Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 107
Filtrar
1.
Am J Public Health ; 114(S1): S55-S58, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38064314

RESUMO

We assessed the impact of an innovative Louisiana community-academic-public health-practice (CAPP) partnership in addressing COVID-19-associated Black-White vaccination disparities over 19 months. Initially (April 2021), the cumulative vaccinations for Black versus White Louisianans were 54 542 per 100 000 versus 62 435 per 100 000, respectively. By October 2022, cumulative vaccinations for Black versus White Louisianans were 142 437 per 100 000 versus 132 488 per 100 000, respectively. The vaccination equity score increased from 908 out of 1000 in April 2021 to 942 out of 1000 in October 2022. CAPP partnership efforts contributed to addressing initial Black-White COVID-19 vaccination disparities. (Am J Public Health. 2024;114(S1):S55-S58. https://doi.org/10.2105/AJPH.2023.307509).


Assuntos
COVID-19 , Equidade em Saúde , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Saúde Pública , Louisiana , Vacinação
2.
J Neurosci ; 42(21): 4311-4325, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35477902

RESUMO

Learning is an essential cognitive mechanism allowing behavioral adaptation through adjustments in neuronal processing. It is associated with changes in the activity of sensory cortical neurons evoked by task-relevant stimuli. However, the exact nature of those modifications and the computational advantages they may confer are still debated. Here, we investigated how learning an orientation discrimination task alters the neuronal representations of the cues orientations in the primary visual cortex (V1) of male and female mice. When comparing the activity evoked by the task stimuli in naive mice and the mice performing the task, we found that the representations of the orientation of the rewarded and nonrewarded cues were more accurate and stable in trained mice. This better cue representation in trained mice was associated with a distortion of the orientation representation space such that stimuli flanking the task-relevant orientations were represented as the task stimuli themselves, suggesting that those stimuli were generalized as the task cues. This distortion was context dependent as it was absent in trained mice passively viewing the task cues and enhanced in the behavioral sessions where mice performed best. Those modifications of the V1 population orientation representation in performing mice were supported by a suppression of the activity of neurons tuned for orientations neighboring the orientations of the task cues. Thus, visual processing in V1 is dynamically adapted to enhance the reliability of the representation of the learned cues and favor generalization in the task-relevant computational space.SIGNIFICANCE STATEMENT Performance improvement in a task often requires facilitating the extraction of the information necessary to its execution. Here, we demonstrate the existence of a suppression mechanism that improves the representation of the orientations of the task stimuli in the V1 of mice performing an orientation discrimination task. We also show that this mechanism distorts the V1 orientation representation space, leading stimuli flanking the task stimuli orientations to be generalized as the task stimuli themselves.


Assuntos
Córtex Visual , Animais , Feminino , Masculino , Camundongos , Orientação/fisiologia , Estimulação Luminosa , Córtex Visual Primário , Reprodutibilidade dos Testes , Córtex Visual/fisiologia , Percepção Visual/fisiologia
4.
Cerebrovasc Dis ; 52(2): 123-129, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36037797

RESUMO

Cardiac rhythm monitoring is performed to search for atrial fibrillation (AF) after ischaemic stroke or transient ischaemic attack (TIA). Prolonged cardiac rhythm monitoring increases AF detection but is challenging to implement in many healthcare settings and is not needed for all people after ischaemic stroke/TIA. We aimed to develop and validate a model that includes clinical, electrocardiogram (ECG), blood-based, and genetic biomarkers to identify people with a low probability of AF detection after ischaemic stroke or TIA. We will recruit 675 consenting participants who are aged over 18 years, who were admitted with ischaemic stroke or TIA in the 5 days prior, who are not known to have AF, and who would be suitable for anticoagulation if AF is found. We will collect baseline demographic and clinical data, a 12-lead ECG, and a venous blood sample for blood biomarkers (including midregional pro-atrial natriuretic peptide, MRproANP) and genetic data. We will perform up to 28 days of cardiac rhythm monitoring using an R-test or patch device to search for AF in all participants. The sample size of 675 participants is based on true sensitivity of 92.5%, null hypothesis sensitivity of 80%, 80% power, and 5% significance. The primary outcome is AF detection ≥30 s duration during 28 days of cardiac rhythm monitoring. Secondary outcomes are AF detection at 1-year, recurrent cardiovascular events, and mortality and will be identified by electronic linkage and telephone follow-up. The results will guide the development of a more personalized care pathway to search for AF after ischaemic stroke or TIA. This could help to reduce cardiac rhythm monitoring for people with a low probability of AF detection and allow more intensive cardiac monitoring to be focused on people who are more likely to have AF and benefit. Participants will be consented for their data to be used in future research studies, providing a rich resource for stroke and cardiovascular research communities.


Assuntos
Fibrilação Atrial , Isquemia Encefálica , AVC Embólico , Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Adulto , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Ataque Isquêmico Transitório/diagnóstico , Isquemia Encefálica/diagnóstico , Fibrilação Atrial/diagnóstico , AVC Isquêmico/complicações
5.
Eur Heart J ; 42(45): 4656-4668, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34279606

RESUMO

AIMS: A fractional flow reserve (FFR) value ≥0.90 after percutaneous coronary intervention (PCI) is associated with a reduced risk of adverse cardiovascular events. TARGET-FFR is an investigator-initiated, single-centre, randomized controlled trial to determine the feasibility and efficacy of a post-PCI FFR-guided optimization strategy vs. standard coronary angiography in achieving final post-PCI FFR values ≥0.90. METHODS AND RESULTS: After angiographically guided PCI, patients were randomized 1:1 to receive a physiology-guided incremental optimization strategy (PIOS) or a blinded coronary physiology assessment (control group). The primary outcome was the proportion of patients with a final post-PCI FFR ≥0.90. Final FFR ≤0.80 was a prioritized secondary outcome. A total of 260 patients were randomized (131 to PIOS, 129 to control) and 68.1% of patients had an initial post-PCI FFR <0.90. In the PIOS group, 30.5% underwent further intervention (stent post-dilation and/or additional stenting). There was no significant difference in the primary endpoint of the proportion of patients with final post-PCI FFR ≥0.90 between groups (PIOS minus control 10%, 95% confidence interval -1.84 to 21.91, P = 0.099). The proportion of patients with a final FFR ≤0.80 was significantly reduced when compared with the angiography-guided control group (-11.2%, 95% confidence interval -21.87 to -0.35], P = 0.045). CONCLUSION: Over two-thirds of patients had a physiologically suboptimal result after angiography-guided PCI. An FFR-guided optimization strategy did not significantly increase the proportion of patients with a final FFR ≥0.90, but did reduce the proportion of patients with a final FFR ≤0.80.


Assuntos
Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Angiografia Coronária , Humanos , Stents , Fatores de Tempo , Resultado do Tratamento
6.
Clin Rehabil ; 35(1): 3-12, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32959679

RESUMO

PURPOSE: This discussion paper argues that holding independence as the central goal for rehabilitation has limitations that hinder successful outcomes. It shows why autonomy and social engagement should also serve as goals of rehabilitation, in order to achieve quality of life and effective functioning. METHODS: The paper reviews problems arising from the over-emphasis on independence in rehabilitation. Although independence is a valuable goal on some tasks, it is sometimes not possible or desirable and is best complimented by autonomy and social engagement. Autonomy recognises that enacting some goals requires the support of other people. Autonomy is thus linked to social engagement (connectivity) in the workplace and personal relationships. The paper applies this framework to motor and cognitive disabilities. RESULTS: The inclusion of autonomy and social engagement as goals for rehabilitation addresses the limitations of independence and can serve the unifying aim of enhancing the person's quality of life. These goals apply equally to motor disabilities and the cognitive and behavioural effects of injuries which affect personal and work relationships. CONCLUSIONS: Rehabilitation is likely to be more effective if it aims at a combination of independence, autonomy and social engagement, in service of the goal of a good quality of life.


Assuntos
Autonomia Pessoal , Qualidade de Vida , Reabilitação , Participação Social , Humanos
7.
Catheter Cardiovasc Interv ; 96(2): 393-401, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32017374

RESUMO

OBJECTIVE: The objective of this study was to investigate the safety and feasibility of treating infrapopliteal lesions using a novel drug delivery catheter locally delivering liquid paclitaxel. BACKGROUND: Balloon angioplasty is currently the Gold Standard to treat below-the-knee disease; however, restenosis continues to be a great challenge following these percutaneous revascularization procedures. METHODS: The Occlusion Perfusion Catheter for Optimal Delivery of Paclitaxel for the Prevention of Endovascular Restenosis (COPPER-A) study-Below-the-Knee Cohort was a prospective, nonrandomized, multicenter, feasibility, and safety study that enrolled 35 patients at 11 participating sites. The safety endpoints at 1, 3, and 6 months were freedom from thrombosis, major amputation in the target limb and target limb related death. The efficacy endpoints were primary patency and freedom from clinically driven target lesion revascularization at 6 months. RESULTS: All patients tolerated the procedure well with no reports of adverse procedural events. Thirty-five patients were treated with a mean lesion length of 112 ± 81.2 mm with the lesion length range of 20-286 mm. At 6-month follow-up, primary patency was 89.3% and freedom from clinically driven target lesion revascularization was 96.4%. No patients demonstrated thrombosis, major amputation in the target limb and target limb related death at the 1-, 3- and 6-months follow-up intervals. CONCLUSIONS: The results of this multi-center study demonstrated that infrapopliteal arteries can be safely and effectively treated with liquid paclitaxel using the occlusion perfusion catheter.


Assuntos
Angioplastia com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Sistemas de Liberação de Medicamentos/instrumentação , Paclitaxel/administração & dosagem , Doença Arterial Periférica/terapia , Artéria Poplítea , Dispositivos de Acesso Vascular , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Angioplastia com Balão/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Grau de Desobstrução Vascular
8.
J Neurophysiol ; 121(6): 2202-2214, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30969800

RESUMO

Multimodal sensory integration facilitates the generation of a unified and coherent perception of the environment. It is now well established that unimodal sensory perceptions, such as vision, are improved in multisensory contexts. Whereas multimodal integration is primarily performed by dedicated multisensory brain regions such as the association cortices or the superior colliculus, recent studies have shown that multisensory interactions also occur in primary sensory cortices. In particular, sounds were shown to modulate the responses of neurons located in layers 2/3 (L2/3) of the mouse primary visual cortex (V1). Yet, the net effect of sound modulation at the V1 population level remained unclear. In the present study, we performed two-photon calcium imaging in awake mice to compare the representation of the orientation and the direction of drifting gratings by V1 L2/3 neurons in unimodal (visual only) or multimodal (audiovisual) conditions. We found that sound modulation depended on the tuning properties (orientation and direction selectivity) and response amplitudes of V1 L2/3 neurons. Sounds potentiated the responses of neurons that were highly tuned to the cue's orientation and direction but weakly active in the unimodal context, following the principle of inverse effectiveness of multimodal integration. Moreover, sound suppressed the responses of neurons untuned for the orientation and/or the direction of the visual cue. Altogether, sound modulation improved the representation of the orientation and direction of the visual stimulus in V1 L2/3. Namely, visual stimuli presented with auditory stimuli recruited a neuronal population better tuned to the visual stimulus orientation and direction than when presented alone. NEW & NOTEWORTHY The primary visual cortex (V1) receives direct inputs from the primary auditory cortex. Yet, the impact of sounds on visual processing in V1 remains controverted. We show that the modulation by pure tones of V1 visual responses depends on the orientation selectivity, direction selectivity, and response amplitudes of V1 neurons. Hence, audiovisual stimuli recruit a population of V1 neurons better tuned to the orientation and direction of the visual stimulus than unimodal visual stimuli.


Assuntos
Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Neurônios/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Percepção Espacial/fisiologia , Córtex Visual/fisiologia , Animais , Camundongos , Microscopia de Fluorescência por Excitação Multifotônica , Córtex Visual/diagnóstico por imagem
9.
Brain Inj ; 33(8): 1070-1077, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31007082

RESUMO

Primary objective: People often misattribute stroke survivors' symptoms to other causes such as their personality, especially when the survivors are young. As a result, these stroke survivors experience feelings of resentment towards and from their acquaintances, and may struggle to retain employment. This study aimed to clarify how people's misattributions for stroke symptoms were affected by varying information about the stroke. Methods: Experiment 1 examined whether the stroke survivor's age (72, 32 or unstated) and the information about the person's stroke (no information, explicit stroke or implied stroke) influenced participants' causal attributions for the stroke survivor's four ambiguous symptoms, such as fatigue. Experiment 2 examined the effect of the rapidity (a week or a year) with which the symptoms appeared. Results: When the scenario explicitly referred to stroke, participants attributed the ambiguous symptoms more to stroke, whereas when it did not mention stroke, participants attributed these symptoms more to other factors. When stroke was merely implied by reference to unilateral paralysis, participants rated stroke the best explanation when the target person was 72 but not when he was 32. Experiment 2 showed that stating that the symptoms happened rapidly heightened attributions to stroke in the 72-year-old but not the 32-year-old. Conclusions: These findings show how different information about stroke survivors affect people's attributions for survivors' behaviour; this has important implications for accurate diagnosis and effective rehabilitation that targets these attributions.


Assuntos
Compreensão , Conhecimentos, Atitudes e Prática em Saúde , Reabilitação do Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/psicologia , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção Social , Sobreviventes/psicologia , Adulto Jovem
11.
Clin Sci (Lond) ; 132(12): 1315-1328, 2018 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-29632138

RESUMO

BACKGROUND: The effect of salt on cerebral small vessel disease (SVD) is poorly understood. We assessed the effect of dietary salt on cerebral tissue of the stroke-prone spontaneously hypertensive rat (SHRSP) - a relevant model of sporadic SVD - at both the gene and protein level. Methods: Brains from 21-week-old SHRSP and Wistar-Kyoto rats, half additionally salt-loaded (via a 3-week regime of 1% NaCl in drinking water), were split into two hemispheres and sectioned coronally - one hemisphere for mRNA microarray and qRT-PCR, the other for immunohistochemistry using a panel of antibodies targeting components of the neurovascular unit. Results: We observed differences in gene and protein expression affecting the acute phase pathway and oxidative stress (ALB, AMBP, APOH, AHSG and LOC100129193, up-regulated in salt-loaded WKY versus WKY, >2-fold), active microglia (increased Iba-1 protein expression in salt-loaded SHRSP versus salt-loaded WKY, p<0.05), vascular structure (ACTB and CTNNB, up-regulated in salt-loaded SHRSP versus SHRSP, >3-fold; CLDN-11, VEGF and VGF down-regulated >2-fold in salt-loaded SHRSP versus SHRSP) and myelin integrity (MBP down-regulated in salt loaded WKY rats versus WKY, >2.5-fold). Changes of salt-loading were more pronounced in SHRSP and occurred without an increase in blood pressure in WKY rats. CONCLUSION: Salt exposure induced changes in gene and protein expression in an experimental model of SVD and its parent rat strain in multiple pathways involving components of the glio-vascular unit. Further studies in pertinent experimental models at different ages would help clarify the short- and long-term effect of dietary salt in SVD.


Assuntos
Encéfalo/metabolismo , Doenças de Pequenos Vasos Cerebrais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Cloreto de Sódio na Dieta/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Estresse Oxidativo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Regulação para Cima/efeitos dos fármacos
12.
Catheter Cardiovasc Interv ; 91(6): 1144-1148, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29513389

RESUMO

The Chocolate BAR study is a prospective multicenter post-market registry designed to evaluate the safety and performance of the Chocolate percutaneous transluminal angioplasty balloon catheter in a broad population with symptomatic peripheral arterial disease. The primary endpoint is acute procedural success (defined as ≤30% residual stenosis without flow-limiting dissection); secondary long-term outcomes include freedom from target lesion revascularization (TLR), major unplanned amputation, survival, and patency. A total of 262 patients (290 femoropopliteal lesions) were enrolled at 30 US centers between 2012 and 2014. The primary endpoint of procedure success was achieved in 85.1% of cases, and freedom from stenting occurred in 93.1%. Bail out stenting by independent adjudication occurred in 1.6% of cases and there were no flow limiting dissections. There was mean improvement of 2.1 Rutherford classes (±1.5) at 12-months, with 78.5% freedom from TLR, 97.2% freedom from major amputation, and 93.3% freedom from all-cause mortality. Core Lab adjudicated patency was 64.1% at 12 months. Use of the Chocolate balloon in an "all-comers" population achieved excellent procedural outcomes with low dissection rates and bailout stent use.


Assuntos
Angioplastia com Balão/instrumentação , Artéria Femoral , Doença Arterial Periférica/terapia , Artéria Poplítea , Dispositivos de Acesso Vascular , Idoso , Angioplastia com Balão/efeitos adversos , Desenho de Equipamento , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Vigilância de Produtos Comercializados , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Grau de Desobstrução Vascular
13.
Disasters ; 42(4): 761-781, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29504146

RESUMO

People tolerate different levels of risk owing to a variety of hazards. Previous research shows that the psychometric properties of hazards predict people's tolerance of them. However, this work has not taken into account events such as earthquakes. The present study tested how earthquakes score vis-à-vis risk properties and risk tolerance as compared to five other familiar hazards. Participants from Wellington, New Zealand (N=139) rated these six hazards using measures of risk characteristics and risk tolerance. Participants demonstrated different levels of risk tolerance for the different hazards and viewed earthquakes as having similar risk features to nuclear power. They also preferred different risk mitigation strategies for earthquakes (more government funding) to the other five hazards (stronger legislation). In addition, earthquake risk tolerance was predicted by different risk characteristics than the other five hazards. These findings will help risk communicators in identifying which risk characteristics to target to influence citizens' risk tolerance.


Assuntos
Desastres , Terremotos , Percepção , Humanos , Nova Zelândia , Psicometria , Risco
14.
Physiol Genomics ; 49(3): 193-200, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28130428

RESUMO

Preeclampsia is a multisystem disease that significantly contributes to maternal and fetal morbidity and mortality. In this study, we used a non-biased microarray approach to identify dysregulated genes in maternal whole blood samples which may be associated with the development of preeclampsia. Whole blood samples were obtained at 28 wk of gestation from 5 women who later developed preeclampsia (cases) and 10 matched women with normotensive pregnancies (controls). Placenta samples were obtained from an independent cohort of 19 women with preeclampsia matched with 19 women with normotensive pregnancies. We studied gene expression profiles using Illumina microarray in blood and validated changes in gene expression in whole blood and placenta tissue by qPCR. We found a transcriptional profile differentiating cases from controls; 336 genes were significantly dysregulated in blood from women who developed preeclampsia. Functional annotation of microarray results indicated that most of the genes found to be dysregulated were involved in inflammatory pathways. While general trends were preserved, only HLA-A was validated in whole blood samples from cases using qPCR (2.30- ± 0.9-fold change) whereas in placental tissue HLA-DRB1 expression was found to be significantly increased in samples from women with preeclampsia (5.88- ± 2.24-fold change). We have identified that HLA-A is upregulated in the circulation of women who went on to develop preeclampsia. In placenta of women with preeclampsia we identified that HLA-DRB1 is upregulated. Our data provide further evidence for involvement of the HLA gene family in the pathogenesis of preeclampsia.


Assuntos
Regulação da Expressão Gênica , Antígenos HLA/genética , Placenta/metabolismo , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/genética , Adulto , Feminino , Antígenos HLA/metabolismo , Humanos , Gravidez , Transcriptoma , Regulação para Cima/genética
15.
BMC Genomics ; 18(Suppl 8): 817, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29143667

RESUMO

BACKGROUND: Recombinant human erythropoietin (rHuEpo) can improve human performance and is therefore frequently abused by athletes. As a result, the World Anti-Doping Agency (WADA) introduced the Athlete Biological Passport (ABP) as an indirect method to detect blood doping. Despite this progress, challenges remain to detect blood manipulations such as the use of microdoses of rHuEpo. METHODS: Forty-five whole-blood transcriptional markers of rHuEpo previously derived from a high-dose rHuEpo administration trial were used to assess whether microdoses of rHuEpo could be detected in 14 trained subjects and whether these markers may be confounded by exercise (n = 14 trained subjects) and altitude training (n = 21 elite runners and n = 4 elite rowers, respectively). Differential gene expression analysis was carried out following normalisation and significance declared following application of a 5% false discovery rate (FDR) and a 1.5 fold-change. Adaptive model analysis was also applied to incorporate these markers for the detection of rHuEpo. RESULTS: ALAS2, BCL2L1, DCAF12, EPB42, GMPR, SELENBP1, SLC4A1, TMOD1 and TRIM58 were differentially expressed during and throughout the post phase of microdose rHuEpo administration. The CD247 and TRIM58 genes were significantly up- and down-regulated, respectively, immediately following exercise when compared with the baseline both before and after rHuEpo/placebo. No significant gene expression changes were found 30 min after exercise in either rHuEpo or placebo groups. ALAS2, BCL2L1, DCAF12, SLC4A1, TMOD1 and TRIM58 tended to be significantly expressed in the elite runners ten days after arriving at altitude and one week after returning from altitude (FDR > 0.059, fold-change varying from 1.39 to 1.63). Following application of the adaptive model, 15 genes showed a high sensitivity (≥ 93%) and specificity (≥ 71%), with BCL2L1 and CSDA having the highest sensitivity (93%) and specificity (93%). CONCLUSIONS: Current results provide further evidence that transcriptional biomarkers can strengthen the ABP approach by significantly prolonging the detection window and improving the sensitivity and specificity of blood doping detection. Further studies are required to confirm, and if necessary, integrate the confounding effects of altitude training on blood doping.


Assuntos
Eritropoetina/administração & dosagem , Eritropoetina/farmacologia , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacologia , Transcriptoma/efeitos dos fármacos , Adulto , Dopagem Esportivo , Relação Dose-Resposta a Droga , Hematologia , Humanos , Masculino , Modelos Biológicos
16.
Circ Res ; 117(10): 870-883, 2015 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-26311719

RESUMO

RATIONALE: The pathogenesis of pulmonary arterial hypertension (PAH) remains unclear. The 4 microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered. OBJECTIVE: To elucidate the transcriptional regulation of the miR-143/145 cluster and the role of miR-143 in PAH. METHODS AND RESULTS: We identified the promoter region that regulates miR-143/145 microRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signaling pathways, including estrogen receptor, liver X factor/retinoic X receptor, transforming growth factor-ß (Smads), and hypoxia (hypoxia response element), that regulated levels of all pri-miR stem loop transcription and resulting microRNA expression. We observed that miR-143-3p is selectively upregulated compared with miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMC-derived exosomes. Using assays with pulmonary arterial endothelial cells, we demonstrated a paracrine promigratory and proangiogenic effect of miR-143-3p-enriched exosomes from PASMC. Quantitative polymerase chain reaction and in situ hybridization showed elevated expression of miR-143 in calf models of PAH and in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role of miR-143 in experimental pulmonary hypertension in vivo in miR-143-/- and anti-miR-143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings. CONCLUSIONS: MiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, whereas inhibition of miR-143-3p blocked experimental pulmonary hypertension. Taken together, these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology.


Assuntos
Comunicação Celular , Células Endoteliais/metabolismo , Hipertensão Pulmonar/metabolismo , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Animais , Pressão Arterial , Sítios de Ligação , Estudos de Casos e Controles , Bovinos , Movimento Celular , Células Endoteliais/patologia , Exossomos/metabolismo , Feminino , Regulação da Expressão Gênica , Células HeLa , Humanos , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/prevenção & controle , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , Músculo Liso Vascular/patologia , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/patologia , Regiões Promotoras Genéticas , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Transdução de Sinais , Fatores de Tempo , Fatores de Transcrição/metabolismo , Transfecção , Remodelação Vascular , Função Ventricular Direita , Pressão Ventricular
17.
Mol Ther ; 24(5): 978-90, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26898221

RESUMO

Despite the increasing importance of long noncoding RNA in physiology and disease, their role in endothelial biology remains poorly understood. Growing evidence has highlighted them to be essential regulators of human embryonic stem cell differentiation. SENCR, a vascular-enriched long noncoding RNA, overlaps the Friend Leukemia Integration virus 1 (FLI1) gene, a regulator of endothelial development. Therefore, we wanted to test the hypothesis that SENCR may contribute to mesodermal and endothelial commitment as well as in endothelial function. We thus developed new differentiation protocols allowing generation of endothelial cells from human embryonic stem cells using both directed and hemogenic routes. The expression of SENCR was markedly regulated during endothelial commitment using both protocols. SENCR did not control the pluripotency of pluripotent cells; however its overexpression significantly potentiated early mesodermal and endothelial commitment. In human umbilical endothelial cell (HUVEC), SENCR induced proliferation, migration, and angiogenesis. SENCR expression was altered in vascular tissue and cells derived from patients with critical limb ischemia and premature coronary artery disease compared to controls. Here, we showed that SENCR contributes to the regulation of endothelial differentiation from pluripotent cells and controls the angiogenic capacity of HUVEC. These data give novel insight into the regulatory processes involved in endothelial development and function.


Assuntos
Células Endoteliais/fisiologia , Neovascularização Patológica/genética , RNA Longo não Codificante/genética , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Transdução de Sinais
18.
Physiol Genomics ; 48(3): 202-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26757800

RESUMO

Recombinant human erythropoietin (rHuEPO) is frequently abused by athletes as a performance-enhancing drug, despite being prohibited by the World Anti-Doping Agency. Although the methods to detect blood doping, including rHuEPO injections, have improved in recent years, they remain imperfect. In a proof-of-principle study, we identified, replicated, and validated the whole blood transcriptional signature of rHuEPO in endurance-trained Caucasian males at sea level (n = 18) and Kenyan endurance runners at moderate altitude (n = 20), all of whom received rHuEPO injections for 4 wk. Transcriptional profiling shows that hundreds of transcripts were altered by rHuEPO in both cohorts. The main regulated expression pattern, observed in all participants, was characterized by a "rebound" effect with a profound upregulation during rHuEPO and a subsequent downregulation up to 4 wk postadministration. The functions of the identified genes were mainly related to the functional and structural properties of the red blood cell. Of the genes identified to be differentially expressed during and post-rHuEPO, we further confirmed a whole blood 34-transcript signature that can distinguish between samples collected pre-, during, and post-rHuEPO administration. By providing biomarkers that can reveal rHuEPO use, our findings represent an advance in the development of new methods for the detection of blood doping.


Assuntos
Dopagem Esportivo/prevenção & controle , Eritropoetina/sangue , Eritropoetina/genética , Proteínas Recombinantes/sangue , Proteínas Recombinantes/genética , Adulto , Eritropoetina/administração & dosagem , Eritropoetina/biossíntese , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/biossíntese , Transcrição Gênica
19.
J Magn Reson Imaging ; 44(3): 541-8, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26946323

RESUMO

PURPOSE: To use magnetic resonance imaging (MRI) at two field strengths to assess healthy adults' regional myocardial noncontrast (native) T1 relaxation time distribution, and global myocardial native T1 between sexes and across age groups. MATERIALS AND METHODS: In all, 84 healthy volunteers underwent MRI at 1.5T and 3.0T. T1 maps were acquired in three left ventricular short axis slices using an optimized modified Look-Locker inversion recovery investigational prototype sequence. T1 measurements in msec were calculated from 16 regions-of-interest, and a global T1 value from all evaluable segments per subject. Associations were assessed with a multivariate linear regression model. RESULTS: In total, 1297 (96.5%) segments were evaluable at 1.5T and 1263 (94.0%) segments at 3.0T. Native T1 was higher in septal than lateral myocardium (1.5T: 956.3 ± 44.4 vs. 939.2 ± 54.2 msec; P < 0.001; 3.0T: 1158.2 ± 45.9 vs. 1148.9 ± 56.9 msec; P = 0.012). Native T1 decreased with increasing age in females but not in males. Among lowest age tertile (<33 years) global native T1 was higher in females than in males at 1.5T (960.0 ± 20.3 vs. 931.5 ± 22.2 msec, respectively; P = 0.003) and 3.0T (1166.5 ± 19.7 vs. 1130.2 ± 20.6 msec; P < 0.001). No sex differences were observed in upper age tertile (≥55 years) at 1.5T (937.7 ± 25.4 vs. 934.7 ± 22.3 msec; P = 0.762) or 3.0T (1153.0 ± 30.0 vs. 1132.3 ± 23.5 msec; P = 0.056). Association of global native T1 to age (P = 0.002) and sex (P < 0.001) was independent of field strength and body size. CONCLUSION: In healthy adults, native T1 values are highest in the ventricular septum. Global native T1 was inversely associated with age in women, but not in men. J. Magn. Reson. Imaging 2016;44:541-548.


Assuntos
Envelhecimento/fisiologia , Técnicas de Imagem Cardíaca/métodos , Ventrículos do Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Caracteres Sexuais , Função Ventricular Esquerda/fisiologia , Envelhecimento/patologia , Feminino , Ventrículos do Coração/anatomia & histologia , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
J Magn Reson Imaging ; 44(5): 1197-1205, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27104306

RESUMO

PURPOSE: To assess myocardial strain using cine displacement encoding with stimulated echoes (DENSE) using 1.5T and 3.0T MRI in healthy adults. MATERIALS AND METHODS: Healthy adults without any history of cardiovascular disease underwent magnetic resonance imaging (MRI) at 1.5T and 3.0T within 2 days. The MRI protocol included balanced steady-state free-precession (b-SSFP), 2D cine-echo planar imaging (EPI)-DENSE, and late gadolinium enhancement in subjects >45 years. Acquisitions were divided into six segments; global and segmental peak longitudinal and circumferential strain were derived and analyzed by field strength, age, and gender. RESULTS: In all, 89 volunteers (mean age 44.8 ± 18.0 years, range: 18-87 years) underwent MRI at 1.5T, and 88 of these subjects underwent MRI at 3.0T (1.4 ± 1.4 days between the scans). Compared with 3.0T, the magnitudes of global circumferential (-19.5 ± 2.6% vs. -18.47 ± 2.6%; P = 0.001) and longitudinal (-12.47 ± 3.2% vs. -10.53 ± 3.1%; P = 0.004) strain were greater at 1.5T. At 1.5T, longitudinal strain was greater in females than in males: -10.17 ± 3.4% vs. -13.67 ± 2.4%; P = 0.001. Similar observations occurred for circumferential strain at 1.5T (-18.72 ± 2.2% vs. -20.10 ± 2.7%; P = 0.014) and at 3.0T (-17.92 ± 1.8% vs. -19.1 ± 3.1%; P = 0.047). At 1.5T, longitudinal and circumferential strain were not associated with age after accounting for sex (longitudinal strain P = 0.178, circumferential strain P = 0.733). At 3.0T, longitudinal and circumferential strain were associated with age (P < 0.05). Longitudinal strain values were greater in the apico-septal, basal-lateral, and mid-lateral segments and circumferential strain in the inferior, infero-lateral, and antero-lateral LV segments. CONCLUSION: Myocardial strain parameters as revealed by cine-DENSE at different MRI field strengths were associated with myocardial region, age, and sex. J. Magn. Reson. Imaging 2016;44:1197-1205.


Assuntos
Envelhecimento/fisiologia , Técnicas de Imagem por Elasticidade/métodos , Ventrículos do Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Função Ventricular Esquerda/fisiologia , Adolescente , Adulto , Idoso , Anisotropia , Força Compressiva/fisiologia , Módulo de Elasticidade/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Estresse Mecânico , Resistência à Tração/fisiologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA