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1.
J Exp Child Psychol ; 203: 105012, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33271396

RESUMO

Recent evidence suggests that infants engage in selective prosocial behavior toward some individuals over others; the ways in which infants are selective can illuminate the origins of prosocial behaviors. Here, we explored selective helping behavior, investigating whether a target recipient's prior adherence to, or defiance of, social conventions affects infants' subsequent likelihood of helping the target individual. 19-month-old infants (N = 120) participated in an interaction with an experimenter who correctly labeled common objects, incorrectly labeled objects, or labeled objects with nonsense English-like labels. Infants' rates of helping were higher when the experimenter adhered to labeling conventions than when she defied labeling conventions by either labeling objects incorrectly or using unfamiliar nonsense labels. The current study provides evidence that infants use information about adhering to conventions to guide their helping behavior. These findings help to document the ways in which infants are selective in their helping behavior as well as possible origins of prosocial obligations toward ingroup members.

2.
Transfusion ; 60(12): 3055-3059, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33047855

RESUMO

Prozone is a known phenomenon affecting immunoassays causing falsely low or negative results when excess target is present in the test system. For assays used to evaluate immune-mediated platelet (PLT) transfusion refractoriness, prozone-like phenomenon has been described in solid-phase human leukocyte antigen (HLA) antibody testing and can be mitigated by diluting samples or pretreating samples with ethylenediaminetetraacetic acid (EDTA) or dithiothreitol. Prozone phenomenon has not yet been described in solid-phase red blood cell (RBC) adherence PLT crossmatch assays. CASE REPORT: A 40-year-old female with myeloid sarcoma and PLT transfusion refractoriness underwent repeated solid-phase PLT crossmatches; however, crossmatch-compatible PLTs units did not yield adequate PLT count responses. Class I HLA antibody testing with neat, diluted, and EDTA-pretreated serum demonstrated significant prozone-like effect and the presence of numerous high strength HLA antibodies. Based on this HLA antibody profile, HLA antigen-negative PLTs gave an adequate PLT count response. It was noted that the HLA types of her crossmatch-compatible PLTs were incompatible with her HLA antibody profile (eg, HLA-A2). With ABO-identical, HLA-A2-positive PLT units, a solid-phase PLT crossmatch was repeated using undiluted and diluted EDTA plasma. Undiluted EDTA plasma demonstrated negative or weakly positive PLT crossmatches while the diluted EDTA plasma demonstrated strongly positive PLT crossmatches. CONCLUSION: The prozone phenomenon can cause false-negative results in solid-phase RBC adherence PLT crossmatch assays, which can be mitigated with sample dilution. In immune-mediated PLT transfusion-refractory patients with high-strength HLA antibodies, sample dilution should be considered to correctly identify compatible PLT inventory.

3.
Am J Surg Pathol ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33027072

RESUMO

Undifferentiated carcinoma of the esophagus and gastroesophageal junction is a recently recognized entity in the fifth edition of the World Health Organization Classification of Digestive Tumors and is diagnostically challenging, particularly on small biopsies. SMARCA4 and SMARCA2 are chromatin remodeling genes with key roles in oncogenesis. We retrieved 14 cases of SMARCA4/SMARCA2-deficient undifferentiated carcinoma of the gastroesophageal junction and esophagus from the authors' institutions. The tumors showed similar histologic findings: the sheet-like proliferation of tumor cells characterized by discohesion, large nuclei, and prominent macronucleoli with many tumor cells exhibiting a rhabdoid appearance. In 8 cases, adjacent specialized intestinal metaplasia was noted and 3 cases exhibited adjacent high-grade dysplasia. Immunohistochemically, tumors variably expressed keratins and disclosed loss of expression of SMARCA4 in 12 and SMARCA2 in 7 cases. In 2 cases SMARCA2 alone was lost without SMARCA4 loss. A mutant p53 immunohistochemical pattern was seen in 4 of 4 cases, 3 of which showed diffuse, strong nuclear expression, and 1 case displayed a complete loss of nuclear expression of p53, including invasive carcinoma and associated dysplasia, when present. Limited clinical follow-up was available, but 3 patients died of disease within 0.6, 2, and 7 months of diagnosis. We present the first series of undifferentiated carcinoma of the esophagus and gastroesophageal junction with this characteristic morphology associated with loss of SMARCA4 and/or SMARCA2 expression. This tumor type likely arises from dedifferentiation of a lower grade carcinoma in some cases, and Barrett esophagus and appears to be associated with an aggressive clinical course.

4.
Front Immunol ; 11: 1833, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922395

RESUMO

Podocytes are an important part of the glomerular filtration barrier and the key player in the development of proteinuria, which is an early feature of complement mediated renal diseases. Complement factors are mainly liver-born and present in circulation. Nevertheless, there is a growing body of evidence for additional sites of complement protein synthesis, including various cell types in the kidney. We hypothesized that podocytes are able to produce complement components and contribute to the local balance of complement activation and regulation. To investigate the relevant balance between inhibiting and activating sides, our studies focused on complement factor H (CFH), an important complement regulator, and on C3, the early key component for complement activation. We characterized human cultured podocytes for the expression and secretion of activating and regulating complement factors, and analyzed the secretion pathway and functional activity. We studied glomerular CFH and C3 expression in puromycin aminonucleoside (PAN) -treated rats, a model for proteinuria, and the physiological mRNA-expression of both factors in murine kidneys. We found, that C3 and CFH were expressed in cultured podocytes and expression levels differed from those in cultivated glomerular endothelial cells. The process of secretion in podocytes was stimulated with interferon gamma and located in the Golgi apparatus. Cultured podocytes could initiate the complement cascade by the splitting of C3, which can be shown by the generation of C3a, a functional C3 split product. C3 contributed to external complement activation. Podocyte-secreted CFH, in conjunction with factor I, was able to split C3b. Podocytes derived from a patient with a CFH mutation displayed impaired cell surface complement regulation. CFH and C3 were synthesized in podocytes of healthy C57Bl/6-mice and were upregulated in podocytes of PAN treated rats. These data show that podocytes produce functionally active complement components, and could therefore influence the local glomerular complement activation and regulation. This modulating effect should therefore be considered in all diseases where glomerular complement activation occurs. Furthermore, our data indicate a potential novel role of podocytes in the innate immune system.

5.
Eur J Hum Genet ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929236

RESUMO

Prenatal genetic testing and analysis in the past was usually only offered when a particular fetal phenotype was noted or suspected, meaning that filtering and interpretation of genetic variants identified could be anchored in attempts to explain an existing health concern. Advanced genomic testing is now increasingly used in "low-risk" pregnancies, producing information on genotype adrift of the phenotypic data that is necessary to give it meaning, thus increasing the difficulty in predicting whether and how particular genetic variants might affect future development and health. A challenge to healthcare scientists, clinicians, and parents therefore is deciding what qualities prenatal genotypic variation should have in order to be constructed as a 'result.' At the same time, such tests are often re requested in order to make binary decisions about whether to continue a pregnancy or not. As a range of professional organizations develop guidelines on the use of advanced genomic testing during pregnancy, we highlight the particular difficulties of discovering ambiguous findings such as variants with uncertain clinical significance, susceptibility loci for neurodevelopmental problems and susceptibility to adult-onset diseases. We aim to foster international discussions about how decisions around disclosure are made and how uncertainty is communicated.

6.
J Neuroeng Rehabil ; 17(1): 51, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299483

RESUMO

BACKGROUND: Participation in physical and therapeutic activities is usually severely restricted after a spinal cord injury (SCI). Reasons for this are the associated loss of voluntary motor function, inefficient temperature regulation of the affected extremities, and early muscle fatigue. Hydrotherapy or swim training offer an inherent weight relief, reduce spasticity and improve coordination, muscle strength and fitness. METHODS: We present a new hybrid exercise modality that combines functional electrical stimulation (FES) of the knee extensors and transcutaneous spinal cord stimulation (tSCS) with paraplegic front crawl swimming. tSCS is used to stimulate the afferent fibers of the L2-S2 posterior roots for spasticity reduction. By activating the tSCS, the trunk musculature is recruited at a motor level. This shall improve trunk stability and straighten the upper body. Within this feasibility study, two complete SCI subjects (both ASIA scale A, lesion level Th5/6), who have been proficient front crawl swimmers, conducted a 10-week swim training with stimulation support. In an additional assessment swim session nine months after the training, the knee extension, hip extension, and trunk roll angles where measured using waterproof inertial measurement units (IMUs) and compared for different swimming conditions (no stimulation, tSCS, FES, FES plus tSCS). RESULTS: For both subjects, a training effect over the 10-week swim training was observed in terms of measured lap times (16 m pool) for all swimming conditions. Swimming supported by FES reduced lap times by 15.4% and 8.7% on average for Subject A and Subject B, respectively. Adding tSCS support yielded even greater mean decreases of 19.3% and 20.9% for Subjects A and B, respectively. Additionally, both subjects individually reported that swimming with tSCS for 30-45 minutes eliminated spasticity in the lower extremities for up to 4 hours beyond the duration of the session. Comparing the median as well as the interquartile range of all different settings, the IMU-based motion analysis revealed that FES as well as FES+tSCS improve knee extension in both subjects, while hip extension was only increased in one subject. Trunk roll angles were similar for all swimming conditions. tSCS had no influence on the knee and hip joint angles. Both subjects reported that stimulation-assisted swimming is comfortable, enjoyable, and they would like to use such a device for recreational training and rehabilitation in the future. CONCLUSIONS: Stimulation-assisted swimming seems to be a promising new form of hybrid exercise for SCI people. It is safe to use with reusable silicone electrodes and can be performed independently by experienced paraplegic swimmers except for transfer to water. The study results indicate that swimming speed can be increased by the proposed methods and spasticity can be reduced by prolonged swim sessions with tSCS and FES. The combination of stimulation with hydrotherapy might be a promising therapy for neurologic rehabilitation in incomplete SCI, stroke or multiples sclerosis patients. Therefore, further studies shall incorporate other neurologic disorders and investigate the potential benefits of FES and tSCS therapy in the water for gait and balance.


Assuntos
Terapia por Estimulação Elétrica/métodos , Terapia por Exercício/métodos , Paraplegia/reabilitação , Traumatismos da Medula Espinal/reabilitação , Natação/fisiologia , Adulto , Terapia por Estimulação Elétrica/instrumentação , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/etiologia , Espasticidade Muscular/reabilitação , Paraplegia/etiologia , Projetos Piloto , Traumatismos da Medula Espinal/complicações
7.
Eur J Hum Genet ; 28(6): 732-741, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31919452

RESUMO

The 100,000 Genomes Project (100kGP)-a hybrid clinical-research initiative-was set up to analyse whole-genome sequences (WGS) from patients living with a rare disease or cancer. The project positioned participant consent as being of central importance, but consent in the context of genomic testing raises challenging issues. In this mixed method study, we surveyed 1337 100kGP participants regarding their experiences of taking part in the project and conducted in-depth interviews with 24 survey respondents to explore these findings further. Survey responses were analysed using descriptive statistics and interview data were analysed thematically. The consent approach of the 100kGP resulted in a proportion of our study's participants not understanding the complexities of the project and what types of results they might receive; for example, 20% of participants who we surveyed from the cancer arm did not recall what decisions they had made regarding additional findings. It is not surprising that a project such as this, with such diverse aims and participant groups, would throw up at least some challenges. However, participants reported being satisfied with their experience of the project to date. Our study highlights that in the context of consent for more complex endeavours, such as the 100kGP, it is important to assess (and document) an agreement to take part, but complicated decisions about what and when to communicate may need revisiting over time in response to changing contexts. We discuss the implications of our findings with reference to participants of the 100kGP and the newly formed NHS Genomic Medicine Service.

8.
Nat Hum Behav ; 4(4): 372-379, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31959925

RESUMO

The ability to decide whether, when and how to try is central to human learning. We investigated whether infants can make rational inferences about when and how to try on a novel problem-solving task. After learning from an adult that the task was either easy, difficult or impossible to solve, infants varied in whether, when and how they tried based on the type of social evidence that they received and on their own ongoing experience with the task. Specifically, infants formed expectations about the task, their own ability to solve the task and the experimenter's ability to solve the task, in light of accumulating evidence across time that impacted their time spent trying, trying force, affect, and help-seeking behaviour on the task. Thus, infants flexibly integrate social input and first-hand experience in a dynamic fashion to engage in adaptive persistence.


Assuntos
Tomada de Decisões , Comportamento do Lactente/psicologia , Resolução de Problemas , Humanos , Lactente , Aprendizado Social , Percepção Social , Análise e Desempenho de Tarefas , Fatores de Tempo
10.
Eur J Hum Genet ; 28(2): 155-164, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31527856

RESUMO

Technological advances have seen the offer of genome sequencing becoming part of mainstream medical practice. Research has elicited patient and health professional views on the ethical issues genome sequencing raises, however, we know little about the general public's views. These views offer an insight into people's faith in such technologies, informing discussion regarding the approach to consent in clinic. We aimed to garner public views regarding genome sequencing, incidental findings (IFs), and sharing genetic information with relatives. Participants (n = 1954) from the British general public completed a survey, distributed via email. Overall, the public had a positive view of genomic sequencing, choosing 'informative' as the most popular word (52%) and 'family legacy' as the most popular analogy (33%) representing genomic sequencing for them. Fifty-three percent  agree that their relative had the right to be told about genetic information relevant to them. Fifty-four percent would expect to be told about IFs whether they had asked for them or not. Clinical practice needs to acknowledge these perspectives and expectations in order to facilitate meaningful discussion during the consent process for genomic tests. We suggest that: (a) optimistic perspectives on the usefulness of genomic tests need to be tempered by discussion in clinic about the likelihood that genomic results might be uninformative, uncertain or unexpected; (b) discussions regarding the familial nature of results are needed before testing: the majority of patients will welcome this and any concerns can be explored further; and (c) a wider discussion is required regarding the consent approach for genomic testing.

11.
Expert Rev Mol Diagn ; 19(11): 963-967, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31603004

RESUMO

Introduction: Clinical practice and research are traditionally seen as distinct activities that are governed by different principles and processes. Innovative technologies such as genomic testing challenge this model, involving many activities that cannot be easily categorized as purely research, or purely clinical care. Areas covered: We discuss the interdependence of research and clinical practice in the context of genomics, for example, when determining the significance of rare genetic variants, or diagnosing newly described rare diseases. We highlight the potential of the symbiotic relationship between clinical practice and research. Expert opinion: In the context of genomics, it is not appropriate to treat clinical practice and research as entirely separable. Forcing binary categorization of activities as one or the other risks losing the many benefits that derive from their integration. We need to explore the hybrid area where clinical practice and research coincide, developing governance that allows us to maximize its potential, rather than insisting that hybrid clinical-research activities conform to processes built for 'pure clinical practice' or 'pure research'. We argue the need for a renegotiation of the contract around genomic testing, recognizing, valuing and facilitating the hybrid space where clinical practice and research co-exist.


Assuntos
Pesquisa Biomédica/métodos , Testes Genéticos/métodos , Genômica/métodos , Comunicação Interdisciplinar , Humanos
13.
Am J Med Genet A ; 179(10): 2049-2055, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400068

RESUMO

Histone Gene Cluster 1 Member E, HIST1H1E, encodes Histone H1.4, is one of a family of epigenetic regulator genes, acts as a linker histone protein, and is responsible for higher order chromatin structure. HIST1H1E syndrome (also known as Rahman syndrome, OMIM #617537) is a recently described intellectual disability (ID) syndrome. Since the initial description of five unrelated individuals with three different heterozygous protein-truncating variants (PTVs) in the HIST1H1E gene in 2017, we have recruited 30 patients, all with HIST1H1E PTVs that result in the same shift in frame and that cluster to a 94-base pair region in the HIST1H1E carboxy terminal domain. The identification of 30 patients with HIST1H1E variants has allowed the clarification of the HIST1H1E syndrome phenotype. Major findings include an ID and a recognizable facial appearance. ID was reported in all patients and is most frequently of moderate severity. The facial gestalt consists of a high frontal hairline and full lower cheeks in early childhood and, in later childhood and adulthood, affected individuals have a strikingly high frontal hairline, frontal bossing, and deep-set eyes. Other associated clinical features include hypothyroidism, abnormal dentition, behavioral issues, cryptorchidism, skeletal anomalies, and cardiac anomalies. Brain magnetic resonance imaging (MRI) is frequently abnormal with a slender corpus callosum a frequent finding.


Assuntos
Facies , Histonas/genética , Deficiência Intelectual/genética , Mutação/genética , Comportamento , Crescimento e Desenvolvimento , Heterozigoto , Humanos , Aprendizagem , Fenótipo , Síndrome
14.
Cognition ; 193: 104025, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31325720

RESUMO

Infants' persistence in the face of challenges predicts their learning across domains. In older children, linguistic input is an important predictor of persistence: when children are praised for their efforts, as opposed to fixed traits, they try harder on future endeavors. Yet, little is known about the impact of linguistic input as individual differences in persistence are first emerging, during infancy. Based on a preliminary investigation of the CHILDES database, which revealed that language surrounding persistence is an early-emerging feature of children's language environment, we conducted an observational study to test how linguistic input in the form of praise and persistence-focused language more broadly impacts infants' persistence. In Study 1, 18-month-olds and their caregivers participated in two tasks: a free-play task (a gear stacker) and a joint-book reading task. We measured parental language and infants' persistent gear stacking. Findings revealed that infants whose parents spent more time praising their efforts and hard work (process praise), and used more persistence-focused language in general, were more persistent than infants whose parents used this language less often. Study 2 extended these findings by examining whether the effects of parental language on persistence carry over to contexts in which parents are uninvolved. The findings revealed that parental use of process praise predicted infants' persistence even in the absence of parental support. Critically, these findings could not be explained by caregivers' reporting on their own persistence. Together, these findings suggest that as early as 18 months, linguistic input is a key predictor of persistence.


Assuntos
Desenvolvimento Infantil/fisiologia , Comportamento do Lactente/fisiologia , Aprendizagem/fisiologia , Motivação/fisiologia , Relações Pais-Filho , Percepção da Fala/fisiologia , Feminino , Humanos , Lactente , Masculino
15.
Curr Genet Med Rep ; 7(2): 85-91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281738

RESUMO

Purpose of Review: Genomic tests offer increased opportunity for diagnosis, but their outputs are often uncertain and complex; results may need to be revised and/or may not be relevant until some future time. We discuss the challenges that this presents for consent and autonomy. Recent Findings: Popular discourse around genomic testing tends to be strongly deterministic and optimistic, yet many findings from genomic tests are uncertain or unclear. Clinical conversations need to anticipate and potentially challenge unrealistic expectations of what a genomic test can deliver in order to enhance autonomy and ensure that consent to genomic testing is valid. Summary: We conclude that 'fully informed' consent is often not possible in the context of genomic testing, but that an open-ended approach is appropriate. We consider that such broad consent can only work if located within systems or organisations that are trustworthy and that have measures in place to ensure that such open-ended agreements are not abused. We suggest that a relational concept of autonomy has benefits in encouraging focus on the networks and relationships that allow decision making to flourish.

16.
Am J Bioeth ; 19(1): 70-71, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-31307358

Assuntos
Genômica , Humanos
17.
J Med Ethics ; 45(6): 357-360, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31189727

RESUMO

We discuss a case where medically optimal investigations of health problems in a donor-conceived child would require their egg donor to participate in genetic testing. We argue that it would be justified to contact the egg donor to ask whether she would consider this, despite her indicating on a historical consent form that she did not wish to take part in future research and that she did not wish to be informed if she was found to be a carrier of a 'harmful inherited condition'. We suggest that we cannot conjecture what her current answer might be if, by participating in clinical genetic testing, she might help reach a diagnosis for the donor-conceived child. At the point that she made choices regarding future contact, it was not yet evident that the interests of the donor-conceived child might be compromised by her answers, as it was not foreseen that the egg donor's genome might one day have the potential to enable diagnosis for this child. Fertility consent forms tend to be conceptualised as representing incontrovertible historical boundaries, but we argue that rapid evolution in genomic practice means that consent in such cases is better seen as an ongoing and dynamic process. It cannot be possible to compel the donor to aid in the diagnosis of the donor-conceived child, but she should be given the opportunity to do so.


Assuntos
Testes Genéticos/ética , Doação de Oócitos/ética , Doadores de Tecidos/ética , Confidencialidade/ética , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/etiologia , Doenças Genéticas Inatas/genética , Humanos
18.
Genet Med ; 21(10): 2216-2223, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30976099

RESUMO

PURPOSE: To provide a detailed electroclinical description and expand the phenotype of PIGT-CDG, to perform genotype-phenotype correlation, and to investigate the onset and severity of the epilepsy associated with the different genetic subtypes of this rare disorder. Furthermore, to use computer-assisted facial gestalt analysis in PIGT-CDG and to the compare findings with other glycosylphosphatidylinositol (GPI) anchor deficiencies. METHODS: We evaluated 13 children from eight unrelated families with homozygous or compound heterozygous pathogenic variants in PIGT. RESULTS: All patients had hypotonia, severe developmental delay, and epilepsy. Epilepsy onset ranged from first day of life to two years of age. Severity of the seizure disorder varied from treatable seizures to severe neonatal onset epileptic encephalopathies. The facial gestalt of patients resembled that of previously published PIGT patients as they were closest to the center of the PIGT cluster in the clinical face phenotype space and were distinguishable from other gene-specific phenotypes. CONCLUSION: We expand our knowledge of PIGT. Our cases reaffirm that the use of genetic testing is essential for diagnosis in this group of disorders. Finally, we show that computer-assisted facial gestalt analysis accurately assigned PIGT cases to the multiple congenital anomalies-hypotonia-seizures syndrome phenotypic series advocating the additional use of next-generation phenotyping technology.


Assuntos
Aciltransferases/metabolismo , Glicosilfosfatidilinositóis/deficiência , Glicosilfosfatidilinositóis/metabolismo , Convulsões/metabolismo , Anormalidades Múltiplas/genética , Aciltransferases/genética , Criança , Pré-Escolar , Deficiências do Desenvolvimento/genética , Epilepsia/genética , Feminino , Estudos de Associação Genética , Genótipo , Glicosilfosfatidilinositóis/genética , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Linhagem , Fenótipo , Convulsões/genética
19.
Clin Sci (Lond) ; 133(5): 697-708, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30837331

RESUMO

Advances in genetic technology are having a major impact in the clinic, and mean that many perceptions of the role and scope of genetic testing are having to change. Genomic testing brings with it a greater opportunity for diagnosis, or predictions of future diagnoses, but also an increased chance of uncertain or unexpected findings, many of which may have impacts for multiple members of a person's family. In the past, genetic testing was rarely able to provide rapid results, but the increasing speed and availability of genomic testing is changing this, meaning that genomic information is increasingly influencing decisions around patient care in the acute inpatient setting. The landscape of treatment options for genetic conditions is shifting, which has evolving implications for clinical discussions around previously untreatable disorders. Furthermore, the point of access to testing is changing with increasing provision direct to the consumer outside the formal healthcare setting. This review outlines the ways in which genetic medicine is developing in light of technological advances.


Assuntos
Testes Genéticos/tendências , Terapia Genética/tendências , Genética Médica/tendências , Genômica/tendências , Animais , Difusão de Inovações , Predisposição Genética para Doença , Humanos , Farmacogenética/tendências , Fenótipo , Medicina de Precisão/tendências , Valor Preditivo dos Testes
20.
J Med Ethics ; 45(8): 526-527, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30862707

RESUMO

Gyngell and colleagues consider that the recent Nuffield Council report does not go far enough: heritable genome editing (HGE) is not just justifiable in a few rare cases; instead, there is a moral imperative to undertake it. We agree that there is a moral argument for this, but in the real world it is mitigated by the fact that it is not usually possible to ensure a better life. We suggest that a moral imperative for HGE can currently only be concluded if one first buys into an overly deterministic view of a genome sequence, and the role of variation within in it, in the aetiology of the disease: most diseases cannot simply be attributed to specific genetic variants that we could edit away. Multiple, poorly understood genetic and environmental factors interact to influence the expression of diseases with a genetic component, even well understood 'monogenic' disorders. Population-level genome analyses are now demonstrating that many genetic 'mutations' are much less predictive than previously thought 1 Furthermore, HGE might introduce new risks just as it reduces old ones; or remove protections not yet clearly delineated.


Assuntos
Edição de Genes , Genoma Humano , Dissidências e Disputas , Humanos , Princípios Morais
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