Extended Reality Head-Mounted Displays Are Likely to Pose a Significant Risk in Medical Settings While Current Classification Remains as Non-Critical.

Extended reality (XR) devices, including virtual and augmented reality head-mounted displays (HMDs), are increasingly utilised within healthcare to provide clinical interventions and education. Currently, XR devices are utilised to assist in reducing pain and improving psychological outcomes for immunocompromised patients in intensive care units, palliative care environments and surgical theatres. However, there is a paucity of research on the risks of infection from such devices in healthcare settings. Identify existing literature providing insights into the infection control risk XR HMDs pose within healthcare facilities and the efficacy of current infection control and cleaning procedures. Three databases (PubMed, Embase and CINAHL) in addition to Google Scholar were systematically searched. A total of seven studies were identified for this review. Microorganisms, including pathogenic bacteria (e.g., Staphylococcus aureus and Pseudomonas aeruginosa), were found to be present on XR HMDs. Published cleaning and infection control protocols designed to disinfect XR HMDs and protect users were heterogeneous in nature. Current cleaning protocols displayed varying levels of efficacy with microbial load affected by multiple factors, including time in use, number of users and XR HMD design features. In healthcare settings, fitting XR HMDs harbouring microorganisms near biological and mucosal entry points presents an infection control risk. An urgent revision of the Spaulding classification is required to ensure flexibility that allows for these devices to be reclassified from 'Non-critical' to 'Semi-Critical' depending on the healthcare setting and patient population (surgery, immunocompromised, burns, etc.). This review identified evidence supporting the presence of microorganisms on XR HMDs. Due to the potential for HMDs to contact mucosal entry points, devices must be re-considered within the Spaulding classification as 'Semi-critical'. The existence of microbial contaminated XR HMDs in high-risk medical settings such as operating wards, intensive care units, emergency departments, labour and delivery wards and clinical areas with immunosuppressed patients requires urgent attention. Public health authorities have a duty of care to develop revised guidelines or new recommendations to ensure efficient sanitation of such devices.

Do mobile phone surfaces carry SARS-CoV-2 virus? A systematic review warranting the inclusion of a "6th" moment of hand hygiene in healthcare.

BACKGROUND: Mobile phones, used in billions throughout the world, are high-touch devices subject to a dynamic contamination of microorganisms and rarely considered as an important fomite to sanitise systematically. The emergence of SARS-CoV-2 resulted in the COVID-19 pandemic, arguably the most impactful pandemic of the 21st century with millions of deaths and disruption of all facets of modern life globally. AIM: To perform a systematic review of the literature exploring SARS-CoV-2 presence as a contaminant on mobile phones. METHODS: A systematic search (PubMed and Google Scholar) of literature was undertaken from December 2019 to March 2023 identifying English language studies. Studies included in this review specifically identified or tested for the contamination of the SARS-CoV-2 virus or genome on mobile phones while studies testing for SARS-COV-2 in environments and/or other fomites samples than but not mobile phones were excluded. RESULTS: A total of 15 studies with reports of SARS-CoV-2 contamination on mobile phones between 2020 and 2023 were included. Amongst all studies, which encompassed ten countries, 511 mobile phones were evaluated for the presence of SARS-CoV-2 contamination and 45% (231/511) were positive for SARS-CoV-2. All studies were conducted in the hospital setting and two studies performed additional testing in residential isolation rooms and a patient's house. Four studies (3 in 2020 and one in 2021) reported 0% contamination while two other studies (in 2020 and 2022) reported 100% of mobile phone contamination with SARS-COV-2. All other studies report mobile phones positive for the virus within a range of 4-77%. CONCLUSION: A total of 45% of mobile phones are contaminated with SARS-CoV-2 virus. These devices might be an important fomite vector for viral dissemination worldwide. Competent health authorities are advised/recommended to start a global implementation of mobile phone decontamination by introducing regulations and protocols in public health and health care settings such as the 6th moment of hand washing.

Ultraviolet-C-Based Mobile Phone Sanitisation for Global Public Health and Infection Control.

INTRODUCTION: Mobile phones act as fomites that pose a global public health risk of disseminating microorganisms, including highly pathogenic strains possessing antimicrobial resistances. The use of ultraviolet-C (UV-C) to sanitise mobile phones presents an alternative means to complement basic hand hygiene to prevent the cross-contamination and dissemination of microorganisms between hands and mobile phones. AIM: This study aimed to evaluate the germicidal efficacy of the Glissner CleanPhone UV-C phone sanitiser (Glissner) device. METHODS: Two experimental trials were performed for the evaluation of the CleanPhone (Glissner). The first was a controlled trial, where the germicidal efficacy of the CleanPhone was evaluated against six different microorganism species that were inoculated onto mobile phones. The second was a field trial evaluating the germicidal efficacy of the CleanPhone on 100 volunteer mobile phones. Efficacy was determined based on colony counts of microorganisms on Columbia sheep blood agar before and after UV-C treatment. RESULTS: In the controlled trial, reduction in growth was observed for all microorganisms after UV-C treatment with ST131 Escherichia coli showing the highest growth reduction at 4 log10 CFU/mL followed by C. albicans and ATCC E. coli at 3 log10 CFU/mL. An overall reduction in microorganism growth after UV-C treatment was also observed for the field trial, with an average growth reduction of 84.4% and 93.6% in colony counts at 24 h and 48 h post-incubation, respectively. CONCLUSION: The findings demonstrated the capability of the CleanPhone (Glissner) to rapidly sanitise mobile phones, thereby providing a means to reduce the potential dissemination of microorganisms, including highly pathogenic strains with antimicrobial resistance.

Mobile phones as fomites for pathogenic microbes: A cross-sectional survey of perceptions and sanitization habits of health care workers in Dubai, United Arab Emirates.

BACKGROUNDS: In 2022, smartphone use continues to expand with the number of smartphone subscriptions surpassing 6 billion and forecasted to grow to 7.5 billion by 2026. The necessity of these 'high touch' devices as essential tools in professional healthcare settings carries great risks of cross-contamination between mobile phones and hands. Current research emphasises mobile phones as fomites enhancing the risk of nosocomial disease dissemination as phone sanitisation is often overlooked. To assess and report via a large-scale E-survey the handling practices and the use of phones by healthcare workers. METHODS: A total of 377 healthcare workers (HCWs) participated in this study to fill in an E-survey online consisting of 14 questions (including categorical, ordinal, and numerical data). Analysis of categorical data used non-parametric techniques such as Pearson's chi-squared test. RESULTS: During an 8-h shift, 92.8% (n/N = 350/377) use their phone at work with 84.6% (n/N = 319/377) considering mobile phones as an essential tool for their job. Almost all HCWs who participated in this survey believe their mobile phones could potentially harbour microorganisms (97.1%; n/N = 366/377). Fifty-seven respondents (15.1%) indicated that they use their phones while wearing gloves and 10.3% (n/N = 39/377) have never cleaned their phones. The majority of respondents (89.3%; n/N = 337/377) agreed that contaminated mobile phones could contribute to dissemination of SARS-CoV-2. CONCLUSION: Mobile phone use is now almost universal and indispensable in healthcare. Medical staff believe mobile phones can act as fomites with a potential risk for dissemination of microbes including SARS-COV-2. There is an urgent call for the incorporation of mobile phone sanitisation in infection prevention protocol. Studies on the use of ultraviolet-C based phone sanitation devices in health care settings are needed.

Healthcare Derived Smart Watches and Mobile Phones are Contaminated Niches to Multidrug Resistant and Highly Virulent Microbes.

Background: 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.

Mobile phones are hazardous microbial platforms warranting robust public health and biosecurity protocols.

Advancements in technology and communication have revolutionised the twenty-first century with the introduction of mobile phones and smartphones. These phones are known to be platforms harbouring microbes with recent research shedding light on the abundance and broad spectrum of organisms they harbour. Mobile phone use in the community and in professional sectors including health care settings is a potential source of microbial dissemination. To identify the diversity of microbial genetic signature present on mobile phones owned by hospital medical staff. Twenty-six mobile phones of health care staff were swabbed. DNA extraction for downstream next generation sequencing shotgun metagenomic microbial profiling was performed. Survey questionnaires were handed to the staff to collect information on mobile phone usage and users' behaviours. Each of the 26 mobile phones of this study was contaminated with microbes with the detection of antibiotic resistance and virulent factors. Taken together the sum of microbes and genes added together across all 26 mobile phones totalised 11,163 organisms (5714 bacteria, 675 fungi, 93 protists, 228 viruses, 4453 bacteriophages) and 2096 genes coding for antibiotic resistance and virulent factors. The survey of medical staff showed that 46% (12/26) of the participants used their mobile phones in the bathroom. Mobile phones are vectors of microbes and can contribute to microbial dissemination and nosocomial diseases worldwide. As fomites, mobile phones that are not decontaminated may pose serious risks for public health and biosecurity.

Metagenomic Sequencing and Reverse Transcriptase PCR Reveal That Mobile Phones and Environmental Surfaces Are Reservoirs of Multidrug-Resistant Superbugs and SARS-CoV-2.

Background: Mobile phones of healthcare workers (HCWs) can act as fomites in the dissemination of microbes. This study was carried out to investigate microbial contamination of mobile phones of HCWs and environmental samples from the hospital unit using a combination of phenotypic and molecular methods. Methods: This point prevalence survey was carried out at the Emergency unit of a tertiary care facility. The emergency unit has two zones, a general zone for non-COVID-19 patients and a dedicated COVID-19 zone for confirmed or suspected COVID-19 patients. Swabs were obtained from the mobile phones of HCWs in both zones for bacterial culture and shotgun metagenomic analysis. Metagenomic sequencing of pooled environmental swabs was conducted. RT-PCR for SARS-CoV-2 detection was carried out. Results: Bacteria contamination on culture was detected from 33 (94.2%) mobile phones with a preponderance of Staphylococcus epidermidis (n/N = 18/35), Staphylococcus hominis (n/N = 13/35), and Staphylococcus haemolyticus (n/N = 7/35). Two methicillin-sensitive and three methicillin-resistant Staphylococcus aureus, and one pan-drug-resistant carbapenemase producer Acinetobacter baumannii were detected. Shotgun metagenomic analysis showed high signature of Pseudomonas aeruginosa in mobile phone and environmental samples with preponderance of P. aeruginosa bacteriophages. Malassezia and Aspergillus spp. were the predominant fungi detected. Fourteen mobile phones and one environmental sample harbored protists. P. aeruginosa antimicrobial resistance genes mostly encoding for efflux pump systems were detected. The P. aeruginosa virulent factor genes detected were related to motility, adherence, aggregation, and biofilms. One mobile phone from the COVID-19 zone (n/N = 1/5; 20%) had positive SARS-CoV-2 detection while all other phone and environmental samples were negative. Conclusion: The findings demonstrate that mobile phones of HCWs are fomites for potentially pathogenic and highly drug-resistant microbes. The presence of these microbes on the mobile phones and hospital environmental surfaces is a concern as it poses a risk of pathogen transfer to patients and dissemination into the community.

A pilot metagenomic study reveals that community derived mobile phones are reservoirs of viable pathogenic microbes.

There is increasing attention focussed on the risks associated with mobile phones possibly serving as 'Trojan Horse' fomites for microbial transmission in healthcare settings. However, little is reported on the presence of microbes on community derived mobile phones which in 2021, numbered in the billions in circulation with majority being used on a daily basis. Identify viable microbial organisms swabbed from smartphones on a university campus. Entire surfaces of 5 mobile phones were swabbed and examined for their microbial content using pre-agar-based growths followed by downstream DNA metagenomic next-generation sequencing analysis. All phones were contaminated with viable microbes. 173 bacteria, 8 fungi, 8 protists, 53 bacteriophages, 317 virulence factor genes and 41 distinct antibiotic resistant genes were identified. While this research represents a pilot study, the snapshot metagenomic analysis of samples collected from the surface of mobile phones has revealed the presence of a large population of viable microbes and an array of antimicrobial resistant factors. With billions of phones in circulation, these devices might be responsible for the rise of community acquired infections. These pilot results highlight the importance of public health authorities considering mobile phones as 'Trojan Horse' devices for microbial transmission and ensure appropriate decontamination campaigns are implemented.

Mobile phones of paediatric hospital staff are never cleaned and commonly used in toilets with implications for healthcare nosocomial diseases.

An ever-increasing number of medical staff use mobile phones as a work aid, yet this may pose nosocomial diseases. To assess and report via a survey the handling practices and the use of phones by paediatric wards healthcare workers. 165 paediatric healthcare workers and staff filled in a questionnaire consisting of 14 questions (including categorical, ordinal and numerical data). Analysis of categorical data used non-parametric techniques such as the Chi-squared test. Although 98% of respondents (165 in total) report that their phones may be contaminated, 56% have never cleaned their devices. Of the respondents that clean their devices, 10% (17/165) had done so with alcohol swabs or disinfectant within that day or week; and an additional 12% respondents (20/165) within that month. Of concern, 52% (86/165) of the respondents use their phones in the bathroom, emphasising the unhygienic environments in which mobile phones/smartphones are constantly used. Disinfecting phones is a practice that only a minority of healthcare workers undertake appropriately. Mobile phones, present in billions globally, are therefore Trojan Horses if contaminated with microbes and potentially contributing to the spread and propagation of micro-organisms as per the rapid spread of SARS-CoV-2 virus in the world.

The role of mobile phones as a possible pathway for pathogen movement, a cross-sectional microbial analysis.

INTRODUCTION: Mobile phones are used the world over, including in healthcare settings. This study aimed to investigate the viable microbial colonisation of mobile phones used by healthcare personnel. METHODS: Swabs collected on the same day from 30 mobile phones belonging to healthcare workers from three separate paediatric wards of an Australian hospital were cultured on five types of agar plate, then colonies from each phone were pooled, extracted and sequenced by shotgun metagenomics. Questionnaires completed by staff whose phones were sampled assisted in the analysis and interpretation of results. RESULTS AND DISCUSSION: All phones sampled cultured viable bacteria. Overall, 399 bacterial operational taxonomic units were identified from 30 phones, with 1432 cumulative hits. Among these were 58 recognised human pathogenic and commensal bacteria (37 Gram-negative, 21 Gram-positive). The total number of virulence factor genes detected was 347, with 1258 cumulative hits. Antibiotic resistance genes (ARGs) were detected on all sampled phones and overall, 133 ARGs were detected with 520 cumulative hits. The most important classes of ARGs detected encoded resistance to beta-lactam, aminoglycoside and macrolide antibiotics and efflux pump mediated resistance mechanisms. CONCLUSION: Mobile phones carry viable bacterial pathogens and may act as fomites by contaminating the hands of their users and indirectly providing a transmission pathway for hospital-acquired infections and dissemination of antibiotic resistance. Further research is needed, but meanwhile adding touching mobile phones to the five moments of hand hygiene is a simple infection control strategy worth considering in hospital and community settings. Additionally, the implementation of practical and effective guidelines to decontaminate mobile phone devices would likely be beneficial to the hospital population and community at large.

Concentrations of plasma-borne extracellular particles differ between multiple sclerosis disease courses and compared to healthy controls.

BACKGROUND: Multiple sclerosis is a neurodegenerative, autoimmune disease of the central nervous system. Both peripheral blood and central nervous system facets play a role in the pathophysiology. Extracellular vesicles are small membrane-bound vesicles that are released by most cells in response to stress, activation, or pathology. As extracellular vesicles can cross the blood-brain barrier, they have the ability to link peripheral blood inflammation to central nervous system pathology in multiple sclerosis. The aim of this study was to obtain a comprehensive picture of the cellular origins of plasma-borne extracellular particles in multiple sclerosis. METHODS: Platelet-free plasma was obtained from 39 multiple sclerosis patients and 27 healthy controls via a series of centrifugation steps and assessed by flow cytometry. Plasma samples were stained with antibodies against CD4, CD8, CD14, CD20, CD41b, CD45, CD146, and CD235a. Gates were set using size-reference beads and extracellular particles were enumerated using commercial counting beads at known concentrations. RESULTS: In relapsing patients (n = 13) erythrocyte-derived (CD235a) extracellular particles were increased, while platelet-derived (CD41b), leukocyte-derived (CD45), and CD4+T cell-derived (CD4) extracellular particles were decreased compared to both healthy controls (n = 27) (p<0.05) and secondary progressive multiple sclerosis patients (n = 9) (p < 0.05). Endothelium-derived extracellular particles (CD146) were increased in stable relapsing-remitting multiple sclerosis patients (n = 17) compared to healthy controls (p < 0.05). Extracellular particles from several different cells of origin correlated with each other and clinical parameters (e.g. disease duration, number of relapses, EDSS), though clinical correlations did not withstand corrections for multiple comparisons. CONCLUSIONS: Concentrations of erythrocyte-, leukocyte-, and platelet-derived extracellular particles were altered in relapsing multiple sclerosis patients and endothelium-derived extracellular particles were increased in stable relapsing-remitting patients compared to healthy controls. Extracellular particles may provide insights into altered the crosstalk between peripheral blood cells in multiple sclerosis, which may lead to the discovery of novel therapeutic targets.

Erythrocyte microRNAs show biomarker potential and implicate multiple sclerosis susceptibility genes.

BACKGROUND: Multiple sclerosis is a demyelinating autoimmune disease, for which there is no blood-borne biomarker. Erythrocytes may provide a source of such biomarkers as they contain microRNAs. MicroRNAs regulate protein translation through complementary binding to messenger RNA. As erythrocytes are transcriptionally inactive, their microRNA profiles may be less susceptible to variation. The aim of this study was to assess the biomarker potential of erythrocyte microRNAs for multiple sclerosis and assess the potential contribution of erythrocyte-derived extracellular vesicle microRNAs to pathology. METHODS: Erythrocytes were isolated from whole blood by density gradient centrifugation. Erythrocyte microRNAs of a discovery cohort (23 multiple sclerosis patients and 22 healthy controls) were sequenced. Increased expression of miR-183 cluster microRNAs (hsa-miR-96-5p, hsa-miR-182-5p and hsa-miR-183-5p) was validated in an independent cohort of 42 patients and 45 healthy and pathological (migraine) controls. Erythrocyte-derived extracellular vesicles were created ex vivo and their microRNAs were sequenced. Targets of microRNAs were predicted using miRDIP. RESULTS: Hsa-miR-182-5p and hsa-miR-183-5p were able to discriminate relapsing multiple sclerosis patients from migraine patients and/or healthy controls with 89-94% accuracy and around 90% specificity. Hsa-miR-182-5p and hsa-miR-183-5p expression correlated with measures of physical disability and hsa-miR-96-5p expression correlated with measures of cognitive disability in multiple sclerosis. Erythrocytes were found to selectively package microRNAs into extracellular vesicles and 34 microRNAs were found to be differentially packaged between healthy controls and multiple sclerosis patients. Several gene targets of differentially expressed and packaged erythrocyte microRNAs overlapped with multiple sclerosis susceptibility genes. Gene enrichment analysis indicated involvement in nervous system development and histone H3-K27 demethylation. CONCLUSIONS: Erythrocyte miR-183 cluster members may be developed into specific multiple sclerosis biomarkers that could assist with diagnosis and disability monitoring. Erythrocyte and their extracellular microRNAs were shown to target multiple sclerosis susceptibility genes and may be contributing to the pathophysiology via previously identified routes.

Mobile phones represent a pathway for microbial transmission: A scoping review.

BACKGROUND: Mobile phones have become an integral part of modern society. As possible breeding grounds for microbial organisms, these constitute a potential global public health risk for microbial transmission. OBJECTIVE: Scoping review of literature examining microbial's presence on mobile phones in both health care (HC) and community settings. METHODS: A search (PubMed&GoogleScholar) was conducted from January 2005-December 2019 to identify English language studies. Studies were included if samples from mobile phones were tested for bacteria, fungi, and/or viruses; and if the sampling was carried out in any HC setting, and/or within the general community. Any other studies exploring mobile phones that did not identify specific microorganisms were excluded. RESULTS: A total of 56 studies were included (from 24 countries). Most studies identified the presence of bacteria (54/56), while 16 studies reported the presence of fungi. One study focused solely on RNA viruses. Staphylococcus aureus, and Coagulase-Negative Staphylococci were the most numerous identified organisms present on mobile phones. These two species and Escherichia coli were present in over a third of studies both in HC and community samples. Methicillin-resistant S. aureus, Acinetobacter sp., and Bacillus sp. were present in over a third of the studies in HC settings. CONCLUSIONS: While this scoping review of literature regarding microbial identification on mobile phones in HC and community settings did not directly address the issue of SARS-CoV-2 responsible for COVID-19, this work exposes the possible role of mobile phones as a 'Trojan horse' contributing to the transmission of microbial infections in epidemics and pandemics.

The Role of Genetic Profile in Functional Performance Adaptations to Exercise Training or Physical Activity: A Systematic Review of the Literature.

Background: Variations in genotype may contribute to heterogeneity in functional adaptations to exercise. Methods: A systematic search of eight databases was conducted, and 9,696 citations were screened. Results: Eight citations from seven studies measuring 10 single-nucleotide polymorphisms and nine different functional performance test outcomes were included in the review. There was one observational study of physical activity and six experimental studies of aerobic or resistance training. The ACE (D) allele, ACTN3 (RR) genotype, UCP2 (GG) genotype, IL-6-174 (GG) genotype, TNF-α-308 (GG) genotype, and IL-10-1082 (GG) genotype all predicted significantly superior adaptations in at least one functional outcome in older men and women after prescribed exercise or in those with higher levels of physical activity. Conclusion: There is a small amount of evidence that older adults may have better functional outcomes after exercise/physical activity if they have specific alleles related to musculoskeletal function or inflammation. However, more robust trials are needed.

Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients.

Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system. The inflammatory process in MS is driven by both T and B cells and current therapies are targeted to each of these cell types. Epigenetic mechanisms may provide a valuable link between genes and environment. DNA methylation is the best studied epigenetic mechanism and is recognized as a potential contributor to MS risk. The objective of this study was to identify DNA methylation changes associated with MS in CD19+ B-cells. We performed an epigenome-wide association analysis of DNA methylation in the CD19+ B-cells from 24 patients with relapsing-remitting MS on various treatments and 24 healthy controls using Illumina 450 K arrays. A large differentially methylated region (DMR) was observed at the lymphotoxin alpha (LTA) locus. This region was hypermethylated and contains 19 differentially methylated positions (DMPs) spanning 860 bp, all of which are located within the transcriptional start site. We also observed smaller DMRs at 4 MS-associated genes: SLC44A2, LTBR, CARD11 and CXCR5. These preliminary findings suggest that B-cell specific DNA-methylation may be associated with MS risk or response to therapy, specifically at the LTA locus. Development of B-cell specific epigenetic therapies is an attractive new avenue of research in MS treatment. Further studies are now required to validate these findings and understand their functional significance.

Erythrocyte microRNA sequencing reveals differential expression in relapsing-remitting multiple sclerosis.

BACKGROUND: There is a paucity of knowledge concerning erythrocytes in the aetiology of Multiple Sclerosis (MS) despite their potential to contribute to disease through impaired antioxidant capacity and altered haemorheological features. Several studies have identified an abundance of erythrocyte miRNAs and variable profiles associated with disease states, such as sickle cell disease and malaria. The aim of this study was to compare the erythrocyte miRNA profile of relapsing-remitting MS (RRMS) patients to healthy sex- and age-matched controls. METHODS: Erythrocytes were purified by density-gradient centrifugation and RNA was extracted. Following library preparation, samples were run on a HiSeq4000 Illumina instrument (paired-end 100 bp sequencing). Sequenced erythrocyte miRNA profiles (9 patients and 9 controls) were analysed by DESeq2. Differentially expressed miRNAs were validated by RT-qPCR using miR-152-3p as an endogenous control and replicated in a larger cohort (20 patients and 18 controls). After logarithmic transformation, differential expression was determined by two-tailed unpaired t-tests. Logistic regression analysis was carried out and receiver operating characteristic (ROC) curves were generated to determine biomarker potential. RESULTS: A total of 236 erythrocyte miRNAs were identified. Of twelve differentially expressed miRNAs in RRMS two showed increased expression (adj. p < 0.05). Only modest fold-changes were evident across differentially expressed miRNAs. RT-qPCR confirmed differential expression of miR-30b-5p (0.61 fold, p < 0.05) and miR-3200-3p (0.36 fold, p < 0.01) in RRMS compared to healthy controls. Relative expression of miR-3200-5p (0.66 fold, NS p = 0.096) also approached significance. MiR-3200-5p was positively correlated with cognition measured by audio-recorded cognitive screen (r = 0.60; p < 0.01). MiR-3200-3p showed greatest biomarker potential as a single miRNA (accuracy = 75.5%, p < 0.01, sensitivity = 72.7%, specificity = 84.0%). Combining miR-3200-3p, miR-3200-5p, and miR-30b-5p into a composite biomarker increased accuracy to 83.0% (p < 0.05), sensitivity to 77.3%, and specificity to 88.0%. CONCLUSIONS: This is the first study to report differences in erythrocyte miRNAs in RRMS. While the role of miRNAs in erythrocytes remains to be elucidated, differential expression of erythrocyte miRNAs may be exploited as biomarkers and their potential contribution to MS pathology and cognition should be further investigated.

Establishing a dose-response relationship between acute resistance-exercise and the immune system: Protocol for a systematic review.

Exercise immunology research has traditionally focussed on aerobic-exercise, however it has become apparent in more recent years that resistance-exercise can also considerably affect host immunobiology. To date however, no systematic process has been used to establish a dose-response relationship between resistance-exercise and the immune system. The present systematic review was thus conducted to determine the dose-response effects of a bout of resistance-exercise on acute leukocyte counts. In accordance with the PRISMA guidelines, a systematic literature search was conducted in the electronic databases, PubMed, Web of Science, and Google Scholar, over the date range of 1989-2016. Following the PICO elements, eligibility criteria included: i) participants: healthy humans aged 18-40; ii) intervention: a single bout of resistance-exercise; iii) comparator: at least one comparator group; iv) outcome: acute measures of circulating leukocyte counts. Specific exclusion criteria were also applied. Risk of bias and quality of evidence was assessed using the PEDro scale. Due to the individual designs of the admitted studies, a qualitative analysis (systematic narrative synthesis) was employed in the present review. The results of the present review demonstrate that a single bout of resistance-exercise induces an acute monocytosis, neutrophilia, and lymphocytosis. It became apparent that the reviewed literature either does not consistently specify, or does not describe with sufficient detail, the time-course between the onset of exercise and the collection of blood. We recommend that researchers consider addressing this in future studies, and also collect blood measures during exercise to aid with comparison of temporal effects. Regarding the determination of a dose-response relationship, an acute neutrophilia, monocytosis and lymphocytosis appears to occur more rapidly and to a greater magnitude following a single bout of high-dose vs low-dose resistance-exercise. Mechanistically, exercise-induced cell trafficking changes are associated with mechanical, metabolic and endocrine factors. Physical aptitude of the host may also affect resistance-exercise-induced lymphocyte trafficking responses.

Decrease of DHEA-S concentration succeeding a micro-dose thumb exertion: mood-state determinants reflect stress-biomarker responses.

BACKGROUND: The present study examined the effect of a micro-dose of resistance-exercise on serum DHEA-S, IL-6 and mood-state determinants. Potential relationships between mood and the biomarkers were also studied with the aim of directing research on non-invasive exercise-monitoring methods. METHODS: 30 male participants (20 weightlifting-trained; 10 untrained) were separated into 3 groups of 10: weightlifting experimental (WLEXP); untrained experimental (UTEXP); weightlifting placebo (WLPLA). WLEXP and UTEXP performed four 60-s isometric thumb exertions separated by 60-s rest intervals in a single-blinded placebo-controlled study. Participants were assessed over a 60-min post-intervention recovery period for changes in serum DHEA-S and IL-6, and mood-state determinants (vigour, tension, fatigue). RESULTS: DHEA-S changed in UTEXP only; a decrease from 20- to 60-min post-exercise (Δ36.9 %, p < 0.01). DHEA-S remained below baseline at the final time-point (Δ35.3 %, p = 0.012). Tension decreased immediately post-exercise in WLEXP (Δ86.7 %, p = 0.022), whereas UTEXP showed a delayed decrease which continued up to 60-min post-intervention (Δ100 %, p < 0.01). Relative to fatigue scores recorded immediately post-exercise, WLEXP decreased within the first 10-min post-intervention (Δ22.2 %, p < 0.01) whereas UTEXP showed a delayed decrease evident at 20-min post-intervention (Δ25 %, p < 0.01). Serum IL-6 and vigour scores remained unchanged across groups (p > 0.05) and WLPLA did not change for any measured variable (p > 0.05). CONCLUSIONS: The authors conclude that a micro-dose of resistance-exercise can reduce serological DHEA-S concentration within 60-min of exercise cessation. Additionally, mood-state assessment in untrained individuals can be considered for non-invasively indicating exercise-induced concentration changes in the stress biomarker, DHEA-S, providing prospects for the development of safer, more sophisticated exercise-monitoring practice.

Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells.

BACKGROUND: Immunoactivation is less evident in secondary progressive MS (SPMS) compared to relapsing-remitting disease. MicroRNA (miRNA) expression is integral to the regulation of gene expression; determining their impact on immune-related cell functions, especially CD4+ T cells, during disease progression will advance our understanding of MS pathophysiology. This study aimed to compare miRNA profiles of CD4+ T cells from SPMS patients to healthy controls (HC) using whole miRNA transcriptome next-generation sequencing (NGS). Total RNA was extracted from CD4+ T cells and miRNA expression patterns analyzed using Illumina-based small-RNA NGS in 12 SPMS and 12 HC samples. Results were validated in a further cohort of 12 SPMS and 10 HC by reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: The ten most dysregulated miRNAs identified by NGS were selected for qPCR confirmation; five (miR-21-5p, miR-26b-5p, miR-29b-3p, miR-142-3p, and miR-155-5p) were confirmed to be down-regulated in SPMS (p < 0.05). SOCS6 is targeted by eight of these ten miRNAs. Consistent with this, SOCS6 expression is up-regulated in SPMS CD4+ T cells (p < 0.05). This is of particular interest as SOCS6 has previously been shown to act as a negative regulator of T cell activation. CONCLUSIONS: Ninety-seven percent of miRNA candidates identified by NGS were down-regulated in SPMS. The down-regulation of miRNAs and increased expression of SOCS6 in SPMS CD4+ T cells may contribute to reduced immune system activity in progressive MS.

Recombinant human growth hormone and insulin-like growth factor-1 do not affect mitochondrial derived highly reactive oxygen species production in peripheral blood mononuclear cells under conditions of substrate saturation in-vitro.

BACKGROUND: The purpose of this study was to investigate the mitochondrial effects exerted by physiological and supra-physiological concentrations of recombinant human growth hormone (rhGH) and recombinant insulin-like growth factor-1 (rIGF-1) under conditions of substrate saturation in peripheral blood mononuclear cells (PBMCs). METHODS: PBMCs from healthy male subjects were treated with either rhGH, at concentrations of 0.5, 5 and 50 µg/L, or rIGF-1 at concentrations of 100, 300 and 500 µg/L for 4 h. Mitochondrial membrane potential (Δψm) and mitochondrial levels of highly reactive oxygen species (hROS) were subsequently analysed. This analysis was performed by flow cytometry in digitonin permeabilized cells, following treatment with saturating concentrations of various respiratory substrate combinations and the use of specific electron transport chain (ETC.) complex inhibitors, enabling control over both the sites of electron entry into the ETC. at complexes I and II and the entry of electrons from reduced carriers involved in ß-oxidation at the level of ubiquinol. RESULTS: Neither rhGH nor rIGF-1 exerted any significant effect on Δψm or the rate of hROS production in either lymphocyte or monocyte sub-populations under any of the respiratory conditions analysed. CONCLUSION: That neither hormone was capable of attenuating levels of oxidative stress mediated via either complex I linked respiration or lipid-derived respiration could have serious health implications for the use of rhGH in healthy individuals, which is frequently associated with significant increases in the bioavailability of free fatty acids (FFA). Such elevated supplies of lipid-derived substrates to the mitochondria could lead to oxidative damage which would negatively impact mitochondrial function.