Pulmonary embolism severity before and during the COVID-19 pandemic

OBJECTIVES: Early in the coronavirus 2019 (COVID-19) pandemic, a high frequency of pulmonary embolism was identified. This audit aims to assess the frequency and severity of pulmonary embolism in 2020 compared to 2019. METHODS: In this retrospective audit, we compared computed tomography pulmonary angiography (CTPA) frequency and pulmonary embolism severity in April and May 2020, compared to 2019. Pulmonary embolism severity was assessed with the Modified Miller score and the presence of right heart strain was assessed. Demographic information and 30-day mortality was identified from electronic health records. RESULTS: In April 2020, there was a 17% reduction in the number of CTPA performed and an increase in the proportion identifying pulmonary embolism (26%, n = 68/265 vs 15%, n = 47/320, p < 0.001), compared to April 2019. Patients with pulmonary embolism in 2020 had more comorbidities (p = 0.026), but similar age and sex compared to 2019. There was no difference in pulmonary embolism severity in 2020 compared to 2019, but there was an increased frequency of right heart strain in May 2020 (29 vs 12%, p = 0.029). Amongst 18 patients with COVID-19 and pulmonary embolism, there was a larger proportion of males and an increased 30 day mortality (28% vs 6%, p = 0.008). CONCLUSION: During the COVID-19 pandemic, there was a reduction in the number of CTPA scans performed and an increase in the frequency of CTPA scans positive for pulmonary embolism. Patients with both COVID-19 and pulmonary embolism had an increased risk of 30-day mortality compared to those without COVID-19. ADVANCES IN KNOWLEDGE: During the COVID-19 pandemic, the number of CTPA performed decreased and the proportion of positive CTPA increased. Patients with both pulmonary embolism and COVID-19 had worse outcomes compared to those with pulmonary embolism alone

Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

To profile the messenger RNA (mRNA) expression for the 23 known genes of matrix metalloproteinases (MMPs), 19 genes of ADAMTS, 4 genes of tissue inhibitors of metalloproteinases (TIMPs), and ADAM genes 8, 10, 12, and 17 in normal, painful, and ruptured Achilles tendons. Tendon samples were obtained from cadavers or from patients undergoing surgical procedures to treat chronic painful tendinopathy or ruptured tendon. Total RNA was extracted and mRNA expression was analyzed by quantitative real-time reverse transcription–polymerase chain reaction, normalized to 18S ribosomal RNA. In comparing expression of all genes, the normal, painful, and ruptured Achilles tendon groups each had a distinct mRNA expression signature. Three mRNA were not detected and 14 showed no significant difference in expression levels between the groups. Statistically significant (P < 0.05) differences in mRNA expression, when adjusted for age, included lower levels of MMPs 3 and 10 and TIMP-3 and higher levels of ADAM-12 and MMP-23 in painful compared with normal tendons, and lower levels of MMPs 3 and 7 and TIMPs 2, 3, and 4 and higher levels of ADAMs 8 and 12, MMPs 1, 9, 19, and 25, and TIMP-1 in ruptured compared with normal tendons. The distinct mRNA profile of each tendon group suggests differences in extracellular proteolytic activity, which would affect the production and remodeling of the tendon extracellular matrix. Some proteolytic activities are implicated in the maintenance of normal tendon, while chronically painful tendons and ruptured tendons are shown to be distinct groups. These data will provide a foundation for further study of the role and activity of many of these enzymes that underlie the pathologic processes in the tendon

The Proteolipid Protein Promoter Drives Expression outside of the Oligodendrocyte Lineage during Embryonic and Early Postnatal Development

The proteolipid protein (Plp) gene promoter is responsible for driving expression of one of the major components of myelin – PLP and its splice variant DM-20. Both products are classically thought to express predominantly in oligodendrocytes. However, accumulating evidence suggests Plp expression is more widespread than previously thought. In an attempt to create a mouse model for inducing oligodendrocyte-specific gene deletions, we have generated transgenic mice expressing a Cre recombinase cDNA under control of the mouse Plp promoter. We demonstrate Plp promoter driven Cre expression is restricted predominantly to mature oligodendrocytes of the central nervous system (CNS) at postnatal day 28. However, crosses into the Rosa26LacZ and mT/mG reporter mouse lines reveal robust and widespread Cre activity in neuronal tissues at E15.5 and E10.5 that is not strictly oligodendrocyte lineage specific. By P28, all CNS tissues examined displayed high levels of reporter gene expression well outside of defined white matter zones. Importantly, our study reinforces the emerging idea that Plp promoter activity is not restricted to the myelinating cell lineage, but rather, has widespread activity both during embryonic and early postnatal development in the CNS. Specificity of the promoter to the oligodendrocyte cell lineage, as shown through the use of a tamoxifen inducible Plp-CreERt line, occurs only at later postnatal stages. Understanding the temporal shift in Plp driven expression is of consequence when designing experimental models to study oligodendrocyte biology

Erratum: Author Correction: Identification of genes required for eye development by high-throughput screening of mouse knockouts.

[This corrects the article DOI: 10.1038/s42003-018-0226-0.]

Translation and validation of the Brazilian version of the Cerebral Palsy Quality of Life Questionnaire for Children – child report

AbstractObjectiveTo verify the psychometric properties of the Cerebral Palsy: Quality of Life Questionnaire Children – child report (CPQol-Child) questionnaire, after it was translated and culturally adapted into Brazilian Portuguese.MethodsAfter the translation and cultural adaptation of the tool into Brazilian Portuguese, the questionnaire was answered by 65 children with cerebral palsy, aged 9–12 years. The intraclass correlation coefficient and Cronbach's alpha were used to assess the reliability and internal consistency of the tool and its validity was analyzed through the association between CPQol-Child: self-report tool and Kidscreen-10 using Pearson's correlation coefficient.ResultsInternal consistency ranged from 0.6579 to 0.8861, the intraobserver reliability from 0.405 to 0.894, and the interobserver from 0.537 to 0.937. There was a weak correlation between the participation domain and physical health of CPQol-Child: self-report tool and Kidscreen-10.ConclusionThe analysis suggests that the tool has psychometric acceptability for the Brazilian population

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function