Prevalence of occupational heat stress across the seasons and its management amongst healthcare professionals in the UK.

Occupational heat stress (OHS) is an issue in healthcare facilities (HCFs) in the United Kingdom (UK). The aims of this study were to evaluate perceived levels of OHS during two seasons and its perceived consequences on healthcare professionals (HCPs) and to assess the efficacy of heat stress management (HSM) policies. An anonymous online survey was distributed to HCPs working in HCFs in the UK. The survey returned 1014 responses (87% women). Descriptive statistics and content analysis of survey data identified that OHS in HCFs is frequently experienced throughout the year and concerned most HCPs. Over 90% perceived OHS impairs their performance and 20% reported heat-related absenteeism. Awareness of HSM policies was poor and 73% deemed them not adequate. To help reduce the financial loss and impact on staff performance, health and well-being and patient safety, it is recommended that revisions and widespread dissemination of HSM policies are made.

The lived experience of food insecurity among adults with obesity: a quantitative and qualitative systematic review.

BACKGROUND: Food insecurity and obesity are increasing both globally and in the UK. In this review we systematically assess the lived experiences of people with obesity who are food insecure and often turn to food banks. METHODS: We systematically searched electronic databases from January 2007 until October 2022. Data from eligible studies were extracted and the studies assessed for quality. Thematic analysis and narrative synthesis approach was used to analyse the extracted data. RESULTS: Six themes were identified among 25 included studies, including: the financial cost of food; psychological aspects related to food insecurity; geographical access and the food environment; food practices in the home; experience of food assistance; and parental-child relationships. The cost of healthy food and psychological factors were identified as key driving factors of the relationship between food insecurity and obesity. Psychological factors such as depression, low self-esteem and stress played an important part in the lived experience of people with obesity and food insecurity. CONCLUSION: The food environment provides context in which food decisions are made, therefore, systems change is necessary to ensure families can afford the food that enables a healthy diet. For clinicians, identification, and attention to the impact of food insecurity on people with obesity are important.

Diabetes specialist intervention in general practices in areas of deprivation and ethnic diversity: A qualitative evaluation (QUAL-ECLIPSE).

AIM: To assess patients' and healthcare professionals' perspectives of a specialist-led Diabetes Risk-based Assessment Clinic (DIRAC) for people with diabetes at high risk of complications (PWDHRC) in areas of deprivation in Coventry, UK. METHODS: A qualitative evaluation of a pilot trial, comprising a specialist team intervention (DIRAC), was undertaken in seven GP practices through observations of weekly virtual or occasional face-to-face patient consultations and monthly interventionists' meetings. Semi-structured interviews were carried out post-intervention, with PWDHRC, primary care clinicians and diabetes specialists (interventionists). Thematic analyses of observations and interviews were undertaken. KEY FINDINGS: Over 12 months, 28 DIRAC clinics comprising 154 patient consultations and five interventionists' meetings, were observed. 19 interviews were undertaken, PWDHRC experienced 'culturally-sensitive care from a specialist-led clinic intervention encompassing integrated care. This model of care was recommended at GP practice level, all participants (PWDHRC, primary care clinicians and diabetes specialist interventionists) felt upskilled to deal with complex diabetes care. The EMIS and ECLIPSE technologies utilised during the intervention were perceived to positively contribute to diabetes management of PWDHRC despite reservations around cost and database. CONCLUSION: The specialist-led DIRACs were largely appreciated by study participants. These qualitative data support the trial progressing to a full-service evaluation.

The experiences of adult patients, families, and healthcare professionals of CPR decision-making conversations in the United Kingdom: A qualitative systematic review.

Aim: To conduct a qualitative systematic review on the experiences of patients, families, and healthcare professionals (HCPs) of CPR decision-making conversations in the United Kingdom (UK). Methods: The databases PubMed, Embase, Emcare, CINAHL, and PsycInfo were searched. Studies published from 1 January 2012 describing experiences of CPR decision-making conversations in the UK were included. Included studies were critically appraised using the CASP tool. Thematic synthesis was conducted. Results: From 684 papers identified, ten studies were included. Four key themes were identified:(i) Initiation of conversations - Key prompts for the discussion included clinical deterioration and poor prognosis. There are different perspectives about who should initiate conversations.(ii) Involvement of patients and families - HCPs were reluctant to involve patients who they thought would become distressed by the conversation, while patients varied in their desire to be involved. Patients wanted family support while HCPs viewed families as potential sources of conflict.(iii) Influences on the content of conversations - Location, context, HCPs' attitudes and emotions, and uncertainty of prognosis influenced the content of conversations.(iv) Conversation outcomes - Range of outcomes included emotional distress, sense of relief and value, disagreements, and incomplete conversations. Conclusions: There is inconsistency in how these conversations occur, patients' desire to be involved, and between patients' and HCPs' views on the role of families in these conversations. CPR discussions raise ethical challenges for HCPs. HCPs need training and pastoral support in conducting CPR discussions. Patients and families need education on CPR recommendations and support after discussions.

CAREPATH: Developing Digital Integrated Care Solutions for Multimorbid Patients with Dementia.

CAREPATH project is focusing on providing an integrated solution for sustainable care for multimorbid elderly patients with dementia or mild cognitive impairment. The project has a digitally enhanced integrated patient-centered care approach clinical decision and associated intelligent tools with the aim to increase patients' independence, quality of life and intrinsic capacity. In this paper, the conceptual aspects of the CAREPATH project, in terms of technical and clinical requirements and considerations, are presented.

Improving diabetes and endocrinology specialty training with modest resources: the Health Education West Midlands model.

INTRODUCTION: In the current pandemic, there is a significant disruption for medical training. It is essential that clinicians can access high-quality, targeted educational content to support their clinical working and training development. This content must be delivered on a background of increasing clinical pressures and budgetary restrictions. METHODS: Educational innovations and supplementary educational content (such as digitisation, simulation, curriculum mapping, trainee representative role definition, research and innovation training) were implemented. We measured the impact of these interventions on cost reductions and changes in trainees' self-reported confidence levels to manage various clinical scenarios post-interventions. RESULTS: Using digital technologies reduced both costs and administrative burdens. Simulation-based learning helped improve trainees' self-reported confidence levels. CONCLUSION: Collaborative working across training programme directors, specialist training committee members, educational supervisors, trainee representatives and trainees themselves can develop high-quality educational programmes that support clinical exposure. We propose that elements of the model described here can be replicated across regions and different specialties to support the highest quality of education for UK trainees.

Non-Hodgkin Lymphoma Causing Hypopituitarism Can Imaging Help Diagnosis and Management?

Non-Hodgkin lymphomas of the hypothalamus and pituitary are rare. They usually remain clinically silent until onset of compressive features affecting surrounding structures. When symptomatic, patients most commonly present with diabetes insipidus, headaches, ophthalmoplegia and/or bilateral hemianopia. We report a case of a 67-year-old Caucasian female with a history of B-cell lymphoma in complete remission. She presented with left oculomotor nerve palsy and was subsequently found to have a sellar/suprasellar mass lesion on MRI. Alongside hypocortisolism and hypogonadotropic hypogonadism, she developed transient diabetes insipidus during her illness. Her clinical course was characterized by rapid intracranial progression of the sellar mass. MR spectroscopy suggested a diagnosis of lymphoma. Diagnostic biopsy confirmed high-grade diffuse large B-cell CNS lymphoma; this changed the definitive management from surgical excision to chemotherapy. Despite treatment, she succumbed to her illness within 7 months of initial presentation. This case highlights the aggressive nature of CNS lymphomas and the need for a high index of suspicion in an unusual presentation of sellar/suprasellar mass lesions. LEARNING POINTS: Novel imaging techniques such as MR spectroscopy might help to differentiate some brain tumours from pituitary macroadenomas, but these are not diagnostic.Tissue diagnosis with biopsy and histopathology is the gold standard for deciding management of pituitary fossa mass lesions with atypical presentation.

Facial twitching: calcium or concussion conundrum? Hypocalcaemia in a young American football player masking an internal carotid artery dissection.

A 30-year-old male American football player presented to the acute medical unit with left-hand and hemifacial spasms. History and examination revealed hemifacial spasms in keeping with seizure-like activity possibly due to symptomatic hypocalcaemia. Subsequent investigations revealed an adjusted calcium of 1.87 mmol/L and, hence, he was managed with intravenous calcium replacement. He presented two further times in a 1-month period, with subjective limb weakness, despite normal adjusted calcium. During his third admission, he developed slurred speech and a marked facial droop, with absence of power in the right upper limb. Imaging revealed acute and old infarctions in the left middle cerebral artery territory and appearances consistent with left internal carotid artery dissection. This presentation of arterial stroke is atypical but with potentially grave consequences if missed. There is limited literature on the presentation of hemifacial spasm, and its association with ischaemic or haemorrhagic stroke represents a key learning point.

E-health for active ageing; A systematic review.

Enabling successful active ageing is an international priority to meet the challenges of increasing life expectancy. Digital strategies, such as telemedicine and e-health, offer the potential to deliver active ageing in a cost-effective manner at scale. This article aims to establish the extent to which the research literature considers e-health-based and telemedicine-based active ageing interventions. A systematic review was conducted according to PRISMA standards. Independently, two authors searched the Cochrane, EMBASE & CINAHL databases, with subsequent independent extraction and semi-quantitative analysis. We report a considerable breadth in digital active ageing research, which is truly international in its scope. There is a diverse range of both interventions and technologies, including a reassuring focus on community-based interventions. Whilst there are a number of quantitative studies, sample sizes are small, with a limited amount of statistical testing of the results. There is significant variation in the outcome measures reported and little consensus as to the most effective intervention strategies. Overall, whilst there is considerable breadth to the research published in the literature, there is a clear restriction in the depth of this research. There is little overall consensus. This lack of depth and consensus may be due to the need to recognize the important role of technical research elements alongside more traditional research methodologies, such as randomized controlled trials. Enabling both technical and clinical research methods to be recognized, in tandem, has enormous potential to support individuals, communities, clinicians and policy makers to make more informed decisions in relation to active ageing.

Allelic diversity of S-RNase alleles in diploid potato species.

KEY MESSAGE: The S-ribonuclease sequences of 16 S-alleles derived from diploid types of Solanum are presented. A phylogenetic analysis and partial phenotypic analysis support the conclusion that these are functional S-alleles. S-Ribonucleases (S-RNases) control the pistil specificity of the self-incompatibility (SI) response in the genus Solanum and several other members of the Solanaceae. The nucleotide sequences of S-RNases corresponding to a large number of S-alleles or S-haplotypes have been characterised. However, surprisingly, few S-RNase sequences are available for potato species. The identification of new S-alleles in diploid potato species is desirable as these stocks are important sources of traits such as biotic and abiotic resistance. S-RNase sequences are reported here from three distinct diploid types of potato: cultivated Solanum tuberosum Group Phureja, S. tuberosum Group Stenotomum, and the wild species Solanum okadae. Partial S-RNase sequences were obtained from pistil RNA by RT-PCR or 3'RACE (Rapid Amplification of cDNA Ends) using a degenerate primer. Full-length sequences were obtained for two alleles by 5'RACE. Database searches with these sequences identified 16 S-RNases in total, all of which are novel. The sequence analysis revealed all the expected features of functional S-RNases. Phylogenetic analysis with selected published S-RNase and S-like-RNase sequences from the Solanaceae revealed extensive trans-generic evolution of the S-RNases and a clear distinction from S-like-RNases. Pollination tests were used to confirm the self-incompatibility status and cross-compatibility relationships of the S. okadae accessions. All the S. okadae accessions were found to be self-incompatible as expected with crosses amongst them exhibiting both cross-compatibility and semi-compatibility consistent with the S-genotypes determined from the S-RNase sequence data. The progeny analysis of four semi-compatible crosses examined by allele-specific PCR provided further confirmation that these are functional S-RNases.

A Health Informatics Approach to Understanding the Discharge Process.

This study characterises the inpatient discharge process for medical patients. Inpatient discharge represents a highly complex, distinct process at the point of transition to community care. It is poorly understood. Data were collected to assess the discharge patterns of 3386 patients admitted to a tertiary referral centre over a 9 day period. Individual patient parameters were extracted from an Electronic Patient Record and analysed for a random stratified sample of (n=150) with 12 months follow-up. Medical discharges represent 37% of non-elective discharges. 36% fewer medical discharges occurred at weekends (p<0.01), patients discharged at weekends were less complex. 63% of discharges had follow up plans. GP follow up was planned for 61% of single admissions compared to 32% of patients who subsequently were readmitted. Health informatics approaches are critical to improving understanding, quality and efficiency of the discharge process.

Comparison of monovalent and divalent ion distributions around a DNA duplex with molecular dynamics simulation and a Poisson-Boltzmann approach.

The ion atmosphere created by monovalent (Na(+) ) or divalent (Mg(2+) ) cations surrounding a B-form DNA duplex were examined using atomistic molecular dynamics (MD) simulations and the nonlinear Poisson-Boltzmann (PB) equation. The ion distributions predicted by the two methods were compared using plots of radial and two-dimensional cation concentrations and by calculating the total number of cations and net solution charge surrounding the DNA. Na(+) ion distributions near the DNA were more diffuse in PB calculations than in corresponding MD simulations, with PB calculations predicting lower concentrations near DNA groove sites and phosphate groups and a higher concentration in the region between these locations. Other than this difference, the Na(+) distributions generated by the two methods largely agreed, as both predicted similar locations of high Na(+) concentration and nearly identical values of the number of cations and the net solution charge at all distances from the DNA. In contrast, there was greater disagreement between the two methods for Mg(2+) cation concentration profiles, as both the locations and magnitudes of peaks in Mg(2+) concentration were different. Despite experimental and simulation observations that Mg(2+) typically maintains its first solvation shell when interacting with nucleic acids, modeling Mg(2+) as an unsolvated ion during PB calculations improved the agreement of the Mg(2+) ion atmosphere predicted by the two methods and allowed for values of the number of bound ions and net solution charge surrounding the DNA from PB calculations that approached the values observed in MD simulations.

Improving communication of inpatient blood transfusion events to GPs.

Patients who have had blood transfusions whilst in hospital must have this information communicated to their General Practitioner at discharge. Audit demonstrated that just 50% of patients (n=15) under medical specialties who had undergone a blood transfusion had this information included in their discharge letter. To improve this, a section was specifically designated on the e-discharge pro-forma for the documentation of blood transfusion events, and focused teaching was delivered to all new FY1 doctors at their induction. Post intervention, 80% of blood transfusions occurring in medical patients were documented on the e-discharge, with an improvement in how detailed this documentation was (n=40). This simple intervention is an easily reproducible, cost neutral method of ensuring that more blood transfusion events are communicated to patients' GPs; improving care and reducing risk.

The Drosophila orthologue of progeroid human WRN exonuclease, DmWRNexo, cleaves replication substrates but is inhibited by uracil or abasic sites : analysis of DmWRNexo activity in vitro.

Werner syndrome (WS) is a rare late-onset premature ageing disease showing many of the phenotypes associated with normal ageing, and provides one of the best models for investigating cellular pathways that lead to normal ageing. WS is caused by mutation of WRN, which encodes a multifunctional DNA replication and repair helicase/exonuclease. To investigate the role of WRN protein's unique exonuclease domain, we have recently identified DmWRNexo, the fly orthologue of the exonuclease domain of human WRN. Here, we fully characterise DmWRNexo exonuclease activity in vitro, confirming 3'-5' polarity, demonstrating a requirement for Mg(2+), inhibition by ATP, and an ability to degrade both single-stranded DNA and duplex DNA substrates with 3' or 5' overhangs, or bubble structures, but with no activity on blunt ended DNA duplexes. We report a novel active site mutation that ablates enzyme activity. Lesional substrates containing uracil are partially cleaved by DmWRNexo, but the enzyme pauses on such substrates and is inhibited by abasic sites. These strong biochemical similarities to human WRN suggest that Drosophila can provide a valuable experimental system for analysing the importance of WRN exonuclease in cell and organismal ageing.

Effect of initial ion positions on the interactions of monovalent and divalent ions with a DNA duplex as revealed with atomistic molecular dynamics simulations.

Monovalent (Na(+)) and divalent (Mg(2+)) ion distributions around the Dickerson-Drew dodecamer were studied by atomistic molecular dynamics (MD) simulations with AMBER molecular modeling software. Different initial placements of ions were tried and the resulting effects on the ion distributions around DNA were investigated. For monovalent ions, results were found to be nearly independent of initial cation coordinates. However, Mg(2+) ions demonstrated a strong initial coordinate dependent behavior. While some divalent ions initially placed near the DNA formed essentially permanent direct coordination complexes with electronegative DNA atoms, Mg(2+) ions initially placed further away from the duplex formed a full, nonexchanging, octahedral first solvation shell. These fully solvated cations were still capable of binding with DNA with events lasting up to 20 ns, and in comparison were bound much longer than Na(+) ions. Force field parameters were also investigated with modest and little differences arising from ion (ions94 and ions08) and nucleic acid description (ff99, ff99bsc0, and ff10), respectively. Based on known Mg(2+) ion solvation structure, we conclude that in most cases Mg(2+) ions retain their first solvation shell, making only solvent-mediated contacts with DNA duplex. The proper way to simulate Mg(2+) ions around DNA duplex, therefore, should begin with ions placed in the bulk water.

Trans-specific S-RNase and SFB alleles in Prunus self-incompatibility haplotypes.

Self-incompatibility in the genus Prunus is controlled by two genes at the S-locus, S-RNase and SFB. Both genes exhibit the high polymorphism and high sequence diversity characteristic of plant self-incompatibility systems. Deduced polypeptide sequences of three myrobalan and three domestic plum S-RNases showed over 97% identity with S-RNases from other Prunus species, including almond, sweet cherry, Japanese apricot and Japanese plum. The second intron, which is generally highly polymorphic between alleles was also remarkably well conserved within these S-allele pairs. Degenerate consensus primers were developed and used to amplify and sequence the co-adapted polymorphic SFB alleles. Sequence comparisons also indicated high degrees of polypeptide sequence identity between three myrobalan and the three domestic plum SFB alleles and the corresponding Prunus SFB alleles. We discuss these trans-specific allele identities in terms of S-allele function, evolution of new allele specificities and Prunus taxonomy and speciation.

Loss of pollen-S function in two self-compatible selections of Prunus avium is associated with deletion/mutation of an S haplotype-specific F-box gene.

Recently, an S haplotype-specific F-box (SFB) gene has been proposed as a candidate for the pollen-S specificity gene of RNase-mediated gametophytic self-incompatibility in Prunus (Rosaceae). We have examined two pollen-part mutant haplotypes of sweet cherry (Prunus avium). Both were found to retain the S-RNase, which determines stylar specificity, but one (S3' in JI 2434) has a deletion including the haplotype-specific SFB gene, and the other (S4' in JI 2420) has a frame-shift mutation of the haplotype-specific SFB gene, causing amino acid substitutions and premature termination of the protein. The loss or significant alteration of this highly polymorphic gene and the concomitant loss of pollen self-incompatibility function provides compelling evidence that the SFB gene encodes the pollen specificity component of self-incompatibility in Prunus. These loss-of-function mutations are inconsistent with SFB being the inactivator of non-self S-RNases and indicate the presence of a general inactivation mechanism, with SFB conferring specificity by protecting self S-RNases from inactivation.

The F-box protein AhSLF-S2 controls the pollen function of S-RNase-based self-incompatibility.

Recently, we have provided evidence that the polymorphic self-incompatibility (S) locus-encoded F-box (SLF) protein AhSLF-S(2) plays a role in mediating a selective S-RNase destruction during the self-incompatible response in Antirrhinum hispanicum. To investigate its role further, we first transformed a transformation-competent artificial chromosome clone (TAC26) containing both AhSLF-S(2) and AhS(2)-RNase into a self-incompatible (SI) line of Petunia hybrida. Molecular analyses showed that both genes are correctly expressed in pollen and pistil in four independent transgenic lines of petunia. Pollination tests indicated that all four lines became self-compatible because of the specific loss of the pollen function of SI. This alteration was transmitted stably into the T1 progeny. We then transformed AhSLF-S(2) cDNA under the control of a tomato (Lycopersicon esculentum) pollen-specific promoter LAT52 into the self-incompatible petunia line. Molecular studies revealed that AhSLF-S(2) is specifically expressed in pollen of five independent transgenic plants. Pollination tests showed that they also had lost the pollen function of SI. Importantly, expression of endogenous SLF or SLF-like genes was not altered in these transgenic plants. These results phenocopy a well-known phenomenon called competitive interaction whereby the presence of two different pollen S alleles within pollen leads to the breakdown of the pollen function of SI in several solanaceaous species. Furthermore, we demonstrated that AhSLF-S(2) physically interacts with PhS(3)-RNase from the P. hybrida line used for transformation. Together with the recent demonstration of PiSLF as the pollen determinant in P. inflata, these results provide direct evidence that the polymorphic SLF including AhSLF-S(2) controls the pollen function of S-RNase-based self-incompatibility.