Regulation and function of miR-214 in pulmonary arterial hypertension

Dysregulation of miRNAs can contribute to the aetiology of diseases including pulmonary arterial hypertension (PAH). Here we investigated a potential role for the miR-214 stem loop miRNA and the closely linked miR-199a miRNAs in PAH. All 4 miRNAs were upregulated in the lung and right ventricle in mice and rats exposed to the SU 5416 hypoxia model of PAH. Further, expression of the miRNAs was increased in PASMCs exposed to TGF-β1 but not BMP4. We then examined miR-214-/- mice exposed to the SU 5416 hypoxia model of PAH or normoxic conditions and littermate controls. There were no changes in systolic right ventricular pressure or remodelling observed between the miR-214-/- and WT hypoxic groups. However, we observed a significant increase in right ventricular hypertrophy in hypoxic miR-214-/- male mice compared to controls. Further, we identified that the validated miR-214 target phosphatase and tensin homolog was upregulated in miR-214-/- mice. Thus, miR-214 stem loop loss leads to elevated right ventricular hypertrophy and may contribute to the heart failure associated with PAH

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Standards for plant synthetic biology: a common syntax for exchange of DNA parts.

Inventors in the field of mechanical and electronic engineering can access multitudes of components and, thanks to standardization, parts from different manufacturers can be used in combination with each other. The introduction of BioBrick standards for the assembly of characterized DNA sequences was a landmark in microbial engineering, shaping the field of synthetic biology. Here, we describe a standard for Type IIS restriction endonuclease-mediated assembly, defining a common syntax of 12 fusion sites to enable the facile assembly of eukaryotic transcriptional units. This standard has been developed and agreed by representatives and leaders of the international plant science and synthetic biology communities, including inventors, developers and adopters of Type IIS cloning methods. Our vision is of an extensive catalogue of standardized, characterized DNA parts that will accelerate plant bioengineering.Biotechnological and Biological Sciences Research Council (BBSRC). Grant Numbers: BB/K005952/1, BB/L02182X/1 Synthetic Biology Research Centre ‘OpenPlant’ award. Grant Number: BB/L014130/1 Spanish MINECO. Grant Number: BIO2013‐42193‐R Engineering Nitrogen Symbiosis for Africa (ENSA) The Bill & Melinda Gates Foundation US Department of Energy, Office of Biological and Environmental. Grant Number: DE‐AC02‐05CH1123 COST Action. Grant Number: FA100

Transmission dynamics of highly pathogenic avian influenza virus at the wildlife-poultry-environmental interface: A case study

Avian influenza viruses (AIVs) regularly circulate between wild and domestic bird populations. Following several high-profile outbreaks, highly pathogenic AIVs (HPAIV) with zoonotic potential have been the subject of increasing attention. While we know that HPAIV is transmitted between domestic birds, wildlife, and the environment, little is known about persistence and spillover/back at these interfaces. We integrated the test results of samples collected on and around an infected domestic poultry premise (IP) where H5N1 HPAIV was confirmed in a flock of poultry in 2022 in Southern Ontario, Canada to explore the transmission cycle of AIVs in wildlife and the environment. We sampled a captive flock of Mallards (Anas platyrhynchos) that resided on site, sediment samples collected from water bodies on site, and examined samples collected through surveillance within a 100 km radius of the IP from live wild ducks and sick and dead wildlife. We found serologic evidence of H5 exposure in the captive mallards that resided on site despite no evidence of morbidity or mortality in these birds and no PCR positive detections from samples collected at two different timepoints. Genetic material from the same H5N1 HPAIV subtype circulating in the domestic birds and from low pathogenicity avian influenza viruses were detected in wetlands on site. The results of live and sick and dead surveillance conducted within a 100 km radius confirmed that the virus was circulating in wildlife before and after IP confirmation. These results suggest that biosecurity remains the most critical aspect of minimising spillover/back risk in a virus that has been shown to circulate in asymptomatic wild birds and persist in the surrounding environment

Key action areas for transforming the UK food system: Insights from the Transforming UK Food Systems (TUKFS) Programme project portfolio

The UK food system is a driver of the public health crisis of non-communicable disease, is linked to the cost-of-living crisis, and contributes to climate change, biodiversity loss and soil degradation. The economy relies strongly on the health of its people and food businesses, while also impacting the livelihoods of food system actors. However, action towards more resilient, equitable and regenerative food systems remains too slow and unambitious to adequately address these challenges. The Transforming UK Food Systems Programme comprises a wide range of research projects which address these challenges in a novel place-based, co-produced and action-oriented way. We provide 27 suggested action areas for supporting food system transformation, grouped in five themes spanning production, manufacturing, supply chain and consumption. Among the suggestions, there is a strong emphasis on the importance of co-production with food system actors and affected citizens. We highlight the vital role of governance and policy in supporting these action areas in both a structural and financial way, noting that this needs both national policy and regional approaches to take into account geographically varying cultural circumstances and values, and to allow the high level of co-production necessary

Transboundary particulate matter, photo-oxidants, acidifying and eutrophying components : EMEP Status Report 1 2017; August 23, 2017

This report presents the EMEP activities in 2016 and 2017 in relation to transboundary fluxes of particulate matter, photo-oxidants, acidifying and eutrophying components, with focus on results for 2015. It presents major results of the activities related to emission inventories, observations and modelling. The report also introduces specific relevant research activities addressing EMEP key challenges, as well as technical developments of the observation and modelling capacities. An important topic this year is the transition to the new EMEP grid and resolution. For the first time, officially reported fine scale emissions (0.1◦×0.1◦ resolution) have been used in the EMEP MSC-W model runs for air pollution assessment. The impacts of this change on model results and its comparisons to observations are analyzed in this report