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A collaborative study between the Kennedy Institute and MRC Weatherall Institute of Molecular Medicine (MRC WIMM) identifies a new pathway that limits the severity of inflammatory skin disease.
Ruxolitinib in Patients With Corticosteroid-Refractory or Corticosteroid-Dependent Chronic Graft-Versus-Host Disease: 3-Year Final Analysis of the Phase III REACH3 Study.
In REACH3 (ClinicalTrials.gov identifier: NCT03112603), ruxolitinib was investigated versus best available therapy (BAT) for 3 years in patients with steroid-refractory/dependent chronic graft-versus-host-disease (SR/D-cGVHD). Patients received ruxolitinib (10 mg twice daily) or BAT for 24 weeks; thereafter (we…
Head-down tilt 15° increases cerebral perfusion before recanalization in acute ischemic stroke. A pre-clinical MRI study.
We investigated the therapeutic effect of head-down tilt at -15° (HDT15) on cerebral collateral flow and early infarct growth in a rat model of large vessel occlusion stroke, using multi-modal MRI. Endovascular occlusion of the proximal middle cerebral artery was induced for 90 min in Wistar rats (n = 28), follo…
Exploring the lived experiences of early/mid-career female academic GPs in the UK: a qualitative study
BACKGROUND: Women are under-represented within academic general practice, particularly after mid-career. AIM: To explore the lived experiences of early/mid-career female academic GPs and inform ways to reduce attrition through the GP academic career path. METHOD: Adapted Biographical Narrativ…
Characterization of quinazolinone calcilytic therapy for autosomal dominant hypocalcemia type 1 (ADH1).
Gain-of-function mutations of the calcium-sensing receptor (CaSR) result in autosomal dominant hypocalcemia type 1 (ADH1), which may cause symptomatic hypocalcemia with low parathyroid hormone concentrations. Negative allosteric CaSR modulators, known as calcilytics, have potential as a targeted ADH1 t…
Engineering antisense oligonucleotides for targeted mRNA degradation through lysosomal trafficking.
Antisense oligonucleotides (ASOs) can modulate gene expression at the mRNA level, providing the ability to tackle conventionally undruggable targets and usher in an era of personalized medicine. A key mode of action for ASOs relies upon RNase H-engagement in the nucleus, however, most mature mRNA is…
Stent-Retriever Thrombectomy in STEMI With Large Thrombus Burden: The RETRIEVE AMI Randomized Trial.
BACKGROUND: Percutaneous coronary intervention (PCI) restores epicardial flow in ST-segment elevation myocardial infarction (STEMI), but large thrombus burden (LTB) can impair myocardial perfusion due to embolization. While manual aspiration (MA) devices have limited efficacy in STEMI, the success of sten…
Early Atrial Remodeling Drives Arrhythmia in Fabry Disease.
BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by α-Gal A (α-galactosidase A) deficiency, resulting in multiorgan accumulation of sphingolipid, namely globotriaosylceramide. This triggers ventricular myocardial hypertrophy, fibrosis, and inflammation, driving arrhythmi…
Self-Assembled Peptide-Based Fibrous Hydrogel as a Biological Catalytic Scaffold for Nitric Oxide Generation and Encapsulation.
Biomolecular hydrogels are promising scaffolds for biomedical applications ranging from controlled drug release to personalized medicine. However, existing macromolecular scaffolds for nitric oxide (NO) release face several challenges, such as a low payload capacity, rapid release, and limited biocompatibility.…
Rapidly self-healing electronic skin for machine learning-assisted physiological and movement evaluation.
Emerging electronic skins (E-Skins) offer continuous, real-time electrophysiological monitoring. However, daily mechanical scratches compromise their functionality, underscoring urgent need for self-healing E-Skins resistant to mechanical damage. Current materials have slow recovery times, impeding reli…
New options and techniques in reconstructing the sacrum.
PURPOSE: Sacral tumours, both benign and malignant, often necessitate surgical removal (sacrectomy) to achieve optimal outcomes. However, this procedure disrupts the pelvic ring's stability, potentially leading to pain and limited mobility. METHODS: This article explores innovative approaches to recon…
Synthesis and characterization of amine-functionalized graphene as a nitric oxide-generating coating for vascular stents.
Drug-eluting stents are commonly utilized for the treatment of coronary artery disease, where they maintain vessel patency and prevent restenosis. However, problems with prolonged vascular healing, late thrombosis, and neoatherosclerosis persist; these could potentially be addressed via the local gen…
The emergence of Fanconi anaemia type S: a phenotypic spectrum of biallelic BRCA1 mutations.
BRCA1 is involved in the Fanconi anaemia (FA) pathway, which coordinates repair of DNA interstrand cross-links. FA is a rare genetic disorder characterised by bone marrow failure, cancer predisposition and congenital abnormalities, caused by biallelic mutations affecting proteins in the FA pathway. Germline m…
Clinical significance of preleukemic somatic GATA1 mutations in children with Down syndrome.
Children with Down syndrome (DS) have a high risk of GATA1-associated myeloid leukemia (ML-DS) before age 4. Somatic N-terminal GATA1 mutations (GATA1s) are necessary, but not sufficient, for ML-DS, but their significance at birth for individual babies and whether mutations occur after birth is unclear.…
Models of Cerebrovascular Reactivity in BOLD-fMRI and Transcranial Doppler Ultrasound.
The ability of cerebrovasculature to respond to meet tissue demands is vital for normal brain function and health. Cerebrovascular reactivity (CVR), a measure of the responsiveness of cerebrovasculature to vasoactive stimuli, is a valuable tool for evaluating cerebrovascular health. While CVR is commonly…