Intact myocardial preparations reveal intrinsic transmural heterogeneity in cardiac mechanics

Determining transmural mechanical properties in the heart provides a foundation to understand physiological and pathophysiological cardiac mechanics. Although work on mechanical characterisation has begun in isolated cells and permeabilised samples, the mechanical profile of living individual cardiac layers has not been examined. Myocardial slices are 300 μm-thin sections of heart tissue with preserved cellular stoichiometry, extracellular matrix, and structural architecture. This allows for cardiac mechanics assays in the context of an intact in vitro organotypic preparation. In slices obtained from the subendocardium, midmyocardium and subepicardium of rats, a distinct pattern in transmural contractility is found that is different from that observed in other models. Slices from the epicardium and midmyocardium had a higher active tension and passive tension than the endocardium upon stretch. Differences in total myocyte area coverage, and aspect ratio between layers underlined the functional readouts, while no differences were found in total sarcomeric protein and phosphoprotein between layers. Such intrinsic heterogeneity may orchestrate the normal pumping of the heart in the presence of transmural strain and sarcomere length gradients in the in vivo heart

Contact heat evoked potentials using simultaneous EEG and fMRI and their correlation with evoked pain

BACKGROUND: The Contact Heat Evoked Potential Stimulator (CHEPS) utilises rapidly delivered heat pulses with adjustable peak temperatures to stimulate the differential warm/heat thresholds of receptors expressed by Adelta and C fibres. The resulting evoked potentials can be recorded and measured, providing a useful clinical tool for the study of thermal and nociceptive pathways. Concurrent recording of contact heat evoked potentials using electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) has not previously been reported with CHEPS. Developing simultaneous EEG and fMRI with CHEPS is highly desirable, as it provides an opportunity to exploit the high temporal resolution of EEG and the high spatial resolution of fMRI to study the reaction of the human brain to thermal and nociceptive stimuli. METHODS: In this study we have recorded evoked potentials stimulated by 51° C contact heat pulses from CHEPS using EEG, under normal conditions (baseline), and during continuous and simultaneous acquisition of fMRI images in ten healthy volunteers, during two sessions. The pain evoked by CHEPS was recorded on a Visual Analogue Scale (VAS). RESULTS: Analysis of EEG data revealed that the latencies and amplitudes of evoked potentials recorded during continuous fMRI did not differ significantly from baseline recordings. fMRI results were consistent with previous thermal pain studies, and showed Blood Oxygen Level Dependent (BOLD) changes in the insula, post-central gyrus, supplementary motor area (SMA), middle cingulate cortex and pre-central gyrus. There was a significant positive correlation between the evoked potential amplitude (EEG) and the psychophysical perception of pain on the VAS. CONCLUSION: The results of this study demonstrate the feasibility of recording contact heat evoked potentials with EEG during continuous and simultaneous fMRI. The combined use of the two methods can lead to identification of distinct patterns of brain activity indicative of pain and pro-nociceptive sensitisation in healthy subjects and chronic pain patients. Further studies are required for the technique to progress as a useful tool in clinical trials of novel analgesics

Accessing Meals on Wheels: A qualitative study exploring the experiences of service users and people who refer them to the service

Meals on Wheels (MoWs) provide access to daily meals and social contact to adults with care and support needs.MoWs could be essential for the increasing rates of an ageing population and adults living with complex needs in England, yet many do not know that the service exists. This study aimed to explore the perceptions of MoWs service users, and people who refer them to MoWs (‘referrers’), with accessing and setting up the service in England, and what information would be valued when considering accessing MoWs services.Semi-structured interviews were conducted in May-July 2022 with seven service users and 21 referrers, recruited from four MoWs providers across England. Data were analysed using thematic analysis. Participants indicated various pathways into the service, but referrers (family members) were more likely to be the ones enquiring about, and setting up, MoWs for service users. Once an enquiry about MoWs had been made, the service was perceived as straightforward to set up.However, existing preconceptions and stereotypes about the service (e.g. bringing to mind ‘school meals’, aimed solely at older adults) were perceived to act as barriers to accessing MoWs.Information that participants deemed important to have available when deciding on whether to access MoWs related to the meals (e.g. nutritional value, variety, need for any preparation, catering for individual needs), the specific services provided (e.g. wellbeing checks, daily social contact), the reliability and flexibility of delivery, and the cost of services. These findings could inform MoWs providers’ public awareness strategies about MoWs, in order to facilitate referrals to the service for adults with care and support needs

Accessing Meals on Wheels:a qualitative study exploring the experiences of service users and people who refer them to the service

Aims:This study aimed to explore the perceptions of Meals on Wheels service users, and people who refer them to Meals on Wheels (‘referrers’), with accessing and commencing the service in England, the barriers that might hinder service uptake, and what information would be valued when considering accessing the service.Methods:Semi-structured interviews were conducted in May-July 2022 with seven service users and 21 referrers, recruited from four Meals on Wheels providers across England. Data were analysed using inductive thematic analysis. Results:Participants indicated various pathways into the service, but referrers (family members) were more likely to be the ones enquiring about, and commencing, Meals on Wheels for service users. Once an enquiry about Meals on Wheels had been made, the service was perceived as straightforward to set up. However, existing preconceptions and stereotypes were perceived to act as barriers to accessing Meals on Wheels. Information that participants deemed important to have available when deciding on whether to access Meals on Wheels related to the meals, the specific services provided, the reliability and flexibility of delivery, and the cost of services. Conclusion:These findings could inform Meals on Wheels service providers’ public awareness strategies about Meals on Wheels, in order to facilitate referrals to the service for adults with care and support needs. Patient or Public Contribution: An advisory group of people with lived experience of Meals on Wheels (users of the service and their family referrers) extensively discussed the findings of the research and advised on the implications and future dissemination steps. <br/

‘The service, I could not do without it…’: A qualitative study exploring the significance of Meals on Wheels among service users and people who refer them to the service

Meals on Wheels (MoWs) is a social care service providing daily meals and social contact to adults who need support to live in the community. Considering the rising number of adults who need help with shopping for food and preparing meals in England, MoWs could be essential for these individuals; yet little is known about the experiences of MoWs service users and people who refer them to MoWs (“referrers”), with the service. The aim of this study was to explore different dimensions of the MoWs service from the perspectives of MoWs service users and referrers. Semistructured interviews were conducted in May–July 2022 with seven service users and 21 referrers, recruited from four MoWs providers across England, and analysed thematically. Participants indicated that benefits of the service encompassed the daily provision of a hot, nutritious meal, an informal welfare check, the service’s efficiency and reliability in promoting independent living and reducing pressures on families and carers, and the daily friendly interactions in reducing social isolation. The pandemic was not perceived to have affected participants’ experiences with MoWs but longer interactions between drivers who deliver the meals and service users would be welcomed to reduce isolation further. Despite the cost-of-living crisis and an increase in MoWs prices, participants perceived that MoWs are value-for-money due to the social care benefits derived from the service. The wide range of benefits exerted by MoWs suggests that the service should be recognised as a crucial preventative resource in maintaining the wellbeing and independence of adults with care and support needs and suggests that MoWs forms an essential part of the care package that people with care and support needs receive in England

Incidence and Prognosis of Clonal Hematopoiesis in patients with Chronic Idiopathic Neutropenia

The incidence and prognosis of clonal hematopoiesis in patients with isolated neutropenia among patients with idiopathic cytopenia of undetermined significance (ICUS), known as ICUS-N or chronic idiopathic neutropenia (CIN) patients, is poorly defined. In the present study we sought to investigate the frequency and clinical significance of mutations of genes implicated in myeloid malignancies using next generation sequencing, in CIN patients (n=185) with a long follow-up. We found that 21/185 patients (11.35%) carried totally 25 somatic mutations in 6 genes with median variant allele frequency (VAF) 12.75%. The most frequently mutated genes were DNMT3A and TET2 involving more than 80% of patients followed by IDH1/2, SRSF2 and ZRSR2. The frequency of transformation to a myeloid malignancy was low in the total group of patients (5/185 patients; 2.70%). However, from the transformed patients four belonged to the clonal (4/21; 19.05%) and one to the non-clonal (1/164; 0.61%) group, indicating that the presence of mutation(s) confers a relative risk for transformation 31.24 (P = 0.0017). The VAF of the mutant clones in the transformed patients was higher than 10% in all cases and the genes most frequently associated with malignant transformation were the SRSF2 and IDH1. No significant differences were identified between clonal and non-clonal groups in the severity of neutropenia. Patients with clonal disease were older compared to non-clonal patients. These data contribute to the better understanding of the heterogeneous entities underlying ICUS and highlight the importance of the mutation analysis for the diagnosis and prognosis of patients with unexplained neutropenias