounters. Of the 65 who received screening, 53 (81%) were classified as overweight/obese. Screening rate was higher for overweight/obese patients (32/100 encounters), when compared with normal weight patients' crude OR 3.8 (11/100 encounters; 95% CI: 1.9-7.6, P<0.005). Of the 242 postintervention patients, 70 (28%) received LEST translating to 28/100 encounters; of these, 58 (82%) were classified as overweight/obese with a rate of 42/100 encounters compared with 11/100 encounters for normal weight patients' crude OR 5.5 (95% CI: 2.8-7.5, P<0.005). CONCLUSION: Obesity is a significant risk factor for NAFLD; one in four obese pediatric patients had LEST. Additional health care practitioner education and interventions are needed to improve LEST to prevent long-term complications such as liver cirrhosis or failure.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30533701

RESUMO

Erwinia amylovora is a plant pathogen belonging to the Enterobacteriaceae family, a family containing many plant and animal pathogens. Herein, we announce nine genome sequences of E. amylovora bacteriophages isolated from infected apple trees along the Wasatch Front in Utah.

8.
Can J Public Health ; 108(4): e403-e408, 2017 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-29120312

RESUMO

SETTING: In 2009, Peel Public Health set a vision to transform the work of public health from efficient delivery of public health services as defined by provincial mandate to the robust analysis of the health status of the local population and selection and implementation of programming to achieve best health outcomes. A strategic approach to the workforce was a key enabler. PPH is a public health unit in Ontario that serves 1.4 million people. INTERVENTION: An organization-wide strategic workforce development program was instituted. It is theory-based, evidence-informed and data-driven. A first step was a conceptual framework, followed by interventions in workforce planning, human resources management, and capacity development. The program was built on evidence reviews, theory, and public health core competencies. Interventions spread across the employee work-life span. OUTCOMES: Capacity development based on the public health core competencies is a main focus, particularly analytical capacity to support decision-making. Employees gain skill and knowledge in comprehensive population health. Leadership evolves as work shifts to the analysis of health status and development of interventions. Effective human resource processes ensure appropriate job design, recruitment and orientation. Analysis of the workforce leads to vigorous employee development to ensure a strong pool of potential leadership successors. IMPLICATIONS: Theory, research evidence, and data provide a robust foundation for workforce development. Competencies are important inputs to job descriptions, recruitment, training, and human resource processes. A comprehensive workforce development strategy enables the development of a skilled workforce capable of responding to the needs of the population it serves.


Assuntos
Saúde Pública , Desenvolvimento de Pessoal/métodos , Prática Clínica Baseada em Evidências , Humanos , Ontário , Competência Profissional , Desenvolvimento de Pessoal/organização & administração
9.
BMC Public Health ; 16: 622, 2016 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-27448561

RESUMO

BACKGROUND: The sale of contraband tobacco allows for tobacco tax evasion, which can undermine the effectiveness of tobacco tax policies in reducing the number of smokers. Estimates of the proportion of contraband vary widely as do the methods used to measure the proportion of contraband being smoked. The purpose of this study is to determine the proportion of contraband use in two different jurisdictions. METHODS: A cross-sectional direct collection of cigarette butts was conducted in Peel and Brantford, Ontario, Canada in 2013 and 2014, respectively. Cigarette butts were collected from a variety of locations within both regions. Cigarette butts were assessed and classified into one of the following categories: contraband, legal Canadian, legal Native, International, unknown, and discards. RESULTS: The overall proportion of contraband cigarettes in Peel was 5.3 %, ranging from 2.8 to 8.6 % by location. In Brantford, the proportion of contraband was 33.0 %, with a range from 32.8 to 33.1 % by location. CONCLUSIONS: The direct collection of cigarette butts was determined to be a feasible method for a local public health unit in determining the proportion of contraband cigarettes. This approach showed that Brantford has a higher proportion of contraband consumption compared to Peel, which may be due to geographic location and proximity to the United States (US)-Canada border and Native Reserves. More research is needed to confirm this geographic association with other jurisdictions.


Assuntos
Abandono do Hábito de Fumar/métodos , Impostos , Indústria do Tabaco/legislação & jurisprudência , Produtos do Tabaco/estatística & dados numéricos , Estudos Transversais , Humanos , Ontário/epidemiologia
10.
Syst Rev ; 5: 54, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27055820

RESUMO

BACKGROUND: There is a growing emphasis in public health on the importance of evidence-based interventions to improve population health and reduce health inequities. Equally important is the need for knowledge about how to implement these interventions successfully. Yet, a gap remains between the development of evidence-based public health interventions and their successful implementation. Conventional systematic reviews have been conducted on effective implementation in health care, but few in public health, so their relevance to public health is unclear. In most reviews, stringent inclusion criteria have excluded entire bodies of evidence that may be relevant for policy makers, program planners, and practitioners to understand implementation in the unique public health context. Realist synthesis is a theory-driven methodology that draws on diverse data from different study designs to explain how and why observed outcomes occur in different contexts and thus may be more appropriate for public health. METHODS: This paper presents a realist review protocol to answer the research question: Why are some public health interventions successfully implemented and others not? Based on a review of implementation theories and frameworks, we developed an initial program theory, adapted for public health from the Consolidated Framework for Implementation Research, to explain the implementation outcomes of public health interventions within particular contexts. This will guide us through the review process, which comprises eight iterative steps based on established realist review guidelines and quality standards. We aim to refine this initial theory into a 'final' realist program theory that explains important context-mechanism-outcome configurations in the successful implementation of public health interventions. DISCUSSION: Developing new public health interventions is costly and policy windows that support their implementation can be short lived. Ineffective implementation wastes scarce resources and is neither affordable nor sustainable. Public health interventions that are not implemented will not have their intended effects on improving population health and promoting health equity. This synthesis will provide evidence to support effective implementation of public health interventions taking into account the variable context of interventions. A series of knowledge translation products specific to the needs of knowledge users will be developed to provide implementation support. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015030052.


Assuntos
Atenção à Saúde , Saúde Pública , Revisões Sistemáticas como Assunto , Humanos , Projetos de Pesquisa
11.
Artigo em Inglês | MEDLINE | ID: mdl-28210422

RESUMO

BACKGROUND: It is challenging to assess the quality of care and detect elder abuse in nursing homes, since patients may be incapable of reporting quality issues or abuse themselves, and resources for sending inspectors are limited. OBJECTIVE: This study correlates Google reviews of nursing homes with Centers for Medicare and Medicaid Services (CMS) inspection results in the Nursing Home Compare (NHC) data set, to quantify the extent to which the reviews reflect the quality of care and the presence of elder abuse. METHODS: A total of 16,160 reviews were collected, spanning 7,170 nursing homes. Two approaches were tested: using the average rating as an overall estimate of the quality of care at a nursing home, and using the average scores from a maximum entropy classifier trained to recognize indications of elder abuse. RESULTS: The classifier achieved an F-measure of 0.81, with precision 0.74 and recall 0.89. The correlation for the classifier is weak but statistically significant: = 0.13, P < .001, and 95% confidence interval (0.10, 0.16). The correlation for the ratings exhibits a slightly higher correlation: = 0.15, P < .001. Both the classifier and rating correlations approach approximately 0.65 when the effective average number of reviews per provider is increased by aggregating similar providers. CONCLUSIONS: These results indicate that an analysis of Google reviews of nursing homes can be used to detect indications of elder abuse with high precision and to assess the quality of care, but only when a sufficient number of reviews are available.

14.
Oecologia ; 171(4): 883-91, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23053225

RESUMO

One of the essential requirements for an introduced plant species to become invasive is an ability to reproduce outside the native range, particularly when initial populations are small. If a reproductive Allee effect is operating, plants in small populations will have reduced reproductive success relative to plants in larger populations. Alternatively, if plants in small populations experience less competition for pollination than those in large populations, they may actually have higher levels of reproductive success than plants in large populations. To resolve this uncertainty, we investigated how the per capita fecundity of plants was affected by population size in three invasive milkweed species. Field surveys of seed production in natural populations of different sizes but similar densities were conducted for three pollinator-dependent invasive species, namely Asclepias curassavica, Gomphocarpus fruticosus and G. physocarpus. Additionally, supplemental hand-pollinations were performed in small and large populations in order to determine whether reproductive output was limited by pollinator activity in these populations. Reproductive Allee effects were not detected in any of the study species. Instead, plants in small populations exhibited remarkably high levels of reproductive output compared to those in large populations. Increased fruit production following supplemental hand-pollinations suggested that the lower reproductive output of naturally pollinated plants in large populations is a consequence of pollen limitation rather than limitation due to abiotic resources. This is consistent with increased intraspecific competition for pollination amongst plants in large populations. It is likely that the invasion of these milkweed species in Australia has been enhanced because plants in small founding populations experience less intraspecific competition for pollinators than those in large populations, and thus have the ability to produce copious amounts of seeds.


Assuntos
Apocynaceae/fisiologia , Ecossistema , Espécies Introduzidas , Polinização/fisiologia , Austrália , Modelos Estatísticos , Densidade Demográfica , Dinâmica Populacional , Especificidade da Espécie
15.
Healthc Manage Forum ; 25(3): 146-50, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23252330

RESUMO

A public health department in Ontario, Canada, set a 10-year strategic direction for evidence-informed decision making, defined as the systematic application of research evidence to program decisions. The multifaceted approach has identified eight key lessons for leadership, funding, infrastructure, staff development, partnerships, and change management. Results after 4 years include systematic and transparent application of research to > 15 program decisions and, increasingly, evidence-informed decision making as a cultural norm.


Assuntos
Tomada de Decisões , Prática Clínica Baseada em Evidências , Cultura Organizacional , Fortalecimento Institucional , Pesquisa sobre Serviços de Saúde , Humanos , Ontário , Estudos de Casos Organizacionais , Inovação Organizacional , Saúde Pública
16.
Healthc Manage Forum ; 24(1 Suppl): S8-16, 2011.
Artigo em Inglês, Francês | MEDLINE | ID: mdl-21717945

RESUMO

A process for systematically applying research to public health decisions was created for a large, public health organization in Canada. The 9-step process is supported by tools and training in accessing, appraising, and applying research. The process has been implemented throughout the organization using the change management theory developed by Kotter and Cohen.


Assuntos
Tomada de Decisões Gerenciais , Prática Clínica Baseada em Evidências , Administração em Saúde Pública , Canadá , Modelos Teóricos , Desenvolvimento de Programas
17.
Brain Res ; 1375: 41-8, 2011 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-21172320

RESUMO

BACKGROUND: Sex-specific trajectories in white matter development during adolescence may help explain cognitive and behavioral divergences between males and females. Knowledge of sex differences in typically developing adolescents can provide a basis for interpreting sexual dimorphisms in abilities and actions. METHOD: We examined 58 healthy adolescents (12-14years of age) with diffusion tensor imaging (DTI). Diffusion parameters fractional anisotropy (FA), and mean (MD), radial (RD), and axial diffusivities (AD) were subjected to whole-brain voxel-wise group comparisons using tract-based spatial statistics. Sex differences in white matter microstructure were examined in relation to pubertal development. RESULTS: Early adolescent females (n=29) evidenced higher FA in the right superior corona radiata, higher FA and AD in bilateral corticospinal tracts (≥164µl, p<.01), and lower MD in the right inferior longitudinal fasciculus (ILF) and left forceps major (≥164µl, p<.01) than age-matched males (n=29). Males did not show any areas of higher FA or lower MD than females, but had higher AD in the right superior longitudinal fasciculus, ILF, and forceps minor (≥ 164µl, p<.01). Pubertal stage did not account for sex disparities. CONCLUSION: In early adolescence, females' motor tracts may reflect widespread changes, while males may undergo relatively more microstructural change in projection and association fibers.


Assuntos
Encéfalo/anatomia & histologia , Adolescente , Envelhecimento/fisiologia , Encéfalo/crescimento & desenvolvimento , Criança , Interpretação Estatística de Dados , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Saúde Mental , Testes Neuropsicológicos , Puberdade/fisiologia , Tratos Piramidais/anatomia & histologia , Tratos Piramidais/crescimento & desenvolvimento , Caracteres Sexuais
18.
Genetics ; 186(4): 1095-109, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20876560

RESUMO

Interchromosomal duplications are especially important for the study of X-linked genes. Males inheriting a mutation in a vital X-linked gene cannot survive unless there is a wild-type copy of the gene duplicated elsewhere in the genome. Rescuing the lethality of an X-linked mutation with a duplication allows the mutation to be used experimentally in complementation tests and other genetic crosses and it maps the mutated gene to a defined chromosomal region. Duplications can also be used to screen for dosage-dependent enhancers and suppressors of mutant phenotypes as a way to identify genes involved in the same biological process. We describe an ongoing project in Drosophila melanogaster to generate comprehensive coverage and extensive breakpoint subdivision of the X chromosome with megabase-scale X segments borne on Y chromosomes. The in vivo method involves the creation of X inversions on attached-XY chromosomes by FLP-FRT site-specific recombination technology followed by irradiation to induce large internal X deletions. The resulting chromosomes consist of the X tip, a medial X segment placed near the tip by an inversion, and a full Y. A nested set of medial duplicated segments is derived from each inversion precursor. We have constructed a set of inversions on attached-XY chromosomes that enable us to isolate nested duplicated segments from all X regions. To date, our screens have provided a minimum of 78% X coverage with duplication breakpoints spaced a median of nine genes apart. These duplication chromosomes will be valuable resources for rescuing and mapping X-linked mutations and identifying dosage-dependent modifiers of mutant phenotypes.


Assuntos
Tecnologia Biomédica/métodos , Drosophila melanogaster/genética , Duplicação Gênica , Genes Ligados ao Cromossomo X/genética , Cromossomo X/genética , Cromossomo Y/genética , Animais , Masculino , Métodos , Mutação , Recombinação Genética/genética
19.
Brain Res ; 1327: 38-46, 2010 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-20206151

RESUMO

BACKGROUND: Late adolescence is comprised of considerable developmental transitions, though brain maturational changes during this period are subtle and difficult to quantitatively evaluate from standard brain imaging acquisitions. To date, primarily cross-sectional studies have characterized typical developmental changes during adolescence, but these processes need further description within a longitudinal framework. METHOD: To assess the developmental trajectory of typical white matter development, we examined 22 healthy adolescents with serial diffusion tensor images (DTI) collected at a mean age of 17.8 years and 16-months later. Diffusion parameters fractional anisotropy, and mean, radial, and axial diffusivity were subjected to whole-brain voxelwise time point comparisons using tract-based spatial statistics. RESULTS: At follow-up, adolescents showed a significant change (>or=153 contiguous voxels each at p<0.01) in diffusion properties, including in bilateral superior longitudinal fasciculi, superior corona radiata, anterior thalamic radiations, and posterior limb of the internal capsule. Overall, correlations with cognitive performances suggested behavioral improvement corresponding with white matter changes. CONCLUSION: These longitudinal DTI findings support continued microstructural change in white matter during late adolescence, and suggest ongoing refinement of projection and association fibers into early adulthood.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Fibras Nervosas Mielinizadas/fisiologia , Adolescente , Anisotropia , Mapeamento Encefálico , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Adulto Jovem
20.
Cancer Res ; 67(15): 7505-11, 2007 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-17671221

RESUMO

Pituitary tumors are a diverse group of neoplasms that are classified based on clinical manifestations, hormone excess, and histomorphologic features. Those that cause growth hormone (GH) excess and acromegaly are subdivided into morphologic variants that have not yet been shown to have pathogenetic significance or predictive value for therapy and outcome. Here, we identify a selective somatic histidine-to-leucine substitution in codon 49 of the extracellular domain of the GH receptor (GHR) in a morphologic subtype of human GH-producing pituitary tumors that is characterized by the presence of cytoskeletal aggresomes. This GHR mutation significantly impairs glycosylation-mediated receptor processing, maturation, ligand binding, and signaling. Pharmacologic GH antagonism recapitulates the morphologic phenotype of pituitary tumors from which this mutation was identified, inducing the formation of cytoskeletal keratin aggresomes. This novel GHR mutation provides evidence for impaired hormone autofeedback in the pathogenesis of these pituitary tumors. It explains the lack of responsiveness to somatostatin analogue therapy of this tumor type, in contrast to the exquisite sensitivity of tumors that lack aggresomes, and has therapeutic implications for the safety of GH antagonism as a therapeutic modality in acromegaly.


Assuntos
Proteínas de Transporte/genética , Retroalimentação Fisiológica/fisiologia , Mutação , Neoplasias Hipofisárias/genética , Transdução de Sinais , Adenoma/genética , Adenoma/patologia , Proteínas de Transporte/metabolismo , Proliferação de Células , Humanos , Técnicas Imunoenzimáticas , Mutagênese Sítio-Dirigida , Fragmentos de Peptídeos/genética , Neoplasias Hipofisárias/patologia
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