RESUMO
BACKGROUND: Heart failure (HF) is a debilitating disease with worsening symptoms and family caregiving burden. HF affects more than 8 million Americans. West Virginia has the highest HF death rate in the U.S. and limited healthcare services. This study tested whether the family HF palliative and end-of-life care intervention (FamPALcare) improved patient and caregiver outcomes at 3- and 6-month study endpoints. METHODS: This study used a randomized controlled trial design. Patients with HF and their caregivers were randomly assigned together to the intervention (n = 21) or control (n = 18) group. The intervention included five telephone coaching sessions on the HF home, palliative, and end-of-life care. The outcome data collected at baseline and at 3 and 6 months were from the patients' (a) HF-related health status and depression/anxiety scale scores; and from caregivers' (b) caregiving burden and depression/anxiety scale scores; and (c) anonymous ratings on the 11-item FamPALcare helpfulness scale, completed by the intervention participants. RESULTS: The mean age of the patients was 65.66 (SD = 13.72) years, and 67% were White males. The mean age of the caregivers was 62.05 (SD = 13.14) years, and 77% were White females. Compared to the controls, patients in the intervention group had significantly greater scores for HF-related health status (p < .05) and lower depression/anxiety scores at 6 months, the study endpoint. The family caregivers in the intervention group had significantly lower scores on caregiving burden (p < .05) and depression/anxiety (p < .01) at 3 months. The mean helpfulness rating was M = 4.46 out of 5 (SD = 0.49). CONCLUSIONS: The FamPALcare intervention was found to be effective at improving patient HF-related health status and reducing caregiver burden and improving both patient and caregiver depression and anxiety scores. The FamPALcare HF intervention was found feasible and consistently delivered (fidelity). The FamPALcare intervention's cost-effectiveness and helpfulness ratings information will be used to plan for subsequent clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04153890, Registered on 4 November 2019, https://clinicaltrials.gov/ct2/show/NCT04153890 .
Assuntos
Cuidadores , Insuficiência Cardíaca , Cuidados Paliativos , População Rural , Humanos , Masculino , Feminino , Cuidadores/psicologia , Insuficiência Cardíaca/psicologia , Insuficiência Cardíaca/terapia , Pessoa de Meia-Idade , Idoso , População Rural/estatística & dados numéricos , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Região dos Apalaches , West Virginia , Idoso de 80 Anos ou mais , AdultoRESUMO
We report the unusual genotypic characterization of a bacterium isolated from a clinical sample of a patient who grew up in Bangladesh and lives in the United States. Using whole-genome sequencing, we identified the bacterium as a member of the Mycobacterium tuberculosis complex (MTBC). Phylogenetic placement of this strain suggests a new MTBC genotype. Even though it had the same spoligotype as M. caprae strains, single-nucleotide polymorphism-based phylogenetic analysis placed the isolate as a sister lineage distinct from M. caprae, most closely related to 5 previously sequenced genomes isolated from primates and elephants in Asia. We propose a new animal-associated lineage, La4, within MTBC.
Assuntos
Mycobacterium tuberculosis , Animais , Bangladesh/epidemiologia , Genótipo , Humanos , Mycobacterium tuberculosis/genética , Filogenia , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Evaluations of human immunodeficiency virus (HIV) curative interventions require reliable and efficient quantification of replication-competent latent reservoirs. The "classic" quantitative viral outgrowth assay (QVOA) has been regarded as the reference standard, although prohibitively resource and labor intensive. We compared 6 "next-generation" viral outgrowth assays, using polymerase chain reaction or ultrasensitive p24 to assess their suitability as scalable proxies for QVOA. METHODS: Next-generation QVOAs were compared with classic QVOA using single leukapheresis-derived samples from 5 antiretroviral therapy-suppressed HIV-infected participants and 1 HIV-uninfected control; each laboratory tested blinded batches of 3 frozen and 1 fresh sample. Markov chain Monte Carlo methods estimated extra-Poisson variation at aliquot, batch, and laboratory levels. Models also estimated the effect of testing frozen versus fresh samples. RESULTS: Next-generation QVOAs had similar estimates of variation to QVOA. Assays with ultrasensitive readout reported higher infectious units per million values than classic QVOA. Within-batch testing had 2.5-fold extra-Poisson variation (95% credible interval [CI], 2.1-3.5-fold) for next-generation assays. Between-laboratory variation increased extra-Poisson variation to 3.4-fold (95% CI, 2.6-5.4-fold). Frozen storage did not substantially alter infectious units per million values (-18%; 95% CI, -52% to 39%). CONCLUSIONS: The data offer cautious support for use of next-generation QVOAs as proxies for more laborious QVOA, while providing greater sensitivities and dynamic ranges. Measurement of latent reservoirs in eradication strategies would benefit from high throughput and scalable assays.
Assuntos
Infecções por HIV , HIV-1/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Latência Viral , Replicação Viral , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos , Estudos de Casos e Controles , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Transcriptase Reversa do HIV , HIV-1/isolamento & purificação , Humanos , Leucaférese , Carga Viral , Replicação Viral/fisiologiaRESUMO
Small proteins of <51 amino acids are abundant across all domains of life but are often overlooked because their small size makes them difficult to predict computationally, and they are refractory to standard proteomic approaches. Ribosome profiling has been used to infer the existence of small proteins by detecting the translation of the corresponding open reading frames (ORFs). Detection of translated short ORFs by ribosome profiling can be improved by treating cells with drugs that stall ribosomes at specific codons. Here, we combine the analysis of ribosome profiling data for Escherichia coli cells treated with antibiotics that stall ribosomes at either start or stop codons. Thus, we identify ribosome-occupied start and stop codons with high sensitivity for â¼400 novel putative ORFs. The newly discovered ORFs are mostly short, with 365 encoding proteins of <51 amino acids. We validate translation of several selected short ORFs, and show that many likely encode unstable proteins. Moreover, we present evidence that most of the newly identified short ORFs are not under purifying selection, suggesting they do not impact cell fitness, although a small subset have the hallmarks of functional ORFs. IMPORTANCE Small proteins of <51 amino acids are abundant across all domains of life but are often overlooked because their small size makes them difficult to predict computationally, and they are refractory to standard proteomic approaches. Recent studies have discovered small proteins by mapping the location of translating ribosomes on RNA using a technique known as ribosome profiling. Discovery of translated sORFs using ribosome profiling can be improved by treating cells with drugs that trap initiating ribosomes. Here, we show that combining these data with equivalent data for cells treated with a drug that stalls terminating ribosomes facilitates the discovery of small proteins. We use this approach to discover 365 putative genes that encode small proteins in Escherichia coli.
Assuntos
Proteômica , Perfil de Ribossomos , Fases de Leitura Aberta , Códon de Terminação , Escherichia coli/genética , Aminoácidos/genética , Biossíntese de ProteínasRESUMO
The pH 6 antigen (PsaA) of Yersinia pestis is a virulence factor that is expressed in response to high temperature (37°C) and low pH (6.0). Previous studies have implicated the PsaE and PsaF regulators in the temperature- and pH-dependent regulation of psaA. Here, we show that PsaE levels are themselves controlled by pH and temperature, explaining the regulation of psaA. We identify hundreds of binding sites for PsaE across the Y. pestis genome, with the majority of binding sites located in intergenic regions bound by the nucleoid-associated protein H-NS. However, we detect direct regulation of only two transcripts by PsaE, likely due to displacement of H-NS from the corresponding promoter regions; our data suggest that most PsaE binding sites are nonregulatory or that they require additional environmental cues. We also identify the precise binding sites for PsaE that are required for temperature- and pH-dependent regulation of psaA and psaE. Thus, our data reveal the critical role that PsaE plays in the regulation of psaA and suggest that PsaE may have many additional regulatory targets. IMPORTANCE Y. pestis, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. The plague bacillus has been used as a biological weapon during human history and is currently one of the most likely biological threats. PsaA and PsaE appear to play important roles during Y. pestis infection. Understanding their regulation by environmental cues would facilitate a solution to impede Y. pestis infection.
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Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Yersinia pestis/metabolismo , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Estudo de Associação Genômica Ampla , Concentração de Íons de Hidrogênio , Complexo de Proteína do Fotossistema I/genética , Complexo de Proteína do Fotossistema I/metabolismo , Ligação Proteica , Processamento Pós-Transcricional do RNA , Temperatura , Transcrição Gênica , Yersinia pestis/genéticaRESUMO
Studies have demonstrated that intensive ART alone is not capable of eradicating HIV-1, as the virus rebounds within a few weeks upon treatment interruption. Viral rebound may be induced from several cellular subsets; however, the majority of proviral DNA has been found in antigen experienced resting CD4+ T cells. To achieve a cure for HIV-1, eradication strategies depend upon both understanding mechanisms that drive HIV-1 persistence as well as sensitive assays to measure the frequency of infected cells after therapeutic interventions. Assays such as the quantitative viral outgrowth assay (QVOA) measure HIV-1 persistence during ART by ex vivo activation of resting CD4+ T cells to induce latency reversal; however, recent studies have shown that only a fraction of replication-competent viruses are inducible by primary mitogen stimulation. Previous studies have shown a correlation between the acquisition of effector memory phenotype and HIV-1 latency reversal in quiescent CD4+ T cell subsets that harbor the reservoir. Here, we apply our mechanistic understanding that differentiation into effector memory CD4+ T cells more effectively promotes HIV-1 latency reversal to significantly improve proviral measurements in the QVOA, termed differentiation QVOA (dQVOA), which reveals a significantly higher frequency of the inducible HIV-1 replication-competent reservoir in resting CD4+ T cells.
Assuntos
Linfócitos T CD4-Positivos/virologia , HIV-1/imunologia , HIV-1/fisiologia , Memória Imunológica/imunologia , Latência Viral/imunologia , Idoso , Antirretrovirais/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Infecções por HIV/imunologia , HIV-1/crescimento & desenvolvimento , Humanos , Masculino , Pessoa de Meia-Idade , Provírus/crescimento & desenvolvimento , Carga Viral/efeitos dos fármacos , Latência Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
Black leg (caused by Plenodomus lingam and P. biglobosus) and chlorotic leaf spot (caused by Pyrenopeziza brassicae) are economically important fungal diseases of Brassicaceae crops. Surveys of seed fields and weed hosts were conducted to understand the distribution and prevalence of these diseases in Oregon after black leg and chlorotic leaf spot outbreaks occurred in Brassicaceae crops in 2014. Postharvest black leg ratings were conducted in seed fields of canola, forage rape, and turnip in 2015 and 2016. The incidence of black leg was greater for turnip (51%) than for canola (29%) and forage rape (25%). The overall average disease incidence was greater for seed crops harvested in 2015 (46%) than for crops harvested in 2016 (28%). A disease survey of wild Brassicaceae plants was conducted along Interstate 5 in Oregon. Brassicaceae weed population sites were identified and 40 sites were sampled for these diseases. Black leg and chlorotic leaf spot were present in 60 and 45%, respectively, of the sampled sites. Both species of Plenodomus were detected in weed populations, with P. lingam being the predominant species recovered (95%). The northernmost sample site with black leg was <32 km from the Oregon-Washington border, and the southernmost site with black leg was within 32 km of the Oregon-California border. Chlorotic leaf spot was detected <32 km from the Oregon-Washington border, whereas the southernmost site where it was detected was approximately 164 km from the Oregon-California border. Based on this study, infected crop residues and weed hosts may facilitate the persistence and spread of these pathogens.
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Brassicaceae , Produtos Agrícolas , Oregon , Doenças das Plantas , WashingtonRESUMO
Telehealth distance health care is a significant resource for young, chronically ill patient populations given their numerous medical complexities and their concomitant depression and/or suicide ideation experiences. This manuscript shares the telehealth methods used to prepare for a larger study of interventions for increasing adolescents' and young adults' chronic care resiliency and skills for preventing depression. The young patients in this study were prescribed lifelong home parenteral nutrition infusions, treatment for those with short gut bowel diseases. The training methods for our mental health nurse and psychologist to conduct depression and suicide ideation assessments from a distance are presented. The study implementation methods of group facilitated interventions and discussion are reviewed. The group discussions were conducted via audiovisual telehealth devices over encrypted firewall-protected connections with patients in their own homes and professionals in an office. The results of assessments of the 40 participants, 25% (n = 10) with depressive symptoms or suicide ideation, are described. Following participants' assessments, their subsequent depression measures were all in the normal range, without any suicide ideation, across the year of the study. Patient evaluation ratings were high in the areas of being able to connect with other young patients in similar situations, using the audiovisual equipment, and learning new useful information from the interventions. The methods developed for the study ensured that the safety and well-being of participants were supported through telehealth.
Assuntos
Depressão/diagnóstico , Depressão/terapia , Serviços de Saúde Mental/normas , Ideação Suicida , Telemedicina/normas , Adolescente , Comportamento do Adolescente/psicologia , Doença Crônica/psicologia , Doença Crônica/terapia , Depressão/psicologia , Feminino , Humanos , Masculino , Serviços de Saúde Mental/tendências , Adulto JovemRESUMO
Fidelity (consistency of intervention implementation) is essential to rigorous research. Intervention fidelity maintains study internal validity, intervention reproducibility, and transparency in the research conduct. The purpose of this manuscript is to describe intervention fidelity strategies/procedures developed for a pilot study testing a new palliative care nursing intervention (FamPALcare) for families managing advanced lung disease. The procedures described herein are based on the fidelity best practices recommendations from the NIH Consortium. An evidence-based checklist guided observational ratings of the fidelity procedures used and the intervention content implemented in each intervention session. Descriptive data on how participants understood (received), enacted, or used the intervention information were summarized. The fidelity checklist observational scores found ≥93% of the planned intervention content was implemented, and the fidelity strategies were adhered to consistently during each intervention session. The small variation (7%) in implementation was expected and related to participants' varying experiences, input, and/or questions. The helpfulness scale items include participants' ability to use home care resources, to anticipate and manage end-of-life symptoms, and to use Advance Directive forms. The high ratings (M = 4.4) on the 1-5 (very helpful) Likert Helpfulness Scale verified participants utilized the information from the intervention. Furthermore, there was an improvement in patients' breathlessness scores and completion of Advance Directive forms at 3 months after baseline. It is essential to plan intervention fidelity strategies to use throughout a study and to report fidelity results.
Assuntos
Serviços de Assistência Domiciliar/estatística & dados numéricos , Serviços de Assistência Domiciliar/normas , Neoplasias Pulmonares/terapia , Pesquisa em Enfermagem/normas , Cuidados Paliativos/estatística & dados numéricos , Cuidados Paliativos/normas , Qualidade da Assistência à Saúde/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Lista de Checagem/métodos , Lista de Checagem/normas , Feminino , Guias como Assunto , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reprodutibilidade dos TestesRESUMO
Next-generation sequencing technologies are being rapidly adopted as a tool of choice for diagnostic and outbreak investigation in public health laboratories. However, costs of operation and the need for specialized staff remain major hurdles for laboratories with limited resources for implementing these technologies. This project aimed to assess the feasibility of using Oxford Nanopore MinION whole-genome sequencing data of Mycobacterium tuberculosis isolates for species identification, in silico spoligotyping, detection of mutations associated with antimicrobial resistance (AMR) to accurately predict drug susceptibility profiles, and phylogenetic analysis to detect transmission between cases. The results were compared prospectively in real time to those obtained with our current clinically validated Illumina MiSeq sequencing assay for M. tuberculosis and phenotypic drug susceptibility testing results when available. Our assessment of 431 sequenced samples over a 32-week period demonstrates that, when using the proper quality controls and thresholds, the MinION can achieve levels of genotyping analysis and phenotypic resistance predictions comparable to those of the Illumina MiSeq at a very competitive cost per sample. Our results indicate that nanopore sequencing can be a suitable alternative to, or complement, currently used sequencing platforms in a clinical setting and has the potential to be widely adopted in public health laboratories in the near future.
Assuntos
Mycobacterium tuberculosis , Sequenciamento por Nanoporos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , FilogeniaRESUMO
AIM: To pilot test a home end-of-life and palliative care intervention for family caregivers and patients with rare advanced lung diseases and to estimate effect-size for the power analysis in a future clinical trial. DESIGN: This study uses a parallel randomized control trial. Families are randomly assigned to the intervention group or the control group in a 1:1 fashion. METHODS: The study population includes patients with rare advanced lung diseases and their family caregivers who are involved in patients' home care. The control group receives standard care through their hospital or outpatient clinics. The intervention group receives standard care plus 2-weekly home end-of-life and palliative care coaching by experienced community nurses. Primary outcome is breathlessness measured by shortness of breath scale. Secondary outcomes are: (a) caregivers' anxiety and depression measures; (b) the presence of patient's signed advance directives in the medical record or not; and (c) Helpfulness of intervention measured by self-report Helpfulness scale. The study was funded in October 2018 and received ethical Institutional Review Board approval in February 2019. DISCUSSION: West Virginia has one of the highest incidence rates of lung disease deaths in the nation. However, there is inadequate home end-of-life and palliative care for this underserved population. This is an initial interventional study of nurse-led coaching home-based palliative care for rare advanced lung diseases in rural Appalachia. Developing research collaboration with clinicians is essential for enrolment. Enrolment was successful due to regular meetings with pulmonologists who screened patients per the study inclusion criteria in their specialty clinic and made direct referrals to the research assistants. Results of this study will be used in the future trial. IMPACT: The findings will contribute to the evidence-based home nursing care, planning for family/patient preferences and supportive end-of-life palliative care for managing advanced lung diseases at home. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03813667; registered January 23, 2019. https://clinicaltrials.gov/ct2/show/NCT03813667.
RESUMO
The current standard in healthcare research is to maintain scientific fidelity of any intervention being tested. Fidelity is defined as the consistent delivery of interventions that ensures that all participants are provided the same information, guidance, and/or materials. Notably, the methods for ensuring fidelity of intervention delivery must also be consistent. This article describes our Intervention and Technology Delivery Fidelity Checklists used to ensure consistency. These checklists were completed by trained nurse observers who rated the intervention implementation and the technology delivery. Across our clinical trials and pilot studies, the fidelity scores were tabulated and compared. Intervention information and materials were delivered by a variety of devices including telehealth monitors, videophones, and/or iPads. Each of the devices allows audiovisual connections between health professionals from their offices and patients and participants in their homes. Our checklists guide the monitoring of fidelity of technology delivery. Overall checklist ratings across our studies demonstrate consistent intervention, implementation, and technology delivery approaches. Uniquely, the fidelity checklist verifies the interventionist's correct use of the technology devices to ensure consistent audiovisual delivery. Checklist methods to ensure intervention fidelity and technology delivery are essential research procedures, which can be adapted for use by researchers across multiple disciplines.
Assuntos
Confiabilidade dos Dados , Pesquisa/normas , Transferência de Tecnologia , Telemedicina/métodos , Lista de Checagem/instrumentação , Humanos , Projetos Piloto , Pesquisa/tendências , Telemedicina/tendênciasRESUMO
In Escherichia coli, one sigma factor recognizes the majority of promoters, and six 'alternative' sigma factors recognize specific subsets of promoters. The alternative sigma factor FliA (σ28 ) recognizes promoters upstream of many flagellar genes. We previously showed that most E. coli FliA binding sites are located inside genes. However, it was unclear whether these intragenic binding sites represent active promoters. Here, we construct and assay transcriptional promoter-lacZ fusions for all 52 putative FliA promoters previously identified by ChIP-seq. These experiments, coupled with integrative analysis of published genome-scale transcriptional datasets, strongly suggest that most intragenic FliA binding sites are active promoters that transcribe highly unstable RNAs. Additionally, we show that widespread intragenic FliA-dependent transcription may be a conserved phenomenon, but that specific promoters are not themselves conserved. We conclude that intragenic FliA-dependent promoters and the resulting RNAs are unlikely to have important regulatory functions. Nonetheless, one intragenic FliA promoter is broadly conserved and constrains evolution of the overlapping protein-coding gene. Thus, our data indicate that intragenic regulatory elements can influence bacterial protein evolution and suggest that the impact of intragenic regulatory sequences on genome evolution should be considered more broadly.
Assuntos
Proteínas de Bactérias/metabolismo , Escherichia coli/genética , Evolução Molecular , Salmonella typhimurium/genética , Fator sigma/metabolismo , Proteínas de Bactérias/genética , Sítios de Ligação , Mapeamento Cromossômico , Plasmídeos/genética , Regiões Promotoras Genéticas/genética , RNA/genética , RNA/metabolismo , Análise de Sequência de DNA , Análise de Sequência de RNA , Fator sigma/genética , Transcrição Gênica/genética , beta-Galactosidase/genéticaRESUMO
BACKGROUND: Heart failure (HF) afflicts 6.5 million Americans with devastating consequences to patients and their family caregivers. Families are rarely prepared for worsening HF and are not informed about end-of-life and palliative care (EOLPC) conservative comfort options especially during the end stage. West Virginia (WV) has the highest rate of HF deaths in the U.S. where 14% of the population over 65 years have HF. Thus, there is a need to investigate a new family EOLPC intervention (FamPALcare), where nurses coach family-managed advanced HF care at home. METHODS: This study uses a randomized controlled trial (RCT) design stratified by gender to determine any differences in the FamPALcare HF patients and their family caregiver outcomes versus standard care group outcomes (N = 72). Aim 1 is to test the FamPALcare nursing care intervention with patients and family members managing home supportive EOLPC for advanced HF. Aim 2 is to assess implementation of the FamPALcare intervention and research procedures for subsequent clinical trials. Intervention group will receive routine standard care, plus 5-weekly FamPALcare intervention delivered by community-based nurses. The intervention sessions involve coaching patients and family caregivers in advanced HF home care and supporting EOLPC discussions based on patients' preferences. Data are collected at baseline, 3, and 6 months. Recruitment is from sites affiliated with a large regional hospital in WV and community centers across the state. DISCUSSION: The outcomes of this clinical trial will result in new knowledge on coaching techniques for EOLPC and approaches to palliative and end-of-life rural home care. The HF population in WV will benefit from a reduction in suffering from the most common advanced HF symptoms, selecting their preferred EOLPC care options, determining their advance directives, and increasing skills and resources for advanced HF home care. The study will provide a long-term collaboration with rural community leaders, and collection of data on the implementation and research procedures for a subsequent large multi-site clinical trial of the FamPALcare intervention. Multidisciplinary students have opportunity to engage in the research process. TRIAL REGISTRATION: ClinicalTrials.gov NCT04153890, Registered on 4 November 2019.
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Protocolos Clínicos , Insuficiência Cardíaca/psicologia , Tutoria/métodos , Assistência Terminal/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cuidadores/psicologia , Dispneia/etiologia , Dispneia/psicologia , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Tutoria/normas , Pessoa de Meia-Idade , Pacientes/psicologia , População Rural , Assistência Terminal/normas , Resultado do Tratamento , West VirginiaRESUMO
BACKGROUND: Heart failure (HF), the leading cause of morbidity and mortality in the US, affects 6.6 million adults with an estimated additional 3 million people by 2030. More than 50% of HF patients have heart failure with preserved left ventricular ejection fraction (HFpEF). These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. Patients with HFpEF experience symptoms of: (1) fatigue; (2) shortness of breath; and (3) swelling (edema) of the lower extremities. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, we propose a biobehavioral symptom science study using ubiquinol and D-ribose (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF. METHODS: Using a randomized, double-blind, placebo-controlled design, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. The measures used to assess patients' perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The 6-min walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics). DISCUSSIONS: Ubiquinol (active form of Coenzyme Q10) and D-ribose are two potential treatments that can positively affect cellular energetic impairment, the major underlying mechanism of HFpEF. Ubiquinol, the reduced form of CoQ10, is more effective in adults over the age of 50. In patients with HFpEF, mitochondrial deficiency of ubiquinol results in decreased adenosine triphosphate (ATP) synthesis and reduced scavenging of reactive oxygen species. D-ribose is a substrate required for ATP synthesis and when administered has been shown to improve impaired myocardial bioenergetics. Therefore, if the biological underpinning of deficient mitochondrial ATP in HFpEF is not addressed, patients will suffer major symptoms including lack of energy, fatigue, exertional dyspnea, and exercise intolerance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03133793 ; Data of Registration: April 28, 2017.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Mitocôndrias Cardíacas/efeitos dos fármacos , Ribose/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Ubiquinona/análogos & derivados , Função Ventricular Esquerda/efeitos dos fármacos , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias Cardíacas/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Ribose/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Ubiquinona/efeitos adversos , Ubiquinona/uso terapêuticoRESUMO
Bacterial RNA polymerases must associate with a σ factor to bind promoter DNA and initiate transcription. There are two families of σ factor: the σ70 family and the σ54 family. Members of the σ54 family are distinct in their ability to bind promoter DNA sequences, in the context of RNA polymerase holoenzyme, in a transcriptionally inactive state. Here, we map the genome-wide association of Escherichia coli σ54, the archetypal member of the σ54 family. Thus, we vastly expand the list of known σ54 binding sites to 135. Moreover, we estimate that there are more than 250 σ54 sites in total. Strikingly, the majority of σ54 binding sites are located inside genes. The location and orientation of intragenic σ54 binding sites is non-random, and many intragenic σ54 binding sites are conserved. We conclude that many intragenic σ54 binding sites are likely to be functional. Consistent with this assertion, we identify three conserved, intragenic σ54 promoters that drive transcription of mRNAs with unusually long 5' UTRs.
Assuntos
Proteínas de Escherichia coli/genética , Escherichia coli/genética , Genoma Bacteriano , RNA Polimerase Sigma 54/genética , Iniciação da Transcrição Genética , Sítios de Ligação , Proteínas de Ligação a DNA/genética , Regiões Promotoras GenéticasRESUMO
PURPOSE: This research explored family caregivers' lived experiences of resistiveness to care when they provided care for people with dementia. The goal was to identify a general meaning of family caregivers' lived experiences to target potential areas for future nursing interventions to help family caregivers manage their caregiving role and provide a base for future research surrounding resistiveness to care. DESIGN: Descriptive phenomenology was used to provide descriptions of eight family caregivers who provided care for someone with dementia and experienced resistiveness to care. Family caregivers were recruited from Alzheimer's support groups from June to November 2014. METHOD: Caregiver interviews were transcribed verbatim and analyzed using scientific phenomenology to identify essential constituents of the experience. FINDINGS: The identified general meaning structure contained five essential constituents. These included self-questioning of abilities; signal for increased future caregiver responsibilities; changed perception of personal self; unexpected emotional responses; and seeing a changed person, not the disease. CONCLUSIONS: Study findings represent family caregivers' lived perceptions of resistiveness to care, which are different from current research findings regarding nurses' perceptions of resistiveness to care. The identified meaning structure indicates focus areas for future research and for nursing interventions to help family caregivers manage their distress when experiencing resistiveness to care. CLINICAL RELEVANCE: Identification of the meaning caregivers ascribe to their lived experience of resistiveness to care (five essential constituents) provides nurses with opportunities to help family caregivers (coproviders of care) holistically. Supporting caregivers in their caregiving role can decrease caregiver distress when resistiveness to care occurs.
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Cuidadores/psicologia , Demência/terapia , Recusa do Paciente ao Tratamento/psicologia , Idoso , Idoso de 80 Anos ou mais , Cuidadores/estatística & dados numéricos , Demência/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa QualitativaRESUMO
Home parenteral nutrition requires a daily life-sustaining intravenous infusion over 12 hours. The daily intravenous infusion home care procedures are stringent, time-consuming tasks for patients and family caregivers who often experience depression. The purposes of this study were (1) to assess home parenteral nutrition patients and caregivers for depression and (2) to assess whether depressive signs can be seen during audiovisual discussion sessions using an Apple iPad Mini. In a clinical trial (N = 126), a subsample of 21 participants (16.7%) had depressive symptoms. Of those with depression, 13 participants were home parenteral nutrition patients and eight were family caregivers; ages ranged from 20 to 79 years (with 48.9 [standard deviation, 17.37] years); 76.2% were female. Individual assessments by the mental health nurse found factors related to depressive symptoms across all 21 participants. A different nurse observed participants for signs of depression when viewing the videotapes of the discussion sessions on audiovisual technology. Conclusions are that depression questionnaires, individual assessment, and observation using audiovisual technology can identify depressive symptoms. Considering the growing provision of healthcare at a distance, via technology, recommendations are to observe and assess for known signs and symptoms of depression during all audiovisual interactions.
Assuntos
Recursos Audiovisuais/estatística & dados numéricos , Cuidadores/psicologia , Computadores de Mão/estatística & dados numéricos , Depressão/diagnóstico , Depressão/psicologia , Serviços de Assistência Domiciliar , Humanos , Nutrição Parenteral no Domicílio/métodos , Nutrição Parenteral no Domicílio/enfermagem , Enfermagem Psiquiátrica , Inquéritos e Questionários , Telenfermagem/métodosRESUMO
OBJECTIVE: To compare the eating behaviors and nutrition-related concerns in children with fetal alcohol spectrum disorder (FASD) with those in typically developing children. STUDY DESIGN: A survey that assessed eating behaviors was completed between October 2013 and May 2014 by the caregivers of children screened for FASD at the University of Minnesota's Fetal Alcohol Spectrum Disorders Program, and typically developing children recruited from that clinic or from the Research Participation Core of the Waisman Center, University of Wisconsin. RESULTS: Compared with controls (N = 81), children with FASD (N = 74) had delayed acquisition of self-feeding behavior (P < .001) and solid food introduction (P < .001). Impaired satiety was common and independent of medication use: 23.0% were never full/satisfied, 31.1% snacked constantly, and 27.0% concealed food (all P ≤ .002). They consumed the equivalent of an additional meal/snack daily (P < .01). Children with FASD were more likely to have a past diagnosis of underweight (P < .001). Mean body mass index was significantly reduced for males (P = .009) but not females (P = .775) with FASD, and only 2 children with FASD were currently underweight. Children with FASD were more physically active (P < .01). CONCLUSIONS: Abnormal eating patterns are common in children with FASD and may contribute to their delayed growth and nutritional inadequacies. Their poor satiety may reflect poor impulse control. Children with FASD may benefit from diet counseling. Conversely, some children with hyperphagia may warrant referral for FASD screening.
Assuntos
Comportamento Alimentar , Transtornos do Espectro Alcoólico Fetal , Criança , Estudos Transversais , Feminino , Transtornos do Espectro Alcoólico Fetal/fisiopatologia , Humanos , MasculinoRESUMO
On September 13, 2015, the Georgia Department of Public Health (DPH) was notified by hospital A of a cluster of pediatric Mycobacterium abscessus odontogenic infections. Hospital A had provided care for nine children who developed presumptive or confirmed M. abscessus infection after having a pulpotomy at pediatric dentistry practice A (dates of onset: July 23, 2014-September 4, 2015). During a pulpotomy procedure, decay and the diseased pulp are removed to preserve a deciduous tooth. DPH initiated an investigation to identify the outbreak source and recommend prevention and control measures.