Children and young people with cancer face barriers when engaging with exercise, such as treatment-related side effects, psychosocial burdens and lack of individualised provisions. Digital health tools, such as smartphone applications, have emerged as a promising driver to support healthcare provisions in exercise prescription among patients. It is vital to explore how such technologies can be developed more effectively in order to strengthen the evidence supporting their use and for more appropriate implementation within healthcare.
View Article and Find Full Text PDFThe secretion of alarmin cytokines by epithelial cells, including thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33, initiates inflammatory cascades in asthma. However, alarmin cytokine expression in the upper airways in asthma remains largely unknown. We recruited 40 participants with asthma into four groups as per the Global Initiative for Asthma (GINA) steps (10 in each group of GINA 1/2, 3, 4, and 5).
View Article and Find Full Text PDFObjective: Neurofilament heavy-chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk.
View Article and Find Full Text PDFIntroduction: Despite epidemiological associations between community acquired pneumonia (CAP) and myocardial infarction, mechanisms that modify cardiovascular disease during CAP are not well defined. In particular, largely due to a lack of relevant experimental models, the effect of pneumonia on atherosclerotic plaques is unclear. We describe the development of a murine model of the commonest cause of CAP, pneumonia, on a background of established atherosclerosis.
View Article and Find Full Text PDFSummary: The current widespread adoption of next-generation sequencing (NGS) in all branches of basic research and clinical genetics fields means that users with highly variable informatics skills, computing facilities and application purposes need to process, analyse, and interpret NGS data. In this landscape, versatility, scalability, and user-friendliness are key characteristics for an NGS analysis software. We developed DNAscan2, a highly flexible, end-to-end pipeline for the analysis of NGS data, which (i) can be used for the detection of multiple variant types, including SNVs, small indels, transposable elements, short tandem repeats, and other large structural variants; (ii) covers all standard steps of NGS analysis, from quality control of raw data and genome alignment to variant calling, annotation, and generation of reports for the interpretation and prioritization of results; (iii) is highly adaptable as it can be deployed and run via either a graphic user interface for non-bioinformaticians and a command line tool for personal computer usage; (iv) is scalable as it can be executed in parallel as a Snakemake workflow, and; (v) is computationally efficient by minimizing RAM and CPU time requirements.
View Article and Find Full Text PDFIf validated, in-shoe pressure measuring technology allows for the field-based quantification of running gait, including kinematic and kinetic measures. Different algorithmic methods have been proposed to determine foot contact events from in-shoe pressure insole systems, however, these methods have not been evaluated for accuracy, reliability against a gold standard using running data across different slopes, and speeds. Using data from a plantar pressure measurement system, seven different foot contact event detection algorithms based on pressure signals (pressure sum) were compared to vertical ground reaction force data collected from a force instrumented treadmill.
View Article and Find Full Text PDFAmyotroph Lateral Scler Frontotemporal Degener
August 2023
: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS.
View Article and Find Full Text PDFHuman endogenous retroviruses (HERVs) integrated into the human genome as a result of ancient exogenous infections and currently comprise ∼8% of our genome. The members of the most recently acquired HERV family, HERV-Ks, still retain the potential to produce viral molecules and have been linked to a wide range of diseases including cancer and neurodegeneration. Although a range of tools for HERV detection in NGS data exist, most of them lack wet lab validation and they do not cover all steps of the analysis.
View Article and Find Full Text PDFDysregulated neutrophilic inflammation can be highly destructive in chronic inflammatory diseases due to prolonged neutrophil lifespan and continual release of histotoxic mediators in inflamed tissues. Therapeutic induction of neutrophil apoptosis, an immunologically silent form of cell death, may be beneficial in these diseases, provided that the apoptotic neutrophils are efficiently cleared from the tissue. Previous research in our group identified ErbB inhibitors as able to induce neutrophil apoptosis and reduce neutrophilic inflammation both and .
View Article and Find Full Text PDFThe COVID-19 crisis in Australia led to a rapid increase in the use of telehealth services to offer psychological therapy (often referred to as 'telepsychology'). In this article, we discuss the intersection of the social psychology concepts of therapeutic holding spaces and containment with more-than-human theory as it relates to Australia's mental health sector during the COVID-19 crisis. Drawing on our recent qualitative survey research into Australian psychologists' use of telepsychology during the crisis, we consider the ways that they worked to build and maintain therapeutic holding spaces and alliances over teleconferencing platforms during this extraordinary time of social crisis and isolation.
View Article and Find Full Text PDFFront Cell Infect Microbiol
June 2021
Exposure to respiratory pathogens is a leading cause of exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Pellino-1 is an E3 ubiquitin ligase known to regulate virally-induced inflammation. We wished to determine the role of Pellino-1 in the host response to respiratory viruses in health and disease.
View Article and Find Full Text PDFMononuclear phagocytes such as monocytes, tissue-specific macrophages, and dendritic cells are primary actors in both innate and adaptive immunity. These professional phagocytes can be parasitized by intracellular bacteria, turning them from housekeepers to hiding places and favoring chronic and/or disseminated infection. One of the most infamous is the bacteria that cause tuberculosis (TB), which is the most pandemic and one of the deadliest diseases, with one-third of the world's population infected and an average of 1.
View Article and Find Full Text PDFS. aureus is a leading cause of bacterial infection. Macrophages, the first line of defence in the human immune response, phagocytose and kill S.
View Article and Find Full Text PDFNon-typeable (NTHi) is a frequent cause of lower respiratory tract infection in people with chronic obstructive pulmonary disease (COPD). Pellino proteins are a family of E3 ubiquitin ligases that are critical regulators of TLR signaling and inflammation. The aim of this study was to identify a role for Pellino-1 in airway defense against NTHi in the context of COPD.
View Article and Find Full Text PDFAntimicrobial resistance challenges therapy of pneumonia. Enhancing macrophage microbicidal responses would combat this problem but is limited by our understanding of how alveolar macrophages (AMs) kill bacteria. To define the role and mechanism of AM apoptosis-associated bacterial killing in the lung.
View Article and Find Full Text PDFThe tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a widely expressed cytokine that can bind five different receptors. TRAIL has been of particular interest for its proposed ability to selectively induce apoptosis in tumour cells. However, it has also been found to regulate a wide variety of non-canonical cellular effects including survival, migration and proliferation via kinase signalling pathways.
View Article and Find Full Text PDFThe Net Promoter Score (NPS) metric, commonly used by Fortune 500 companies to measure the customer experience, is calculated using a 0-to-10 scale to answer 1 question: "How likely is it that you would recommend [company X] to a friend or colleague?" Despite the value of this methodology as a predictor of growth and indicator of customer satisfaction in for-profit industries, uptake of the NPS has been slower in the social sector due to concerns about its applicability and acceptability in noncommercial settings, particularly among low-literacy populations. To address these concerns, we conducted a series of small-scale pilots in El Salvador, India, Kenya, and Nigeria to test different implementation approaches of the NPS in sexual and reproductive health clinics-including face-to-face interviews, a guided drop box, integration of the NPS question into an existing client exit interview, and self-administered and volunteer-assisted online surveys using tablets in clinics-and compared the traditional 0-to-10 number scale with an emoji-face scale. Findings showed that the NPS can be effectively adapted for use in low-resource health clinics among low-literacy clients using the number scale.
View Article and Find Full Text PDFThe common ancestry of archaea and eukaryotes is evident in their genome architecture. All eukaryotic and several archaeal genomes consist of multiple chromosomes, each replicated from multiple origins. Three scenarios have been proposed for the evolution of this genome architecture: 1) mutational diversification of a multi-copy chromosome; 2) capture of a new chromosome by horizontal transfer; 3) acquisition of new origins and splitting into two replication-competent chromosomes.
View Article and Find Full Text PDFWe report the sequencing and assembly of a reference genome for the human GM12878 Utah/Ceph cell line using the MinION (Oxford Nanopore Technologies) nanopore sequencer. 91.2 Gb of sequence data, representing ∼30× theoretical coverage, were produced.
View Article and Find Full Text PDFRationale: People living with HIV are at significantly increased risk of invasive pneumococcal disease, despite long-term antiretroviral therapy (ART). The mechanism explaining this observation remains undefined.
Objectives: To determine if apoptosis-associated microbicidal mechanisms, required to clear intracellular pneumococci that survive initial phagolysosomal killing, are perturbed.
The objectives of this study were to validate the application of Bluetooth technology to determine maternal pedigree and to determine ewe-lamb spatial relationships in extensive farming systems. A total of 35 first-cross Merino ewes (Merino × Border Leicester and East Friesian) and 23 of their lambs aged 1 to 3 wk were fitted with activity monitors equipped with Bluetooth (BT) technology (ActiGraph wGT3X-BT) by means of halters and collars, respectively. The BT devices on lambs were programmed to receive wireless signals once every minute from nearby BT units on ewes, which were programmed as beacons sending BT signals 4 times every second.
View Article and Find Full Text PDFFully activated innate immune cells are required for effective responses to infection, but their prompt deactivation and removal are essential for limiting tissue damage. Here, we have identified a critical role for the prolyl hydroxylase enzyme Phd2 in maintaining the balance between appropriate, predominantly neutrophil-mediated pathogen clearance and resolution of the innate immune response. We demonstrate that myeloid-specific loss of Phd2 resulted in an exaggerated inflammatory response to Streptococcus pneumonia, with increases in neutrophil motility, functional capacity, and survival.
View Article and Find Full Text PDFRationale: Chronic obstructive pulmonary disease (COPD) is characterized by impaired clearance of pulmonary bacteria.
Objectives: The effect of COPD on alveolar macrophage (AM) microbicidal responses was investigated.
Methods: AMs were obtained from bronchoalveolar lavage from healthy donors or patients with COPD and challenged with opsonized serotype 14 Streptococcus pneumoniae.
Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both and infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise.
View Article and Find Full Text PDF