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Hereditary transthyretin-mediated amyloidosis (hATTR) is challenging to diagnose early owing to the heterogeneity of clinical presentation, which differs according to the TTR gene variant and its penetrance in each individual. The TTR variants seen most frequently in the UK and Ireland (T80A, V142I and V50M) differ to those commonly occurring in other geographic locations and warrant a specific consideration for diagnosis and genetic testing. In addition, recent availability of treatment for this condition has reinforced the need for a more consistent approach to the management of patients, including access to specialist services, genetic testing and counselling, and clinical investigation for families living in the UK and Ireland. A multidisciplinary panel of experts from the UK and Ireland was convened to identify the current challenges, provide recommendations, and develop a consensus for the diagnosis and screening of people with, or at risk of, hATTR. Over a series of meetings, experts shared their current practices and drafted, refined and approved a consensus statement. This consensus statement provides recommendations for three different groups: (1) people with symptoms raising a possibility of hATTR amyloidosis; (2) people with biopsy-confirmed hATTR amyloidosis; and (3) people without symptoms who may have hATTR amyloidosis (i.e. relatives of people with identified TTR variants). For each group, recommendations are made for the required steps for the diagnosis and follow-up of symptomatic patients, and for guidance on the specialist support for counselling and pre-symptomatic genetic testing of at-risk individuals. This guidance is intended to be practical and based on available evidence. The aim is for regional amyloid specialist centres to provide timely diagnosis, clinical screening, and treatment for individuals and their families with hATTR amyloidosis., (© 2022. The Author(s).)

Objective: The aim of this study was to determine whether serum urate (SU)-associated genetic variants differ in their influence on gout risk in people taking a diuretic compared to those not taking a diuretic., Methods: This research was conducted using the UK Biobank Resource (n = 359,876). Ten SU-associated single-nucleotide polymorphisms (SNP) were tested for their association with gout according to diuretic use. Gene-diuretic interactions for gout association were tested using a genetic risk score (GRS) and individual SNP by logistic regression adjusting for relevant confounders., Results: After adjustment, use of a loop diuretic was positively associated with prevalent gout (OR 2.34, 95% CI 2.08-2.63), but thiazide diuretics were inversely associated with prevalent gout (OR 0.60, 95% CI 0.55-0.66). Compared with a lower GRS (< mean), a higher GRS (≥ mean) was positively associated with gout in those not taking diuretics (OR 2.63, 2.49-2.79), in those taking loop diuretics (OR 2.04, 95% CI 1.65-2.53), in those taking thiazide diuretics (OR 2.70, 2.26-3.23), and in those taking thiazide-like diuretics (OR 2.11, 95% CI 1.37-3.25). No nonadditive gene-diuretic interactions were observed., Conclusion: In people taking diuretics, SU-associated genetic variants contribute strongly to gout risk, with a similar effect to that observed in those not taking a diuretic. These findings suggest that the contribution of genetic variants is not restricted to people with "primary" gout, and that genetic variants can play an important role in gout susceptibility in the presence of other risk factors.

Human prion diseases constitute a group of infectious and invariably fatal neurodegenerative disorders associated with misfolding of the prion protein. Variant Creutzfeldt-Jakob disease (vCJD) is a zoonotic prion disease linked to oral exposure to the infectious agent that causes bovine spongiform encephalopathy (BSE) in cattle. The most recent case of definite vCJD was heterozygous (MV) at polymorphic codon 129 of the prion protein gene PRNP while all of the previous 177 definite or probable vCJD cases who underwent genetic analysis were methionine homozygous (MM). Retrospective prevalence studies conducted on lympho-reticular tissue suggest that the number of asymptomatic vCJD carriers in the United Kingdom might be around 1 in 2000 people. In addition, there have been four known cases of the transmission of vCJD infection via blood transfusion. For these reasons, a sensitive, reliable, and fast diagnostic test is currently needed. We describe a rapid and highly sensitive seeding conversion assay that detects disease-associated prion protein in the brain and cerebrospinal fluid in vCJD after 48-96 h of amplification, with 100% sensitivity and specificity. This method can amplify prions from definite, probable, and possible vCJD cases from patients who are either MM or MV at PRNP-codon 129., (© 2017 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

This paper extends the account of a joint project of education and training of doctors and nurses in St. Petersburg, Russia funded by the Know How Fund Health Sector Small Partnership Scheme (Russia) (). It reports the findings of two evaluations of the project. The first, an external evaluation was carried on behalf of the sponsors, the KHF. The second was an 'insider' evaluation utilising a framework developed for the English National Board by Cranfield and Stoneman. The paper concludes with a discussion of issues arising from the cross-cultural evaluations.