RESUMO
Porphyry-type molybdenum deposits, many of which are in China, supply most of the World's molybdenum. Of particular importance are the molybdenum deposits located in the Qinling-Dabie region that are responsible for more than half of China's molybdenum production. A feature that distinguishes this suite of deposits from the better-known Climax and Endako sub-types of porphyry molybdenum deposits is their formation from CO2-rich magmatic-hydrothermal fluids. The role of CO2, if any, in the transport of molybdenum by these fluids, however, is poorly understood. We conducted experiments on the partitioning of molybdenum between H2O-CO2, H2O-NaCl, and H2O-NaCl-CO2 fluids and a felsic melt at 850 °C and 100 and 200 MPa. Here we show that the exsolution of separate (immiscible) brine and vapor leads to the very high brine DMo values needed for efficient extraction of Mo from the magmas forming Dabie-type porphyry molybdenum deposits.
RESUMO
Obesity is a leading risk factor of pancreatic ductal adenocarcinoma (PDAC) that contributes to poor disease prognosis and outcomes. Retrospective studies have identified this link, but interactions surrounding obesity and PDAC are still unclear. Research has shifted to contributions of fibrosis (desmoplasia) on malignancy, which involves increased deposition of collagens and other extracellular matrix (ECM) molecules and increased ECM crosslinking, all of which contribute to increased tissue stiffening. However, fibrotic stiffening is underrepresented as a model feature in current PDAC models. Fibrosis is shared between PDAC and obesity, and can be leveraged for in vitro model design, as current animal obesity models of PDAC are limited in their ability to isolate individual components of fibrosis to study cell behavior. In the current study, methacrylated type I collagen (PhotoCol®) was photo-crosslinked to pathological stiffness levels to recapitulate fibrotic ECM stiffening. PANC-1 cells were encapsulated within PhotoCol®, and the tumor-tissue constructs were prepared to represent normal (healthy) (~600 Pa) and pathological (~2000 Pa) tissues. Separately, human mesenchymal stem cells were differentiated into adipocytes representing lean (2D differentiation) and obese fat tissue (3D collagen matrix differentiation), and conditioned media was applied to PANC-1 tumor-tissue constructs. Conditioned media from obese adipocytes showed increased vimentin expression, a hallmark of invasiveness and progression, that was not seen after exposure to media from lean adipocytes or control media. Characterization of the obese adipocyte secretome suggested that some PANC-1 differences may arise from increased interleukin-8 and -10 compared to lean adipocytes. Additionally, high matrix stiffness associated induced an amoeboid morphology in PANC-1 cells that was not present at low stiffness. Amoeboid morphology is an accessory to epithelial-to-mesenchymal transition and is used to navigate complex ECM environments. This plasticity has greater implications for treatment efficacy of metastatic cancers. Overall, this work 1) highlights the importance of investigating PDAC-obesity interactions to study the effects on disease progression and persistence, 2) establishes PhotoCol® as a matrix material that can be leveraged to study amoeboid morphology and invasion in PDAC, and 3) emphasizes the importance of integrating both biophysical and biochemical interactions associated within both pathologies for in vitro PDAC models.
RESUMO
We analyse the network structure of the British salmonid aquaculture industry from the perspective of infectious disease control. We combine for the first time live fish transport (or movement) data covering England and Wales with data covering Scotland and include network layers representing potential transmission by rivers, sea water and local transmission via human or animal vectors in the immediate vicinity of each farm or fishery site. We find that 7.2% of all live fish transports cross the England-Scotland border and network analysis shows that 87% of English and Welsh nodes and 72% of Scottish nodes are reachable from cross-border connections via live fish transports alone. Consequently, from a disease-control perspective, the contact structures of England and Wales and of Scotland should not be considered in isolation. We also show that large epidemics require the live fish movement network and so control strategies targeting movements can be very effective. While there is relatively low risk of widespread epidemics on the live fish transport network alone, the potential risk is substantially amplified by the combined interaction of multiple network layers.
Assuntos
Aquicultura/organização & administração , Doenças dos Peixes/epidemiologia , Salmão , Truta , Animais , Epidemias , Meios de Transporte , Reino UnidoRESUMO
The Asian tiger mosquito Aedes albopictus is able to transmit various pathogens to humans and animals and it has already caused minor outbreaks of dengue and chikungunya in southern Europe. Alarmingly, it is spreading northwards and its eggs have been found in the UK in 2016 and 2017. Climate-driven models can help to analyse whether this originally subtropical species could become established in northern Europe. But so far, these models have not considered the impact of the diurnal temperature range (DTR) experienced by mosquitoes in the field. Here, we describe a dynamical model for the life cycle of Ae. albopictus, taking into account the DTR, rainfall, photoperiod and human population density. We develop a new metric for habitat suitability and drive our model with different climate data sets to analyse the UK's suitability for this species. For now, most of the UK seems to be rather unsuitable, except for some densely populated and high importation risk areas in southeast England. But this picture changes in the next 50 years: future scenarios suggest that Ae. albopictus could become established over almost all of England and Wales, indicating the need for continued mosquito surveillance.
Assuntos
Aedes/fisiologia , Mudança Climática , Ecossistema , Modelos Biológicos , Mosquitos Vetores/fisiologia , Animais , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/transmissão , Dengue/epidemiologia , Dengue/transmissão , Inglaterra/epidemiologia , Humanos , País de Gales/epidemiologiaRESUMO
Four dogs presented for evaluation and treatment of severe pulmonic valve stenosis and underwent stenting of the pulmonic valve annulus using bare-metal balloon-expandable stents. All dogs survived the procedure with immediate reduction of the transpulmonary valve pressure gradient and increase in activity levels. One dog had a stent fracture and migration 1 month after the intervention. This dog underwent a second procedure, in which multiple stents were used to alleviate the obstruction. The stents that were placed at the level of the right ventricular outflow tract fractured within 1 month of the procedure, and the patient died when a third (surgical) approach was attempted. The other three dogs remain alive 54, 42, and 29 months after the procedure. Stent angioplasty may be a viable option for dogs with valvular pulmonic stenosis in which routine balloon valvuloplasty does not provide a successful outcome. Aggressive attempts to diminish RVOT dynamic obstruction with high-dose beta blockade and avoiding deployment of the stent within the RVOT are recommended to prevent stent fracture and migration.
Assuntos
Valvuloplastia com Balão/veterinária , Doenças do Cão/terapia , Estenose da Valva Pulmonar/veterinária , Stents/veterinária , Animais , Valvuloplastia com Balão/métodos , Doenças do Cão/diagnóstico por imagem , Cães , Ecocardiografia/veterinária , Feminino , Masculino , Falha de Prótese , Estenose da Valva Pulmonar/diagnóstico por imagem , Estenose da Valva Pulmonar/terapia , Radiografia Torácica , Stents/efeitos adversosRESUMO
In 2006, bluetongue (BT), a disease of ruminants, was introduced into northern Europe for the first time and more than two thousand farms across five countries were affected. In 2007, BT affected more than 35,000 farms in France and Germany alone. By contrast, the UK outbreak beginning in 2007 was relatively small, with only 135 farms in southeast England affected. We use a model to investigate the effects of three factors on the scale of BT outbreaks in the UK: (1) place of introduction; (2) temperature; and (3) animal movement restrictions. Our results suggest that the UK outbreak could have been much larger had the infection been introduced into the west of England either directly or as a result of the movement of infected animals from southeast England before the first case was detected. The fact that air temperatures in the UK in 2007 were marginally lower than average probably contributed to the UK outbreak being relatively small. Finally, our results indicate that BT movement restrictions are effective at controlling the spread of infection. However, foot-and-mouth disease restrictions in place before the detection and control of BT in 2007 almost certainly helped to limit BT spread prior to its detection.
Assuntos
Bluetongue/epidemiologia , Doenças dos Bovinos/epidemiologia , Surtos de Doenças/veterinária , Febre Aftosa/epidemiologia , Animais , Bovinos , Temperatura Baixa , Fazendas/tendências , Modelos Biológicos , Ovinos , Reino UnidoRESUMO
The right ventricular apex has been the traditional site for lead placement in veterinary patients who require permanent cardiac pacing therapy for atrioventricular block and sick sinus syndrome. Implantation of leads in this location is a straightforward procedure that most veterinary cardiologists perform routinely. Pacing at the right ventricular apex, however, has been demonstrated to have long-term deleterious effects on the left ventricular function in numerous patient populations and animal models. Alternative lead placement sites and pacing system configurations have been developed, and the purpose of this review article is not to review the literature or the decision-making process in selecting a specific pacing system but rather to share the experiences of our group with the use of alternative pacing implantation techniques for veterinary patients in need of permanent cardiac pacing.
Assuntos
Estimulação Cardíaca Artificial/veterinária , Marca-Passo Artificial/veterinária , Animais , Bloqueio Atrioventricular/terapia , Bloqueio Atrioventricular/veterinária , Estimulação Cardíaca Artificial/métodos , Ventrículos do Coração , Síndrome do Nó Sinusal/terapia , Síndrome do Nó Sinusal/veterináriaRESUMO
The ability to accurately determine the metal content of crude oils is necessary for reasons ranging from the need to identify the source of the oils (Ni and V) to removing components that might inhibit catalysis during refining or impact negatively on the environment during hydrocarbon combustion. Here we show that ashing followed by chemical oxidation and acid digestion, coupled with ICP-MS analysis, provides an accurate method for determining the concentration of metals in crude oil. Nickel and vanadium concentrations were measured in certified Ni and V oil standards and in various light, intermediate and heavy crude oils after application of a single vessel ashing-chemical oxidation-acid digestion sample preparation and storing technique. Prior to the ashing, chemical oxidation and acid digestion, an aliquot of the crude oil was placed in a 10 ml Pyrex™ culture tube and capped with quartz wool. The capped culture tubes were then subjected to thermal combustion, followed by chemical oxidation and leaching. The leachates and the aqueous standards were diluted and analyzed for their Ni and V contents using inductively coupled plasma mass spectrometry (ICP-MS). The measured concentrations of Ni in oil standards, reported to contain 1, 100, and 1000 mg kg-1 Ni (±2% error), were 1.1 ± 0.01, 99.8 ± 1.46, and 1025 ± 24 mg kg-1 respectively. The corresponding concentrations of V in these standards, reported to contain 2, 100, and 1000 mg kg-1 V, were measured to be 1.93 ± 0.06, 104 ± 1.3, and 1027 ± 7.5 mg kg-1, respectively. Crude oil samples, A, B, C, D and E, that varied significantly in their composition, and ranged from light to heavy, were determined to contain 5.59 ± 0.32, 4.05 ± 0.03, 6.22 ± 0.22, 33.8 ± 0.7 and 41.6 ± 3.5 mg kg-1 Ni, respectively. Their V contents were determined to be 11.98 ± 0.1, 12.2 ± 0.1, 16.5 ± 0.4, 34.7 ± 0.4, and 104 ± 8.9 mg kg-1, respectively. The results were thus repeatable on average to 4.1% and 2.75% for Ni and V, respectively; the repeatability was worst (â¼8.5%) for crude oil E, a heavy (viscous) oil with a very high asphaltene content (27.2%). This modified single vessel ashing-digestion technique (combustion, chemical oxidation, acid leaching and storing) minimizes contamination and significantly reduces the loss of ash. Our results are repeatable, comparable to, and in some cases superior to those of other methods. The method is applicable to a wide range of crude oil compositions, is very accessible and robust, easy to use, and does not require costly equipment in preparing the samples for analysis by ICP-MS.
RESUMO
There is a solid theoretical basis for expecting climate change to have a considerable effect on the infectious diseases of humans, animals and plants. Vector-borne diseases are the most likely to be affected. It is, however, rare to observe such impacts, as diseases are also influenced by many other drivers, some of which may have stronger effects over shorter time scales than climate change. Nevertheless, there is evidence that our warming climate has already influenced some animal diseases, of which bluetongue is considered a prime example. Bluetongue emerged dramatically in southern Europe after 1998 and in northern Europe from 2006. While the speed and scale of this emergence is a challenge to explain, there is evidence, principally from the development of climate-driven models, that recent climate change has played a significant role. Climate-driven models point to an increase in the risk of bluetongue transmission in Europe in recent decades, caused by an increased suitability of parts of southern Europe for the Afro-tropical biting midge, Culicoides imicola, as well as an increase in the vectorial capacity of indigenous Culicoides vectors in northern Europe. Farm-to-farm transmission models of bluetongue in England and Wales under predicted climatic conditions further suggest that, under high-emission scenarios, the scale of future outbreaks could far exceed those experienced to date. The role of climate change in the developing threat of animal disease is, therefore, likely to be economically and socially costly, unless lower emission targets can be set and followed.
Nombre d'arguments théoriques sérieux confirment l'ampleur des effets du changement climatique sur les maladies infectieuses affectant l'être humain, les animaux et les végétaux. Les maladies à transmission vectorielle sont probablement les plus sujettes à cette influence. Toutefois, il est très rare de pouvoir observer ces effets directement, dans la mesure où d'autres facteurs exercent également une influence sur les maladies, dont certains ont des effets plus marquants et plus rapides que le changement climatique. L'influence du réchauffement climatique sur certaines maladies animales a néanmoins été prouvée ; à ce titre, le cas de la fièvre catarrhale ovine est considéré comme exemplaire. La fièvre catarrhale ovine a fait son apparition en Europe méridionale après 1998, puis en Europe du Nord à partir de 2006. Si la rapidité et l'envergure de cette émergence sont difficiles à expliquer, plusieurs démonstrations, recourant pour la plupart à des modèles axés sur le climat font état du rôle important joué par le changement climatique. Les modèles axés sur le climat font ressortir un risque accru de transmission de la fièvre catarrhale ovine en Europe au cours des dernières décennies, associé, d'une part, à l'adéquation croissante de régions entières de l'Europe méridionale vis-à-vis du moucheron afro-tropical Culicoides imicola et, d'autre part, à l'accroissement de la capacité vectorielle des vecteurs Culicoides autochtones dans le nord de l'Europe. D'après les études basées sur des modèles de transmission de la fièvre catarrhale ovine entre exploitations en Angleterre et au Pays de Galles, dans les conditions climatiques prévisibles, il apparaît qu'en cas de fortes émissions, l'ordre de grandeur des foyers futurs serait considérablement plus élevé que dans les épisodes que nous avons connus jusqu'à présent. Par conséquent, le rôle du changement climatique dans les menaces évolutives de santé animale risque d'avoir un coût économique et social élevé, à moins que des objectifs de réduction de l'émission soient mis en place et fassent l'objet d'un suivi approprié.
Existen sólidas bases teóricas para prever que el cambio climático tendrá efectos considerables en las enfermedades infecciosas que afectan al hombre, los animales o las plantas. Las que más probablemente se verán afectadas son las enfermedades transmitidas por vectores. Sin embargo, rara vez pueden observarse tales efectos, pues hay otros muchos factores que influyen en las enfermedades, algunos de los cuales, a una escala temporal más breve, pueden tener una influencia más marcada que el cambio climático. Aun así, hay pruebas de que el clima, en pleno proceso de calentamiento, ya ha incidido en algunas enfermedades animales, de las que la lengua azul se considera un perfecto ejemplo. La lengua azul hizo una espectacular aparición en el sur de Europa a partir de 1998, y en la Europa septentrional a partir de 2006. Aunque resulta difícil explicar la velocidad y las proporciones de tal aparición, existen sólidos indicios, obtenidos principalmente de la elaboración de modelos regidos por variantes climáticas, de que el reciente cambio climático ha cumplido una función importante. Estos modelos apuntan a un incremento del riesgo de transmisión de la lengua azul en Europa en los últimos decenios, lo que se explica por las condiciones más propicias al jején afrotropical, Culicoides imicola, que ofrecen ciertas partes de Europa meridional y por un aumento de la capacidad vectorial de los Culicoides autóctonos del norte de Europa. Los modelos de transmisión de la lengua azul entre explotaciones agropecuarias de Inglaterra y Gales en las condiciones climáticas predichas indican además que, en la hipótesis de un elevado volumen de emisiones, los futuros brotes pueden revestir una escala muy superior a cuanto hemos conocido hasta ahora. Por consiguiente, a menos que se logre establecer y cumplir objetivos de emisiones menos cuantiosas, es probable que el cambio climático resulte económica y socialmente gravoso por su incidencia en la creciente amenaza que plantean las enfermedades animales.
Assuntos
Vírus Bluetongue/fisiologia , Bluetongue/epidemiologia , Ceratopogonidae/fisiologia , Mudança Climática , Insetos Vetores/virologia , Animais , Bluetongue/transmissão , Ceratopogonidae/virologia , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/veterinária , Doenças Transmissíveis Emergentes/virologia , Surtos de Doenças/veterinária , Europa (Continente)/epidemiologia , Humanos , Insetos Vetores/fisiologia , OvinosRESUMO
BACKGROUND: Acute pulmonary embolism (PE) can worsen quality of life due to persistent dyspnea or exercise intolerance. OBJECTIVE: Test if tenecteplase increases the probability of a favorable composite patient-oriented outcome after submassive PE. METHODS: Normotensive patients with PE and right ventricular (RV) strain (by echocardiography or biomarkers) were enrolled from eight hospitals. All patients received low-molecular-weight heparin followed by random assignment to either a single weight-based bolus of tenecteplase or placebo, administered in a double-blinded fashion. The primary composite outcome included: (i) death, circulatory shock, intubation or major bleeding within 5 days or (ii) recurrent PE, poor functional capacity (RV dysfunction with either dyspnea at rest or exercise intolerance) or an SF36(®) Physical Component Summary (PCS) score < 30 at 90-day follow-up. RESULTS: Eighty-three patients were randomized; 40 to tenecteplase and 43 to placebo. The trial was terminated prematurely. Within 5 days, adverse outcomes occurred in three placebo-treated patients (death in one and intubation in two) and one tenecteplase-treated patient (fatal intracranial hemorrhage). At 90 days, adverse outcomes occurred in 13 unique placebo-treated patients and five unique tenecteplase-treated patients Thus, 16 (37%) placebo-treated and six (15%) tenecteplase-treated patients had at least one adverse outcome (exact two-sided P = 0.017). CONCLUSIONS: Treatment of patients with submassive pulmonary embolism with tenecteplase was associated with increased probability of a favorable composite outcome.
Assuntos
Fibrinolíticos/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Dispneia/complicações , Feminino , Hemorragia/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Estudos Prospectivos , Embolia Pulmonar/mortalidade , Qualidade de Vida , Choque/complicações , Tenecteplase , Resultado do TratamentoRESUMO
Human Campylobacter jejuni infection can result in an asymptomatic carrier state, watery or bloody diarrhea, bacteremia, meningitis, or autoimmune neurological sequelae. Infection outcomes of C57BL/6 IL-10(-/-) mice orally infected with twenty-two phylogenetically diverse C. jejuni strains were evaluated to correlate colonization and disease phenotypes with genetic composition of the strains. Variation between strains was observed in colonization, timing of development of clinical signs, and occurrence of enteric lesions. Five pathotypes of C. jejuni in C57BL/6 IL-10(-/-) mice were delineated: little or no colonization, colonization without disease, colonization with enteritis, colonization with hemorrhagic enteritis, and colonization with neurological signs with or without enteritis. Virulence gene content of ten sequenced strains was compared in silico; virulence gene content of twelve additional strains was compared using a C. jejuni pan-genome microarray. Neither total nor virulence gene content predicted pathotype; nor was pathotype correlated with multilocus sequence type. Each strain was unique with regard to absences of known virulence-related loci and/or possession of point mutations and indels, including phase variation, in virulence-related genes. An experiment in C. jejuni 11168-infected germ-free mice showed that expression levels of ninety open reading frames (ORFs) were significantly up- or down-regulated in the mouse cecum at least two-fold compared to in vitro growth. Genomic content of these ninety C. jejuni 11168 ORFs was significantly correlated with the capacity to colonize and cause enteritis in C57BL/6 IL-10(-/-) mice. Differences in gene expression levels and patterns are thus an important determinant of pathotype in C. jejuni strains in this mouse model.
Assuntos
Infecções por Campylobacter/imunologia , Infecções por Campylobacter/patologia , Campylobacter jejuni/imunologia , Campylobacter jejuni/patogenicidade , Interleucina-10/deficiência , Fases de Leitura Aberta , Fatores de Virulência/genética , Animais , Infecções por Campylobacter/microbiologia , Campylobacter jejuni/classificação , Campylobacter jejuni/genética , Feminino , Expressão Gênica , Genótipo , Interleucina-10/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Tipagem de Sequências Multilocus , Virulência , Fatores de Virulência/metabolismoRESUMO
Poly vinyl chloride (PVC) infusion equipment contains substantial amounts of the plasticiser di(2-ethylhexyl) phthalate (DEHP). We determined the amount of DEHP leached from Mediplus Dual TIVA(®) Infusion sets, into lipid and non-lipid infusates. Two propofol admixtures (Diprivan(®) 1%, Propoven(®) 1%), Intralipid(®) 10% and 0.9% saline were evaluated as infusates. Solutions were infused through TIVA sets at 12 ml.h(-1) for 6 h at 24, 32 and 37 °C. In addition, TIVA sets were filled with 2 ml infusates, sealed and incubated at 24 and 37 °C for 6 h. Di(2-ethylhexyl) phthalate was detected in all lipid infusates after dynamic infusion and static contact, and in 0.9% saline after dynamic infusion at 37 °C. At 32 and 37 °C, the quantity of di(2-ethylhexyl) phthalate leaching into the lipid infusates may exceed the recommended maximum exposure amount set by the European Union for DEHP of 20-48 µg.kg(-1) day(-1) if lipid based infusates are used for sedation or intravenous feeding of infants or neonates.
Assuntos
Dietilexilftalato/química , Contaminação de Equipamentos , Emulsões Gordurosas Intravenosas/química , Temperatura Alta , Infusões Intravenosas/instrumentação , Cloreto de Polivinila/química , Análise de Variância , Cromatografia , Contaminação de Medicamentos , Emulsões/química , Concentração Máxima Permitida , Fosfolipídeos/química , Plastificantes/química , Propofol , Cloreto de Sódio , Óleo de Soja/química , TemperaturaRESUMO
BACKGROUND: Increasing the threshold to define a positive D-dimer could reduce unnecessary computed tomographic pulmonary angiography (CTPA) for a suspected pulmonary embolism (PE) but might increase rates of a missed PE and missed pneumonia, the most common non-thromboembolic diagnosis seen on CTPA. OBJECTIVE: Measure the effect of doubling the standard D-dimer threshold for 'PE unlikely' Revised Geneva (RGS) or Wells' scores on the exclusion rate, frequency and size of a missed PE and missed pneumonia. METHODS: Patients evaluated for a suspected PE with 64-channel CTPA were prospectively enrolled from emergency departments (EDs) and inpatient units of four hospitals. Pretest probability data were collected in real time and the D-dimer was measured in a central laboratory. Criterion standard was CPTA interpretation by two independent radiologists combined with clinical outcome at 30 days. RESULTS: Of 678 patients enrolled, 126 (19%) were PE+ and 93 (14%) had pneumonia. Use of either Wells' ≤ 4 or RGS ≤ 6 produced similar results. For example, with RGS ≤ 6 and standard threshold (< 500 ng mL(-1)), D-dimer was negative in 110/678 (16%), and 4/110 were PE+ (posterior probability 3.8%) and 9/110 (8.2%) had pneumonia. With RGS ≤ 6 and a threshold < 1000 ng mL(-1) , D-dimer was negative in 208/678 (31%) and 11/208 (5.3%) were PE+, but 10/11 missed PEs were subsegmental and none had concomitant DVT. Pneumonia was found in 12/208 (5.4%) with RGS ≤ 6 and D-dimer < 1000 ng mL(-1). CONCLUSIONS: Doubling the threshold for a positive D-dimer with a PE unlikely pretest probability could reduce CTPA scanning with a slightly increased risk of missed isolated subsegmental PE, and no increase in rate of missed pneumonia.
Assuntos
Erros de Diagnóstico/prevenção & controle , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Pneumonia/diagnóstico , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico , Tomografia Computadorizada por Raios X , Procedimentos Desnecessários , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/sangue , Pneumonia/diagnóstico por imagem , Valor Preditivo dos Testes , Probabilidade , Prognóstico , Estudos Prospectivos , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico por imagem , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados UnidosAssuntos
Transtorno Conversivo/terapia , Doenças Faríngeas/terapia , Fonoterapia/métodos , Fala/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno Conversivo/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Faríngeas/fisiopatologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Although well established in clinical practice, both propofol and midazolam have limitations. New hypnotics with different and potentially superior pharmacokinetics and pharmacodynamics are under development. These include the benzodiazepine receptor agonists CNS7056 and JM-1232 (-), the etomidate-based methoxycarbonyl-etomidate and carboetomidate, the propofol-related structures PF0713 and fospropofol, and THRX-918661/AZD3043. The basic pharmacology and the initial anaesthesia studies for each of these agents are reviewed. Several of the agents (CNS7056, THRX-918661/AZD3043, and fospropofol) have reached the stage of clinical trials. To be successful, novel compounds need to establish clear clinical advantages over existing agents and where possible the new agents are discussed in this context. Computer-controlled drug administration offers the ability to automatically implement infusion schemes too complex for manual use and the possibility of linking patient monitoring to administration to enhance patient safety.
Assuntos
Anestesia Intravenosa/tendências , Anestésicos Intravenosos/farmacologia , Anestesia Intravenosa/métodos , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/química , Sistemas de Liberação de Medicamentos , Etomidato/análogos & derivados , Etomidato/farmacologia , Agonistas de Receptores de GABA-A , HumanosRESUMO
A study of air-borne microbial biodiversity over an isolated scientific research station on an ice-shelf in continental Antarctica was undertaken to establish the potential source of microbial colonists. The study aimed to assess: (1) whether microorganisms were likely to have a local (research station) or distant (marine or terrestrial) origin, (2) the effect of changes in sea ice extent on microbial biodiversity and (3) the potential human impact on the environment. Air samples were taken above Halley Research Station during the austral summer and austral winter over a 2-week period. Overall, a low microbial biodiversity was detected, which included many sequence replicates. No significant patterns were detected in the aerial biodiversity between the austral summer and the austral winter. In common with other environmental studies, particularly in the polar regions, many of the sequences obtained were from as yet uncultivated organisms. Very few marine sequences were detected irrespective of the distance to open water, and around one-third of sequences detected were similar to those identified in human studies, though both of these might reflect prevailing wind conditions. The detected aerial microorganisms were markedly different from those obtained in earlier studies over the Antarctic Peninsula in the maritime Antarctic.
Assuntos
Microbiologia do Ar , Biodiversidade , Regiões Antárticas , Sequência de Bases , Primers do DNA/genética , Humanos , Gelo , Dados de Sequência Molecular , RNA Bacteriano/genética , RNA Bacteriano/isolamento & purificação , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/isolamento & purificação , Estações do Ano , Tempo (Meteorologia)Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Neoplasias Colorretais/cirurgia , Fator VIII/administração & dosagem , Hemofilia A/complicações , Neoplasias Hepáticas/cirurgia , Idoso , Neoplasias Colorretais/tratamento farmacológico , Fator VIII/antagonistas & inibidores , Hemofilia A/tratamento farmacológico , Hemofilia A/cirurgia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: As a result of its very low water solubility, propofol is generally presented as a lipid-based formulation with well-characterized limitations. METHODS: Propofol (99.7%) was added directly to an aqueous solution of poly(N-vinyl-2-pyrrolidone)-block-poly(D,L-lactide)copolymers (PVP-PLA) block copolymers and stirred in order to obtain a clear solution. This formulation was filtered sterile and then lyophilized to its solid form Propofol-PM (propofol polymeric micelle) which reconstitutes to a propofol 1%w/v (10 mg ml(-1)) clear aqueous solution of 30-60 nm propofol-containing micelles. Population pharmacokinetic data from whole blood and plasma were obtained by administering reconstituted Propofol-PM formulations and a 1% oil in water formulation, Diprivan to male Sprague-Dawley rats (n = 40) at a dose of 10 mg kg(-1). Preliminary recovery data were obtained from a further small study. RESULTS: The pharmacokinetics were best described using a two-compartment mamillary population model, which incorporated sample matrix (blood or plasma) and propofol formulation (Diprivan) or Propofol-PM) as covariates. Sample matrix was applied to all structural model parameters as a dichotomous covariate. An influence of propofol formulation was observed for all parameters (excluding distributional clearance) but only when plasma was used for propofol quantification. In this preliminary pharmacodynamic study, there was no statistically significant difference in the timing of the recovery endpoints between the Propofol-PM formulation and Diprivan groups. CONCLUSIONS: Propofol-PM formulations produce anaesthesia in rats. Whole blood pharmacokinetics of Propofol-PM did not differ from those observed with Diprivan.