Hyperammonemic encephalopathy as a manifestation of Reye syndrome in a previously-healthy 14-year-old girl: A case report

Reye syndrome is seldom considered in the older child presenting with acute encephalopathy. The paucity of literature on Reye syndrome in the past 30 years highlights the importance of sharing new observations of this less-commonly considered disease. This case details an atypical presentation of Reye syndrome in an adolescent girl whose course was unexpectedly complicated by dialysis disequilibrium syndrome, occurring as a result of rapid metabolic shifts in the setting of urgent hemodialysis. A 14-year-old, previously healthy girl born to non-consanguineous Pakistani parents presented with acute-onset encephalopathy characterized by aggressive behaviour and altered level of consciousness. This was preceded by frequent vomiting and weeks of disordered eating. Laboratory findings included high anion-gap [30 (normal range, \u3c14)] metabolic acidosis [pH 7.23 (normal range, 7.35-7.45), bicarbonate 10 mmol/L (normal range, 22-29 mmol/L)] with markedly elevated peak levels of lactate [13.6 mmol/L (normal range, 0.5-2.2 mmol/L)] and ammonia [573 μmol/L (normal range, 11-48 μmol/L)]. Emergent hemodialysis was undertaken for management of severe hyperammonemia, with subsequent worsening of cerebral edema, elevated intracranial pressure, and consequent uncal and tonsillar herniation, in keeping with the development of dialysis disequilibrium syndrome. The patient was ultimately diagnosed with Reye syndrome after extensive biochemical and molecular testing including exome sequencing were non-contributory. This diagnosis would be consistent with her poor nutritional state, depleted carnitine levels, mild liver dysfunction and hyperammonemia. Two weeks of intensive care were required. The patient was ultimately discharged to a rehabilitation facility with ongoing fatigue and regression in motor and cognitive domains. Hyperammonemic encephalopathy should prompt consideration for Reye syndrome. Hyperammonemia is a medical emergency; the extremely time-sensitive nature of hyperammonemia management mandates that ammonia level testing be undertaken for any unexplained encephalopathy. Severe elevations can result in neurological impairment, cerebral edema, and are acutely life-threatening. Hemodialysis may be indicated for levels \u3e150 μmol/L; the urgency of ammonia clearance must be balanced against the risk of developing dialysis disequilibrium syndrome

A novel ICK mutation causes ciliary disruption and lethal endocrine-cerebro-osteodysplasia syndrome

Background: Endocrine-cerebro-osteodysplasia (ECO) syndrome [MIM:612651] caused by a recessive mutation (p.R272Q) in Intestinal cell kinase (ICK) shows significant clinical overlap with ciliary disorders. Similarities are strongest between ECO syndrome, the Majewski and Mohr-Majewski short-rib thoracic dysplasia (SRTD) with polydactyly syndromes, and hydrolethalus syndrome. In this study, we present a novel homozygous ICK mutation in a fetus with ECO syndrome and compare the effect of this mutation with the previously reported ICK variant on ciliogenesis and cilium morphology. Results: Through homozygosity mapping and whole-exome sequencing, we identified a second variant (c.358G\u3eT; p.G120C) in ICK in a Turkish fetus presenting with ECO syndrome. In vitro studies of wild-type and mutant mRFP-ICK (p.G120C and p.R272Q) revealed that, in contrast to the wild-type protein that localizes along the ciliary axoneme and/or is present in the ciliary base, mutant proteins rather enrich in the ciliary tip. In addition, immunocytochemistry revealed a decreased number of cilia in ICK p.R272Q-affected cells. Conclusions: Through identification of a novel ICK mutation, we confirm that disruption of ICK causes ECO syndrome, which clinically overlaps with the spectrum of ciliopathies. Expression of ICK-mutated proteins result in an abnormal ciliary localization compared to wild-type protein. Primary fibroblasts derived from an individual with ECO syndrome display ciliogenesis defects. In aggregate, our findings are consistent with recent reports that show that ICK regulates ciliary biology in vitro and in mice, confirming that ECO syndrome is a severe ciliopathy

Polymerization-induced self-assembly of block copolymer nanoparticles via RAFT non-aqueous dispersion polymerization

There is considerable current interest in polymerization-induced self-assembly (PISA) via reversible addition–fragmentation chain transfer (RAFT) polymerization as a versatile and efficient route to various types of block copolymer nano-objects. Many successful PISA syntheses have been conducted in water using either RAFT aqueous dispersion polymerization or RAFT aqueous emulsion polymerization. In contrast, this review article is focused on the growing number of RAFT PISA formulations developed for non-aqueous media. A wide range of monomers have been utilized for both the stabilizer and core-forming blocks to produce diblock copolymer nanoparticles in either polar or non-polar media (including supercritical CO2 and ionic liquids) via RAFT dispersion polymerization. Such nanoparticles possess spherical, worm-like or vesicular morphologies, often with controllable size and functionality. Detailed characterization of such sterically stabilized diblock copolymer dispersions provides important insights into the various morphological transformations that can occur both during the PISA synthesis and also on subsequent exposure to a suitable external stimulus (e.g. temperature)

Lysosomes in iron metabolism, ageing and apoptosis

The lysosomal compartment is essential for a variety of cellular functions, including the normal turnover of most long-lived proteins and all organelles. The compartment consists of numerous acidic vesicles (pH ∼4 to 5) that constantly fuse and divide. It receives a large number of hydrolases (∼50) from the trans-Golgi network, and substrates from both the cells’ outside (heterophagy) and inside (autophagy). Many macromolecules contain iron that gives rise to an iron-rich environment in lysosomes that recently have degraded such macromolecules. Iron-rich lysosomes are sensitive to oxidative stress, while ‘resting’ lysosomes, which have not recently participated in autophagic events, are not. The magnitude of oxidative stress determines the degree of lysosomal destabilization and, consequently, whether arrested growth, reparative autophagy, apoptosis, or necrosis will follow. Heterophagy is the first step in the process by which immunocompetent cells modify antigens and produce antibodies, while exocytosis of lysosomal enzymes may promote tumor invasion, angiogenesis, and metastasis. Apart from being an essential turnover process, autophagy is also a mechanism by which cells will be able to sustain temporary starvation and rid themselves of intracellular organisms that have invaded, although some pathogens have evolved mechanisms to prevent their destruction. Mutated lysosomal enzymes are the underlying cause of a number of lysosomal storage diseases involving the accumulation of materials that would be the substrate for the corresponding hydrolases, were they not defective. The normal, low-level diffusion of hydrogen peroxide into iron-rich lysosomes causes the slow formation of lipofuscin in long-lived postmitotic cells, where it occupies a substantial part of the lysosomal compartment at the end of the life span. This seems to result in the diversion of newly produced lysosomal enzymes away from autophagosomes, leading to the accumulation of malfunctioning mitochondria and proteins with consequent cellular dysfunction. If autophagy were a perfect turnover process, postmitotic ageing and several age-related neurodegenerative diseases would, perhaps, not take place

Body appreciation around the world: Measurement invariance of the Body Appreciation Scale-2 (BAS-2) across 65 nations, 40 languages, gender identities, and age.

The Body Appreciation Scale-2 (BAS-2) is a widely used measure of a core facet of the positive body image construct. However, extant research concerning measurement invariance of the BAS-2 across a large number of nations remains limited. Here, we utilised the Body Image in Nature (BINS) dataset - with data collected between 2020 and 2022 - to assess measurement invariance of the BAS-2 across 65 nations, 40 languages, gender identities, and age groups. Multi-group confirmatory factor analysis indicated that full scalar invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional BAS-2 model has widespread applicability. There were large differences across nations and languages in latent body appreciation, while differences across gender identities and age groups were negligible-to-small. Additionally, greater body appreciation was significantly associated with higher life satisfaction, being single (versus being married or in a committed relationship), and greater rurality (versus urbanicity). Across a subset of nations where nation-level data were available, greater body appreciation was also significantly associated with greater cultural distance from the United States and greater relative income inequality. These findings suggest that the BAS-2 likely captures a near-universal conceptualisation of the body appreciation construct, which should facilitate further cross-cultural research. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Body appreciation around the world: Measurement invariance of the Body Appreciation Scale-2 (BAS-2) across 65 nations, 40 languages, gender identities, and age

Abstract The Body Appreciation Scale-2 (BAS-2) is a widely used measure of a core facet of the positive body image construct. However, extant research concerning measurement invariance of the BAS-2 across a large number of nations remains limited. Here, we utilised the Body Image in Nature (BINS) dataset – with data collected between 2020 and 2022 – to assess measurement invariance of the BAS-2 across 65 nations, 40 languages, gender identities, and age groups. Multi-group confirmatory factor analysis indicated that full scalar invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional BAS-2 model has widespread applicability. There were large differences across nations and languages in latent body appreciation, while differences across gender identities and age groups were negligible-to-small. Additionally, greater body appreciation was significantly associated with higher life satisfaction, being single (versus being married or in a committed relationship), and greater rurality (versus urbanicity). Across a subset of nations where nation-level data were available, greater body appreciation was also significantly associated with greater cultural distance from the United States and greater relative income inequality. These findings suggest that the BAS-2 likely captures a near-universal conceptualisation of the body appreciation construct, which should facilitate further cross-cultural research

Exposure and connectedness to natural environments: An examination of the measurement invariance of the Nature Exposure Scale (NES) and Connectedness to Nature Scale (CNS) across 65 nations, 40 languages, gender identities, and age groups

Detachment from nature is contributing to the environmental crisis and reversing this trend requires detailed monitoring and targeted interventions to reconnect people to nature. Most tools measuring nature exposure and attachment were developed in high-income countries and little is known about their robustness across national and linguistic groups. Therefore, we used data from the Body Image in Nature Survey to assess measurement invariance of the Nature Exposure Scale (NES) and the Connectedness to Nature Scale (CNS) across 65 nations, 40 languages, gender identities, and age groups (N = 56,968). While multi-group confirmatory factor analysis (MG-CFA) of the NES supported full scalar invariance across gender identities and age groups, only partial scalar invariance was supported across national and linguistic groups. MG-CFA of the CNS also supported full scalar invariance across gender identities and age groups, but only partial scalar invariance of a 7-item version of the CNS across national and linguistic groups. Nation-level associations between NES and CNS scores were negligible, likely reflecting a lack of conceptual clarity over what the NES is measuring. Individual-level associations between both measures and sociodemographic variables were weak. Findings suggest that the CNS-7 may be a useful tool to measure nature connectedness globally, but measures other than the NES may be needed to capture nature exposure cross-culturally