Search Results (35)

We have used a rapid, portable assay (Bacterisk) to determine the bacterial water quality along several inland waters in SW England. Water samples were compared by a conventional membrane filter and culture methods for faecal indicator bacteria (FIB; E. coli and enterococci) and endotoxin measurement by Bacterisk. The Bacterisk data, measured in near-real-time, correlate well with both E. coli and enterococci, but also allow the presence of potential pathogens of a non-faecal origin to be detected. The sensitivity was calculated to be 92.96% with a specificity of 46.3% for E. coli with an expanded uncertainty of 22.07% and an Endotoxin Risk detection limit of 25 units. The presence of Bacterisk detectable non-faecal pathogenic bacteria in the water samples was successfully confirmed by Illumina MiSeq sequencing followed by target species-specific qPCR. Sequencing showed the presence of pathogens including Pseudomonas aeruginosa, Salmonella typhi, Acinetobacter baumannii, Shigella spp., and Legionella spp. as well as antimicrobial resistance genes. Furthermore, the portable Bacterisk assay was able to acquire data on the water quality from different locations and at different time points, providing a comprehensive surveillance tool that challenges the time to results by conventional methods (minutes instead of days), yielding compatible results. Full article

Wolman disease (WD) is a lethal disorder defined by the deficiency of the lysosomal acid lipase enzyme. Patients present with intestinal failure, malnutrition, and hepatosplenomegaly. Enzyme replacement therapy (ERT) with dietary substrate reduction (DSR) significantly improves survival. We sought to determine the outcomes of two siblings with WD treated after the onset of symptoms (sibling 1) and presymptomatic (sibling 2). A chart review was conducted on two siblings with WD treated with ERT and DSR at 4 months of age (sibling 1) and immediately after birth (sibling 2) to determine clinical outcomes based on survival, laboratory results, growth, dietary records, and gut biopsies. Sibling 1 presented with hepatosplenomegaly and liver dysfunction and developed hemophagocytic lymphohistiocytosis despite treatment. She received a bone marrow transplant at 8 months of age but died at 13 months. Sibling 2 is alive at 16 months of age with height, weight, and MUAC above the 95th centile, fully orally fed, with no gastrointestinal symptoms, normal liver function, and normal oxysterols. Sibling 2 duodenal biopsies show normal villus architecture with no foamy macrophage infiltration. Initiation of treatment prior to the onset of symptoms can prevent clinical manifestations and increase survival. The divergent trajectory in these siblings raises the question of WD’s candidacy for newborn screening. Full article

COVID-19, a novel infectious disease caused by the emergence of the SARS-CoV-2 virus in 2020, has had a profound impact on healthcare, both at the individual and population level. The impact at the population level was felt most acutely during the emergency phase of the pandemic, with hospital capacity issues leading to widespread disruptions and delays in the delivery of healthcare services such as screening programs and elective surgeries. While hospitals are no longer being acutely overwhelmed by COVID-19 patients, the impact of the virus on vulnerable patient populations such as cancer patients continues to be of ongoing consequence. Cancer patients remain at high risk of hospitalization, ICU admission, and death due to COVID-19, even in the era of vaccination. Infection prevention and risk mitigation strategies such air quality control, masking, testing, vaccination, and treatment should therefore be integrated into the usual care and counseling of cancer patients moving forward to avoid preventable morbidity and mortality from this infection and ensure the safety of this vulnerable cohort as they navigate their cancer diagnosis and treatment in the era of COVID-19. Full article

Extracellular vesicles (EVs) are lipid bilayer structures released by all cells that mediate cell-to-cell communication via the transfer of bioactive cargo. Because of the natural origin of EVs, their efficient uptake by recipient cells, capacity to stabilize and transport biomolecules and their potential for cell/tissue targeting and preferential uptake by cancer cells, they have enormous potential for bioengineering into improved and targeted drug delivery systems. In this work, we investigated the use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) as a tool to measure the loading of platinum-based chemotherapeutic agents. The EV loading of oxaliplatin via co-incubation was demonstrated, and LA-ICP-MS imaging showed greater efficiency of delivery to colorectal cancer cells compared to free oxaliplatin, leading to enhanced cytotoxic effect. Further, the impact of EV co-loading with a porphyrin (C5SHU, known as ‘C5’) photosensitizer on oxaliplatin delivery was assessed. Fluorescence analysis using nano-flow cytometry showed dose-dependent EV loading as well as a trend towards the loading of larger particles. Exposure of OXA-C5-EV-treated colorectal cancer cells to light indicated that delivery was enhanced by both light exposure and porphyrins, with a synergistic effect on cell viability observed between oxaliplatin, EVs and light exposure after the delivery of the co-loaded EVs. In summary, this work demonstrates the utility of LA-ICP-MS and mass spectrometry imaging in assessing the loading efficiency and cellular delivery of platinum-based therapeutics, which would also be suitable for agents containing other elements, confirms that EVs are more efficient at delivery compared to free drugs, and describes the use of light exposure in optimizing delivery and therapeutic effects of EV-mediated drug delivery both in combination and independently of porphyrin-based photosensitizers. Full article

We have carried out a series of experiments to measure the Cl K-absorption edge for shock-compressed samples of chlorinated parylene. Colliding shocks allowed us to compress samples up to four times the initial density with temperatures up to 10 eV. Red shifts in the edge of about 10 eV have been measured. We have compared the measured shifts to analytical modelling using the Stewart–Pyatt model and adaptions of it, combined with estimates of density and temperature based on hydrodynamic modelling. Modelling of the edge position using density functional theory molecular dynamics (DFT-MD) was also used and it was found that good agreement was only achieved when the DFT simulations assumed conditions of lower temperature and slightly higher density than indicated by hydrodynamic simulations using a tabular equation of state. Full article

Escherichia coli NfsB has been studied extensively for its potential for cancer gene therapy by reducing the prodrug CB1954 to a cytotoxic derivative. We have previously made several mutants with enhanced activity for the prodrug and characterised their activity in vitro and in vivo. Here, we determine the X-ray structure of our most active triple and double mutants to date, T41Q/N71S/F124T and T41L/N71S. The two mutant proteins have lower redox potentials than wild-type NfsB, and the mutations have lowered activity with NADH so that, in contrast to the wild-type enzyme, the reduction of the enzyme by NADH, rather than the reaction with CB1954, has a slower maximum rate. The structure of the triple mutant shows the interaction between Q41 and T124, explaining the synergy between these two mutations. Based on these structures, we selected mutants with even higher activity. The most active one contains T41Q/N71S/F124T/M127V, in which the additional M127V mutation enlarges a small channel to the active site. Molecular dynamics simulations show that the mutations or reduction of the FMN cofactors of the protein has little effect on its dynamics and that the largest backbone fluctuations occur at residues that flank the active site, contributing towards its broad substrate range. Full article

Rehabilitation in South Africa (SA) operates independently of major health services and reforms, despite the increasing rehabilitation need. With the introduction of National Health Insurance (NHI), SA is facing another major health reform. Evidence is needed on the current SA rehabilitation situation, regarding shortcomings, opportunities, and priority strategic strengthening actions. We aimed to describe the current rehabilitation capacity in the SA public health sector, which serves the majority and most vulnerable South Africans. A cross-sectional survey was conducted in five provinces, using the World Health Organisation’s Template for Rehabilitation Information Collection (TRIC). Participants were purposively selected for their insights and experiences of rehabilitation in specific government departments, health sectors, organisations, and/or services. TRIC responses were analysed descriptively. Participants explained how timely and effective rehabilitation produced long-term health, social, and economic benefits. Positive initiatives were reported for rehabilitation data collection, service design, and innovation. Challenges included inadequacies in human resources, the integration of rehabilitation at primary care, guidelines, and specialised long-term care facilities. The continuity of care across levels of care was sub-optimal due to inefficient referral systems. Promoting and improving rehabilitation nationally requires concerted, innovative, collaborative, and integrated efforts from multiple stakeholders within, and outside, the health system. Full article

Patients feel more vulnerable when accessing community mental health programs for the first time or after being discharged from psychiatric inpatient units. Long wait times for follow-up appointments, shortage of mental health professionals, lack of service integration, and scarcity of tailored support can weaken their connection to the health care system. As a result, patients can present low adherence, dissatisfaction with treatment, and recurrent hospitalizations. Finding solutions to avoid unnecessary high-cost services and providing tailored and cost-effective mental health interventions may reduce the health system burden and augment patient support. We propose implementing an add-on, supportive text messaging service (Text4Support), developed using cognitive–behavioural therapy (CBT) principles to augment mental health support for patients attending to or being discharged from psychiatric care in Nova Scotia, Canada. This randomized controlled trial aims to investigate the effectiveness of Text4Support in improving mental health outcomes and overall mental well-being compared with usual care. We also will examine the intervention’s impact on health services utilization and patient satisfaction. The results from this study will provide evidence on stepped and technology-based mental health care, which will contribute to generating new knowledge about mental health innovations in various clinical contexts, which is not only helpful for the local context but to other jurisdictions in Canada and abroad that are seeking to improve their health care. Full article

Background: The characteristics of night-time environments (NTEs) in which alcohol is consumed and that contribute to violence are poorly described. We explore competing explanations for violence in the NTE, with a particular focus on the number of patrons and its association with assault-related visits to a hospital emergency department. Other environmental features including the weather and notable events were also considered. The primary aim was to stimulate debate around the causal mechanisms responsible for violence. Methods: Assault-related ED visits occurring between 8 pm and 4 am were recorded at the University Hospital of Wales, the single Emergency Department (ED) serving Cardiff, Wales, United Kingdom. Footfall was derived from the total number of unique MAC addresses recorded per hour collected from ten wireless fidelity monitoring tools located in the city centre. A narrative review of the literature concerning alcohol and violence informed exploratory analyses into the association between night-time footfall, sporting events, the weather, and other potential predictors of assault-related visits to the ED. We developed analytic methods from formal accounts of queueing. Results: International rugby matches at home, the weather (temperature), national holidays, the day of the week, and number of patrons in the NTE predicted assault-related injury (R² = 0.70), with footfall yielding a positive non-linear exponential association consistent with predictions derived from mathematical models of queueing. Discussion: Assault-related visits to the ED have a non-linear association with the number of people socialising in the night-time environment and are further influenced by the weather and notable events. Opportunities for further research that might inform policy and interventions aimed at better managing NTEs are discussed. Full article

Innovative cross-over study designs were explored in non-human primate (NHP) studies to determine the value of this approach for the evaluation of drug efficacy against tuberculosis (TB). Firstly, the pharmacokinetics (PK) of each of the drugs Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E), that are standardly used for the treatment of tuberculosis, was established in the blood of macaques after oral dosing as a monotherapy or in combination. Two studies were conducted to evaluate the pharmacokinetics and pharmacodynamics of different drug combinations using cross-over designs. The first employed a balanced, three-period Pigeon design with an extra period; this ensured that treatment by period interactions and carry-over could be detected comparing the treatments HR, HZ and HRZ using H37Rv as the challenge strain of Mycobacterium tuberculosis (M. tb). Although the design accounted for considerable variability between animals, the three regimens evaluated could not be distinguished using any of the alternative endpoints assessed. However, the degree of pathology achieved using H37Rv in the model during this study was less than expected. Based on these findings, a second experiment using a classical AB/BA design comparing HE with HRZ was conducted using the M. tb Erdman strain. More extensive pathology was observed, and differences in computerized tomography (CT) scores and bacteriology counts in the lungs were detected, although due to the small group sizes, clearer differences were not distinguished. Type 1 T helper (Th1) cell response profiles were characterized using the IFN-γ ELISPOT assay and revealed differences between drug treatments that corresponded to decreases in disease burden. Therefore, the studies performed support the utility of the NHP model for the determination of PK/PD of TB drugs, although further work is required to optimize the use of cross-over study designs. Full article

STEM has become a pervasive part of global education reform. The STEM discourse positions the purpose of scientific education as being to prepare young people for work in a hyper-competitive 21st century knowledge economy, pushing aside alternative approaches focussed on interrogating social, moral and political issues in context. This narrative does not always sit comfortably with the holistic ambitions of many state and faith-based education systems. In this paper we will argue that these tensions emerge from deeper conflicts in the cultural-discursive arrangements around education in the advanced democratic states through an exploration of the response to a STEM curriculum project in a Catholic education system. The exploration is based on a phenomenographic analysis of reflective interviews conducted with participating teachers. We conclude that while the teachers are aware of the tensions, they may benefit from access to a language for discussing the various pressures on learning design and meaning making. Full article

Conditions have been identified in which phenolic aldoximes and ketoximes of the types used in commercial solvent extraction processes can be doubly deprotonated and generate polynuclear Cu complexes with lower extractant:Cu molar ratios than those found in commercial operations. Electrospray mass spectrometry has provided an insight into the solution speciation in extraction experiments and has identified conditions to allow isolation and characterization of polynuclear Cu-complexes. Elevation of pH is effective in enhancing the formation of trinuclear complexes containing planar {Cu₃-μ₃-O}⁴⁺ or {Cu₃-μ₃-OH}⁵⁺ units. DFT calculations suggest that such trinuclear complexes are more stable than other polynuclear species. Solid structures of complexes formed by a salicylaldoxime with a piperidino substituent ortho to the phenolic OH group (L⁹H₂) contain two trinuclear units in a supramolecular assembly, {[Cu₃OH(L⁹H)₃(ClO₄)](ClO₄)} ₂, formed by H-bonding between the central {Cu₃-μ₃-OH}⁵⁺ units and oxygen atoms in the ligands of an adjacent complex. Whilst the lower ligand:Cu molar ratios provide more efficient Cu-loading in solvent extraction processes, the requirement to raise the pH of the aqueous phase to achieve this will make it impractical in most commercial operations because extraction will be accompanied by the precipitation (as oxyhydroxides) of Fe(III) which is present in significant quantities in feed solutions generated by acid leaching of most Cu ores. Full article

Numerous health benefits have been reported from the consumption of cranberry-derived products, and recent studies have identified bioactive polysaccharides and oligosaccharides from cranberry pomace. This study aimed to further characterize xyloglucan and pectic oligosaccharide structures from pectinase-treated cranberry pomace and measure the growth and short-chain fatty acid production of 86 Lactobacillus strains using a cranberry oligosaccharide fraction as the carbon source. In addition to arabino-xyloglucan structures, cranberry oligosaccharides included pectic rhamnogalacturonan I which was methyl-esterified, acetylated and contained arabino-galacto-oligosaccharide side chains and a 4,5-unsaturated function at the non-reducing end. When grown on cranberry oligosaccharides, ten Lactobacillus strains reached a final culture density (ΔOD) ≥ 0.50 after 24 h incubation at 32 °C, which was comparable to L. plantarum ATCC BAA 793. All strains produced lactic, acetic, and propionic acids, and all but three strains produced butyric acid. This study demonstrated that the ability to metabolize cranberry oligosaccharides is Lactobacillus strain specific, with some strains having the potential to be probiotics, and for the first time showed these ten strains were capable of growth on this carbon source. The novel cranberry pectic and arabino-xyloglucan oligosaccharide structures reported here combined with the Lactobacillus strains that can metabolize cranberry oligosaccharides and produce short-chain fatty acids, have excellent potential as health-promoting synbiotics. Full article

Taiwan has been a world leader in controlling the spread of SARS-CoV-2 during the COVID-19 pandemic. Recently, the Taiwan Government launched its COVID-19 tracing app, ‘Taiwan Social Distancing App’; however, the effectiveness of this tracing app depends on its acceptance and uptake among the general population. We measured the acceptance of three hypothetical tracing technologies (telecommunication network tracing, a government app, and the Apple and Google Bluetooth exposure notification system) in four nationally representative Taiwanese samples. Using Bayesian methods, we found a high acceptance of all three tracking technologies, with acceptance increasing with the inclusion of additional privacy measures. Modeling revealed that acceptance increased with the perceived technology benefits, trust in the providers’ intent, data security and privacy measures, the level of ongoing control, and one’s level of education. Acceptance decreased with data sensitivity perceptions and a perceived low policy compliance by others among the general public. We consider the policy implications of these results for Taiwan during the COVID-19 pandemic and in the future. Full article

Ginger is best known for its aromatic odour, spicy flavour and health-benefiting properties. Its flavour is derived primarily from two compound classes (gingerols and shogaols), with the overall quality of the product depending on the interaction between these compounds. Consequently, a robust method for determining the ratio of these compounds would be beneficial for quality control purposes. This study investigated the feasibility of using hyperspectral imaging to rapidly determine the ratio of 6-gingerol to 6-shogoal in dried ginger powder. Furthermore, the performance of several pre-processing methods and two multivariate models was explored. The best-performing models used partial least squares regression (PSLR) and least absolute shrinkage and selection operator (LASSO), using multiplicative scatter correction (MSC) and second derivative Savitzky–Golay (2D-SG) pre-processing. Using the full range of wavelengths (~400–1000 nm), the performance was similar for PLSR (R² ≥ 0.73, RMSE ≤ 0.29, and RPD ≥ 1.92) and LASSO models (R² ≥ 0.73, RMSE ≤ 0.29, and RPD ≥ 1.94). These results suggest that hyperspectral imaging combined with chemometric modelling may potentially be used as a rapid, non-destructive method for the prediction of gingerol-to-shogaol ratios in powdered ginger samples. Full article