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Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated disease pathology observed in co-infected individuals are poorly understood. Moreover, there is limited data available on the impact of Plasmodium co-infection on antiretroviral (ART)-treated HIV infection. Here, we used the rhesus macaque (RM) model to conduct a pilot study to establish a model of Plasmodium fragile co-infection during ART-treated simian immunodeficiency virus (SIV) infection, and to begin to characterize the immunopathogenic effect of co-infection in the context of ART. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VLs) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was also associated with increased levels of neutrophil elastase, a plasma marker of neutrophil extracellular trap (NET) formation, but significant decreases in markers of neutrophil degranulation, potentially indicating a shift in the neutrophil functionality during co-infection. Finally, we characterized the levels of plasma markers of gastrointestinal (GI) barrier permeability and microbial translocation and observed significant correlations between indicators of GI dysfunction, clinical markers of SIV and Plasmodium infection, and neutrophil frequency and function. Taken together, these pilot data verify the utility of using the RM model to examine ART-treated SIV/P. fragile co-infection, and indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV/P. fragile co-infection pathogenesis.
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Coinfecção , Inflamação , Macaca mulatta , Malária , Neutrófilos , Plasmodium , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Animais , Coinfecção/tratamento farmacológico , Coinfecção/parasitologia , Coinfecção/virologia , Malária/tratamento farmacológico , Malária/imunologia , Malária/complicações , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/complicações , Projetos Piloto , Neutrófilos/imunologia , Antirretrovirais/uso terapêutico , Carga Viral , Biomarcadores/sangue , Citocinas/sangue , Modelos Animais de Doenças , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologiaRESUMO
BACKGROUND: Melioidosis is a disease caused by the bacterium Burkholderia pseudomallei, infecting humans and non-human primates (NHP) through contaminated soil or water. World-wide there are an estimated 165,000 human melioidosis cases each year, but recordings of NHP cases are sporadic. Clinical detection of melioidosis in humans is primarily by culturing B. pseudomallei, and there are no standardized detection protocols for NHP. NHP are an important animal model for melioidosis research including clinical trials and development of biodefense countermeasures. METHODOLOGY/PRINCIPLE FINDINGS: We evaluated the diagnostic potential of the multiple antigen serological assay, BurkPx, in NHP using two sera sets: (i) 115 B. pseudomallei-challenged serum samples from 80 NHP collected each week post-exposure (n = 52) and at euthanasia (n = 47), and (ii) 126 B. pseudomallei-naïve/negative serum samples. We observed early IgM antibody responses to carbohydrate antigens followed by IgG antibody recognition to multiple B. pseudomallei protein antigens during the second week of infection. B. pseudomallei negative serum samples had low to intermediate antibody cross reactivity to the antigens in this assay. Infection time was predicted as the determining factor in the variation of antibody responses, with 77.67% of variation explained by the first component of the principal component analysis. A multiple antigen model generated a binary prediction metric ([Formula: see text]), which when applied to all data resulted in 100% specificity and 63.48% sensitivity. Removal of week 1 B. pseudomallei challenged serum samples increased the sensitivity of the model to 95%. CONCLUSION/SIGNIFICANCE: We employed a previously standardized assay for humans, the BurkPx assay, and assessed its diagnostic potential for detection of B. pseudomallei exposure in NHP. The assay is expected to be useful for surveillance in NHP colonies, in investigations of suspected accidental releases or exposures, and for identifying vaccine correlates of protection.
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Burkholderia pseudomallei , Melioidose , Animais , Humanos , Melioidose/diagnóstico , Melioidose/veterinária , Melioidose/epidemiologia , Anticorpos Antibacterianos , Antígenos de Bactérias , PrimatasRESUMO
BACKGROUND: A single state-wide upper gastrointestinal (GI) cancer video-linked multidisciplinary team (MDT) meeting guides management and evidence-based care for all newly diagnosed upper GI cancer patients in South Australia. This study determined the patterns of care and outcomes for patients diagnosed with gastric and gastro-oesophageal junction (GOJ) cancers. METHODS: Patients diagnosed with gastric cancer and GOJ (Siewert III) cancer between June 2012 and June 2016 were included. Patient demographics, cancer stage, histology, diagnostic modalities and treatment data was analysed from a prospective database. Stage-specific survival outcomes were determined and analysed for each treatment modality. RESULTS: The study included 218 patients and at diagnosis 132 (61%) patients had stage I-III and 86 (39%) patients had stage IV disease. One hundred and ninety-five (89%) patients had gastric cancer and 23 (11%) had GOJ cancer (Siewert III). One hundred and nine (50%) patients underwent surgery, with 92% R0 resection rate. Forty-six patients received perioperative chemotherapy and 111 (51%) patients received palliative intent treatment. Median overall survival for stage II, III and IV cancers was 57.6 (95% CI 57.6-NR), 22.8 (95% CI 20.4-43.2), and 6.0 months (95% CI 4.8-8.4) respectively (p < 0.001). Median overall survival for patients who underwent perioperative chemotherapy and surgery was not reached as compared to 44.4 months (95% CI 28.8-NR) for patients who underwent surgery alone. CONCLUSION: Treatment outcomes for patients with gastric and GOJ cancer managed across South Australia met contemporary evidence-based practice. However, as most patients continue to present with late-stage disease, longer-term survival remains poor.
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Neoplasias Gástricas , Neoplasias Testiculares , Austrália/epidemiologia , Junção Esofagogástrica , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/terapiaRESUMO
Lifestyle-based disease prevention and self-management strategies play an important role in the mitigation of health, social, and economic burdens associated with type 2 diabetes mellitus (T2DM) and other chronic diseases. However, there are significant implementation and translational challenges associated with the design and delivery of effective interventions. In this study, data-driven techniques for the identification of optimal target audiences and intervention targets for T2DM prevention interventions were applied. Australian adults (N = 3159) with differing T2DM status (no diabetes diagnosis, pre-diabetes, or T2DM) completed self-report assessments of diet quality, physical activity, psychological distress, future orientation, health literacy, and socio-demographic characteristics. K-medoids cluster analysis was conducted to identify homogenous groups within the research sample and proportional odds ordinal logistic regressions conducted to identify signficant predictors of T2DM status within each cluster. Results identified a two-factor optimal solution that stratified participants based on sex (male/female). Within each cluster, psychosocial variables explained approximately 25% of the variance in T2DM status, with future orientation identified as a significant modifiable predictor of T2DM. For the male cluster, health literacy was also significant (p ≤0.01). Findings indicate that men and women should be targeted separately in T2DM prevention or management programs and that future interventional research targeting future orientation is warranted.
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Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Adulto , Austrália/epidemiologia , Análise por Conglomerados , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Estilo de Vida , MasculinoRESUMO
ObjectiveMindStep™ is an Australian low-intensity cognitive behaviour therapy (LICBT) program for individuals with mild-to-moderate symptoms of anxiety and depression. UK-produced LICBT guided self-help (GSH) materials were originally used in the MindStep™ program. In 2017, Australian LICBT GSH materials were developed to better suit Australian users. This study explored whether the Australian-produced materials continued to achieve the benchmark recovery rates established in the UK and maintained in recent Australian studies.MethodsBinomial logistic regression was conducted using retrospective client data, including the Patient Health Questionnaire-9 and the Generalised Anxiety Disorder 7-item scale, between 2016 and 2019.ResultsDuring time periods in which the Australian-produced materials were used, equivalent rates of reliable recovery and improvement were achieved compared with time periods in which the UK-produced materials were used. Australian-trained LICBT coaches, using Australian-produced LICBT GSH materials, achieve client recovery rates of up to 60%, reliable improvement rates of 58% and reliable recovery rates of 46% (with the probability of recovery increasing with client age).ConclusionsThese findings are particularly pertinent with COVID-19 changing the landscape of mental health service delivery, requiring greater flexibility in the use of teleservices to ensure access to effective mental health care for populations that may already experience problems with isolation, access and service engagement.What is known about the topic?LICBT is an acceptable, feasible and effective treatment approach for people experiencing mild-to-moderate anxiety and depression in Australia. LICBT GSH materials used with clients in Australia originated from the UK. However, according to guidelines, LICBT GSH materials should be contextualised to suit the audience they are being used with.What does this paper add?This paper demonstrates that LICBT GSH materials tailored to an Australian context can be used in place of UK-produced materials because they yield equivalent and consistent therapeutic outcomes. Although contextualising the LICBT GSH materials for health services users was important, it is likely that the evidence-based cognitive behaviour therapy techniques sitting 'under the hood' of these materials are most important to ensure successful therapeutic outcomes.What are the implications for practitioners?As we face unprecedented challenges following 2020, the physical, social, psychological and economic impacts of life-changing events must not inhibit access to treatments for common mental health conditions. It is anticipated that more non-traditional, alternative providers of mental health services will be needed to scale-up and respond to increasing demand. This paper shows that the provision of telephone-based LICBT in Australia, by trained coaches using Australian-produced GSH materials, is an evidenced-based support pathway that can reduce the access gap to treatments.
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BACKGROUND: Risk assessment models must be continuously validated and updated to ensure that predictions remain valid. Here, the Endovascular Aneurysm Repair Risk Assessment Model, developed in 2008, is updated and improved. METHODS: We used prospectively collected data from Australian patients who underwent elective endovascular aneurysm repair between 2009 and 2013 (n = 695). Data were provided by treating surgeons and the National Death Index. Key outcomes were early and midterm survival, early complications (endoleak, operative, and graft-related) and late complications (endoleak and graft-related). Multinomial logistic regression determined which preoperative variables best predicted each outcome. Area under Receiver Operating Characteristic curve (AUROC), model P-value and internal validation statistics were used to select the best model. RESULTS: Ten preoperative variables were included in the modeling for 10 key outcomes. The most valid outcomes with AUROC>0.7 were 1- and 3-year survival, 30 and 90-day mortality, early and late endoleak (types I, III and IV) and type II endoleak (with an increase in sac size ≥5 mm). The 10 preoperative variables that contributed to outcome models were self-reported fitness, American Society of Anesthesiologists physical status score, history of stroke/transient ischemic attack, age, aneurysm angle, infrarenal neck length, white cell count, respiratory assessment, diabetes and statin therapy. Fitness alone statistically significantly predicted 30 and 90-day deaths better than any other preoperative variable; achieving high AUROCs (0.78 and 0.80), and high odds ratios (12.8 [95% CI: 1.5-110.4] and 18.1 [95% CI: 2.2-149]). CONCLUSIONS: An updated interactive predictive model of outcomes after endovascular aneurysm repair has been created. Many of the variables used in the 2008 model continued to be significant, however, new variables including fitness and respiratory assessment, improved the model. The new model uses variables routinely collected preoperatively, and hence can better support surgeon-patient discussions prior to operation. Informing patients of potential risks or likely outcomes following elective surgery can assist with preoperative shared decision-making.
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Aneurisma Aórtico/cirurgia , Implante de Prótese Vascular , Técnicas de Apoio para a Decisão , Idoso , Idoso de 80 Anos ou mais , Aneurisma Aórtico/diagnóstico , Aneurisma Aórtico/mortalidade , Austrália , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Tomada de Decisão Clínica , Tomada de Decisão Compartilhada , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Participação do Paciente , Complicações Cognitivas Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a wide range of disease severity, ranging from asymptomatic infection to a life-threating illness, particularly in the elderly population and individuals with comorbid conditions. Among individuals with serious coronavirus 2019 (COVID-19) disease, acute respiratory distress syndrome (ARDS) is a common and often fatal presentation. Animal models of SARS-CoV-2 infection that manifest severe disease are needed to investigate the pathogenesis of COVID-19-induced ARDS and evaluate therapeutic strategies. We report two cases of ARDS in two aged African green monkeys (AGMs) infected with SARS-CoV-2 that had pathological lesions and disease similar to severe COVID-19 in humans. We also report a comparatively mild COVID-19 phenotype characterized by minor clinical, radiographic, and histopathologic changes in the two surviving, aged AGMs and four rhesus macaques (RMs) infected with SARS-CoV-2. Notable increases in circulating cytokines were observed in three of four infected, aged AGMs but not in infected RMs. All the AGMs had increased levels of plasma IL-6 compared with baseline, a predictive marker and presumptive therapeutic target in humans infected with SARS-CoV-2. Together, our results indicate that both RMs and AGMs are capable of modeling SARS-CoV-2 infection and suggest that aged AGMs may be useful for modeling severe disease manifestations, including ARDS.
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COVID-19/etiologia , Pulmão/virologia , SARS-CoV-2/patogenicidade , Envelhecimento , Animais , Chlorocebus aethiops/virologia , Infecções por Coronavirus/tratamento farmacológico , Citocinas/metabolismo , Humanos , Pulmão/patologia , Macaca mulatta/virologia , Carga Viral/métodosRESUMO
Despite abundant cross-sectional evidence that low vitamin D status is associated with risk of cognitive decline in ageing, interventional evidence for benefits of vitamin D supplementation is lacking. This study was a 6 month randomised, double-blinded placebo-controlled clinical trial of the effects of vitamin D3 (D3), enhanced vitamin D2 in a mushroom matrix (D2M), standard mushroom (SM) and placebo (PL) on cognition and mood in n = 436 healthy older male (49%) and female volunteers aged ≥ 60 years. Primary end points were change in serum vitamin D metabolites (25-OH-D, 25-OH-D2 and 25-OH-D3), cognitive performance, and mood over 24 weeks. Levels of total 25-OH-D and 25-OH-D3 were maintained in the D3 arm but decreased significantly (p < 0.05) in the remaining arms (D2M, SM and PL). Analysis also revealed differential changes in these metabolites depending on total vitamin D status at baseline. There were no significant effects of treatment on any of the measures of cognitive function or mood. Overall, the results show that daily supplementation of ~600 IU of vitamin D3 was sufficient to maintain 25-OH-D throughout winter months, but in contrast to existing cross-sectional studies there was no support for benefit of vitamin D supplementation for mood or cognition in healthy elderly people.
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Agaricales , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Ergocalciferóis/administração & dosagem , Deficiência de Vitamina D/terapia , Vitamina D/sangue , 25-Hidroxivitamina D 2/sangue , Afeto/efeitos dos fármacos , Calcifediol/sangue , Cognição/efeitos dos fármacos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estações do Ano , Resultado do Tratamento , Vitamina D/análogos & derivados , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/psicologiaRESUMO
Elemental mercury (Hg0) contamination in artisanal and small-scale gold mining (ASGM) communities is widespread, and Hg0-contaminated tailings are often reprocessed with cyanide (-CN) to extract residual gold remaining after amalgamation. Hg0 reacts with -CN under aerobic conditions to produce Hg(CN)42- and other Hg(CN)nn-2 complexes. The production of solvated Hg(CN)nn-2 complexes increases upon agitation in the presence of synthetic and authentic Hg0-contaminated tailings that aid in dispersing the Hg0, increasing its reactive surface area. Adult rats were exposed to various concentrations of Hg(CN)2, and accumulation in organs and tissues was quantified using direct mercury analysis. The primary site of Hg(CN)2 accumulation was the kidney, although accumulation was also detected in the liver, spleen, and blood. Little accumulation was observed in the brain, suggesting that Hg(CN)2 complexes do not cross the blood-brain barrier. Renal tissue was particularly sensitive to the effects of Hg(CN)2, with pathological changes observed at low concentrations. Hg(CN)2 complexes are handled by mammalian systems in a manner similar to other inorganic species of Hg, yet appear to be more toxic to organ systems. The findings from this study are the first to show that Hg(CN)2 complexes are highly stable complexes that can lead to cellular injury and death in mammalian organ systems.
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Cianetos/toxicidade , Ouro/toxicidade , Compostos de Mercúrio/toxicidade , Mercúrio/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Monitoramento Ambiental , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Mineração , Ratos , Ratos Wistar , Solubilidade , Baço/efeitos dos fármacosRESUMO
BACKGROUND: Traditional methods for the quantification of OSA severity may not encapsulate potential relationships between hypoxemia in OSA and cardiovascular risk. RESEARCH QUESTION: Do novel nocturnal oxygen saturation (Spo2) metrics have prognostic value in patients with OSA and high cardiovascular event risk? STUDY DESIGN AND METHODS: We conducted post hoc analyses of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial. In 2687 individuals, Cox proportional hazards models that were stratified for treatment allocation were used to determine the associations between clinical characteristics, pulse oximetry-derived metrics that were designed to quantify sustained and episodic features of hypoxemia, and cardiovascular outcomes. Metrics included oxygen desaturation index, time <90% Spo2, average Spo2 for the entire recording (mean Spo2), average Spo2 during desaturation events (desaturation Spo2), average baseline Spo2 interpolated across episodic desaturation events (baseline Spo2), episodic desaturation event duration and desaturation/resaturation-time ratio, and mean and SD of pulse rate. RESULTS: Neither apnea-hypopnea index, oxygen desaturation index, nor any of the novel Spo2 metrics were associated with the primary SAVE composite cardiovascular outcome. Mean and baseline Spo2 were associated with heart failure (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .009; and HR, 0.78; 95% CI, 0.67-0.90; P = .001, respectively) and myocardial infarction (HR, 0.86; 95% CI, 0.77-0.95; P = .003; and HR, 0.81; 95% CI, 0.73-0.90; P < .001, respectively). Desaturation duration and desaturation/resaturation time ratio, with established risk factors, predicted future heart failure (area under the curve, 0.86; 95% CI, 0.79-0.93). INTERPRETATION: Apnea-hypopnea index and oxygen desaturation index were not associated with cardiovascular outcomes. In contrast, the pattern of oxygen desaturation was associated with heart failure and myocardial infarction. However, concomitant risk factors remained the predominant determinants for secondary cardiovascular events and thus deserve the most intensive management.
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Doenças Cardiovasculares , Insuficiência Cardíaca , Hipóxia , Infarto do Miocárdio , Oximetria , Polissonografia , Medição de Risco , Apneia Obstrutiva do Sono , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Correlação de Dados , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Frequência Cardíaca , Humanos , Hipóxia/complicações , Hipóxia/diagnóstico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Avaliação de Resultados em Cuidados de Saúde , Oximetria/métodos , Oximetria/estatística & dados numéricos , Polissonografia/métodos , Polissonografia/estatística & dados numéricos , Valor Preditivo dos Testes , Prognóstico , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapiaRESUMO
The sorption behaviour of three perfluoroalkyl substances (PFASs), namely perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS), was determined on 28 tropical soils. Tropical soils are often highly weathered, richer in sesquioxides than temperate soils and may contain variable charge minerals. There are little data on sorption of PFASs in tropical soils. The highest Kd values were found for PFOS with mean values ranging from 0 to 31.6 L/kg. The Kd values for PFOA and PFHxS ranged from 0 to 4.9 L/kg and from 0 to 5.6 L/kg, respectively. While these values are in the range of literature sorption data, the average Kd values for PFOS and PFOA from the literature were 3.7 times and 3.6 times higher, respectively, than those measured in this study. Stepwise regression analysis did explain some of the variance, but with different explanatory variables for the different PFASs. The main soil properties explaining sorption for PFOS and PFOA were oxalate-extractable Al and pH, and for PFHxS was pH.
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Ácidos Alcanossulfônicos/química , Caprilatos/química , Fluorocarbonos/química , Poluentes do Solo/química , Ácidos Sulfônicos/química , Clima Tropical , SoloRESUMO
Mercury (Hg) is a common environmental toxicant to which humans are exposed regularly through occupational and dietary means. Although selenium supplementation has been reported to prevent the toxic effects of Hg in animals, the mechanisms for this prevention are not well understood. The purpose of the current study was to determine the effects of selenium on the disposition and toxicity of Hg. Wistar rats were injected intravenously with a non-nephrotoxic dose (0.5 µmol kg-1) or a nephrotoxic dose (2.5 µmol kg-1) of HgCl2 (containing radioactive Hg) with or without co-administration of sodium selenite (Na2SeO3). Twenty-four hours after exposure, rats were euthanized, and organs were harvested. Co-administration of SeO32- with HgCl2 reduced the renal burden of Hg and the urinary excretion of Hg while increasing the amount of Hg in blood and spleen. We propose that Hg reacts with reduced selenite in the blood to form large Hg-Se complexes that are unable to be filtered at the glomerulus. Consequently, these complexes remain in the blood and are able to accumulate in blood-rich organs. These complexes, which may have fewer toxic effects than other species of Hg, may be eliminated slowly over the course of weeks to months.
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Cloreto de Mercúrio/toxicidade , Mercúrio/metabolismo , Selenito de Sódio/farmacologia , Animais , Feminino , Injeções Intravenosas , Íons/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Cloreto de Mercúrio/administração & dosagem , Cloreto de Mercúrio/sangue , Ratos , Ratos Wistar , Selenito de Sódio/administração & dosagem , Selenito de Sódio/sangue , Baço/efeitos dos fármacos , Baço/metabolismo , Distribuição TecidualRESUMO
Age-related cataract is the major cause of blindness worldwide. Both genetic and environmental factors contribute to the disease. Genetic variation in the Ephrin type-A receptor 2 (EPHA2) gene is associated with the risk of age-related cataract in multiple populations, and exposure to ultraviolet-B (UV-B) radiation is a well-established risk factor for the disease. Epha2 knockout and UV-B radiation independently lead to cataract in mice, and UV-B radiation reportedly alters EPHA2 expression in cultured cells. We hypothesised that an interaction between UV-B radiation exposure and Epha2 signalling may influence cataract development. To test this hypothesis, 5-week-old Epha2+/+ and Epha2+/- mice (nâ¯=â¯8 per group) were exposed to repeated below-threshold doses of UV-B radiation (0.0125-0.05â¯J/cm2), before development of Epha2-mediated cataract. Cataract development was monitored after termination of exposure and at least one month later. Histological analysis of exposed and unexposed lenses was performed to assess pathological changes, and gene expression analysis to investigate the mechanism underlying cataract. Both Epha2+/+ and Epha2+/- mice developed UV-B dose-dependent anterior polar cataract; cataract severity in both genotypes of mice exposed to either 0.025 or 0.05â¯J/cm2 UV-B was significantly higher than that in matched unexposed mice (pâ¯<â¯0.05). Histological analysis of lenses of both genotypes of mice exposed to 0.025 or 0.05â¯J/cm2 UV-B radiation consistently revealed disruption of the lens architecture. A month after the exposure, cataract severity increased in Epha2+/+ mice treated with the highest dose of UV-B radiation (pâ¯=â¯0.03) but remained unchanged in Epha2+/- mice. Gene expression analysis of lenses of both genotypes of mice showed significant upregulation of the cell proliferation marker Mki67 in Epha2+/+ (pâ¯=â¯0.036) but not in Epha2+/- mice exposed to the highest dose of UV-B radiation compared to matched unexposed mice. In conclusion, this study suggests that repeated exposure to doses of UV-B radiation lower than the single minimum dose required for inducing cataract leads to cataract in wild-type and Epha2 heterozygous knockout mice. Furthermore, this study indicates, for the first time, a potentially favourable effect of partial Epha2 deficiency against UV radiation-induced damage in the lens.
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Catarata/genética , Interação Gene-Ambiente , Cristalino/efeitos da radiação , Lesões Experimentais por Radiação/genética , Receptor EphA2/genética , Raios Ultravioleta/efeitos adversos , Animais , Catarata/patologia , Relação Dose-Resposta à Radiação , Proteínas do Olho/genética , Regulação da Expressão Gênica/fisiologia , Genótipo , Técnicas de Genotipagem , Cristalino/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Doses de Radiação , Lesões Experimentais por Radiação/patologia , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND AND OBJECTIVES: Recognizing the important role that dementia-specific adult day centers have in maintaining persons with a neurocognitive disorder in their home, this article examines three critical indicators at the time when people first enroll in such a center: cognitive and functional impairment of the enrollee, and burden reported by their family caregivers. We also considered variations in these 3 indicators by race/ethnicity and by the relationship of caregiver to the new enrollee. RESEARCH DESIGN AND METHODS: We conducted a secondary analysis of data collected by a nonprofit organization operating 11 dementia-specific adult day centers located on the east coast of Florida. Nursing staff conducted intake interviews with enrollees and their caregivers, and assessed functional status within one month of admission. Instruments included the Zarit Burden Scale and components of the Minimum Data Set: the Brief Interview for Mental Status (BIMS) and 4 measures of functional status. RESULTS: On average the cognitive scores of newly enrollees were well-within the range indicated for severe impairment, and these levels did not differ by race/ethnicity. Burden reported by caregivers however differed significantly, with Latinx caregivers reporting the greatest burden and African American/Black caregivers reporting the least. Further, while daughters generally reported higher levels of burden than other family caregivers, Black daughters reported the least. DISCUSSION AND IMPLICATIONS: Results suggest a need for greater dissemination efforts about adult day programs to the Latinx community, as well as attention to the disparate burden placed upon differing family relationships of caregivers to enrollees.
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BACKGROUND AND OBJECTIVES: Empirical treatment of sore throat with antibiotics has historically been aimed at preventing complications of group A ß-haemolytic streptococcus infection. Threats posed by multi-resistant organisms mean that antimicrobial stewardship is important. The aim of this study was to investigate antibiotic prescribing for tonsillopharyngitis in relation to components of the Modified Centor Criteria (MCC) documented in consultation records. METHOD: Analysis of two rural Australian general practices was performed using clinic management software. A keyword search for 'tonsillopharyngitis/tonsillitis/pharyngitis' identified consultations. RESULTS: Antibiotic prescribing was frequent and congruent with existing studies; however, documented evidence of history and examination covering MCC components was associated with lower antibiotic prescribing (77.7% versus 85.5%, P <0.001; odds ratio: 2.4; 95% confidence interval: 1.8, 3.3, P <0.0001). DISCUSSION: We believe this is the first study that assesses the correlation between documentation and prescribing. Adopting and documenting MCC may improve appropriate prescription and patient safety and significantly reduce antibiotic prescription rates.
Assuntos
Gestão de Antimicrobianos/classificação , Gestão de Antimicrobianos/normas , Faringite/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/estatística & dados numéricos , Austrália , Medicina Geral/métodos , Medicina Geral/normas , Medicina Geral/tendências , Humanos , Faringite/fisiopatologia , Padrões de Prática Médica/normas , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/fisiopatologia , Tonsilite/tratamento farmacológico , Tonsilite/fisiopatologiaRESUMO
BACKGROUND: The randomized goal-directed perfusion trial confirmed retrospective findings that a goal-directed perfusion strategy to maintain oxygen delivery index (DO2i) during cardiopulmonary bypass greater than 280 mL/min/m2 reduces the incidence of acute kidney injury (AKI). We developed a predictive model for AKI using data from the Australian and New Zealand Collaborative Perfusion Registry to determine whether these findings could be validated in a real-world clinical setting and to identify an optimal DO2i threshold for predictive diagnostic accuracy. METHODS: Data in 19,410 cardiopulmonary bypass procedures were randomly divided into training (n = 9705) and validation (n = 9705) datasets. Multivariate logistic regression was used to determine the best predictive models for AKI (RIFLE [renal Risk, Injury, Failure, Loss of renal function and End-stage renal disease] classification), incremental predictive value of minimum cardiopulmonary bypass DO2i, and optimal threshold. RESULTS: Minimum DO2i was significantly associated with any AKI, AKI risk, and AKI injury or greater class in both datasets (validation dataset; any AKI odds ratio [OR], 0.993; 95% confidence interval [CI], 0.991-0.995; P < .001; AKI risk OR, 0.994; 95% CI, 0.992-0.996; P < .001, AKI injury or greater 0.993; 95% CI, 0.991-0.996; P < .001), representing on average a 7% increase in the likelihood of AKI for every 10-mL/min/m2 decrease in DO2i. Diagnostic accuracy was similar for both datasets, with an optimal DO2i threshold of 270 mL/min/m2. The odds of any AKI were increased by 52% in those below the threshold (OR, 1.52; 95% CI, 1.29-1.77; P < .001). CONCLUSIONS: This study confirms previous findings that minimum DO2i during cardiopulmonary bypass is independently associated with AKI, supporting previous findings in a broader-risk, multicenter cohort.
Assuntos
Injúria Renal Aguda/prevenção & controle , Ponte Cardiopulmonar/métodos , Doença da Artéria Coronariana/cirurgia , Consumo de Oxigênio/fisiologia , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/metabolismo , Idoso , Austrália/epidemiologia , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/metabolismo , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Oxigênio/metabolismo , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/metabolismo , Estudos Prospectivos , Curva ROC , Fatores de RiscoRESUMO
This study investigated the effect of surface charge on the sorption of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS) onto 7 tropical soils as a function of pH. The net surface charge became less negative with decreasing pH (from 7.5 to 3.5) in all soils. The rate of change in net surface charge varied from -0.6 to -2.8â¯(cmol/kg)/pH unit. The effect on sorption behaviour of PFASs was variable among soils. For two soils, the average sorption increased 54- and 45-fold for PFOS, 33- and 9-fold for PFOA, and 39- and 400-fold for PFHxS, across the pH range 7.5 to 3.5. Sorption in another sandier soil showed negligible change with decreasing pH. Sorption in the other soils did not change significantly until the pH decreased to approximately 5.5. The soils with high contents of sesquioxides (Fe and Al oxides) showed the most marked increase in sorption with decreasing pH. This study demonstrated that in addition to hydrophobic interactions with OC and other processes, electrostatic interactions are also important in the sorption process for these chemicals in soils. In acidic, variably charged tropical soils there is the possibility that any PFOS, PFOA or PFHxS sorbed to the soils may become desorbed if management practices (e.g. liming) raised soil pH.
RESUMO
Mercury is a toxic metal that is found ubiquitously in the environment. Humans are exposed to different forms of mercury via ingestion, inhalation, and/or dermal absorption. Following exposure, mercuric ions may gain access to target cells and subsequently lead to cellular intoxication. The mechanisms by which mercury accumulation leads to cellular injury and death are not understood fully. Therefore, purpose of this study was to identify the specific intracellular mechanisms that are altered by exposure to inorganic mercury (Hg2+). Normal rat kidney (NRK) cells were exposed to a physiologically relevant form of Hg2+, as a conjugate of cysteine (10 µM or 50 µM). Alterations in oxidative stress were estimated by measuring lipid peroxidation and mitochondrial oxidative stress. Alterations in actin and tubulin were measured using specific fluorescent dyes. Calcium levels were measured using Fluo-3 AM Calcium Indicator while autophagy was identified with Premo™ Autophagy Sensor LC3B-GFP. The current findings show that exposure to Hg2+ leads to enhanced oxidative stress, alterations in cytoskeletal structure, increases in intracellular calcium, and enhanced autophagy. We have established a more complete understanding of intoxication and cellular injury induced by a relevant form of Hg2+ in proximal tubule cells.