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Healthcare derived smart watches and mobile phones are contaminated niches to multidrug resistant and highly virulent microbes
Get PDFBackground: As high touch wearable devices, the potential for microbial contamination of smart watches is high. In this study, microbial contamination of smart watches of healthcare workers (HCWs) was assessed and compared to the individual’s mobile phone and hands.
Methods: This study was part of a larger point prevalence survey of microbial contamination of mobile phones of HCWs at the emergency unit of a tertiary care facility. Swabs from smart watches, mobile phones and hands were obtained from four HCWs with dual ownership of these digital devices. Bacterial culture was carried out for all samples and those from smart watches and mobile phones were further assessed using shotgun metagenomic sequencing.
Results: Majority of the participants were females (n/N = 3/4; 75%). Although they all use their digital devices at work and believe that these devices could harbour microbes, cleaning in the preceding 24 hours was reported by one individual. Predominant organisms identified on bacterial culture were multidrug resistant Staphylococcus hominis and Staphylococcus epidermidis. At least one organism identified from the hands was also detected on all mobile phones and two smart watches. Shotgun metagenomics analysis demonstrated greater microbial number and diversity on mobile phones compared to smart watches. All devices had high signatures of Pseudomonas aeruginosa and associated bacteriophages and antibiotic resistance genes. Almost half of the antibiotic resistance genes (n/N = 35/75;46.6%) were present on all devices and majority were related to efflux pumps. Of the 201 virulence factor genes (VFG) identified, majority (n/N = 148/201;73%) were associated with P. aeruginosa with 96% (n/N = 142/148) present on smart watches and mobile phones.
Conclusion: This first report on microbial contamination of smart watches using metagenomics next generation sequencing showed similar pattern of contamination with microbes, VFG and antibiotic resistance genes across digital devices. Further studies on microbial contamination of wearable digital devices are urgently needed
JS04.5.A Enhancing the activity of anti-CD47 antibody therapy with radiotherapy in preclinical models of medulloblastoma
No full textBackground
Brain cancers are the most common solid cancer in children and the leading cause of cancer-related deaths in children. Medulloblastoma is the most common paediatric brain tumour. Treatment for medulloblastoma involves surgery, craniospinal irradiation (CSI) and chemotherapy. These therapies are extremely damaging to the developing brain and have not changed in decades, resulting in stagnation in the survival outcomes for children with medulloblastoma, and poor quality of life for children who survive their treatment. Immunotherapy has become a focus of novel treatment development. While there are multiple clinical trials aiming to increase immune recognition of medulloblastoma, none have been successful to date. Anti-CD47 is an immune-modulating therapeutic antibody which blocks the anti-phagocytic signal, CD47, expressed by brain cancer cells. Anti-CD47 has shown promising preliminary efficacy in brain cancer models.
Material and Methods
Using a small animal radiotherapy platform, we have developed a preclinical CSI protocol which mimics clinical radiotherapy. Using an orthotopic xenograft model of medulloblastoma, mice were treated with either anti-CD47 antibody therapy, CSI, or the combination of both anti-CD47 and CSI.
Results
CSI was found to deplete adaptive immune cells in the brain, while myeloid cells remained the dominant populations. Anti-CD47 antibody therapy was ineffective as a single agent against a patient derived xenograft model of Group 3 medulloblastoma, and CSI as a monotherapy resulted in temporary tumour regression. We found that the combination of anti-CD47 with CSI resulted in marked and persistent tumour regression.
Conclusion
This preclinical work has shown promising efficacy of anti-CD47 in combination with CSI, which we are currently testing in additional models. Our work is currently employing a range of techniques such as high dimensional flow cytometry and single cell sequencing to elucidate the mechanisms by which radiotherapy enhances the anti-tumour activity of myeloid cells. This work will enable the rational design and translation of optimal combination therapies for medulloblastoma clinical trials
Immunoregulatory effects of testosterone supplementation combined with exercise training in men with Inclusion Body Myositis: A double‐blind, placebo‐controlled, cross‐over trial
Get PDFObjectives
Sporadic Inclusion Body Myositis (IBM) is an inflammatory muscle disease affecting individuals over the age of 45, leading to progressive muscle wasting, disability and loss of independence. Histologically, IBM is characterised by immune changes including myofibres expressing major histocompatibility complex molecules and invaded by CD8+ T cells and macrophages, and by degenerative changes including protein aggregates organised in inclusion bodies, rimmed vacuoles and mitochondrial abnormalities. There is currently no cure, and regular exercise is currently the only recognised treatment effective at limiting muscle weakening, atrophy and loss of function. Testosterone exerts anti-inflammatory effects, inhibiting effector T-cell differentiation and pro-inflammatory cytokine production.
Methods
We conducted a double-blind, placebo-controlled, cross-over trial in men with IBM, to assess whether a personalised progressive exercise training combined with application of testosterone, reduced the inflammatory immune response associated with this disease over and above exercise alone. To assess intervention efficacy, we immunophenotyped blood immune cells by flow cytometry, and measured serum cytokines and chemokines by Luminex immunoassay.
Results
Testosterone supplementation resulted in modest yet significant count reduction in the classical monocyte subset as well as eosinophils. Testosterone-independent immunoregulatory effects attributed to exercise included altered proportions of some monocyte, T- and B-cell subsets, and reduced IL-12, IL-17, TNF-α, MIP-1β and sICAM-1 in spite of interindividual variability.
Conclusion
Overall, our findings indicate anti-inflammatory effects of exercise training in IBM patients, whilst concomitant testosterone supplementation provides some additional changes. Further studies combining testosterone and exercise would be worthwhile in larger cohorts and longer testosterone administration periods
A comprehensive analysis of Trehalose-6-phosphate synthase (TPS) gene for salinity tolerance in chickpea (Cicer arietinum L.)
Get PDFSoil salinity affects various crop cultivation but legumes are the most sensitive to salinity. Osmotic stress is the first stage of salinity stress caused by excess salts in the soil on plants which adversely affects the growth instantly. The Trehalose-6-phosphate synthase (TPS) genes play a key role in the regulation of abiotic stresses resistance from the high expression of different isoform. Selected genotypes were evaluated to estimate for salt tolerance as well as genetic variability at morphological and molecular level. Allelic variations were identified in some of the selected genotypes for the TPS gene. A comprehensive analysis of the TPS gene from selected genotypes was conducted. Presence of significant genetic variability among the genotypes was found for salinity tolerance. This is the first report of allelic variation of TPS gene from chickpea and results indicates that the SNPs present in these conserved regions may contribute largely to functional distinction. The nucleotide sequence analysis suggests that the TPS gene sequences were found to be conserved among the genotypes. Some selected genotypes were evaluated to estimate for salt tolerance as well as for comparative analysis of physiological, molecular and allelic variability for salt responsive gene Trehalose-6-Phosphate Synthase through sequence similarity. Allelic variations were identified in some selected genotypes for the TPS gene. It is found that Pusa362, Pusa1103, and IG5856 are the most salt-tolerant lines and the results indicates that the identified genotypes can be used as a reliable donor for the chickpea improvement programs for salinity tolerance
Correction: Who are the chiropractic students favouring a limitless scope of practice? Exploring the relationship with personality, magical thinking, and academic achievement
Get PDFFollowing the publication of the original article [1], it has been brought to our attention that several of the provided references are mismatched in the Background section and are incorrectly recorded in the Reference section..
Reduced nitrogen fertilization under flooded conditions cut down soil N2O and CO2 efflux: An incubation experiment
No full textUnreasonable water (W) and inorganic nitrogen (N) fertilization cause an intensification of soil greenhouse gas (GHGs) emissions. W–N interactions (W × N) patterns can maximise the regulation of soil GHGs efflux through the rational matching of W and N fertilization factors. However, the effects of W × N patterns on soil GHGs efflux and the underlying mechanism remain unclear. In this study, urea fertilizers were applied to paddy soils in a gradient of 100 (N100), 80 (N80), and 60 mg kg−1 (N60) concentrations. Flooding (W1) and 60% field holding capacity (W2) was set for each N fertilizer application to observe the effects of W × N patterns on soil properties and GHGs efflux through incubation experiments. The results showed that W significantly affected soil electrical conductivity and different N forms (i.e., alkali hydrolyzed N, ammonium N, nitrate N and microbial biomass N) contents. Soil organic carbon (C) content was reduced by 14.40% in W1N60 relative to W1N100, whereas microbial biomass C content was increased by 26.87%. Moreover, soil methane (CH4) fluxes were low in all treatments, with a range of 1.60–1.65 μg CH4 kg−1. Soil nitrous oxide (N2O) and carbon dioxide (CO2) fluxes were significantly influenced by W, N and W × N. Global warming potential was maintained at the lowest level in W1N60 treatment at 0.67 g CO2-eq kg−1, suggesting W1N60 as the preferred W × N pattern with high environmental impact. Our findings demonstrate that reduced N fertilization contributes to the effective mitigation of soil N2O and CO2 efflux by lowering the soil total N and organic C contents and regulating soil microbial biomass C and N
Fossil flowers of Phylica support a 250 Ma origin for Rhamnaceae
No full textA new fossil discovery reported by Shi et al. changes our understanding of the biogeographic history of the cosmopolitan family, Rhamnaceae. Flowering shoots of the African genus Phylica (Rhamnaceae) dated at 100 million years ago (Ma) imply a 250 Ma origin of the family in fire-prone Gondwanan vegetation that enabled overland dispersal to all continents where it is currently widespread
Hope, performative diversity and re-production: Hamilton and COVID-era politics
No full textDuring the COVID-19 pandemic, theatres around the world closed and performances moved online. Consequently, when the musical Hamilton opened in March 2021 in Australia, it was the only version of the show being performed live on stage anywhere in the world and was marketed as a ‘beacon of hope’ for the performing arts industry [Crompton, S. 2017, Francis, L., and Ky, J. 2021, Millar, L. 2021]. Hamilton’s story is based on White American grand narratives such as the War of Independence, nation building and a ‘bootstraps’ mentality, which have traditionally excluded persons of colour; however, the musical primarily features Black, Indigenous and People of Colour (BIPOC) performers. After its debut in the US, Hamilton was praised for its diverse storytelling [Clark, J. 2015. Gardner, E. 2015, Quinn, D. 2015.] and this narrative has been repeated for the Australian re-production. Through the lens of racial neoliberal inclusion, this paper explores the COVID-era Australian re-production of Hamilton, interrogating how diversity is performed and the impact the global pandemic has had on these performances. However, while the internal message of the show remains problematic, the depth brought by Indigenous performers in particular, marks a shift in Australian theatre culture
Nonsequential Pre-mRNA Splicing: From basic understanding to impacts on Splice-Manipulating therapies
No full textThe pre-mRNA splicing process is an essential aspect of gene expression and function and plays a substantial role in the complexity of higher eukaryotes. The development of antisense oligonucleotides (AOs) to harness the splicing process and manipulate it to treat various inherited and acquired diseases has been boosted by its flexibility and customisation capability. As the amount of research in this space increases, certain aspects need to be considered, in particular, how nonsequential splicing of pre-mRNA can impact AO-mediated splicing manipulation. In this chapter, we reviewed literature discussing intron removal order and several examples of disease-causing mutations impacted by this phenomenon. We also compared two strategies used to study intron removal order and the occasions that they are best suited. Finally, we discuss how nonsequential splicing could facilitate or impede the development of splice-manipulating AOs and aspects to consider when analysing AO effectiveness
Long-term performance of a full-scale intermittently decanted extended aeration (IDEA) plant: The effect of dissolved oxygen and the relocation of alum dosing to bioselector
No full textDosing alum to remove phosphorus (P) from wastewater is a common practice. However, the dosing-location and quantity of alum required to meet P discharge limits are vaguely defined. As such, utilities overdose alum to avoid noncompliance, but this leads to wastage and costs. This study aimed to address this issue through a long-term evaluation of an alum-assisted full-scale intermittently decanted extended aeration (IDEA) plant. Specifically, the effects of relocating alum dosing from a low P containing IDEA-tank to a bioselector containing elevated P concentrations were examined. The plant is fitted with two IDEA-tanks, each retrofitted with a bioselector at the inlet end. Over 359 d, key parameters (dissolved oxygen (DO), NH4+-N, NO2−-N, NO3−-N, PO43–-P) were quantified to account for the effects of switching alum-dosing into the bioselector and varying dosages (429, 643, 1072 and 1286 g-Al3+ per treatment cycle). Results indicated a 52% reduction of alum usage with no impact on discharge limit (≤0.85 mg-P/L). As expected, a failure to maintain DO setpoint (1.6 mg/L) reduced both NH4+-N and PO43–-P removal. Increasing alum dosage simply could not alleviate this problem, but maintenance of DO at least 85% of setpoint enabled effective rectification. This 15% DO buffer zone offers operators an opportunity to rectify imminent operational failures related to DO, prior to escalating alum dosage. An operational framework to manage DO related failures is proposed. Overall, this study offers insights on how to cost effectively apply alum and manage DO failures to achieve P discharge limits in IDEA plants