High-level cognition is supported by information-rich but compressible brain activity patterns.

To efficiently yet reliably represent and process information, our brains need to produce information-rich signals that differentiate between moments or cognitive states, while also being robust to noise or corruption. For many, though not all, natural systems, these two properties are often inversely related: More information-rich signals are less robust, and vice versa. Here, we examined how these properties change with ongoing cognitive demands. To this end, we applied dimensionality reduction algorithms and pattern classifiers to functional neuroimaging data collected as participants listened to a story, temporally scrambled versions of the story, or underwent a resting state scanning session. We considered two primary aspects of the neural data recorded in these different experimental conditions. First, we treated the maximum achievable decoding accuracy across participants as an indicator of the "informativeness" of the recorded patterns. Second, we treated the number of features (components) required to achieve a threshold decoding accuracy as a proxy for the "compressibility" of the neural patterns (where fewer components indicate greater compression). Overall, we found that the peak decoding accuracy (achievable without restricting the numbers of features) was highest in the intact (unscrambled) story listening condition. However, the number of features required to achieve comparable classification accuracy was also lowest in the intact story listening condition. Taken together, our work suggests that our brain networks flexibly reconfigure according to ongoing task demands and that the activity patterns associated with higher-order cognition and high engagement are both more informative and more compressible than the activity patterns associated with lower-order tasks and lower engagement.

Heterogeneous Fenton's-like catalyst potentiation of hydrogen peroxide disinfection: an investigation into mechanisms of action.

AIMS: This study aimed to establish the mechanisms of action (MOA) of a novel surface-functionalized polyacrylonitrile (PAN) catalyst, which was previously shown to have potent antimicrobial activity in conjunction with hydrogen peroxide (H2O2). METHODS AND RESULTS: Bactericidal activity was determined using a disinfectant suspension test. The MOA was investigated by measuring the loss of 260 nm absorbing material, membrane potential, permeability assays, analysis of intra- and extracellular ATP and pH, and tolerance to sodium chloride and bile salts.The catalyst lowered sub-lethal concentrations of H2O2 from 0.2 to 0.09%. H2O2 ± 3 g PAN catalyst significantly (P ≤ 0.05) reduced sodium chloride and bile salt tolerance, suggesting the occurance of sublethal cell membrane damage. The catalyst significantly increased (P ≤ 0.05) N-Phenyl-l-Napthylamine uptake (1.51-fold) and leakage of nucleic acids, demonstrating increased membrane permeability. A significant (P ≤ 0.05) loss of membrane potential (0.015 a.u.), coupled with pertubation of intracellular pH homeostasis and depletion of intracellular ATP, suggests potentiation of H2O2-mediated cell membrane damage. CONCLUSIONS: This is the first study to investigate the catalyst's antimicrobial mechanism of action, with the cytoplasmic membrane being a target for cellular injury.

Antiviral plant-derived natural products to combat RNA viruses: Targets throughout the viral life cycle.

There is a need for new effective antivirals, particularly in response to the development of antiviral drug resistance and emerging RNA viruses such as SARS-CoV-2. Plants are a significant source of structurally diverse bioactive compounds for drug discovery suggesting that plant-derived natural products could be developed as antiviral agents. This article reviews the antiviral activity of plant-derived natural products against RNA viruses, with a focus on compounds targeting specific stages of the viral life cycle. A range of plant extracts and compounds have been identified with antiviral activity, often against multiple virus families suggesting they may be useful as broad-spectrum antiviral agents. The antiviral mechanism of action of many of these phytochemicals is not fully understood and there are limited studies and clinical trials demonstrating their efficacy and toxicity in vivo. Further research is needed to evaluate the therapeutic potential of plant-derived natural products as antiviral agents.

A Gaussian Process Model of Human Electrocorticographic Data.

We present a model-based method for inferring full-brain neural activity at millimeter-scale spatial resolutions and millisecond-scale temporal resolutions using standard human intracranial recordings. Our approach makes the simplifying assumptions that different people's brains exhibit similar correlational structure, and that activity and correlation patterns vary smoothly over space. One can then ask, for an arbitrary individual's brain: given recordings from a limited set of locations in that individual's brain, along with the observed spatial correlations learned from other people's recordings, how much can be inferred about ongoing activity at other locations throughout that individual's brain? We show that our approach generalizes across people and tasks, thereby providing a person- and task-general means of inferring high spatiotemporal resolution full-brain neural dynamics from standard low-density intracranial recordings.

From formulation to in vivo model: A comprehensive study of a synergistic relationship between vancomycin, carvacrol, and cuminaldehyde against Enterococcus faecium.

Vancomycin-resistant Enterococcus faecium (VRE) has become endemic in healthcare settings, reducing treatment options for enterococcal infections. New antimicrobials for VRE infections are a high priority, but the development of novel antibiotics is time-consuming and expensive. Essential oils (EOs) synergistically enhance the activity of some existing antibiotics, suggesting that EO-antibiotic combinations could resensitise resistant bacteria and maintain the antibiotic repertoire. The mechanism of resensitisation of bacteria to antibiotics by EOs is relatively understudied. Here, the synergistic interactions between carvacrol (1.98 mM) and cuminaldehyde (4.20 mM) were shown to reestablish susceptibility to vancomycin (0.031 mg/L) in VRE, resulting in bactericidal activity (4.73 log10 CFU/ml reduction). Gene expression profiling, coupled with ß-galactosidase leakage and salt tolerance assays, suggested that cell envelope damage contributes to the synergistic bactericidal effect against VRE. The EO-vancomycin combination was also shown to kill clinical isolates of VRE (2.33-5.25 log10 CFU/ml reduction), and stable resistance did not appear to develop even after multiple passages. The in vivo efficacy of the EO-vancomycin combination was tested in a Galleria mellonella larvae assay; however, no antimicrobial action was observed, indicating that further drug development is required for the EO-vancomycin combination to be clinically useful for treatment of VRE infections.

Characterisation and screening of antimicrobial essential oil components against clinically important antibiotic-resistant bacteria using thin layer chromatography-direct bioautography hyphenated with GC-MS, LC-MS and NMR.

INTRODUCTION: The antimicrobial activity of many essential oils (EOs) is well established, indicating that EOs may be a source of compounds for antimicrobial drug development. Thin layer chromatography-direct bioautography (TLC-DB) can quickly identify antimicrobial components in complex mixtures and can be applied to the screening of EOs for lead compounds. OBJECTIVES: This study aimed to identify antimicrobial components of oregano, rosewood and cumin EOs against antibiotic-sensitive and -resistant bacteria using TLC-DB and a multi-faceted approach of GC-MS, LC-MS and NMR techniques to characterise bioactive compounds. The study also aimed to quantify the antimicrobial activity of bioactive compounds in order to evaluate their potential for the development of therapies against antibiotic-resistant bacteria. MATERIALS AND METHODS: EOs were eluted on TLC plates and sprayed with a suspension of Staphylococcus aureus, Enterococcus faecium, Escherichia coli or Pseudomonas aeruginosa (antibiotic-sensitive and -resistant isolates). Zones of inhibition, visualised with iodonitrotetrazolium chloride, were subject to GC-MS, LC-MS and NMR to characterise the bioactive compounds. RESULTS: Seven compounds were identified from the three EOs using GC-MS, while LC-MS and NMR failed to detect the presence of any further non-volatile or heat labile compounds. Carvacrol was most antimicrobial compound identified, with minimum inhibitory concentrations ranging 0.99-31.62 mM. CONCLUSION: The identified antimicrobial compounds present in oregano, rosewood and cumin EOs including carvacrol may be candidates for the development of novel antimicrobial therapies against antibiotic-resistant bacteria.

Synchronous application of antibiotics and essential oils: dual mechanisms of action as a potential solution to antibiotic resistance.

Antibiotic resistance has increased dramatically in recent years, yet the antibiotic pipeline has stalled. New therapies are therefore needed to continue treating antibiotic resistant infections. One potential strategy currently being explored is the use of non-antibiotic compounds to potentiate the activity of currently employed antibiotics. Many natural products including Essential Oils (EOs) possess broad spectrum antibacterial activity and so have been investigated for this purpose. This article aims to review recent literature concerning the antibacterial activity of EOs and their interactions with antibiotics, with consideration of dual mechanisms of action of EOs and antibiotics as a potential solution to antibiotic resistance. Synergistic interactions between EOs and their components with antibiotics have been reported, including several instances of antibiotic resensitization in resistant isolates, in support of this strategy to control antibiotic resistance. However, a lack of consistency in methods and interpretation criteria makes drawing conclusions of efficacy of studied combinations difficult. Synergistic effects are often not explored beyond preliminary identification of antibacterial interactions and mechanism of action is rarely defined, despite many hypotheses and recommendations for future study. Much work is needed to fully understand EO-antibiotic associations before they can be further developed into novel antibacterial formulations.

Structure-activity modelling of essential oils, their components, and key molecular parameters and descriptors.

Many essential oil components are known to possess broad spectrum antimicrobial activity, including against antibiotic resistant bacteria. These compounds may be a useful source of new and novel antimicrobials. However, there is limited research on the structure-activity relationship (SAR) of essential oil compounds, which is important for target identification and lead optimization. This study aimed to elucidate SARs of essential oil components from experimental and literature sources. Minimum Inhibitory Concentrations (MICs) of essential oil components were determined against Escherichia coli and Staphylococcus aureus using a microdilution method and then compared to those in published in literature. Of 12 essential oil components tested, carvacrol and cuminaldehyde were most potent with MICs of 1.98 and 2.10 mM, respectively. The activity of 21 compounds obtained from the literature, MICs ranged from 0.004 mM for limonene to 36.18 mM for α-terpineol. A 3D qualitative SAR model was generated from MICs using FORGE software by consideration of electrostatic and steric parameters. An r2 value of 0.807 for training and cross-validation sets was achieved with the model developed. Ligand efficiency was found to correlate well to the observed activity (r2 = 0.792), while strongly negative electrostatic regions were present in potent molecules. These descriptors may be useful for target identification of essential oils or their major components in antimicrobial/drug development.

A Multifactorial Comparison of Ternary Combinations of Essential Oils in Topical Preparations to Current Antibiotic Prescription Therapies for the Control of Acne Vulgaris-Associated Bacteria.

Acne vulgaris, a chronic condition associated with overgrowth of Propionibacterium acnes and Staphylococcus epidermidis, is commonly treated with antibiotics. However, the emergence of antibiotic resistance has resulted in a need for alternative therapies. The aim of this study is to develop a topical preparation incorporating essential oils (EOs) for use against acne-associated bacteria and assess its efficacy against prescription therapies Dalacin T and Stiemycin. Antimicrobial screening of rosewood, clove bud and litsea EOs was conducted before interactions between binary and ternary combinations were determined against P. acnes and S. epidermidis (type and clinical isolates) using minimum inhibitory concentrations and fractional inhibitory concentrations. The EOs were characterised by both gas chromatography-mass spectrometry and nuclear magnetic resonance. A combination of 0.53 mg/mL litsea, 0.11 mg/mL rosewood and 0.11 mg/mL clove bud was formulated into herbal distillates and compared with Dalacin T and Stiemycin against antibiotic sensitive and resistant isolates (erythromycin). The distillate with EO had synergistic activity against P. acnes (7log10 reduction) and indifferent activity against S. epidermidis (6log10 reduction); antimicrobial activity was either significantly (p ≤ 0.05) more antimicrobial or equivalent to that of Dalacin T and Stiemycin. This formulation may serve as a valuable alternative for the control of acne vulgaris-associated bacteria. Copyright © 2017 John Wiley & Sons, Ltd.

A descriptive study of domestic and family violence presentations to an emergency department in the Northern Territory.

OBJECTIVE: Examine the nature of domestic and family violence (DFV) presentations to an ED in the Northern Territory and identify potential gaps in service delivery. METHODS: Prospective descriptive study of DFV presentations in November 2021. RESULTS: A total of 70 presentations were identified, representing 1.2% of all presentations aged 16 years and older. Disproportionately impacted were First Nations people (90%), women (77.1%) and those aged less than 40 years (67.1%). Most (81.4%) arrived outside of business hours and only 37.1% were assessed by the social worker. Case complexity was increased by high rates of homelessness (30%), concurrent alcohol consumption (44.3%) and pregnancy (11.1% of females). More than a third (37.1%) had attended on one to four occasions in the previous 6 months with a DFV-related injury. Compared to non-DFV attendances, the median ED length of stay was approximately twice as long (456 vs 210 min), admissions rates to the ED short stay unit five times higher (25.7% vs 5.7%; P < 0.01, odds ratio [OR] = 5.7 and 95% confidence interval [CI] = 3.3-9.8) and rates of self-discharge prior to completion of care 9 times higher (12.9% vs 1.5%; P < 0.01, OR = 9.5 and 95% CI = 4.6-19.7). CONCLUSION: The data highlights the need for a 24 h trauma-informed, culturally safe and integrated service to support people experiencing DFV. This could be achieved by a specialist unit designed and staffed by First Nations health practitioners.

SOMAScience: A Novel Platform for Multidimensional, Longitudinal Pain Assessment.

Chronic pain is one of the most significant health issues in the United States, affecting more than 20% of the population. Despite its contribution to the increasing health crisis, reliable predictors of disease development, progression, or treatment outcomes are lacking. Self-report remains the most effective way to assess pain, but measures are often acquired in sparse settings over short time windows, limiting their predictive ability. In this paper, we present a new mobile health platform called SOMAScience. SOMAScience serves as an easy-to-use research tool for scientists and clinicians, enabling the collection of large-scale pain datasets in single- and multicenter studies by facilitating the acquisition, transfer, and analysis of longitudinal, multidimensional, self-report pain data. Data acquisition for SOMAScience is done through a user-friendly smartphone app, SOMA, that uses experience sampling methodology to capture momentary and daily assessments of pain intensity, unpleasantness, interference, location, mood, activities, and predictions about the next day that provide personal insights into daily pain dynamics. The visualization of data and its trends over time is meant to empower individual users' self-management of their pain. This paper outlines the scientific, clinical, technological, and user considerations involved in the development of SOMAScience and how it can be used in clinical studies or for pain self-management purposes. Our goal is for SOMAScience to provide a much-needed platform for individual users to gain insight into the multidimensional features of their pain while lowering the barrier for researchers and clinicians to obtain the type of pain data that will ultimately lead to improved prevention, diagnosis, and treatment of chronic pain.

Preserved motor memory in Parkinson's disease.

Patients with Parkinson's disease, who lose the dopaminergic projections to the striatum, are impaired in certain aspects of motor learning. Recent evidence suggests that, in addition to its role in motor performance, the striatum plays a key role in the memory of motor learning. Whether Parkinson's patients have impaired motor memory and whether motor memory is modulated by dopamine at the time of initial learning is unknown. To address these questions, we measured memory of a learned motor sequence in Parkinson's patients who were either On or Off their dopaminergic medications at the time of initial learning. We compared them to a group of older and younger controls. Contrary to our predictions, motor memory was not impaired in patients compared to older controls, and was not influenced by dopamine state at the time of initial learning. To probe post-learning consolidation processes, we also tested whether learning a new sequence shortly after learning the initial sequence would interfere with later memory. We found that, in contrast to younger adults, neither older adults nor patients were susceptible to this interference. These findings suggest that motor memory is preserved in Parkinson's patients and raise the possibility that motor memory in patients is supported by compensatory non-dopamine sensitive mechanisms. Furthermore, given the similar performance characteristics observed in the patients and older adults and the absence of an effect of dopamine, these results raise the possibility that aging and Parkinson's disease affect motor memory in similar ways.

Health care worker knowledge and attitudes towards uniform laundering during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic raised concerns towards domestic laundering of healthcare worker (HCW) uniforms; this is common practice in countries such as the United Kingdom (UK) and United States. Previous research suggested 4-32% of nurses did not adhere to laundry policies, which could be an infection control risk. This study aimed to investigate the knowledge and attitudes of UK healthcare workers towards domestic laundering of uniforms during the COVID-19 pandemic. METHODS: Online and paper questionnaires were distributed to HCWs and nursing students who regularly wear uniforms. Differences in knowledge between HCWs were analyzed by Chi-squared tests and attitudes were examined using exploratory factor analysis. RESULTS: About 86% of participants (n = 1099 of 1277) laundered their uniforms domestically. Respondents were confident in laundering their uniforms appropriately (71%), however 17% failed to launder at the recommended temperature (60°C). Most participants (68%) would prefer their employer launder their uniforms, with mixed negative emotions towards domestic laundering. Limited provision of uniforms and changing and/or storage facilities were a barrier to following guidelines. CONCLUSION: Most HCWs domestically launder their uniforms, despite a preference for professional laundering. One-fifth of HCWs deviated from the UK National Health Service uniform guidelines; onsite changing facilities were the most significant barrier towards adherence.

Porous surfaces: stability and recovery of coronaviruses.

The role of indirect contact in the transmission of SARS-CoV-2 is not clear. SARS-CoV-2 persists on dry surfaces for hours to days; published studies have largely focused on hard surfaces with less research being conducted on different porous surfaces, such as textiles. Understanding the potential risks of indirect transmission of COVID-19 is useful for settings where there is close contact with textiles, including healthcare, manufacturing and retail environments. This article aims to review current research on porous surfaces in relation to their potential as fomites of coronaviruses compared to non-porous surfaces. Current methodologies for assessing the stability and recovery of coronaviruses from surfaces are also explored. Coronaviruses are often less stable on porous surfaces than non-porous surfaces, for example, SARS-CoV-2 persists for 0.5 h-5 days on paper and 3-21 days on plastic; however, stability is dependent on the type of surface. In particular, the surface properties of textiles differ widely depending on their construction, leading to variation in the stability of coronaviruses, with longer persistence on more hydrophobic materials such as polyester (1-3 days) compared to highly absorbent cotton (2 h-4 days). These findings should be considered where there is close contact with potentially contaminated textiles.

A multidisciplinary simulation programme to improve advance care planning skills and engagement across primary and secondary care.

BACKGROUND: In the context of an ageing population, many healthcare professionals have limited experience and confidence in having necessary advance care planning (ACP) conversations. METHODS: We conducted nine half-day simulation sessions, using professional actors. One-hundred and thirty-two participants attended from multidisciplinary backgrounds across primary and secondary care. RESULTS: Following the course, 90.2% felt confident or very confident initiating conversations, compared with 14.4% beforehand. Understanding of when ACP is appropriate also increased from 70% to 100%. Post-course, 98% of participants stated that they would be more likely to initiate an ACP. Three months later, 86% had a sustained change in practice. All participants said they would recommend this simulation course and multidisciplinary approach. CONCLUSION: Multidisciplinary simulation training is an effective way to teach ACP to doctors, nurses and allied healthcare professionals. The simulation was shown to improve participant understanding, confidence and reduce barriers to discussions, both immediately and 3 months later.

The Stability of Model Human Coronaviruses on Textiles in the Environment and during Health Care Laundering.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists on stainless steel and plastic for up to 7 days, suggesting that coronavirus disease 2019 (COVID-19) could be spread by fomite transmission. There is limited research on the stability of SARS-CoV-2 on textiles, with the risk of textiles acting as fomites not being well understood. To date, there does not appear to be any published research on the stability of coronaviruses during laundering, which is required to determine the efficacy of current laundering policies in the decontamination of health care textiles. The aim of this study was to investigate the environmental stability of human coronaviruses HCoV-OC43 and HCoV-229E on different textile fiber types and the persistence of HCoV-OC43 on textiles during domestic and industrial laundering. This study demonstrated that human coronaviruses (5 log10 50% tissue culture infective doses [TCID50]) remain infectious on polyester for ≥72 h, cotton for ≥24 h, and polycotton for ≥6 h; HCoV-OC43 was also able to transfer from polyester to PVC or polyester after 72 h. Under clean conditions, HCoV-OC43 was not detectable on cotton swatches laundered with industrial and domestic wash cycles without temperature and detergent (≥4.57-log10-TCID50 reduction), suggesting that the dilution and agitation of wash cycles are sufficient to remove human coronaviruses from textiles. In the presence of interfering substances (artificial saliva), ≤1.78 log10 TCID50 HCoV-OC43 was detected after washing domestically without temperature and detergent, unlike industrial laundering, where the virus was completely removed. However, no infectious HCoV-OC43 was detected when washed domestically with detergent.IMPORTANCE Synthetic textiles such as polyester could potentially act as fomites of human coronaviruses, indicating the importance of infection control procedures during handling of contaminated textiles prior to laundering. This study provides novel evidence that human coronaviruses can persist on textiles for up to 3 days and are readily transferred from polyester textile to other surfaces after 72 h of incubation. This is of particular importance for the domestic laundering of contaminated textiles such as health care uniforms in the United Kingdom and United States, where there may be a risk of cross-contaminating the domestic environment. It was demonstrated that human coronaviruses are removed from contaminated textiles by typical domestic and commercial wash cycles, even at low temperatures without detergent, indicating that current health care laundering policies are likely sufficient in the decontamination of SARS-CoV-2 from textiles.

Investigation of the stability and risks of fomite transmission of human coronavirus OC43 on leather.

Limited research exists on the potential for leather to act as a fomite of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or endemic coronaviruses including human coronavirus (HCoV) OC43; this is important for settings such as the shoe manufacturing industry. Antiviral coating of leather hides could limit such risks. This study aimed to investigate the stability and transfer of HCoVOC43 on different leathers, as a surrogate for SARS-CoV-2, and assess the antiviral efficacy of a silver-based leather coating. The stability of HCoV-OC43 (6.6 log10) on patent, full-grain calf, corrected grain finished and nubuck leathers (silver additive-coated and uncoated) was measured by titration on BHK-21 cells. Transfer from leather to cardboard and stainless steel was determined. HCoV-OC43 was detectable for 6 h on patent, 24 h on finished leather and 48 h on calf leather; no infectious virus was recovered from nubuck. HCoV-OC43 transferred from patent, finished and calf leathers onto cardboard and stainless steel up to 2 h post-inoculation (≤3.1-5.5 log10), suggesting that leathers could act as fomites. Silver additive-coated calf and finished leathers were antiviral against HCoV-OC43, with no infectious virus recovered after 2 h and limited transfer to other surfaces. The silver additive could reduce potential indirect transmission of HCoV-OC43 from leather.

High-level cognition during story listening is reflected in high-order dynamic correlations in neural activity patterns.

Our thoughts arise from coordinated patterns of interactions between brain structures that change with our ongoing experiences. High-order dynamic correlations in neural activity patterns reflect different subgraphs of the brain's functional connectome that display homologous lower-level dynamic correlations. Here we test the hypothesis that high-level cognition is reflected in high-order dynamic correlations in brain activity patterns. We develop an approach to estimating high-order dynamic correlations in timeseries data, and we apply the approach to neuroimaging data collected as human participants either listen to a ten-minute story or listen to a temporally scrambled version of the story. We train across-participant pattern classifiers to decode (in held-out data) when in the session each neural activity snapshot was collected. We find that classifiers trained to decode from high-order dynamic correlations yield the best performance on data collected as participants listened to the (unscrambled) story. By contrast, classifiers trained to decode data from scrambled versions of the story yielded the best performance when they were trained using first-order dynamic correlations or non-correlational activity patterns. We suggest that as our thoughts become more complex, they are reflected in higher-order patterns of dynamic network interactions throughout the brain.

Distributed Subnetworks of Depression Defined by Direct Intracranial Neurophysiology.

Major depressive disorder is a common and disabling disorder with high rates of treatment resistance. Evidence suggests it is characterized by distributed network dysfunction that may be variable across patients, challenging the identification of quantitative biological substrates. We carried out this study to determine whether application of a novel computational approach to a large sample of high spatiotemporal resolution direct neural recordings in humans could unlock the functional organization and coordinated activity patterns of depression networks. This group level analysis of depression networks from heterogenous intracranial recordings was possible due to application of a correlational model-based method for inferring whole-brain neural activity. We then applied a network framework to discover brain dynamics across this model that could classify depression. We found a highly distributed pattern of neural activity and connectivity across cortical and subcortical structures that was present in the majority of depressed subjects. Furthermore, we found that this depression signature consisted of two subnetworks across individuals. The first was characterized by left temporal lobe hypoconnectivity and pathological beta activity. The second was characterized by a hypoactive, but hyperconnected left frontal cortex. These findings have applications toward personalization of therapy.