RESUMO
BACKGROUND: Obesity is a growing health problem worldwide. Morbid obesity has been associated with significant barriers to effective thoracic cage compression during cardiopulmonary resuscitation. OBJECTIVE: The BariBoard™ purports to improve adequacy of chest compressions in morbidly obese patients. This study uses a simulation model to evaluate this. METHODS: This was a prospective blinded randomised-controlled crossover pilot trial using a simulation model of obesity. Participants, recruited from hospital departments and prehospital services, performed 2 minutes of continuous compressions on mannequins modified to emulate a morbidly obese patient. Participants were randomised by coin toss to a sequence of either control/intervention or intervention/control, with the BariBoard™ in the intervention arm. Accelerometers measured chest wall movement during compressions. The primary endpoint was a composite measure of compression adequacy (rate, depth, and recoil). Secondary endpoints comprised the individual components of the composite outcome, as both dichotomous outcomes (adequate vs. inadequate) and continuous variables. All endpoints were adjusted for potential confounders. RESULTS: Of 205 participants recruited, 201 were analysed. There was a significant difference in the primary outcome between the control and intervention arms (13.4% vs. 4.5%, respectively, p = 0.001) and between the control and intervention arms for the secondary endpoints of adequate compression depth (31.3% vs. 15.9%, p < 0.001) and recoil (63.7% vs. 41.3%, p < 0.001). After adjustment for confounders and interactions, there was no difference in overall efficacy (odds ratio: 0.62, 95% confidence interval: 0.20-1.90, p = 0.40). CONCLUSION: This pilot study describes the successful assessment of a device using a simulation model of obesity. Within these constraints and after adjustment for confounders, use of the BariBoard ™ did not improve efficacy of chest compressions.
Assuntos
Reanimação Cardiopulmonar , Obesidade Mórbida , Humanos , Projetos Piloto , Obesidade Mórbida/terapia , Estudos Prospectivos , ManequinsRESUMO
Each year, large quantities of waste cooking oils are produced worldwide which are currently reused mainly for biodiesel production. Since lipids have a very high potential for biomethanation, the production of biogas is a possible alternative for the recycling of edible used oils. The digestion of fats is hindered mainly by their hydrophobicity, which implies a biphasic system with problems of floating and foaming of the oily materials, and by the accumulation of long-chain fatty acids, which are toxic to microbial consortia. The objectives of this review were to highlight the recycling potential of waste cooking oil to biogas production and to facilitate the application of the technology by identifying solutions to overcome biological and engineering limits to its diffusion. Particular attention was paid to the microbial populations involved, to the process factors whose control is important to improve the digestion of fats such as lipid concentration, pH, temperature, and agitation, and to technological solutions whose application also aims to improve digestion, such as pretreatment of raw materials and co-digestion of fats with other feedstocks. The state of the art in reactor designs suitable for lipid digestion was also examined.
Assuntos
Biocombustíveis , Culinária , Óleos/metabolismo , Eliminação de Resíduos Líquidos , Anaerobiose , Biocombustíveis/microbiologia , Reatores Biológicos/microbiologia , Gorduras/metabolismo , Lipídeos/análise , Lipídeos/química , Redes e Vias Metabólicas , Metano/biossíntese , Óleos/químicaRESUMO
Recycling of waste cooking oil greatly reduces the environmental impact of its disposal. As fats can give rise to high methane yields, the use of waste cooking oil for biogas production seems a promising solution. The aim of this work was to test the anaerobic digestion performances of waste cooking oil in co-digestion with pig slurry, the fat degradation dynamics and the relationships between digestion performances and pig slurry compositional properties. In laboratory batch, static, mesophilic anaerobic conditions, the treatments waste cooking oil in synthetic hydration medium (WCO + HM) and waste cooking oil in pig slurry (WCO + PS) were compared. Pig slurry alone was included for reference. Co-digestion with pig slurry greatly shortened the lag phase (by 58.3%) and increased the overall methane production per reactor (by 15.5%). An increase in emulsion stability of the biphasic system and an earlier triglyceride degradation were associated with the better anaerobic digestion performances in the WCO + PS reactors. A negative, however reversible, effect of palmitic acid accumulation on methane production was also observed. These results are encouraging for the application of co-digestion of waste cooking oil and pig slurry in agricultural biogas plants.
Assuntos
Anaerobiose , Resíduos Industriais , Metano/metabolismo , Óleos/metabolismo , Águas Residuárias/microbiologia , Animais , Biotransformação , SuínosRESUMO
Mutations in the chloroquine resistance transporter (PfCRT) are the primary determinant of chloroquine (CQ) resistance in the malaria parasite Plasmodium falciparum. A number of distinct PfCRT haplotypes, containing between 4 and 10 mutations, have given rise to CQ resistance in different parts of the world. Here we present a detailed molecular analysis of the number of mutations (and the order of addition) required to confer CQ transport activity upon the PfCRT as well as a kinetic characterization of diverse forms of PfCRT. We measured the ability of more than 100 variants of PfCRT to transport CQ when expressed at the surface of Xenopus laevis oocytes. Multiple mutational pathways led to saturable CQ transport via PfCRT, but these could be separated into two main lineages. Moreover, the attainment of full activity followed a rigid process in which mutations had to be added in a specific order to avoid reductions in CQ transport activity. A minimum of two mutations sufficed for (low) CQ transport activity, and as few as four conferred full activity. The finding that diverse PfCRT variants are all limited in their capacity to transport CQ suggests that resistance could be overcome by reoptimizing the CQ dosage.
Assuntos
Cloroquina/metabolismo , Resistência a Medicamentos , Malária Falciparum/metabolismo , Proteínas de Membrana Transportadoras/genética , Mutação/genética , Parasitos/metabolismo , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/genética , Sequência de Aminoácidos , Animais , Transporte Biológico , Haplótipos , Cinética , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/metabolismo , Dados de Sequência Molecular , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Oócitos , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade , Transfecção , Xenopus laevisRESUMO
Microbial pathogens use environmental cues to trigger the developmental events needed to infect mammalian hosts or transmit to disease vectors. The parasites causing African sleeping sickness respond to citrate or cis-aconitate (CCA) to initiate life-cycle development when transmitted to their tsetse fly vector. This requires hypersensitization of the parasites to CCA by exposure to low temperature, conditions encountered after tsetse fly feeding at dusk or dawn. Here we identify a carboxylate-transporter family, PAD (proteins associated with differentiation), required for perception of this differentiation signal. Consistent with predictions for the response of trypanosomes to CCA, PAD proteins are expressed on the surface of the transmission-competent 'stumpy-form' parasites in the bloodstream, and at least one member is thermoregulated, showing elevated expression and surface access at low temperature. Moreover, RNA-interference-mediated ablation of PAD expression diminishes CCA-induced differentiation and eliminates CCA hypersensitivity under cold-shock conditions. As well as being molecular transducers of the differentiation signal in these parasites, PAD proteins provide the first example of a surface marker able to discriminate the transmission stage of trypanosomes in their mammalian host.
Assuntos
Proteínas de Protozoários/metabolismo , Trypanosoma brucei brucei/crescimento & desenvolvimento , Trypanosoma brucei brucei/metabolismo , Ácido Aconítico/análogos & derivados , Ácido Aconítico/metabolismo , Animais , Diferenciação Celular , Ácido Cítrico/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Insetos Vetores/parasitologia , Oócitos , Proteínas de Protozoários/genética , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA de Protozoário/genética , RNA de Protozoário/metabolismo , Temperatura , Trypanosoma brucei brucei/citologia , Trypanosoma brucei brucei/genética , Tripanossomíase Africana/parasitologia , Moscas Tsé-Tsé/parasitologia , Xenopus laevisRESUMO
Large amounts of livestock manure solids are expected to become available in the near future due to the development of technologies for the separation of the solid fraction of animal effluents. The charring of manure solids for biochar (BC) production represents an opportunity for recycling organic matter (OM) of high nutrient value. The objectives of this study were to evaluate the suitability of BC from swine solids (SS) to improve soil fertility through nutrient supply and decomposition of the OM incorporated into soil and to verify a possible interaction effect on soil nutrient dynamics between digestate application and soil amendment with BC. We monitored at laboratory scale the soil mineral nitrogen (N) and Olsen phosphorus (P) content, and the cumulative carbon dioxide (CO-C) release in treatments with or without a supply of digestate obtained from a biogas plant. The experiment was performed in laboratory microcosms during a 3-mo incubation period. Compared treatments were soil amendments with SS, BC from SS, wood chip, BC from wood chip, and soil with no amendment, each of them with and without incorporation of digestate (10 treatments in total). Soil N levels were unaffected by BC amendments and only increased temporarily when digestate was applied to soil amended with SS or BC from SS. For the same N content, the BC from SS supplied much more P than the nontreated OM. The amount of cumulative CO-C released from soil with BC with or without digestate did not differ from that in the unamended control soil and was lower than that in the soils with noncharred amendments. Soil amendment with BC from SS does not modify soil N availability, whereas it increases the content of P available for crops and reduces the release of CO-C from digestate applied to soil for agricultural purposes.
Assuntos
Dióxido de Carbono , Solo , Agricultura , Animais , Esterco , Nitrogênio , SuínosRESUMO
The aim of this research has been to assess the effect of the dietary protein level on piglet growth and post-weaning diarrhea (PWD) incidence. Piglet fecal microbiota and feces composition were also assessed. The experiment was carried out on 144 weaned piglets (Duroc × Large White; 72 piglets per treatment) and lasted from weaning (at 25 days of age) until the end of the post-weaning phase (at 95 days). Two dietary protein levels were compared: high (HP; 17.5% crude protein on average, during the experiment) and low (LP; 15.5% on average). Lower (p < 0.01) average daily gain and feed conversion ratio were observed in LP piglets in the first growth phase. However, at the end of the post-weaning period, the growth parameters were not significantly different in the two diets. Diarrhea scores were lower in piglets fed LP diets than in piglets fed HP diets (28.6% of the total vs. 71.4% in the HP piglets). Fibrobacteres, Proteobacteria, and Spirochaetes were more abundant in the feces of the piglets fed LP diets. Feces nitrogen content was lower in piglets fed LP diets. In conclusion, low protein levels in the diet can reduce the incidence of PWD while only marginally affecting growth parameters.
RESUMO
In the era of personalized medicine, where transition from organ-based to individualized genetic diagnosis takes place, the tailoring of treatment in cancer becomes increasingly important. This is particularly true for high-grade, advanced FIGO stage serous adenocarcinomas of the ovary (OC), fallopian tube (TC), and peritoneum (PC), which are currently all treated identically. We analyzed three independent patient cohorts using histopathologically classified diagnosis and various molecular approaches (transcriptomics, immunohistochemistry, next-generation sequencing, fluorescent and chromogenic in situ hybridization). Using multivariate Cox regression model, we found that PC is more aggressive compared with advanced-stage OC independent of residual disease as shown by an earlier relapse-free survival in two large cohorts (HR: 2.63, CI: 1.59-4.37, P < 0.001, and HR: 1.66, CI: 1.04-2.63, P < 0.033). In line with these findings, transcriptomic data revealed differentially expressed gene signatures identifying PC as high stromal response tumors. The third independent cohort (n = 4054) showed a distinction between these cancer types for markers suggested to be predictive for chemotherapy drug response. Our findings add additional evidence that ovarian and peritoneal cancers are epidemiologically and molecularly distinct diseases. Moreover, our data also suggest consideration of the tumor-sampling site for future diagnosis and treatment decisions.
Assuntos
Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imunidade/genética , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/imunologia , Células Estromais/patologia , Resultado do TratamentoRESUMO
The intraerythrocytic malaria parasite relies primarily on glycolysis to fuel its rapid growth and reproduction. The major byproduct of this metabolism, lactic acid, is extruded into the external medium. In this study, we show that the human malaria parasite Plasmodium falciparum expresses at its surface a member of the microbial formate-nitrite transporter family (PfFNT), which, when expressed in Xenopus laevis oocytes, transports both formate and lactate. The transport characteristics of PfFNT in oocytes (pH-dependence, inhibitor-sensitivity and kinetics) are similar to those of the transport of lactate and formate across the plasma membrane of mature asexual-stage P. falciparum trophozoites, consistent with PfFNT playing a major role in the efflux of lactate and hence in the energy metabolism of the intraerythrocytic parasite.
Assuntos
Formiatos/metabolismo , Ácido Láctico/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Animais , Glicólise , Oócitos/metabolismo , Xenopus laevisRESUMO
Within the framework of an interregional project in the Emilia Romagna region of northern Italy, the coupled MACRO-SOILN model was chosen to estimate soil protective capacity against pollutants. The aim of our study was to evaluate the model to better identify key parameters and processes that influence N losses in agricultural soils. Nitrate N content was monitored in soil under corn (Zea mays L.) fertilized with urea and/or pig slurry, in two field experiments performed on four different soils: a Fienili clay, a Barco-like silt, a Sant'Omobono silt loam, and a La Boaria silty clay soil. Measurements were compared with model predictions. For all soils, nitrate content was underestimated on average by 24 to 88% at lower N rates; it was overestimated by 1 to 104% at higher N rates. The root mean square error (RMSE) was equal to 81.1%. Simulation of crop N uptake and soil water flow, estimation of the ammonia losses at pig slurry spreading, and N transformation parameter setting were considered as possible error sources. The calibration of crop N uptake gave rise to good model efficiency index values. The RMSE for the simulation of soil water content varied between 9.8 and 20.2%. A more accurate setting of the ammonia losses and of the feces transformation parameter values could allow the RMSE for the simulation of soil nitrate content to be reduced by no more than 10 to 15%. It is possible for the model not to include the simulation of processes that could have relevant effects on the soil N dynamics.
Assuntos
Modelos Teóricos , Nitrogênio/metabolismo , Poluentes do Solo/metabolismo , Agricultura , Animais , Esterco , Medição de Risco , Suínos , Ureia , Eliminação de Resíduos LíquidosRESUMO
The emergence and spread of chloroquine-resistant Plasmodium falciparum malaria parasites has been a disaster for world health. Resistance is conferred by mutations in the Chloroquine Resistance Transporter (PfCRT), an integral membrane protein localized to the parasite's internal digestive vacuole. These mutations result in a marked reduction in the accumulation of chloroquine (CQ) by the parasite. However, the mechanism by which this occurs is unclear. We expressed both wild-type and resistant forms of PfCRT at the surface of Xenopus laevis oocytes. The resistant form of PfCRT transported CQ, whereas the wild-type protein did not. CQ transport via the mutant PfCRT was inhibited by CQ analogs and by the resistance-reverser verapamil. Thus, CQ resistance is due to direct transport of the drug via mutant PfCRT.
Assuntos
Antimaláricos/metabolismo , Cloroquina/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Sequência de Aminoácidos , Animais , Antimaláricos/farmacologia , Transporte Biológico/efeitos dos fármacos , Membrana Celular/metabolismo , Cloroquina/análogos & derivados , Cloroquina/farmacologia , Resistência a Medicamentos , Concentração de Íons de Hidrogênio , Potenciais da Membrana , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/genética , Dados de Sequência Molecular , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Mutação , Oligopeptídeos/farmacologia , Oócitos/metabolismo , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Verapamil/farmacologia , Xenopus laevisRESUMO
To survive, the human malaria parasite Plasmodium falciparum must acquire pantothenate (vitamin B5) from the external medium. Pantothenol (provitamin B5) inhibits parasite growth by competing with pantothenate for pantothenate kinase, the first enzyme in the coenzyme A biosynthesis pathway. In this study we investigated pantothenol uptake by P. falciparum and in doing so gained insights into the regulation of the parasite's coenzyme A biosynthesis pathway. Pantothenol was shown to enter P. falciparum-infected erythrocytes via two routes, the furosemide-inhibited "new permeation pathways" induced by the parasite in the infected erythrocyte membrane (the sole access route for pantothenate) and a second, furosemide-insensitive pathway. Having entered the erythrocyte, pantothenol is taken up by the intracellular parasite via a mechanism showing functional characteristics distinct from those of the parasite's pantothenate uptake mechanism. On reaching the parasite cytosol, pantothenol is phosphorylated and thereby trapped by pantothenate kinase, shown here to be under feedback inhibition control by coenzyme A. Furosemide reduced this inherent feedback inhibition by competing with coenzyme A for binding to pantothenate kinase, thereby increasing pantothenol uptake.