Adaptive Long-Read Sequencing Reveals GGC Repeat Expansion in ZFHX3 Associated with Spinocerebellar Ataxia Type 4.

BACKGROUND: Spinocerebellar ataxia type 4 (SCA4) is an autosomal dominant ataxia with invariable sensory neuropathy originally described in a family with Swedish ancestry residing in Utah more than 25 years ago. Despite tight linkage to the 16q22 region, the molecular diagnosis has since remained elusive. OBJECTIVES: Inspired by pathogenic structural variation implicated in other 16q-ataxias with linkage to the same locus, we revisited the index SCA4 cases from the Utah family using novel technologies to investigate structural variation within the candidate region. METHODS: We adopted a targeted long-read sequencing approach with adaptive sampling on the Oxford Nanopore Technologies (ONT) platform that enables the detection of segregating structural variants within a genomic region without a priori assumptions about any variant features. RESULTS: Using this approach, we found a heterozygous (GGC)n repeat expansion in the last coding exon of the zinc finger homeobox 3 (ZFHX3) gene that segregates with disease, ranging between 48 and 57 GGC repeats in affected probands. This finding was replicated in a separate family with SCA4. Furthermore, the estimation of this GGC repeat size in short-read whole genome sequencing (WGS) data of 21,836 individuals recruited to the 100,000 Genomes Project in the UK and our in-house dataset of 11,258 exomes did not reveal any pathogenic repeats, indicating that the variant is ultrarare. CONCLUSIONS: These findings support the utility of adaptive long-read sequencing as a powerful tool to decipher causative structural variation in unsolved cases of inherited neurological disease. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Pairing lab and field studies to predict thermal performance of wild fish.

In thermally variable ecosystems, temperatures can change extensively on hourly and seasonal timescales requiring ectotherms to possess a broad thermal tolerance (critical thermal minima [CTmin] and maxima [CTmax]). However, whether fish acclimate in the laboratory similarly as they acclimatize in the field under comparable thermal variation is unclear. We used temperature data from a tidal salt marsh to design 21-day lab-acclimation treatments (static: 12, 17, 22, 27 °C; daily variation with mean 22 °C: i) range 17-27 °C, ii) range 17-27 °C with irregular extremes within 12-32 °C). We compared thermal limits in lab-acclimated and field-acclimatized eurythermal arrow goby (Clevelandia ios). Variable temperature-acclimated and acclimatized fish had similar CTmin and CTmax. Notably, arrow gobies showed rapid plasticity in their absolute thermal tolerance within one tidal cycle. The daily mean and max temperatures experienced were positively related to CTmax and CTmin, respectively. This study demonstrates that ecologically informed lab acclimation treatments can yield tolerance results that are applicable to wild fish.

Evaluating the role of primary care pharmacy technicians in antimicrobial stewardship (AMS) and acne management using TARGET resources.

Background: Inappropriate antibiotic prescribing is accelerating antimicrobial resistance (AMR) (Antibiotic resistant infections and associated deaths increase  https://www.gov.uk/government/news/antibiotic-resistant-infections-and-associated-deaths-increase). Pharmacy professionals (pharmacists and pharmacy technicians) promote good antibiotic prescribing practice. The traditional role of pharmacy technicians in supporting pharmacists and patients has expanded alongside the clinical expansion of pharmacist roles. (Boughen M, Fenn T. Practice, skill mix and education: the evolving role of pharmacy technicians in Great Britain. Pharmacy (Basel) 2020; 8(2): 50. doi:10.3390/pharmacy8020050) This paper focuses on the opinion of pharmacy technicians and their role in the review of acne management and the evaluation of the UKHSA TARGET acne 'How to…' review resources. Aims and objectives: To explore the impact of the TARGET resources on the capability, opportunity and motivation of pharmacy technicians in general practice in managing patients with acne.To evaluate the usefulness of the acne 'How to…' review resources. Materials and methods: A primarily quantitative study using an electronic survey asking UK-based pharmacy technicians to rate their agreement on a five-point Likert scale with 21 predefined statements, themed on the COM-B model and usefulness of the TARGET resources for acne. Discussion: The survey found that capability and opportunity in managing acne in the group familiar with TARGET resources was higher than the group not familiar with TARGET resources. Scores for motivation in both groups were high; pharmacy technicians have the motivation to undertake infection management roles, whether or not they are familiar with the TARGET toolkit.The acne 'How to…' review resources were overall rated as useful in supporting the review of patients with acne. Conclusion: The TARGET materials are effective resources that helps to upskill pharmacy technicians in the area of AMS, increasing capability and opportunity in the management of acne.

Pilot and quantitative evaluation of the TARGET acne toolkit by UK pharmacy professionals working in general practice.

BACKGROUND: Acne vulgaris (acne) is a common skin condition sometimes needing topical or oral antibiotic treatment. Pharmacists and pharmacy technicians (together known as pharmacy professionals) working in general practice are well placed to ensure their appropriate use. OBJECTIVES: The objectives of this study are to pilot an evidence-based intervention ('How to…' tool) to review treatments in the management of acne and evaluate the capability, opportunity, motivation and behaviour (COM-B) of pharmacy professionals working in general practice before and after the use of this tool. DESIGN, SETTING AND PARTICIPANTS: A quantitative electronic survey was developed asking UK-based pharmacy professionals working in general practice to rate their agreement with 21 predefined statements related to the COM-B model. INTERVENTION: Participants were sent an initial survey, given time to access and use the 'How to…' acne resources and then sent a follow-up survey 2 weeks later. OUTCOME MEASURES: Primary outcome was change in 5-point Likert scale responses to statements on capability, opportunity and motivation in the management of acne. Secondary outcome was the perceived usefulness of the toolkit. RESULTS: 141 pharmacy professionals completed the initial survey; 19 completed the follow-up survey. Significant improvement in the 5-point Likert scale means that responses were observed after implementation of the acne 'How to' resource; capability 3.68 (SD 0.40) versus 4.11 (SD 0.29), t(189) =-5.10, p <0.001; opportunity 3.85 (SD 0.24) versus 4.07 (SD 0.29), t(94)=-2.50, p=0.007 and motivation 4.35 (SD 0.47) versus 4.51 (SD 0.32), t(113)=-2.51, p=0.007. The 'How to' resources were rated as being useful (4.06, SD 0.12) and supportive (4.08, SD 0.18) to help pharmacy professionals in all areas of managing acne. CONCLUSION: The acne 'How to' resources are useful to pharmacy professionals in managing acne in general practice and may improve their capability. Further work is needed with greater numbers of participants to demonstrate generalisability of this outcome.

How can community pharmacists be supported to manage skin conditions? A multistage stakeholder research prioritisation exercise.

OBJECTIVE: To establish research priorities which will support the development and delivery of community pharmacy initiatives for the management of skin conditions. DESIGN: An iterative, multistage stakeholder consultation consisting of online survey, participant workshops and prioritisation meeting. SETTING: All data collection took place online with participants completing a survey (delivered via the JISC Online Survey platform, between July 2021 and January 2022) and participating in online workshops and meetings (hosted on Microsoft Teams between April and July 2022). PARTICIPANTS: 174 community pharmacists and pharmacy staff completed the online survey.53 participants participated in the exploratory workshops (19 community pharmacists, 4 non-pharmacist members of pharmacy staff and 30 members of the public). 4 healthcare professionals who were unable to attend a workshop participated in a one-to-one interview.29 participants from the workshops took part in the prioritisation meeting (5 pharmacists/pharmacy staff, 1 other healthcare professional and 23 members of the public). RESULTS: Five broad areas of potential research need were identified in the online survey: (1) identifying and diagnosing skin conditions; (2) skin conditions in skin of colour; (3) when to refer skin conditions; (4) disease-specific concerns and (5) product-specific concerns.These were explored and refined in the workshops to establish 10 potential areas for research, which will support pharmacists in managing skin conditions. These were ranked in the prioritisation meeting. Among those prioritised were topics which consider how pharmacists work with other healthcare professionals to identify and manage skin conditions. CONCLUSIONS: Survey responses and stakeholder workshops all recognised the potential for community pharmacists to play an active role in the management of common skin conditions. Future research may support this in the generation of resources for pharmacists, in encouraging public take-up of pharmacy services, and in evaluating the most effective provision for dealing with skin conditions.