Improved adherence to hip fracture standards reduces mortality after hip fractures.

BACKGROUND: Hip fractures are increasing in incidence due to increasing life expectancy. Mortality continues to improve but it is important to explore which factors are responsible for driving improvements. METHODS: A cohort of hip fracture patients predating SARS-CoV-2 was examined to determine the predictors of adherence to the six Irish Hip Fracture Standards (IHFS) and the impact of adherence on short (30 day) and long term (1 year) mortality. Our primary aim was assess the impact of a single HFS and cumulative number of HFS on mortality after hip fracture. Our secondary aim was to determine the impact of the HFS which are intrinsically linked to specialist Geriatric care. RESULTS: Across 962 patients, over 5 years, the factors which were associated with adherence to HFS were female gender, increasing ASA grade and being nursed on an orthopaedic ward. Patients with increasing ASA were more likely to have met HFS 4-6 (Geriatrician review HFS4, bone health HFS5 & specialist falls assessment HFS6), less likely to have surgery within 48 h are more likely to develop a pressure ulcer. If the patient was not nursed on an orthopaedic ward all HFS were less likely to be met. At 30 days HFS 4-6 were associated with a statistically significant odds ratio (OR) of being alive, while at one year HFS 1 (admitted to an orthopaedic ward within 4 h), 5 and 6 were associated with a statistically significant OR of being alive. As increasing numbers of hip fracture standards were met patients were more likely to be alive at 30 days and one year. CONCLUSION: This study has identified that improved adherence to hip fracture standards are associated with improved mortality at 30 days and one year.

Systemic juvenile idiopathic arthritis: The Great Ormond Street Hospital experience (2005-2021).

Systemic juvenile idiopathic arthritis (sJIA) is a complex, systemic inflammatory disorder driven by both innate and adaptive immunity. Improved understanding of sJIA pathophysiology has led to recent therapeutic advances including a growing evidence base for the earlier use of IL-1 or IL-6 blockade as first-line treatment. We conducted a retrospective case notes review of patients diagnosed with sJIA over a 16-year period (October 2005-October 2021) at Great Ormond Street Hospital for Children. We describe the clinical presentation, therapeutic interventions, complications, and remission rates at different timepoints over the disease course. We examined our data, which spanned a period of changing therapeutic landscape, to try and identify potential therapeutic signals in patients who received biologic treatment early in the disease course compared to those who did not. A total of 76-children (female n = 40, 53%) were diagnosed with sJIA, median age 4.5 years (range 0.6-14.1); 36% (27/76) presented with suspected or confirmed macrophage activation syndrome. A biologic disease-modifying anti-rheumatic drug (bDMARD) alone was commenced as first-line treatment in 28% (n = 21/76) of the cohort; however, at last review, 84% (n = 64/76) had received treatment with a bDMARD. Clinically inactive disease (CID) was achieved by 88% (n = 67/76) of the cohort at last review; however, only 32% (24/76) achieved treatment-free CID. At 1-year follow-up, CID was achieved in a significantly greater proportion of children who received treatment with a bDMARD within 3 months of diagnosis compared to those who did not (90% vs. 53%, p = 0.002). Based on an ever-increasing evidence base for the earlier use of bDMARD in sJIA and our experience of the largest UK single-centre case series described to date, we now propose a new therapeutic pathway for children diagnosed with sJIA in the UK based on early use of bDMARDs. Reappraisal of the current National Health Service commissioning pathway for sJIA is now urgently required.

Phylogenomics illuminates the phylogeny of flower weevils (Curculioninae) and reveals ten independent origins of brood-site pollination mutualism in true weevils.

Weevils are an unusually species-rich group of phytophagous insects for which there is increasing evidence of frequent involvement in brood-site pollination. This study examines phylogenetic patterns in the emergence of brood-site pollination mutualism among one of the most speciose beetle groups, the flower weevils (subfamily Curculioninae). We analysed a novel phylogenomic dataset consisting of 214 nuclear loci for 202 weevil species, with a sampling that mainly includes flower weevils as well as representatives of all major lineages of true weevils (Curculionidae). Our phylogenomic analyses establish a uniquely comprehensive phylogenetic framework for Curculioninae and provide new insights into the relationships among lineages of true weevils. Based on this phylogeny, statistical reconstruction of ancestral character states revealed at least 10 independent origins of brood-site pollination in higher weevils through transitions from ancestral associations with reproductive structures in the larval stage. Broadly, our results illuminate the unexpected frequency with which true weevils-typically specialized phytophages and hence antagonists of plants-have evolved mutualistic interactions of ecological significance that are key to both weevil and plant evolutionary fitness and thus a component of their deeply intertwined macroevolutionary success.

The UHRF1 protein is a key regulator of retrotransposable elements and innate immune response to viral RNA in human cells.

While epigenetic mechanisms such as DNA methylation and histone modification are known to be important for gene suppression, relatively little is still understood about the interplay between these systems. The UHRF1 protein can interact with both DNA methylation and repressive chromatin marks, but its primary function in humans has been unclear. To determine what that was, we first established stable UHRF1 knockdowns (KD) in normal, immortalized human fibroblasts using targeting shRNA, since CRISPR knockouts (KO) were lethal. Although these showed a loss of DNA methylation across the whole genome, transcriptional changes were dominated by the activation of genes involved in innate immune signalling, consistent with the presence of viral RNA from retrotransposable elements (REs). We confirmed using mechanistic approaches that 1) REs were demethylated and transcriptionally activated; 2) this was accompanied by activation of interferons and interferon-stimulated genes and 3) the pathway was conserved across other adult cell types. Restoring UHRF1 in either transient or stable KD systems could abrogate RE reactivation and the interferon response. Notably, UHRF1 itself could also re-impose RE suppression independent of DNA methylation, but not if the protein contained point mutations affecting histone 3 with trimethylated lysine 9 (H3K9me3) binding. Our results therefore show for the first time that UHRF1 can act as a key regulator of retrotransposon silencing independent of DNA methylation.

Oxytocin promotes epicardial cell activation and heart regeneration after cardiac injury.

Cardiovascular disease (CVD) is one of the leading causes of mortality worldwide, and frequently leads to massive heart injury and the loss of billions of cardiac muscle cells and associated vasculature. Critical work in the last 2 decades demonstrated that these lost cells can be partially regenerated by the epicardium, the outermost mesothelial layer of the heart, in a process that highly recapitulates its role in heart development. Upon cardiac injury, mature epicardial cells activate and undergo an epithelial-mesenchymal transition (EMT) to form epicardium-derived progenitor cells (EpiPCs), multipotent progenitors that can differentiate into several important cardiac lineages, including cardiomyocytes and vascular cells. In mammals, this process alone is insufficient for significant regeneration, but it might be possible to prime it by administering specific reprogramming factors, leading to enhanced EpiPC function. Here, we show that oxytocin (OXT), a hypothalamic neuroendocrine peptide, induces epicardial cell proliferation, EMT, and transcriptional activity in a model of human induced pluripotent stem cell (hiPSC)-derived epicardial cells. In addition, we demonstrate that OXT is produced after cardiac cryoinjury in zebrafish, and that it elicits significant epicardial activation promoting heart regeneration. Oxytocin signaling is also critical for proper epicardium development in zebrafish embryos. The above processes are significantly impaired when OXT signaling is inhibited chemically or genetically through RNA interference. RNA sequencing data suggests that the transforming growth factor beta (TGF-ß) pathway is the primary mediator of OXT-induced epicardial activation. Our research reveals for the first time an evolutionary conserved brain-controlled mechanism inducing cellular reprogramming and regeneration of the injured mammalian and zebrafish heart, a finding that could contribute to translational advances for the treatment of cardiac injuries.

A fast radio burst associated with a Galactic magnetar.

Since their discovery in 20071, much effort has been devoted to uncovering the sources of the extragalactic, millisecond-duration fast radio bursts (FRBs)2. A class of neutron stars known as magnetars is a leading candidate source of FRBs3,4. Magnetars have surface magnetic fields in excess of 1014 gauss, the decay of which powers a range of high-energy phenomena5. Here we report observations of a millisecond-duration radio burst from the Galactic magnetar SGR 1935+2154, with a fluence of 1.5 ± 0.3 megajansky milliseconds. This event, FRB 200428 (ST 200428A), was detected on 28 April 2020 by the STARE2 radio array6 in the 1,281-1,468 megahertz band. The isotropic-equivalent energy released in FRB 200428 is 4 × 103 times greater than that of any radio pulse from the Crab pulsar-previously the source of the brightest Galactic radio bursts observed on similar timescales7. FRB 200428 is just 30 times less energetic than the weakest extragalactic FRB observed so far8, and is drawn from the same population as the observed FRB sample. The coincidence of FRB 200428 with an X-ray burst9-11 favours emission models that describe synchrotron masers or electromagnetic pulses powered by magnetar bursts and giant flares3,4,12,13. The discovery of FRB 200428 implies that active magnetars such as SGR 1935+2154 can produce FRBs at extragalactic distances.

A re-evaluation of teenage sunbed use following the introduction of banning legislation for under 18-year-olds.

BACKGROUND: There is little information on the effectiveness of introducing age restriction legislation alone to reduce the rate of sunbed usage by teenagers. Prior to the Public Health (Sunbed) Act of 2014 prohibiting the use of sunbeds in under 18-year-olds in Ireland we reported the rate of sunbed use at 7.5%. OBJECTIVES: The aim of the study was to compare the rate of sunbed usage among Irish teenagers before and after the introduction of banning legislation to determine if it had the desired effect of reducing its rate of use. METHODS: In a cross-sectional survey, students from the same schools as in our previous study completed an anonymous, written questionnaire pertaining to sunbed usage. RESULTS: In total, 783 questionnaires, from 13 schools across Ireland, were completed. The rate of sunbed use in the current study was 7.2%, compared to 7.5% in the pre-ban study, (P = 0.76). A higher rate of sunbed use was observed in Dublin schools and female public students. CONCLUSION: Our study suggests that legislation alone is ineffective at reducing sunbed usage in a teenage population. A multifaceted approach is required that includes enforcement of the legislation together with targeted public education and awareness campaigns using all aspects of the media.

The diversity and evolution of odorant receptors in beetles (Coleoptera).

The insect odorant receptors (ORs) are amongst the largest gene families in insect genomes and the primary means by which insects recognize volatile compounds. The evolution of ORs is thus instrumental in explaining the chemical ecology of insects and as a model of evolutionary biology. However, although ORs have been described from numerous insect species, their analysis within and amongst the insect orders has been hindered by a combination of limited genomic information and a tendency of the OR family toward rapid divergence, gain, and loss. We addressed these issues in the insect order Coleoptera through a targeted genomic annotation effort that included 1181 ORs from one species of the sister order Strepsiptera and 10 species representing the four coleopteran suborders. The numbers of ORs in each species varied from hundreds to fewer than 10, but coleopteran ORs could nevertheless be represented within a scheme of nine monophyletic subfamilies. We observed many radiations and losses of genes amongst OR subfamilies, and the diversity of ORs appeared to parallel the host breadth of the study species. However, some small lineages of ORs persisted amongst many coleopteran families, suggesting receptors of key function that underlie the olfactory ecology of beetles.

Experience of skin disease and relationships with healthcare providers: a qualitative study of Traveller women in Ireland.

BACKGROUND: Significant health disparities exist between members of the Travelling community and those of the general population. Barriers to Traveller engagement with health services include the experience or perception of discrimination, and cultural and health literacy barriers. Experience of skin disease and interactions with healthcare providers has not been widely explored in this ethnic minority. The formation of positive relationships between the Travelling community and healthcare providers is important in the promotion of treatment adherence and improving health outcomes. OBJECTIVES: To investigate Travellers' experience of skin disease and their relationships with healthcare providers. METHODS: Focus groups were conducted with a purposive sample of female members of the Irish Travelling community with experience of skin health issues, between January 2018 and April 2018. Three focus groups were conducted at three separate locations with 10 participants in each group. Themes were identified from the focus group transcripts using an inductive thematic analysis framework. RESULTS: Emergent themes surrounding relationships between Travellers and healthcare providers included health literacy, discrimination, information inconsistency, trust and communication. Factors that were valued in the creation of positive relationships included an appreciation of varying degrees of health literacy, the provision of sufficient information tailored to an individual's needs and a demonstration of cultural competence. CONCLUSIONS: Dermatologists are well placed to provide practical, customized, treatment guidance and engage patients while integrating their culturally based beliefs.

Artificial intelligence and amniotic fluid multiomics: prediction of perinatal outcome in asymptomatic women with short cervix.

OBJECTIVE: To evaluate the application of artificial intelligence (AI), i.e. deep learning and other machine-learning techniques, to amniotic fluid (AF) metabolomics and proteomics, alone and in combination with sonographic, clinical and demographic factors, in the prediction of perinatal outcome in asymptomatic pregnant women with short cervical length (CL). METHODS: AF samples, which had been obtained in the second trimester from asymptomatic women with short CL (< 15 mm) identified on transvaginal ultrasound, were analyzed. CL, funneling and the presence of AF 'sludge' were assessed in all cases close to the time of amniocentesis. A combination of liquid chromatography coupled with mass spectrometry and proton nuclear magnetic resonance spectroscopy-based metabolomics, as well as targeted proteomics analysis, including chemokines, cytokines and growth factors, was performed on the AF samples. To determine the robustness of the markers, we used six different machine-learning techniques, including deep learning, to predict preterm delivery < 34 weeks, latency period prior to delivery < 28 days after amniocentesis and requirement for admission to a neonatal intensive care unit (NICU). Omics biomarkers were evaluated alone and in combination with standard sonographic, clinical and demographic factors to predict outcome. Predictive accuracy was assessed using the area under the receiver-operating characteristics curve (AUC) with 95% CI, sensitivity and specificity. RESULTS: Of the 32 patients included in the study, complete omics, demographic and clinical data and outcome information were available for 26. Of these, 11 (42.3%) patients delivered ≥ 34 weeks, while 15 (57.7%) delivered < 34 weeks. There was no statistically significant difference in CL between these two groups (mean ± SD, 11.2 ± 4.4 mm vs 8.9 ± 5.3 mm, P = 0.31). Using combined omics, demographic and clinical data, deep learning displayed good to excellent performance, with an AUC (95% CI) of 0.890 (0.810-0.970) for delivery < 34 weeks' gestation, 0.890 (0.790-0.990) for delivery < 28 days post-amniocentesis and 0.792 (0.689-0.894) for NICU admission. These values were higher overall than for the other five machine-learning methods, although each individual machine-learning technique yielded statistically significant prediction of the different perinatal outcomes. CONCLUSIONS: This is the first study to report use of AI with AF proteomics and metabolomics and ultrasound assessment in pregnancy. Machine learning, particularly deep learning, achieved good to excellent prediction of perinatal outcome in asymptomatic pregnant women with short CL in the second trimester. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

The molecular characterisation of Cryptosporidium species in relinquished dogs in Great Britain: a novel zoonotic risk?

Surveillance was conducted to investigate the occurrence of protozoan parasites of the genus Cryptosporidium in dogs newly admitted to a dog rehoming charity in London, Great Britain. Voided faecal samples were collected from all new admissions between 2011 and 2012 during six separate 4-week sampling periods. Information on host signalment, including age, breed and reason for submission and faecal consistency, was collected. Polymerase Chain Reaction (PCR) targeting the 18S ribosomal RNA gene, confirmed by sequencing, was conducted on the faecal samples to detect Cryptosporidium genomic DNA and determine Cryptosporidium identity. In total, 677 dogs were included in the study. The prevalence of Cryptosporidium-positive faecal samples was 4.6% (31/676). There were positive samples in all of the six sampling periods. Cryptosporidium canis (n = 28), C. parvum (n = 2) and C. andersoni (n = 1) were identified. Sixty KDa glycoprotein (gp60) gene amplicon sequencing of the C. parvum samples identified genotypes IIaA17G1R1 and IIaA15G2R1 for the first time from a dog. There were no significant associations between signalment data and Cryptosporidium status. While this was a study of one rehoming shelter, the presence of the potentially zoonotic C. parvum and C. canis in dogs highlights a public health concern. Further research is needed to better understand the epidemiology and potential impacts of Cryptosporidium infection in dogs.

Effects of ractopamine hydrochloride on the growth performance and carcass characteristics of heavy-weight finishing pigs sent for slaughter using a 3-phase marketing strategy.

A total of 2,158 crossbred pigs was used to evaluate the effects of feeding 7.4 mg/kg ractopamine hydrochloride (RAC) on the growth performance and carcass characteristics of heavy-weight finishing pigs sent to slaughter using a 3-phase marketing strategy. The study was performed from 121.0 ± 4.28 kg to 144.5 ± 4.73 BW using a randomized complete block design (blocking factor was d of start on test) with 2 treatments (0 vs. 7.4 mg/kg RAC). Pigs were housed in a commercial wean-to-finish facility in groups of approximately 25 (44 groups/treatment), with ad libitum access to feed and water throughout the study, and pen weights of pigs were recorded at the start (d 0), and on d 7, 21, and 35 of study. Pigs were sent for slaughter according to the following marketing strategy: 1) after 7 d on RAC, the heaviest 16% of each pen was sent for slaughter (Phase 1), 2) after 21 d on RAC, the next 40% of each pen was sent for slaughter (Phase 2), and 3) after 35 d on RAC, the remaining 44% of each pen was sent for slaughter (Phase 3). Pigs were selected for slaughter by visual appraisal and shipped to a commercial facility where standard carcass measurements (HCW, LM depth, and backfat depth) were measured. Overall, feeding RAC increased (P < 0.001) ADG (18.8%) and G:F (23.7%) compared to the control, but lowered (P < 0.001) ADFI (3.3%). In addition, feeding RAC increased (P < 0.001) HCW (3.9 kg), carcass yield (0.7% units), LM depth (5.0%), and predicted lean content (1.0% units), and reduced backfat depth (6.3% lower) compared to controls. With each subsequent phase of marketing, the magnitude of improvements in response to feeding RAC decreased for ADG (43.1, 20.9, and -3.1% for Phase 1, 2, and 3, respectively) and G:F (37.5, 25.8, and 6.4% for Phase 1, 2, and 3, respectively); however, improvements in HCW (1.6, 4.5, and 4.2 kg for Phase 1, 2, and 3, respectively), carcass yield (0.2, 0.6, and 0.9% units for Phase 1, 2, and 3, respectively), LM depth (2.3, 5.7, and 5.2% for Phase 1, 2, and 3, respectively), and predicted lean content (0.2, 1.0, and 1.3% units for Phase 1, 2, and 3, respectively) generally increased from feeding RAC. These results suggest that while improvements in growth performance from feeding RAC will generally decline after 21 d of feeding, improvements in carcass traits, particularly carcass yield and lean content, will continue with feeding RAC until d 35.