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1.
Semin Immunol ; 66: 101725, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36706520

RESUMO

T-cell immunity, mediated by CD4+ and CD8+ T cells, represents a cornerstone in the control of viral infections. Virus-derived T-cell epitopes are represented by human leukocyte antigen (HLA)-presented viral peptides on the surface of virus-infected cells. They are the prerequisite for the recognition of infected cells by T cells. Knowledge of viral T-cell epitopes provides on the one hand a diagnostic tool to decipher protective T-cell immune responses in the human population and on the other hand various prophylactic and therapeutic options including vaccination approaches and the transfer of virus-specific T cells. Such approaches have already been proven to be effective against various viral infections, particularly in immunocompromised patients lacking sufficient humoral, antibody-based immune response. This review provides an overview on the state of the art as well as current studies regarding the identification and characterization of viral T-cell epitopes and approaches of clinical application. In the first chapter in silico prediction tools and direct, mass spectrometry-based identification of viral T-cell epitopes is compared. The second chapter provides an overview of commonly used assays for further characterization of T-cell responses and phenotypes. The final chapter presents an overview of clinical application of viral T-cell epitopes with a focus on human immunodeficiency virus (HIV), human cytomegalovirus (HCMV) and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), being representatives of relevant viruses.


Assuntos
Linfócitos T CD8-Positivos , COVID-19 , Humanos , Epitopos de Linfócito T , SARS-CoV-2 , Antígenos de Histocompatibilidade Classe I
2.
Clin Infect Dis ; 76(3): e240-e249, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35717657

RESUMO

BACKGROUND: The rapid emergence of the Omicron variant and its large number of mutations led to its classification as a variant of concern (VOC) by the World Health Organization. Subsequently, Omicron evolved into distinct sublineages (eg, BA.1 and BA.2), which currently represent the majority of global infections. Initial studies of the neutralizing response toward BA.1 in convalescent and vaccinated individuals showed a substantial reduction. METHODS: We assessed antibody (immunoglobulin G [IgG]) binding, ACE2 (angiotensin-converting enzyme 2) binding inhibition, and IgG binding dynamics for the Omicron BA.1 and BA.2 variants compared to a panel of VOCs/variants of interest, in a large cohort (N = 352) of convalescent, vaccinated, and infected and subsequently vaccinated individuals. RESULTS: While Omicron was capable of efficiently binding to ACE2, antibodies elicited by infection or immunization showed reduced binding capacities and ACE2 binding inhibition compared to wild type. Whereas BA.1 exhibited less IgG binding compared to BA.2, BA.2 showed reduced inhibition of ACE2 binding. Among vaccinated samples, antibody binding to Omicron only improved after administration of a third dose. CONCLUSIONS: Omicron BA.1 and BA.2 can still efficiently bind to ACE2, while vaccine/infection-derived antibodies can bind to Omicron. The extent of the mutations within both variants prevents a strong inhibitory binding response. As a result, both Omicron variants are able to evade control by preexisting antibodies.


Assuntos
Enzima de Conversão de Angiotensina 2 , Imunoglobulina G , Humanos , Imunização , Mutação , Complicações Pós-Operatórias , Anticorpos Antivirais , Anticorpos Neutralizantes
3.
J Artif Organs ; 25(2): 91-104, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34342807

RESUMO

Self-management is a health behavior known to predict treatment outcomes in patients with multiple co-morbidities and/or chronic conditions. However, the self-management process and outcomes in the left-ventricular assist device (LVAD) population are understudied. This pilot randomized control trial (RCT) evaluated the feasibility of a novel "smartphone app-directed and nurse-supported self-management intervention" in patients implanted with durable LVADs. Assessments included behavioral (self-efficacy and adherence), clinical (complications), and healthcare utilization (unplanned clinic, emergency room (ER) visits, and re-hospitalization) outcomes, completed at baseline (pre-hospital discharge) and months 1, 3, and 6 post-hospital discharge. Intervention patients (n = 14) had favorable patterns/trends of results across study outcomes than control patients (n = 16). Notably, intervention patients had much lower complications and healthcare utilization rates than controls. For example, intervention patients had 2 (14.3%) driveline infections in 6 months while control patients had 3 (19.0%). Additionally, at month 3, intervention patients had 0% ER visits versus 36% of control patients. At month 6, the mean cumulative number of re-hospitalizations for the control group was higher (0.9 ± 0.93) than intervention (0.3 ± 0.61) group. Despite the small sample size and limitations of feasibility/pilot studies, our outcomes data appeared to favor the novel intervention. Lessons learned from this study suggest the intervention should be implemented for 6 months post-hospital discharge. Further research is needed including large and rigorous multi-center RCTs to generate knowledge explaining the mechanism of the effect of self-management on LVAD treatment outcomes.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Autogestão , Hospitalização , Humanos , Resultado do Tratamento
4.
J Cardiovasc Nurs ; 36(2): 172-184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33306621

RESUMO

BACKGROUND: Patients with a left ventricular assist device are a unique and growing population who deserve their own valid, reliable instrument for health-related quality of life. OBJECTIVE: We developed and tested the Health-Related Quality of Life with a Left Ventricular Assist Device (QOLVAD) questionnaire. METHODS: In a prospective, descriptive study, patients from 7 sites completed the QOLVAD and comparator questionnaires. Construct validity was tested using confirmatory factor analysis. Convergent validity was tested using correlations of QOLVAD scores to well-established measures of subjective health status, depression, anxiety, and meaning/faith. Reliability and test-retest reliability were quantified. RESULTS: Patients (n = 213) were 58.7 ± 13.9 years old; 81.0% were male, 73.7% were White, and 48.0% had bridge to transplant. Questionnaires were completed at a median time of 44 weeks post ventricular assist device. The 5 QOLVAD domains had acceptable construct validity (root mean square error of approximation = 0.064, comparative and Tucker-Lewis fit indices > 0.90, weighted root mean square residual = 0.95). The total score and domain-specific scores were significantly correlated with the instruments to which they were compared. Internal consistency reliability was acceptable for all subscales (α = .79-.83) except the cognitive domain (α = .66). Unidimensional reliability for the total score was acceptable (α = .93), as was factor determinacy for multidimensional reliability (0.95). Total test-retest reliability was 0.875 (P < .001). CONCLUSION: Our analysis provided initial support for validity and reliability of the QOLVAD for total score, physical, emotional, social, and meaning/spiritual domains. The QOLVAD has potential in research and clinical settings to guide decision making and referrals; further studies are needed.


Assuntos
Coração Auxiliar , Qualidade de Vida , Adulto , Idoso , Análise Fatorial , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
5.
Artif Organs ; 42(11): 1095-1103, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29575048

RESUMO

This study tested the applicability of the individual and family self-management theory (IFSMT) to self-management (SM) in patients with left ventricular assist devices (LVADs). From an existing data set, we extracted the following variables that correspond to IFSMT's conceptual dimensions: anxiety, depression, and cognition (context dimension); self-efficacy (SM process dimension); adherence and quality of life (QOL; outcome dimensions). Descriptive statistics and partial least squares path modeling procedures were used for data analyses. A total of 100 patients (mean age 52 ± 13.4 years) with continuous flow LVAD designs comprised the present study. Most patients were White (78%), married (69%), college-educated (72%), and on disability (53%). Their mean anxiety and depression scores were slightly above normal, while their cognitive function scores were slightly lower than normal. LVAD care self-efficacy, adherence, and QOL were within normal ranges. Factor loadings ranged from 0.50 to 1.0, and there were significant forward path relationships among the context, process, and outcome dimensions (ß ranges from 0.02 to 0.60, all P values < 0.05). In conclusion, the IFSMT provides a good fit for SM in LVAD. Further research is needed to clarify how best to improve LVAD SM practice and treatment outcomes.


Assuntos
Coração Auxiliar , Qualidade de Vida , Autogestão , Adulto , Idoso , Ansiedade/diagnóstico , Cognição , Depressão/diagnóstico , Feminino , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Resultado do Tratamento
6.
Appl Microbiol Biotechnol ; 101(23-24): 8607-8619, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29063174

RESUMO

Previous studies have shown that enhanced biological phosphorus removal (EBPR) performance under continuous aerobic conditions always eventually deteriorates; however, the speed at which this happens depends on the carbon source supplied. The published data suggest that propionate is a better carbon source than acetate is for maintaining operational stability, although it is not clear why. A lab-scale sequencing batch reactor was run initially under conventional anaerobic/aerobic conditions with either acetate or propionate as the carbon source. Chemical and microbiological analyses revealed that both sources performed as expected for such systems. When continuous aerobic conditions were imposed on both these established communities, marked shifts of the "Candidatus Accumulibacter" clades were recorded for both carbon sources. Here, we discuss whether this shift could explain the prolonged EBPR stability observed with propionate.


Assuntos
Betaproteobacteria/classificação , Betaproteobacteria/metabolismo , Biota , Carbono/metabolismo , Fósforo/metabolismo , Acetatos/metabolismo , Aerobiose , Reatores Biológicos/microbiologia , Propionatos/metabolismo
7.
Int J Infect Dis ; 139: 69-77, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38016500

RESUMO

OBJECTIVES: T cell immunity is key for the control of viral infections including SARS-CoV-2, in particular with regard to immune memory and protection against arising genetic variants. METHODS: We recently evaluated a peptide-based SARS-CoV-2 T cell activator termed CoVac-1 in a first-in-human trial in healthy adults. Here, we report on long-term safety and efficacy data of CoVac-1 until month 12. RESULTS: CoVac-1 is well tolerated without long-term immune-related side effects and induces long-lasting anti-viral T cell responses in 100% of study participants, with potent expandability of clusters of differentiation (CD4+) and CD8+ T cells targeting multiple different CoVac-1 T cell epitopes. T cell responses were associated with stronger injection site reaction. Beyond induction of T cell immunity, 89% of subjects developed CoVac-1-specific immunoglobulin G antibodies which associated with the intensity of the T cell response, indicating that CoVac-1-specific CD4+ T cells support the induction of B-cell responses. Vaccination with approved COVID-19 vaccines boosted CoVac-1-specific T cell responses. Overall, a low SARS-CoV-2 infection rate (8.3%) was observed. CONCLUSION: Together, a single application of CoVac-1 elicits long-lived and broad SARS-CoV-2-specific T cell immunity, which further supports the current evaluation of our T cell activator in patients with congenital or acquired B-cell defects.


Assuntos
COVID-19 , Adulto , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Linfócitos T CD8-Positivos , SARS-CoV-2 , Peptídeos , Anticorpos Antivirais
8.
Nurs Clin North Am ; 58(3): 421-437, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37536790

RESUMO

Mechanical circulatory support (MCS) includes temporary and durable mechanical devices used for two sets of indications: 1. acute heart failure (HF) secondary sepsis, a myocardial infarction, or pulmonary emboli, and 2. for chronic end-stage HF secondary to worsening cardiomyopathy despite guideline driven medical treatment. This article is to aide cardiac intensive care unit (ICU) nurses in understanding the history of MCS therapy, the care of the MCS patient in the cardiac ICU, the critical and collaborative role of transplant teams with MCS therapy, educational needs for a successful discharge, and implications for education and shared decision-making when placing these devices.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Humanos , Insuficiência Cardíaca/terapia , Unidades de Terapia Intensiva
9.
Ann Thorac Surg ; 115(2): 311-327, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36462544

RESUMO

The 13th annual report from The Society of Thoracic Surgeons (STS) Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) highlights outcomes for 27,314 patients receiving continuous-flow durable left ventricular assist devices (LVAD) during the last decade (2012-2021). In 2021, 2464 primary LVADs were implanted, representing a 23.5% reduction in the annual volume compared with peak implantation in 2019 and an ongoing trend from the prior year. This decline is likely a reflection of the untoward effects of the coronavirus disease 2019 pandemic and the change in the United States heart transplant allocation system in 2018. The last several years have been characterized by a shift in device indication and type, with 81.1% of patients now implanted as destination therapy and 92.7% receiving an LVAD with full magnetic levitation in 2021. However, despite an older, more ill population being increasingly supported preimplant with temporary circulatory devices in the recent (2017-2021) vs prior (2012-2016) eras, the 1- and 5-year survival continues to improve, at 83.0% and 51.9%, respectively. The adverse events profile has also improved, with a significant reduction in stroke, gastrointestinal bleeding, and hospital readmissions. Finally, we examined the impact of the change in the heart transplant allocation system in 2018 on LVAD candidacy, implant strategy, and outcomes. In the competing-outcomes analysis, the proportion of transplant-eligible patients receiving a transplant has declined from 56.5% to 46.0% at 3 years, whereas the proportion remaining alive with ongoing support has improved from 24.1% to 38.1% at 3 years, underscoring the durability of the currently available technology.


Assuntos
COVID-19 , Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Cirurgiões , Humanos , Estados Unidos/epidemiologia , COVID-19/epidemiologia , COVID-19/etiologia , Coração Auxiliar/efeitos adversos , Sistema de Registros , Insuficiência Cardíaca/terapia , Resultado do Tratamento , Estudos Retrospectivos
10.
Nat Commun ; 14(1): 7472, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978195

RESUMO

T cell recognition of human leukocyte antigen (HLA)-presented tumor-associated peptides is central for cancer immune surveillance. Mass spectrometry (MS)-based immunopeptidomics represents the only unbiased method for the direct identification and characterization of naturally presented tumor-associated peptides, a key prerequisite for the development of T cell-based immunotherapies. This study reports on the implementation of ion mobility separation-based time-of-flight (TOFIMS) MS for next-generation immunopeptidomics, enabling high-speed and sensitive detection of HLA-presented peptides. Applying TOFIMS-based immunopeptidomics, a novel extensive benignTOFIMS dataset was generated from 94 primary benign samples of solid tissue and hematological origin, which enabled the expansion of benign reference immunopeptidome databases with > 150,000 HLA-presented peptides, the refinement of previously described tumor antigens, as well as the identification of frequently presented self antigens and not yet described tumor antigens comprising low abundant mutation-derived neoepitopes that might serve as targets for future cancer immunotherapy development.


Assuntos
Antígenos de Histocompatibilidade Classe I , Neoplasias , Humanos , Antígenos de Neoplasias , Espectrometria de Massas/métodos , Antígenos HLA , Neoplasias/terapia , Peptídeos/química , Antígenos de Histocompatibilidade Classe II
11.
Blood Cancer Discov ; 4(6): 468-489, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37847741

RESUMO

Therapy-resistant leukemia stem and progenitor cells (LSC) are a main cause of acute myeloid leukemia (AML) relapse. LSC-targeting therapies may thus improve outcome of patients with AML. Here we demonstrate that LSCs present HLA-restricted antigens that induce T-cell responses allowing for immune surveillance of AML. Using a mass spectrometry-based immunopeptidomics approach, we characterized the antigenic landscape of patient LSCs and identified AML- and AML/LSC-associated HLA-presented antigens absent from normal tissues comprising nonmutated peptides, cryptic neoepitopes, and neoepitopes of common AML driver mutations of NPM1 and IDH2. Functional relevance of shared AML/LSC antigens is illustrated by presence of their cognizant memory T cells in patients. Antigen-specific T-cell recognition and HLA class II immunopeptidome diversity correlated with clinical outcome. Together, these antigens shared among AML and LSCs represent prime targets for T cell-based therapies with potential of eliminating residual LSCs in patients with AML. SIGNIFICANCE: The elimination of therapy-resistant leukemia stem and progenitor cells (LSC) remains a major challenge in the treatment of AML. This study identifies and functionally validates LSC-associated HLA class I and HLA class II-presented antigens, paving the way to the development of LSC-directed T cell-based immunotherapeutic approaches for patients with AML. See related commentary by Ritz, p. 430 . This article is featured in Selected Articles from This Issue, p. 419.


Assuntos
Antígenos HLA , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Peptídeos , Células-Tronco
12.
Nat Commun ; 14(1): 5032, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596280

RESUMO

T-cell immunity is central for control of COVID-19, particularly in patients incapable of mounting antibody responses. CoVac-1 is a peptide-based T-cell activator composed of SARS-CoV-2 epitopes with documented favorable safety profile and efficacy in terms of SARS-CoV-2-specific T-cell response. We here report a Phase I/II open-label trial (NCT04954469) in 54 patients with congenital or acquired B-cell deficiency receiving one subcutaneous CoVac-1 dose. Immunogenicity in terms of CoVac-1-induced T-cell responses and safety are the primary and secondary endpoints, respectively. No serious or grade 4 CoVac-1-related adverse events have been observed. Expected local granuloma formation has been observed in 94% of study subjects, whereas systemic reactogenicity has been mild or absent. SARS-CoV-2-specific T-cell responses have been induced in 86% of patients and are directed to multiple CoVac-1 peptides, not affected by any current Omicron variants and mediated by multifunctional T-helper 1 CD4+ T cells. CoVac-1-induced T-cell responses have exceeded those directed to the spike protein after mRNA-based vaccination of B-cell deficient patients and immunocompetent COVID-19 convalescents with and without seroconversion. Overall, our data show that CoVac-1 induces broad and potent T-cell responses in patients with B-cell/antibody deficiency with a favorable safety profile, which warrants advancement to pivotal Phase III safety and efficacy evaluation. ClinicalTrials.gov identifier NCT04954469.


Assuntos
Agamaglobulinemia , COVID-19 , Humanos , SARS-CoV-2 , Linfócitos T , Peptídeos/uso terapêutico
13.
Insects ; 13(7)2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35886822

RESUMO

We surveyed the insect fauna associated with Urophora cardui L. (Diptera: Tephritidae) galls on Canada thistle, Cirsium arvense L. (Asterales, Asteraceae), in parts of the northern Great Plains, U.S., by field-collecting galls and rearing or dissecting out the insects. We also examined the relationships between gall biomass and insect density and biomass. Urophora cardui were widespread, and the gall biomass was positively correlated with fly density and fly biomass. We recovered Isohydnocera tabida (LeConte) (Coleoptera: Cleridae) from galls in two counties, which represents a new host record and provides vital information on the little-known immatures of this predatory species. Pteromalus elevatus (Walker) (Hymenoptera: Pteromalidae) was the dominant parasitoid that emerged from the U. cardui galls. Individual galls typically only had one insect species, and occasionally both U. cardui and P. elevatus were present, but it was rare for other insects to be present in galls housing I. tabida. This study adds to the taxonomic literature of gall-inhabiting insect species and provides new information on the predators of U. cardui, specifically a little-known clerid beetle species.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35162160

RESUMO

The objective of this study was to design a user-centered mobile health (mHealth) application for individuals with gastroesophageal reflux disease (GERD) and evaluate its design features and effectiveness for use by doctors. Prior to designing, our team undertook a discovery process that involved creating personas, conducting a competitor analysis and heuristic evaluation of existing apps, along with interviews with acid reflux patients. Then, we created a low-fidelity prototype, which was revised on the basis of several rounds of user testing. During the design phase, each round of user testing included a mix of surveys, concurrent think-alouds, and interviews to gather user feedback on the prototypes. Lastly, an evaluation phase consisting of gathering feedback on the user-centered design approach from user experience experts and medical doctors specialized in GERD was conducted. Overall, the final GERD app includes important features for tracking symptoms and triggers, analytics, data export, and community information, while promoting individualization, accessibility, and usability. The documentation of the design process of this app serves as a reference point for future medical app developers as it followed an empirically supported user-centered design strategy and resulted in an app which received positive feedback from users and human factors experts. We also intend to share some of the limitations due to the constrained resources, as well as potential ways to strengthen the design process for mHealth applications.


Assuntos
Refluxo Gastroesofágico , Aplicativos Móveis , Telemedicina , Humanos , Inquéritos e Questionários , Telemedicina/métodos , Design Centrado no Usuário
15.
Sci Immunol ; 7(78): eadd3899, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36318037

RESUMO

Several COVID-19 vaccines are approved to prevent severe disease outcome after SARS-CoV-2 infection. Whereas induction and functionality of antiviral antibody response are largely studied, the induction of T cells upon vaccination with the different approved COVID-19 vaccines is less studied. Here, we report on T cell immunity 4 weeks and 6 months after different vaccination regimens and 4 weeks after an additional booster vaccination in comparison with SARS-CoV-2 T cell responses in convalescents and prepandemic donors using interferon-gamma ELISpot assays and flow cytometry. Increased T cell responses and cross-recognition of B.1.1.529 Omicron variant-specific mutations were observed ex vivo in mRNA- and heterologous-vaccinated donors compared with vector-vaccinated donors. Nevertheless, potent expandability of T cells targeting the spike protein was observed for all vaccination regimens, with frequency, diversity, and the ability to produce several cytokines of vaccine-induced T cell responses comparable with those in convalescent donors. T cell responses for all vaccinated donors significantly exceeded preexisting cross-reactive T cell responses in prepandemic donors. Booster vaccination led to a significant increase in anti-spike IgG responses, which showed a marked decline 6 months after complete vaccination. In contrast, T cell responses remained stable over time after complete vaccination with no significant effect of booster vaccination on T cell responses and cross-recognition of Omicron BA.1 and BA.2 mutations. This suggested that booster vaccination is of particular relevance for the amelioration of antibody response. Together, our work shows that different vaccination regimens induce broad and long-lasting spike-specific CD4+ and CD8+ T cell immunity to SARS-CoV-2.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , SARS-CoV-2 , COVID-19/prevenção & controle , Vacinação , Anticorpos Antivirais
16.
Nat Commun ; 13(1): 6401, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36302754

RESUMO

The DNAJB1-PRKACA fusion transcript is the oncogenic driver in fibrolamellar hepatocellular carcinoma, a lethal disease lacking specific therapies. This study reports on the identification, characterization, and immunotherapeutic application of HLA-presented neoantigens specific for the DNAJB1-PRKACA fusion transcript in fibrolamellar hepatocellular carcinoma. DNAJB1-PRKACA-derived HLA class I and HLA class II ligands induce multifunctional cytotoxic CD8+ and T-helper 1 CD4+ T cells, and their cellular processing and presentation in DNAJB1-PRKACA expressing tumor cells is demonstrated by mass spectrometry-based immunopeptidome analysis. Single-cell RNA sequencing further identifies multiple T cell receptors from DNAJB1-PRKACA-specific T cells. Vaccination of a fibrolamellar hepatocellular carcinoma patient, suffering from recurrent short interval disease relapses, with DNAJB1-PRKACA-derived peptides under continued Poly (ADP-ribose) polymerase inhibitor therapy induces multifunctional CD4+ T cells, with an activated T-helper 1 phenotype and high T cell receptor clonality. Vaccine-induced DNAJB1-PRKACA-specific T cell responses persist over time and, in contrast to various previous treatments, are accompanied by durable relapse free survival of the patient for more than 21 months post vaccination. Our preclinical and clinical findings identify the DNAJB1-PRKACA protein as source for immunogenic neoepitopes and corresponding T cell receptors and provide efficacy in a single-patient study of T cell-based immunotherapy specifically targeting this oncogenic fusion.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Regulação Neoplásica da Expressão Gênica , Recidiva Local de Neoplasia/genética , Proteínas de Fusão Oncogênica/genética , Imunoterapia , Peptídeos/genética , Proteínas de Choque Térmico HSP40/genética , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico
17.
Arch Microbiol ; 193(9): 687-92, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21617984

RESUMO

Hydrogen-oxidising bacteria play a key ecological role in a variety of habitats including the rhizosphere and hot springs. To investigate the possibly of interspecies hydrogen exchange between cyanobacteria and hydrogen-oxidising bacteria, we developed a sensitive and reliable reverse-transcriptase qPCR assay for up-regulation of the hupS gene in the knallgas bacterium Alcaligenes hydrogenophilus DSM2625. The assay detected up-regulation of the gene at initial hydrogen concentrations as low as 0.12 µM. Expression of hupS also increased in the presence of hydrogen-producing cyanobacteria, both when Ah DSM2625 was directly added to a hydrogen-producing culture of the cyanobacteria, and when cultures were physically separated in a vessel that allowed gas exchange. Additional refinements and development of the sensitive assay will lead to a better understanding of hydrogen exchange in aerobic ecosystems and development of reporter strains to detect hydrogen-producing organisms.


Assuntos
Alcaligenes/genética , Cianobactérias/metabolismo , Hidrogênio/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Alcaligenes/enzimologia , Alcaligenes/metabolismo , Hidrogênio/metabolismo , Hidrogenase/genética , Hidrogenase/metabolismo , Regulação para Cima
18.
AACN Adv Crit Care ; 32(4): 452-460, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34879128

RESUMO

Health care providers face a unique set of decision-making, assessment, and equipment challenges at the end of life of patients supported with a left ventricular assist device. The aim for this article is to assist the multidisciplinary team in caring for patients with a left ventricular assist device in all phases of end-of-life care. This review includes common causes of death for patients with a left ventricular assist device, assessment at end of life, physiological and palliative care considerations, withdrawal of left ventricular assist device support, and equipment considerations.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Assistência Terminal , Adolescente , Morte , Insuficiência Cardíaca/terapia , Humanos , Cuidados Paliativos
19.
Heart Lung ; 50(6): 941-952, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34433112

RESUMO

IMPORTANCE: Post-operative risk is increased with frail individuals undergoing cardiac surgery. Yet, there is no consensus for frailty assessment prior to durable left ventricular assist device (dLVAD) evaluation. OBJECTIVE: The objectives of this integrative review were to describe frailty measures, examine psychometrics of measures used, and identify variables related to frailty in heart failure with reduced ejection fraction (HFrEF) and dLVAD populations. DESIGN, SETTING, PARTICIPANTS: PubMed, CINAHL, and Embase databases were searched for terms related to frailty, HFrEF and dLVAD that met inclusion criteria. RESULTS: Fourteen articles met inclusion criteria. Frailty was inconsistently defined. The Fried Phenotype Criteria was the most widely used approach to measurement. Validity was reported in all articles. Variables related to frailty included readmissions, higher mortality and increased adverse events. CONCLUSION: There was variability in frailty definition and frailty measurement across studies. Further research in HFrEF and dLVAD populations is needed for frailty evaluation.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Fragilidade , Insuficiência Cardíaca , Coração Auxiliar , Fragilidade/epidemiologia , Insuficiência Cardíaca/epidemiologia , Humanos , Volume Sistólico , Estados Unidos/epidemiologia
20.
AACN Adv Crit Care ; 32(4): 443-451, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34879126

RESUMO

BACKGROUND: A thorough psychosocial assessment is needed during the evaluation of candidacy for ventricular assist device placement to identify potential barriers that would limit success with the device. Ventricular assist device coordinators are generally involved in the psychosocial assessment of the patient, allowing them to provide a more holistic approach to ventricular assist device candidacy during discussions at multidisciplinary meetings. There is a gap in the literature describing the psychological journey of patients after ventricular assist device implantation and the challenges ventricular assist device coordinators face when caring for this complex population. OBJECTIVE: The psychological journey of 3 patients with a ventricular assist device was explored to determine if common themes exist and to describe the experiences faced by the ventricular assist device coordinators with each patient. METHODS: Three patient case scenarios are described, as are the interactions with the patients' ventricular assist device coordinator team members. RESULTS: All 3 case scenarios demonstrate similarities of younger ages, the need of family and social support, and ventricular assist device coordinators who went beyond the call of duty to assist in the successful heart transplantation for 2 cases and the successful decommission of the ventricular assist device in another case. CONCLUSION: The psychosocial needs of patients with a ventricular assist device and ventricular assist device coordinators require ongoing assessment because of the many physical and emotional challenges that arise during the time a patient has an implanted ventricular assist device.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Insuficiência Cardíaca/terapia , Humanos
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