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1.
HGG Adv ; : 100297, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38637989

RESUMO

Over the past century, genetics and genomics ("genomics") have contributed significantly to knowledge of human biology and disease. Genomics has also bolstered inaccurate and harmful arguments about "essential" differences between socially defined groups. These purported differences have reinforced class hierarchies and justified the mistreatment of groups such as Black, Indigenous, and other people of color and people with disabilities. With this history in mind, we explore how genomics is used to reinforce scientifically unsound understandings of the relationship between two fundamental aspects of the human experience: sex and gender. We argue that imprecise, inaccurate practices for collecting data and conducting genomic research have adversely influenced genomic science and can contribute to the stigmatization of people whose sex and/or gender challenge binary expectations. The results have been to preclude transgender and intersex people from accessing high-quality, evidence-based healthcare and to hinder their participation in scientifically sound research. In this article, we use the lens of queer theory to render this situation more visible. First, we highlight the theoretical contributions queer theory can make to genomic science. Second, we examine practices in research and clinical genomics that exclude and stigmatize transgender and intersex people. Third, we highlight ways that many current genomic research practices generate false conclusions that are used to support unjust public policies. We conclude by recommending ways that clinicians and researchers can-and should-harness the scientific, social, and cultural power of genomics to advance knowledge and improve lives across the spectra of sex and gender.

2.
J Genet Couns ; 33(1): 118-123, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38351603

RESUMO

Educational use of clinical simulation is a way for students to immerse themselves within a realistic yet safe and structured environment as they practice clinical skills. It is widely used in healthcare training and evaluation, and there are best practices for design, implementation, debriefing, and assessment. An increasing number of genetic counseling graduate programs use simulation in various ways, ranging from role-plays to working with professional simulated/standardized patient (SP) actors. At this time, there is very little consistency across programs, research on the approaches, and standards by which simulation is incorporated into training. Simulation is an understudied but promising approach for genetic counselor (GC) education and assessment. After graduation, GCs demonstrate their competence as entry-level providers through American Board of Genetic Counseling (ABGC) multiple-choice examination (MCE), along with their participatory clinical encounters from graduate training. Data from genetic counseling and other professions highlight the limitations and biases of MCEs, suggesting they not only fail to accurately capture competency, but also that they disadvantage underrepresented individuals from entering the field. In addition, MCEs are limited as a tool for assessing nuanced counseling and communication skills, as compared to more quantitative scientific knowledge. We propose that innovative, evidence-based approaches such as simulation have the potential to not only enhance learning, but also to allow GCs to better demonstrate competency during training and in relation to the board examination. Collaborative approaches, research, and funding are needed to further explore the viability of routinely incorporating simulation into GC training and assessment.


Assuntos
Aconselhamento Genético , Testes Genéticos , Humanos , Escolaridade , Aprendizagem , Estudantes
3.
J Genet Couns ; 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38342966

RESUMO

Transgender and gender diverse (TGD) individuals are a significant yet underrepresented population within genetic counseling research and broader LGBTQI+ health studies. This underrepresentation perpetuates a cycle of exclusion from the production of medical knowledge, impacting the quality and equity of care received by TGD individuals. This issue is particularly poignant in cancer genetic counseling, where TGD individuals with elevated cancer risk receive risk assessment, counseling, and referral to support based on risk figures and standards of care developed for cisgender individuals. The experiences of TGD individuals navigating inherited cancer syndromes remain largely undocumented in medical literature, posing challenges to the provision of inclusive care by genetics providers. To bridge this knowledge gap, we conducted a cross-sectional qualitative study. Nineteen semi-structured interviews were held with gender diverse adults having hereditary cancer syndromes, family histories of such syndromes, or personal histories of chest cancer. Our study employed thematic analysis using combined inductive and deductive methods to illuminate how hereditary cancer care intersects with participants' gender identities, gender expression, and gender-affirming care experiences. Participants reflected on care experiences that felt affirming or triggered gender dysphoria. Participants also discussed the interplay between risk-reducing mastectomy and top surgery, exploring co-emergent dynamics between cancer risk management and gender expression. Significantly, participants identified actionable strategies for healthcare providers to enhance support for gender diverse patients, including the mindful use of gendered language, collaborative decision-making, and conveying allyship. These findings offer valuable insights into tailoring genetic counseling to meet the unique needs of TGD individuals, advancing the path toward inclusive and appropriate care for LGBTQI+ individuals with hereditary cancer syndromes.

4.
J Immunol ; 212(4): 576-585, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38180084

RESUMO

SARS-CoV-2 variants of concern (VOCs) continue to evolve and reemerge with chronic inflammatory long COVID sequelae, necessitating the development of anti-inflammatory therapeutic molecules. Therapeutic effects of the receptor for advanced glycation end products (RAGE) were reported in many inflammatory diseases. However, a therapeutic effect of RAGE in COVID-19 has not been reported. In the present study, we investigated whether and how the RAGE-Ig fusion protein would have an antiviral and anti-inflammatory therapeutic effect in the COVID-19 system. The protective therapeutic effect of RAGE-Ig was determined in vivo in K18-hACE2 transgenic mice and Syrian golden hamsters infected with six VOCs of SARS-CoV-2. The underlying antiviral mechanism of RAGE-Ig was determined in vitro in SARS-CoV-2-infected human lung epithelial cells (BEAS-2B). Following treatment of K18-hACE2 mice and hamsters infected with various SARS-CoV-2 VOCs with RAGE-Ig, we demonstrated (1) significant dose-dependent protection (i.e., greater survival, less weight loss, lower virus replication in the lungs); (2) a reduction of inflammatory macrophages (F4/80+/Ly6C+) and neutrophils (CD11b+/Ly6G+) infiltrating the infected lungs; (3) a RAGE-Ig dose-dependent increase in the expression of type I IFNs (IFN-α and IFN-ß) and type III IFN (IFNλ2) and a decrease in the inflammatory cytokines (IL-6 and IL-8) in SARS-CoV-2-infected human lung epithelial cells; and (4) a dose-dependent decrease in the expression of CD64 (FcgR1) on monocytes and lung epithelial cells from symptomatic COVID-19 patients. Our preclinical findings revealed type I and III IFN-mediated antiviral and anti-inflammatory therapeutic effects of RAGE-Ig protein against COVID-19 caused by multiple SARS-CoV-2 VOCs.


Assuntos
COVID-19 , Melfalan , SARS-CoV-2 , gama-Globulinas , Cricetinae , Humanos , Camundongos , Animais , Mesocricetus , Receptor para Produtos Finais de Glicação Avançada/genética , Síndrome Pós-COVID-19 Aguda , Camundongos Transgênicos , Antivirais/farmacologia , Antivirais/uso terapêutico , Modelos Animais de Doenças , Pulmão
5.
Circ Genom Precis Med ; 16(6): e004133, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38014565

RESUMO

BACKGROUND: Limiting high-intensity exercise is recommended for patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) due to its association with penetrance, arrhythmias, and structural progression. Guidelines recommend shared decision-making (SDM) for exercise level, but there is little evidence regarding its impact. Therefore, we sought to evaluate the extent and implications of SDM for exercise, decisional conflict, and decisional regret in patients with ARVC and at-risk relatives. METHODS: Adults diagnosed with ARVC or with positive genetic testing enrolled in the Johns Hopkins ARVC Registry were invited to complete a questionnaire that included exercise history and current exercise, SDM (SDM-Q-9), decisional conflict, and decisional regret. RESULTS: The response rate was 64.8%. Two-thirds of participants (68.0%, n=121) reported clinically significant decisional conflict regarding exercise at diagnosis/genetic testing (DCS [decisional conflict scale]≥25), and half (55.1%, n=98) in the past year. Prevalence of decisional regret was also high with 55.3% (n=99) reporting moderate to severe decisional regret (DRS [decisional regret scale]≥25). The extent of SDM was highly variable ranging from no (0) to perfect (100) SDM (mean, 59.6±25.0). Those diagnosed in adolescence (≤age 21) reported significantly more SDM (P=0.013). Importantly, SDM was associated with less decisional conflict (ß=-0.66, R2=0.567, P<0.01) and decisional regret (ß=-0.37, R2=0.180, P<0.001) and no difference in vigorous intensity aerobic exercise in the 6 months after diagnosis/genetic testing or the past year (P=0.56; P=0.34, respectively). CONCLUSIONS: SDM is associated with lower decisional conflict and decisional regret; and no difference in postdiagnosis exercise. Our data thus support SDM as the preferred model for exercise discussions for ARVC.


Assuntos
Displasia Arritmogênica Ventricular Direita , Adulto , Humanos , Adulto Jovem , Conflito Psicológico , Emoções , Inquéritos e Questionários
6.
J Genet Couns ; 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37641538

RESUMO

The majority of genomic sequencing and microarray results are clinically uninformative, meaning that they do not suggest a need for any behavioral action or medical intervention. Prior studies have shown that recipients of uninformative genomic testing results ("uninformative results" hereafter) may incorrectly interpret them to imply a lowered risk of disease or false reassurance about future health risks. Few studies have examined how patients understand uninformative results when they are returned in a research setting, where there is wide variation in analytical specifications of testing, interpretation and reporting practices, and resources to support the return of results. We conducted cross-sectional interviews (N = 17) to explore how a subset of research participants in one genomics study at the National Institutes of Health reacted to and understood their uninformative test results, which were returned to them via a patient portal without genetic counseling. We found that most participants did not remember the details of the informed consent process, including the distinction between "primary" and "secondary" findings. Participants had questions about what genes were tested for and, in most cases, requested a list of the genes covered. Several participants incorrectly assumed that autosomal recessive carrier results would have been reported to them if detected. Some participants interpreted their uninformative results to mean that they could forgo prenatal testing, and participants had mixed expectations about whether their results might be reinterpreted in the future. These themes suggest that there are specific challenges to returning uninformative results in research settings. Educational supplements to uninformative test reports may be most useful if they contextualize results in relation to other types of clinical genetic or genomic testing that may be made available to research participants in their lifetimes.

7.
Front Immunol ; 14: 1172004, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37215141

RESUMO

Purpose: Though copy number variants (CNVs) have been suggested to play a significant role in inborn errors of immunity (IEI), the precise nature of this role remains largely unexplored. We sought to determine the diagnostic contribution of CNVs using genome-wide chromosomal microarray analysis (CMA) in children with IEI. Methods: We performed exome sequencing (ES) and CMA for 332 unrelated pediatric probands referred for evaluation of IEI. The analysis included primary, secondary, and incidental findings. Results: Of the 332 probands, 134 (40.4%) received molecular diagnoses. Of these, 116/134 (86.6%) were diagnosed by ES alone. An additional 15/134 (11.2%) were diagnosed by CMA alone, including two likely de novo changes. Three (2.2%) participants had diagnostic molecular findings from both ES and CMA, including two compound heterozygotes and one participant with two distinct diagnoses. Half of the participants with CMA contribution to diagnosis had CNVs in at least one non-immune gene, highlighting the clinical complexity of these cases. Overall, CMA contributed to 18/134 diagnoses (13.4%), increasing the overall diagnostic yield by 15.5% beyond ES alone. Conclusion: Pairing ES and CMA can provide a comprehensive evaluation to clarify the complex factors that contribute to both immune and non-immune phenotypes. Such a combined approach to genetic testing helps untangle complex phenotypes, not only by clarifying the differential diagnosis, but in some cases by identifying multiple diagnoses contributing to the overall clinical presentation.


Assuntos
Cromossomos , Testes Genéticos , Humanos , Criança , Sequenciamento do Exoma , Análise em Microsséries , Fenótipo
8.
Genet Med ; 24(11): 2220-2227, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35980380

RESUMO

PURPOSE: Whether and how to disclose secondary finding (SF) information to children is ethically debated. Some argue that genetic testing of minors should be limited to preserve the child's future autonomy. Others suggest that disclosure of SFs can occur if it is in the best interests of the child. However, the ways that parents conceptualize and weigh their child's future autonomy against the interests of their child and other family members are unknown. METHODS: To explore how parents understand SF disclosure in the context of their child and other family members' lives, we conducted semistructured interviews with 30 families (40 parents in total). All parents had children who were enrolled in a genetic sequencing protocol that returned results by default. RESULTS: We found that parents did not routinely conceptualize SFs as distinctive health information. Rather parents saw this information as part of their child's overall health. To make decisions about disclosure, parents weighed their child's ability to understand the SF information and their other family member's need to know. CONCLUSION: Because most families desired SF information, we argue that disclosure of SF be reconceptualized to reflect the lived experiences of those who may receive this information.


Assuntos
Família , Pais , Criança , Humanos , Revelação , Genômica , Testes Genéticos
9.
J Allergy Clin Immunol ; 150(4): 947-954, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35753512

RESUMO

BACKGROUND: Prospective genetic evaluation of patients at this referral research hospital presents clinical research challenges. OBJECTIVES: This study sought not only a single-gene explanation for participants' immune-related presentations, but viewed each participant holistically, with the potential to have multiple genetic contributions to their immune phenotype and other heritable comorbidities relevant to their presentation and health. METHODS: This study developed a program integrating exome sequencing, chromosomal microarray, phenotyping, results return with genetic counseling, and reanalysis in 1505 individuals from 1000 families with suspected or known inborn errors of immunity. RESULTS: Probands were 50.8% female, 71.5% were ≥18 years, and had diverse immune presentations. Overall, 327 of 1000 probands (32.7%) received 361 molecular diagnoses. These included 17 probands with diagnostic copy number variants, 32 probands with secondary findings, and 31 probands with multiple molecular diagnoses. Reanalysis added 22 molecular diagnoses, predominantly due to new disease-gene associations (9 of 22, 40.9%). One-quarter of the molecular diagnoses (92 of 361) did not involve immune-associated genes. Molecular diagnosis was correlated with younger age, male sex, and a higher number of organ systems involved. This program also facilitated the discovery of new gene-disease associations such as SASH3-related immunodeficiency. A review of treatment options and ClinGen actionability curations suggest that at least 251 of 361 of these molecular diagnoses (69.5%) could translate into ≥1 management option. CONCLUSIONS: This program contributes to our understanding of the diagnostic and clinical utility whole exome analysis on a large scale.


Assuntos
Exoma , Testes Genéticos , Exoma/genética , Feminino , Testes Genéticos/métodos , Genômica , Humanos , Masculino , Fenótipo , Estudos Prospectivos
10.
Blood Adv ; 6(13): 3974-3978, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35476126

RESUMO

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by chronic nonmalignant lymphadenopathy, splenomegaly, cytopenias, and other autoimmune manifestations. ALPS is caused by lymphocyte accumulation from defects in FAS-mediated apoptosis. Heterozygous germline or somatic pathogenic single nucleotide variants in FAS are the most common molecular etiology of ALPS. Through the Centralized Sequencing Program at the National Institute of Allergy and Infectious Diseases, we performed exome sequencing on subjects with a clinical diagnosis of ALPS, with a subset receiving copy number variant (CNV) analysis. In this cohort, we identified 3 subjects from unrelated families with CNVs at the FAS locus. One subject had a de novo ∼0.828 Mb copy number loss encompassing all of FAS. The second subject had a maternally inherited ∼1.004 Mb copy number loss encompassing all of FAS. The third subject had a paternally inherited ∼0.044 Mb copy number loss encompassing exons 7 through 9 of FAS. Subjects with deletions in FAS had clinical presentations and biomarker profiles similar to those with ALPS and with germline and somatic FAS variants. We demonstrate that CNV analysis should be pursued if there is clinical and biomarker evidence of ALPS because it can lead to a molecular diagnosis and appropriate treatment when FAS sequencing is inconclusive.


Assuntos
Síndrome Linfoproliferativa Autoimune , Síndrome Linfoproliferativa Autoimune/diagnóstico , Síndrome Linfoproliferativa Autoimune/genética , Variações do Número de Cópias de DNA , Heterozigoto , Humanos , Esplenomegalia/patologia , Receptor fas/genética
12.
J Virol ; 96(5): e0205721, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-34985998

RESUMO

Reactivation of herpes simplex virus 1 (HSV-1) from latently infected neurons of the trigeminal ganglia (TG) leads to blinding recurrent herpetic disease in symptomatic (SYMP) individuals. Although the role of T cells in herpes immunity seen in asymptomatic (ASYMP) individuals is heavily explored, the role of B cells is less investigated. In the present study, we evaluated whether B cells are associated with protective immunity against recurrent ocular herpes. The frequencies of circulating HSV-specific memory B cells and of memory follicular helper T cells (CD4+ Tfh cells), which help B cells produce antibodies, were compared between HSV-1-infected SYMP and ASYMP individuals. The levels of IgG/IgA and neutralizing antibodies were compared in SYMP and ASYMP individuals. We found that (i) the ASYMP individuals had increased frequencies of HSV-specific CD19+CD27+ memory B cells, and (ii) high frequencies of HSV-specific switched IgG+CD19+CD27+ memory B cells detected in ASYMP individuals were directly proportional to high frequencies of CD45R0+CXCR5+CD4+ memory Tfh cells. However, no differences were detected in the level of HSV-specific IgG/IgA antibodies in SYMP and ASYMP individuals. Using the UV-B-induced HSV-1 reactivation mouse model, we found increased frequencies of HSV-specific antibody-secreting plasma HSV-1 gD+CD138+ B cells within the TG and circulation of ASYMP mice compared to those of SYMP mice. In contrast, no significant differences in the frequencies of B cells were found in the cornea, spleen, and bone-marrow. Our findings suggest that circulating antibody-producing HSV-specific memory B cells recruited locally to the TG may contribute to protection from symptomatic recurrent ocular herpes. IMPORTANCE Reactivation of herpes simplex virus 1 (HSV-1) from latently infected neurons of the trigeminal ganglia (TG) leads to blinding recurrent herpetic disease in symptomatic (SYMP) individuals. Although the role of T cells in herpes immunity against blinding recurrent herpetic disease is heavily explored, the role of B cells is less investigated. In the present study, we found that in both asymptomatic (ASYMP) individuals and ASYMP mice, there were increased frequencies of HSV-specific memory B cells that were directly proportional to high frequencies of memory Tfh cells. Moreover, following UV-B-induced reactivation, we found increased frequencies of HSV-specific antibody-secreting plasma B cells within the TG and circulation of ASYMP mice compared to those of SYMP mice. Our findings suggest that circulating antibody-producing HSV-specific memory B cells recruited locally to the TG may contribute to protection from recurrent ocular herpes.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Ceratite Herpética , Células B de Memória , Reinfecção , Animais , Antígenos CD19/imunologia , Imunidade/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Ceratite Herpética/imunologia , Células B de Memória/imunologia , Células B de Memória/virologia , Camundongos , Reinfecção/imunologia , Reinfecção/virologia , Gânglio Trigeminal/virologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Ativação Viral/imunologia
13.
Am J Law Med ; 48(2-3): 187-199, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-36715254

RESUMO

Recent advances in prenatal genetic testing have made testing for congenital disorders more accessible, with emerging technologies promising further expansion of available testing options. In particular, non-invasive prenatal testing ("NIPT") has allowed women to identify more fetal disorders earlier in pregnancy than was possible only a decade ago. In addition to allowing women to prepare for the birth of a child with a disability, prenatal diagnoses give women the ability to terminate a pregnancy to avoid raising a child with a disability, a choice driven by myriad factors.


Assuntos
Aborto Induzido , Testes Genéticos , Gravidez , Criança , Feminino , Humanos , Diagnóstico Pré-Natal
14.
Ann Transl Med ; 9(14): 1192, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430633

RESUMO

In the United States, trauma claims the lives of over 150,000 civilians each year. In military settings, trauma and exsanguination result in 50% of combat related deaths. The majority of these deaths result from uncontrolled non-compressible hemorrhage. Non-compressible hemorrhage often results from deep vascular injuries within the torso, however can also occur secondary to penetrating injuries that involve the extremities. Given the high mortality rates for non-compressible hemorrhage, rapid and effective management of patients suffering from hemorrhage is essential to good patient outcomes. Consequently, there has been increasing interest in solutions for point-of-injury hemorrhage control in trauma and military medicine. Undoubtedly there is a great need for prehospital hemostatic interventions that can be deployed by trained and untrained personnel. Since 2001, various hemostatic agents have been developed, each with its advantages based upon the type and severity of injury, wound size, wound location, accessibility to injury site, and the coagulation status of the patient. These agents are often used in the military setting as a temporizing measure prior to definitive therapy and include techniques such as resuscitative endovascular balloon occlusion of the aorta (REBOA) and bioengineered agents including ResQFoam, RevMedx's XSTAT, Tranexamic acid (TXA), and QuikClot Combat Gauze (QCG). Here, we review the indications, composition, technique, efficacy, and outcomes of these hemostatic agents.

15.
Ann Transl Med ; 9(14): 1197, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430638

RESUMO

Minimally invasive endovascular interventions including stenting and embolization have been widely adopted for the treatment of emergent and traumatic thoracoabdominal injuries. In recent years, these techniques have been utilized in the setting of extremity vascular trauma with promising outcomes. By allowing for the rapid diagnosis and subsequent treatment of penetrating or blunt vascular extremity trauma, these techniques can help to minimize blood loss, reduce operative complications, and potentially prevent limb amputation. Here, we present a narrative review of the ever-increasing role of minimally invasive interventions in the management of extremity trauma and compare its use and outcomes to open surgical repair. A special focus is placed on diagnostic imaging modalities in trauma and the role of interventional radiologists in the work-up and treatment of extremity trauma. We discuss diagnostic imaging modalities that aid in the triaging of extremity trauma, such as Doppler sonography, CT angiography, and catheter-based angiography. We present an overview on the literature related to endovascular interventions such as embolotherapy and stent grafting as well as the technical challenges associated with each technique. Finally, we present our own cases on the workup and endovascular treatment of extremity trauma, including CT angiography, particulate and coil embolization, and stent graft placement.

16.
Front Genet ; 12: 626845, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777099

RESUMO

Genetic testing has the potential to revolutionize primary care, but few health systems have developed the infrastructure to support precision population medicine applications or attempted to evaluate its impact on patient and provider outcomes. In 2018, Sanford Health, the nation's largest rural nonprofit health care system, began offering genetic testing to its primary care patients. To date, more than 11,000 patients have participated in the Sanford Chip Program, over 90% of whom have been identified with at least one informative pharmacogenomic variant, and about 1.5% of whom have been identified with a medically actionable predisposition for disease. This manuscript describes the rationale for offering the Sanford Chip, the programs and infrastructure implemented to support it, and evolving plans for research to evaluate its real-world impact.

17.
Ethics Hum Res ; 43(2): 2-18, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33620774

RESUMO

In the early days of a pandemic, repurposing biospecimens from established research projects could prove to be extraordinarily useful in achieving substantial and timely public health benefits. Nonetheless, there are potential ethical and regulatory uncertainties that may impede access to those valuable biospecimens. In this article, we argue that there should be a presumption in favor of using previously collected identifiable research biospecimens without reconsent to directly address an infectious disease pandemic, assuming certain conditions are met. This argument fills a unique yet critical gap in decision-making where the specific consent accompanying the identifiable biospecimens would not otherwise permit repurposing. Further, it suggests that even if gaining reconsent is feasible, doing so in a fast-moving crisis is not necessary. This analysis also attempts to address the ethical concerns of public health authorities who already may have the power to use such specimens but are reluctant to do so.


Assuntos
Bancos de Espécimes Biológicos/ética , Pesquisa Biomédica/ética , Consentimento Livre e Esclarecido/ética , Pandemias , Saúde Pública/ética , Humanos
18.
Sci Transl Med ; 13(580)2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568519

RESUMO

Percutaneous locoregional therapies (LRTs), such as thermal ablation, are performed to limit the progression of hepatocellular carcinoma (HCC) and offer a bridge for patients waiting for liver transplantation. However, physiological challenges related to tumor location, size, and existence of multiple lesions as well as safety concerns related to potential thermal injury to adjacent tissues may preclude the use of thermal ablation or lead to its failure. Here, we showed a successful injection of an ionic liquid into tissue under image guidance, ablation of tumors in response to the injected ionic liquid, and persistence (28 days) of coinjected chemotherapy with the ionic liquid in the ablation zone. In a rat HCC model, the rabbit VX2 liver tumor model, and 12 human resected tumors, injection of the ionic liquid led to consistent tumor ablation. Combining the ionic liquid with the chemotherapy agent, doxorubicin, resulted in synergistic cytotoxicity when tested with cultured HCC cells and uniform drug distribution throughout the ablation zone when percutaneously injected into liver tumors in the rabbit liver tumor model. Because this ionic liquid preparation is simple to use, is efficacious, and has a low cost, we propose that this new LRT may bridge more patients to liver transplantation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Preparações Farmacêuticas , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Coelhos , Resultado do Tratamento
19.
J Genet Couns ; 30(3): 766-773, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33320394

RESUMO

The most appropriate strategies for managing secondary genomic findings (SF) in clinical research are being developed and evaluated. We surveyed patients at the National Institute of Allergy and Infectious Diseases (NIAID) to evaluate decisional conflict regarding enrolling in a study that returns SF. Responses were collected using a cross-sectional survey after informed consent but before return of SF. Sixty-six adults of 116 eligible participants responded. No participant explicitly declined because they did not want to possibly receive a SF. Sixty-five of 66 (98%) participants thought it was appropriate to return SFs in research; one participant was unsure. Decisional conflict regarding enrolling in a study returning SF was low overall with 68% of participants reporting a score of less than 10 on a 100-point decisional conflict scale, implying that they felt informed, clear on what they wanted, and supported. Lower genetic literacy was weakly associated with higher decisional conflict (Spearman's rho = -0.297, p = .015). Six participants reported confusion related to the choices about SFs. Our data suggest that participants in our study feel it is appropriate to receive SF and have little decisional conflict about potentially receiving such information; however, some participants may need further education and counseling.


Assuntos
Tomada de Decisões , Exoma , Adulto , Estudos Transversais , Genômica , Humanos , Inquéritos e Questionários
20.
Adv Mater ; 32(52): e2005603, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33174305

RESUMO

Vascular embolization is a life-saving minimally invasive catheter-based procedure performed to treat bleeding vessels. Through these catheters, numerous metallic coils are often pushed into the bleeding artery to stop the blood flow. While there are numerous drawbacks to coil embolization, physician expertise, availability of these coils, and their costs further limit their use. Here, a novel blood-derived embolic material (BEM) with regenerative properties, that can achieve instant and durable intra-arterial hemostasis regardless of coagulopathy, is developed. In a large animal model of vascular embolization, it is shown that the BEM can be prepared at the point-of-care within 26 min using fresh blood, it can be easily delivered using clinical catheters to embolize renal and iliac arteries, and it can achieve rapid hemostasis in acutely injured vessels. In swine arteries, the BEM increases cellular proliferation, angiogenesis, and connective tissue deposition, suggesting vessel healing and durable vessel occlusion. The BEM has significant advantages over embolic materials used today, making it a promising new tool for embolization.


Assuntos
Artérias , Materiais Biocompatíveis/farmacologia , Sangue , Cateteres , Embolização Terapêutica/instrumentação , Animais , Proliferação de Células/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Suínos
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