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BACKGROUND: Transvenous endomyocardial biopsy is an invasive procedure which is used to diagnose rejection following an orthotopic heart transplant. Endomyocardial biopsy is widely regarded as low risk with all-cause complication rates below 5% in most safety studies. Following transplant, some patients require therapeutic anticoagulation. It is unknown whether anticoagulation increases endomyocardial biopsy bleeding risk. METHODS: Records from 2061 endomyocardial biopsies performed for post-transplant rejection surveillance at our institution between November 2016 and August 2022 were reviewed. Bleeding complications were defined as vascular access-related hematoma or bleeding, procedure-related red blood cell transfusion, and new pericardial effusion. Relative risk and small sample-adjusted 95% confidence interval was calculated to investigate the association between bleeding complications and anticoagulation. RESULTS AND CONCLUSIONS: The overall risk of bleeding was 1.2% (25/2061 cases). There was a statistically significant increase in bleeding among patients on intravenous (RR 4.46, CI 1.09-18.32) but not oral anticoagulants (RR .62, CI .15-2.63) compared to patients without anticoagulant exposure. There was a trend toward increased bleeding among patients taking warfarin with INR ≥ 1.8 (RR 3.74, CI .90-15.43). Importantly, no bleeding events occurred in patients taking direct oral anticoagulants such as apixaban. Based on these results, intravenous rather than oral anticoagulation was associated with a significantly higher risk of bleeding complications following endomyocardial biopsy.
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Anticoagulantes , Transplante de Coração , Humanos , Anticoagulantes/efeitos adversos , Estudos Retrospectivos , Varfarina/efeitos adversos , Biópsia , Hemorragia , Transplante de Coração/efeitos adversosRESUMO
Food fraud is an ever-present threat that regulators, food business operators (FBOs), and consumers need to be aware of, prevent where possible, and address by developing mitigation strategies to detect and reduce its negative consequences. While extant literature focuses on food fraud detection, there is less attention given to prevention strategies, a knowledge gap this review seeks to address. The aim of this review was to consider food-related fraud prevention initiatives, understand what has worked well, and develop a series of recommendations on preventing food fraud, both policy related and for future research. Reactive (including intelligence based) food fraud detection dominates over prevention strategies, especially where financial, knowledge, and time resources are scarce. First-generation tools have been developed for food fraud vulnerability assessment, risk analysis, and development of food fraud prevention strategies. However, examples of integrated food control management systems at FBO, supply chain, and regulatory levels for prevention are limited. The lack of hybrid (public/private) integration of food fraud prevention strategies, as well as an effective verification ecosystem, weakens existing food fraud prevention plans. While there are several emergent practice models for food fraud prevention, they need to be strengthened to focus more specifically on capable guardians and target hardening. This work has implications for policymakers, Official Controls bodies, the food industry, and ultimately consumers who seek to consistently purchase food that is safe, legal, and authentic.
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Fraude , Fraude/prevenção & controle , Inocuidade dos Alimentos/métodos , Humanos , Medição de RiscoRESUMO
BACKGROUND: Acute Rheumatic Fever (ARF) is a critically important condition for which there is no diagnostic test. Diagnosis requires the use of a set of criteria comprising clinical, laboratory, electrocardiographic and echocardiographic findings. The complexity of the algorithm and the fact that clinicians lack familiarity with ARF, make ARF diagnosis ideally suited to an electronic decision support tool. The ARF Diagnosis Calculator was developed to assist clinicians in diagnosing ARF and correctly assign categories of 'possible, 'probable' or 'definite' ARF. This research aimed to evaluate the acceptability, accuracy, and test performance of the ARF Diagnosis Calculator. METHODS: Three strategies were used to provide triangulation of data. Users of the calculator employed at Top End Health Service, Northern Territory, Australia were invited to participate in an online survey, and clinicians with ARF expertise were invited to participate in semi-structured interviews. Qualitative data were analysed using inductive analysis. Performance of the calculator in correctly diagnosing ARF was assessed using clinical data from 35 patients presenting with suspected ARF. Diagnoses obtained from the calculator were compared using the Kappa statistic with those obtained from a panel of expert clinicians. RESULTS: Survey responses were available from 23 Top End Health Service medical practitioners, and interview data were available from five expert clinicians. Using a 6-point Likert scale, participants highly recommended the ARF Diagnosis Calculator (median 6, IQR 1), found it easy to use (median 5, IQR 1) and believed the calculator helped them diagnose ARF (median 5, IQR 1). Clinicians with ARF expertise noted that electronic decision making is not a substitute for clinical experience. There was high agreement between the ARF Diagnosis Calculator and the 'gold standard' ARF diagnostic process (κ = 0.767, 95% CI: 0.568-0.967). Incorrect assignment of diagnosis occurred in 4/35 (11%) patients highlighting the greater accuracy of expert clinical input for ambiguous presentations. Sixteen changes were incorporated into a revised version of the calculator. CONCLUSIONS: The ARF Diagnosis Calculator is an easy-to-use, accessible tool, but it does not replace clinical expertise. The calculator performed well amongst clinicians and is an acceptable tool for use within the clinical setting with a high level of accuracy in comparison to the gold standard diagnostic process. Effective resources to support clinicians are critically important for improving the quality of care of ARF.
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Febre Reumática , Ecocardiografia , Humanos , Northern Territory , Febre Reumática/diagnóstico , Inquéritos e QuestionáriosRESUMO
Transient receptor potential vanilloid 4 (TRPV4) channels expressed on pulmonary endothelial cells are activated by elevated pulmonary vascular pressure, resulting in endothelial shape change, pulmonary barrier disruption, and edema. As such, TRPV4 blocker GSK2798745 was recently investigated in phase I/IIa trials to reduce pulmonary edema caused by heart failure (HF). In the absence of a suitable TRPV4 target engagement biomarker, we hypothesized that an ex vivo assay could be used to predict pharmacological activity at the intended site of action (endothelial cells) of subjects. In this assay, the ability of GSK2798745 to block TRPV4 agonist GSK1016790-induced impendence reduction in human umbilical vein endothelial cells (HUVECs) in the presence of human whole blood was assessed. Blood from healthy volunteers drawn 1-12 hours after single or repeated dose of GSK2798745 (5 mg) inhibited GSK1016790-induced impedance reduction by ≥85%. Similarly, blood samples from 16 subjects with HF dosed with GSK2798745 (2.4 mg) inhibited GSK1016790-induced HUVEC impedance reduction by ≥58% 1-24 hours after single dosing and ≥78% 1-24 hours after 7 days of repeated dosing. No inhibition was detected using blood from placebo subjects. Using matched GSK2798745 plasma levels, a pharmacokinetic/pharmacodynamic (PK/PD) relationship was calculated as 2.9 nM IC50, consistent with the 6.5 nM IC50 of GSK2798745 obtained from a rat in vivo PK/PD model of pulmonary edema after correcting for rat-to-human differences. These results indicate that circulating levels of GSK2798745 in the recently completed phase I/IIa trials were sufficient to block TRPV4 in lung vascular endothelial cells to a large extent, supporting this dosing regimen for assessing efficacy in HF. SIGNIFICANCE STATEMENT: In the absence of a suitable target engagement biomarker, we developed an ex vivo assay to predict the pharmacological activity of the transient receptor potential vanilloid 4 (TRPV4) blocker GSK2798745 in healthy volunteers and subjects with heart failure (HF) from phase I/IIa trials. The potency values from the ex vivo assay were consistent with those predicted from a rat in vivo pharmacokinetic/pharmacodynamic model of pulmonary edema, strongly suggesting that circulating levels of GSK2798745 were sufficient to robustly block TRPV4, supporting use of GSK2798745 for assessing efficacy in HF.
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Benzimidazóis/sangue , Benzimidazóis/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Compostos de Espiro/sangue , Compostos de Espiro/farmacologia , Canais de Cátion TRPV/metabolismo , Animais , Benzimidazóis/farmacocinética , Impedância Elétrica , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Masculino , Terapia de Alvo Molecular , Ratos , Compostos de Espiro/farmacocinética , Canais de Cátion TRPV/antagonistas & inibidoresRESUMO
OBJECTIVES: Using echocardiographic screening, to estimate the prevalence of rheumatic heart disease (RHD) in a remote Northern Territory town. DESIGN: Prospective, cross-sectional echocardiographic screening study; results compared with data from the NT rheumatic heart disease register. SETTING, PARTICIPANTS: People aged 5-20 years living in Maningrida, West Arnhem Land (population, 2610, including 2366 Indigenous Australians), March 2018 and November 2018. INTERVENTION: Echocardiographic screening for RHD by an expert cardiologist or cardiac sonographer. MAIN OUTCOME MEASURES: Definite or borderline RHD, based on World Heart Federation criteria; history of acute rheumatic fever (ARF), based on Australian guidelines for diagnosing ARF. RESULTS: The screening participation rate was 72%. The median age of the 613 participants was 11 years (interquartile range, 8-14 years); 298 (49%) were girls or women, and 592 (97%) were Aboriginal Australians. Definite RHD was detected in 32 screened participants (5.2%), including 20 not previously diagnosed with RHD; in five new cases, RHD was classified as severe, and three of the participants involved required cardiac surgery. Borderline RHD was diagnosed in 17 participants (2.8%). According to NT RHD register data at the end of the study period, 88 of 849 people in Maningrida and the surrounding homelands aged 5-20 years (10%) were receiving secondary prophylaxis following diagnoses of definite RHD or definite or probable ARF. CONCLUSION: Passive case finding for ARF and RHD is inadequate in some remote Australian communities with a very high burden of RHD, placing children and young people with undetected RHD at great risk of poor health outcomes. Active case finding by regular echocardiographic screening is required in such areas.
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Programas de Rastreamento/métodos , Havaiano Nativo ou Outro Ilhéu do Pacífico , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/etnologia , Cardiopatia Reumática/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Northern Territory/epidemiologia , Prevalência , Estudos Prospectivos , Febre Reumática/diagnóstico por imagem , Febre Reumática/epidemiologia , Febre Reumática/etnologia , Adulto JovemRESUMO
An outbreak of Salmonella Muenchen gastroenteritis occurred in a remote coastal Aboriginal community in the Northern Territory (NT) of Australia. There were 22 people sick (attack rate 55%); 7 had laboratory confirmed S. Muenchen infection; 2 required medical evacuation and admission to the intensive care unit (ICU). We conducted a descriptive case series to investigate the outbreak. All cases ate meat from a single green turtle (Chelonia mydas). The animal's pre-death stress, improper butchering, insufficient cooking and the unsatisfactory storage of meat all likely contributed to the outbreak. Turtle meat should be prepared safely, cooked thoroughly and stored appropriately to avoid Salmonella infection.
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Surtos de Doenças , Microbiologia de Alimentos , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Intoxicação Alimentar por Salmonella/epidemiologia , Intoxicação Alimentar por Salmonella/microbiologia , Salmonella , Tartarugas/microbiologia , Animais , Feminino , Doenças Transmitidas por Alimentos/história , História do Século XXI , Humanos , Masculino , Northern Territory/epidemiologia , Prevalência , Intoxicação Alimentar por Salmonella/históriaRESUMO
The domestic refrigerator is now a common household device with very few households in the developed world not possessing 1, or more, for the storage of chilled foods. Domestic storage is the last, and in many respects the most important, link in the food chill chain. Inadequate domestic refrigeration or cooling is frequently cited as a factor in incidents of food poisoning. The authors reviewed the temperature performance of refrigerators in 2008. This new review builds on that review, covering studies that have been published since (and those that were unfortunately missed in the first review), and also seeks to put this important stage of the food cold chain in its context. It is clear from the published data that many refrigerators throughout the world are running at higher than recommended temperatures. It is also clear that, despite improvements in energy use, the temperature performance and use of refrigerators have not changed significantly in the last 40 or so years. Many householders still remain unaware of the recommended refrigeration temperature range, how to ensure that the correct refrigeration temperature range is achieved, the importance of monitoring that it is being maintained, and the potential hazards of temperature abuse.
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The aim of this study is to evaluate the effect of meat content and surface smoothness on the deactivation of Listeria monocytogenes in beef-agar food models achieved by shortwave ultraviolet (UVC) light. Food models with various meat contents were made using chopped beef slices and agar solution. Prepared models together with a Listeria selective agar (LSA) plate and a slice of cooked beef were inoculated with L. monocytogenes and then exposed to UVC light. Population of Listeria reduced to below the level of detection on the LSA plates. As the content of beef in the beef-agar models increased, more L. monocytogenes cells survived. Survival was greatest on the treated cooked slice of beef. To better understand the effect of surface irregularities, a white light interferometer was used to analyse the surface smoothness of beef-agar media and LSA plates. No correlation was observed between the surface roughness of seven out of nine types of produced beef-agar media and the degree of inactivation resulting from UVC radiation at the given dose, whereas, less bacterial cells were killed as beef content of the food models increased. The findings of the current study show that the chemical composition of the treated sample also plays an important role in pathogen resistance and survival, meaning that two samples with similar surface irregularities but different chemical composition might produce very different inactivation results when exposed to UVC light.
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UNLABELLED: This study sought to investigate frontline mental health professionals' perceptions of work stress and the rewards and demands associated with their work. Locally known as 'linkworkers', and from a variety of professional backgrounds, these staff worked mainly in general practice settings. Individual interviews were conducted with nine linkworkers, and the interview transcripts were analysed thematically. The main themes identified were the following: demands, coping, individual resilience, ownership and creativity, boundaries, secure base and service philosophy and ethos. Themes, categories and sub categories were presented and discussed with seven of the linkworkers in two focus groups. Focus group transcripts were analysed, and additional themes of recognizing limitations, disillusionment and the dilemma of setting boundaries were identified. These themes overlapped with those previously identified but were associated with service changes over time. The themes of ownership and creativity and service philosophy and ethos are significant, not only in relation to their impact on individual linkworkers but also in terms of their relevance for establishing and maintaining morale, engagement and a reflective culture within a service. The relevance of this work to accessible and newly developing mental health services is considered. KEY PRACTITIONER MESSAGE: Supporting and listening to staff and allowing time for informal contact are valued by staff and enable the provision of empathic, compassionate services. Without space for reflection, staff groups may be vulnerable to the development and effects of unhelpful organizational defences, which reduce the effectiveness, quality and efficiency of caring services and increase perceived workplace stress. Services which foster staff engagement, ownership and creativity and employ "bottom up" approaches to service development are valued by staff and appear to increase staff morale and capacity to cope adaptively to change.
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Atitude do Pessoal de Saúde , Emprego/psicologia , Pessoal de Saúde/psicologia , Serviços de Saúde Mental , Recompensa , Estresse Psicológico/psicologia , Adaptação Psicológica , Grupos Focais , Humanos , Entrevistas como Assunto , Resiliência PsicológicaRESUMO
The focus of this review was to assess what evidence exists on whether, and to what extent, the use of biocides (disinfectants and sanitizers) and certain metals (used in feed and other uses) in animal production (both land and aquatic) leads to the development and spread of AMR within the food chain. A comprehensive literature search identified 3434 publications, which after screening were reduced to 154 relevant publications from which some data were extracted to address the focus of the review. The review has shown that there is some evidence that biocides and metals used in food animal production may have an impact on the development of AMR. There is clear evidence that metals used in food animal production will persist, accumulate, and may impact on the development of AMR in primary animal and food production environments for many years. There is less evidence on the persistence and impact of biocides. There is also particularly little, if any, data on the impact of biocides/metal use in aquaculture on AMR. Although it is recognized that AMR from food animal production is a risk to human health there is not sufficient evidence to undertake an assessment of the impact of biocide or metal use on this risk and further focused in-field studies are needed provide the evidence required.
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Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. Although this environmental organism is endemic in certain regions of Australia, it is not considered endemic in Southern Queensland, where the last case was reported 21 years ago. We report a climate change-associated outbreak of melioidosis occurring during two La Niña events in a region previously considered nonendemic for B. pseudomallei. During a 15-month period, 14 cases of locally acquired melioidosis were identified. Twelve patients were adults (> 50 years), with diabetes mellitus the most common risk factor in 6 of 12 patients (50%). Eleven patients (79%) had direct exposure to floodwaters or the flooded environment. This study suggests an association between climate change and an increased incidence of melioidosis. In addition, this is the first report of environmental sampling and whole-genome analysis to prove endemicity and local acquisition in this region.
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Burkholderia pseudomallei , Melioidose , Humanos , Melioidose/epidemiologia , Melioidose/microbiologia , Queensland/epidemiologia , Austrália/epidemiologia , Surtos de DoençasRESUMO
Pachydermoperiostosis is a rare genetic disease known as primary or idiopathic hypertrophic osteoarthropathy (HOA)/Touraine-Solente-Gole syndrome. It is an autosomal dominant or recessive disorder comprising digital clubbing, periostosis, hyperhidrosis, and pachydermia (thickening of facial skin). Ocular manifestations are uncommon; however, blepharoptosis may occur. This case presented with severe bilateral ptosis due to the disease progression. A large 20 mm upper lid resection with levator advancement was performed to improve his ability to see. This is the first reported case of pachydermoperiostosis (PDP) in Jamaica. We present a rare case of pachydermoperiostosis with severe blepharoptosis, who attained a good result with surgical intervention.
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Blefaroptose , Osteoartropatia Hipertrófica Primária , Humanos , Osteoartropatia Hipertrófica Primária/diagnóstico , Blefaroptose/etiologia , Comorbidade , Face , Olho , Doenças RarasRESUMO
The dissemination of antibiotic resistance genes (ARGs) is a global health concern. This study identifies and critically reviews the published evidence on whether cooking (heating) food to eliminate bacterial contamination induces sufficient damage to the functionality of ARGs. Overall, the review found that there is evidence in the literature that Antimicrobial Resistant (AMR) bacteria are no more heat resistant than non-AMR bacteria. Consequently, recommended heat treatments sufficient to kill non-AMR bacteria in food (70 °C for at least 2 min, or equivalent) should be equally effective in killing AMR bacteria. The literature shows there are several mechanisms through which functional genes from AMR bacteria could theoretically persist in heat-treated food and be transferred to other bacteria. The literature search found sparce published evidence on whether ARGs may actually persist in food after effective heat treatments, and whether functional genes can be transferred to other bacteria. However, three publications have demonstrated that functional ARGs in plasmids may be capable of persisting in foods after effective heat treatments. Given the global impact of AMR, there is clearly a need for further practical research on this topic to provide sufficient evidence to fully assess whether there is a risk to human health from the persistence of functional ARGs in heat-treated and cooked foods.
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BACKGROUND: Echocardiographic screening can detect asymptomatic cases of rheumatic heart disease (RHD), facilitating access to treatment. Barriers to implementation of echocardiographic screening include the requirement for expensive equipment and expert practitioners. We aimed to evaluate the diagnostic accuracy of an abbreviated echocardiographic screening protocol (single parasternal-long-axis view with a sweep of the heart) performed by briefly trained, nonexpert practitioners using handheld ultrasound devices. METHODS: Participants aged 5 to 20 years in Timor-Leste and the Northern Territory of Australia had 2 echocardiograms: one performed by an expert echocardiographer using a GE Vivid I or Vivid Q portable ultrasound device (reference test), and one performed by a nonexpert practitioner using a GE Vscan handheld ultrasound device (index test). The accuracy of the index test, compared with the reference test, for identifying cases with definite or borderline RHD was determined. RESULTS: There were 3111 enrolled participants; 2573 had both an index test and reference test. Median age was 12 years (interquartile range, 10-15); 58.2% were female. Proportion with definite or borderline RHD was 5.52% (95% CI, 4.70-6.47); proportion with definite RHD was 3.23% (95% CI, 2.61-3.98). Compared with the reference test, sensitivity of the index test for definite or borderline RHD was 70.4% (95% CI, 62.2-77.8), specificity was 78.1% (95% CI, 76.4-79.8). CONCLUSIONS: Nonexpert practitioners can be trained to perform single parasternal-long-axis view with a sweep of the heart echocardiography. However, the specificity and sensitivity are inadequate for echocardiographic screening. Improved training for nonexpert practitioners should be investigated.
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Competência Clínica , Ecocardiografia Doppler em Cores , Capacitação em Serviço , Cardiopatia Reumática/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Ecocardiografia Doppler em Cores/instrumentação , Educação Médica Continuada , Educação Continuada em Enfermagem , Feminino , Humanos , Masculino , Nova Zelândia , Northern Territory , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
This study evaluated the effect of plugging the anuses of pork carcasses prior to scalding and dehairing on Enterobacteriaceae contamination on pork carcass surfaces. Results showed that Enterobacteriaceae counts around the anuses of unplugged carcasses increased by 1.15 log CFU/cm(2) after the scalding and dehairing process, while counts in the same sample area from plugged carcasses showed no significant change in Enterobacteriaceae numbers. The percentage of plugged carcasses with Enterobacteriaceae counts (measured around the anuses of carcasses) below the level of detection (<1 log) was 23.5%, whereas only 2.9% of unplugged carcasses were below this level. In the context of a multiple-hurdle approach where incremental reductions in microbiological counts may be seen as positive, anal plugging may have particular benefit.
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Matadouros , Enterobacteriaceae/isolamento & purificação , Contaminação de Alimentos/prevenção & controle , Manipulação de Alimentos/métodos , Suínos/microbiologia , Canal Anal/microbiologia , Animais , Contagem de Colônia Microbiana , Contaminação de Alimentos/análise , Humanos , HigieneRESUMO
BACKGROUND: Scabies is listed as a neglected tropical disease by the World Health Organization. Crusted scabies affects vulnerable and immunosuppressed individuals and is highly contagious because of the enormous number of Sarcoptes scabiei mites present in the hyperkeratotic skin. Undiagnosed and untreated crusted scabies cases can result in outbreaks of scabies in residential facilities and can also undermine the success of scabies mass drug administration programs. METHODS AND PRINCIPAL FINDINGS: Crusted scabies became a formally notifiable disease in the Northern Territory of Australia in 2016. We conducted a 2-year prospective study of crusted scabies cases notified between March 2016 and February 2018, with subsequent follow up for 22 months. Demographics, clinical and laboratory data, treatment and outcomes were analysed, with cases classified by severity of disease. Over the 2-year study period, 80 patients had 92 episodes of crusted scabies; 35 (38%) were Grade 1 crusted scabies, 36 (39%) Grade 2 and 21 (23%) Grade 3. Median age was 47 years, 47 (59%) were female, 76 (95%) Indigenous Australians and 57 (71%) from remote Indigenous communities. Half the patients were diabetic and 18 (23%) were on dialysis for end-stage kidney failure. Thirteen (16%) patients had no comorbidities, and these were more likely to have Grade 3 disease. Eosinophilia was present in 60% and high immunoglobulin E in 94%. Bacteremia occurred in 11 episodes resulting in one fatality with methicillin-susceptible Staphylococcus aureus bacteremia. Two other deaths occurred during admission and 10 others died subsequent to discharge consequent to comorbidities. Treatment generally followed the recommended guidelines, with 3, 5 or 7 doses of oral ivermectin depending on the documented grade of crusted scabies, together with daily alternating topical scabicides and topical keratolytic cream. While response to this therapy was usually excellent, there were 33 episodes of recurrent crusted scabies with the majority attributed to new infection subsequent to return to a scabies-endemic community. CONCLUSIONS: Crusted scabies can be successfully treated with aggressive guideline-based therapy, but high mortality remains from underlying comorbidities. Reinfection on return to community is common while scabies remains endemic.
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Antiparasitários/uso terapêutico , Ivermectina/uso terapêutico , Sarcoptes scabiei/fisiologia , Escabiose/epidemiologia , Animais , Feminino , Hospitalização , Humanos , Hospedeiro Imunocomprometido , Masculino , Northern Territory/epidemiologia , Estudos Prospectivos , Sarcoptes scabiei/efeitos dos fármacos , Escabiose/parasitologiaRESUMO
Mammalian orthologues of the Drosophila tribbles protein (Trb1, Trb2 and Trb3) are a recently described family of signalling molecules that regulate gene expression by modulation of protein kinase signalling pathways. In the present study, a screen for mRNA species specifically regulated in vulnerable regions of human atherosclerotic plaque demonstrated the up-regulation of both Trb1 and Trb2, the latter by more than 8-fold. In vitro experiments in primary human monocyte-derived macrophages showed that Trb2 expression was up-regulated by treatment with oxidized LDL (low-density lipoprotein), and that expression of recombinant Trb2 specifically reduced macrophage levels of IL-10 (interleukin-10) mRNA. Our results thus identify Trb2 as a highly regulated gene in vulnerable atherosclerotic lesions, and demonstrate inhibition of macrophage IL-10 biosynthesis as a potential pro-inflammatory consequence of high Trb2 expression, which may contribute to plaque instability.
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Doenças das Artérias Carótidas/metabolismo , Interleucina-10/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina , Doenças das Artérias Carótidas/cirurgia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Endarterectomia das Carótidas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-10/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Lipoproteínas LDL/farmacologia , Macrófagos/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismoRESUMO
Nerve stimulation typically employs charge-balanced current injection with a delay between the cathodal and anodal phases. Typically these waveforms are produced using a microprocessor. However, once appropriate stimulus parameters are chosen, they tend to remain fixed within an application, making computational power unnecessary. In such cases, it would be advantageous to replace the microprocessor with integrated circuitry and hardware controls for maintaining fixed pulse parameters. We describe here an architecture that generates controllable charge-balanced pulses but requires no computer processing components. The circuitry has been engineered such that minimum size and power consumption can be achieved when fabricated into an IC chip, making it ideal for many long term, portable nerve stimulation devices and applications.
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Estimulação Elétrica/instrumentação , Estimulação Elétrica/métodos , Microcomputadores , Sistema Nervoso Periférico/efeitos da radiação , Animais , Eletrodos Implantados , Humanos , Sistema Nervoso Periférico/fisiologiaRESUMO
OBJECTIVE: Comparison of gene expression in stable versus unstable atherosclerotic plaque may be confounded by interpatient variability. The aim of this study was to identify differences in gene expression between stable and unstable segments of plaque obtained from the same patient. METHODS AND RESULTS: Human carotid endarterectomy specimens were segmented and macroscopically classified using a morphological classification system. Two analytical methods, an intraplaque and an interplaque analysis, revealed 170 and 1916 differentially expressed genes, respectively using Affymetrix gene chip analysis. A total of 115 genes were identified from both analyses. The differential expression of 27 genes was also confirmed using quantitative-polymerase chain reaction on a larger panel of samples. Eighteen of these genes have not been associated previously with plaque instability, including the metalloproteinase, ADAMDEC1 (approximately 37-fold), retinoic acid receptor responder-1 (approximately 5-fold), and cysteine protease legumain (approximately 3-fold). Matrix metalloproteinase-9 (MMP-9), cathepsin B, and a novel gene, legumain, a potential activator of MMPs and cathepsins, were also confirmed at the protein level. CONCLUSIONS: The differential expression of 18 genes not previously associated with plaque rupture has been confirmed in stable and unstable regions of the same atherosclerotic plaque. These genes may represent novel targets for the treatment of unstable plaque or useful diagnostic markers of plaque instability.
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Aterosclerose/genética , Aterosclerose/patologia , Expressão Gênica , Biomarcadores/metabolismo , Catepsina B/metabolismo , Cisteína Endopeptidases/genética , Endotélio Vascular/metabolismo , Perfilação da Expressão Gênica , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , Metaloproteinase 9 da Matriz/metabolismo , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismo , Linfócitos T/metabolismoRESUMO
The effects of the application of steam at atmospheric pressure for times up to 20 s on the numbers of inoculated Campylobacter jejuni and Escherichia coli on whole chicken carcasses were investigated in a pilot steam cabinet. Steam treatments reduced the numbers of C. jejuni AR6 by ca. 1.8, 2.6 and 3.3 log(10) cfu cm(-2) in 10, 12 and 20 s, respectively. Corresponding reductions in numbers of E. coli K12 were 1.7, 2.3 and 2.8 log(10) cfu cm(-2). However, such treatments caused the skin to shrink and change colour. The optimum treatment for maximum reductions of C. jejuni and E. coli, least skin shrinkage and change of colour was concluded to be <12 s. Further work was carried out to determine whether a modified air chilling system in combination with steam or hot water decontamination treatments could be used to reduce numbers of pathogens, particularly campylobacters, on the surface of poultry carcasses. Whole chicken carcasses inoculated with C. jejuni and E. coli were either not treated, treated with steam at atmospheric pressure for up to 10 s or treated with hot water at 80 degrees C for up to 20 s, then either chilled by crust freezing, chilled at 0 degrees C, or chilled at 15 degrees C, in a pilot chilling chamber. The optimum combination was treatment with water at 80 degrees C for 20 s followed by crust freezing, which reduced the numbers of C. jejuni and E. coli by ca. 2.9 and 3.2 log(10) cfu cm(-2), respectively, without extensive degradation of carcass appearance.