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1.
Cancer ; 2024 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-39306697

RESUMO

BACKGROUND: Cancer rehabilitation and exercise oncology (CR/EO) have documented benefits for people living with and beyond cancer. The authors examined proximity to CR/EO programs across the United States with respect to population density, race and ethnicity, socioeconomic status, and cancer incidence and mortality rates. METHODS: This cross-sectional study was conducted in 2022-2023. Online searches were initiated to identify CR/EO programs. Geocoding was used to obtain latitudinal and longitudinal geospatial coordinates. Demographic data were abstracted from the 2020 5-year American Community Survey. Cancer incidence and mortality data were obtained from the Centers for Disease Control and Prevention. US 2013 Rural-Urban Continuum Code (RUCC) classification was used to define counties as either urban (RUCC 1-3) or rural (RUCC 4-9). Multivariable logistic regression was used to evaluate the association between being far from a program and census-tract level factors. RESULTS: In total, 2133 CR/EO programs were identified nationwide. The distance from a program increased with decreasing population density: rural tracts were 17.68 ± 0.24 miles farther from a program compared with urban tracts (p < .001). Program proximity decreased as the neighborhood deprivation index increased (p < .001). Exercise oncology programs were less common than cancer rehabilitation programs in tracts with a larger proportion of minority residents (p < .001). CONCLUSIONS: Prior research has documented that underrepresented populations have worse cancer-related symptoms and higher cancer mortality. Herein, the authors document their findings that these same populations are less likely to have proximity to CR/EO programs, which are associated with improved cancer-related symptoms and cancer mortality outcomes. To realize the positive outcomes from CR/EO programming, efforts must focus on supporting expanded programming and sustainable payment for these services.

2.
Bioinformatics ; 38(6): 1631-1638, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-34978570

RESUMO

MOTIVATION: A gradient boosting decision tree (GBDT) is a powerful ensemble machine-learning method that has the potential to accelerate biomarker discovery from high-dimensional molecular data. Recent algorithmic advances, such as extreme gradient boosting (XGB) and light gradient boosting (LGB), have rendered the GBDT training more efficient, scalable and accurate. However, these modern techniques have not yet been widely adopted in discovering biomarkers for censored survival outcomes, which are key clinical outcomes or endpoints in cancer studies. RESULTS: In this paper, we present a new R package 'Xsurv' as an integrated solution that applies two modern GBDT training frameworks namely, XGB and LGB, for the modeling of right-censored survival outcomes. Based on our simulations, we benchmark the new approaches against traditional methods including the stepwise Cox regression model and the original gradient boosting function implemented in the package 'gbm'. We also demonstrate the application of Xsurv in analyzing a melanoma methylation dataset. Together, these results suggest that Xsurv is a useful and computationally viable tool for screening a large number of prognostic candidate biomarkers, which may facilitate future translational and clinical research. AVAILABILITY AND IMPLEMENTATION: 'Xsurv' is freely available as an R package at: https://github.com/topycyao/Xsurv. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Melanoma , Humanos , Prognóstico , Modelos de Riscos Proporcionais , Biomarcadores
3.
Bioinformatics ; 38(9): 2645-2647, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35258565

RESUMO

SUMMARY: Spatially resolved transcriptomics promises to increase our understanding of the tumor microenvironment and improve cancer prognosis and therapies. Nonetheless, analytical methods to explore associations between the spatial heterogeneity of the tumor and clinical data are not available. Hence, we have developed spatialGE, a software that provides visualizations and quantification of the tumor microenvironment heterogeneity through gene expression surfaces, spatial heterogeneity statistics that can be compared against clinical information, spot-level cell deconvolution and spatially informed clustering, all using a new data object to store data and resulting analyses simultaneously. AVAILABILITY AND IMPLEMENTATION: The R package and tutorial/vignette are available at https://github.com/FridleyLab/spatialGE. A script to reproduce the analyses in this manuscript is available in Supplementary information. The Thrane study data included in spatialGE was made available from the public available from the website https://www.spatialresearch.org/resources-published-datasets/doi-10-1158-0008-5472-can-18-0747/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Neoplasias , Transcriptoma , Humanos , Microambiente Tumoral , Software , Análise por Conglomerados , Neoplasias/genética
4.
Bioinformatics ; 37(23): 4584-4586, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34734969

RESUMO

SUMMARY: Multiplex immunofluorescence (mIF) staining combined with quantitative digital image analysis is a novel and increasingly used technique that allows for the characterization of the tumor immune microenvironment (TIME). Generally, mIF data is used to examine the abundance of immune cells in the TIME; however, this does not capture spatial patterns of immune cells throughout the TIME, a metric increasingly recognized as important for prognosis. To address this gap, we developed an R package spatialTIME that enables spatial analysis of mIF data, as well as the iTIME web application that provides a robust but simplified user interface for describing both abundance and spatial architecture of the TIME. The spatialTIME package calculates univariate and bivariate spatial statistics (e.g. Ripley's K, Besag's L, Macron's M and G or nearest neighbor distance) and creates publication quality plots for spatial organization of the cells in each tissue sample. The iTIME web application allows users to statistically compare the abundance measures with patient clinical features along with visualization of the TIME for one tissue sample at a time. AVAILABILITY AND IMPLEMENTATION: spatialTIME is implemented in R and can be downloaded from GitHub (https://github.com/FridleyLab/spatialTIME) or CRAN. An extensive vignette for using spatialTIME can also be found at https://cran.r-project.org/web/packages/spatialTIME/index.html. iTIME is implemented within a R Shiny application and can be accessed online (http://itime.moffitt.org/), with code available on GitHub (https://github.com/FridleyLab/iTIME). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Software , Humanos , Análise por Conglomerados , Imunofluorescência
5.
BMC Geriatr ; 21(1): 520, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598692

RESUMO

BACKGROUND: Reduced falls and fall risks have been observed among older adults referred to the HOP-UP-PT (Home-based Older Persons Upstreaming Prevention-Physical Therapy) program. The purpose of this study was to describe outcomes of HOP-UP-PT program participants and then to compare these outcomes to non-participants. METHODS: Six Michigan senior centers referred adults ≥65 years who were at-risk for functional decline or falls. 144 participants (n = 72 per group) were randomized to either the experimental group (EG) or the control group (CG). Physical therapists (PTs) delivered physical, environmental, and health interventions to the EG over nine encounters (six in-person, three telerehabilitation) spanning seven months. The CG participants were told to continue their usual physical activity routines during the same time frame. Baseline and re-assessments were conducted at 0-, 3-, and 7-months in both groups. Descriptions and comparisons from each assessment encounter were analyzed. RESULTS: Participants ages were: EG = 76.6 (7.0) years and CG = 77.2 (8.2). Baseline measures were not significantly different apart from the Short Physical Performance Battery (SPPB) which favored the EG (P = 0.02). While no significant differences were identified in the survey outcomes or home environment assessments, significant differences in favor of the EG were identified in common fall risk indicators including the Timed Up and Go (P = 0.04), Four Test Balance Scale (P = 0.01), and the modified SPPB (P = 0.02) at the 3-month assessment visit. However, these differences were not sustained at the 7-month assessment as, notably, both groups demonstrated positive improvements in the Four Test Balance Score and SPPB. For individuals at a moderate/high fall risk at baseline, 47.8% of CG reported falling at seven months; whereas, only 6.3% of EG participants meeting the same criteria reported a fall after HOP-UP-PT participation. CONCLUSIONS: A prevention-focused multimodal program provided by PTs in older adults' homes proved beneficial and those with the highest fall risk demonstrated a significant decrease in falls. A collaboration between PTs and community senior centers resulted in upstreaming care delivery that may reduce both the financial and personal burdens associated with falls in an older adult population. TRIAL REGISTRATION: This study was retrospective registered at Clinical Trials.gov , TRN: NCT04814459 on 24/03/2021.


Assuntos
Exercício Físico , Modalidades de Fisioterapia , Idoso , Idoso de 80 Anos ou mais , Terapia por Exercício , Humanos , Equilíbrio Postural , Estudos Retrospectivos , Fatores de Risco
6.
BMC Bioinformatics ; 20(1): 426, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416413

RESUMO

BACKGROUND: Advances in medical technology have allowed for customized prognosis, diagnosis, and treatment regimens that utilize multiple heterogeneous data sources. Multiple kernel learning (MKL) is well suited for the integration of multiple high throughput data sources. MKL remains to be under-utilized by genomic researchers partly due to the lack of unified guidelines for its use, and benchmark genomic datasets. RESULTS: We provide three implementations of MKL in R. These methods are applied to simulated data to illustrate that MKL can select appropriate models. We also apply MKL to combine clinical information with miRNA gene expression data of ovarian cancer study into a single analysis. Lastly, we show that MKL can identify gene sets that are known to play a role in the prognostic prediction of 15 cancer types using gene expression data from The Cancer Genome Atlas, as well as, identify new gene sets for the future research. CONCLUSION: Multiple kernel learning coupled with modern optimization techniques provides a promising learning tool for building predictive models based on multi-source genomic data. MKL also provides an automated scheme for kernel prioritization and parameter tuning. The methods used in the paper are implemented as an R package called RMKL package, which is freely available for download through CRAN at https://CRAN.R-project.org/package=RMKL .


Assuntos
Algoritmos , Mineração de Dados , Genômica/métodos , Bases de Dados Genéticas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética
7.
Nat Methods ; 13(10): 849-51, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27571549

RESUMO

A rapidly growing bacterial host would be desirable for a range of routine applications in molecular biology and biotechnology. The bacterium Vibrio natriegens has the fastest growth rate of any known organism, with a reported doubling time of <10 min. We report the development of genetic tools and methods to engineer V. natriegens and demonstrate the advantages of using these engineered strains in common biotech processes.


Assuntos
Biotecnologia/métodos , Biologia Molecular/métodos , Organismos Geneticamente Modificados/crescimento & desenvolvimento , Vibrio/crescimento & desenvolvimento , Vibrio/genética , Proteínas de Bactérias/biossíntese , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Genes Bacterianos , Organismos Geneticamente Modificados/genética , Regiões Promotoras Genéticas
8.
J Exp Biol ; 219(Pt 20): 3227-3236, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27510962

RESUMO

Although neural modulation of heart rate is well established among chordate animals, the Pacific hagfish (Eptatretus stoutii) lacks any cardiac innervation, yet it can increase its heart rate from the steady, depressed heart rate seen in prolonged anoxia to almost double its normal normoxic heart rate, an almost fourfold overall change during the 1-h recovery from anoxia. The present study sought mechanistic explanations for these regulatory changes in heart rate. We provide evidence for a bicarbonate-activated, soluble adenylyl cyclase (sAC)-dependent mechanism to control heart rate, a mechanism never previously implicated in chordate cardiac control.


Assuntos
Feiticeiras (Peixe)/fisiologia , Frequência Cardíaca/fisiologia , Adenilil Ciclases/metabolismo , Animais , Membrana Celular/enzimologia , AMP Cíclico/metabolismo , Feminino , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Masculino , Miocárdio/enzimologia , Receptores Adrenérgicos beta/metabolismo , Simportadores de Sódio-Bicarbonato/metabolismo , Solubilidade
9.
Artigo em Inglês | MEDLINE | ID: mdl-25178563

RESUMO

In order for an animal to survive, the heart beat must go on in all environmental conditions, or at least restart its beat. This review is about maintaining a rhythmic heartbeat under the extreme conditions of anoxia (or very severe hypoxia) and high temperatures. It starts by considering the primitive versions of the protein channels that are responsible for initiating the heartbeat, HCN channels, divulging recent findings from the ancestral craniate, the Pacific hagfish (Eptatretus stoutii). It then explores how a heartbeat can maintain a rhythm, albeit slower, for hours without any oxygen, and sometimes without autonomic innervation. It closes with a discussion of recent work on fishes, where the cardiac rhythm can become arrhythmic when a fish experiences extreme heat.


Assuntos
Feiticeiras (Peixe)/fisiologia , Frequência Cardíaca/fisiologia , Animais , Relógios Biológicos/genética , Relógios Biológicos/fisiologia , Evolução Molecular , Proteínas de Peixes/genética , Proteínas de Peixes/fisiologia , Feiticeiras (Peixe)/genética , Frequência Cardíaca/genética , Temperatura Alta/efeitos adversos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/fisiologia , Hipóxia/fisiopatologia , Modelos Cardiovasculares , Filogenia
10.
Cureus ; 16(8): e67290, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39310421

RESUMO

Introduction Traditionally, physical therapist (PT) services do not commence until an injury, fall, or health issue has already occurred although there is increasing evidence that preventative programs administered by PTs may decrease the fall risk among elderly individuals. The purpose of this study was to examine billing, reimbursement, and administrative outcomes of the previously established and investigated prevention-based screening and intervention HOP-UP-PT (Home-based Older Persons Upstreaming Prevention-Physical Therapy) program delivered by a physical therapist in the home of older adults after being referred by a community partner. A randomized controlled trial of the HOP-UP-PT program demonstrated an 8-fold reduction in falls for participants at moderate and high fall risk compared to those who did not participate in the program. Methods A prospective observational study was performed to examine administrative and payment outcomes of HOP-UP-PT participation. Participants were referred into the HOP-UP-PT program via a local community center. Physician authorization for physical therapy participation was obtained for each participant as required for payment under United States' Center for Medicare and Medicaid Services (CMS) guidelines. The HOP-UP-PT program is preventative physical therapy delivered in the person's home with five in person visits (approximately one per month) followed by a monthly telehealth visit and a final in-person visit. Interventions included a balance program, home safety recommendations, health coaching, and addressing individual risks of falling or becoming homebound. A retrospective analysis was performed on the administrative and insurance payment data from this study which was then analyzed descriptively. Results Six participants with four different insurances completed the 7-month program (mean age=77 years) in 2021. The physical therapy visits were submitted to the participants' Medicare Part B plan. One participant's physical therapy visits were not submitted for payment as the health system did not have an active agreement with that health insurer. Due to the unclear status of telehealth visits in 2021, these services were not submitted to the insurance company for payment. All other PT visits were paid by the insurance companies. The mean amount paid for the initial evaluation code was $102.83 and the mean payment for the ~15 minute treatment codes was $25.90 per unit. Initial pilot data demonstrated a potential for a 4.2% positive operating margin when considering salary costs and travel. The mean delay from the initial referral into the HOP-UP-PT program until the physician provided written authorization for physical therapy was 69.7 days. Conclusion This study demonstrated initial evidence that payment for prevention-focused outpatient physical therapist services delivered in the home was feasible, however delays and costs in procuring physician authorization was a substantial barrier to prevention-focused physical therapy. A 4.2% operating margin demonstrated that, when efficiently operated, similar programs are likely to be viable. Furthermore, if telehealth services would have been paid, the operating margin was estimated to increase to 32%. Physical therapists are highly qualified to deliver efficient, effective preventative services which has the potential to reduce falls and institutionalization and subsequent healthcare cost savings.

11.
Home Healthc Now ; 42(3): 130-139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709579

RESUMO

High fall rates among older adults in combination with prolonged time on the floor after a fall have created an urgent need to preventatively address fall recovery strategies. The purpose of this study is to describe the outcomes of a novel safe fall recovery (SFR) educational module provided by physical therapists to older adults in their homes. A pre- and post-test descriptive study used a convenience sample to recruit 30 adults (≥65 years). A baseline assessment and SFR in-home education were provided. Pre- and post-education measures included the Steps for Safe Fall Recovery (Steps for SFR) tool, the Activity Specific Balance Confidence (ABC) scale, and a fall confidence survey. The Wilcoxon matched-pairs signed-rank test determined significance (P < .05). Participants were age 77.2 (6.8) years and 20 females. Eight reported a fall during the prior year. Statistically significant improvements were identified in the Steps to SFR tool (P = .001), the ABC scale (P = .004), and the fall recovery confidence survey (P = .001). Integration of an SFR educational intervention delivered to an older adult population in their home demonstrated improved safety and confidence to recover from a fall.


Assuntos
Acidentes por Quedas , Humanos , Acidentes por Quedas/prevenção & controle , Feminino , Masculino , Idoso , Idoso de 80 Anos ou mais , Educação de Pacientes como Assunto/métodos
12.
Home Healthc Now ; 42(4): 206-218, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38975818

RESUMO

Emergency preparedness initiatives are a Medicare condition of participation in home healthcare, yet limited evidence on the impact of associated programming is available. The purpose of this exploratory pilot study was to examine the outcomes of an individualized emergency preparedness educational program provided by a physical therapist (PT) in the homes of older adults. The investigators recruited older adults (n = 30) using convenience sampling. An emergency preparedness education module was developed. Demographics, functional and environmental outcome measures, a pre- and post-education confidence survey, and learning outcomes were ascertained and analyzed. Participants reported being female (n = 23), 70 to 79 years (n = 15), and 19 individuals reported 35 different lifetime emergency events. Hearing and vision impairments, inability to change a battery or navigate stairs, and environmental deficits including clutter and poor lighting were identified. Closing bedroom doors at nighttime, functioning carbon monoxide and smoke detectors, creating an evacuation plan, and assembling first aid kits were learning outcomes. Trends toward increased confidence were identified, with statistically significant improvements in the ability to respond to a fire (P = .01), a heat wave (P = .03), and to crawl on hands and knees (P = .05) identified. This study provides emerging evidence that PTs have a role in improving an older adult's confidence to prepare for and respond to an emergency event.


Assuntos
Serviços de Assistência Domiciliar , Humanos , Feminino , Idoso , Masculino , Projetos Piloto , Defesa Civil/educação , Estados Unidos , Planejamento em Desastres
13.
Nat Commun ; 15(1): 3065, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594258

RESUMO

Superconducting quantum circuits are a natural platform for quantum simulations of a wide variety of important lattice models describing topological phenomena, spanning condensed matter and high-energy physics. One such model is the bosonic analog of the well-known fermionic Kitaev chain, a 1D tight-binding model with both nearest-neighbor hopping and pairing terms. Despite being fully Hermitian, the bosonic Kitaev chain exhibits a number of striking features associated with non-Hermitian systems, including chiral transport and a dramatic sensitivity to boundary conditions known as the non-Hermitian skin effect. Here, using a multimode superconducting parametric cavity, we implement the bosonic Kitaev chain in synthetic dimensions. The lattice sites are mapped to frequency modes of the cavity, and the in situ tunable complex hopping and pairing terms are created by parametric pumping at the mode-difference and mode-sum frequencies, respectively. We experimentally demonstrate important precursors of nontrivial topology and the non-Hermitian skin effect in the bosonic Kitaev chain, including chiral transport, quadrature wavefunction localization, and sensitivity to boundary conditions. Our experiment is an important first step towards exploring genuine many-body non-Hermitian quantum dynamics.

14.
Cancer Med ; 13(14): e70004, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39046221

RESUMO

INTRODUCTION: Integration of exercise into standard oncology care requires a highly skilled workforce of exercise professionals; however, competency requirements have not kept pace with advancements in the field. Therefore, the aim of this study was to obtain consensus on core competencies required for an exercise professional to be qualified to work with adults undergoing active cancer treatment. MATERIALS AND METHODS: A three-round modified electronic Delphi process was used. In Round 1, an international group of 64 exercise oncology stakeholders (i.e., exercise oncology professionals (n = 29), clinical referrers (n = 21), and people with lived experience (n = 14)) responded to open-ended prompts eliciting perspectives regarding competencies needed for an exercise oncology professional to work with adults receiving active cancer treatment. Subsequently, only exercise oncology professionals participated, ranking the importance of competencies. In Round 2, professionals received summary feedback, ranked new competencies generated from open-ended responses, and reranked competencies not reaching consensus. In the final round, professionals finalized consensus ranking and rated frequency and mastery level for each. RESULTS: Consensus was reached on 103 core competencies required for exercise professionals to be qualified to deliver care to adults undergoing active cancer treatment. The core competencies represent 10 content areas and reflect the needs of clinical referrers and people with lived experience of receiving cancer treatment. CONCLUSIONS: The core competencies identified reflect significant advancements in the field of exercise oncology. Results will underpin the development of education, certification, and employment requirements for exercise oncology professionals, providing a critical step toward achieving routine integration of exercise into standard oncology care.


Assuntos
Competência Clínica , Técnica Delphi , Neoplasias , Humanos , Austrália , Estados Unidos , Feminino , Masculino , Neoplasias/terapia , Terapia por Exercício/normas , Oncologia/normas , Adulto , Consenso , Pessoa de Meia-Idade
15.
J Neurotrauma ; 41(7-8): 942-956, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37950709

RESUMO

Exposure to blast overpressure has been a pervasive feature of combat-related injuries. Studies exploring the neurological correlates of repeated low-level blast exposure in career "breachers" demonstrated higher levels of tumor necrosis factor alpha (TNFα) and interleukin (IL)-6 and decreases in IL-10 within brain-derived extracellular vesicles (BDEVs). The current pilot study was initiated in partnership with the U.S. Special Operations Command (USSOCOM) to explore whether neuroinflammation is seen within special operators with prior blast exposure. Data were analyzed from 18 service members (SMs), inclusive of 9 blast-exposed special operators with an extensive career history of repeated blast exposures and 9 controls matched by age and duration of service. Neuroinflammation was assessed utilizing positron emission tomography (PET) imaging with [18F]DPA-714. Serum was acquired to assess inflammatory biomarkers within whole serum and BDEVs. The Blast Exposure Threshold Survey (BETS) was acquired to determine blast history. Both self-report and neurocognitive measures were acquired to assess cognition. Similarity-driven Multi-view Linear Reconstruction (SiMLR) was used for joint analysis of acquired data. Analysis of BDEVs indicated significant positive associations with a generalized blast exposure value (GBEV) derived from the BETS. SiMLR-based analyses of neuroimaging demonstrated exposure-related relationships between GBEV, PET-neuroinflammation, cortical thickness, and volume loss within special operators. Affected brain networks included regions associated with memory retrieval and executive functioning, as well as visual and heteromodal processing. Post hoc assessments of cognitive measures failed to demonstrate significant associations with GBEV. This emerging evidence suggests neuroinflammation may be a key feature of the brain response to blast exposure over a career in operational personnel. The common thread of neuroinflammation observed in blast-exposed populations requires further study.


Assuntos
Traumatismos por Explosões , Militares , Humanos , Traumatismos por Explosões/complicações , Projetos Piloto , Doenças Neuroinflamatórias , Militares/psicologia , Explosões , Interleucina-6
16.
J Exp Biol ; 216(Pt 23): 4462-72, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23997200

RESUMO

The aneural heart of the Pacific hagfish, Eptatretus stoutii, varies heart rate fourfold during recovery from anoxia. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which play an important role in establishing the pacemaker rate of vertebrate hearts, were postulated to be present in this ancestral vertebrate heart, and it was also theorized that changes in hagfish heart rate with oxygen availability involved altered HCN expression. Partial gene cloning revealed six HCN isoforms in the hagfish heart. Hagfish representatives of HCN2, HCN3 and HCN4 were discovered, with HCN2 and HCN3 existing as isoforms designated as HCN2a, HCN2b, HCN3a, two paralogs of HCN3b, and HCN3c. Phylogenetic analysis revealed HCN3b and HCN3c to be ancestral, followed by HCN3a, HCN4 and HCN2. Moreover, HCN3a expression was dominant in both the atrial and ventricular chambers, suggesting that the HCN4 dominance in adult mammalian hearts appeared after hagfish divergence. HCN expression was higher in the atrium than in the ventricle, as might be expected given that atrial beating rate is known to be faster than the ventricular rate. In addition, mRNA expression under normoxic conditions was compared with that following 24 h of anoxia, and either a 2-h or 36-h recovery in normoxic water. In the ventricle, anoxia decreased HCN3a but not HCN4 expression. In contrast, atrial HCN3a expression significantly increased following 2 h of recovery, before returning to control levels following 36 h of recovery, possibly contributing to heart rate changes previously observed under these conditions.


Assuntos
Proteínas de Peixes/genética , Regulação da Expressão Gênica , Feiticeiras (Peixe)/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Miocárdio/metabolismo , Sequência de Aminoácidos , Animais , Hipóxia Celular , Clonagem Molecular , Proteínas de Peixes/química , Proteínas de Peixes/metabolismo , Feiticeiras (Peixe)/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/química , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência
17.
Artigo em Inglês | MEDLINE | ID: mdl-23010241

RESUMO

Pharmacological ion-channel blockers were used to investigate the spontaneous heart rates in Pacific hagfish, Eptatretus stoutii. Zatebradine, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, vastly reduced atrial and ventricular contraction rates in a similar concentration-dependent manner, indicating a major role for HCN in setting intrinsic heart rate. When voltage-gated Na(+) channels were blocked with tetrodotoxin (TTX), atrial contraction rate declined in a dose-dependent manner, but remained faster than ventricular rate even at very high TTX concentrations. This TTX resistance compared with other fish suggests an important role for a TTX-sensitive inactivation-resistant Na(+) current in atrioventricular conduction and chamber synchrony, and a lesser role in setting intrinsic heart rate. T and L-type calcium channel blockers, nickel and nifedipine respectively, also reduced atrial and ventricular contraction rates, nickel having a larger effect on the atrium. These novel results for hagfish are consistent with intrinsic atrial and ventricular rates being set mostly by HCN, with lesser contributions from other ion channels. We suggest that future electrophysiological studies will reveal that hagfishes, with their ancestral position in the evolution of the vertebrate-type chambered heart, share some but not all features of vertebrate intrinsic heart rate control.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Feiticeiras (Peixe)/fisiologia , Átrios do Coração/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Contração Miocárdica/efeitos dos fármacos , Animais , Bloqueio Atrioventricular/metabolismo , Bloqueio Atrioventricular/patologia , Benzazepinas/farmacologia , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo T/metabolismo , Relação Dose-Resposta a Droga , Técnicas Eletrofisiológicas Cardíacas/métodos , Feiticeiras (Peixe)/metabolismo , Átrios do Coração/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Técnicas In Vitro , Níquel/farmacologia , Nifedipino/farmacologia , Tetrodotoxina/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Canais de Sódio Disparados por Voltagem/metabolismo
18.
Methods Mol Biol ; 2629: 247-269, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36929081

RESUMO

In this chapter, we review the cutting-edge statistical and machine learning methods for missing value imputation, normalization, and downstream analyses in mass spectrometry metabolomics studies, with illustration by example datasets. The missing peak recovery includes simple imputation by zero or limit of detection, regression-based or distribution-based imputation, and prediction by random forest. The batch effect can be removed by data-driven methods, internal standard-based, and quality control sample-based normalization. We also summarize different types of statistical analysis for metabolomics and clinical outcomes, such as inference on metabolic biomarkers, clustering of metabolomic profiles, metabolite module building, and integrative analysis with transcriptome.


Assuntos
Metabolômica , Análise por Conglomerados , Espectrometria de Massas/métodos , Metabolômica/métodos , Controle de Qualidade
19.
Cureus ; 15(10): e47865, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38021598

RESUMO

Introduction Technology literacy is the ability to comfortably understand, use, and navigate digital devices. It is considered a "super social determinant of health", and yet 39% of adults aged 65+ report not using a smartphone, and 25% of seniors still lack internet access. The purpose of this study was to examine the applicability of a physical therapist-delivered clinical assessment tool related to technological literacy and to identify relationships between technology utilization and perceptions related to sociodemographic factors in community-dwelling older adults. Methods A prospective mixed-methods observational-descriptive study where physical therapists (PTs) administered a newly designed technology literacy algorithm to older adults and evaluated the results of the algorithm. A convenience sample of 30 participants aged 65 and older was evaluated for their technology literacy. The exclusion criteria were if the person had a vision deficit, lived in a nursing home or extended care facility, was unable to fluently read and understand the English language, or was not willing to have an in-home visit by a licensed PT. After informed consent was obtained, the participant completed a Past Experience with Technology Questionnaire assessing participant confidence with technology usage and a demographic questionnaire. A PT data collector visited participants' homes and administered a novel technology literacy algorithm. The PTs also provided subjective feedback after patient visits as to their perceptions of the algorithm. Inferential statistics were performed for key variables, including a Kruskal-Wallis test being utilized for variables with three or more levels and a two-sample Wilcoxon test being utilized for variables with two levels. The binary results were evaluated with chi-squared tests. Trends in distribution and measures of central tendency were analyzed for demographic data. Statistical significance was set at P<0.05 with a confidence interval of 95%. Results Participants (n=30) were evenly distributed with regard to age, and 66% of people had a college degree. Most were female, of the white race, and retired. There were statistically significant relationships between older age and decreased comfort level with using the internet (P=0.30) and sending messages (P=0.31), with individuals 80+ years old having a mean confidence of 6.78 out of 10. A statistically significant relationship was also found between higher income and increased confidence in browsing the internet (P = 0.07). Most qualitative data from physical therapist experiences included positive trends such as ease of use, efficiency, and confidence instilled. Constructive feedback included a lack of resources to assist with more advanced technology-related needs and recommendations to refine the algorithm when advanced needs were identified. Conclusion Technology literacy is a vital component of accessing health and medical care and maximizing the quality of that care, especially in the older adult population. The tools created may assist clinicians with identifying and addressing issues related to technology in older adults. This may help a patient navigate health issues that require the use of technology in their home. This study provided evidence that a PT-administered algorithm may be feasible to address technology literacy issues in the homes of older adults.

20.
Cureus ; 15(3): e35784, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37025707

RESUMO

Background The purpose of this study was to determine if the use of evidence-based cognitive and cardiovascular screening prior to initiating a prevention-focused exercise program that utilizes a physical therapist (PT) direct consumer access referral model is safe. Methods A retrospective descriptive analysis of data from a prior randomized controlled trial (RCT) was performed. Two data sets emerged: Group S was screened for study inclusion but not enrolled, and Group E was enrolled and participated in preventative exercise. Participant outcomes of cognitive screenings (Mini-Cog, Trail Making Test-Part B) and cardiovascular screening (American College of Sports Medicine Exercise Pre-participation Health Screening) were extracted. Descriptive statistics were generated for demographic and outcome variables and inferential statistics were analyzed (p < 0.05). Results Records from 70 individuals (Group S) and 144 individuals (Group E) were available for analysis. Overall, 18.6% (n = 13) in Group S were not enrolled due to medical instability or potential safety considerations. The need for medical clearance prior to initiating an exercise program was identified and then clearance was obtained for 40% (n = 58) of the participants in Group E. No adverse events related to program participation were reported. Conclusions A PT-led program utilizing direct access referrals from senior centers offers a safe option for older adults to participate in individualized preventative exercise programming.

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