Search

Introduction. Secure airway for proper ventilation during anesthesia is one important component of a successful surgery. Endotracheal intubation is one of the most important methods in this context. Intubation method and used medication are considerably important in attenuating complications. This research aimed to investigate the impact of two different doses of dexmedetomidine in mitigating cardiovascular responses to endotracheal intubation in candidate cases supporting voluntary operation. Methods. The current research contained 90 cases in the range of 18 and 50 old, with ASA I,II supporting voluntary operation, who were randomly classified into three teams, each group consisting of 30 cases. The first set (A) got 0.5 μg/ kg dexmedetomidine, the second set (B) got 1 μg/ kg dexmedetomidine and the third set (C) got an equal volume of saline as placebo, 600 seconds earlier the initiation of anesthesia. Hemodynamic parameters were recorded at baseline (T0), then after the injection and the earlier initiation of anesthesia (T1), after the induction of anesthesia and before the endotracheal intubation (T2), promptly after tracheal intubation, 180, and 300 after endotracheal intubation (T4, T5). Data was analyzed and p < 0.05 was supposed notable. Findings. In this research, 3 teams were similar regarding weight, age, height, sex and duration of laryngoscopy. The diastolic mean arterial pressure, heart rate, and systolic arterial pressure were significantly lower in dexmedetomidine teams (A,B) at all times after the endotracheal intubation compared to group C. There were no significant differences in hemodynamic factors among group A, B. Conclusion. Dexmedetomidine effectively and significantly attenuates cardiovascular and hemodynamic responses during endotracheal intubation. In addition, different doses of dexmedetomidine did not cause any significant distinct result in mitigating cardiovascular responses. [ABSTRACT FROM AUTHOR]

Relatively little is known about long term effects of wood smoke on population health. A wood burning marker -- levoglucosan -- was measured using a highly standardized sampling and measurement method in four study areas across Europe (Oslo, the Netherlands, Munich/Augsburg, Catalonia) to assess within and between study area spatial variation. Levoglucosan was analyzed in addition to other components: PM2.5, PM2.5 absorbance, PM10, polycyclic aromatic hydrocarbons (PAH), nitrogen oxides (NOx), elemental and organic carbon (EC/OC), hopanes, steranes and elemental composition. Measurements were conducted at street, urban and regional background sites. Three two-week samples were taken per site and the annual average concentrations of pollutants were calculated using continuous measurements at one background site as a reference. Land use regression (LUR) models were developed to explain the spatial variation of levoglucosan using standardized procedures. Much larger within than between study area contrast in levoglucosan concentration was found. Spatial variation patterns differed substantially from other measured pollutants including PM2.5, NOx and EC. Levoglucosan had the highest spatial correlation with ΣPAH (r = 0.65) and the lowest with traffic markers -- NOx, Σhopanes/steranes (r = -0.22). The correlation of levoglucosan with potassium (K), which is also used as a wood burning marker, was moderate to low (median r = 0.33). Levoglucosan concentrations in the cold (heating) period were between 3 and 20 times higher compared to the warm period. The contribution of wood-smoke calculated based on levoglucosan measurements and previous European emission data to OC and PM2.5 mass were 13 to 28% and 3 to 9% respectively in the full year. Larger contributions were calculated for the cold period. The median model R² of the LUR models was 60 %. In Catalonia the model R² was the highest (71 %). The LUR models included population and natural land related variables but no traffic associated variables. In conclusion, substantial spatial variability was found in levoglucosan concentrations particularly within study areas.Wood smoke contributed substantially to especially wintertime PM2.5 OC and mass. The low to moderate correlation with PM2.5 mass and traffic markers offers the potential to assess health effects of wood smoke separate from traffic-related air pollution. [ABSTRACT FROM AUTHOR]

Systematic reviews (SRs) and meta-analyses (MAs) require a comprehensive and reproducible strategy to assess the methodological quality of the included studies. This research-on-research study evaluated the methods used to assess research quality by SRs and MAs published in leading neurosurgical journals, and identified factors associated with the publication of a comprehensive and reproducible assessment. We systematically surveyed SRs published in the 10 leading neurosurgical journals between 01/11/2019 and 31/12/2021. PubMed was used to search the MEDLINE database, which was supplemented by individual journal searches. Included SRs were assessed using a standardised data extraction tool. Descriptive statistics were utilised to identify factors associated with methodological and reporting quality of the tool-based quality assessment. A total of 564 SRs were included in the analysis. 326 (57.80%) included MAs, 165 (29.26%) included at least one Randomized Controlled Trial (RCT) and 29 (5.14%) included only RCTs. Scales were the most commonly used tool for methodological quality assessment (32.45%), followed by domain-based tools (24.82%) and checklists (9.93%). The number of included studies was inversely associated with multiple methodological quality assessment metrics. A positive association was observed between the number of included patients and multiple methodological quality assessment metrics. We established that the methodological and reporting quality of tool-based quality assessment requires improvement. This issue is particularly pertinent for SRs limited to non-randomised studies, which account for the vast majority of neurosurgical SRs. We recommend the use of domain-based tools for methodological quality assessment as these provide a more nuanced assessment of methodological quality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study introduces a novel ion-imprinted polymer for the ultrasensitive detection of mercury(II) in water. The ion-imprinted polymer was synthesized via a simple bulk polymerization process using methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the cross-linker, morpholine-4-carbodithioic acid phenyl ester as the chelating agent, and ammonium persulfate as the initiator. The electrochemical mercury(II) sensing capability of the ion-imprinted polymer was studied via the modification of a cost-effective carbon paste electrode. A stripping voltammetric technique was utilized to quantify the analyte ions following open-circuit enrichment. Critical experimental parameters, including the nature and concentration of the eluent, solution pH, preconcentration duration, ion-imprinted polymer dosage, sample solution volume and reduction potential, were systematically studied and optimized. Under optimal conditions, the sensor exhibited a linear response in the range of 1.0 to 240.0 nM, with a low detection limit of 0.2 nM. The sensor demonstrated remarkable selectivity against potential interfering ions, including lead(II), cadmium(II), copper(II), zinc(II), manganese(II), iron(II), magnesium(II), calcium(II), sodium(I) and cobalt(II). The practical applicability of the developed method was successfully validated through the analysis of real water samples, suggesting its potential for environmental monitoring applications., (© 2024. The Author(s).)

Objectives: To investigate health consumers' ethical concerns towards the use of artificial intelligence (AI) in EDs., Methods: Qualitative semi-structured interviews with health consumers, recruited via health consumer networks and community groups, interviews conducted between January and August 2022., Results: We interviewed 28 health consumers about their perceptions towards the ethical use of AI in EDs. The results discussed in this paper highlight the challenges and barriers for the effective and ethical implementation of AI from the perspective of Australian health consumers. Most health consumers are more likely to support AI health tools in EDs if they continue to be involved in the decision-making process. There is considerably more approval of AI tools that support clinical decision-making, as opposed to replacing it. There is mixed sentiment about the acceptability of AI tools influencing clinical decision-making and judgement. Health consumers are mostly supportive of the use of their data to train and develop AI tools but are concerned with who has access. Addressing bias and discrimination in AI is an important consideration for some health consumers. Robust regulation and governance are critical for health consumers to trust and accept the use of AI., Conclusion: Health consumers view AI as an emerging technology that they want to see comprehensively regulated to ensure it functions safely and securely with EDs. Without considerations made for the ethical design, implementation and use of AI technologies, health consumer trust and acceptance in the use of these tools will be limited., (© 2024 The Author(s). Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

Recently developed small-molecule inhibitors of the lysosomal protease dipeptidyl peptidase 1 (DPP1), also known as cathepsin C (CatC), can suppress suppurative inflammation in vivo by blocking the processing of zymogenic (pro-) forms of neutrophil serine proteases (NSPs), including neutrophil elastase, proteinase 3, and cathepsin G. DPP1 also plays an important role in activating granzyme serine proteases that are expressed by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. Therefore, it is critical to determine whether DPP1 inhibition can also cause off-target suppression of CTL/NK-cell-mediated killing of virus-infected or malignant cells. Herein, we demonstrate that the processing of human granzymes A and B, transitioning from zymogen to active proteases, is not solely dependent on DPP1. Thus, the killing of target cells by primary human CD8 + T cells, NK cells, and gene-engineered anti-CD19 CAR T cells was not blocked in vitro even after prior exposure to high concentrations of the reversible DPP1 inhibitor brensocatib. Consistent with this observation, the turnover of model granzyme A/B peptide substrates in the human CTL/NK cell lysates was not significantly reduced by brensocatib. In contrast, preincubation with brensocatib almost entirely abolished (>90%) both the cytotoxic activity of mouse CD8 + T cells and granzyme substrate turnover. Overall, our finding that the effects of DPP1 inhibition on human cytotoxic lymphocytes are attenuated in comparison to those of mice indicates that granzyme processing/activation pathways differ between mice and humans. Moreover, the in vitro data suggest that human subjects treated with reversible DPP1 inhibitors, such as brensocatib, are unlikely to experience any appreciable deficits in CTL/NK-cell-mediated immunities., Competing Interests: Authors DC, K-JC, DLaS, and PMcD were employed by Insmed Incorporated. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sutton, Watt, Akhlaghi, Cipolla, Chen, LaSala, McDonald, Beavis, Munoz, Hodel, Noori, Voskoboinik and Trapani.)

Background: A noninvasive and accurate method of determining fluid responsiveness in ventilated patients would help to mitigate unnecessary fluid administration. Although carotid ultrasound has been previously studied for this purpose, several studies have recently been published. We performed an updated systematic review and meta-analysis to evaluate the accuracy of carotid ultrasound as a tool to predict fluid responsiveness in ventilated patients., Methods: Studies eligible for review investigated the accuracy of carotid ultrasound parameters in predicting fluid responsiveness in ventilated patients, using sensitivity and specificity as markers of diagnostic accuracy (International Prospective Register of Systematic Reviews [PROSPERO] CRD42022380284). All included studies had to use an independent method of determining cardiac output and exclude spontaneously ventilated patients. Six bibliographic databases and 2 trial registries were searched. Medline, Embase, Emcare, APA PsycInfo, CINAHL, and the Cochrane Library were searched on November 4, 2022. Clinicaltrials.gov and Australian New Zealand Clinical Trials Registry were searched on February 24, 2023. Results were pooled, meta-analysis was conducted where possible, and hierarchical summary receiver operating characteristic models were used to compare carotid ultrasound parameters. Bias and evidence quality were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines., Results: Thirteen prospective clinical studies were included (n = 648 patients), representing 677 deliveries of volume expansion, with 378 episodes of fluid responsiveness (58.3%). A meta-analysis of change in carotid Doppler peak velocity (∆CDPV) yielded a sensitivity of 0.79 (95% confidence interval [CI], 0.74-0.84) and a specificity of 0.85 (95% CI, 0.76-0.90). Risk of bias relating to recruitment methodology, the independence of index testing to reference standards and exclusionary clinical criteria were evaluated. Overall quality of evidence was low. Study design heterogeneity, including a lack of clear parameter cutoffs, limited the generalizability of our results., Conclusions: In this meta-analysis, we found that existing literature supports the ability of carotid ultrasound to predict fluid responsiveness in mechanically ventilated adults. ∆CDPV may be an accurate carotid parameter in certain contexts. Further high-quality studies with more homogenous designs are needed to further validate this technology., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: A noninvasive and accurate method of identifying fluid responsiveness in hemodynamically unstable patients has long been sought by physicians. Carotid ultrasound (US) is one such modality previously canvassed for this purpose. The aim of this novel systematic review and meta-analysis is to investigate whether critically unwell patients who are requiring intravenous (IV) fluid resuscitation (fluid responders) can be identified accurately with carotid US., Methods: The protocol was registered with PROSPERO on the 30/11/2022 (ID number: CRD42022380284). Studies investigating carotid ultrasound accuracy in assessing fluid responsiveness in hemodynamically unstable patients were included. Studies were identified through searches of six databases, all run on 4 November 2022, Medline, Embase, Emcare, APA PsycInfo, CINAHL, and Cochrane Library. Risk of bias was assessed using the QUADAS-2 and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines. Results were pooled, meta-analysis was conducted where amenable, and hierarchical summary receiver operating characteristic models were established to compare carotid ultrasound measures., Results: Seventeen studies were included ( n  = 842), with 1048 fluid challenges. 441 (42.1%) were fluid responsive. Four different carotid US measures were investigated, including change in carotid doppler peak velocity (∆CDPV), carotid blood flow (CBF), change in carotid artery velocity time integral (∆CAVTI), and carotid flow time (CFT). Pooled carotid US had a pooled sensitivity, specificity, and AUROC with 95% confidence intervals (CI) of 0.73 (0.66-0.78), 0.82 (0.72-0.90), and 0.81 (0.78-0.85), respectively. ∆CDPV had sensitivity, specificity, and AUROC with 95% CI of 0.72 (0.64-0.80), 0.87 (0.73-0.94), and 0.82 (0.78-0.85), respectively. CBF had sensitivity, specificity, and AUROC with 95% CI of 0.70 (0.56-0.80), 0.80 (0.50-0.94), and 0.77 (0.78-0.85), respectively. Risk of bias and assessment was undertaken using the QUADAS-2 and GRADE tools. The QUADAS-2 found that studies generally had an unclear or high risk of bias but with low applicability concerns. The GRADE assessment showed that ∆CDPV and CBF had low accuracy for sensitivity and specificity., Conclusion: It appears that carotid US has a limited ability to predict fluid responsiveness in critically unwell patients. ∆CDPV demonstrates the greatest accuracy of all measures analyzed. Further high-quality studies using consistent study design would help confirm this., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Samuel C. D. Walker et al.)

Objective: To assess Australian and New Zealand emergency clinicians' attitudes towards the use of artificial intelligence (AI) in emergency medicine., Methods: We undertook a qualitative interview-based study based on grounded theory. Participants were recruited through ED internal mailing lists, the Australasian College for Emergency Medicine Bulletin, and the research teams' personal networks. Interviews were transcribed, coded and themes presented., Results: Twenty-five interviews were conducted between July 2021 and May 2022. Thematic saturation was achieved after 22 interviews. Most participants were from either Western Australia (52%) or Victoria (16%) and were consultants (96%). More participants reported feeling optimistic (10/25) than neutral (6/25), pessimistic (2/25) or mixed (7/25) towards the use of AI in the ED. A minority expressed scepticism regarding the feasibility or value of implementing AI into the ED. Multiple potential risks and ethical issues were discussed by participants including skill loss from overreliance on AI, algorithmic bias, patient privacy and concerns over liability. Participants also discussed perceived inadequacies in existing information technology systems. Participants felt that AI technologies would be used as decision support tools and not replace the roles of emergency clinicians. Participants were not concerned about the impact of AI on their job security. Most (17/25) participants thought that AI would impact emergency medicine within the next 10 years., Conclusions: Emergency clinicians interviewed were generally optimistic about the use of AI in emergency medicine, so long as it is used as a decision support tool and they maintain the ability to override its recommendations., (© 2023 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

Nowadays, it is well-established that the consumption of poultry meat, especially chicken meat products has been drastically increasing. Even though more attentions are being paid to the major foodborne pathogens, it seems that scientists in the area of food safety and public health would prefer tackling the minor food borne zoonotic emerging or reemerging pathogens, namely Helicobacter species. Recently, understanding the novel aspects of zoonotic Enterohepatic Helicobacter species, including pathogenesis, isolation, identification, and genomic features is regarded as a serious challenge. In this regard, considerable attention is given to emerging elusive zoonotic Enterohepatic Helicobacter species, comprising Helicobacter pullorum and Helicobacter canadensis. In conclusion, the current review paper would attempt to elaborately summarize and somewhat compare the etiology, pathogenesis, cultivation process, identification, genotyping, and antimicrobial resistance profile of both H. pullorum and H. Canadensis. Further, H. pullorum has been introduced as the most significant food borne pathogen in chicken meat products., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder causing abdominal pain, altered bowel habits and bloating without structural issues. Gallbladder dysfunction may be linked to IBS due to disrupted cholecystokinin release. This study aims to assess gallbladder function and related hemodynamic parameters using Doppler ultrasound in IBS before and after meals., Method: In this case-control study, we investigated gallbladder function differences between constipation-predominant IBS (C-IBS) patients and healthy volunteers. Participants underwent ultrasonography to measure gallbladder parameters before and after consuming a predefined meal. Gallbladder volume, wall thickness and resistance index (RI) of cystic and superior mesenteric arteries (SMA) were assessed. Student t-test and paired t-test were used to compare case and control groups and pre- and post-meal data, respectively., Results: A total of 34 people (18 C-IBS and 16 healthy control) were included. The mean (Standard deviation) of gallbladder fasting volume was measured 24.74 (8.85) and 29.73 (9.65) cubic millimeter for case and controls, respectively. Postprandial volume was 11.34 (5.66) and 16.9 (6.16) cubic millimeter for case and controls respectively. We observed a statistically significant difference in emptying fractions (EF) between groups (p value = 0.009). IBS patients had a smaller fasting SMA RI (p value = 0.016) but the fraction of change after meal was not significant (p value = 0.10). The cystic artery RI did not reach statistical significance between the fasting and post-meal values (p value = 0.067)., Conclusion: IBS patients have a higher emptying fraction and lower change in SMA RI compared to healthy controls. Further studies with larger sample size, inclusion of patients with different coexisting conditions and subtypes of IBS and combining colon transit study with gallbladder ejection fraction evaluation can be used to further provide more meaning to this study.

Background: Emerging evidence suggests that traumatic brain injury (TBI) is a major risk factor for developing neurodegenerative disease later in life. Quantitative susceptibility mapping (QSM) has been used by an increasing number of studies in investigations of pathophysiological changes in TBI. However, generating artefact-free quantitative susceptibility maps in brains with large focal lesions, as in the case of moderate-to-severe TBI (ms-TBI), is particularly challenging. To address this issue, we utilized a novel two-pass masking technique and reconstruction procedure (two-pass QSM) to generate quantitative susceptibility maps (QSMxT; Stewart et al., 2022, Magn Reson Med.) in combination with the recently developed virtual brain grafting (VBG) procedure for brain repair (Radwan et al., 2021, NeuroImage) to improve automated delineation of brain areas. We used QSMxT and VBG to generate personalised QSM profiles of individual patients with reference to a sample of healthy controls., Methods: Chronic ms-TBI patients (N = 8) and healthy controls (N = 12) underwent (multi-echo) GRE, and anatomical MRI (MPRAGE) on a 3T Siemens PRISMA scanner. We reconstructed the magnetic susceptibility maps using two-pass QSM from QSMxT. We then extracted values of magnetic susceptibility in grey matter (GM) regions (following brain repair via VBG) across the whole brain and determined if they deviate from a reference healthy control group [Z-score < -3.43 or > 3.43, relative to the control mean], with the aim of obtaining personalised QSM profiles., Results: Using two-pass QSM, we achieved susceptibility maps with a substantial increase in quality and reduction in artefacts irrespective of the presence of large focal lesions, compared to single-pass QSM. In addition, VBG minimised the loss of GM regions and exclusion of patients due to failures in the region delineation step. Our findings revealed deviations in magnetic susceptibility measures from the HC group that differed across individual TBI patients. These changes included both increases and decreases in magnetic susceptibility values in multiple GM regions across the brain., Conclusions: We illustrate how to obtain magnetic susceptibility values at the individual level and to build personalised QSM profiles in ms-TBI patients. Our approach opens the door for QSM investigations in more severely injured patients. Such profiles are also critical to overcome the inherent heterogeneity of clinical populations, such as ms-TBI, and to characterize the underlying mechanisms of neurodegeneration at the individual level more precisely. Moreover, this new personalised QSM profiling could in the future assist clinicians in assessing recovery and formulating a neuroscience-guided integrative rehabilitation program tailored to individual TBI patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objective: Artificial intelligence (AI) has gradually found its way into healthcare, and its future integration into clinical practice is inevitable. In the present study, we evaluate the accuracy of a novel AI algorithm designed to predict admission based on a triage note after clinical implementation. This is the first of such studies to investigate real-time AI performance in the emergency setting., Methods: The novel AI algorithm that predicts admission using a triage note was translated into clinical practice and integrated within St Vincent's Hospital Melbourne's electronic emergency patient management system. The data were collected from 1 January 2021 to 17 August 2022 to evaluate the diagnostic accuracy of the AI system after implementation., Results: A total of 77 125 ED presentations were included. The live AI algorithm has a sensitivity of 73.1% (95% confidence interval 72.5-73.8), specificity of 74.3% (73.9-74.7), positive predictive value of 50% (49.6-50.4) and negative predictive value of 88.7% (88.5-89) with a total accuracy of 74% (73.7-74.3). The accuracy of the system was at the lowest for admission to psychiatric units (34%) and at the highest for gastroenterology and medical admission (84% and 80%, respectively)., Conclusion: Our study showed the diagnostic evaluation of a real-time AI clinical decision-support tool became less accurate than the original. Although real-time sensitivity and specificity of the AI tool was still acceptable as a decision-support tool in the ED, we propose that continuous training and evaluation of AI-enabled clinical support tools in healthcare are conducted to ensure consistent accuracy and performance to prevent inadvertent consequences., (© 2023 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

Perforin is a pore-forming protein whose normal function enables cytotoxic T and natural killer (NK) cells to kill virus-infected and transformed cells. Conversely, unwanted perforin activity can also result in auto-immune attack, graft rejection and aberrant responses to pathogens. Perforin is critical for the function of the granule exocytosis cell death pathway and is therefore a target for drug development. In this study, by screening a fragment library using NMR and surface plasmon resonance, we identified 4,4-diaminodiphenyl sulfone (dapsone) as a perforin ligand. We also found that dapsone has modest (mM) inhibitory activity of perforin lytic activity in a red blood cell lysis assay in vitro. Sequential modification of this lead fragment, guided by structural knowledge of the ligand binding site and binding pose, and supported by SPR and ligand-detected 19 F NMR, enabled the design of nanomolar inhibitors of the cytolytic activity of intact NK cells against various tumour cell targets. Interestingly, the ligands we developed were largely inert with respect to direct perforin-mediated red blood cell lysis but were very potent in the context of perforin's action on delivering granzymes in the immune synapse, the context in which it functions physiologically. Our work indicates that a fragment-based, structure-guided drug discovery strategy can be used to identify novel ligands that bind perforin. Moreover, these molecules have superior physicochemical properties and solubility compared to previous generations of perforin ligands., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Desmoplastic fibroma (DF) is an aggressive benign tumor that commonly affects long tubular bones. Also, the skull, mandible, pelvis and spine involvement have been reported. However, its occurrence in the scapula is extremely rare. In this case report, we present the challenging diagnosis and successful treatment of DF in a 27-year-old woman who had been experiencing worsening pain in her right shoulder for 5 years. Plain radiographs and magnetic resonance imaging revealed a lucent, trabeculated and expansile infiltrative lesion, disrupting the posterior cortex and extended to the posterior soft tissue. After ruling out malignancy through a core needle biopsy, the patient underwent wide surgical resection of the tumor, which involved a hemi-scapulectomy. And histologic diagnosis consistent with DF, no postoperative radiation was administered. Remarkably, the patient became pain-free just 2 weeks after surgery. Follow-up examinations, X-rays and computed tomography scans conducted 6 weeks, 6 months and 18 months after surgery revealed no signs of recurrence., Competing Interests: The authors declared no conflict of interest., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2023.)

Background and Purpose: Approximately 65% of moderate-to-severe traumatic brain injury (m-sTBI) patients present with poor long-term behavioural outcomes, which can significantly impair activities of daily living. Numerous diffusion-weighted MRI studies have linked these poor outcomes to decreased white matter integrity of several commissural tracts, association fibres and projection fibres in the brain. However, most studies have focused on group-based analyses, which are unable to deal with the substantial between-patient heterogeneity in m-sTBI. As a result, there is increasing interest and need in conducting individualised neuroimaging analyses., Materials and Methods: Here, we generated a detailed subject-specific characterisation of microstructural organisation of white matter tracts in 5 chronic patients with m-sTBI (29 - 49y, 2 females), presented as a proof-of-concept. We developed an imaging analysis framework using fixel-based analysis and TractLearn to determine whether the values of fibre density of white matter tracts at the individual patient level deviate from the healthy control group (n = 12, 8F, M age  = 35.7y, age range 25 - 64y)., Results: Our individualised analysis revealed unique white matter profiles, confirming the heterogenous nature of m-sTBI and the need of individualised profiles to properly characterise the extent of injury. Future studies incorporating clinical data, as well as utilising larger reference samples and examining the test-retest reliability of the fixel-wise metrics are warranted., Conclusions: Individualised profiles may assist clinicians in tracking recovery and planning personalised training programs for chronic m-sTBI patients, which is necessary to achieve optimal behavioural outcomes and improved quality of life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Ketamine is a fast-acting, dissociative anesthetic with a favorable adverse effect profile that is effective for managing acute agitation as a chemical restraint in the prehospital and emergency department (ED) settings. However, some previously published individual studies have reported high intubation rates when ketamine was administered prehospitally., Objective: This systematic review aims to determine the rate and settings in which intubation following prehospital administration of ketamine for agitation is occurring, as well as associated indications and adverse events., Methods: We searched PubMed, Scopus, Ovid MEDLINE, Embase, CINAHL Plus, PsycINFO, the Cochrane Library, ClinicalTrials.gov, OpenGrey, Open Access Theses and Dissertation, and Google Scholar from the earliest possible date until 13/February/2022. Inclusion criteria required studies to describe agitated patients who received ketamine in the prehospital setting as a first-line drug to control acute agitation. Reference lists of appraised studies were screened for additional relevant articles. Study quality was assessed using the Newcastle-Ottawa quality assessment scale. Synthesis of results was completed via meta-analysis, and the GRADE tool was used for certainty assessment., Results: The search yielded 1466 unique records and abstracts, of which 50 full texts were reviewed, resulting in 18 being included in the analysis. All studies were observational in nature and 15 were from USA. There were 3476 patients in total, and the overall rate of intubation was 16% (95% confidence interval [CI] = 8%-26%). Most intubations occurred in the ED. Within the studies, the prehospital intubation rate ranged from 0% to 7.9% and the ED intubation rate ranged from 0 to 60%. The overall pooled prehospital intubation rate was 1% (95% CI = 0%-2%). The overall pooled ED intubation rate was 19% (95% CI = 11%-30%). The most common indications for intubation were for airway protection and respiratory depression/failure., Conclusions: There is wide variation in intubation rates between and within studies. The majority of intubations performed following prehospital administration of ketamine for agitation took place in the ED.

Graph theoretical analysis of the structural connectome has been employed successfully to characterize brain network alterations in patients with traumatic brain injury (TBI). However, heterogeneity in neuropathology is a well-known issue in the TBI population, such that group comparisons of patients against controls are confounded by within-group variability. Recently, novel single-subject profiling approaches have been developed to capture inter-patient heterogeneity. We present a personalized connectomics approach that examines structural brain alterations in five chronic patients with moderate to severe TBI who underwent anatomical and diffusion magnetic resonance imaging. We generated individualized profiles of lesion characteristics and network measures (including personalized graph metric GraphMe plots, and nodal and edge-based brain network alterations) and compared them against healthy reference cases ( N = 12) to assess brain damage qualitatively and quantitatively at the individual level. Our findings revealed alterations of brain networks with high variability between patients. With validation and comparison to stratified, normative healthy control comparison cohorts, this approach could be used by clinicians to formulate a neuroscience-guided integrative rehabilitation program for TBI patients, and for designing personalized rehabilitation protocols based on their unique lesion load and connectome., (© 2022 Massachusetts Institute of Technology.)

Assault is the leading preventable cause of death, traumatic brain injury (TBI), and associated mental health problems. The COVID-19 pandemic has had a profound impact on patterns of interpersonal violence across the world. In this retrospective cross-sectional study, we analysed medical records of 1232 assault victims (domestic violence: 111, random assault: 900, prison assault: 221) with head injuries who presented to the emergency department (ED) at St Vincent's Hospital in Melbourne, Australia, a city with one of the longest and most severe COVID-19 restrictions worldwide. We examined changes in prevalence in the assault group overall and in domestic violence, random assault, and prison assault victims, comparing data from 19.5 months before and after the first day of COVID-19 restrictions in Melbourne. Moreover, we investigated differences driven by demographic factors ( Who : age group, sex, and nationality) and clinical variables ( Where : assault location, and When : time of arrival to the ED and time from moment of injury until presentation at ED). Descriptive statistics and chi-square analyses were performed. We found the COVID-19 pandemic significantly affected the Where of assault-related TBI, with a shift in the location of assaults from the street to the home, and the increase at home being driven by random assaults on middle-aged adults. Overall, we observed that 86% of the random assault cases were males, whereas 74% of the domestic assault cases were females. Meanwhile, nearly half (44%) of the random assault victims reported alcohol consumption versus a fifth (20%) of domestic violence victims. These findings will have direct implications for developing screening tools and better preventive and ameliorative interventions to manage the sequelae of assault TBI, particularly in the context of future large-scale health crises or emergencies.

Objectives: Alcohol is the most widely consumed psychoactive substance in Australia and the consequences of alcohol consumption have enormous personal and social impacts. This study aimed to describe the principal diagnoses of emergency department (ED) presentations involving alcohol use in the previous 12 hours at eight hospitals in Victoria and the Australian Capital Territory, Australia., Methods: Twelve months' data (1 July 2018 - 30 June 2019) were collected from eight EDs, including demographics, ICD-10 codes, hospital location and self-reported drinking in the preceding 12 hours. The ten most common ICD-10 discharge codes were analysed based on age, sex and hospital geographic area., Results: ICD codes pertaining to mental and behavioural disorders due to alcohol use accounted for the highest proportion in most EDs. Suicide ideation/attempt was in the five highest ICD codes for all but one hospital. It was the second most common alcohol-related presentation for both males and females., Conclusions: Alcohol plays a major role in a range of presentations, especially in relation to mental health and suicide., Implications for Public Health: The collection of alcohol involvement in ED presentations represents a major step forward in informing the community about the burden of alcohol on their health resources., (© 2022 The Authors.)

Objective: The World Health Organization declared the COVID-19 pandemic on 11 March 2020. In 2021, several vaccines were provisionally approved to reduce the risk of transmission and hospitalisation of COVID-19 infection. A surge in COVID-19 vaccination was seen between August and October 2021 in Victoria, Australia. We hypothesised this led to an increase in ED presentations., Methods: Patients in the present study were adults who presented to the ED within 21 days of receiving a dose of a COVID-19 vaccine between 11 August 2021 and 14 November 2021. All cases underwent chart reviews to extract epidemiological features, clinical presentations, ED assessments, investigations and disposition., Results: Notably, 968 patients were included in the study, comprising 6.1% of all ED presentations during the study period. The median age was 31 years. 82.9% of patients were younger than 45 years. 20.1% of patients arrived by ambulance. Chest pain was the most common presenting complaint (43.6%), followed by headache (10.3%) and palpitations (8.2%). The most common investigations were a full blood examination (73.5%), an ECG (63.8%) and serum troponin (49.1%). 64.8% of patients were directly discharged home and 22.1% were sent home after a short stay admission. Only 2.2% of patients were admitted to the hospital., Conclusion: A majority of patients who presented to the ED after their COVID vaccinations were young and discharged home after the initial assessment. These presentations have significantly increased the workload in prehospital settings and EDs, contributing to increased investigation usage, ED treatment space occupancy, and increased costs to the health system., (© 2022 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

New drugs that precisely target the immune mechanisms critical for cytotoxic T lymphocyte (CTL) and natural killer (NK) cell driven pathologies are desperately needed. In this perspective, we explore the cytolytic protein perforin as a target for therapeutic intervention. Perforin plays an indispensable role in CTL/NK killing and controls a range of immune pathologies, while being encoded by a single copy gene with no redundancy of function. An immunosuppressant targeting this protein would provide the first-ever therapy focused specifically on one of the principal cell death pathways contributing to allotransplant rejection and underpinning multiple autoimmune and postinfectious diseases. No drugs that selectively block perforin-dependent cell death are currently in clinical use, so this perspective will review published novel small molecule inhibitors, concluding with in vivo proof-of-concept experiments performed in mouse models of perforin-mediated immune pathologies that provide a potential pathway toward a clinically useful therapeutic agent.

The COVID-19 pandemic has imposed significant mental health burdens upon the general population worldwide, either directly owing to the disease or indirectly through aggressive public health measures to control spread of the virus that causes COVID-19. In this narrative review, we used a systematic approach to summarize the impact of restrictive lockdown measures on the general mental health of people living in Victoria, Australia during 2020 and to identify the groups with an increased risk of adverse mental health outcomes. A systematic database search (Ovid Medline, PsycINFO, Embase) for articles examining the mental health of Victorians in the context of the COVID-19 pandemic during 2020 yielded 88 articles, of which 15 articles were finally included in this review. We found that the general mental health of Victorians was negatively affected by COVID-19 restrictions during 2020. Although studies reported heterogeneous mental health outcomes, we found that the general population consistently used coping strategies and demonstrated mental health help-seeking behaviors in response to the restrictions. Women, children, young people, carers, people who became unemployed owing to the pandemic, and those with pre-existing psychiatric conditions had a higher risk of adverse mental health consequences during the COVID-19 pandemic in 2020.

Background: Healthcare inequity has widely affected marginalized and immigrant communities globally during the COVID-19 pandemic., Aims: This study assessed the effect of COVID-19 pandemic on health care delivery to immigrant populations in Isfahan Province, Islamic Republic of Iran., Methods: All 67 hospitals across Isfahan Province were included in this study conducted from 1 March to 31 May 2020. Data on clinical manifestations, comorbidities, patient management, and outcomes of patients during hospital admission were extracted from medical records and analysed using SPSS for chi-square and odds ratio (OR)., Results: One hundred and sixty-eight (3.3%) of 5128 PCR-confirmed COVID-19 cases during the study period were immigrants and were included in the study. There were no differences in sex, clinical presentation, comorbidities, and length of hospital stay between the non-immigrant and immigrant groups. Immigrant patients were significantly younger and had poorer outcomes, including tracheal intubation [OR = 1.9, 95% confidence interval (CI): 1.2-3.1); P = 0.009] and in-hospital mortality (OR = 1.6; 95% CI: 1.1-2.4; P = 0.02)., Conclusion: Adverse health outcomes among immigrant communities may be an indication of health inequity and should be addressed by the relevant policymakers., (Copyright © Authors 2022; licensee World Health Organization. EMHJ is an open access journal. This paper is available under the Creative Commons Attribution Non-Commercial ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Objective: To quantify the attitude ED clinicians hold towards patients presenting with different medical conditions, including a novel pandemic condition., Methods: A cross-sectional study of emergency doctors and nurses utilising the Medical Condition Regard Scale (MCRS); a validated tool used to capture the bias and emotions of clinicians towards individual medical conditions. The five conditions presented to participants each represent a classical medical, complex medical, psychiatric/substance use, somatoform and a novel medical condition., Results: One hundred and ninety-six clinicians were included in the study including 116 nurses and 80 doctors. Concerning each condition, both medical and nursing staff demonstrated the highest regard for a classical medical condition (58 ± 5 and 57 ± 6, respectively). Significantly different from the classical medical condition, the lowest MCRS scores were for the somatoform condition (36 ± 10) for emergency doctors and the substance use condition (39 ± 11) for emergency nurses. Regard for a novel condition (i.e., COVID-19 infection) was comparably high among both cohorts., Conclusion: Emergency doctors and nurses generally hold lower regard for complex medical conditions with behavioural components, including substance use disorders and somatoform conditions., (© 2022 Australasian College for Emergency Medicine.)

According to the World Health Organization, diseases which are naturally transmissible from vertebrate animals to human beings or from humans to vertebrates are defined as the zoonotic diseases. Among the most common zoonotic pathogens, Helicobacter pullorum has earned public recognition regarding its public health significance. This Enterohepatic Helicobacter species has been shown to be a very dangerous and life-threatening microorganism, accounting for several clinically important infections in the human population. However, despite the several studies indicating the significance of H.pullorum in both humans and animals, there is a lack of documented information and reliable statistics about this pathogen throughout the world. Thus, in this review, we would provide a novel knowledge about the general characteristics, isolation methods, host ranges and transmission routes, and occurrences of H.pullorum in poultry, chicken meat, and human in Iran. We would also clarify the status of antimicrobial resistance (AMR) profile of the H.pullorum isolates from various samples in this country., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Perforin is a key effector of lymphocyte-mediated cell death pathways and contributes to transplant rejection of immunologically mismatched grafts. We have developed a novel series of benzenesulfonamide (BZS) inhibitors of perforin that can mitigate graft rejection during allogeneic bone marrow/stem cell transplantation. Eight such perforin inhibitors were tested for their murine pharmacokinetics, plasma protein binding, and their ability to block perforin-mediated lysis in vitro and to block the rejection of major histocompatibility complex (MHC)-mismatched mouse bone marrow cells. All compounds showed >99% binding to plasma proteins and demonstrated perforin inhibitory activity in vitro and in vivo . A lead compound, compound 1 , that showed significant increases in allogeneic bone marrow preservation was evaluated for its plasma pharmacokinetics and in vivo efficacy at multiple dosing regimens to establish a pharmacokinetic/pharmacodynamic (PK/PD) relationship. The strongest PK/PD correlation was observed between perforin inhibition in vivo and time that total plasma concentrations remained above 900 μM, which correlates to unbound concentrations similar to 3× the unbound in vitro IC 90 of compound 1 . This PK/PD relationship will inform future dosing strategies of BZS perforin inhibitors to maintain concentrations above 3× the unbound IC 90 for as long as possible to maximize efficacy and enhance progression toward clinical evaluation., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Objective: Patients, families and community members would like emergency department wait time visibility. This would improve patient journeys through emergency medicine. The study objective was to derive, internally and externally validate machine learning models to predict emergency patient wait times that are applicable to a wide variety of emergency departments., Methods: Twelve emergency departments provided 3 years of retrospective administrative data from Australia (2017-2019). Descriptive and exploratory analyses were undertaken on the datasets. Statistical and machine learning models were developed to predict wait times at each site and were internally and externally validated. Model performance was tested on COVID-19 period data (January to June 2020)., Results: There were 1 930 609 patient episodes analysed and median site wait times varied from 24 to 54 min. Individual site model prediction median absolute errors varied from±22.6 min (95% CI 22.4 to 22.9) to ±44.0 min (95% CI 43.4 to 44.4). Global model prediction median absolute errors varied from ±33.9 min (95% CI 33.4 to 34.0) to ±43.8 min (95% CI 43.7 to 43.9). Random forest and linear regression models performed the best, rolling average models underestimated wait times. Important variables were triage category, last-k patient average wait time and arrival time. Wait time prediction models are not transferable across hospitals. Models performed well during the COVID-19 lockdown period., Conclusions: Electronic emergency demographic and flow information can be used to approximate emergency patient wait times. A general model is less accurate if applied without site-specific factors., Competing Interests: Competing interests: Some authors and collaborators are emergency physicians or directors, and others work in community health (prehospital and district nursing). One collaborator is a consumer. The Australian government, Medical Research Future Fund, via Monash Partners, funded this study. Researchers contributed in-kind donations of time. The Cabrini Institute and Monash University provided research infrastructure support., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To compare the clinical and demographic variables of patients who present to the ED at different times of the day in order to determine the nature and extent of potential selection bias inherent in convenience sampling METHODS: We undertook a retrospective, observational study of data routinely collected in five EDs in 2019. Adult patients (aged ≥18 years) who presented with abdominal or chest pain, headache or dyspnoea were enrolled. For each patient group, the discharge diagnoses (primary outcome) of patients who presented during the day (08:00-15:59), evening (16:00-23:59), and night (00:00-07:59) were compared. Demographics, triage category and pain score, and initial vital signs were also compared., Results: 2500 patients were enrolled in each of the four patient groups. For patients with abdominal pain, the diagnoses differed significantly across the time periods (p<0.001) with greater proportions of unspecified/unknown cause diagnoses in the evening (47.4%) compared with the morning (41.7%). For patients with chest pain, heart rate differed (p<0.001) with a mean rate higher in the evening (80 beats/minute) than at night (76). For patients with headache, mean patient age differed (p=0.004) with a greater age in the daytime (46 years) than the evening (41). For patients with dyspnoea, discharge diagnoses differed (p<0.001). Asthma diagnoses were more common at night (12.6%) than during the daytime (7.5%). For patients with dyspnoea, there were also differences in gender distribution (p=0.003), age (p<0.001) and respiratory rates (p=0.003) across the time periods. For each patient group, the departure status differed across the time periods (p<0.001)., Conclusion: Patients with abdominal or chest pain, headache or dyspnoea differ in a range of clinical and demographic variables depending upon their time of presentation. These differences may potentially introduce selection bias impacting upon the internal validity of a study if convenience sampling of patients is undertaken., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of the present study was to describe the characteristics and outcomes of patients presenting to Australian EDs with suspected and confirmed COVID-19 during 2020, and to determine the predictors of in-hospital death for SARS-CoV-2 positive patients., Methods: This analysis from the COVED Project presents data from 12 sites across four Australian states for the period from 1 April to 30 November 2020. All adult patients who met local criteria for suspected COVID-19 and underwent testing for SARS-CoV-2 in the ED were eligible for inclusion. Study outcomes were mechanical ventilation and in-hospital mortality., Results: Among 24 405 eligible ED presentations over the whole study period, 423 tested positive for SARS-CoV-2. During the 'second wave' from 1 July to 30 September 2020, 26 (6%) of 406 SARS-CoV-2 patients received invasive mechanical ventilation, compared to 175 (2%) of the 9024 SARS-CoV-2 negative patients (odds ratio [OR] 3.5; 95% confidence interval [CI] 2.3-5.2, P < 0.001), and 41 (10%) SARS-CoV-2 positive patients died in hospital compared to 312 (3%) SARS-CoV-2 negative patients (OR 3.2; 95% CI 2.2-4.4, P = 0.001). For SARS-CoV-2 positive patients, the strongest independent predictors of hospital death were age (OR 1.1; 95% CI 1.1-1.1, P < 0.001), higher triage category (OR 3.5; 95% CI 1.3-9.4, P = 0.012), obesity (OR 4.2; 95% CI 1.2-14.3, P = 0.024) and receiving immunosuppressive treatment (OR 8.2; 95% CI 1.8-36.7, P = 0.006)., Conclusions: ED patients who tested positive for SARS-CoV-2 had higher odds of mechanical ventilation and death in hospital. The strongest predictors of death were age, a higher triage category, obesity and receiving immunosuppressive treatment., (© 2021 Australasian College for Emergency Medicine.)

Study Objective: To derive and internally and externally validate machine-learning models to predict emergency ambulance patient door-to-off-stretcher wait times that are applicable to a wide variety of emergency departments., Methods: Nine emergency departments provided 3 years (2017 to 2019) of retrospective administrative data from Australia. Descriptive and exploratory analyses were undertaken on the datasets. Statistical and machine-learning models were developed to predict wait times at each site and were internally and externally validated., Results: There were 421,894 episodes analyzed, and median site off-load times varied from 13 (interquartile range [IQR], 9 to 20) to 29 (IQR, 16 to 48) minutes. The global site prediction model median absolute errors were 11.7 minutes (95% confidence interval [CI], 11.7 to 11.8) using linear regression and 12.8 minutes (95% CI, 12.7 to 12.9) using elastic net. The individual site model prediction median absolute errors varied from the most accurate at 6.3 minutes (95% CI, 6.2 to 6.4) to the least accurate at 16.1 minutes (95% CI, 15.8 to 16.3). The model technique performance was the same for linear regression, random forests, elastic net, and rolling average. The important variables were the last k-patient average waits, triage category, and patient age. The global model performed at the lower end of the accuracy range compared with models for the individual sites but was within tolerable limits., Conclusion: Electronic emergency demographic and flow information can be used to estimate emergency ambulance patient off-stretcher times. Models can be built with reasonable accuracy for multiple hospitals using a small number of point-of-care variables., (Copyright © 2021 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: To demonstrate the potential of machine learning and capability of natural language processing (NLP) to predict disposition of patients based on triage notes in the ED., Methods: A retrospective cohort of ED triage notes from St Vincent's Hospital (Melbourne) was used to develop a deep-learning algorithm that predicts patient disposition. Bidirectional Encoder Representations from Transformers, a recent language representation model developed by Google, was utilised for NLP. Eighty percent of the dataset was used for training the model and 20% was used to test the algorithm performance. Ktrain library, a wrapper for TensorFlow Keras, was employed to develop the model., Results: The accuracy of the algorithm was 83% and the area under the curve was 0.88. Sensitivity, specificity, precision and F1-score of the algorithm were 72%, 86%, 56% and 63%, respectively., Conclusion: Machine learning and NLP can be together applied to the ED triage note to predict patient disposition with a high level of accuracy. The algorithm can potentially assist ED clinicians in early identification of patients requiring admission by mitigating the cognitive load, thus optimises resource allocation in EDs., (© 2020 Australasian College for Emergency Medicine.)

Objective: The aim of the present study was to describe the epidemiology and clinical features of patients presenting to the ED with suspected and confirmed COVID-19 during Australia's 'second wave'., Methods: The COVID-19 ED (COVED) Project is an ongoing prospective cohort study in Australian EDs. This analysis presents data from 12 sites across four Australian states for the period from 1 July to 31 August 2020. All adult patients who met the criteria for 'suspected COVID-19' and underwent testing for SARS-CoV-2 in the ED were eligible for inclusion. Study outcomes included a positive SARS-CoV-2 test result, mechanical ventilation and in-hospital mortality., Results: There were 106 136 presentations to the participating EDs and 12 055 (11.4%; 95% confidence interval [CI] 11.2-11.6) underwent testing for SARS-CoV-2. Of these, 255 (2%) patients returned a positive result. Among positive cases, 13 (5%) received mechanical ventilation during their hospital admission compared to 122 (2%) of the SARS-CoV-2 negative patients (odds ratio 2.7; 95% CI 1.5-4.9, P = 0.001). Nineteen (7%) SARS-CoV-2 positive patients died in hospital compared to 212 (3%) of the SARS-CoV-2 negative patients (odds ratio 2.3; 95% CI 1.4-3.7, P = 0.001). Strong clinical predictors of the SARS-CoV-2 test result included self-reported fever, sore throat, bilateral infiltrates on chest X-ray, and absence of a leucocytosis on first ED blood tests (P < 0.05)., Conclusions: In this prospective multi-site study during Australia's 'second wave', a substantial proportion of ED presentations required SARS-CoV-2 testing and isolation. Presence of SARS-CoV-2 on nasopharyngeal swab was associated with an increase in the odds of death and mechanical ventilation in hospital., (© 2020 Australasian College for Emergency Medicine.)

Objective: The aim of the present study was to describe the epidemiology and clinical features of patients presenting to the ED with suspected and confirmed COVID-19., Methods: The COVID-19 ED (COVED) Project is an ongoing prospective cohort study in Australian EDs. This analysis presents data from eight sites across Victoria and Tasmania for July 2020 (during Australia's 'second wave'). All adult patients who met criteria for 'suspected COVID-19' and underwent testing for SARS-CoV-2 in the ED were eligible for inclusion. Study outcomes included a positive SARS-CoV-2 test result and mechanical ventilation., Results: In the period 1 July to 31 July 2020, there were 30 378 presentations to the participating EDs and 2917 (9.6%; 95% confidence interval 9.3-9.9) underwent testing for SARS-CoV-2. Of these, 50 (2%) patients returned a positive result. Among positive cases, two (4%) received mechanical ventilation during their hospital admission compared to 45 (2%) of the SARS-CoV-2 negative patients (odds ratio 1.7, 95% confidence interval 0.4-7.3; P = 0.47). Two (4%) SARS-CoV-2 positive patients died in hospital compared to 46 (2%) of the SARS-CoV-2 negative patients (odds ratio 1.7, 95% confidence interval 0.4-7.1; P = 0.49). Strong clinical predictors of a positive SARS-CoV-2 result included self-reported fever, non-smoking status, bilateral infiltrates on chest X-ray and absence of a leucocytosis on first ED blood tests (P < 0.05)., Conclusion: In this prospective multi-site study from July 2020, a substantial proportion of ED patients required SARS-CoV-2 testing, isolation and enhanced infection prevention and control precautions. Presence of SARS-CoV-2 on nasopharyngeal swab was not associated with death or mechanical ventilation., (© 2020 Australasian College for Emergency Medicine.)

Objective: Acute migraine is associated with significant personal, economic and work-related disability. Management guidelines advise the use of simple analgesia, triptans, chlorpromazine and anti-emetics based on severity, with avoidance of opioids. We aimed to determine consistency of prescribing patterns in our ED with national guidelines., Methods: We performed a retrospective cohort analysis of migraine presentations (ICD-10-AM G439) between 2012 and 2016. Exclusion criteria included migraine without headache, other primary headaches and secondary headaches. Demographic and prescribing data were extracted from medical records. Results have been reported as proportions., Results: Of 4769 headache presentations, the application of exclusion criteria led to a total of 744 patients who received a migraine diagnosis (G439). Most were female (558/744, 75%), young (mean age 36.4 years) and had a self-reported migraine history (558/744, 75%). There were 54 different medications prescribed. Paracetamol was more frequently prescribed (385/744, 52%) than aspirin (134/744, 18%). Opioid prescription occurred in nearly half of all presentations (345/744, 46%). Similar opioid prescriptions were also observed in those with a documented history of migraines (253/558, 45%). A minority of patients received triptans (51/744, 7%). Overall, a quarter of patients (189/744, 25%) received no guideline-recommended medications., Conclusion: We observed considerable polypharmacy in ED migraine management with inconsistent prescribing patterns. Recommended medications were infrequently used and opioid use was common. Factors influencing prescribing patterns require further investigation in order to improve rates of guideline recommended treatment., (© 2020 Australasian College for Emergency Medicine.)

Perforin is a key effector protein in the vertebrate immune system and is secreted by cytotoxic T lymphocytes and natural killer cells to help eliminate virus-infected and transformed target cells. The ability to modulate perforin activity in vivo could be extremely useful, especially in the context of bone marrow stem cell transplantation where early rejection of immunologically mismatched grafts is driven by the recipient's natural killer cells, which overwhelmingly use perforin to kill their targets. Bone marrow stem cell transplantation is a potentially curative treatment for both malignant and nonmalignant disorders, but when the body recognizes the graft as foreign, it is rejected by this process, often with fatal consequences. Here we report optimization of a previously identified series of benzenesulfonamide-based perforin inhibitors for their physicochemical and pharmacokinetic properties, resulting in the identification of 16 , the first reported small molecule able to prevent rejection of transplanted bone marrow stem cells in vivo by blocking perforin function.

Background: Auto-immune mediated anti-NMDA receptor encephalitis is a very common delayed diagnosed encephalitis which predominately affecting young population., Objectives: This encephalitis is relatively unknown amongst emergency physicians and a majority of patients are admitted to psychiatric wards before their diagnosis is confirmed and appropriate treatments are commenced. We reported a case of a 22-year-old female presented to our emergency department with acute psychiatric symptoms. She was initially diagnosed with first presentation of acute psychosis and was hospitalised under mental health act. further assessment in the emergency department identified possible an organic cause for her acute psychosis and she was later admitted under medical team after her mental health assessment order was revoke. Several days later, her CSF result was positive with anti-NMDA receptor anti-bodies. Appropriate treatments were instituted leading to her full recovery., Conclusion: This case was the first confirmed anti-NMDA receptor encephalitis in our emergency department. It highlights the importance of thorough assessment of psychiatric presentations to emergency departments and consideration of auto-immune medicated encephalitis as one of the differential diagnosis in young patients presenting with first acute psychotic episode., Competing Interests: Authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2019 Chanaka Amugoda et al.)

This paper investigates anti-Fourier heat transfer phenomenon in a rarefied gas confined within a lid-driven cavity using a novel flow decomposition technique in the direct simulation Monte Carlo (DSMC) method proposed by Stefanov and co-workers. An isothermal cavity with different degrees of flow rarefaction from near continuum to mid transition regimes was considered to investigate cold-to-hot heat transfer from ballistic/collision flow decomposition viewpoint. A new cold-to-hot heat transfer indicator in the form of a scalar product of normalized heat flow vector and normalized temperature gradient vector has been introduced for the overall, ballistic and collision parts of these vectors. Using the new indicator, contributions of ballistic and collision flow parts to temperature and heat flux components was investigated with a specific emphasis on the cold-to-hot heat transfer phenomenon. We demonstrated that both ballistic and collision flow parts contribute to the occurrence of cold-to-hot heat transfer. However, it was found out that considered separately both ballistic and collision parts of heat transfer, when related to corresponding ballistic and collision temperature fields, they are ever hot-to-cold for all degrees of flow rarefaction. Thus, cold-to-hot heat transfer is a result of a subtle interplay between ballistic and collision parts in the slip and transition Knudsen regimes.

The ability of cytotoxic lymphocytes (CL) to eliminate virus-infected or cancerous target cells through the granule exocytosis death pathway is critical to immune homeostasis. Congenital loss of CL function due to bi-allelic mutations in PRF1, UNC13D, STX11 , or STXBP2 leads to a potentially fatal immune dysregulation, familial haemophagocytic lymphohistiocytosis (FHL). This occurs due to the failure of CLs to release functional pore-forming protein perforin and, therefore, inability to kill the target cell. Bi-allelic mutations in partner proteins STXBP2 or STX11 impair CL cytotoxicity due to failed docking/fusion of cytotoxic secretory granules with the plasma membrane. One unique feature of STXBP2- and STX11-deficient patient CLs is that their short-term in vitro treatment with a low concentration of IL-2 partially or completely restores natural killer (NK) cell degranulation and cytotoxicity, suggesting the existence of a secondary, yet unknown, pathway for secretory granule exocytosis. In the current report, we studied NK and T-cell function in an individual with late presentation of FHL due to hypomorphic bi-allelic mutations in STXBP2 . Intriguingly, in addition to the expected alterations in the STXBP2 and STX11 proteins, we also observed a concomitant significant reduction in the expression of homologous STXBP1 protein and its partner STX1, which had never been implicated in CL function. Further analysis of human NK and T cells demonstrated a functional role for the STXBP1/STX1 axis in NK and CD8+ T-cell cytotoxicity, where it appears to be responsible for as much as 50% of their cytotoxic activity. This discovery suggests a unique and previously unappreciated interplay between STXBP/Munc proteins regulating the same essential granule exocytosis pathway.

The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore-forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy-induced conditions such as allograft rejection and graft versus host disease. Since perforin is expressed exclusively by cells of the immune system, inhibition of this protein would be a highly selective strategy for the immunosuppressive treatment of these disorders. Compounds from this series were demonstrated to be potent inhibitors of the lytic action of both isolated recombinant perforin and perforin secreted by natural killer cells in vitro. Several potent and soluble examples were assessed for in vivo pharmacokinetic properties and found to be suitable for progression to an in vivo model of transplant rejection., (Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The pore-forming protein perforin is a key component of mammalian cell-mediated immunity and essential to the pathway that allows elimination of virus-infected and transformed cells. Perforin activity has also been implicated in certain auto-immune conditions and therapy-induced conditions such as allograft rejection and graft versus host disease. An inhibitor of perforin activity could be used as a highly specific immunosuppressive treatment for these conditions, with reduced side-effects compared to currently accepted therapies. Previously identified first-in-class inhibitors based on a 2-thioxoimidazolidin-4-one core show suboptimal physicochemical properties and toxicity toward the natural killer (NK) cells that secrete perforin in vivo. The current benzenesulphonamide-based series delivers a non-toxic bioisosteric replacement possessing improved solubility., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The dentate nucleus (DN) is the major relay station for neural connection between the cerebellum and cerebrum via the thalamus, and is a significant component of the neuropathological profile of Friedreich ataxia (FRDA). We have previously shown that the size of the superior cerebellar peduncle (SCP), which links the DN to cortical and subcortical structures via the thalamus, is significantly reduced in individuals with FRDA compared to control participants. This study used magnetization transfer imaging (MTI) to examine and contrast the integrity of white matter (WM) in the SCP and the corpus callosum (CC) (control region) in ten individuals with FRDA and ten controls. Individuals with FRDA demonstrated a significant reduction in the magnetization transfer ratio (MTR) in the SCP compared to control participants. However, there was no significant difference between groups in MTR in the CC. When comparing regions within groups, there was a significant reduction in MTR in the SCP compared to CC in participants with FRDA only. We suggest that the reduction in MTR in the SCP may be indicative of lack of myelin secondary to axonal loss and oligodendroglial dysfunction in WM tracts in individuals with FRDA., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Brain pathology in Friedreich ataxia is characterized by progressive degeneration of nervous tissue in the brainstem, cerebellum and cerebellar peduncles. Evidence of cerebral involvement is however equivocal. This brain imaging study investigates cerebello-cerebral white matter connectivity in Friedreich ataxia with diffusion MRI and tractography performed in 13 individuals homozygous for a GAA expansion in intron one of the frataxin gene and 14 age- and gender-matched control participants. New evidence is presented for disrupted cerebello-cerebral connectivity in the disease, leading to secondary effects in distant cortical and subcortical regions. Remote regions affected by primary cerebellar and brainstem pathology include the supplementary motor area, cingulate cortex, frontal cortices, putamen and other subcortical nuclei. The connectivity disruptions identified provide an explanation for some of the non-ataxic symptoms observed in the disease and support the notion of reverse cerebellar diaschisis. This is the first study to comprehensively map white matter connectivity disruptions in Friedreich ataxia using tractography, connectomic techniques and super-resolution track density imaging.