Extensive Bilateral Extraluminal Perivascular Pulmonary Haemorrhage Associated with Stanford Type A Aortic Dissection

We present the case of an 80-year old man with a Stanford Type A dissecting thoracic aortic aneurysm plus the unusual CT finding of extramural haemorrhage along the pulmonary vessels. The clinical and radiological picture has an extremely high mortalit

De Novo Loss-of-Function Mutations in USP9X Cause a Female-Specific Recognizable Syndrome with Developmental Delay and Congenital Malformations

Mutations in more than a hundred genes have been reported to cause X-linked recessive intellectual disability (ID) mainly in males. In contrast, the number of identified X-linked genes in which de novo mutations specifically cause ID in females is limited. Here, we report 17 females with de novo loss-of-function mutations in USP9X, encoding a highly conserved deubiquitinating enzyme. The females in our study have a specific phenotype that includes ID/developmental delay (DD), characteristic facial features, short stature, and distinct congenital malformations comprising choanal atresia, anal abnormalities, post-axial polydactyly, heart defects, hypomastia, cleft palate/bifid uvula, progressive scoliosis, and structural brain abnormalities. Four females from our cohort were identified by targeted genetic testing because their phenotype was suggestive for USP9X mutations. In several females, pigment changes along Blaschko lines and body asymmetry were observed, which is probably related to differential (escape from) X-inactivation between tissues. Expression studies on both mRNA and protein level in affected-female-derived fibroblasts showed significant reduction of USP9X level, confirming the loss-of-function effect of the identified mutations. Given that some features of affected females are also reported in known ciliopathy syndromes, we examined the role of USP9X in the primary cilium and found that endogenous USP9X localizes along the length of the ciliary axoneme, indicating that its loss of function could indeed disrupt cilium-regulated processes. Absence of dysregulated ciliary parameters in affected female-derived fibroblasts, however, points toward spatiotemporal specificity of ciliary USP9X (dys-)function

Proceedings of the 13th annual conference of INEBRIA

CITATION: Watson, R., et al. 2016. Proceedings of the 13th annual conference of INEBRIA. Addiction Science & Clinical Practice, 11:13, doi:10.1186/s13722-016-0062-9.The original publication is available at https://ascpjournal.biomedcentral.comENGLISH SUMMARY : Meeting abstracts.https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-016-0062-9Publisher's versio

Acute Legionella pneumophila infection masquerading as acute alcoholic hepatitis

A middle-aged man had deteriorated rapidly in hospital after being misdiagnosed with acute alcoholic hepatitis. Acute Legionnaires disease (Legionellosis) was subsequently diagnosed on rapid antigen urinary testing and further confirmed serologically. This led to appropriate antibiotic treatment and complete clinical resolution. Physicians caring for patients with alcoholrelated liver disease should consider Legionella pneumophila in their differential diagnosis even with a paucity of respiratory symptoms. Copyright 2013 BMJ Publishing Group. All rights reserved

A case of Aggregatibacter actinomycetemcomitans endocarditis presenting as quadriceps myositis

An 80 year old female was admitted with an eight week history of fever associated with painful swelling of her right thigh, and a long history of poor dentition. Culture of blood stained fluid aspirated from the abscess grew Aggregatibacter actinomycetemcomitans (Aa) sensitive to ampicillin and cephalosporins. Transoesophageal echocardiography indicated endocarditis. Four weeks treatment with intravenous ceftriaxone and appropriate dental care was followed by full recovery

Predictors of endometrial carcinoma in patients with atypical endometrial hyperplasia at a tertiary gynaecological cancer centre in Western Australia

© 2021 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists Aim: Our objective was to assess clinical and pathological factors associated with a final diagnosis of endometrial carcinoma in patients with atypical endometrial hyperplasia with a particular emphasis on the grading of atypia. Materials and methods: A retrospective review over five years on patients (N = 97) who underwent hysterectomy for a diagnosis of atypical endometrial hyperplasia at a statewide public tertiary gynaecologic oncology centre. Clinical and pathological characteristics were obtained. Results: The rate of concurrent endometrial carcinoma was 34% (n = 33) with most being stage 1A endometrioid. A significant group difference was reported for age at diagnosis (t = −2.20 P = 0.031 d = 0.43) with carcinoma patients on average older (Mage = 60.2 (8.9) years) than patients without carcinoma (Mage = 55.5 (12.3) years). No significant group differences were found for body mass index, endometrial thickness or time between diagnosis and treatment. Significantly higher rates of carcinoma were reported in patients with moderate atypical hyperplasia (27.6%) and severe atypical hyperplasia (66.7%), compared to mild atypical hyperplasia (7.1%). Only severe atypical hyperplasia (odds ratio (OR) = 21.5, 95% CI 2.8–163.1, P = 0.003) and postmenopausal status (OR = 13.2, 95% CI 1.3–139.0, P = 0.032) significantly increased the risk of carcinoma in a multivariate model. Conclusion: Severe atypical hyperplasia and postmenopausal status were significant predictors of concurrent endometrial carcinoma in patients with atypical endometrial hyperplasia. The grading of atypical hyperplasia may be utilised by gynaecologic oncologists in the triage and referral process of managing these patients; however, the grading system requires external validation in larger prospective studies

Expression and Characterization of a Novel Recombinant Version of the Secreted Human Mucin MUC5AC in Airway Cell Lines

Molecular manipulation and expression of mucins, large glycoproteins that provide the structural framework of mucus, are challenging due to mucins’ size and numerous domains, including variable number tandem repeat (VNTRs) regions that are sites of O-glycosylation. Only individual human mucin domains have been expressed in mammalian cells. We produced recombinant versions of MUC5AC, a major secreted mucin in the respiratory tract, encoding the N-terminus, C-terminus, N- and C-termini together, and N- and C-termini interspersed with two native tandem repeat sequences (N+2TR+C) in both tracheal and bronchial cell lines. The latter protein contains all of the functional domains required for the biosynthesis and secretion of glycosylated mucin. The N-terminus protein was found in monomeric and higher molecular mass forms suggesting that secreted MUC5AC may form a branched netlike structure analogous to that described for MUC2. At the C-terminus, proteins underwent cleavage, polymerization, and glycosylation. Thus, they appear to undergo pivotal processing steps as predicted for native MUC5AC, which is analogous to that for other individual recombinant mucin domains. Secretion occurred when cells were grown on transwell filter inserts but not on plastic, indicating that the extracellular environment likely plays a role in mucin processing. The secreted N+2TR+C protein differed in molecular mass from the intracellular form, indicating that additional processing occurred. These recombinant proteins, expressed in different backgrounds, can potentially address the role of different mucin domains on MUC5AC processing and function as well as the role of MUC5AC in health and disease