Search Results (156)

Background: Lysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of undegraded substrates within lysosomes, disrupting cellular function across multiple organ systems. While classical phenotypes typically manifest in infancy or early childhood with severe multisystem involvement, a combination of advances in molecular diagnostics [particularly next-generation sequencing (NGS)] and improved understanding of disease heterogeneity have enabled the identification of attenuated forms characterised by residual enzyme activity and later-onset presentations. These milder phenotypes often evade early recognition due to nonspecific or isolated symptoms, resulting in significant diagnostic delays and missed therapeutic opportunities. Objectives/Methods: This study characterises the clinical, biochemical, and molecular profiles of 10 adult patients diagnosed with LSDs, all representing attenuated forms, and discusses them alongside a narrative review. Results: Enzyme activity, molecular data, and phenotypic assessments are described to explore genotype–phenotype correlations and identify diagnostic challenges. Conclusions: These findings highlight the variable expressivity and organ involvement of attenuated LSDs and reinforce the importance of maintaining clinical suspicion in adults presenting with unexplained cardiovascular, neurological, ophthalmological, or musculoskeletal findings. Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members. Full article

Background/Objectives: Patients with an ileoanal pouch change their diet to manage their symptoms and will often resort to the internet for nutrition advice. Currently, no evidence-based dietary guidelines exist to inform online resources. Hence, this study aims to assess the quality of online nutrition information directed towards patients with an ileoanal pouch. Methods: A systematic Google search was conducted to identify consumer websites including information on nutrition for those with ileoanal pouches. Quality was assessed using the DISCERN instrument, and the readability of written content was assessed using the Flesch–Kincaid score. A summative content analysis was used to identify the frequency of particular topics. Websites were also assessed against standards from the National Institute for Health and Care Excellence (NICE) framework for shared decision-making support tools. Results: A total of 12 websites met the inclusion criteria. Mean total DISCERN scores across all websites are 33 out of 75, indicating that overall, the websites were of poor quality. The mean Flesch–Kincaid score was 57 out of 100, or “fairly difficult” in terms of readability. The main themes according to the content analysis were “general dietary advice for pouch”, “dietary strategies for symptom management”, “addressing risks associated with having a pouch”, and “optimisation of nutritional intake”. Overall, websites did not meet the standards for shared decision-making. Conclusions: Online nutrition information for patients with an ileoanal pouch is of poor quality and difficult to understand. There is a need for higher quality online resources for these patients, ideally co-produced with a multidisciplinary team and patient, to provide patients with good quality, understandable, and accessible nutrition information. Full article

Unionid mussel populations in a section of the Clinch River in Virginia, USA, has declined substantially, but the causes of the decline remain unknown. To investigate this zone of decline (ZOD), we deployed juvenile freshwater mussels (Villosa iris in 2012 and Lampsilis fasciola in 2013) in both cages and silos at sites within the Clinch River System. We analyzed mussel tissues for trace element and organic contaminant concentrations, shells for trace elements, and environmental media (total water, dissolved water, particulate sediment, and bedload sediment) for both inorganic and organic contaminants. We found a few differences between mussels deployed in cages and those deployed in silos: survival was slightly lower in cages due to periodic sedimentation. Our results identified the ZOD based on the accumulation of trace elements (notably As, Cu, Fe, Mn, Ni, and Sr), polycyclic aromatic hydrocarbons (PAHs), and δ¹⁵N enrichment, with especially high concentrations found in the human-impacted tributaries, Dumps Creek and Guest River. Some correlations were found between environmental media and both mussel tissues and shells. In particular, PAHs and Mn had several significant relationships between bioaccumulated concentrations and environmental concentrations. Finally, Co, Cu, Fe, and V in soft tissues negatively correlated with mussel growth, whereas bioaccumulated PAH concentrations correlated negatively with resident mussel densities. Full article

Local governments are increasingly navigating accelerating change and escalating complexity caused by interconnected crises, commonly referred to as a global polycrisis. These crises, including climate change, lack of affordable housing, declining mental health, and geopolitical instability, both shape and are shaped by local conditions. Cities face growing pressure to equitably provide services that are responsive to evolving community needs while contending with the systemic nature of contemporary challenges. However, local governments are often constrained by conventional management frameworks and practices that do not match the complexity of today’s challenges. The purpose of this conceptual paper is to explore how systems science can be leveraged to define and characterize a transformative new type of management designed to enable local governments to more adequately address emerging complexity. To this end, the authors review the literature on contemporary management practice and explore how management for local government can be reframed in alignment with the insights from systems science, using a service ecosystem lens. The findings point to a needed shift toward systemic management practices that are integrative, collective, and adaptive. The authors illustrate the practical relevance of these three characteristics and conclude with recommendations for research, policy, and practice aimed at building the institutional capabilities required to transition toward systemic management frameworks and practices that match the complexity of the polycrisis. Full article

A series of nickel (II) bis-phosphine organometallic complexes along with two pseudo [M₇] (M = Ni(II), Zn(II)) metallocalix[6]arene complexes and a dysprosium acetate coordination polymer have each been crystallised in the presence of localized magnetic fields set up using neodymium magnets, using custom made Magnetic Crystallization Towers (MCTs). In all cases, whether the product complex is diamagnetic or paramagnetic, a complex spatial patterning of the crystals occurs based on the orientation of the magnetic field lines. When using magnetic block towers, the crystallization generally occurs adjacent to the magnet face. The effects of nucleation and solution concentration gradients on the crystallization process are also explored. These observations show how the crystallization process is affected by magnetic fields and thus these results have far-reaching effects which most certainly will include crystallization and ion migrations in biology. Full article

This paper reports studies on the thermal chemistry of the flash pyrolysis (heating rate of 20,000 °C/s up to 800 °C) of non-fossil fuel carbon (NFF-C) waste (or refuse-derived fuel, RDF) in the context of using this as an alternative reductant for blast furnace ironmaking. Gas chromatography–mass spectrometry (GCMS) analysis linked to the pyrolyser was used to simulate the thermal processes that take place during injection in the blast furnace raceway, where material experiences extreme temperature (ca. 1000 °C) over very short residence times (<300 ms). Species identification and qualitative analysis of evolved species generated are reported. Whilst the pyrolyser uses flash heating of a static sample, a drop tube furnace was also employed to study a sample moving rapidly through a pre-heated furnace held at 1000 °C to enable reductant burnout rates to be measured. The overarching aim of this piece of work is to study the suitability of replacing fossil fuel with non-recyclable plastic and paper as blast furnace reductants. Full article

Blade leading edge erosion (LEE) is a persistent challenge in the wind industry, resulting in reduced aerodynamic efficiency and increased maintenance costs, with an estimated total expense of GBP 1.3M over a 25-year turbine lifetime. To mitigate these effects, leading edge protection (LEP) systems are widely used, but their real-world performance often falls short of predictions based on the standard rain erosion test (RET). This study investigates the limitations of current RET practices, which are designed to accelerate testing but fail to replicate the diverse environmental conditions experienced by wind turbines. Two LEPs with contrasting viscoelastic properties were tested using a novel design of experiments (DoEs) approach. The study explored the droplet impact frequency, combination and sequencing of high or low rainfall intensities, recovery during the inspection period and droplet size effects on erosion behaviour, to uncover significant differences in material performance compared to standard RET conditions. Results, supported by dynamic mechanical analysis (DMA), indicated that the chosen LEPs undergo a transition between elastic and brittle failure modes at a critical impact frequency, influenced by the viscoelastic properties of the material. Importantly, the findings emphasise the need for revised testing protocols across a range of parameters that incorporate realistic environmental conditions to improve the predictability of LEP performance. Full article

Background: Visual impairment can significantly impact an individual’s daily activities. Patients require regular monitoring, typically occurring within hospital eye services. Capacity constraints have necessitated innovative solutions to improve patient care. Existing digital solutions rely on task-based digital home monitoring such as visual acuity testing. These require active involvement from patients and do not typically offer an indication of quality of life. Digital phenotyping refers to the use of personal digital devices to quantify passive behaviour for detecting clinically significant changes in vision and act as biomarkers for disease. Its uniqueness lies in the ability to detect changes passively. The objective was to co-design an accessible smartphone app (OverSight) for the purposes of digital phenotyping in people with sight impairment. Methods: Development of OverSight included stakeholder consultations following principles of user-centred design. Apple iOS software frameworks (HealthKit, ResearchKit, and SensorKit) and a SwiftUI developer toolkit were used to enable the collection of active and passive data streams. Accessibility and usability were assessed using the System Usability Scale (SUS) and feedback following a 3-month pilot study. Consultations with patients informed the design of OverSight, including preferred survey scheduling and the relevancy of patient support resources. Results: Twenty visually impaired participants (mean age 42 ± 19 years) were recruited to the pilot study. The average score on the SUS was 76.8 (±8.9), indicating good usability. There was a statistically significant moderate negative correlation between SUS scores and visual acuity in both the better (r = −0.494; p ≤ 0.001) and worse eye (r = −0.421; p ≤ 0.001). Conclusions: OverSight offers promising potential for collecting patient-generated health data for the purposes of digital phenotyping in patients with eye disease. Through further testing and validation, this novel approach to patient care may ultimately provide opportunities for remote monitoring in ophthalmology. Full article

Gold compositional studies have been advocated to resolve genetic relationships between alluvial and in situ occurrences based on the assumption that the P-T-X conditions at the sites of mineral deposition are reflected in common compositional signatures of gold. Here, we explore two refinements to a simple ‘same or different’ approach, namely (i) in situ gold sources at different localities may correspond to multiple stages of mineralization and, therefore, different gold grade, and (ii) any duplication of gold signatures between localities requires fluid conduits compatible with the prevailing structural framework. The high-grade gold paragenetic stage at the Cononish Mine, Scotland, is characterized by relatively low Ag alloy associated with Ag-Au and Ag tellurides. This signature is replicated in the inclusion signature of alluvial gold from the adjacent drainage and is also present in two other drainages for which there are no known in situ sources. There is a strong correlation between the spatial extent of this signature and the fault linkage zone, but outside this zone, gold exhibits other compositional signatures. The study shows how structural considerations provide an independent and robust framework to evaluate genetic relationships suggested by compositional studies of alluvial gold in areas where the source location and economic potential are unknown. Full article

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is considered the main cause of nosocomial and community-associated infections. Because of antimicrobial resistance, MRSA infections are difficult or impossible to treat, leading to high mortality rates and significant economic and societal costs. In view of the MRSA challenge to public health all over the world, the identification of new and effective anti-MRSA agents is a high medical priority. Objectives: A new series of tricyclic flavonoids with a methyl substituent on ring A of the flavonoid skeleton was synthesized to assess their antimicrobial properties. Methods: The structures of novel synthetic tricyclic flavonoids and their 3-dithiocarbamic flavanones were proven by X-ray structural analyses. Minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) were used to evaluate antimicrobial activity. Growth kinetic and time–kill assays were employed to confirm the antibacterial effectiveness. The mechanism of action was investigated using fluorescence microscopy. Results: Our results show that the tricyclic flavonoids exhibited important antibacterial and antifungal activities, with MIC and MBC values as low as 1.95 µg/mL and 3.90 µg/mL recorded for compound 5e against a multidrug-resistant MRSA strain. Flavonoid 5e induced a more important bacteriostatic effect compared with chloramphenicol, inhibiting the bacterial growth for up to 24 h at concentrations equivalent to 2 × MIC. Also, 5e exhibited a significant bactericidal activity, with no viable cells evidenced after 6 h of incubation in the presence of MBC and a total kill effect recorded up to 24 h. The anti-MRSA activity may be explained by the cell membrane impairment induced by 5e. Conclusions: All the data support the idea that flavonoid 5e is a reliable candidate to develop effective anti-MRSA agents, but further studies are necessary. Full article

The combination of different wood-modification technologies to obtain improved performance is increasingly receiving attention in research. In this study, Scots pine (Pinus sylvestris) sapwood was impregnated with furfuryl alcohol (FFA) in pure aqueous 20, 40, and 60% solution strength without adding any catalyst. In a second step, the FFA was polymerized while simultaneously performing thermal modification in a closed system at 130, 150, or 180 °C. After leaching and ageing tests, the nine different combinations were tested in use class 4 applications (in contact with or very close to the ground and frequently wet) according to CEN/TS 15083-2 (2005) decay laboratory test. It was noted that even the minimum-intensity combination of 20% FFA at 130 °C resulted in maximum durability class (DC) 1 performance. On the contrary, DC 4 was assigned to thermally modified control samples, even at the maximum intensity of thermal modification. Similarly, for FFA modifications, previous research has suggested that an uptake of 35% solution strength is required to obtain an adequate durability performance in use class 4 applications. High levels of resistance against termites were also noted by corresponding termite lab tests. Moisture studies showed the combined treatments resulted in improved stability and reduced moisture uptakes. Thus, the results obtained by this study revealed synergistic performance effects, which originate from the combined thermo-chemical modification approach, and which were higher than simple accumulation of the individual performance of purely thermally or chemically modified wood. Thus, the presented findings have provided positive implications for industrial applications of thermo-chemical modification techniques and offers an array of new research opportunities. Full article

N-alkylated C₂-symmetric amino acid amide derivatives were shown to catalyse the Michael addition of 2-hydroxy-1,4-napthoquinone to β-nitrostyrene, achieving a maximum ee of 44%. The corresponding trifluoroacetic acid salts also catalysed the aldol reaction between 4-nitrobenzaldehyde and hydroxyacetone, leading to the formation of predominantly syn-aldol products in up to 55% ee. Aspects of the solvent dependence of the aldol reaction and the H-bonding of the catalyst were investigated. Full article

The association of thyroid function with essential and non-essential amino acids is understudied, despite their common metabolic roles. Thus, our aim was to evaluate the association of thyroid function with the levels of branched-chain amino acids (BCAAs—leucine, isoleucine, and valine) and of alanine in the general population. We utilized data from the São Paulo research center of ELSA-Brasil, a longitudinal population-based cohort study. Thyroid parameters included thyroid stimulating hormone (TSH), free T4 and free T3 levels, and the FT4:FT3 ratio. BCAAs and alanine were analyzed on a fully automated NMR platform. The current analysis included euthyroid participants and participants with subclinical hyperthyroidism and hypothyroidism. We used Pearson’s coefficient to quantify the correlation between thyroid-related parameters and amino acids. Linear regression models were performed to analyze whether thyroid parameters were associated with BCAAs and alanine levels. We included 4098 participants (51.3 ± 9.0 years old, 51.5% women) in this study. In the most adjusted model, higher levels of TSH were associated with higher levels of alanine, FT4 levels were inversely associated with isoleucine levels, FT3 levels were statistically significant and positively associated with valine and leucine, and the T3:T4 ratio was positively associated with all amino acids. We observed that subclinical hypothyroidism was positively associated with isoleucine and alanine levels in all models, even after full adjustment. Our findings highlight the association of subclinical hypothyroidism and thyroid-related parameters (including TSH, free T4, free T3, and FT4:FT3 ratio) with BCAAs and alanine. Further studies are needed to explore the mechanisms underlying this association. These insights contribute to our understanding of the influence of thyroid-related parameters on BCAA and alanine metabolism. Full article

Chitosan (CS), a biopolymer, holds significant potential in bone regeneration due to its biocompatibility and biodegradability attributes. While crustacean-derived CS is conventionally used in research, there is growing interest in fungal-derived CS for its equally potent properties in bone regenerative applications. Here, we investigated the physicochemical and biological characteristics of fungal (MDC) and crustacean (ADC)-derived CS scaffolds embedded with different concentrations of tricalcium phosphate minerals (TCP), i.e., 0(wt)%: ADC/MDC-1, 10(wt)%: ADC/MDC-2, 20(wt)%: ADC/MDC-3 and 30(wt)%: ADC/MDC-4. ADC-1 and MDC-1 lyophilised scaffolds lacking TCP minerals presented the highest zeta potentials of 47.3 ± 1.2 mV and 55.1 ± 1.6 mV, respectively. Scanning electron microscopy revealed prominent distinctions whereby MDC scaffolds exhibited striation-like structural microarchitecture in contrast to the porous morphology exhibited by ADC scaffold types. With regard to the 4-week scaffold mass reductions, MDC-1, MDC-2, MDC-3, and MDC-4 indicated declines of 55.98 ± 4.2%, 40.16 ± 3.6%, 27.05 ± 4.7%, and 19.16 ± 5.3%, respectively. Conversely, ADC-1, ADC-2, ADC-3, and ADC-4 presented mass reductions of 35.78 ± 5.1%, 25.19 ± 4.2%, 20.23 ± 6.3%, and 13.68 ± 5.4%, respectively. The biological performance of the scaffolds was assessed through in vitro bone marrow mesenchymal stromal cell (BMMSCs) attachment via indirect and direct cytotoxicity studies, where all scaffold types presented no cytotoxic behaviours. MDC scaffolds indicated results comparable to ADC, where both CS types exhibited similar physiochemical properties. Our data suggest that MDC scaffolds could be a potent alternative to ADC-derived scaffolds for bone regeneration applications, particularly for 10(wt)% TCP concentrations. Full article

The concept of nature positive has recently emerged from the widespread recognition of the global scale at which nature is being lost and the threat this poses to the collective survival of the human race. Much of the interest in nature positive reflects the initial commitment to it by conservation organisations and by a number of international political initiatives. However, the pursuit of nature positive approaches by businesses has received little attention in the business and management literature. Building upon an analysis of secondary sources, this entry paper first examines how three international organisations suggest a nature positive strategy could be pursued. This paper then focuses on two multinational companies and how they plan to pursue a nature positive approach to their business activities. This article identifies a number of critical factors in developing a nature positive strategy: incorporating suppliers in this strategy, assessing corporate dependencies and impacts on nature, and reporting on nature positive initiatives and outcomes. At the same time, this article raises concerns that nature positive approaches could be driven more by business imperatives rather than fundamental corporate concerns about biodiversity and that many business commitments to nature positive could be seen as mainly aspirational. Full article