The importance of establishing genetic phase in clinical medicine.

Haplotyping or determination of genetic phase has always played a pivotal role in MHC (HLA studies) both in helping to understand inheritance patterns in diseases such as type 1 diabetes (T1D) and in ensuring better matching in transplantation scenarios such as haematopoietic stem cell transplantation (HSCT), using donors genetically related to the patient. In recent years the need to establish genetic phase in a number of clinical scenarios has become apparent. These include: Genetic phasing for hematopoietic stem cell transplants using unrelated donors, where the HLA haplotypes are not known but where haplotype-matched recipients fare better clinically than allele matched, but haplotype mismatched patients.

Management of Hsp90-Dependent Protein Folding by Small Molecules Targeting the Aha1 Co-Chaperone.

Hsp90 plays an important role in health and is a therapeutic target for managing misfolding disease. Compounds that disrupt co-chaperone delivery of clients to Hsp90 target a subset of Hsp90 activities, thereby minimizing the toxicity of pan-Hsp90 inhibitors. Here, we have identified SEW04784 as a first-in-class inhibitor of the Aha1-stimulated Hsp90 ATPase activity without inhibiting basal Hsp90 ATPase.

The Perceptions and Rehabilitation Experience of Older People After Falling in the Hospital.

Purpose: Falls are a major cause of disability and mortality due to injury. To reduce fall rates and improve health outcomes, it is important to design services based on patient experience and engagement. This study aimed to explore the experiences of older patients who fell during their hospital stay.

Evidence of decreased HPV vaccine acceptance in Polish communities within Scotland.

Human papillomavirus (HPV) vaccines are currently utilised globally in national immunisation programmes. Many new European migrants have settled in the United Kingdom (UK) since the 2004 European Union expansion with approximately 91,000 Polish people resident in Scotland. Following anecdotal reports from several NHS Boards within Scotland of lower HPV vaccine uptake in Polish communities compared with other ethnic minorities, an extract containing both forename and surname, was taken from the Scottish Immunisation Recall System (SIRS) for all girls in S2 and S3 in school years 2014/15 to 2016/17.

Use of a High-Throughput Phenotypic Screening Strategy to Identify Amplifiers, a Novel Pharmacological Class of Small Molecules That Exhibit Functional Synergy with Potentiators and Correctors.

Cystic fibrosis (CF) is a lethal genetic disorder caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite recent groundbreaking approval of genotype-specific small-molecule drugs, a significant portion of CF patients still lack effective therapeutic options that address the underlying cause of the disease. Through a phenotypic high-throughput screen of approximately 54,000 small molecules, we identified a novel class of CFTR modulators called amplifiers.