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OBJECTIVE: To evaluate a relatively new half-face-piece powered air-purifying respirator (PAPR) device called the HALO (CleanSpace). We assessed its communication performance, its degree of respiratory protection, and its usability and comfort level. DESIGN AND SETTING: This simulation study was conducted at the simulation center of the Royal Melbourne Hospital. PARTICIPANTS: In total, 8 voluntary healthcare workers participated in the study: 4 women and 4 men comprising 3 nursing staff and 5 medical staff. METHODS: We performed the modified rhyme test, outlined by the National Institute for Occupational Safety and Health (NIOSH), for the communication assessment. We conducted quantitative fit test and simulated workplace protection factor studies to assess the degree of respiratory protection for participants at rest, during, and immediately after performing chest compression. We also invited the participants to complete a usability and comfort survey. RESULTS: The HALO PAPR met the NIOSH minimum standard for speech intelligibility, which was significantly improved with the addition of wireless communication headsets. The HALO provided consistent and adequate level of respiratory protection at rest, during and after chest compression regardless of the device power mode. It was rated favorably for its usability and comfort. However, participants criticized doffing difficulty and perceived communication interference. CONCLUSIONS: The HALO device can be considered as an alternative to a filtering face-piece respirator. Thorough doffing training and mitigation planning to improve the device communication performance are recommended. Further research is required to examine its clinical outcomes and barriers that may potentially affect patient or healthcare worker safety.

OBJECTIVE: Discomfort and device-related pressure injury (DRPI) caused by N95 filtering facepiece respirators (FFRs) are common. The use of prophylactic hydrocolloid dressings is one of the strategies that may improve comfort and reduce DRPI. In this study, we investigated the impact of these dressings on N95 respirator fit. METHODS: We performed a repeat quantitative fit testing through the Respiratory Protection Program on 134 healthcare workers (HCWs), who applied hydrocolloid dressings on the bridge of their nose under the N95 FFRs that they passed the initial fit test with, but reported discomfort with the FFR. RESULTS: With the hydrocolloid dressings in place, the fit-test pass rate for the semirigid cup style (3M 1860) was 94% (108 of 115); for the the vertical flat-fold style (BYD), the pass rate was 85% (44 of 52); for the duckbill style (BSN medical ProShield and Halyard Fluidshield), the pass rate was 81% (87 of 108); and for the 3-panel flat-fold style (3M Aura) N95 FFRs, the pass rate was 100% (3 of 3). There was a statistically significant reduction in the overall fit factors for both the vertical flat-fold and duckbill type N95 respirators after the application of hydrocolloid dressings. CONCLUSIONS: Hydrocolloid dressings are likely to disturb the mask seal for nonrigid-style N95 FFRs, particularly the vertical flat-fold style and the duckbill style N95 FFRs. Given the risk of mask seal disturbance of N95 respirators as shown in this study, we advocate that any HCW requiring the use of prophylactic dressings should undergo repeat quantitative fit testing with the dressing in place prior to using the dressing and mask in combination.

BACKGROUND: Implantable brain-computer interfaces (BCIs), functioning as motor neuroprostheses, have the potential to restore voluntary motor impulses to control digital devices and improve functional independence in patients with severe paralysis due to brain, spinal cord, peripheral nerve or muscle dysfunction. However, reports to date have had limited clinical translation. METHODS: Two participants with amyotrophic lateral sclerosis (ALS) underwent implant in a single-arm, open-label, prospective, early feasibility study. Using a minimally invasive neurointervention procedure, a novel endovascular Stentrode BCI was implanted in the superior sagittal sinus adjacent to primary motor cortex. The participants undertook machine-learning-assisted training to use wirelessly transmitted electrocorticography signal associated with attempted movements to control multiple mouse-click actions, including zoom and left-click. Used in combination with an eye-tracker for cursor navigation, participants achieved Windows 10 operating system control to conduct instrumental activities of daily living (IADL) tasks. RESULTS: Unsupervised home use commenced from day 86 onwards for participant 1, and day 71 for participant 2. Participant 1 achieved a typing task average click selection accuracy of 92.63% (100.00%, 87.50%-100.00%) (trial mean (median, Q1-Q3)) at a rate of 13.81 (13.44, 10.96-16.09) correct characters per minute (CCPM) with predictive text disabled. Participant 2 achieved an average click selection accuracy of 93.18% (100.00%, 88.19%-100.00%) at 20.10 (17.73, 12.27-26.50) CCPM. Completion of IADL tasks including text messaging, online shopping and managing finances independently was demonstrated in both participants. CONCLUSION: We describe the first-in-human experience of a minimally invasive, fully implanted, wireless, ambulatory motor neuroprosthesis using an endovascular stent-electrode array to transmit electrocorticography signals from the motor cortex for multiple

beta-(1,3)-Glucan is present in mould cell walls and frequently detected in house dust mite (HDM) faeces. beta-Glucan exposure is thought to be associated with pulmonary allergic inflammation in mouse and man, although the published data are inconsistent. Here, we show that highly purified beta-glucan exacerbates HDM-induced eosinophilic, T helper 2 type airway responses by acting as an adjuvant, promoting activation, proliferation and polarisation of HDM-specific T cells (1-Der beta T cells). We therefore provide definitive evidence that beta-glucan can influence allergic pulmonary inflammation.

Asthma is a heterogeneous disease whose etiology is poorly understood but is likely to involve innate responses to inhaled microbial components that are found in allergens. The influence of these components on pulmonary inflammation has been largely studied in the context of individual agonists, despite knowledge that they can have synergistic effects when used in combination. Here we have explored the effects of LPS and β-glucan, two commonly-encountered microbial agonists, on the pathogenesis of allergic and non-allergic respiratory responses to house dust mite allergen. Notably, sensitization with these micro-bial components in combination acted synergistically to promote robust neutrophilic inflammation, which involved both Dectin-1 and TLR-4. This pulmonary neutrophilic inflammation was corticosteroid-refractory, resembling that found in patients with severe asthma. Thus our results provide key new insights into how microbial components influence the development of respiratory pathology.

Background: Theory-of-mind (ToM), the ability to infer people's thoughts and feelings, is a pivotal skill in effective social interactions. Individuals with autism spectrum disorders (ASD) have been found to have altered ToM skills, which significantly impacts the quality of their social interactions. Neuroimaging studies have reported altered activation of the ToM cortical network, especially in adults with autism, yet little is known about the brain responses underlying ToM in younger individuals with ASD. This functional magnetic resonance imaging (fMRI) study investigated the neural mechanisms underlying ToM in high-functioning children and adolescents with ASD and matched typically developing (TD) peers. Methods: fMRI data were acquired from 13 participants with ASD and 13 TD control participants while they watched animations involving two "interacting" geometrical shapes. Results: Participants with ASD showed significantly reduced activation, relative to TD controls, in regions considered part of the ToM network, the mirror network, and the cerebellum. Functional connectivity analyses revealed underconnectivity between frontal and posterior regions during task performance in the ASD participants. Conclusions: Overall, the findings of this study reveal disruptions in the brain circuitry underlying ToM in ASD at multiple levels, including decreased activation and decreased functional connectivity.

The cyclooctadepsipeptide emodepside and its parent compound PF1022A are broad-spectrum nematicidal drugs which are able to eliminate nematodes resistant to other anthelmintics. The mode of action of cyclooctadepsipeptides is only partially understood, but involves the latrophilin Lat-1 receptor and the voltage- and calcium-activated potassium channel Slo-1. Genetic evidence suggests that emodepside exerts its anthelmintic activity predominantly through Slo-1. Indeed, slo-1 deficient Caenorhabditis elegans strains are completely emodepside resistant. However, direct effects of emodepside on Slo-1 have not been reported and these channels have only been characterized for C. elegans and related Strongylida. Molecular and bioinformatic analyses identified full-length Slo-1 cDNAs of Ascaris suum, Parascaris equorum, Toxocara canis, Dirofilaria immitis, Brugia malayi, Onchocerca gutturosa and Strongyloides ratti. Two paralogs were identified in the trichocephalids Trichuris muris, Trichuris suis and Trichinella spiralis. Several splice variants encoding truncated channels were identified in Trichuris spp. Slo-1 channels of trichocephalids form a monophyletic group, showing that duplication occurred after the divergence of Enoplea and Chromadorea. To explore the function of a representative protein, C. elegans Slo-1a was expressed in Xenopus laevis oocytes and studied in electrophysiological (voltage-clamp) experiments. Incubation of oocytes with 1-10 µM emodepside caused significantly increased currents over a wide range of step potentials in the absence of experimentally increased intracellular Ca2+, suggesting that emodepside directly opens C. elegans Slo-1a. Emodepside wash-out did not reverse the effect and the Slo-1 inhibitor verruculogen was only effective when applied before, but not after, emodepside. The identification of several splice variants and paralogs in some parasitic nematodes suggests that there are substantial differences in channel properties among s

This prospective observational study investigated the effect of focused transthoracic echocardiography in 99 patients who had suspected cardiac disease or were ≥ 65 years old, and were scheduled for emergency non-cardiac surgery. The treating anaesthetist completed a diagnosis and management plan before and after transthoracic echocardiography, which was performed by an independent operator. Clinical examination rated cardiac disease present in 75%; the remainder were asymptomatic. The cardiac diagnosis was changed in 67% and the management plan in 44% of patients after echocardiography. Cardiac disease was identified by echocardiography in 64% of patients, which led to a step-up of treatment in 36% (4% delay for cardiology referral, 2% altered surgery, 4% intensive care and 26% intra-operative haemodynamic management changes). Absence of cardiac disease in 36% resulted in a step-down of treatment in 8% (no referral 3%, intensive care 1% or haemodynamic treatment 4%). Pre-operative focused transthoracic echocardiography in patients admitted for emergency surgery and with known cardiac disease or suspected to be at risk of cardiac disease frequently alters diagnosis and management.

We conducted a randomised single-blind controlled trial comparing the LMA-Unique (LMAU) and the AMBU AuraOnce (AMBU) disposable laryngeal mask in spontaneously breathing adult patients undergoing general anaesthesia. Eighty-two adult patients (ASA status I-IV) were randomly allocated to receive the LMAU or AMBU and were blinded to device selection. Patients received a standardized anesthetic and all airway devices were inserted by trained anaesthetists. Size selection was guided by manufacturer recommendations. All data were collected by a single, unblinded observer. When compared with the LMAU, the AMBU produced significantly higher airway sealing pressures (AMBU 20 ± 6; LMAU 15 ± 7 cm H(2)O; P = 0.001). There was no statistical difference between the two devices for overall success rate, insertion time, number of adjustments, laryngeal alignment, blood-staining, and sore throat (P ≥ 0.05). The AMBU AuraOnce disposable laryngeal mask provided a higher oropharyngeal leak pressure compared to the LMA Unique in spontaneously breathing adult patients.

Individuals with autism often violate social rules and have lower accuracy in identifying and explaining inappropriate social behavior. Twelve children with autism (AD) and thirteen children with typical development (TD) participated in this fMRI study of the neurofunctional basis of social judgment. Participants indicated in which of two pictures a boy was being bad (Social condition) or which of two pictures was outdoors (Physical condition). In the within-group Social-Physical comparison, TD children used components of mentalizing and language networks [bilateral inferior frontal gyrus (IFG), bilateral medial prefrontal cortex (mPFC), and bilateral posterior superior temporal sulcus (pSTS)], whereas AD children used a network that was primarily right IFG and bilateral pSTS, suggesting reduced use of social and language networks during this social judgment task. A direct group comparison on the Social-Physical contrast showed that the TD group had greater mPFC, bilateral IFG, and left superior temporal pole activity than the AD group. No regions were more active in the AD group than in the group with TD in this comparison. Both groups successfully performed the task, which required minimal language. The groups also performed similarly on eyetracking measures, indicating that the activation results probably reflect the use of a more basic strategy by the autism group rather than performance disparities. Even though language was unnecessary, the children with TD recruited language areas during the social task, suggesting automatic encoding of their knowledge into language; however, this was not the case for the children with autism. These findings support behavioral research indicating that, whereas children with autism may recognize socially inappropriate behavior, they have difficulty using spoken language to explain why it is inappropriate. The fMRI results indicate that AD children may not automatically use language to encode their social understanding, making e

During helminth infections, alternatively activated macrophages (AAMacs) are key to promoting Th2 responses and suppressing Th1-driven inflammatory pathology. Th2 cytokines IL-4 and/or IL-13 are believed to be important in the induction and activation of AAMacs. Using murine models for the helminth infections caused by Fasciola hepatica (Fh) and Schistosoma mansoni (Sm), we show that a secreted antioxidant, peroxiredoxin (Prx), induces alternative activation of macrophages. These activated, Ym1-expressing macrophages enhanced the secretion of IL-4, IL-5, and IL-13 from naive CD4+ T cells. Administration of recombinant FhPrx and SmPrx to wild-type and IL-4 -/- and IL-13-/- mice induced the production of AAMacs. In addition, Prx stimulated the expression of markers of AAMacs (particularly, Ym1) in vitro, and therefore can act independently of IL-4/IL-13 signaling. The immunomodulatory property of Prx is not due to its antioxidant activity, as an inactive recombinant variant with active site Cys residues replaced by Gly could also induce AAMacs and Th2 responses. Immunization of mice with recombinant Prx or passive transfer of anti-Prx antibodies prior to infection with Fh not only blocked the induction of AAMacs but also the development of parasite-specific Th2 responses. We propose that Prx activates macrophages as an initial step in the induction of Th2 responses by helminth parasites and is thereby a novel pathogen-associated molecular pattern. © FASEB.

Alveolar macrophages represent a first-line innate host defense mechanism for clearing inhaled Aspergillus fumigatus from the lungs, yet contradictory data exist as to which alveolar macrophage recognition receptor is critical for innate immunity to A. fumigatus. Acknowledging that the A. fumigatus cell wall contains a high beta-1,3-glucan content, we questioned whether the beta-glucan receptor dectin-1 played a role in this recognition process. Monoclonal antibody, soluble receptor, and competitive carbohydrate blockage indicated that the alveolar macrophage inflammatory response, specifically the production of tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-1β, IL-6, CXCL2/macrophage inflammatory protein-2 (MIP-2), CCL3/macrophage inflammatory protein-1α (MIP-1α), granulocyte-colony stimulating factor (G-CSF), and granulocyte monocyte-CSF (GM-CSF), to live A. fumigatus was dependent on recognition via the beta-glucan receptor dectin-1. The inflammatory response was triggered at the highest level by A. fumigatus swollen conidia and early germlings and correlated to the levels of surface-exposed beta glucans, indicating that dectin-1 preferentially recognizes specific morphological forms of A. fumigatus. Intratracheal administration of A. fumigatus conidia to mice in the presence of a soluble dectin-Fc fusion protein reduced both lung proinflammatory cytokine/chemokine levels and cellular recruitment while modestly increasing the A. fumigatus fungal burden, illustrating the importance of beta-glucan-initiated dectin-1 signaling in defense against this pathogen. Collectively, these data show that dectin-1 is centrally required for the generation of alveolar macrophage proinflammatory responses to A. fumigatus and to our knowledge provides the first in vivo evidence for the role of dectin-1 in fungal innate defense. © 2005 Steele et al.