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Potentially modifiable respiratory variables contributing to outcome in ICU patients without ARDS: a secondary analysis of PRoVENT
No full textAbstract
Background
The majority of critically ill patients do not suffer from acute respiratory distress syndrome (ARDS). To improve the treatment of these patients, we aimed to identify potentially modifiable factors associated with outcome of these patients.
Methods
The PRoVENT was an international, multicenter, prospective cohort study of consecutive patients under invasive mechanical ventilatory support. A predefined secondary analysis was to examine factors associated with mortality. The primary endpoint was all-cause in-hospital mortality.
Results
935 Patients were included. In-hospital mortality was 21%. Compared to patients who died, patients who survived had a lower risk of ARDS according to the ‘Lung Injury Prediction Score’ and received lower maximum airway pressure (Pmax), driving pressure (ΔP), positive end-expiratory pressure, and FiO2 levels. Tidal volume size was similar between the groups. Higher Pmax was a potentially modifiable ventilatory variable associated with in-hospital mortality in multivariable analyses. ΔP was not independently associated with in-hospital mortality, but reliable values for ΔP were available for 343 patients only. Non-modifiable factors associated with in-hospital mortality were older age, presence of immunosuppression, higher non-pulmonary sequential organ failure assessment scores, lower pulse oximetry readings, higher heart rates, and functional dependence.
Conclusions
Higher Pmax was independently associated with higher in-hospital mortality in mechanically ventilated critically ill patients under mechanical ventilatory support for reasons other than ARDS.
Trial Registration ClinicalTrials.gov (NCT01868321)
Antiplasmodial and trypanocidal activity of violacein and deoxyviolacein produced from synthetic operons
No full textAbstract\ud
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Background\ud
Violacein is a deep violet compound that is produced by a number of bacterial species. It is synthesized from tryptophan by a pathway that involves the sequential action of 5 different enzymes (encoded by genes vioA to vioE). Violacein has antibacterial, antiparasitic, and antiviral activities, and also has the potential of inducing apoptosis in certain cancer cells.\ud
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Results\ud
Here, we describe the construction of a series of plasmids harboring the complete or partial violacein biosynthesis operon and their use to enable production of violacein and deoxyviolacein in E.coli. We performed in vitro assays to determine the biological activity of these compounds against Plasmodium, Trypanosoma, and mammalian cells. We found that, while deoxyviolacein has a lower activity against parasites than violacein, its toxicity to mammalian cells is insignificant compared to that of violacein.\ud
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Conclusions\ud
We constructed E. coli strains capable of producing biologically active violacein and related compounds, and propose that deoxyviolacein might be a useful starting compound for the development of antiparasite drugs.This study has supported by Sao Paulo Research Foundation (FAPESP) Grant 2012/16525-2 to FTMC and Grant 2015/03553-6 to EB, contract from the European Commission under the FP7 Collaborative Program, UNICELLSYS to SGO, UK Biotechnology and Biological Sciences Research Council (BB/F008228/1) to SGO and The Bill and Melinda Gates foundation (OPP1087646 to EB and SGO). TAT was supported by a CNPq fellowship and FTMC is a CNPq research fellow level 1C
Engineering xylose metabolism for production of polyhydroxybutyrate in the non-model bacterium Burkholderia sacchari
No full textAbstract\ud
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Background\ud
Despite its ability to grow and produce high-value molecules using renewable carbon sources, two main factors must be improved to use Burkholderia sacchari as a chassis for bioproduction at an industrial scale: first, the lack of molecular tools to engineer this organism and second, the inherently slow growth rate and poly-3-hydroxybutyrate [P(3HB)] production using xylose. In this work, we have addressed both factors.\ud
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Results\ud
First, we adapted a set of BglBrick plasmids and showed tunable expression in B. sacchari. Finally, we assessed growth rate and P(3HB) production through overexpression of xylose transporters, catabolic or regulatory genes. Overexpression of xylR significantly improved growth rate (55.5% improvement), polymer yield (77.27% improvement), and resulted in 71% of cell dry weight as P(3HB).\ud
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Conclusions\ud
These values are unprecedented for P(3HB) accumulation using xylose as a sole carbon source and highlight the importance of precise expression control for improving utilization of hemicellulosic sugars in B. sacchari.This work was supported by the São Paulo Research Foundation (FAPESP\ud
2010/51989-4 and 2016/00842-0, granted to L.F.S.), National Council for Sci‑\ud
entifc and Technological Development CNPq-Brazil (454371/2014-4, granted\ud
to L.F.S.; 140321/2017-9 E.R.O.F. Ph.D. Scholarship) and Universidad Técnica de\ud
Ambato, Ecuador, through Department of Research and Development (DIDE)\ud
(Projects 0932-CU-P-2016 and 2456-CU-P-2017, granted to C.B.O.). Thanks\ud
to the National Council for Science Technology and Innovation of Ecuador\ud
(SENESCYT) for the Ph.D. fellowship granted to L.P.G
Point-of-care ultrasonography in Brazilian intensive care units: a national survey
No full textAbstract
Background
Point-of-care ultrasonography (POCUS) has recently become a useful tool that intensivists are incorporating into clinical practice. However, the incorporation of ultrasonography in critical care in developing countries is not straightforward.
Methods
Our objective was to investigate current practice and education regarding POCUS among Brazilian intensivists. A national survey was administered to Brazilian intensivists using an electronic questionnaire. Questions were selected by the Delphi method and assessed topics included organizational issues, POCUS technique and training patterns, machine availability, and main applications of POCUS in daily practice.
Results
Of 1533 intensivists who received the questionnaire, 322 responded from all of Brazil’s regions. Two hundred and five (63.8%) reported having access to an ultrasound machine dedicated to the intensive care unit (ICU); however, this was more likely in university hospitals than in non-university hospitals (80.6 vs. 59.6%; risk ratio [RR] = 1.35 [1.16–1.58], p = 0.002). The main applications of POCUS were ultrasound-guided central vein catheterization (49.4%) and bedside echocardiographic assessment (33.9%). Two hundred and fifty-eight (80.0%) reported having at least one POCUS-trained intensivist in their staff (trained units). Trained units were more likely to perform routine ultrasound-guided jugular vein catheterization than non-trained units (38.6 vs. 16.4%; RR = 2.35 [1.31–4.23], p = 0.001). The proportion of POCUS-trained intensivists and availability of a dedicated ultrasound machine were both independently associated with performing ultrasound-guided jugular vein catheterization (RR = 1.91 [1.32–2.77], p = 0.001) and (RR = 2.20 [1.26–3.29], p = 0.005), respectively.
Conclusions
A significant proportion of Brazilian ICUs had at least one intensivist with POCUS capability in their staff. Although ultrasound-guided central vein catheterization constitutes the main application of POCUS, adherence to guideline recommendations is still suboptimal
Prevalence and risk factors associated with ectoparasite infestation of buffaloes in an Amazonian ecosystem
No full textAbstract\ud
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Background\ud
The water buffalo (Bubalus bubalis) is well adapted in some regions of the Amazon. Of all Brazilian states, Pará contains the largest number of this species, with 510,000 animals, approximately 38% of the Brazilian buffaloes. Despite the socioeconomic importance of bubaline farming in the northern region, little is known about the prevalence of ectoparasites that affect buffalo herds. This study aimed to identify the species of buffalo ectoparasites in the municipality of Santarém, Pará, and to determine possible risk factors related to ectoparasitic infestation. A cross-sectional study was conducted by sampling 60 rural properties and 621 buffaloes for ectoparasites. When present, ectoparasites were collected for subsequent identification.\ud
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Results\ud
Of all the animals sampled, 18.5% (115/621) had ectoparasites, 7.8% (49/621) had ticks from the species Rhipicephalus (Boophilus) microplus and Amblyomma cajennense (sensu stricto), and 11.5% (72/621) had lice from the Haematopinus tuberculatus species. Six animals presented mixed infestations of ticks and lice. Among the sampled farms, 51.6% (31/60) had at least one animal infested with ectoparasites. The prevalence of ticks and lice on buffaloes was associated with the farm site, with higher prevalence (11.5% ticks, 15.4% lice) in animals at dry land (OR: 16.7 and 5.7 for ticks and lice, respectively) when compared with floodplains (0.5% ticks, 3.4% lice). Buffaloes aged 1 to 12 months had more ticks whereas buffaloes aged 13 to 24 months had more lice (P < 0.05).\ud
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Conclusions\ud
Buffaloes bred in the municipality of Santarém present different levels of tick and lice infestation according to the direct influence of Amazon ecosystem characteristics. The floodplain environment, widely used for buffalo farming, contributes toward minor ectoparasite infestations in these animals.This research was funded by National Council for Scientific and\ud
Technological Development - CNPq, Brazil (Grant # 486318/2013-3)
Lipodystrophy diagnosis in people living with HIV/AIDS: prediction and validation of sex-specific anthropometric models
No full textAbstract\ud
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Background\ud
Body composition alterations, or lipodystrophy, can lead to serious health problems in people living with HIV/AIDS (PLWHA). The objectives of this study are to predict and validate sex-specific anthropometric predictive models for the diagnosis of lipodystrophy in PLWHA.\ud
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Methods\ud
A cross-sectional design was employed to recruit 106 PLWHA (men = 65 and women = 41) in Brazil during 2013–2014. They were evaluated using dual-energy X-ray absorptiometry, and 19 regions of body perimeters and 6 skinfold thicknesses were taken. Sex-specific predictive models for lipodystrophy diagnosis were developed through stepwise linear regression analysis. Cross-validations using predicted residual error sum of squares was performed to validate each predictive model.\ud
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Results\ud
Results support the use of anthropometry for the diagnosis of lipodystrophy in men and women living with HIV/AIDS. A high power of determination with a small degree of error was observed for lipodystrophy diagnosis for men in model six (r2 = 0.77, SEE = 0.14, r2PRESS = 0.73, SEE PRESS = 0.15), that included ratio of skinfold thickness of subscapular to medial calf, skinfold thickness of thigh, body circumference of waist, formal education years, time of diagnosis to HIV months, and type of combined antiretroviral therapy (cART) (with protease inhibitor “WI/PI = 1” or without protease inhibitor “WO/PI = 0”); and model five for women (r2 = 0.78, SEE = 0.11, r2PRESS = 0.71, SEE PRESS = 0.12), that included skinfold thickness of thigh, skinfold thickness of subscapular, time of exposure to cART months, body circumference of chest, and race (Asian) (“Yes” for Asian race = 1; “No” = 0).\ud
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Conclusions\ud
The proposed anthropometric models advance the field of public health by facilitating early diagnosis and better management of lipodystrophy, a serious adverse health effect experienced by PLWHA.This study was supported by the National Council for Scientific and\ud
Technological Development (CNPq, Brazil) grant number 141536/2016–0 and\ud
the Brazilian Federal Agency for Support and Evaluation of Graduate\ud
Education (CAPES, Brazil) grant number 88881.132032/2016–01
Spatial and temporal relationships between human and canine visceral leishmaniases in Belo Horizonte, Minas Gerais, 2006–2013
No full textAbstract\ud
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Background\ud
Visceral leishmaniasis is a serious public health problem in Brazil, and control of this disease constitutes a major challenge. The purpose of this study was to assess the existing spatial and temporal relationships between cases of canine visceral leishmaniasis (CanL) and human visceral leishmaniasis (HVL) recorded in Belo Horizonte, State of Minas Gerais, from 2006 to 2013.\ud
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Methods\ud
Data provided by the Belo Horizonte Health Services regarding the disease control routine were analyzed in order to perform a retrospective observational and ecological study. Information regarding the incidence rate of HVL and canine seroprevalence was examined in relation to control actions performed atthe 148 coverage areas of healthcare centers for the period between 2006 and 2013. A time series analysis was performed using the Gretl 1.9.12 software followed by the assessment of the existing increasing or declining trend and seasonality in the occurrence of CanL and HVL. Autoregressive integrated moving average (ARIMA) models were adjusted, intervention analysis was performed, vector autoregressive models were developed, and Granger causality was used for testing temporal relationships between variables. The hot spot analysis tool was used for cluster identification through Getis-OrdGi statistics. The ArcGis for desktop 10.2.1 software was used for spatial analysis.\ud
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Results\ud
We identified 866 HVL cases in Belo Horizonte between 2006 and 2013. The mean proportion of canine seroprevalence (PCP) was 7.31% and the mean proportion of monitored hosts (PMH) was 6.73%.HVL and PCP showed a decreasing trend, while PMH increased over time (P<0.05). Vector Autoregressive (VAR) and Granger analysis showed a temporal relation between CanL and HVL cases. Maps illustrating the spatial distribution of cases and obituaries of HVL and CanL cases also showed an apparent association between the occurrence of leishmaniasis in humans, and data about canine cases recorded in the previous years.\ud
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Conclusions\ud
Cases of HVL were preceded by PMH and PCP cases. Similar results were observed for intraspecific cases (i.e. between PCP and other canine cases and between HVL and other HVL cases), which indicated the existence of favorable environmental conditions for the transmission and spread of L. infantum in Belo Horizonte.This study was funded by the Conselho Nacional de Desenvolvimento\ud
Científico e Tecnológico (CNPq) that granted research scholarship to\ud
CMBMR
Association of adiponectin with cognitive function precedes overt diabetes in the Brazilian Longitudinal Study of Adult Health: ELSA
No full textAbstract\ud
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Background\ud
Adiponectin is an insulin-sensitizer adipocytokine endowed with neuroprotective actions. Whether adiponectin regulates neuronal functioning toward delaying cognitive decline independently of the glucose metabolism disturbance has been poorly explored. This study evaluated if the performance in cognitive tests was associated with adiponectin levels prior the development of type 2 diabetes in middle-aged individuals.\ud
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Methods\ud
A sample of 938 non-diabetic participants of ELSA had their cognitive function assessed by the CERAD delayed word recall test, the verbal fluency test and the trail making test. Stepwise multiple linear regression using forward selection had the response to cognitive tests as the dependent variable and adiponectin as the independent variable of main interest, adjusted for glucose tolerance status and confounders.\ud
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Results\ud
Mean age was 45.7 ± 4.9 years, 54.5% were women, 43.0% had high education level, 59.3% weight excess and 70.0% prediabetes. In crude model, only the delayed recall memory was associated with adiponectin levels. In an initial regression model, delayed recall memory remained independently associated with adiponectin levels and prediabetes. After complete adjustments, adiponectin but not prediabetes maintained independently associated with delayed recall memory (β 0.067; 95% CI 0.006–0.234; p = 0.040). On the other hand, learning memory showed to be associated with prediabetes (β 0.71 95% CI 0.17; 1.24; p = 0.009) but not with adiponectin.\ud
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Conclusions\ud
The association of memory with adiponectin in middle-aged individuals, prior overt diabetes, suggests that this adipocytokine could anticipate cognitive impairmentρ detection, when preventive strategies could be more effectively implemented. The usefulness of adiponectin to identify increased risk for cognitive dysfunction before advanced age needs to be prospectively investigated in ELSA cohort.The current work was supported by grant from the São Paulo Research\ud
Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo—\ud
FAPESP—Protocol 2009/15041-9), São Paulo, SP, Brazil and from the National\ud
Postdoctoral Program (PNPD-CAPES), Brazil. The ELSA-Brasil baseline study\ud
was supported by the Brazilian Ministry of Health (Science and Technology\ud
Department) and the Brazilian Ministry of Science and Technology and CNPqNational\ud
Research Council) (Grants # 01 06 0010.00 RS, 01 06 0212.00 BA, 01 06\ud
0300.00 ES, 01 06 0278.00 MG, 01 06 0115.00 SP, 01 06 0071.00 RJ)
Antiproliferative and proapoptotic effects of DODAC/synthetic phosphoethanolamine on hepatocellular carcinoma cells
No full textAbstract\ud
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Background\ud
Current studies have demonstrated that DODAC/PHO-S (Dioctadecyldimethylammonium Chloride/Synthetic phosphoethanolamine) liposomes induces cytotoxicity in Hepa1c1c7 and B16F10 murine tumor cells, with a higher proportion than PHO-S. Therefore, our aim was to evaluate the potential of DODAC/PHO-S to elucidate the mechanism of cell death whereby the liposomes induces cytotoxicity in hepatocellular carcinoma Hepa1c1c7, compared to the PHO-S alone.\ud
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Methods\ud
Liposomes (DODAC/PHO-S) were prepared by ultrasonication. The cell cycle phases, protein expression and types of cell’s death on Hepa1c1c7 were analyzed by flow cytometry. The internalisation of liposomes, mitochondrial electrical potential and lysosomal stability were also evaluated by confocal laser scanning microscopy.\ud
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Results\ud
After treatment with liposomes (DODAC/PHO-S), we observed a significant increase in the population of Hepa1c1c7 cells experiencing cell cycle arrest in the S and G2/M phases, and this treatment was significantly more effective to promote cell death by apoptosis. There also was a decrease in the mitochondrial electrical potential; changes in the lysosomes; nuclear fragmentation and catastrophic changes in Hepa1c1c7 cells. The liposomes additionally promoted increases in the expression of DR4 receptor, caspases 3 and 8, cytochrome c, p53, p21, p27 and Bax. There was also a decrease in the expression of Bcl-2, cyclin D1, CD90 and CD44 proteins.\ud
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Conclusion\ud
The overall results showed that DODAC/PHO-S liposomes were more effective than PHO-S alone, in promoting cytotoxicity Hepa1c1c7 tumor cells, activating the intrinsic and extrinsic pathways of programmed cell death.This study was funded by Sao Paulo Research Foundation, process number:\ud
2015/02950–1
Repellent efficacy of a new combination of fipronil and permethrin against Lutzomyia longipalpis
No full textAbstract\ud
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Background\ud
Lutzomyia longipalpis is the main vector of Leishmania infantum, the agent of canine and human visceral leishmaniosis in the Americas. Considering that the dog is the main domestic host of the parasite, repellent treatment is a measure that might contribute to the prevention of canine visceral leishmaniosis. The repellent efficacy of a single treatment of a new spot-on topical combination of fipronil and permethrin (Frontline Tri-Act®, Merial, now part of Boehringer-Ingelheim) to repel Lu. longipalpis sand flies was evaluated.\ud
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Methods\ud
Sixteen healthy Beagle dogs, eight females and eight males, weighing 8.4–14.4 kg, and 2 to 4 years-old were included in the study. Animals were blocked on decreasing body weight and randomly allocated within the blocks to one of two treatment groups of eight animals each. Dogs in Group 1 were untreated and Dogs in Group 2 were treated with a combination containing 67.6 mg/ml fipronil + 504.8 mg/ml permethrin (Frontline Tri-Act®) once on Day 0. Sand fly exposures were performed on Days 1, 14, 21 and 30 with Lu. longipalpis female sand flies. After 65 (± 15 min), sand flies were assessed for engorgement status.\ud
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Results\ud
The percent repellency of the treated group compared to the untreated control group was 95.7, 94.3, 81.7 and 72.2% for exposure days 1, 14, 21 and 30, respectively. The two treatment groups were significantly different for all exposure days (P ≤ 0.016 for days 1, 14, 21 and 30). No adverse reactions were observed during the study.\ud
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Conclusion\ud
A single topical administration of a new combination of fipronil and permethrin demonstrated a significant repellent effect against Lu. longipalpis bites as soon as it was applied on the dogs and its repellent efficacy lasted for 4 weeks with results greater than 80% for 3 weeks. The results suggest that in endemic areas the regular application of the new combination could contribute to protect dogs from Leishmania infection and therefore serve as an additional tool for the prevention of canine visceral leishmaniosis.The work reported herein was funded by Boehringer Ingelheim GA, US