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Within the past decade, an alarm was raised about microplastics in the remote and seemingly pristine Arctic Ocean. To gain further insight about the issue, microplastic abundance, distribution and composition in sea ice cores (n = 25) and waters underlying ice floes (n = 22) were assessed in the Arctic Central Basin (ACB). Potential microplastics were visually isolated and subsequently analysed using Fourier Transform Infrared (FT-IR) Spectroscopy. Microplastic abundance in surface waters underlying ice floes (0–18 particles m −3 ) were orders of magnitude lower than microplastic concentrations in sea ice cores (2–17 particles L −1 ). No consistent pattern was apparent in the vertical distribution of microplastics within sea ice cores. Backward drift trajectories estimated that cores possibly originated from the Siberian shelves, western Arctic and central Arctic. Knowledge about microplastics in environmental compartments of the Arctic Ocean is important in assessing the potential threats posed by microplastics to polar organisms.

Plastic, as a form of marine litter, is found in varying quantities and sizes around the globe from surface waters to deep-sea sediments. Identifying patterns of microplastic distribution will benefit an understanding of the scale of their potential effect on the environment and organisms. As sea ice extent is reducing in the Arctic, heightened shipping and fishing activity may increase marine pollution in the area. Microplastics may enter the region following ocean transport and local input, although baseline contamination measurements are still required. Here we present the first study of microplastics in Arctic waters, south and southwest of Svalbard, Norway. Microplastics were found in surface (top 16 cm) and sub-surface (6 m depth) samples using two independent techniques. Origins and pathways bringing microplastic to the Arctic remain unclear. Particle composition (95% fibres) suggests they may either result from the breakdown of larger items (transported over large distances by prevailing currents, or derived from local vessel activity), or input in sewage and wastewater from coastal areas. Concurrent observations of high zooplankton abundance suggest a high probability for marine biota to encounter microplastics and a potential for trophic interactions. Further research is required to understand the effects of microplastic-biota interaction within this productive environment.

The lithium-ion battery (LIB) recycling market is becoming increasingly important because of the widespread use of LIBs in every aspect of our lives. Mobile devices and electric cars represent the largest application areas for LIBs. Vigorous innovation in these sectors is spurring continuous deployment of LIB powered devices, and consequently more and more LIBs will become waste as they approach end of life. Considering the significant economic and environmental impacts, recycling is not only necessary, but also urgent. The WPI group has successfully developed a closed-loop recycling process, and has previously demonstrated it on a relatively small scale 1 kg spent batteries per experiment. Here, we show that the closed-loop recycling process can be successfully scaled up to 30 kg of spent LIBs from electric vehicle recycling streams, and the recovered cathode powder shows similar (or better) performance to equivalent commercial powder when evaluated in both coin cells and single layer pouch cells. All of these results demonstrate the closed-loop recycling process has great adaptability and can be further developed into industrial scale.

Base editing (BE) can permanently correct over half of known human pathogenic genetic variants without requiring a repair template, thus serving as a promising therapeutic tool to treat a broad spectrum of genetic diseases. However, the broad activity windows of current base editors pose a major challenge to their therapeutic application. Here, we show that integrating a naturally occurring oligonucleotide binding module into the deaminase active center of TadA-8e, a highly active deoxyadenosine deaminase, enhances its editing specificity. When conjugated with a Cas9 nickase or alternative PAM Cas9 variants, the engineered TadA variant—TadA-NW1—consistently achieves robust A-to-G editing efficiencies within an editing window consisting of four nucleotides, substantially narrower than the 10-bp editing window of the TadA-8e-derived ABEs. Moreover, compared to ABE8e, ABE-NW1 shows significantly decreased Cas9-dependent and -independent off-target activity while maintaining similar on-target editing efficiency. Further, TadA-NW1 can be reprogrammed to perform desired cytidine deamination and adenine transversion within a restricted editing window. Finally, in a cystic fibrosis (CF) cell model, ABE-NW1 outperforms existing ABEs in accurately and efficiently correcting the CFTR W1282X variant, one of the most common CF-causing mutations. In all, we engineered a suite of base editors with refined activity windows, enabling more precise base editing. Importantly, this study presents a streamlined genome editor re-engineering strategy to accelerate the development of therapeutic base editing. The broad activity windows of current base editors pose a major challenge to their therapeutic application. Here, the authors established a generalizable re-engineering framework to narrow the activity windows of diverse base editors, streamlining the development of therapeutic base editing.

Amoebic gill disease (AGD) is one of the main diseases affecting Atlantic salmon ( Salmo salar L.) mariculture. Hallmarks of AGD are hyperplasia of the lamellar epithelium and increased production of gill mucus. This study investigated the expression of genes involved in mucus secretion, cell cycle regulation, immunity and oxidative stress in gills using a targeted 21-gene PCR array. Gill samples were obtained from experimental and natural Neoparamoeba perurans infections, and sampling points included progressive infection stages and post-freshwater treatment. Up-regulation of genes related to mucin secretion and cell proliferation, and down-regulation of pro-inflammatory and pro-apoptotic genes were associated with AGD severity, while partial restoration of the gill homeostasis was detected post-treatment. Mucins and Th2 cytokines accoun ted for most of the variability observed between groups highlighting their key role in AGD. Two mucins ( muc5 , muc 1 8 ) showed differential regulation upon disease. Substantial up-regulation of the secreted muc5 was detected in clinical AGD, and the membrane bound muc18 showed an opposite pattern. Th2 cytokines, il4/13a and il4/13b2 , were significantly up-regulated from 2 days post-infection onwards, and changes were lesion-specific. Despite the differences between experimental and natural infections, both yielded comparable results that underline the importance of the studied genes in the respiratory organs of fish, and during AGD progression.

IntroductionInitiation & optimisation of disease-modifying medicines in patients with heart failure with a reduced ejection fraction (HFrEF) is the cornerstone of management(1). Delivering optimal medical therapy (OMT)* has proven morbidity & mortality benefits(1). The rising prevalence of heart failure (HF) & backlog pressure due the impact of COVID have put enormous pressure on the majority of heart failure services in the country. There is a need to build capacity within HF services to meet demands. With appropriate training & support, GP practice based, clinical pharmacists could deliver HF medicines optimisation clinics in the community. This would aim to complement existing specialist services, strengthen capacity & improve patient access to medicines with significant prognostic value. In a pilot project, we aim to determine the efficacy & safety to conduct community based, pharmacist-led clinics to optimise pharmacotherapy for patients with chronic heart failure.MethodPharmacist prescribers working in participating GP surgeries completed a variety of HF training. A HF competency framework was utilised, evidence of learning & skills was documented. Patients with HFrEF were identified by the local hospital HF team after new diagnosis or decompensation. Patients were also identified after auditing existing primary care HF registers, prioritising patients who had not yet achieved OMT. Pharmacists delivered consultations; performed clinical examination, prescribed medication, reviewed blood results & arranged follow-up. Patient education was provided together with HF self-management plans. Pharmacists had access to multi-disciplinary team meetings & HF consultant advice throughout. All appointments were recorded together with details of symptom burden, drug interventions and adverse events (ADRs). Where clinical advice from the HF consultant was sought, this was recorded. Patients continued under pharmacist follow-up until they were taking OMT, after which a repeat echocardiogram & BNP serology was arranged. Patient questionnaires were provided.Results59 patients were seen in pharmacist-led clinics (Table 1). A total of 170 pharmacist appointments yielded 93 new drug initiations (Picture 1) & 71 dose titrations. After pharmacist-led medicines optimisation, HF symptoms reduced by half a point on the NYHA scale (1.81 to 1.34, N=59), NT-pro-BNP reduced from 5265pg/L to 1265pg/L (N=21), LVEF increased from 37% to 42% (N=18) for the average patient (Table 2). There were 29 ADRs reported. The most common were hyperkalaemia (N=11), renal function decline (N= 5) and hypotension (N=4). All of the ADRs were safely managed in primary care. Pharmacists were largely working autonomously; only 18% (30/170) of consultations required specialist advice & 6 patients were referred back to the hospital team, due to complexity. Overwhelmingly patients felt the service was effective. Patients had confidence in the pharmacist & the majority would recommend the same type of appointment to another person who had a similar condition (Picture 2).ConclusionHeart failure medicines optimisation can be delivered safely, efficiently & competently in primary care, by suitably trained pharmacist prescribers. Further service evaluation & expansion is urgently needed to improve access to heart failure care in primary care.ReferencesMcDonagh, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42:3599-3726. doi:10.1093/eurheartj/ehab368.Footnote: * OMT is defined as maximal tolerated doses of ‘quadruple therapy’; beta-blockers; mineralocorticoid receptor antagonists (MRA); angiotensin receptor neprilysin inhibitors (ARNi); and sodium-glucose cotransporter-2 inhibitAbstract 82 Figure 1Abstract 82 Table 1Patients and appointments profile (12 months, Sept 2021 – Sept 2022) Patients Number Total Number of Patients59Male34Female25Average age (years) (range – 38–91)73 Workload Number Appointments (including Pharmacist, Health Care Assistant / Phlebotomist)352Pharmacist Consultations170Pharmacist Initial HF consultation 23Pharmacist HF follow-up consultation 147Health Care Assistant/Phlebotomist consultations182Bloods test/monitoring reviewed 180Abstract 82 Table 2Patient outcomesAverage (at baseline)Average (after optimisation) NYHA score (N=59)1.811.34NT-pro-BNP (N=21)52651265Ejection Fraction (N=18)3742Number of patients at OMT* 21*Optimal medical therapy (OMT) was strictly defined as those being prescribed maximal tolerated doses of quadruple therapy (ARNi, MRA, Beta-blockers and SLGT-2i) at the end of the project. Patients who had contraindications and/or significant risks that precluded them from being able to take all four medicine classes, were not included in the figure.Abstract 82 Figure 2Conflict of InterestAstra-Zeneca funded the 12 month pilot

Amoebic Gill Disease (AGD), caused by the protozoan extracellular parasite Paramoeba perurans ( P. perurans ) is a disease affecting Atlantic salmon ( Salmo salar ). This study investigated the gill transcriptomic profile of pre-clinical AGD using RNA-sequencing (RNA-seq) technology. RNA-seq libraries generated at 0, 4, 7, 14 and 16 days post infection (dpi) identified 19,251 differentially expressed genes (DEGs) of which 56.2% were up-regulated. DEGs mapped to 224 Gene Ontology (GO) terms including 140 biological processes (BP), 45 cellular components (CC), and 39 molecular functions (MF). A total of 27 reference pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and 15 Reactome gene sets were identified. The RNA-seq data was validated using real-time, quantitative PCR (qPCR). A host immune response though the activation of complement and the acute phase genes was evident at 7 dpi, with a concurrent immune suppression involving cytokine signalling, notably in interleukins, interferon regulatory factors and tumour necrosis factor-alpha ( tnf- α) genes. Down-regulated gene expression with involvement in receptor signalling pathways (NOD-like, Toll-like and RIG-1) were also identified. The results of this study support the theory that P. perurans can evade immune surveillance during the initial stages of gill colonisation through interference of signal transduction pathways.

Background Traditional treatments for pathological fractures of the proximal femur resulting from metastatic bone disease include fixation with intramedullary nailing supplemented with polymethylmethacrylate, osteosynthesis with a plate-screw construct and polymethylmethacrylate, or endoprosthetic reconstruction. Despite the frequent practice of these treatments, treatment outcomes have not been rigorously compared. In addition, very few studies examine specific approaches to endoprosthetic reconstruction such as long stem hemiarthroplasty. Questions/purposes This study examines survival, functional outcomes, and complications associated with long stem hemiarthroplasty in a small group of patients treated for impending and actual pathologic fractures of the proximal femur resulting from metastatic bone disease. Methods Between 2012 and 2015, 21 patients were treated with long stem cemented hemiarthroplasty in 22 limbs. During that time, indications for this approach included lesions from metastases, myeloma, or lymphoma involving the proximal femur that resulted in an impending or actual pathological fracture. An impending fracture was classified as a painful lesion with at least 50% cortical erosion. During the study period, six patients with proximal femoral metastases not deemed to meet these indications were treated with other surgical approaches such as intramedullary nailing supplemented with polymethylmethacrylate and osteosynthesis with a plate-screw construct and polymethylmethacrylate. Mortality was tracked through medical records and phone calls to the patients and their families. Followup for the entire group of patients (n = 22) ranged from 1 to 27 months with a mean duration of 11 months. For patients with at least 1 year of followup (n = 11), the mean duration was 18 months (range, 12–27 months) and for patients with less than 1 year of followup (n = 11), the mean duration was 3 months (range, 1–11 months). Functional outcomes were evaluated according to the Musculoskeletal Tumor Society (MSTS) scoring system for lower extremities, the Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status, and the Karnofsky Performance Scale (KPS) Index. Scores and complications were determined by direct patient examination, retrospective chart review, review of a longitudinally maintained institutional database, and followup phone calls. Results Ten patients died of disease within the followup period. Before surgery, the median total MSTS score for the entire group of patients (n = 22) was 4.5 (range, 0–23), the median ECOG score was 3.5 (range, 1–4), and the median KPS score was 40 (range, 30–70). Postoperatively, the median total MSTS score (measured at most recent followup) for the entire group of patients was 21 (range, 5–30), the median ECOG score was 2 (range, 0–3, 68% ≤ 2), and the median KPS score was 60 (range, 40–100). For the 11 patients with at least 1 year of followup, the median total MSTS score (measured at most recent followup) was 27 (range, 21–30), the median ECOG score was 1 (range, 0–2, 100% ≤ 2), and the median KPS score was 80 (range, 60–100). For the remaining 11 patients with less than 1 year of followup, the median total MSTS score (measured at most recent followup) was 11 (range, 5–25), the median ECOG score was 3 (range, 1–3, 36% ≤ 2), and the median KPS score was 40 (range, 40–80). Complications included one periprosthetic fracture resulting from a fall, three cases of radiation-induced edema, and two cases of sciatica that developed unrelated to the procedure. Conclusions Long stem cemented hemiarthroplasty results in fair levels of function in a complex population of patients whose prognosis is sometimes measured only in months and who otherwise might be disabled by their metastatic lesions. Comparative trials applying consistent indications and inclusion criteria should be performed between this approach and fixation with intramedullary nailing supplemented with polymethylmethacrylate as well as osteosynthesis with a plate-screw construct and polymethylmethacrylate. Level of Evidence Level IV, therapeutic study.