Concentration and origin of lead (Pb) in liver and bone of Eurasian buzzards (Buteo buteo) in the United Kingdom.

Ingestion of lead (Pb) derived from ammunition used in the hunting of game animals is recognised to be a significant potential source of Pb exposure of wild birds, including birds of prey. However, there are only limited data for birds of prey in Europe regarding tissue concentrations and origins of Pb. Eurasian buzzards (Buteo buteo) found dead in the United Kingdom during an 11-year period were collected and the concentrations of Pb in the liver and femur were measured. Concentrations in the liver consistent with acute exposure to Pb were found in 2.7% of birds and concentration in the femur consistent with exposure to lethal levels were found in 4.0% of individuals. Pb concentration in the femur showed no evidence of consistent variation among or within years, but was greater for old than for young birds. The Pb concentration in the liver showed no effect of the birds' age, but varied markedly among years and showed a consistent tendency to increase substantially within years throughout the UK hunting season for gamebirds. The resemblance of the stable isotope composition of Pb from buzzard livers to that of Pb from the types of shotgun ammunition most widely-used in the UK increased markedly with increasing Pb concentration in the liver. Stable isotope results were consistent with 57% of the mass of Pb in livers of all of the buzzards sampled being derived from shotgun pellets, with this proportion being 89% for the birds with concentrations indicating acute exposure to Pb. Hence, most of the Pb acquired by Eurasian buzzards which have liver concentrations likely to be associated with lethal and sublethal effects is probably obtained when they prey upon or scavenge gamebirds and mammals shot using Pb shotgun pellets

Harnessing inter-disciplinary collaboration to improve emergency care in low- and middle-income countries (LMICs): results of research prioritisation setting exercise

Background More than half of deaths in low- and middle-income countries (LMICs) result from conditions that could be treated with emergency care - an integral component of universal health coverage (UHC) - through timely access to lifesaving interventions. Methods The World Health Organization (WHO) aims to extend UHC to a further 1 billion people by 2023, yet evidence supporting improved emergency care coverage is lacking. In this article, we explore four phases of a research prioritisation setting (RPS) exercise conducted by researchers and stakeholders from South Africa, Egypt, Nepal, Jamaica, Tanzania, Trinidad and Tobago, Tunisia, Colombia, Ethiopia, Iran, Jordan, Malaysia, South Korea and Phillipines, USA and UK as a key step in gathering evidence required by policy makers and practitioners for the strengthening of emergency care systems in limited-resource settings. Results The RPS proposed seven priority research questions addressing: identification of context-relevant emergency care indicators, barriers to effective emergency care; accuracy and impact of triage tools; potential quality improvement via registries; characteristics of people seeking emergency care; best practices for staff training and retention; and cost effectiveness of critical care – all within LMICs. Conclusions Convened by WHO and facilitated by the University of Sheffield, the Global Emergency Care Research Network project (GEM-CARN) brought together a coalition of 16 countries to identify research priorities for strengthening emergency care in LMICs. Our article further assesses the quality of the RPS exercise and reviews the current evidence supporting the identified priorities

The importance of perceptual experience in the esthetic appreciation of the body.

Several studies suggest that sociocultural models conveying extreme thinness as the widespread ideal of beauty exert an important influence on the perceptual and emotional representation of body image. The psychological mechanisms underlying such environmental influences, however, are unclear. Here, we utilized a perceptual adaptation paradigm to investigate how perceptual experience modulates body esthetic appreciation. We found that the liking judgments of round bodies increased or decreased after brief exposure to round or thin bodies, respectively. No change occurred in the liking judgments of thin bodies. The results suggest that perceptual experience may shape our esthetic appreciation to favor more familiar round body figures. Importantly, individuals with more deficits in interoceptive awareness were less prone to increase their liking ratings of round bodies after exposure, suggesting a specific risk factor for the susceptibility to the influence of the extreme thin vs. round body ideals of beauty portrayed by the media

Sustainable Supply Chain Management and the transition towards a Circular Economy: Evidence and some Applications

In the last decades, green and sustainable supply chain management practices have been developed, trying to integrate environmental concerns into organisations by reducing unintended negative consequences on the environment of production and consumption processes. In parallel to this, the circular economy discourse has been propagated in the industrial ecology literature and practice. Circular economy pushes the frontiers of environmental sustainability by emphasising the idea of transforming products in such a way that there are workable relationships between ecological systems and economic growth. Therefore, circular economy is not just concerned with the reduction of the use of the environment as a sink for residuals but rather with the creation of self-sustaining production systems in which materials are used over and over again. Through two case studies from different process industries (chemical and food), this paper compares the performances of traditional and circular production systems across a range of indicators. Direct, indirect and total lifecycle emissions, waste recovered, virgin resources use, as well as carbon maps (which provide a holistic visibility of the entire supply chain) are presented. The paper asserts that an integration of circular economy principles within sustainable supply chain management can provide clear advantages from an environmental point view. Emerging supply chain management challenges and market dynamics are also highlighted and discussed

Targeting Sphingosine Kinase 1 in Carcinoma Cells Decreases Proliferation and Survival by Compromising PKC Activity and Cytokinesis

Sphingosine kinases (SK) catalyze the phosphorylation of proapoptotic sphingosine to the prosurvival factor sphingosine 1-phosphate (S1P), thereby promoting oncogenic processes. Breast (MDA-MB-231), lung (NCI-H358), and colon (HCT 116) carcinoma cells were transduced with shRNA to downregulate SK-1 expression or treated with a pharmacologic SK-1 inhibitor. The effects of SK-1 targeting were investigated by measuring the level of intracellular sphingosine, the activity of protein kinase C (PKC) and cell cycle regulators, and the mitotic index. Functional assays included measurement of cell proliferation, colony formation, apoptosis, and cell cycle analysis. Downregulation of SK-1 or its pharmacologic inhibition increased intracellular sphingosine and decreased PKC activity as shown by reduced phosphorylation of PKC substrates. In MDA-MB-231 cells this effect was most pronounced and reduced cell proliferation and colony formation, which could be mimicked using exogenous sphingosine or the PKC inhibitor RO 31-8220. SK-1 downregulation in MDA-MB-231 cells increased the number of cells with 4N and 8N DNA content, and similar effects were observed upon treatment with sphingosine or inhibitors of SK-1 or PKC. Examination of cell cycle regulators unveiled decreased cdc2 activity and expression of Chk1, which may compromise spindle checkpoint function and cytokinesis. Indeed, SK-1 kd cells entered mitosis but failed to divide, and in the presence of taxol also failed to sustain mitotic arrest, resulting in further increased endoreduplication and apoptosis. Our findings delineate an intriguing link between SK-1, PKC and components of the cell cycle machinery, which underlines the significance of SK-1 as a target for cancer therapy

Increased Incidence of Vestibular Disorders in Patients With SARS-CoV-2

OBJECTIVE: Determine the incidence of vestibular disorders in patients with SARS-CoV-2 compared to the control population. STUDY DESIGN: Retrospective. SETTING: Clinical data in the National COVID Cohort Collaborative database (N3C). METHODS: Deidentified patient data from the National COVID Cohort Collaborative database (N3C) were queried based on variant peak prevalence (untyped, alpha, delta, omicron 21K, and omicron 23A) from covariants.org to retrospectively analyze the incidence of vestibular disorders in patients with SARS-CoV-2 compared to control population, consisting of patients without documented evidence of COVID infection during the same period. RESULTS: Patients testing positive for COVID-19 were significantly more likely to have a vestibular disorder compared to the control population. Compared to control patients, the odds ratio of vestibular disorders was significantly elevated in patients with untyped (odds ratio [OR], 2.39; confidence intervals [CI], 2.29-2.50; CONCLUSIONS: The incidence of vestibular disorders differed between COVID-19 variants and was significantly elevated in COVID-19-positive patients compared to the control population. These findings have implications for patient counseling and further research is needed to discern the long-term effects of these findings

Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds

Glioma Through the Looking GLASS: Molecular Evolution of Diffuse Gliomas and the Glioma Longitudinal AnalySiS Consortium

Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas (TCGA) and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal AnalySiS Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities, and ultimately, improved outcomes for a patient population in need

Highlights From the Annual Meeting of the American Epilepsy Society 2022

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia