RESUMO
BACKGROUND: Individuals infected with SARS-CoV-2 vary greatly in their disease severity, ranging from asymptomatic infection to severe disease. The regulation of gene expression is an important mechanism in the host immune response and can modulate the outcome of the disease. miRNAs play important roles in post-transcriptional regulation with consequences on downstream molecular and cellular host immune response processes. The nature and magnitude of miRNA perturbations associated with blood phenotypes and intensive care unit (ICU) admission in COVID-19 are poorly understood. RESULTS: We combined multi-omics profiling-genotyping, miRNA and RNA expression, measured at the time of hospital admission soon after the onset of COVID-19 symptoms-with phenotypes from electronic health records to understand how miRNA expression contributes to variation in disease severity in a diverse cohort of 259 unvaccinated patients in Abu Dhabi, United Arab Emirates. We analyzed 62 clinical variables and expression levels of 632 miRNAs measured at admission and identified 97 miRNAs associated with 8 blood phenotypes significantly associated with later ICU admission. Integrative miRNA-mRNA cross-correlation analysis identified multiple miRNA-mRNA-blood endophenotype associations and revealed the effect of miR-143-3p on neutrophil count mediated by the expression of its target gene BCL2. We report 168 significant cis-miRNA expression quantitative trait loci, 57 of which implicate miRNAs associated with either ICU admission or a blood endophenotype. CONCLUSIONS: This systems genetics study has given rise to a genomic picture of the architecture of whole blood miRNAs in unvaccinated COVID-19 patients and pinpoints post-transcriptional regulation as a potential mechanism that impacts blood traits underlying COVID-19 severity. The results also highlight the impact of host genetic regulatory control of miRNA expression in early stages of COVID-19 disease.
Assuntos
COVID-19 , MicroRNAs , Humanos , COVID-19/genética , SARS-CoV-2/genética , Genômica , MicroRNAs/genética , RNA MensageiroRESUMO
A 23-year-old man presented with a history characterized by a myoclonic syndrome developing over a period of seven years. Predominant symptoms were intention and activity myoclonus, generalized epileptic seizures occurring infrequently from the age of 20, a slowly progressive cerebellar syndrome first apparent at 19 years, and the sudden onset of loss of visual acuity at 19, which then partially regressed; optic atrophy and clinical and campimetric signs were suggestive of Leber's disease. Intellectual ability was not affected. E.E.G. records showed generalized spike-waves with photosensitivity, progressive reduction in basal rhythm, and sleep organization disturbances with focal abnormalities. Obvious clinical signs of muscle disease were lacking but muscle biopsy confirmed the presence of a mitochondrial myopathy (ragged-red fibers). An indefinite history of familial neurological disease was obtained. Diagnosis was established as myoclonic cerebellar dyssynergy with spastic hereditary ataxia and Leber's disease. Their association with a mitochondrial myopathy has been previously reported by Tsairis et al, Fukuhara et al, Fitzimons et al (familial case), and Niedermeyer et al (sporadic case). In spite of the non-specific nature of associated mitochondrial abnormalities, all these cases would appear to correspond to a single nosological entity.
Assuntos
Ataxia Cerebelar/diagnóstico , Epilepsias Mioclônicas/diagnóstico , Mitocôndrias Musculares/ultraestrutura , Dissinergia Cerebelar Mioclônica/diagnóstico , Degeneração Neural , Atrofia Óptica/diagnóstico , Doenças da Medula Espinal/diagnóstico , Adulto , Ataxia Cerebelar/genética , Eletroencefalografia , Eletromiografia , Epilepsias Mioclônicas/genética , Potenciais Evocados , Humanos , Masculino , Contração Muscular , Dissinergia Cerebelar Mioclônica/genética , Doenças da Medula Espinal/genética , SíndromeRESUMO
OBJECTIVES: In order to evaluate the impact of recent progress in anesthesia and cataract surgery, we conducted a national survey in France to determine which techniques are used. METHODS: A questionnaire was sent to the most representative French ophthalmology teams: 66 teams participated in the survey. RESULTS: Seventy-one percent of the surgeons routinely used phacoemulsification: 91% of the anesthesists prefer locoregional anesthesia: contraindications most often involved general health status (89%). Ambulatory anesthesia was preferred by 16.7% of the teams. CONCLUSION: Phacoemulsification under peribulbal anesthesia is currently the technique most frequently used in cataract surgery in France. Ambulatory anesthesia is not yet widely used for this type of surgery.