Williams (United Kingdom)

Introduction The widespread prevalence of obesity and its adverse health effects have made sustained weight loss strategies a public health priority.

AimFamilies from socioeconomically deprived backgrounds appear to have been greatly impacted and face worsening inequalities as a result of the COVID-19 pandemic. With more than half of children in Newham, East London, living in poverty, this study aimed to investigate the impact of the COVID-19 lockdowns on families with a child under 5 years-old in Newham and identify their immediate needs to inform recovery efforts.Subjects and methodsThis was a qualitative study. Semi-structured interviews were conducted with 13 participants (2 fathers; 11 mothers) exploring the impact of the COVID-19 lockdowns on family life, neighbourhood and community and important relationships in the child’s world.ResultsAll parents experienced significant impacts on family life and well-being because of the pandemic. Families were placed under increased stress and were concerned about the impacts on child development. Low-income families were most disadvantaged, experiencing lack of professional support, community engagement and inadequate housing.ConclusionFamilies were placed under increasing pressure during the pandemic and recovery efforts need to target those most affected, such as families from low-income households. Recovery efforts should target child social and language development, family mental health, professional service engagement and community involvement.

BackgroundCurrent electrocardiographic (ECG) devices built into cardiovascular magnetic resonance (CMR) scanners have a narrow bandwidth (0.5–60Hz) and signals suffer from distortion due to magnetic field gradient artefact and magnetohydrodynamic effects, so ECGs are non-diagnostic except for R-peak detection. Despite advanced QRS detection algorithms, incorrect R peak detection hampers image acquisition, especially at higher field strengths, thus prolonging scan time and producing suboptimal images. Previous feasibility studies at 1.5 and 3 Tesla (T) using external ECG devices were small: n=14 and n=4 healthy volunteers respectively. We implemented a novel hardware and software system for integrating an external device into a clinical 3T CMR scanner to derive diagnostic 12-lead ECGs from inside the scanner bore and during stress perfusion acquisition.MethodsStandard 12-lead ECGs were first recorded on participants of the MyoFit46 cardiovascular sub-study of the National Survey of Health and Development outside the CMR environment using conventional electrode placement. CMR was then performed using Siemens Prisma 3T magnet. Three electrodes (each with 3 measurement and 1 reference electrodes, figure 1a) were applied to the chest of participants. Short leads connected each electrode to a sensor for signal amplification and digitalisation (figure 1b). Signals were then transmitted via 10 m-long dual fibre-optic cables running through a penetration hole into the adjacent room to reach an electronics signal module and connected laptop (32 cores, 5.2GHz) equipped with easyG/truzyG/Epsidy software (figure 1c). ECGs were recorded for 30 seconds prior to image acquisition in all participants and repeated during stress perfusion acquisition in one participant as proof-of-principle. Post-processing denoise filtering removed gradient artefact and a subject-specific matrix was applied to reconstruct 12-lead ECGs from the raw signal. The morphology of each beat of the in-bore 12-lead ECG was compared to the reference ECG (outside the scanner) using Pearson’s correlation coefficient on the PQRST waveform.Results20 participants were prospectively recruited (60% male, 76±0 years). In-bore 12-lead ECGs were safe and successfully reconstructed in all cases (3 examples at rest: figures 2A-C). The reconstructed 12-lead ECGs (red lines) correlated closely with the standard ECGs (green lines)- mean correlation coefficient r=0.86 (95% confidence interval 0.82;0.90) when comparing PQRST morphology. The mean difference (MD) in QRS duration between ECGs was 4 ms (limit of agreement [LOA] -17 to 25 ms) and MD in cQT interval 1 ms(LOA -22 to 21 ms).ECG recording during adenosine infusion proved feasible in the exemplar (figure 2D- green line, same participant as figure 2C). Recording at peak stress (after 4 minutes of adenosine) showed evolving ST elevation in leads II, III, aVf, V1 and V2 and ST depression in I and aVl.ConclusionHigh-quality diagnostic 12-lead ECGs can be collected in real-time during a 3T CMR scan with potential to improve triggering and image acquisition. Our ability to detect transient ischaemic changes during stress perfusion may enhance the interpretation of quantitative perfusion maps and the technology may have several neurocardiology applications. BS19 Figure 1A) Example electrode patch with 3 separate measurement electrodes and 1 reference (black) electrode. B) Electrode configuration on a participant’s chest (if female, lateral electrode is positioned under the breast). Each electrode connects to a sensor (grey box) via a short lead (black line) for signal amplification and digitalization. Short leads prevent overheating from the radiofrequency gradient minimizing the risk of burns. C) Hardware set-up inside and out of the CMR environment. Cables are bound together and passed through a penetration hole to reach the adjacent control room BS19 Figure 2A, B and C) Examples from 3 participants each showing reference 12-lead ECG from outside the CMR environment (green line) and superimposed reconstructed 12-lead ECG from inside the CMR bore (red line). A: mean correlation 89.7%; B mean correlation 90.1%; C: mean correlation 76.7%. D) Feasibility of 12-lead ECG recording during adenosine stress perfusion for same participant as figure 2D showing ST elevation in leads II, III , aVf, V1 and V2 and ST depression in I and aVl when compared to the resting in-bore ECGConflict of InterestNo

Alcohol-related liver disease (ALD) encompasses a range of pathological conditions that are complex to study at the clinical and preclinical levels. Despite the global burden of ALD, there is a lack of effective treatments, and mortality is high. One of the reasons for the unsuccessful development of novel therapies is that experimental studies are hindered by the challenge of recapitulating this multifactorial disorder in vitro, including the contributions of hepatotoxicity, impaired lipid metabolism, fibrosis and inflammatory cytokine storm, which are critical drivers in the pathogenesis of ALD in patients and primary targets for drug development. Here, we present the unique characteristics of the culture of human precision-cut liver slices (PCLS) to replicate key disease processes in ALD. PCLS were prepared from human liver specimens and treated with ethanol alone or in combination with fatty acids and lipopolysaccharide (FA + LPS) for up to 5 days to induce hepatotoxic, inflammatory and fibrotic events associated with ALD. Alcohol insult induced hepatocyte death which was more pronounced with the addition of FA + LPS. This mixture showed a significant increase in the cytokines conventionally associated with the prototypical inflammatory response observed in severe ALD, and interestingly, alcohol alone exhibited a different effect. Profibrogenic activation was also observed in the slices and investigated in the context of slice preparation. These results support the versatility of this organotypic model to study different pathways involved in alcohol-induced liver damage and ALD progression and highlight the applicability of the PCLS for drug discovery, confirming their relevance as a bridge between preclinical and clinical studies.

Hepatocellular carcinoma (HCC) is the main liver malignancy and has a high mortality rate. The discovery of novel biomarkers for early diagnosis, prognosis, and stratification purposes has the potential to alleviate its disease burden. Mass spectrometry (MS) is one of the principal technologies used in metabolomics, with different experimental methods and machine types for different phases of the biomarker discovery process. Here, we review why MS applications are useful for liver cancer, explain the MS technique, and briefly summarise recent findings from metabolomic MS studies on HCC. We also discuss the current challenges and the direction for future research.

Introduction: We recently discovered C57BL/6N male mice develop dilated cardiomyopathy (DCM) at 12 months, while the closely related C57BL/6J do not. We identified a variant (Chr8:85365179A>T, c.-5T>A) in myosin light chain kinase 3 ( Mylk3 ) in the B/6N substrain that abolishes translation of the predominant transcript (ENSMUST00000034133). MYLK3 phosphorylates many sarcomere proteins, in particular myosin light chain 2 (MYL2), vital for cardiac development and function. We therefore hypothesise this variant drives the DCM in the B/6N mice. Results: To determine whether the Mylk3 variant alone can cause DCM in mice, we generated two novel isogenic mouse lines. The first carries the Mylk3 c.-5T>A variant on the C57BL/6J background. The second carries the ‘wildtype’ Mylk3 variant on the C57BL/6N background (c.-5A>T, C57BL/6N Mylk3.6J ). While wildtype male C57BL/6J mice developed normally, male littermates expressing the mutant Mylk3 allele (C57BL/6J Mylk3.6N ) show signs of DCM at just 4 weeks old, with increased left ventricular diameter and volume, thinning of the posterior wall and a reduced ejection fraction. In contrast, the C57BL/6N mice develop DCM symptoms, but the C57BL/6N Mylk3.6J mice have smaller left ventricles, thicker left ventricular posterior wall and elevated ejection fraction. We assessed MYL2 phosphorylation by western blot, and contradictory to previous reports, found no difference between any of our mice lines. This may be due to the persistence of a shorter Mylk3 isoform that is unaffected by the variant due to a distinct N-terminus (ENSMUST00000122452; D3Z630). There was no difference between the isoforms in their ability to phosphorylate MYL2 suggesting the shorter isoform could compensate. Phosphoproteomics identified over 500 differentially phosphorylated peptides in 3-day old C57BL/6J and C57BL/6J Mylk3.6N mice. These include many key cardiac transcription factors, such as NFATC2 and FOXK1. Conclusion: We hypothesise that loss of MYLK3 may cause dilated cardiomyopathy in our mice by a MYL2-independent mechanism, possibly by altering vital cardiac transcription causing altered heart development.

Renewable fuel demand is growing to meet carbon neutrality mandates. With this move, owners want flexibility for storage, and tanks are needed for renewable feedstocks and fuels. Due to the chemistry of renewables (e.g., fatty acids), production/storage facilities face different corrosion challenges as it cannot be assumed that linings will offer similar protection where degradation may lead to corrosion of tanks. Sherwin-Williams is testing linings in lipid feedstocks up to 82 °C (180 °F), and we have observed greater temperature dependency than with petroleum products. Testing has been expanded to other feedstocks and temperatures.

Conceptualizes Gerrymandering as segregation and adopts spatial segregation measures to detect legislative districts that have the effect of disenfranchising black and Latino populations.

L’articolo si sofferma su una quasi sconosciuta prefazione scritta da William Carlos Williams ai sonetti dialettali di Giuseppe Gioachino Belli tradotti da Harold Norse alla fine degli anni Cinquanta. Nel breve saggio, qui tradotto per la prima volta in italiano, il poeta americano ribadisce con forza la sua poetica realista basata sull’uso dell’American Idiom, una lingua considerata diversa dall’inglese parlato nel Regno Unito, e il cui valore letterario viene paragonato a quello raggiunto da Belli nello scrivere i suoi sonetti in dialetto