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1.
Epigenomics ; 13(23): 1853-1866, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34802257

RESUMO

Background: Epigenomic changes occurring during surgery have been neglected in research; diabetes and hypertension can affect the epigenome but little is known about the epigenetics of skeletal muscle (SKM). Methods: DNA methylation was profiled via Illumina MethylationEPIC arrays in SKM samples obtained at the beginning and end of heart surgery with cardiopulmonary bypass. Results: Methylation in patients with hypertension and diabetes was significantly different, more so for uncontrolled diabetes; hypertension alone produced minimal effect. The affected pathways involved IL-1, IL-12, IL-18, TNF-α, IFN-γ, VEGF, NF-κB and Wnt signaling, apoptosis and DNA damage response. Significant changes occurred during surgery and included loci in the Hippo-YAP/TAZ pathway. Conclusion: Cardiopulmonary bypass surgery affects the SKM methylome, and the combination of hypertension and diabetes induces changes in the SKM epigenome in contrast to hypertension alone.

2.
Pediatr Res ; 89(7): 1848-1854, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32967004

RESUMO

BACKGROUND: Preterm birth places infants at higher risk of adverse long-term behavioral and cognitive outcomes. Combining biobehavioral measures and molecular biomarkers may improve tools to predict the risk of long-term developmental delays. METHODS: The Neonatal Neurobehavior and Outcomes in Very Preterm Infants study was conducted at nine neonatal intensive care units between April 2014 and June 2016. Cries were recorded and buccal swabs collected during the neurobehavioral exam. Cry episodes were extracted and analyzed using a computer system and the data were summarized using factor analysis. Genomic DNA was extracted from buccal swabs, quantified using the Qubit Fluorometer, and aliquoted into standardized concentrations. DNA methylation was measured with the Illumina MethylationEPIC BeadArray, and an epigenome-wide association study was performed using cry factors (n = 335). RESULTS: Eighteen CpGs were associated with the cry factors at genome-wide significance (α = 7.08E - 09). Two CpG sites, one intergenic and one linked to gene TCF3 (important for B and T lymphocyte development), were associated with acoustic measures of cry energy. Increased methylation of TCF3 was associated with a lower energy-related cry factor. We also found that pitch (F0) and hyperpitch (F0 > 1 kHz) were associated with DNA methylation variability at 16 CpG sites. CONCLUSIONS: Acoustic cry characteristics are related to variation in DNA methylation in preterm infants. IMPACT: Preterm birth is a major public health problem and its long-term impact on health is not well understood. Cry acoustics, related to prematurity, has been linked to a variety of medical conditions. Biobehavioral measures and molecular biomarkers can improve prediction tools for long-term developmental risks of preterm birth. Variation in epigenetic modulation in preterm infants provides a potential link between preterm birth and unfavorable developmental outcomes.

3.
Neurocrit Care ; 34(3): 1062-1071, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32661794

RESUMO

As the current understanding of COVID-19 continues to evolve, a synthesis of the literature on the neurological impact of this novel virus may help inform clinical management and highlight potentially important avenues of investigation. Additionally, understanding the potential mechanisms of neurologic injury may guide efforts to better detect and ameliorate these complications. In this review, we synthesize a range of clinical observations and initial case series describing potential neurologic manifestations of COVID-19 and place these observations in the context of coronavirus neuro-pathophysiology as it may relate to SARS-CoV-2 infection. Reported nervous system manifestations range from anosmia and ageusia, to cerebral hemorrhage and infarction. While the volume of COVID-19-related case studies continues to grow, previous work examining related viruses suggests potential mechanisms through which the novel coronavirus may impact the CNS and result in neurological complications. Namely, animal studies examining the SARS-CoV have implicated the angiotensin-converting-enzyme-2 receptor as a mediator of coronavirus-related neuronal damage and have shown that SARS-CoV can infect cerebrovascular endothelium and brain parenchyma, the latter predominantly in the medial temporal lobe, resulting in apoptosis and necrosis. Human postmortem brain studies indicate that human coronavirus variants and SARS-CoV can infect neurons and glia, implying SARS-CoV-2 may have similar neurovirulence. Additionally, studies have demonstrated an increase in cytokine serum levels as a result of SARS-CoV infection, consistent with the notion that cytokine overproduction and toxicity may be a relevant potential mechanism of neurologic injury, paralleling a known pathway of pulmonary injury. We also discuss evidence that suggests that SARS-CoV-2 may be a vasculotropic and neurotropic virus. Early reports suggest COVID-19 may be associated with severe neurologic complications, and several plausible mechanisms exist to account for these observations. A heightened awareness of the potential for neurologic involvement and further investigation into the relevant pathophysiology will be necessary to understand and ultimately mitigate SARS-CoV-2-associated neurologic injury.


Assuntos
COVID-19/complicações , Doenças do Sistema Nervoso/virologia , SARS-CoV-2/fisiologia , COVID-19/diagnóstico , COVID-19/terapia , Humanos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/terapia
4.
Rev Med Virol ; 31(1): 1-10, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32845042

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency that continues to strain healthcare systems. Emerging research describes a plethora of patient factors-including demographic, clinical, immunologic, hematological, biochemical, and radiographic findings-that may be of utility to clinicians to predict COVID-19 severity and mortality. We present a synthesis of the current literature pertaining to factors predictive of COVID-19 clinical course and outcomes. Findings associated with increased disease severity and/or mortality include age > 55 years, multiple pre-existing comorbidities, hypoxia, specific computed tomography findings indicative of extensive lung involvement, diverse laboratory test abnormalities, and biomarkers of end-organ dysfunction. Hypothesis-driven research is critical to identify the key evidence-based prognostic factors that will inform the design of intervention studies to improve the outcomes of patients with COVID-19 and to appropriately allocate scarce resources.


Assuntos
COVID-19 , Índice de Gravidade de Doença , Adulto , Envelhecimento , Biomarcadores , COVID-19/mortalidade , COVID-19/patologia , COVID-19/transmissão , Criança , Comorbidade , Humanos , Hipóxia/patologia , Prognóstico , SARS-CoV-2/patogenicidade
5.
Epidemiol Infect ; 148: e242, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33023703

RESUMO

The current pandemic is defined by the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that can lead to coronavirus disease 2019 (COVID-19). How is SARS-CoV-2 transmitted? In this review, we use a global lens to examine the sociological contexts that are potentially and systematically involved in high rates of SARS-CoV-2 transmission, including lack of personal protective equipment, population density and confinement. Altogether, this review provides an in-depth conspectus of the current literature regarding how SARS-CoV-2 disproportionately impacts many minority communities. By contextualising and disambiguating transmission risks that are particularly prominent for disadvantaged populations, this review can assist public health efforts throughout and beyond the COVID-19 pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Saúde Pública , SARS-CoV-2 , Sociologia
7.
J Card Surg ; 35(6): 1302-1305, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32306491

RESUMO

BACKGROUND: Respiratory complications have been well remarked in the novel coronavirus disease (SARS-CoV-2/COVID-19), yet an emerging body of research indicates that cardiac involvement may be implicated in poor outcomes for these patients. AIMS: This review seeks to gather and distill the existing body of literature that describes the cardiac implications of COVID-19. MATERIALS AND METHODS: The English literature was reviewed for papers dealing with the cardiac effects of COVID-19. RESULTS: Notably, COVID-19 patients with pre-existing cardiovascular disease are counted in greater frequency in intensive care unit settings, and ultimately suffer greater rates of mortality. Other studies have noted cardiac presentations for COVID-19, rather than respiratory, such as acute pericarditis and left ventricular dysfunction. In some patients there has been evidence of acute myocardial injury, with correspondingly increased serum troponin I levels. With regard to surgical interventions, there is a dearth of data describing myocardial protection during cardiac surgery for COVID-19 patients. Although some insights have been garnered in the study of cardiovascular diseases for these patients, these insights remain fragmented and have yet to cement clear guidelines for actionable clinical practice. CONCLUSION: While some information is available, further studies are imperative for a more cohesive understanding of the cardiac pathophysiology in COVID-19 patients to promote more informed treatment and, ultimately, better clinical outcomes.


Assuntos
Doenças Cardiovasculares/epidemiologia , Causas de Morte , Infecções por Coronavirus/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Betacoronavirus , COVID-19 , Doenças Cardiovasculares/diagnóstico , Comorbidade , Infecções por Coronavirus/diagnóstico , Feminino , Saúde Global , Humanos , Masculino , Pandemias , Pneumonia Viral/diagnóstico , Prevalência , Medição de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Análise de Sobrevida
8.
Front Behav Neurosci ; 13: 294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32009914

RESUMO

Early life stress can result in persistent alterations of an individual's stress regulation through epigenetic modifications. Epigenetic alteration of the NR3C1 gene is associated with changes in the stress response system during infancy as measured by cortisol reactivity. Although autonomic nervous system (ANS) reactivity is a key component of the stress response, we have a limited understanding of the effects of NR3C1 DNA methylation on ANS reactivity. To examine this relation, ANS stress responses of term, 4-5-month-old healthy infants were elicited using the face-to-face still-face paradigm, which involved five, 2-min episodes. Two of these episodes were the "still-face" in which the mother was non-responsive to her infant. EKG was acquired continuously and analyzed in 30 s-intervals. Cheek swabs were collected, and DNA was extracted from buccal cells. Respiratory sinus arrhythmia (RSA) was measured as heart rate variability (HRV). Mean HRV was calculated for each 30-s "face to face" episode. DNA methylation of NR3C1 was calculated using bisulfite pyrosequencing. Percent DNA methylation was computed for each of the 13 NR3C1 CpG sites. The relations between mean HRV for each "face to face" episode and percent DNA methylation was examined averaged over CpG sites 1-6 and 7-13 and at each individual CpG site. Higher HRV at baseline, first reunion, and second still-face was related to greater methylation of NR3C1 CpG sites 1-6. Higher HRV at the second reunion was related to greater methylation of NR3C1 CpG sites 12 and 13. These data provide evidence that increased methylation of NR3C1 at CpG sites 12 and 13 are associated with increased activation of parasympathetic pathways as represented by increased HRV.

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