IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis.

Dupilumab is a fully human antibody to interleukin-4 receptor α that improves the signs and symptoms of moderate to severe atopic dermatitis (AD). To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate to severe AD randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S ribosomal RNA, and absolute S. aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S. aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S. aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S. aureus abundance during dupilumab treatment correlated with clinical improvement of AD and biomarkers of type 2 immunity. We conclude that clinical improvement of AD that is mediated by interleukin-4 receptor α inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus

Potato mop-top virus co-opts the stress sensor HIPP26 for long-distance movement

The work of LT, GC, SJ and AR is funded by the Scottish Government’s Rural and Environmental Science and Analytical Services (RESAS) Division, PH by the BBSRC (grant BB/M024911/1) and The Royal Society and EIS by the Swedish Research Council Formas and the Carl Tryggers Foundation.Virus movement proteins facilitate virus entry into the vascular system to initiate systemic infection. The potato mop-top virus (PMTV) movement protein, TGB1, is involved in long-distance movement of both viral ribonucleoprotein complexes and virions. Here, our analysis of TGB1 interactions with host Nicotiana benthamiana proteins revealed an interaction with a member of the heavy metal-associated isoprenylated plant protein family, HIPP26, which acts as a plasma membrane-to-nucleus signal during abiotic stress. We found that knockdown of NbHIPP26 expression inhibited virus long-distance movement but did not affect cell-to-cell movement. Drought and PMTV infection up-regulated NbHIPP26 gene expression, and PMTV infection protected plants from drought. In addition, NbHIPP26 promoter-reporter fusions revealed vascular tissue-specific expression. Mutational and biochemical analyses indicated that NbHIPP26 subcellular localization at the plasma membrane and plasmodesmata was mediated by lipidation (S-acylation and prenylation), as nonlipidated NbHIPP26 was predominantly in the nucleus. Notably, coexpression of NbHIPP26 with TGB1 resulted in a similar nuclear accumulation of NbHIPP26. TGB1 interacted with the carboxyl-terminal CVVM (prenyl) domain of NbHIPP26, and bimolecular fluorescence complementation revealed that the TGB1-HIPP26 complex localized to microtubules and accumulated in the nucleolus, with little signal at the plasma membrane or plasmodesmata. These data support a mechanism where interaction with TGB1 negates or reverses NbHIPP26 lipidation, thus releasing membrane-associated NbHIPP26 and redirecting it via microtubules to the nucleus, thereby activating the drought stress response and facilitating virus long-distance movement.PostprintPeer reviewe

Foot health education for people with rheumatoid arthritis : the practitioner's perspective

Background: Patient education is considered to be a key role for podiatrists in the management of patients with rheumatoid arthritis (RA). Patient education has undoubtedly led to improved clinical outcomes, however no attempts have been made to optimise its content or delivery to maximise benefits within the context of the foot affected by rheumatoid arthritis. The aim of this study was to identify the nature and content of podiatrists' foot health education for people with RA. Any potential barriers to its provision were also explored. Methods: A focus group was conducted. The audio dialogue was recorded digitally, transcribed verbatim and analysed using a structured, thematic approach. The full transcription was verified by the focus group as an accurate account of what was said. The thematic analysis framework was verified by members of the research team to ensure validity of the data. Results: Twelve members (all female) of the north west Podiatry Clinical Effectiveness Group for Rheumatology participated. Six overarching themes emerged: (i) the essence of patient education; (ii) the content; (iii) patient-centred approach to content and timing; (iv) barriers to provision; (v) the therapeutic relationship; and (vi) tools of the trade. Conclusion: The study identified aspects of patient education that this group of podiatrists consider most important in relation to its: content, timing, delivery and barriers to its provision. General disease and foot health information in relation to RA together with a potential prognosis for foot health, the role of the podiatrist in management of foot health, and appropriate self-management strategies were considered to be key aspects of content, delivered according to the needs of the individual. Barriers to foot health education provision, including financial constraints and difficulties in establishing effective therapeutic relationships, were viewed as factors that strongly influenced foot health education provision. These data will contribute to the development of a patient-centred, negotiated approach to the provision of foot health education for people with RA

Reflections on the teaching symposium at the Microbiology Society Annual Conference 2023

The Microbiology Society Education and Outreach Network (EON) recently hosted the Teaching Symposium at the Microbiology Society Annual Conference, sponsored by Access Microbiology. The presence of the Symposium as an established parallel session within the wider Annual Conference reflects the importance of high-quality, contemporary microbiology education and outreach delivered in an enthusiastic and inclusive manner. At the 2023 Symposium, a variety of pedagogical research projects in higher education learning, teaching and assessment, as well as public engagement projects, were showcased through invited talks, offered talks, flash talks and posters. The event was attended by up to 70 delegates. Several themes were noted throughout the day: engaging with Gen Z (Generation Z, those born between 1996 and 2010), active learning, art in science and engaging with non-higher education (HE) audiences. Inclusivity was a key driver in the organization of the Symposium; the room was set up to encourage discussion and participants could ask questions using an online platform as well as speaking in the room. We now encourage all speakers to consider publishing their work as a peer-reviewed article for further dissemination and impact

EXPERTS II - How are patient and caregiver participation in health and social care shaped by experienced burden of treatment and social inequalities? Protocol for a qualitative synthesis

Background: The workload health and social care service users and caregivers take on, and their capacity to do this work is important. It may play a key part in shaping the implementation of innovations in health service delivery and organisation; the utilisation and satisfaction with services; and the outcomes of care. Previous research has often focused on experiences of a narrow range of long-term conditions, and on factors that shape adherence to self-care regimes. Aims: With the aim of deriving policy and practice implications for service redesign, this evidence synthesis will extend our understanding of service user and caregiver workload and capacity by comparing how they are revealed in qualitative studies of lived experience of three kinds of illness trajectories: long-term conditions associated with significant disability (Parkinson’s disease, schizophrenia); serious relapsing remitting disease (Inflammatory Bowel Disease, bipolar disorder); and rapidly progressing acute disease (brain cancer, early onset dementia). Methods: We will review and synthesise qualitative studies of lived experience of participation in health and social care that are shaped by interactions between experienced treatment burdens, social inequalities and illness trajectories. The review will involve: 1. Construction of a theory-informed coding manual; systematic search of bibliographic databases to identify, screen and quality assess full-text papers. 2. Analysis of papers using manual coding techniques, and text mining software; construction of taxonomies of service user and caregiver work and capacity. 3. Designing a model of core components and identifying common factors across conditions, trajectories, and contexts. 4. Work with practitioners, and a Patient and Public Involvement (PPI) group, to explore the validity of the models produced; to develop workload reduction strategies; and to consider person-centred service design. Dissemination: We will promote workload reduction models to support service users and caregivers and produce policy briefs and peer-reviewed publications for practitioners, policy-makers, and researchers

Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies

We have developed a novel real-time quaking-induced conversion RT-QuICbased assay to detect alpha-synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson’s disease patients. This assay can detect alpha-synuclein aggregation in Dementia with Lewy bodies and Parkinson’s disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results. These results suggest that RT-QuiC analysis of cerebrospinal fluid is potentially useful for the early clinical assessment of patients with alpha-synucleinopathies

IL-4R alpha blockade by dupilumab decreases Staphylococcus aureus colonization and increases microbial diversity in atopic dermatitis

Dupilumab is a fully human antibody to interleukin-4 receptor alpha that improves the signs and symptoms of moderate to severe atopic dermatitis (AD). To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate to severe AD randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S ribosomal RNA, and absolute S. aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S. aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S. aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S. aureus abundance during dupilumab treatment correlated with clinical improvement of AD and biomarkers of type 2 immunity. We conclude that clinical improvement of AD that is mediated by interleukin-4 receptor alpha inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus

Identification of Melatonin-Regulated Genes in the Ovine Pituitary Pars Tuberalis, a Target Site for Seasonal Hormone Control

The pars tuberalis (PT) of the pituitary gland expresses a high density of melatonin (MEL) receptors and is believed to regulate seasonal physiology by decoding changes in nocturnal melatonin secretion. Circadian clock genes are known to be expressed in the PT in response to the decline (Per1) and onset (Cry1) of MEL secretion, but to date little is known of other molecular changes in this key MEL target site. To identify transcriptional pathways that may be involved in the diurnal and photoperiod-transduction mechanism, we performed a whole genome transcriptome analysis using PT RNA isolated from sheep culled at three time points over the 24-h cycle under either long or short photoperiods. Our results reveal 153 transcripts where expression differs between photoperiods at the light-dark transition and 54 transcripts where expression level was more globally altered by photoperiod (all time points combined). Cry1 induction at night was associated with up-regulation of genes coding for NeuroD1 (neurogenic differentiation factor 1), Pbef / Nampt (nicotinamide phosphoribosyltransferase) , Hif1α (hypoxia-inducible factor-1α), and Kcnq5 (K channel) and down-regulation of Rorβ, a key clock gene regulator. Using in situ hybridization, we confirmed day-night differences in expression for Pbef / Nampt, NeuroD1, and Rorβ in the PT. Treatment of sheep with MEL increased PT expression for Cry1, Pbef / Nampt, NeuroD1, and Hif1α, but not Kcnq5. Our data thus reveal a cluster of Cry1-associated genes that are acutely responsive to MEL and novel transcriptional pathways involved in MEL action in the PT

The variation in acute and community service provision of care of the elderly services across the Scotland: Findings from the Scottish Care of Older People (SCoOP) National Audit initial scoping survey

We gratefully acknowledge the support of the British Geriatrics Society (BGS) in raising awareness of this work and the BGS Scotland Council for dissemination of the scoping survey. We also would like to thank Mr Tiberiu Pana, Mr Jesus Perdomo, Dr Maryam Barma and Dr Adrian Wood for their assistance with the project. We would also like to thank the SCoOP Steering Committee Members and Dr Claire Copeland (NHS Forth Valley) for their contribution. The SCoOP Steering Group includes: Dr Louise Beveridge (NHS Tayside), Professor Corri Black (University of Aberdeen), Ms Penny Bond (Healthcare Improvement Scotland), Dr Jennifer Burns (NHS Greater Glasgow and Clyde), Dr Tony Byrne (NHS Forth Valley), Dr Andrew Coull (NHS Lothian), Dr Alison Donaldson (University of Aberdeen), Dr Alice Einarsson (NHS Grampian), Professor Graham Ellis (NHS Lanarkshire, Glasgow Caledonian University and Co-Chair), Ms Karen Goudie(Healthcare Improvement Scotland) , Dr Graeme Hoyle (NHS Grampian), Dr Allan MacDonald (NHS Highland), Dr Christine McAlpine (NHS Greater Glasgow and Clyde), Dr Morven McElroy (NHS Greater Glasgow and Clyde), Professor Phyo Kyaw Myint (University of Aberdeen, Co-Chair), Dr Terence J Quinn (University of Glasgow), Professor Sir Lewis Ritchie (University of Aberdeen), Dr Susan Shenkin (University of Edinburgh), Dr Ralph Thomas (NHS Fife) and Dr Andrew Watt (NHS Ayrshire and Arran).Peer reviewedPublisher PD

EXPERTS II - How are patient and caregiver participation in health and social care shaped by experienced burden of treatment and social inequalities? Protocol for a qualitative synthesis.

BackgroundThe workload health and social care service users and caregivers take on, and their capacity to do this work is important. It may play a key part in shaping the implementation of innovations in health service delivery and organisation; the utilisation and satisfaction with services; and the outcomes of care. Previous research has often focused on experiences of a narrow range of long-term conditions, and on factors that shape adherence to self-care regimes.AimsWith the aim of deriving policy and practice implications for service redesign, this evidence synthesis will extend our understanding of service user and caregiver workload and capacity by comparing how they are revealed in qualitative studies of lived experience of three kinds of illness trajectories: long-term conditions associated with significant disability (Parkinson's disease, schizophrenia); serious relapsing remitting disease (Inflammatory Bowel Disease, bipolar disorder); and rapidly progressing acute disease (brain cancer, early onset dementia).MethodsWe will review and synthesise qualitative studies of lived experience of participation in health and social care that are shaped by interactions between experienced treatment burdens, social inequalities and illness trajectories. The review will involve: 1. Construction of a theory-informed coding manual; systematic search of bibliographic databases to identify, screen and quality assess full-text papers. 2. Analysis of papers using manual coding techniques, and text mining software; construction of taxonomies of service user and caregiver work and capacity. 3. Designing a model of core components and identifying common factors across conditions, trajectories, and contexts. 4. Work with practitioners, and a Patient and Public Involvement (PPI) group, to explore the validity of the models produced; to develop workload reduction strategies; and to consider person-centred service design.DisseminationWe will promote workload reduction models to support service users and caregivers and produce policy briefs and peer-reviewed publications for practitioners, policy-makers, and researchers