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1.
PLoS Negl Trop Dis ; 15(1): e0008267, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33406097

RESUMO

African trypanosomiasis (AT) is a neglected disease of both humans and animals caused by Trypanosoma parasites, which are transmitted by obligate hematophagous tsetse flies (Glossina spp.). Knowledge on tsetse fly vertebrate hosts and the influence of tsetse endosymbionts on trypanosome presence, especially in wildlife-human-livestock interfaces, is limited. We identified tsetse species, their blood-meal sources, and correlations between endosymbionts and trypanosome presence in tsetse flies from the trypanosome-endemic Maasai Mara National Reserve (MMNR) in Kenya. Among 1167 tsetse flies (1136 Glossina pallidipes, 31 Glossina swynnertoni) collected from 10 sampling sites, 28 (2.4%) were positive by PCR for trypanosome DNA, most (17/28) being of Trypanosoma vivax species. Blood-meal analyses based on high-resolution melting analysis of vertebrate cytochrome c oxidase 1 and cytochrome b gene PCR products (n = 354) identified humans as the most common vertebrate host (37%), followed by hippopotamus (29.1%), African buffalo (26.3%), elephant (3.39%), and giraffe (0.84%). Flies positive for trypanosome DNA had fed on hippopotamus and buffalo. Tsetse flies were more likely to be positive for trypanosomes if they had the Sodalis glossinidius endosymbiont (P = 0.0002). These findings point to complex interactions of tsetse flies with trypanosomes, endosymbionts, and diverse vertebrate hosts in wildlife ecosystems such as in the MMNR, which should be considered in control programs. These interactions may contribute to the maintenance of tsetse populations and/or persistent circulation of African trypanosomes. Although the African buffalo is a key reservoir of AT, the higher proportion of hippopotamus blood-meals in flies with trypanosome DNA indicates that other wildlife species may be important in AT transmission. No trypanosomes associated with human disease were identified, but the high proportion of human blood-meals identified are indicative of human African trypanosomiasis risk. Our results add to existing data suggesting that Sodalis endosymbionts are associated with increased trypanosome presence in tsetse flies.

2.
Biosci Rep ; 41(1)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33439992

RESUMO

BACKGROUND: Mitochondria-nuclear cross-talk and mitochondrial retrograde regulation are involved in the genesis and development of breast cancer (BC). Therefore, mitochondria can be regarded as a promising target for BC therapeutic strategies. The present study aimed to construct regulatory network and seek the potential biomarkers of BC diagnosis and prognosis as well as the molecular therapeutic targets from the perspective of mitochondrial dysfunction. METHODS: The microarray data of mitochondria-related encoding genes in BC cell lines were downloaded from GEO including GSE128610 and GSE72319. GSE128610 was treated as test set and validation sets consisted of GSE72319 and TCGA tissue samples, intending to identify mitochondria-related differentially expressed genes (mrDEGs). We performed enrichment analysis, PPI network, hub mrDEGs and overall survival analysis and constructed transcription factor (TF)-miRNA-hub mrDEGs network. RESULTS: A total of 23 up-regulated and 71 down-regulated mrDEGs were identified and validated in BC cell lines and tissues. Enrichment analyses indicated that mrDEGs were associated with several cancer-related biological processes. Moreover, 9 hub mrDEGs were identified and validated in BC cell lines and tissues. Finally, 5 hub coregulated mrDEGs, 21 miRNAs and 117 TFs were used to construct TF-miRNA-hub mrDEGs network. MYC associated zinc finger protein (MAZ), heparin binding growth factor (HDGF) and Sp2 transcription factor (SP2) regulated 3 hub mrDEGs. Hsa-mir-21-5p, hsa-mir-1-3p, hsa-mir-218-5p, hsa-mir-26a-5p and hsa-mir-335-5p regulated 2 hub mrDEGs. Overall survival analysis suggested that the up-regulation of fibronectin 1 (FN1), as well as the down-regulation of discoidin domain receptor tyrosine kinase 2 (DDR2) correlated with unfavorable prognosis in BC. CONCLUSION: TF-miRNA-hub mrDEGs had instruction significance for the exploration of BC etiology. The hub mrDEGs such as FN1 and DDR2 were likely to regulate mitochondrial function and be novel biomarkers for BC diagnosis and prognosis as well as the therapeutic targets.

3.
Glob Chang Biol ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33484031

RESUMO

The effects of nitrogen (N) deposition on forests largely depend on its fate after entering the ecosystem. While several studies have addressed the forest fate of N deposition using 15 N tracers, the long-term fate and redistribution of deposited N in tropical forests remains unknown. Here, we applied 15 N tracers to examine the fates of deposited ammonium ( NH 4 + ) and nitrate ( NO 3 - ) separately over 3 years in a primary and a secondary tropical montane forest in southern China. Three months after 15 N tracer addition, over 60% of 15 N was retained in the forests studied. Total ecosystem retention did not change over the study period, but between 3 months and 3 years following deposition 15 N recovery in plants increased from 10% to 19% and 13% to 22% in the primary and secondary forests, respectively, while 15 N recovery in the organic soil declined from 16% to 2% and 9% to 2%. Mineral soil retained 50% and 35% of 15 N in the primary and secondary forests, with retention being stable over time. The total ecosystem retention of the two N forms did not differ significantly, but plants retained more 15 NO 3 - than 15 NH 4 + and the organic soil more 15 NH 4 + than NO 3 - . Mineral soil did not differ in 15 NH 4 + and 15 NO 3 - retention. Compared to temperate forests, proportionally more 15 N was distributed to mineral soil and plants in these tropical forests. Overall, our results suggest that atmospherically deposited NH 4 + and NO 3 - is rapidly lost in the short term (months) but thereafter securely retained within the ecosystem, with retained N becoming redistributed to plants and mineral soil from the organic soil. This long-term N retention may benefit tropical montane forest growth and enhance ecosystem carbon sequestration.

4.
New Phytol ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226653

RESUMO

Conifers are considered to prefer to take up ammonium over nitrate. However, this conclusion is mainly based on hydroponic experiments that separate roots from soils. It remains unclear to what extent mature conifers can use nitrate compared to ammonium under field conditions where both roots and soil microbes compete for N. We conducted an in situ whole mature tree 15 N labelling experiment (15 NH4 + vs. 15 NO3 - ) over 15 days to quantify ammonium and nitrate uptake and assimilation rates in four 40-year-old monoculture coniferous plantations (Pinus koraiensis, Pinus sylvestris, Picea koraiensis and Larix olgensis, respectively). For the whole tree, 15 NO3 - contributed 39% to 90% to total 15 N tracer uptake among four plantations during the study period. At day 3, the 15 NO3 - accounted for 77%, 64%, 62% and 59% by Larix olgensis, Pinus koraiensis, Pinus sylvestris and Picea koraiensis, respectively. Our study indicates that mature coniferous trees assimilated nitrate as efficiently as ammonium from soils even at low soil nitrate concentration, in contrast to the results from hydroponic experiments showing that ammonium uptake dominated over nitrate. This implies that mature conifers can adapt to increasing availability of nitrate in soil, e.g., under the context of globalization of N deposition and global warming.

5.
PLoS One ; 15(8): e0228366, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866142

RESUMO

The role of questing ticks in the epidemiology of tick-borne diseases in Kenya's Maasai Mara National Reserve (MMNR), an ecosystem with intensified human-wildlife-livestock interactions, remains poorly understood. We surveyed the diversity of questing ticks, their blood-meal hosts, and tick-borne pathogens to understand potential effects on human and livestock health. By flagging and hand-picking from vegetation in 25 localities, we collected 1,465 host-seeking ticks, mostly Rhipicephalus and Amblyomma species identified by morphology and molecular analysis. We used PCR with high-resolution melting (HRM) analysis and sequencing to identify Anaplasma, Babesia, Coxiella, Ehrlichia, Rickettsia, and Theileria pathogens and blood-meal remnants in 231 tick pools. We detected blood-meals from humans, wildebeest, and African buffalo in Rh. appendiculatus, goat in Rh. evertsi, sheep in Am. gemma, and cattle in Am. variegatum. Rickettsia africae was detected in Am. gemma (MIR = 3.10) that had fed on sheep and in Am. variegatum (MIR = 250) that had fed on cattle. We found Rickettsia spp. in Am. gemma (MIR = 9.29) and Rh. evertsi (MIR = 200), Anaplasma ovis in Rh. appendiculatus (MIR = 0.89) and Rh. evertsi (MIR = 200), Anaplasma bovis in Rh. appendiculatus (MIR = 0.89), and Theileria parva in Rh. appendiculatus (MIR = 24). No Babesia, Ehrlichia, or Coxiella pathogens were detected. Unexpectedly, species-specific Coxiella sp. endosymbionts were detected in all tick genera (174/231 pools), which may affect tick physiology and vector competence. These findings show that ticks from the MMNR are infected with zoonotic R. africae and unclassified Rickettsia spp., demonstrating risk of African tick-bite fever and other spotted-fever group rickettsioses to locals and visitors. The protozoan pathogens identified may also pose risk to livestock production. The diverse vertebrate blood-meals of questing ticks in this ecosystem including humans, wildlife, and domestic animals, may amplify transmission of tick-borne zoonoses and livestock diseases.


Assuntos
Infestações por Carrapato/epidemiologia , Doenças Transmitidas por Carrapatos/epidemiologia , Carrapatos/patogenicidade , Animais , Animais Selvagens , Babesia , Bovinos , Doenças dos Bovinos/microbiologia , Coxiella , Ecossistema , Ehrlichia , Humanos , Ixodidae/microbiologia , Quênia/epidemiologia , Rhipicephalus , Rickettsia , Ovinos , Theileria , Infestações por Carrapato/veterinária , Doenças Transmitidas por Carrapatos/microbiologia , Carrapatos/parasitologia , Zoonoses
6.
Pathol Res Pract ; 216(9): 153050, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32825936

RESUMO

Methylation, as an epigenetic modification, can affect gene expression and play a role in the occurrence and development of cancer. This research is devoted to discover methylated-differentially expressed genes (MDEGs) in esophageal squamous cell carcinoma (ESCC) and explore special associated pathways. We downloaded GSE51287 methylation profiles and GSE26886 expression profiles from GEO DataSets, and performed a comprehensive bioinformatics analysis. Totally, 19 hypermethylated, lowly expressed genes (Hyper-LGs) were identified, and involved in regulation of cell proliferation, phosphorus metabolic process and protein kinase activity. Meanwhile, 17 hypomethylated, highly expressed genes (Hypo-HGs) were participated in collagen catabolic process, metallopeptidase and cytokine activity. Pathway analysis determined that Hyper-LGs were enriched in arachidonic acid metabolism pathway, while Hypo-HGs were primarily associated with the cytokine-cytokine receptor interaction pathway. IL 6, MMP3, MMP9, SPP1 were identified as hub genes based on the PPI network that combined 7 ranked methods included in cytoHubba, and verification was performed in human tissues. Our integrated analysis identified many novel genetic lesions in ESCC and provides a crucial molecular foundation to improve our understanding of ESCC. Hub genes, including IL 6, MMP3, MMP9 and SPP1, could be considered for use as aberrant methylation-based biomarkers to facilitate the accurate diagnosis and therapy of ESCC.

7.
J Burn Care Res ; 41(1): 113-120, 2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-31600384

RESUMO

The objective of this study is to explore the relevant risk factors of deep venous thrombosis (DVT) in burn patients. A retrospective analysis was conducted for the medical records of 845 hospitalized burn patients from September 2012 to August 2017. Caprini thrombosis risk assessment scale (CTRAS) was employed for evaluating the risks of DVT. Based upon whether or not DVT occurred, they were divided into non-DVT group (n = 830) and DVT group (n = 15). Among 360 (42.7%) patients with high-risk Caprini scores, only 30 patients received color Doppler examination of lower limb veins, and 15 patients were diagnosed as DVT with a diagnostic rate of 1.8%. Caprini scores of non-DVT and DVT groups were 4.30 ± 2.71 and 9.87 ± 1.46 points, respectively. There was statistically significant difference (P < .05). As revealed by stepwise Logistic regression analysis, age, lower limb burn, wound infection, femoral vein catheterization, and long bedriddening time (>40 days) were independent risk factors for DVT. Burn patients are particularly prone to develop DVT. Age, wound infection, femoral vein catheterization, and long bedriddening time (>40 days) are risk factors. Aggressive preventive measures of DVT should be implemented.

8.
J Immunol Res ; 2020: 2450569, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33426088

RESUMO

Gastric mucosal immune microenvironment plays an important role in the occurrence and development of diseases such as inflammation and cancer. In the present study, single-sample gene set enrichment analysis (ssGSEA) was used to evaluate the expression of cytokines and the degree of immune cell infiltration in four different gastric mucosa tissues from normal gastric mucosa, simple gastritis, and atrophic gastritis to gastric cancer. Here, we show the immune microenvironments of these four gastric mucosae were significantly different. From inflammation to gastric cancer, most immunoinflammatory cells showed a downward trend such as central memory CD4 T cell. Instead, several cells showed an upward trend such as macrophage. Additionally, we found some chemokines/interleukins were illustrated to be low expressed (or highly expressed) in precancerous stage and highly expressed (or low expressed) in postcancerous stage, which demonstrated an opposite expression characteristic in pre-/postcancerous stage.

9.
Opt Lett ; 44(18): 4479-4482, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31517911

RESUMO

Multispectral analyzers based on nanostructured plasmonic spectral filters can potentially find a wide range of applications. However, spectral filters based on the widely reported microhole or ring arrays suffer from relatively wide filtering bands, resulting in a relatively low spectral resolution. In this work, we fabricate high-performance spectral filters based on vertically standing micropipes on a silver film. An infrared spectral microscope is used to investigate the properties of these micropipe spectral filters. The results indicate that the micropipe spectral filters have a full width at half-maximum ∼5 times smaller than the microhole filters at the same wavelength. Micropipe spectral filters are expected to significantly improve the spectral resolution of multispectral analyzers.

10.
Front Microbiol ; 10: 1261, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31231345

RESUMO

The link between microbiota and gastric cancer (GC) has attracted widespread attention. However, the phylogenetic profiles of niche-specific microbiota in the tumor microenvironment is still unclear. Here, mucosa-associated microorganisms from 62 pairs of matched GC tissues and adjacent non-cancerous tissues were characterized by 16S rRNA gene sequencing. Functional profiles of the microbiota were predicted using PICRUSt, and a co-occurrence network was constructed to analyze interactions among gastric microbiota. Results demonstrated that mucosa-associated microbiota from cancerous and non-cancerous tissues established micro-ecological systems that differed in composition, structure, interaction networks, and functions. Microbial richness and diversity were increased in cancerous tissues, with the co-occurrence network exhibiting greater complexity compared with that in non-cancerous tissue. The bacterial taxa enriched in the cancer samples were predominantly represented by oral bacteria (such as Peptostreptococcus, Streptococcus, and Fusobacterium), while lactic acid-producing bacteria (such as Lactococcus lactis and Lactobacillus brevis) were more abundant in adjacent non-tumor tissues. Colonization by Helicobacter pylori, which is a GC risk factor, also impacted the structure of the microbiota. Enhanced bacterial purine metabolism, carbohydrate metabolism and denitrification functions were predicted in the cancer associated microbial communities, which was consistent with the increased energy metabolism and concentration of nitrogen-containing compounds in the tumor microenvironment. Furthermore, the microbial co-occurrence networks in cancerous and non-cancerous tissues of GC patients were described for the first time. And differential taxa and functions between the two groups were identified. Changes in the abundance of certain bacterial taxa, especially oral microbiota, may play a role in the maintenance of the local microenvironment, which is associated with the development or progression of GC.

11.
Ecol Appl ; 29(6): e01920, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31058370

RESUMO

The impacts of anthropogenic nitrogen (N) deposition on forest ecosystems depend in large part on its fate. However, our understanding of the fates of different forms of deposited N as well as the redistribution over time within different ecosystems is limited. In this study, we used the 15 N-tracer method to investigate both the short-term (1 week to 3 months) and long-term (1-3 yr) fates of deposited NH4 + or NO3 - by following the recovery of the 15 N in different ecosystem compartments in a larch plantation forest and a mixed forest located in northeastern China. The results showed similar total ecosystem retention for deposited NH4 + and NO3 - , but their distribution within the ecosystems (plants vs. soil) differed distinctly particularly in the short-term, with higher 15 NO3 - recoveries in plants (while lower recoveries in organic layer) than found for 15 NH4 + . The different short-term fate was likely related to the higher mobility of 15 NO3 - than 15 NH4 + in soils instead of plant uptake preferences for NO3 - over NH4 + . In the long-term, differences between N forms became less prevalent but higher recoveries in trees (particularly in the larch forest) of 15 NO3 - than 15 NH4 + tracer persisted, suggesting that incoming NO3 - may contribute more to plant biomass increment and forest carbon sequestration than incoming NH4 + . Differences between the two forests in recoveries were largely driven by a higher 15 N recovery in the organic layer (both N forms) and in trees (for 15 NO3 - ) in the larch forest compared to the mixed forest. This was due to a more abundant organic layer and possibly higher tree N demand in the larch forest than in the mixed forest. Leachate 15 N loss was minor (<1% of the added 15 N) for both N forms and in both forests. Total 15 N recovery averaged 78% in the short-term and decreased to 55% in the long-term but with increasing amount of 15 N label (re)-redistributed into slow turn-over pools (e.g., trees and mineral soil). The different retention dynamics of deposited NH4 + and NO3 - may have implications in environmental policy related to the anthropogenic emissions of the two N forms.


Assuntos
Ecossistema , Florestas , China , Nitrogênio , Solo , Árvores
12.
Sci Rep ; 8(1): 11257, 2018 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-30050145

RESUMO

A miniaturized mid-infrared spectral analyzer will find a wide range of applications as a portable device in non-invasive disease diagnosis, environmental monitoring, food safety and others. In this work, we report an integrated spectral analyzer that can be constructed by using Au subwavelength hole arrays as multispectral filters. The hole arrays were fabricated with CMOS compatible processes. The transmission peak of the subwavelength hole arrays is continuously tuned from 3 µm to 14 µm by linearly increasing the periodicity of the holes in each array. Fourier transform infrared (FTIR) microscopy was applied to spatially map out the transmission of the hole arrays. The results show that each hole array can selectively allow for transmission at a specific wavelength. We further constructed an IR spectral analyzer model based on the microhole multispectral filters to retrieve IR spectral information of two test samples. Our experimental results show that the spectra from the integrated spectral analyzer follow nearly the same pattern of the FTIR spectra of the test samples, proving the potential of the miniaturized spectral analyzer for chemical analysis.

13.
Sci Total Environ ; 633: 1078-1088, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29758860

RESUMO

Denitrification is a major process contributing to the removal of nitrogen (N) from ecosystems, but its rate is difficult to quantify. The natural abundance of isotopes can be used to identify the occurrence of denitrification and has recently been used to quantify denitrification rates at the ecosystem level. However, the technique requires an understanding of the isotopic enrichment factor associated with denitrification, which few studies have investigated in forest soils. Here, soils collected from two tropical and two temperate forests in China were incubated under anaerobic or aerobic laboratory conditions for two weeks to determine the N and oxygen (O) isotope enrichment factors during denitrification. We found that at room temperature (20°C), NO3- was reduced at a rate of 0.17 to 0.35µgNg-1h-1, accompanied by the isotope fractionation of N (15ε) and O (18ε) of 31‰ to 65‰ (48.3±2.0‰ on average) and 11‰ to 39‰ (18.9±1.7‰ on average), respectively. The N isotope effects were, unexpectedly, much higher than reported in the literature for heterotrophic denitrification (typically ranging from 5‰ to 30‰) and in other environmental settings (e.g., groundwater, marine sediments and agricultural soils). In addition, the ratios of Δδ18O:Δδ15N ranged from 0.28 to 0.60 (0.38±0.02 on average), which were lower than the canonical ratios of 0.5 to 1 for denitrification reported in other terrestrial and freshwater systems. We suggest that the isotope effects of denitrification for soils may vary greatly among regions and soil types and that gaseous N losses may have been overestimated for terrestrial ecosystems in previous studies in which lower fractionation factors were applied.

14.
Oecologia ; 174(2): 567-80, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24085637

RESUMO

The foliar stable N isotope ratio (δ(15)N) can provide integrated information on ecosystem N cycling. Here we present the δ(15)N of plant and soil in four remote typical tropical rainforests (one primary and three secondary) of southern China. We aimed to examine if (1) foliar δ(15)N in the study forests is negative, as observed in other tropical and subtropical sites in eastern Asia; (2) variation in δ(15)N among different species is smaller compared to that in many N-limited temperate and boreal ecosystems; and (3) the primary forest is more N rich than the younger secondary forests and therefore is more (15)N enriched. Our results show that foliar δ(15)N ranged from -5.1 to 1.3‰ for 39 collected plant species with different growth strategies and mycorrhizal types, and that for 35 species it was negative. Soil NO3 (-) had low δ(15)N (-11.4 to -3.2‰) and plant NO3 (-) uptake could not explain the negative foliar δ(15)N values (NH4 (+) was dominant in the soil inorganic-N fraction). We suggest that negative values might be caused by isotope fractionation during soil NH4 (+) uptake and mycorrhizal N transfer, and by direct uptake of atmospheric NH3/NH4 (+). The variation in foliar δ(15)N among species (by about 6‰) was smaller than in many N-limited ecosystems, which is typically about or over 10‰. The primary forest had a larger N capital in plants than the secondary forests. Foliar δ(15)N and the enrichment factor (foliar δ(15)N minus soil δ(15)N) were higher in the primary forest than in the secondary forests, albeit differences were small, while there was no consistent pattern in soil δ(15)N between primary and secondary forests.


Assuntos
Ecossistema , Ciclo do Nitrogênio , Isótopos de Nitrogênio/análise , Solo/química , Biomassa , China , Micorrizas , Folhas de Planta/química , Plantas/química , Plantas/microbiologia , Árvores
15.
J Feline Med Surg ; 14(8): 540-4, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22403416

RESUMO

The pharmacokinetics of terbinafine was studied in six healthy fasted cats following a single intravenous and oral administration at a dose of 10 mg/kg and 30 mg/kg, respectively, according to a two-period crossover design. Plasma terbinafine concentrations were determined using a reverse phase liquid chromatographic method. The pharmacokinetic parameters were calculated by non-compartmental analysis with WinNonlin 5.2.1 software. After intravenous administration, the terminal half-life and area under the curve from time 0 to infinity were 10.40 ± 4.56 h, 15.20 ± 3.61 h·µg/ml, respectively. After oral dosing, the mean maximum concentration was 3.22 ± 0.60 µg/ml, reached at 1.33 ± 0.41 h. The terminal half-life, area under the curve from time 0 to infinity and apparent volume of distribution were 8.01 ± 3.46 h, 13.77 ± 4.99 h·µg/ml, 25.63 ± 6.29 l/kg, respectively. The absolute bioavailability of terbinafine hydrochloride tablets after oral administration was 31.00 ± 10.85%. Although bioavailability was low, excellent penetration at the site of infection and low minimum inhibitory concentrations values provided terbinafine with good efficacy against dermatophyte infections.


Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Gatos/sangue , Naftalenos/administração & dosagem , Naftalenos/farmacocinética , Administração Oral , Animais , Área Sob a Curva , Cromatografia Líquida de Alta Pressão/veterinária , Estudos Cross-Over , Esquema de Medicação/veterinária , Meia-Vida , Comprimidos , Terbinafina
16.
Comput Methods Programs Biomed ; 99(2): 208-17, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20398957

RESUMO

The optimisation of ventilatory support is a crucial issue for the management of respiratory failure in critically ill patients, aiming at improving gas exchange while preventing ventilator-induced dysfunction of the respiratory system. Clinicians often rely on their knowledge/experience and regular observation of the patient's response for adjusting the level of respiratory support. Using a similar data-driven decision-making methodology, an adaptive model-based advisory system has been designed for the clinical monitoring and management of mechanically ventilated patients. The hybrid blood gas patient model SOPAVent developed in Part I of this paper and validated against clinical data for a range of patients lung abnormalities is embedded into the advisory system to predict continuously and non-invasively the patient's respiratory response to changes in the ventilator settings. The choice of appropriate ventilator settings involves finding a balance among a selection of fundamentally competing therapeutic decisions. The design approach used here is based on a goal-directed multi-objective optimisation strategy to determine the optimal ventilator settings that effectively restore gas exchange and promote improved patient's clinical conditions. As an initial step to its clinical validation, the advisory system's closed-loop stability and performance have been assessed in a series of simulations scenarios reconstructed from real ICU patients data. The results show that the designed advisory system can generate good ventilator-setting advice under patient state changes and competing ventilator management targets.


Assuntos
Cuidados Críticos , Respiração Artificial/métodos , Adulto , Idoso , Gasometria , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/terapia
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