Delandistrogene moxeparvovec is an rAAVrh74 vector-based gene transfer therapy that delivers a transgene encoding delandistrogene moxeparvovec micro-dystrophin, an engineered, functional form of dystrophin shown to stabilize or slow disease progression in DMD. It is approved in the US and in other select countries. Two serious adverse event cases of immune-mediated myositis (IMM) were reported in the phase Ib ENDEAVOR trial (NCT04626674).
View Article and Find Full Text PDFBackground: Outcome measurement is essential to progress clinical practice and improve patient care.
Aim: To develop a Core Outcome Set for best care for the dying person.
Design: We followed the Core Outcome Measures in Effectiveness Trials (COMET) Initiative guidelines, which involved identifying potential outcomes via a systematic literature review (n = 619 papers) and from participants in the "iLIVE" project (10 countries: 101 patients, 37 family members, 63 clinicians), followed by a two-round Delphi study, and a consensus meeting.
Correction for 'Impacts of trace level chromium on formation of superoxide within uranyl triperoxide complexes' by Sarah K. Scherrer , , 2024, , 10584-10587, https://doi.org/10.
View Article and Find Full Text PDFHen egg-white lysozyme (HEWL) is a widely used model protein in crystallographic studies and its enzymatic mechanism has been extensively investigated for decades. Despite this, the interaction between the reaction intermediate and the catalytic Asp52, as well as the orientation of Asn44 and Asn46 side chains, remain ambiguous. Here, we report the crystal structures of perdeuterated HEWL and DO buffer-exchanged HEWL from 0.
View Article and Find Full Text PDFBackground: Health care staff should be given the opportunity to participate in research, but recruiting clinicians via their employing organisation is not always straightforward or quick in the UK. Unlike many countries outside the UK, very low-risk survey, interview or focus group studies can be subject to some of the same governance approval procedures as interventional studies. An exemplar study carried out by the NIHR funded Palliative Care Research Partnership North West Coast is used to highlight the challenges still faced by researchers and health care organisations when setting up a low-risk staff study across multiple NHS and non-NHS sites.
View Article and Find Full Text PDFThe use of archival formalin-fixed paraffin-embedded (FFPE) tissue samples for biochemical analyses is problematic because of the formation of a Schiff base, leading to low protein and metabolite yields during analytical extractions. Here, we overcome this issue using a unified protocol on FFPE tissue for metabolomics and proteomics analyses. Using 20 mg of wet mass tissue, this protocol consistently extracted more than 50 metabolites (across 11 classes of metabolites) and over 900 proteins.
View Article and Find Full Text PDFIntroduction: Community-level disadvantage is associated with reduced quality of life after burn injury. We evaluated the association between community-level disadvantage and return to work after burn injury.
Methods: A multicenter burn injury database was queried from 1998-2021.
Understanding species' critical habitat requirements is crucial for effective conservation and management. However, such information can be challenging to obtain, particularly for highly mobile, wide-ranging species such as cetaceans. In the absence of systematic surveys, alternative economically viable methods are needed, such as the use of data collected from platforms of opportunity, and modelling techniques to predict species distribution in un-surveyed areas.
View Article and Find Full Text PDFThe early accumulation of AD pathology such as Aβ and tau in cognitively normal older people is predictive of cognitive decline, but it has been difficult to dissociate the cognitive effects of these two proteins. Early Aβ and tau target distinct brain regions that have different functional roles. Here, we assessed specific longitudinal pathology-cognition associations in seventy-six cognitively normal older adults from the Berkeley Aging Cohort Study who underwent longitudinal PiB PET, FTP PET, and cognitive assessments.
View Article and Find Full Text PDFBackground: Attempting to improve emergency care (EC) advanced clinical practitioner (ACP) training, Health Education England (HEE) South West (SW) implemented a pilot, whereby emergency departments (ED) were provided with enhanced funding and support to help ED consultants deliver teaching and supervision to EC ACPs to ensure more timely completion of EC ACP training compared with previous cohorts training in the region.We explored the experiences of trainee EC ACPs and consultant EC ACP leads working in EDs, which had implemented the new regional pilot.
Methods: We used a qualitative design to conduct semi-structured interviews with trainee EC ACPs and consultant EC ACP leads across five EDs that had implemented the HEE SW pilot.
Antiretroviral therapy (ART) has reduced the mortality and morbidity associated with HIV. However, irrespective of treatment, people living with HIV remain at a higher risk of developing non-AIDS-associated diseases. In 2019, the World Health Organization recommended the transition from efavirenz (EFV)- to dolutegravir (DTG)-based ART.
View Article and Find Full Text PDFTransforming Growth Factor-β (TGF-β) can have both tumour-promoting and tumour-suppressing activity in breast cancer. Elucidating the key downstream mediators of pro-tumorigenic TGF-β signalling in this context could potentially give rise to new therapeutic opportunities and/or identify biomarkers for anti-TGF-β directed therapy. Here, we identify (also known as innate immunity activator ) as a novel TGF-β target gene which is induced in a SMAD3-dependent but SMAD2/SMAD4-independent manner in human and murine cell lines.
View Article and Find Full Text PDFAlthough the World Health Organization's (WHO's) framework on social and structural determinants of health and health inequities (SSDHHI) has done much to raise awareness of these determinants, it does not go far enough in considerations of politics and power. The framework has become more de-politicized since its publication, with the definition of social determinants shifting toward downstream and individualized factors. In the meantime, new research fields on legal, commercial and political determinants of health and health inequities have emerged; however, these have not become integrated adequately into broader SSDHHI frameworks.
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