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1.
J Vasc Interv Radiol ; 34(2): 261-267.e2, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-37190972

RESUMO

PURPOSE: To describe the natural history of Gunther Tulip filter (GTF) strut penetration based on the computed tomography (CT)-documented distance penetrated over time and any clinical manifestations. MATERIALS AND METHODS: The records of 203 patients (mean age, 59.1 years; 59.4% men) who had had an infrarenal GTF placed for venous thromboembolism (84.2%) with contraindications to anticoagulation (95.1%) and had CT follow-up were reviewed retrospectively for clinical or imaging evidence of complications. Filter strut penetration was measured on axial images from the outer caval wall to the inner edge of the distal end of each strut. Filter strut behavior over time was modeled using a linear mixed model. RESULTS: The extent of penetration correlated positively with filter dwell time (P < .001) but plateaued at 3.3 mm at 10-year follow-up. At median 4.7-year follow-up 79.3% of patients had at least 1 strut that was >0.2 mm and 31% had a strut >3 mm from the inferior vena caval wall. The extent of strut penetration was greater at all time points for women (P = .002). Abutment or entry into an adjacent structure was identified in 183 struts of 105 (52.7%) filters; of the 80 filters with CT follow-up, 47% showed progression and 19% regressed. There were no symptoms referable to filter strut penetration. CONCLUSIONS: GTF struts often penetrate the inferior vena cava progressively; however, this tends to plateau by 10 years. The limited long-term progression and a very low incidence of symptomatic complications together support a noninterventional approach to the finding of an asymptomatic GTF strut penetration.


Assuntos
Tulipa , Filtros de Veia Cava , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Seguimentos , Desenho de Prótese , Estudos Retrospectivos , Remoção de Dispositivo/métodos , Fatores de Tempo , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgia
2.
Perspect Biol Med ; 66(1): 89-106, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38662010

RESUMO

Long before COVID-19 made social distancing familiar, people with cystic fibrosis (CF) already practiced such behaviors. CF is held up as a classic example of genetic disease, yet people with CF are also susceptible to bacteria from the environment and from other CF patients. Starting in the 1980s, a bacterial epidemic in the CF population highlighted clashing priorities of connection, physical safety, and environmental protection. Policymakers ultimately called for the physical separation of people with CF from one another via recommendations that reconfigured the CF community. Simultaneously, medical researchers recognized that one highly transmissible CF pathogen called cepacia was being developed for environmental applications and got the EPA to limit cepacia's environmental deployment. Environmental regulations speak to the challenge of useful microbes that harm a minority, but CF cross-infection also involves legal implications for microbial and genetic discrimination, social consequences for CF communities, and ethical questions about balancing autonomy, harms, and benefits. As scientists increasingly study connections between host genetics, microbial genetics, and infectious risks, CF is a vital referent.


Assuntos
Fibrose Cística , Fibrose Cística/microbiologia , Humanos , Burkholderia cepacia , COVID-19/prevenção & controle , Infecções por Burkholderia , SARS-CoV-2
3.
J Genet Couns ; 32(4): 762-767, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36575577

RESUMO

Despite the moniker "precision medicine," genetic diagnoses are often imprecise with respect to prognosis. In a period when prognoses are evolving in lockstep with advances in genetic diagnostics and therapeutics, it is critical that clinicians and researchers consider how prognosis is communicated beyond the moment of diagnosis. Research has shown that genetic diagnoses are described differently in pre- and postnatal contexts, but we know relatively little about how patients and families make sense of prognostic information as affected children grow up. Here, I draw on research and personal narratives to describe how prognostic information impacts individuals' conceptions of the future. A deeper understanding of how patients and families view prognosis is important because parents may need support as prognostic conversations arise and because perceptions of prognosis may influence ideas about the future, psychological health, decisions, and planning. By exploring how specific ideas about an individuals' future take hold, clinicians and researchers may begin to identify the benefits, harms, and accuracy of varied sources of prognostic information, opening new areas of bioethical investigation. In closing, I propose prognostic imagination as a useful concept for considering how patients and families experience prognostic information amidst therapeutic innovations and evolving futures.


Assuntos
Aconselhamento Genético , Imaginação , Criança , Humanos , Prognóstico , Comunicação , Medicina de Precisão
4.
J Genet Couns ; 32(2): 342-350, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36245263

RESUMO

Germline genetic testing for inherited cancer risk is increasingly being performed with multigene panel testing with MUTYH often included on colorectal cancer- and polyposis-focused panels, as well as on broader pan-cancer panels. With up to 1%-2% of the general population being monoallelic MUTYH carriers, pathogenic/likely pathogenic (P/LP) variants in MUTYH are one of the most common findings on multigene cancer panels. However, little is known about patient experience and understanding of monoallelic MUTYH P/LP variants, nor whether such findings influence medical management recommendations and familial communication, which this study aims to better understand. Monoallelic P/LP MUTYH carriers were recruited from the Prospective Registry of Multiplex Testing (PROMPT) and completed a cross-sectional self-report survey on sociodemographic characteristics, medical and family history, experiences with MUTYH genetic testing, genetics and MUTYH knowledge, perceived cancer risk, and familial communication. Of 115 eligible PROMPT participants, 49 (43%) completed the survey who were primarily female (94%), white (96%), had a history of cancer (61%), and a median age of 51.4 years. Most participants (61%) reported satisfaction with how their healthcare provider managed their genetic test result and care, and 65% of survey participants reported their provider recommended colonoscopy based on their genetic test results. Participants' responses also reflected variable levels of knowledge regarding cancer risks and screening recommendations for MUTYH carriers. The majority (98%) of participants shared their genetic test results with at least some of their relatives; however, only 13% of eligible relatives reportedly underwent cascade testing. Taken together, this study provides needed insight into the overall experiences of monoallelic MUTYH carriers and highlights numerous areas for improvement in clinician education, communication, and management of these individuals.


Assuntos
Neoplasias Colorretais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Estudos Transversais , Predisposição Genética para Doença , Testes Genéticos , Heterozigoto , Mutação
5.
J Neurosci ; 41(45): 9431-9451, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34607969

RESUMO

Pathologic tau modifications are characteristic of Alzheimer's disease and related dementias, but mechanisms of tau toxicity continue to be debated. Inherited mutations in tau cause early onset frontotemporal lobar dementias (FTLD-tau) and are commonly used to model mechanisms of tau toxicity in tauopathies. Previous work in the isolated squid axoplasm model demonstrated that several pathogenic forms of tau inhibit axonal transport through a mechanism involving activation of protein phosphatase 1 (PP1). Here, we determined that P301L and R5L FTLD mutant tau proteins elicit a toxic effect on axonal transport as monomeric proteins. We evaluated interactions of wild-type or mutant tau with specific PP1 isoforms (α, ß, and γ) to examine how the interaction contributes to this toxic effect using primary rat hippocampal neurons from both sexes. Pull-down and bioluminescence resonance energy transfer experiments revealed selective interactions of wild-type tau with PP1α and PP1γ isoforms, but not PP1ß, which were significantly increased by the P301L tau mutation. The results from proximity ligation assays confirmed the interaction in primary hippocampal neurons. Moreover, expression of FTLD-linked mutant tau in these neurons enhanced levels of active PP1, also increasing the pausing frequency of fluorescently labeled vesicles in both anterograde and retrograde directions. Knockdown of PP1γ, but not PP1α, rescued the cargo-pausing effects of P301L and R5L tau, a result replicated by deleting a phosphatase-activating domain in the amino terminus of P301L tau. These findings support a model of tau toxicity involving aberrant activation of a specific PP1γ-dependent pathway that disrupts axonal transport in neurons.SIGNIFICANCE STATEMENT Tau pathology is closely associated with neurodegeneration in Alzheimer's disease and other tauopathies, but the toxic mechanisms remain a debated topic. We previously proposed that pathologic tau forms induce dysfunction and degeneration through aberrant activation of a PP1-dependent pathway that disrupts axonal transport. Here, we show that tau directly interacts with specific PP1 isoforms, increasing levels of active PP1. Pathogenic tau mutations enhance this interaction, further increasing active PP1 levels and impairing axonal transport in isolated squid axoplasm and primary hippocampal neurons. Mutant-tau-mediated impairment of axonal transport was mediated by PP1γ and a phosphatase-activating domain located at the amino terminus of tau. This work has important implications for understanding and potentially mitigating tau-mediated neurotoxicity in tauopathies.


Assuntos
Transporte Axonal/efeitos dos fármacos , Demência Frontotemporal , Neurônios/metabolismo , Proteína Fosfatase 1/metabolismo , Proteínas tau/farmacologia , Animais , Células Cultivadas , Decapodiformes , Feminino , Hipocampo , Humanos , Masculino , Mutação , Neurônios/efeitos dos fármacos , Ratos , Proteínas tau/genética
6.
Appl Environ Microbiol ; 88(1): e0095821, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-34669438

RESUMO

The microbial degradation of lignocellulose in natural ecosystems presents numerous biotechnological opportunities, including biofuel production from agricultural waste and feedstock biomass. To explore the degradation potential of specific thermophiles, we have identified and characterized extremophilic microorganisms isolated from hot springs environments that are capable of biodegrading lignin and cellulose substrates under thermoalkaline conditions, using a combination of culturing, genomics, and metabolomics techniques. Organisms that can use lignin and cellulose as a sole carbon source at 60 to 75°C were isolated from sediment slurry of thermoalkaline hot springs (71 to 81°C and pH 8 to 9) of Yellowstone National Park. Full-length 16S rRNA gene sequencing indicated that these isolates were closely related to Geobacillus thermoleovorans. Interestingly, most of these isolates demonstrated biofilm formation on lignin, a phenotype that is correlated with increased bioconversion. Assessment of metabolite level changes in two Geobacillus isolates from two representative springs were undertaken to characterize the metabolic responses associated with growth on glucose versus lignin carbon source as a function of pH and temperature. Overall, results from this study support that thermoalkaline springs harbor G. thermoleovorans microorganisms with lignocellulosic biomass degradation capabilities and potential downstream biotechnological applications. IMPORTANCE Since lignocellulosic biomass represents a major agro-industrial waste and renewable resource, its potential to replace nonrenewable petroleum-based products for energy production is considerable. Microbial ligninolytic and cellulolytic enzymes are of high interest in biorefineries for the valorization of lignocellulosic biomass, as they can withstand the extreme conditions (e.g., high temperature and high pH) required for processing. Of great interest is the ligninolytic potential of specific Geobacillus thermoleovorans isolates to function at a broad range of pH and temperatures, since lignin is the bottleneck in the bioprocessing of lignocellulose. In this study, results obtained from G. thermoleovorans isolates originating from YNP springs are significant because very few microorganisms from alkaline thermal environments have been discovered to have lignin- and cellulose-biodegrading capabilities, and this work opens new avenues for the biotechnological valorization of lignocellulosic biomass at an industrial scale.


Assuntos
Geobacillus , Lignina , Biomassa , Ecossistema , Geobacillus/genética , Parques Recreativos , RNA Ribossômico 16S/genética
7.
Neurobiol Dis ; 148: 105175, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33188920

RESUMO

Prevalent in approximately 20% of the worldwide human population, the rs6265 (also called 'Val66Met') single nucleotide polymorphism (SNP) in the gene for brain-derived neurotrophic factor (BDNF) is a common genetic variant that can alter therapeutic responses in individuals with Parkinson's disease (PD). Possession of the variant Met allele results in decreased activity-dependent release of BDNF. Given the resurgent worldwide interest in neural transplantation for PD and the biological relevance of BDNF, the current studies examined the effects of the rs6265 SNP on therapeutic efficacy and side-effect development following primary dopamine (DA) neuron transplantation. Considering the significant reduction in BDNF release associated with rs6265, we hypothesized that rs6265-mediated dysfunctional BDNF signaling contributes to the limited clinical benefit observed in a subpopulation of PD patients despite robust survival of grafted DA neurons, and further, that this mutation contributes to the development of aberrant graft-induced dyskinesias (GID). To this end, we generated a CRISPR knock-in rat model of the rs6265 BDNF SNP to examine for the first time the influence of a common genetic polymorphism on graft survival, functional efficacy, and side-effect liability, comparing these parameters between wild-type (Val/Val) rats and those homozygous for the variant Met allele (Met/Met). Counter to our hypothesis, the current research indicates that Met/Met rats show enhanced graft-associated therapeutic efficacy and a paradoxical enhancement of graft-derived neurite outgrowth compared to wild-type rats. However, consistent with our hypothesis, we demonstrate that the rs6265 genotype in the host rat is strongly linked to development of GID, and that this behavioral phenotype is significantly correlated with neurochemical signatures of atypical glutamatergic neurotransmission by grafted DA neurons.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Transplante de Células/métodos , Neurônios Dopaminérgicos/transplante , Discinesias/genética , Animais , Antiparkinsonianos/efeitos adversos , Transplante de Células/efeitos adversos , Neurônios Dopaminérgicos/metabolismo , Discinesia Induzida por Medicamentos/etiologia , Discinesias/etiologia , Embrião de Mamíferos , Técnicas de Introdução de Genes , Levodopa/efeitos adversos , Mesencéfalo/citologia , Oxidopamina/toxicidade , Doença de Parkinson Secundária/induzido quimicamente , Ratos , Simpatolíticos/toxicidade , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo
8.
Genet Med ; 23(11): 2105-2113, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34257420

RESUMO

PURPOSE: To address demands for timely germline information to guide treatments, we evaluated experiences of patients with ovarian, pancreatic, and prostate cancer with a mainstreaming genetic testing model wherein multigene panel testing was ordered by oncologists with standardized pretest patient education, and genetic counselors delivered results and post-test genetic counseling via telephone. METHODS: Among 1,203 eligible patients, we conducted a prospective single-arm study to examine patient uptake and acceptability (via self-report surveys at baseline and three weeks and three months following result return) of this mainstreaming model. RESULTS: Only 10% of eligible patients declined participation. Among 1,054 tested participants, 10% had pathogenic variants (PV), 16% had variants of uncertain significance (VUS), and 74% had no variant identified (NV). Participants reported high initial acceptability, including high satisfaction with their testing decision. Variability over time in several outcomes existed for participants with PV or NV: those with NV experienced a temporary increase in depression (pTime < 0.001; pTime2 < 0.001), and those with PV experienced a small increase in genetic testing distress (p = 0.03). Findings suggested that result type, sex, and cancer type were also associated with outcomes including clinical depression and uncertainty. CONCLUSION: This mainstreaming model may offer a feasible approach for extending access to germline genetic information.


Assuntos
Predisposição Genética para Doença , Neoplasias da Próstata , Aconselhamento Genético , Testes Genéticos , Humanos , Masculino , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética
9.
J Genet Couns ; 30(4): 1010-1023, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34355459

RESUMO

The COVID-19 pandemic has pushed medical providers to trial telemedicine on a scale that lacks precedent. In genetic medicine, nearly overnight genetics providers were asked to transition to telemedicine platforms, irrespective of their previous experience with these modalities. This push to telegenetics prompted a reappraisal of the practice, as genetics providers learned firsthand about the feasibility, benefits, and drawbacks of telegenetics and telesupervision, all of which raise questions about the potential incorporation of these platforms beyond the pandemic. Adding to nascent literature on the transition to telegenetics amidst the COVID-19 pandemic, we aimed to evaluate provider experiences and preferences with respect to telegenetics through qualitative semi-structured interviews with genetics providers. Nineteen providers from seven institutions participated in a semi-structured interview focused on the rapid shift to telegenetics, the benefits and drawbacks of the practice, experiences supervising students on virtual platforms, and providers' preferences. We employed a qualitative methodology so that providers working across diverse subspecialties could expand upon previously reported benefits and drawbacks. Qualitative data revealed the nuanced benefits of telegenetics which included overcoming geographic, spatial, and temporal barriers to care as well as greater involvement of patients' family members in sessions. In addition, the data indicated drawbacks related to additional tasks such as completing paperwork electronically and facilitating the collection of specimens from patients' homes. Interviews with providers from different subspecialties revealed how telegenetics may be uniquely useful for particular subspecialties, patient populations, or clinics for whom the aforementioned barriers are more significant. Providers reported that telesupervision made the provision of feedback to students more cumbersome and identified a number of methods for enriching the telesupervision experience. In keeping with previous research, most genetics providers appraised telegenetics as a valuable addition to patient care (68%, N = 13) and hoped to offer it as an option beyond the pandemic (63%, N = 12).


Assuntos
COVID-19 , Aconselhamento Genético , Curva de Aprendizado , Telemedicina , Adulto , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pandemias , Adulto Jovem
10.
Comput Inform Nurs ; 38(2): 71-79, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31804242

RESUMO

Patients frequently download mHealth apps, which can be used to support health promotion. It remains unclear, however, if family nurse practitioners are recommending apps to patients. This study identified family nurse practitioners' current practices of recommending apps to patients and described their use and intent to use mHealth apps for health promotion with their patients. Nearly 70% of the 303 participants surveyed recommended mHealth apps to their patients, with the most common types comprising patient portal, diet and nutrition, and fitness apps. However, the frequency with which apps were recommended was low. Participants reported that apps complement patient care, enable health promotion behaviors, are easy to use, and improve clarity of patient data. These factors facilitated their intent to recommend mHealth apps to patients. Healthcare organizational support influenced participants' intent to recommend apps, and access to trustworthy apps and electronic health records compatibility increased usage. Barriers to recommending involved patient-specific characteristics and provider concerns about reliability, privacy, and efficacy of apps. Family nurse practitioners must be supported in guiding patients to use reliable, safe, and HIPAA-compliant apps. To help engage patients, clinicians should be educated on methods to evaluate mHealth apps and how to incorporate them into patient care.


Assuntos
Enfermeiros de Saúde da Família , Promoção da Saúde , Aplicativos Móveis , Encaminhamento e Consulta , Telemedicina , Comportamentos Relacionados com a Saúde , Humanos , Internet , Inquéritos e Questionários , Estados Unidos
11.
New Phytol ; 224(1): 155-165, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31209891

RESUMO

Successive droughts have resulted in extensive tree mortality in the southwestern United States. Recovery of these areas is dependent on the survival and recruitment of young trees. For trees that rely on ectomycorrhizal fungi (EMF) for survival and growth, changes in soil fungal communities following tree mortality could negatively affect seedling establishment. We used tree-focused and stand-scale measurements to examine the impact of pinyon pine mortality on the performance of surviving juvenile trees and the potential for mutualism limitation of seedling establishment via altered EMF communities. Mature pinyon mortality did not affect the survival of juvenile pinyons, but increased their growth. At both tree and stand scales, high pinyon mortality had no effect on the abundance of EMF inocula, but led to altered EMF community composition including increased abundance of Geopora and reduced abundance of Tuber. Seedling biomass was strongly positively associated with Tuber abundance, suggesting that reductions in this genus with pinyon mortality could have negative consequences for establishing seedlings. These findings suggest that whereas mature pinyon mortality led to competitive release for established juvenile pinyons, changes in EMF community composition with mortality could limit successful seedling establishment and growth in high-mortality sites.


Assuntos
Micorrizas/fisiologia , Pinus/microbiologia , Árvores/microbiologia , Biomassa , Microclima , Caules de Planta/crescimento & desenvolvimento , Plântula/crescimento & desenvolvimento , Plântula/microbiologia
12.
Can J Urol ; 26(5 Suppl 2): 57-59, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31629436

RESUMO

Demand for cancer genetic counseling has grown rapidly in recent years as germline genomic information has integrated into cancer care. There are currently an insufficient number of genetic counselors (GC) to address genetic testing need through traditional pre- and post-test counseling. Alternative genetic counseling frameworks, discussed here, are under study to increase access to genetic testing while optimizing the skillsets of existent master's-trained GCs.


Assuntos
Aconselhamento Genético , Testes Genéticos , Neoplasias da Próstata/diagnóstico , Atenção à Saúde/métodos , Humanos , Masculino , Neoplasias da Próstata/genética
13.
Adv Exp Med Biol ; 1184: 81-95, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32096030

RESUMO

Tau is a microtubule-associated protein that is involved in both normal and pathological processes in neurons. Since the discovery and characterization of tau over 40 years ago, our understanding of tau's normal functions and toxic roles in neurodegenerative tauopathies has continued to expand. Fast axonal transport is a critical process for maintaining axons and functioning synapses, critical subcellular compartments underlying neuronal connectivity. Signs of fast axonal transport disruption are pervasive in Alzheimer's disease and other tauopathies and various mechanisms have been proposed for regulation of fast axonal transport by tau. Post-translational modifications of tau including phosphorylation at specific sites, FTDP-17 point mutations, and oligomerization, confer upon tau a toxic effect on fast axonal transport. Consistent with the well-established dependence of axons on fast axonal transport, these disease-related modifications are closely associated temporally and spatially with axonal degeneration in the early disease stages. These factors position tau as a potentially critical factor mediating the disruption of fast axonal transport that precedes synaptic dysfunction and axonal degeneration at later disease stages. In this chapter, we review the evidence that tau affects fast axonal transport and examine several potential mechanisms proposed to underlie this toxicity.


Assuntos
Transporte Axonal , Tauopatias/metabolismo , Tauopatias/patologia , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Humanos , Fosforilação , Proteínas tau/química
14.
J Strength Cond Res ; 33(6): 1480-1487, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30946264

RESUMO

Chen, L, Davison, SW, Selimovic, EA, Mueller, RE, Beatty, SR, Carter, KA, Parmar, PJ, Symons, TB, Pantalos, GM, and Caruso, JF. Load-power relationships for high-speed knee extension exercise. J Strength Cond Res 33(6): 1480-1487, 2019-Seventy subjects did 4 knee extensor workouts with their left legs to assess load-power relationships produced on a high-speed trainer (HST; Newnan, GA, USA). Each workout is composed of 4 sets done on the HST at a different load (1, 4.4, 6.7, 9 kg). A Latin Squares Design determined load sequence per workout. Average power (AP) and peak power (PP) and those same values normalized to body mass (BM) and fat-free mass (AP/BM, PP/BM, AP/FFM, PP/FFM) were each analyzed with 2 (gender) × 4 (load) analysis of variances, with repeated measures for load. We assessed relationships between normalized loads and AP and PP values with correlation coefficients. Average power results revealed a significant interaction, with men > women at 9 kg. Peak power/body mass also yielded an interaction, with women > men at 6.7 and 9 kg. Average power/fat-free mass and PP/FFM each produced interactions, with women > men at 4.4, 6.7, and 9 kg. Correlation coefficients showed significant (r = 0.80-0.82) relationships between normalized loads and AP and PP values. In conclusion, the very low inertial resistance to initiate each repetition on this novel device may in part explain our PP/BM, AP/FFM, PP/FFM results, in which higher values were achieved by women. Our practical applications imply that the low inertial resistance for HST repetitions negates male size and strength advantages typically seen when power is measured.


Assuntos
Teste de Esforço/instrumentação , Força Muscular , Músculo Quadríceps/fisiologia , Adolescente , Peso Corporal , Feminino , Humanos , Articulação do Joelho , Masculino , Treinamento Resistido/instrumentação , Adulto Jovem
15.
Am J Med Genet A ; 176(3): 578-588, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29446570

RESUMO

Clinical genome and exome sequencing (CGES) may identify variants leading to targeted management of existing conditions. Yet, CGES often fails to identify pathogenic diagnostic variants and introduces uncertainties by detecting variants of uncertain significance (VUS) and secondary findings. This study investigated how families understand findings and adjust their perspectives on CGES. As part of NIH's Clinical Sequencing Exploratory Research Consortium, children were recruited from clinics at the Children's Hospital of Pennsylvania (CHOP) and offered exome sequencing. Primary pathogenic and possibly pathogenic, and some secondary findings were returned. Investigators digitally recorded results disclosure sessions and conducted 3-month follow up interviews with 10 adolescents and a parent. An interdisciplinary team coded all transcripts. Participants were initially disappointed with findings, yet reactions evolved within disclosure sessions and at 3-month interviews toward acceptance and satisfaction. Families erroneously expected, and prepared extensively, to learn about risk for common conditions. During disclosure sessions, parents and adolescents varied in how they monitored and responded to each others reactions. Several misinterpreted, or overestimated, the utility of findings to attribute meaning and achieve closure for the CGES experience. Participants perceived testing as an opportunity to improve disease management despite results that did not introduce new treatments or diagnoses. Future research may examine whether families experience cognitive dissonance regarding discrepancies between expectations and findings, and how protective buffering minimizes the burden of disappointment on loved ones. As CGES is increasingly integrated into clinical care providers must contend with tempering family expectations and interpretations of findings while managing complex medical care.


Assuntos
Dissonância Cognitiva , Sequenciamento do Exoma , Pais/psicologia , Adaptação Psicológica , Adolescente , Adulto , Criança , Revelação , Medo , Feminino , Frustração , Aconselhamento Genético , Testes Genéticos , Genoma Humano , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Inquéritos e Questionários , Incerteza , Adulto Jovem
16.
J Phycol ; 54(1): 56-65, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29054124

RESUMO

The palaeoceanography of southern Australia has been characterized by fluctuating sea levels during glacial periods, changing temperature regimes and modified boundary currents. Previous studies on genetic structuring of species in southeastern Australia have focused mainly on the differentiation of eastern and western populations while the potential role of Bass Strait as a region of overlap for three biogeographic provinces (Peronia, Maugea, and Flindersia) has been largely ignored. This study aimed to explore the likely roles of historic and contemporary factors in determining divergence patterns in the habitat-forming intertidal seaweed Hormosira banksii in southeastern Australia with a special focus on postglacial dispersal into Bass Strait. We examined the genetic diversity of 475 Hormosira specimens collected from 19 sites around southern Australia using DNA sequence analysis of cytochrome oxidase 1. Three major haplotype groups were identified (western, centre and eastern) corresponding with the three existing biogeographical provinces in this region. Historic break points appeared to be retained and reinforced by modern day dispersal barriers. Phylogeographic grouping of Hormosira reflected a combination of historic and contemporary oceanography. As western and eastern group haplotypes were largely absent within Bass Strait, re-colonization after the last glacial maximum appeared to have originated from refuges within or near present day Bass Strait. Patterns of genetic structure for Hormosira are consistent with other marine species in this region and highlight the importance of biogeographical barriers in contributing to modern genetic structure.


Assuntos
Variação Genética , Phaeophyceae/fisiologia , Alga Marinha/fisiologia , Proteínas de Algas/análise , Complexo IV da Cadeia de Transporte de Elétrons/análise , Genoma Mitocondrial , New South Wales , Phaeophyceae/genética , Alga Marinha/genética , Tasmânia , Vitória
17.
J Psychosoc Oncol ; 36(5): 529-544, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29863445

RESUMO

Deleterious mutations in BRCA1 or BRCA2 genes increase a woman's lifetime risk of breast and ovarian cancer. Risk management guidelines endorse early detection and prevention behaviors. Despite expressed intent, uptake of these measures remains low. This longitudinal, qualitative study integrated retrospective and prospective data to distinguish factors shaping intent to act from those that are catalysts to taking action to reduce cancer risk. Twelve BRCA1/2 mutation-positive women participating in the National Cancer Institute's Breast Imaging Study aged 18-35 completed two semi-structured interviews three years apart. Researchers completed focused coding to identify points of behavioral intent and action and contextual factors acting as catalysts upon participant narratives. All women shared only two action steps: seeking information about cancer risk and completing genetic testing. The constellation of action steps created a unique action trajectory that was defined, with precise ideas about risk perception and clear behavioral response, or iterative, in which unanticipated life events shifted the speed, accessibility, or order in which risk management and family planning goals were prioritized, planned, or executed. Factors shifting action steps included salient, unanticipated life events, such as infertility, insurance/financial constraints, birth of the last child, or a relative's cancer diagnosis. Focus on cancer morbidity may obfuscate how women prioritize actions, and ignore varied pragmatic, relational, and social factors affecting how intended actions are completed, particularly during the reproductive years. We recommend providers update patients' risk management plans at each visit to assess readiness for next steps and reduce reluctance to discuss, or guilt associated with, change.


Assuntos
Neoplasias da Mama/prevenção & controle , Genes BRCA1 , Genes BRCA2 , Mutação , Neoplasias Ovarianas/prevenção & controle , Adolescente , Adulto , Neoplasias da Mama/genética , Feminino , Testes Genéticos , Humanos , Estudos Longitudinais , Neoplasias Ovarianas/genética , Estudos Prospectivos , Pesquisa Qualitativa , Estudos Retrospectivos , Comportamento de Redução do Risco , Adulto Jovem
18.
Environ Microbiol ; 19(4): 1600-1611, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28120480

RESUMO

Nitrogen (N) deposition affects myriad aspects of terrestrial ecosystem structure and function, and microbial communities may be particularly sensitive to anthropogenic N inputs. However, our understanding of N deposition effects on microbial communities is far from complete, especially for drylands where data are comparatively rare. To address the need for an improved understanding of dryland biological responses to N deposition, we conducted a two-year fertilization experiment in a semiarid grassland on the Colorado Plateau in the southwestern United States. We evaluated effects of varied levels of N inputs on archaeal, bacterial, fungal and chlorophyte community composition within three microhabitats: biological soil crusts (biocrusts), soil below biocrusts, and the plant rhizosphere. Surprisingly, N addition did not affect the community composition or diversity of any of these microbial groups; however, microbial community composition varied significantly among sampling microhabitats. Further, while plant richness, diversity, and cover showed no response to N addition, there were strong linkages between plant properties and microbial community structure. Overall, these findings highlight the potential for some dryland communities to have limited biotic ability to retain augmented N inputs, possibly leading to large N losses to the atmosphere and to aquatic systems.


Assuntos
Pradaria , Nitrogênio/metabolismo , Microbiologia do Solo , Archaea , Biomassa , Colorado , Ecossistema , Fungos/metabolismo , Plantas/metabolismo , Rizosfera , Solo/química
20.
J Psychosoc Oncol ; 35(4): 393-408, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28332940

RESUMO

Young women with BRCA1/2 mutations face difficult health-care decisions regarding family formation, fertility, breastfeeding, and whether/when to undergo cancer risk-reducing surgery. This longitudinal qualitative study investigated these life choices during the reproductive years. We conducted two semistructured interviews over three years with 12 reproductive-age BRCA1/2-positive women. Researchers coded transcripts to examine the evolution of risk perceptions, risk management, and family planning decisions. To cope with the conflict between cancer risk reduction versus plans for pregnancy, breastfeeding, and child rearing, participants deliberately prioritized either risk reducing surgery or family formation goals. Implications for mutation carriers and health-care providers are outlined.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Mutação , Neoplasias Ovarianas/genética , Adolescente , Adulto , Neoplasias da Mama/psicologia , Neoplasias da Mama/cirurgia , Tomada de Decisões , Serviços de Planejamento Familiar , Feminino , Humanos , Estudos Longitudinais , Neoplasias Ovarianas/psicologia , Neoplasias Ovarianas/cirurgia , Pesquisa Qualitativa , Comportamento de Redução do Risco , Adulto Jovem
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