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BACKGROUND: Multidrug-resistant organisms (MDROs) are prevalent on high-touch surfaces in multi-patient rooms. AIM: To quantify the impact of hanging single-use cleaning/disinfecting wipes next to each bed. Pre-specified outcomes were: (1) hospital-acquired infections (HAIs), (2) cleaning frequency, (3) MDRO room contamination, (4) new MDRO acquisitions, and (5) mortality. METHODS: Clustered randomized crossover trial at Shamir Medical Center, Israel (October 2016 to January 2018). Clusters were randomly assigned to use for cleaning either single-use quaternary ammonium wipes (Clinell) or standard practices (reusable cloths and buckets with bleach). Six-month intervention periods were implemented in alternating sequence, separated by a washout period. Five high-touch surfaces were monitored by fluorescent markers. Study outcomes were compared between periods using generalized estimating equations, Poisson regression, and Cox proportional hazards models. FINDINGS: Overall, 7725 patients were included (47,670 person-days), 3793 patients in rooms with intervention cleaning and 3932 patients in rooms with standard practices. During the intervention, there was no significant difference in HAI rates (incidence rate ratio: 1.6; 95% confidence interval (CI): 0.7-3.5; P = 0.3). However, in intervention rooms, the frequency of environmental cleaning was higher (odds ratio: 3.73; 95% CI: 2.0-7.1; P < 0.0001), MDRO environmental contamination rate was insignificantly lower (odds ratio: 0.7; 95% CI: 0.5-1.0; P = 0.06), new MDRO acquisition rate was lower (hazard ratio: 0.4; 95% CI: 0.2-1.0; P = 0.04), and in-hospital mortality rate was lower (incidence rate ratio: 0.8; 95% CI: 0.7-1.0; P = 0.03). CONCLUSION: Hanging single-use cleaning/disinfecting wipes next to each bed did not affect the HAI rates but did improve the frequency of cleaning, reduce MDRO environmental contamination, and was associated with reduced incidence of new MDRO acquisitions and reduced mortality. This is a feasible, recommended practice to improve patient outcomes in multi-patient rooms.
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Infecção Hospitalar , Quartos de Pacientes , Humanos , Desinfecção , Estudos Prospectivos , Estudos Cross-Over , Hospitais , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controleRESUMO
BACKGROUND: The COVID-19 pandemic and the associated economic recession has increased parental psychosocial stress and mental health challenges. This has adversely impacted child development and wellbeing, particularly for children from priority populations (culturally and linguistically diverse (CALD) and rural/regional communities) who are at an already increased risk of health inequality. The increased mental health and psychosocial needs were compounded by the closure of in-person preventive and health promotion programs resulting in health organisations embracing technology and online services. Watch Me Grow- Electronic (WMG-E) - developmental surveillance platform- exemplifies one such service. WMG-E was developed to monitor child development and guide parents towards more detailed assessments when risk is identified. This Randomised Controlled Trial (RCT) aims to expand WMG-E as a digital navigation tool by also incorporating parents' mental health and psychosocial needs. Children and families needing additional assessments and supports will be electronically directed to relevant resources in the 'care-as-usual' group. In contrast, the intervention group will receive continuity of care, with additional in-person assessment and 'warm hand over' by a 'service navigator' to ensure their needs are met. METHODS: Using an RCT we will determine: (1) parental engagement with developmental surveillance; (2) access to services for those with mental health and social care needs; and (3) uptake of service recommendations. Three hundred parents/carers of children aged 6 months to 3 years (recruited from a culturally diverse, or rural/regional site) will be randomly allocated to the 'care-as-usual' or 'intervention' group. A mixed methods implementation evaluation will be completed, with semi-structured interviews to ascertain the acceptability, feasibility and impact of the WMG-E platform and service navigator. CONCLUSIONS: Using WMG-E is expected to: normalise and de-stigmatise mental health and psychosocial screening; increase parental engagement and service use; and result in the early identification and management of child developmental needs, parental mental health, and family psychosocial needs. If effective, digital solutions such as WMG-E to engage and empower parents alongside a service navigator for vulnerable families needing additional support, will have significant practice and policy implications in the pandemic/post pandemic period. TRIAL REGISTRATION: The trial (Protocol No. 1.0, Version 3.1) was registered with ANZCTR (registration number: ACTRN12621000766819 ) on July 21st, 2021 and reporting of the trial results will be according to recommendations in the CONSORT Statement.
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COVID-19 , Desenvolvimento Infantil , Criança , Eletrônica , Humanos , Saúde Mental , Pais , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2RESUMO
Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease that leads to joint destruction and disability. Despite a significant progress in administration of biological agents for RA patients, there is still a need for improved therapy. Intravenous immunoglobulins (IVIG), a pooled polyspecific immunoglobulin (Ig)G extracted from 5000 to 20 000 healthy subjects, showed beneficial therapeutic effect in patients with immune deficiency, sepsis and autoimmune diseases. The current study aimed to investigate the beneficial effect of treatment with IVIG in established collagen-induced arthritis in DBA/1j mice. Murine arthritis was induced in DBA/1j mice. Treatment with IVIG began when the disease was established. The clinical score was followed twice a week until day 48. The mice were bled for plasma and the paws were hematoxylin and eosin (H&E)-stained. Cytokine profile in the plasma was analyzed by Luminex technology and titers of circulating anti-collagen antibodies in the plasma was tested by enzyme-linked immunosorbent assay. Our results show that treatment with IVIG in murine significantly reduced the clinical arthritis score (P < 0·001). Moreover, mode of action showed that IVIG significantly reduced circulating levels of inflammatory cytokines [interferon (IFN)-γ, interleukin (IL)-1ß, IL-17, IL-6, tumor necrosis factor (TNF)-α, P < 0·001], inhibiting anti-collagen antibodies (P < 0·001) in the plasma of collagen-induced arthritis mice. Importantly, histopathological examination revealed that IVIG treatment prevented the migration of inflammatory immune cells into the cartilage and synovium, reduced the extent of joint damage and preserved joint architecture. Our results proved for the first time the valuable anti-inflammatory treatment of IVIG in experimental RA. We propose IVIG therapy for a subgroup of patients with rheumatologically related diseases.
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Artrite Experimental/prevenção & controle , Artrite Reumatoide/prevenção & controle , Cartilagem/efeitos dos fármacos , Modelos Animais de Doenças , Imunoglobulinas Intravenosas/farmacologia , Membrana Sinovial/efeitos dos fármacos , Animais , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Cartilagem/imunologia , Cartilagem/metabolismo , Citocinas/sangue , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/imunologia , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/prevenção & controle , Mediadores da Inflamação/sangue , Masculino , Camundongos Endogâmicos DBA , Infiltração de Neutrófilos/efeitos dos fármacos , Infiltração de Neutrófilos/imunologia , Membrana Sinovial/imunologia , Membrana Sinovial/metabolismoRESUMO
The Th17 profile immune response is influenced by the presence of cytokines such as IL-1, IL-6, TGF-ß, IL-17, and IL-23. We sought to characterize the Th17 profile in CNS samples from human rabies cases transmitted by dogs and examine its possible influence on disease pathogenesis. We observed a high expression of TGF-ß, followed by IL-23, IL-17 and IL-6, and a low expression of IL-1ß and IFN-γ. Those results suggest the participation of Th17 in rabies virus neuroinfection transmitted by dogs. IL-23 probably plays a role in maintaining the Th17 profile, but it can also interfere with the establishment of the Th1 profile and viral clearance.
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Encéfalo/imunologia , Citocinas/imunologia , Imunidade Celular/imunologia , Raiva/imunologia , Raiva/transmissão , Células Th17/imunologia , Adolescente , Adulto , Animais , Encéfalo/metabolismo , Citocinas/metabolismo , Cães , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Raiva/metabolismo , Células Th17/metabolismo , Adulto JovemRESUMO
Noble gases are chemically inert, and it was therefore thought they would have little effect on biology. Paradoxically, it was found that they do exhibit a wide range of biological effects, many of which are target-specific and potentially useful and some of which have been demonstrated in vivo. The underlying mechanisms by which useful pharmacology, such as tissue and neuroprotection, anti-addiction effects, and analgesia, is elicited are relatively unexplored. Experiments to probe the interactions of noble gases with specific proteins are more difficult with gases than those with other chemicals. It is clearly impractical to conduct the large number of gas-protein experiments required to gain a complete picture of noble gas biology. Given the simplicity of atoms as ligands, in silico methods provide an opportunity to gain insight into which noble gas-protein interactions are worthy of further experimental or advanced computational investigation. Our previous validation studies showed that in silico methods can accurately predict experimentally determined noble gas binding sites in X-ray structures of proteins. Here, we summarize the largest reported in silico reverse docking study involving 127 854 protein structures and the five nonradioactive noble gases. We describe how these computational screening methods are implemented, summarize the main types of interactions that occur between noble gases and target proteins, describe how the massive data set that this study generated can be analyzed (freely available at group18.csiro.au), and provide the NDMA receptor as an example of how these data can be used to understand the molecular pharmacology underlying the biology of the noble gases. We encourage chemical biologists to access the data and use them to expand the knowledge base of noble gas pharmacology, and to use this information, together with more efficient delivery systems, to develop "atomic drugs" that can fully exploit their considerable and relatively unexplored potential in medicine.
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Gases Nobres/metabolismo , Proteínas/metabolismo , Animais , Sítios de Ligação , Bases de Dados de Proteínas , Descoberta de Drogas , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Proteínas/química , Proteoma/química , Proteoma/metabolismo , TermodinâmicaRESUMO
BACKGROUND: High flow nasal cannula therapy is a form of respiratory support which delivers high flow rates of heated, humidified gas to the nares via specialized cannula. Two primary mechanisms of action attributed to the therapy are the provision of positive airway pressure as well as clearance of CO2-rich exhaled gas from the upper airways. METHODS: Physiologically accurate nose-throat airway replicas were connected at the trachea to a lung simulator, where CO2 was supplied to mimic the CO2 content in exhaled gas. Cannula delivered either air, oxygen or heliox (80/20%volume helium/oxygen) to the replicas at flow rates ranging from 0 to 60â¯l/min. Five replicas and three cannulas were compared. Tracheal pressure and CO2 concentration were continuously measured. The lung simulator provided breaths with tidal volume of 500â¯ml and frequency of 18â¯breaths/min. Additional clearance measurements were conducted for tidal volume and breathing frequency of 750â¯ml and 27â¯breaths/min, respectively. FINDINGS: Cannula flow rate was the dominant factor governing CO2 concentration. Average CO2 concentration decreased with increasing cannula flow rate, but above 30â¯L/min this effect was less pronounced. Tracheal positive end-expiratory pressure increased with flow rate and was lower for heliox than for air or oxygen. A predictive correlation was developed and used to predict positive end-expiratory pressure for a given cannula size as a function of supplied flow rate and occlusion of the nares. INTERPRETATION: Compared with administration of air or oxygen, administration of heliox is expected to result in similar CO2 clearance from the upper airway, but markedly lower airway pressure.
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Cânula , Dióxido de Carbono/metabolismo , Hélio/administração & dosagem , Intubação , Oxigenoterapia , Oxigênio/administração & dosagem , Adulto , Feminino , Humanos , Intubação/instrumentação , Intubação/métodos , Masculino , Nariz , Oxigenoterapia/instrumentação , Oxigenoterapia/métodosRESUMO
14-3-3η protein is a proinflammatory mediator that may represent a novel diagnostic and prognostic biomarker for rheumatoid arthritis (RA). We assessed the correlation between changes in serum 14-3-3η levels and changes in clinical disease activity measures in RA patients treated with Tofacitinib (TOF). Paired serum samples from 35 patients with RA were obtained at baseline and 5 months after the initiation of treatment with TOF. The levels of 14-3-3η were measured by JOINT stat 14-3-3η ELISA test kits (Augurex Life Sciences Corp.). The cut-off was defined as 0.19 ng/ml. 14-3-3η positivity was found in 57% of the patients at baseline and in 37% of the patients after 5 months of treatment. Mean ± SD baseline 14-3-3η levels [4.92 ± 8.86 ng/ml] were significantly higher (p < 0.005) than 14-3-3η levels following treatment [1.97 ± 4.59 ng/ml]. A statistically significant improvement (p < 0.001) of CDAI, SDAI, DAS4ESR and DAS4CRP was achieved after 5 month of treatment. Decrease in 14-3-3η protein levels was highly correlated with improvement in DAS4ESR (r = 0.50, p < 0.01), DAS4CRP (r = 0.46, p < 0.01) and ESR (r = 0.36, p = 0.03) and moderately correlated with improvement in CDAI (r = 0.32, p = 0.065) and SDAI (r = 0.33, p = 0.051). The correlation between decrease in 14-3-3η levels and improvement in DAS4ESR remained significant in a partial correlation analysis controlling for ESR (r = 0.39, p = 0.02). This study demonstrates that in RA patients who were treated with TOF, decrease in 14-3-3η levels is correlated with improvement in clinical disease activity parameters. The 14-3-3η protein may serve as an objective biomarker for monitoring of TOF therapy response.
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Proteínas 14-3-3/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Adulto , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
In asthma and chronic obstructive pulmonary disease, some airways of the tracheobronchial tree can be constricted, from moderate narrowing up to closure. Those pathological patterns of obstructions affect the lung ventilation distribution. While some imaging techniques enable visualization and quantification of constrictions in proximal generations, no noninvasive technique exists to provide the airway morphology and obstruction distribution in distal areas. In this work, we propose a method that exploits lung ventilation measures to access positions of airway obstructions (restrictions and closures) in the tree. This identification approach combines a lung ventilation model, in which a 0D tree is strongly coupled to a 3D parenchyma description, along with a machine learning approach. On the basis of synthetic data generated with typical temporal and spatial resolutions as well as reconstruction errors, we obtain very encouraging results of the obstruction distribution, with a detection rate higher than 85%.
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Obstrução das Vias Respiratórias/fisiopatologia , Aprendizado de Máquina , Ventilação Pulmonar/fisiologia , Asma/fisiopatologia , Humanos , Pulmão/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologiaRESUMO
Rabies is a zoonotic viral disease that remains a serious threat to public health worldwide. The rabies lyssavirus (RABV) genome encodes five structural proteins, multifunctional and significant for pathogenicity. The large protein (L) presents well-conserved genomic regions, which may be a good alternative to generate informative datasets for development of new methods for rabies diagnosis. This paper describes the development of a technique for the identification of L protein in several RABV strains from different hosts, demonstrating that MS-based proteomics is a potential method for antigen identification and a good alternative for rabies diagnosis.
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Genoma Viral/genética , Vírus da Raiva/genética , Raiva/diagnóstico , Raiva/virologia , Proteínas Virais/genética , Animais , Antígenos Virais/genética , Proteômica/métodosRESUMO
In spite of numerous clinical studies, there is no consensus on the benefit Heliox mixtures can bring to asthmatic patients in terms of work of breathing and ventilation distribution. In this article we use a 3D finite element mathematical model of the lung to study the impact of asthma on effort and ventilation distribution along with the effect of Heliox compared to air. Lung surface displacement fields extracted from computed tomography medical images are used to prescribe realistic boundary conditions to the model. Asthma is simulated by imposing bronchoconstrictions to some airways of the tracheo-bronchial tree based on statistical laws deduced from the literature. This study illuminates potential mechanisms for patient responsiveness to Heliox when affected by obstructive pulmonary diseases. Responsiveness appears to be function of the pathology severity, as well as its distal position in the tracheo-bronchial tree and geometrical position within the lung.
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Asma/tratamento farmacológico , Asma/fisiopatologia , Hélio/uso terapêutico , Pulmão/fisiopatologia , Modelos Biológicos , Oxigênio/uso terapêutico , Análise de Elementos Finitos , Humanos , Ventilação PulmonarRESUMO
Roughton and Forster (RF) proposed to split the lung diffusing capacity into two contributions describing first, diffusion to red blood cells (RBC), and second, capture by diffusion from the RBC surface and reaction with haemoglobin. Solving the diffusion-reaction equations for simplified capillary-RBC structures, we investigate the RF interpretation. This reveals first that the conventional extrapolation to zero pressure of 1/DLCO on PO2 is not a correct measure of the diffusive component. Consequently the capillary volumes deduced from this extrapolation are erroneous. Secondly, capture mechanisms are different for CO and NO: while DLCO characterizes "volume absorption" in the RBC and is correlated with hematocrit, DLNO quantifies "surface absorption" and provide information about the morphology of the space between the alveolar surface and the RBC surfaces. In conclusion, the RF approach may lead to erroneous physiological interpretations of DLCO; nevertheless, the measurement of DLCO and DLNO bring different types of information that give the potential for a better understanding of respiratory diseases.
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Monóxido de Carbono , Modelos Cardiovasculares , Óxido Nítrico , Capacidade de Difusão Pulmonar , Capilares/fisiologia , Monóxido de Carbono/sangue , Difusão , Eritrócitos/fisiologia , Humanos , Pulmão/irrigação sanguínea , Óxido Nítrico/sangue , Capacidade de Difusão Pulmonar/fisiologiaRESUMO
Legalization of cannabis' medicinal use is rapidly increasing worldwide, raising the need to evaluate medical implications of cannabis. Currently, evidence supports cannabis and its active ingredients as immune-modulating agents, affecting T-cells, B-cells, monocytes, and microglia cells, causing an overall reduction in pro-inflammatory cytokine expression and an increase in anti-inflammatory cytokines. Due to the supporting evidence of cannabinoids as an immune-modulating agent, research focusing on cannabinoids and autoimmunity has emerged. Several clinical trials in multiple sclerosis, inflammatory bowel disease, and fibromyalgia suggest cannabis' effectiveness as an immune-modulator. However, contradicting results and lack of large-scale clinical trials obscure these results. Although lacking clinical research, in vitro and in vivo experiments in rheumatoid arthritis, diabetes type 1, and systemic sclerosis demonstrate a correlation between disease activity and cannabinoids.
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Canabinoides/farmacologia , Canabinoides/uso terapêutico , Sistema Imunitário/efeitos dos fármacos , Maconha Medicinal/farmacologia , Maconha Medicinal/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Linfócitos B/efeitos dos fármacos , Canabinoides/administração & dosagem , Canabinoides/efeitos adversos , Citocinas/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Interações Medicamentosas , Fibromialgia/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Canais Iônicos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Maconha Medicinal/administração & dosagem , Maconha Medicinal/efeitos adversos , Monócitos/efeitos dos fármacos , Esclerose Múltipla/tratamento farmacológico , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Escleroderma Sistêmico/tratamento farmacológico , Linfócitos T/efeitos dos fármacosRESUMO
Rabies is a zoonotic viral disease that remains a serious threat to public health worldwide. The rabies lyssavirus (RABV) genome encodes five structural proteins, multifunctional and significant for pathogenicity. The large protein (L) presents well-conserved genomic regions, which may be a good alternative to generate informative datasets for development of new methods for rabies diagnosis. This paper describes the development of a technique for the identification of L protein in several RABV strains from different hosts, demonstrating that MS-based proteomics is a potential method for antigen identification and a good alternative for rabies diagnosis.
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Leadership positions in global health are greatly skewed toward men; the imbalance is more pronounced in low- and middle-income countries (LMICs). The under-representation of women in leadership is a threat to gender equality, and also impacts the improvement of women's health outcomes globally. In this perspectives piece, we assert that the promotion and retention of women in global health leadership has a ripple effect that can achieve improvement in global health outcomes. We present pragmatic, actionable solutions to promote and retain female global health leaders in this field.
Les positions de dirigeant dans la santé du monde sont largement orientées vers les hommes et ce déséquilibre est encore plus prononcé dans les pays à revenu faible et moyen. La sous-représentation des femmes en termes de dirigeant menace l'égalité des genres et a également un impact sur l'amélioration de l'état de santé des femmes dans le monde. Dans cette perspective, nous affirmons que la promotion et la rétention des femmes au sein du leadership de la santé dans le monde a un effet d'entraînement qui peut aboutir à une amélioration de l'état de santé dans le monde. Nous présentons des solutions pragmatiques et réalisables pour promouvoir et retenir des leaders féminins en matière de santé dans le monde.
Los puestos directivos en materia de salud mundial se asignan de manera desproporcionada a los hombres; este desequilibrio es aun más notorio en los países de ingresos bajos y medianos. La subrepresentación de las mujeres en los cargos de responsabilidad pone en peligro la equidad entre los hombres y las mujeres y tiene además repercusiones en los resultados de salud de las mujeres en el mundo. En el presente artículo de opinión, se sostiene que promover a las mujeres a las funciones directivas relacionadas con la salud mundial y facilitar su permanencia en ellas genera una reacción en cadena que puede dar lugar a mejores resultados de salud a escala mundial. Se proponen soluciones viables y prácticas encaminadas a estimular la presencia de las mujeres en los cargos de responsabilidad en materia de salud mundial y a respaldar su permanencia en esta actividad.
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One of the primary science goals of the Mars Science Laboratory (MSL) Rover, Curiosity, is the detection of organics in Mars rock and regolith. To achieve this, the Curiosity rover includes a robotic sampling system that acquires rock and regolith samples and delivers it to the Sample Analysis at Mars (SAM) instrument on board the rover. In order to provide confidence that any significant organics detection result was Martian and not terrestrial in origin, a requirement was levied on the flight system (i.e., all sources minus the SAM instrument) to impart no more than 36 parts per billion (ppb by weight) of total reduced carbon terrestrial contamination to any sample transferred to the SAM instrument. This very clean level was achieved by a combination of a rigorous contamination control program on the project, and then using the first collected samples for a "dilution cleaning" campaign of the sample chain prior to delivering a sample to the SAM instrument. Direct cleanliness assays of the sample-contacting and other Flight System surfaces during pre-launch processing were used as inputs to determine the number of dilution cleaning samples needed once on Mars, to enable delivery of suitably clean samples to the SAM experiment. Taking into account contaminant redistribution during launch thorough landing of the MSL on Mars, the amount of residue present on the sampling hardware prior to the time of first dilution cleaning sample acquisition was estimated to be 60 ng/cm(2) on exposed outer surfaces of the sampling hardware and 20 ng/cm(2) on internal sample contacting surfaces; residues consisting mainly of aliphatic hydrocarbons and esters. After three dilution cleaning samples, estimated in-sample contamination level for the first regolith sample delivered to the SAM instrument at the Gale Crater "Rocknest" site was bounded at ≤10 ppb total organic carbon. A Project decision to forego ejecting the dilution cleaning sample and instead transfer the first drill-acquired sample at the "John Klein" site to SAM resulted in an estimated level of terrestrial contamination of ≤430 ppb. The estimated terrestrial contamination for portions from the second drill-acquired sample, at Cumberland, was ≤69 ppb; the estimate for a future, third, drilled sample is ≤38 ppb. These levels are comparable in magnitude to the SAM instrument blanks at the nanomole level (as chlorohydrocarbon).
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BACKGROUND: Helium-oxygen has been used for decades as a respiratory therapy conjointly with aerosols. It has also been shown under some conditions to be a means to provide more peripheral, deeper, particle deposition for inhalation therapies. Furthermore, we can also consider deposition along parallel paths that are quite different, especially in a heterogeneous pathological lung. It is in this context that it is hypothesized that helium-oxygen can improve regional deposition, leading to more homogeneous deposition by increasing deposition in ventilation-deficient lung regions. METHODS: Analytical models of inertial impaction, sedimentation, and diffusion are examined to illustrate the importance of gas property values on deposition distribution through both fluid mechanics- and particle mechanics-based mechanisms. Also considered are in vitro results from a bench model for a heterogeneously obstructed lung. In vivo results from three-dimensional (3D) imaging techniques provide visual examples of changes in particle deposition patterns in asthmatics that are further analyzed using computational fluid dynamics (CFD). RESULTS AND CONCLUSIONS: Based on analytical modeling, it is shown that deeper particle deposition is expected when breathing helium-oxygen, as compared with breathing air. A bench model has shown that more homogeneous ventilation distribution is possible breathing helium-oxygen in the presence of heterogeneous obstructions representative of central airway obstructions. 3D imaging of asthmatics has confirmed that aerosol delivery with a helium-oxygen carrier gas results in deeper and more homogeneous deposition distributions. CFD results are consistent with the in vivo imaging and suggest that the mechanics of gas particle interaction are the source of the differences seen in deposition patterns. However, intersubject variability in response to breathing helium-oxygen is expected, and an example of a nonresponder is shown where regional deposition is not significantly changed.
Assuntos
Asma/metabolismo , Hélio/administração & dosagem , Inalação , Pulmão/metabolismo , Compostos de Organotecnécio/administração & dosagem , Compostos de Organotecnécio/metabolismo , Oxigenoterapia , Compostos Radiofarmacêuticos/metabolismo , Albumina Sérica/administração & dosagem , Albumina Sérica/metabolismo , Administração por Inalação , Aerossóis , Asma/diagnóstico por imagem , Asma/fisiopatologia , Estudos de Casos e Controles , Estudos Cross-Over , Gases , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Modelos Biológicos , Tamanho da Partícula , Compostos Radiofarmacêuticos/administração & dosagem , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Rabies is a widespread zoonotic disease responsible for approximately 55,000 human deaths/year. The direct fluorescent antibody test (DFAT) and the mouse inoculation test (MIT) used for rabies diagnosis, have high sensitivity and specificity, but are expensive and time-consuming. These disadvantages and the identification of new strains of the virus encourage the use of new techniques that are rapid, sensitive, specific and economical for the detection and research of the Rabies Virus (RABV). Real-time RT-PCR, phylogeographic analysis, proteomic assays and DNA recombinant technology have been used in research laboratories. Together, these techniques are effective on samples with low virus titers in the study of molecular epidemiology or in the identification of new disease markers, thus improving the performance of biological assays. In this context, modern advances in molecular technology are now beginning to complement more traditional approaches and promise to revolutionize the diagnosis of rabies. This brief review presents some of the recent molecular tools used for RABV analysis, with emphasis on rabies diagnosis and research.
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Biotecnologia/métodos , Imunofluorescência , Epidemiologia Molecular/métodos , Vírus da Raiva , Animais , Biomarcadores/metabolismo , Biotecnologia/tendências , Humanos , Camundongos , Epidemiologia Molecular/tendências , Raiva/diagnóstico , Raiva/epidemiologia , Raiva/genética , Raiva/imunologia , Raiva/metabolismo , Vírus da Raiva/genética , Vírus da Raiva/imunologia , Vírus da Raiva/metabolismoRESUMO
A method is presented for in situ cleaning of spacecraft instruments that analyze planetary soil and rock. We have found that vibrating hardware, used to facilitate powder transport, was also effective at removing contamination. Surfaces can be cleaned below monolayer levels using vibrating surfaces in the presence of mineral powder. Both organic and particulate contamination is efficiently removed. Fine grained regolith from the planetary surface or an organic free reference material may serve as the powder used for cleaning. We present both analytical and experimental results for the contamination transfer fraction and the conditions required to clean the hardware prior to sensitive chemical analysis.
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The aims of this paper are to examine whether early detection programs are needed to assist in detecting and managing chronic kidney disease (CKD). It draws on existing material which indicates that CKD and its precursor risk factors or illnesses such as hypertension, diabetes mellitus and HIV infection are very clearly major challenges faced by health systems worldwide. This paper evaluates whether CKD meets the epidemiological criteria to justify early screening. More compelling evidence is becoming available which indicates that the prevalence of CKD is significant in both developing and developed countries and that CKD can be easily detected and treated with only small changes to existing practice and this may be improved through screening programs. A brief evaluation of the challenges of establishing early detection programs is provided, as well as an examination of the capacity which exists for establishing such programs. It concludes that, despite the lack of randomized studies, these programs appear to provide an opportunity to integrate CKD management with common chronic illnesses and, through this approach, provide clinical and cost-effective management of both CKD and cardiovascular disease.
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Nefropatias/diagnóstico , Doença Crônica , Análise Custo-Benefício , Diagnóstico Precoce , Humanos , Nefropatias/economia , Programas de Rastreamento/métodosRESUMO
OBJECTIVE: To explore grant and country characteristics associated with the performance of tuberculosis (TB) grants supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund), which uses performance-based funding of grants. METHODS: We used Global Fund grant data to compute the average programmatic performance of 108 TB grants in 88 countries. Using stepwise regression models, we examined the correlation of grant performance with a range of grant and country characteristics. RESULTS: Funding duration and funding per estimated smear-positive TB case were positively correlated with grant performance (partial correlations of 0.386-0.416 for the former, 0.200 for the latter). Successful completion of an evaluation of a grant during the second year of funding was linked to higher performance (0.357). Performance was further influenced by the independent organisation hired by the Global Fund to provide ongoing monitoring of the grants (0.197-0.243). Two country-specific factors were significantly correlated with performance: political stability (0.197-0.234) and disease burden (-0.211). DISCUSSION: Successful evaluation that leads to continued funding predicts higher performance of TB grants, even in challenging settings such as weak health services. However, other contextual factors affect grant performance and should be considered when assessing grants to ensure that countries that have a high disease burden and are politically unstable are not penalized.