Peripheral neuropathy secondary to a ‘domino’ liver transplant: a case report

Background: Peripheral neuropathy caused by amyloidosis is one of the well-recognised sequelae of mutations in the transthyretin gene (TTR).// Case presentation: We describe a case of peripheral neuropathy in a White British 74 year old man with wild-type TTR, 8 years following receipt of a ‘domino’ liver transplant (from a donor with a TTR mutation). The clinical phenotype and neurophysiology, coupled with presence of ATTR amyloid deposits on fat biopsy, established the diagnosis of ATTR amyloid neuropathy, as a consequence of receipt of a variant-TTR secreting liver. A nerve biopsy was not clinically appropriate for this patient. Such cases are rare since recipients of such livers are typically restricted to people whose natural lifespan is unlikely to stretch into the anticipated symptomatic period of ATTR amyloidosis. However, novel “gene silencing” therapeutics are now available which can dramatically alter the course of this disorder, by reducing the proportion of abnormal proteins.// Conclusions: This represents a rare but predictable iatrogenic side effect, and doctors should be aware of this eventuality occurring in a shorter time span than previously anticipated

Peripheral neuropathy secondary to a ‘domino’ liver transplant:a case report

Abstract Background Peripheral neuropathy caused by amyloidosis is one of the well-recognised sequelae of mutations in the transthyretin gene (TTR). Case presentation We describe a case of peripheral neuropathy in a White British 74 year old man with wild-type TTR, 8 years following receipt of a ‘domino’ liver transplant (from a donor with a TTR mutation). The clinical phenotype and neurophysiology, coupled with presence of ATTR amyloid deposits on fat biopsy, established the diagnosis of ATTR amyloid neuropathy, as a consequence of receipt of a variant-TTR secreting liver. A nerve biopsy was not clinically appropriate for this patient. Such cases are rare since recipients of such livers are typically restricted to people whose natural lifespan is unlikely to stretch into the anticipated symptomatic period of ATTR amyloidosis. However, novel “gene silencing” therapeutics are now available which can dramatically alter the course of this disorder, by reducing the proportion of abnormal proteins. Conclusions This represents a rare but predictable iatrogenic side effect, and doctors should be aware of this eventuality occurring in a shorter time span than previously anticipated

Reasons to Be Skeptical about Sentience and Pain in Fishes and Aquatic Invertebrates

The welfare of fishes and aquatic invertebrates is important, and several jurisdictions have included these taxa under welfare regulation in recent years. Regulation of welfare requires use of scientifically validated welfare criteria. This is why applying Mertonian skepticism toward claims for sentience and pain in fishes and aquatic invertebrates is scientifically sound and prudent, particularly when those claims are used to justify legislation regulating the welfare of these taxa. Enacting welfare legislation for these taxa without strong scientific evidence is a societal and political choice that risks creating scientific and interpretational problems as well as major policy challenges, including the potential to generate significant unintended consequences. In contrast, a more rigorous science-based approach to the welfare of aquatic organisms that is based on verified, validated and measurable endpoints is more likely to result in “win-win” scenarios that minimize the risk of unintended negative impacts for all stakeholders, including fish and aquatic invertebrates. The authors identify as supporters of animal welfare, and emphasize that this issue is not about choosing between welfare and no welfare for fish and aquatic invertebrates, but rather to ensure that important decisions about their welfare are based on scientifically robust evidence. These ten reasons are delivered in the spirit of organized skepticism to orient legislators, decision makers and the scientific community, and alert them to the need to maintain a high scientific evidential bar for any operational welfare indicators used for aquatic animals, particularly those mandated by legislation. Moving forward, maintaining the highest scientific standards is vitally important, in order to protect not only aquatic animal welfare, but also global food security and the welfare of humans

Tissue proteomic analysis identifies mechanisms and stages of immunopathology in fatal COVID-19

Funding: This work was funded by UK Research and Innovation (UKRI) (Coronavirus Disease [COVID-19] Rapid Response Initiative; MR/V028790/1 to C.D.L., D.A.D., and J.A.H.), LifeArc (through the University of Edinburgh STOPCOVID funding award, to K.D, D.A.D., C.D.L), The Chief Scientist Office (RARC-19 Funding Call, ‘Inflammation in Covid-19: Exploration of Critical Aspects of Pathogenesis; COV/EDI/20/10’ to D.A.D, C.D.L, C.D.R, J.K.B and D.J.H), and Medical Research Scotland (CVG-1722- 2020 to DAD, CDL, CDR, JKB, and DJH). C.D.L is funded by a Wellcome Trust Clinical Career Development Fellowship (206566/Z/17/Z). J.K.B. and C.D.R. are supported by the Medical Research Council (grant MC_PC_19059) as part of the ISARIC Coronavirus Clinical Characterisation Consortium (ISARIC-4C). C.D.R. is supported by an Edinburgh Clinical Academic Track (ECAT)/Wellcome Trust PhD Training Fellowship for Clinicians award (214178/Z/18/Z). J.A.H. is supported by the U.S. Food and Drug Administration (contract 75F40120C00085, Characterization of severe coronavirus infection in humans and model systems for medical countermeasure development and evaluation’). G.C.O is funded by an NRS Clinician award. N.N.G. is funded by a Pathological Society Award. A.R.A. is supported by a Cancer Research UK Clinician Scientist Fellowship award (A24867).Immunopathology occurs in the lung and spleen in fatal COVID-19, involving monocytes/macrophages and plasma cells. Anti-inflammatory therapy reduces mortality but additional therapeutic targets are required. We aimed to gain mechanistic insight into COVID-19 immunopathology by targeted proteomic analysis of pulmonary and splenic tissues. Lung parenchymal and splenic tissue was obtained from 13 post-mortem examinations of patients with fatal COVID-19. Control tissue was obtained from cancer resection samples (lung) and deceased organ donors (spleen). Protein was extracted from tissue by phenol extraction. Olink® multiplex immunoassay panels were used for protein detection and quantification. Proteins with increased abundance in the lung included MCP-3, antiviral TRIM21 and pro-thrombotic TYMP. OSM and EN-RAGE/S100A12 abundance was correlated, and associated with inflammation severity. Unsupervised clustering identified ‘early viral’ and ‘late inflammatory’ clusters with distinct protein abundance profiles, and differences in illness duration prior to death and presence of viral RNA. In the spleen, lymphocyte chemotactic factors and CD8A were decreased in abundance, and pro-apoptotic factors were increased. B-cell receptor signalling pathway components and macrophage colony stimulating factor (CSF-1) were also increased. Additional evidence for a sub-set of host factors (including DDX58, OSM, TYMP, IL-18, MCP-3 and CSF-1) was provided by overlap between (i) differential abundance in spleen and lung tissue, (ii) meta-analysis of existing datasets, and (iii) plasma proteomic data. This proteomic analysis of lung parenchymal and splenic tissue from fatal COVID-19 provides mechanistic insight into tissue anti-viral responses, inflammation and disease stages, macrophage involvement, pulmonary thrombosis, splenic B-cell activation and lymphocyte depletion.Publisher PDFPeer reviewe

Cobalt containing glass fibres and their synergistic effect on the HIF-1 pathway for wound healing applications

Introduction and Methods: Chronic wounds are a major healthcare problem, but their healing may be improved by developing biomaterials which can stimulate angiogenesis, e.g. by activating the Hypoxia Inducible Factor (HIF) pathway. Here, novel glass fibres were produced by laser spinning. The hypothesis was that silicate glass fibres that deliver cobalt ions will activate the HIF pathway and promote the expression of angiogenic genes. The glass composition was designed to biodegrade and release ions, but not form a hydroxyapatite layer in body fluid. Results and Discussion: Dissolution studies demonstrated that hydroxyapatite did not form. When keratinocyte cells were exposed to conditioned media from the cobalt-containing glass fibres, significantly higher amounts of HIF-1α and Vascular Endothelial Growth Factor (VEGF) were measured compared to when the cells were exposed to media with equivalent amounts of cobalt chloride. This was attributed to a synergistic effect of the combination of cobalt and other therapeutic ions released from the glass. The effect was also much greater than the sum of HIF-1α and VEGF expression when the cells were cultured with cobalt ions and with dissolution products from the Co-free glass, and was proven to not be due to a rise in pH. The ability of the glass fibres to activate the HIF-1 pathway and promote VEGF expression shows the potential for their use in chronic wound dressings.National Institute for Health Research (Reino Unido) | Ref. II-ES-1010-10094Agencia Estatal de Investigación | Ref. PID2020-117900RB-I0

Global Intraurban Intake Fractions for Primary Air Pollutants from Vehicles and Other Distributed Sources

We model intraurban intake fraction (iF) values for distributed ground-level emissions in all 3646 global cities with more than 100,000 inhabitants, encompassing a total population of 2.0 billion. For conserved primary pollutants, population-weighted median, mean, and interquartile range iF values are 26, 39, and 14-52 ppm, respectively, where 1 ppm signifies 1 g inhaled/t emitted. The global mean urban iF reported here is roughly twice as large as previous estimates for cities in the United States and Europe. Intake fractions vary among cities owing to differences in population size, population density, and meteorology. Sorting by size, population-weighted mean iF values are 65, 35, and 15 ppm, respectively, for cities with populations larger than 3, 0.6-3, and 0.1-0.6 million. The 20 worldwide megacities (each >10 million people) have a population-weighted mean iF of 83 ppm. Mean intraurban iF values are greatest in Asia and lowest in land-rich high-income regions. Country-average iF values vary by a factor of 3 among the 10 nations with the largest urban populations

Cosmic CARNage II: the evolution of the galaxy stellar mass functionin observations and galaxy formation models

We present a comparison of the observed evolving galaxy stellar mass functions with the predictions of eight semi-analytic models and one halo occupation distribution model. While most models are able to fit the data at low redshift, some of them struggle to simultaneously fit observations at high redshift. We separate the galaxies into ‘passive’ and ‘star-forming’ classes and find that several of the models produce too many low-mass star-forming galaxies at high redshift compared to observations, in some cases by nearly a factor of 10 in the redshift range 2.5 < z < 3.0. We also find important differences in the implied mass of the dark matter haloes the galaxies inhabit, by comparing with halo masses inferred from observations. Galaxies at high redshift in the models are in lower mass haloes than suggested by observations, and the star formation efficiency in low-mass haloes is higher than observed. We conclude that many of the models require a physical prescription that acts to dissociate the growth of low-mass galaxies from the growth of their dark matter haloes at high redshift

Cosmic CARNage II: the evolution of the galaxy stellar mass function in observations and galaxy formation models

We present a comparison of the observed evolving galaxy stellar mass functions with the predictions of eight semi-analytic models and one halo occupation distribution model. While most models are able to fit the data at low redshift, some of them struggle to simultaneously fit observations at high redshift. We separate the galaxies into 'passive' and 'star-forming' classes and find that several of the models produce too many low-mass star-forming galaxies at high redshift compared to observations, in some cases by nearly a factor of 10 in the redshift range 2.5 < z < 3.0. We also find important differences in the implied mass of the dark matter haloes the galaxies inhabit, by comparing with halo masses inferred from observations. Galaxies at high redshift in the models are in lower mass haloes than suggested by observations, and the star formation efficiency in low-mass haloes is higher than observed. We conclude that many of the models require a physical prescription that acts to dissociate the growth of low-mass galaxies from the growth of their dark matter haloes at high redshift.Facultad de Ciencias Astronómicas y GeofísicasInstituto de Astrofísica de La Plat

Cosmic CARNage II: the evolution of the galaxy stellar mass function in observations and galaxy formation models

We present a comparison of the observed evolving galaxy stellar mass functions with the predictions of eight semi-analytic models and one halo occupation distribution model. While most models are able to fit the data at low redshift, some of them struggle to simultaneously fit observations at high redshift. We separate the galaxies into 'passive' and 'star-forming' classes and find that several of the models produce too many low-mass star-forming galaxies at high redshift compared to observations, in some cases by nearly a factor of 10 in the redshift range 2.5 < z < 3.0. We also find important differences in the implied mass of the dark matter haloes the galaxies inhabit, by comparing with halo masses inferred from observations. Galaxies at high redshift in the models are in lower mass haloes than suggested by observations, and the star formation efficiency in low-mass haloes is higher than observed. We conclude that many of the models require a physical prescription that acts to dissociate the growth of low-mass galaxies from the growth of their dark matter haloes at high redshift.Facultad de Ciencias Astronómicas y GeofísicasInstituto de Astrofísica de La Plat

A threatened ecological community: Research advances and priorities for Banksia woodlands

The rapid expansion of urban areas worldwide is leading to native habitat loss and ecosystem fragmentation and degradation. Although the study of urbanisation\u27s impact on biodiversity is gaining increasing interest globally, there is still a disconnect between research recommendations and urbanisation strategies. Expansion of the Perth metropolitan area on the Swan Coastal Plain in south-western Australia, one of the world\u27s thirty-six biodiversity hotspots, continues to affect the Banksia Woodlands (BWs) ecosystem, a federally listed Threatened Ecological Community (TEC). Here, we utilise the framework of a 1989 review of the state of knowledge of BWs ecology and conservation to examine scientific advances made in understanding the composition, processes and functions of BWs and BWs\u27 species over the last 30 years. We highlight key advances in our understanding of the ecological function and role of mechanisms in BWs that are critical to the management of this ecosystem. The most encouraging change since 1989 is the integration of research between historically disparate ecological disciplines. We outline remaining ecological knowledge gaps and identify key research priorities to improve conservation efforts for this TEC. We promote a holistic consideration of BWs with our review providing a comprehensive document that researchers, planners and managers may reference. To effectively conserve ecosystems threatened by urban expansion, a range of stakeholders must be involved in the development and implementation of best practices to conserve and maintain both biodiversity and human wellbeing