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Neurally Adjusted Ventilatory Assist (NAVA) or Pressure Support Ventilation (PSV) during spontaneous breathing trials in critically ill patients: a crossover trial
No full textAbstract\ud
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Background\ud
Neurally Adjusted Ventilatory Assist (NAVA) is a proportional ventilatory mode that uses the electrical activity of the diaphragm (EAdi) to offer ventilatory assistance in proportion to patient effort. NAVA has been increasingly used for critically ill patients, but it has not been evaluated during spontaneous breathing trials (SBT). We designed a pilot trial to assess the feasibility of using NAVA during SBTs, and to compare the breathing pattern and patient-ventilator asynchrony of NAVA with Pressure Support (PSV) during SBTs.\ud
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Methods\ud
We conducted a crossover trial in the ICU of a university hospital in Brazil and included mechanically ventilated patients considered ready to undergo an SBT on the day of the study. Patients underwent two SBTs in randomized order: 30 min in PSV of 5 cmH2O or NAVA titrated to generate equivalent peak airway pressure (Paw), with a positive end-expiratory pressure of 5 cmH2O. The ICU team, blinded to ventilatory mode, evaluated whether patients passed each SBT. We captured flow, Paw and electrical activity of the diaphragm (EAdi) from the ventilator and used it to calculate respiratory rate (RR), tidal volume (VT), and EAdi. Detection of asynchrony events used waveform analysis and we calculated the asynchrony index as the number of asynchrony events divided by the number of neural cycles.\ud
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Results\ud
We included 20 patients in the study. All patients passed the SBT in PSV, and three failed the SBT in NAVA. Five patients were reintubated and the extubation failure rate was 25% (95% CI 9–49%). Respiratory parameters were similar in the two modes: VT = 6.1 (5.5–6.5) mL/Kg in NAVA vs. 5.5 (4.8–6.1) mL/Kg in PSV (p = 0.076) and RR = 27 (17–30) rpm in NAVA vs. 26 (20–30) rpm in PSV, p = 0.55. NAVA reduced AI, with a median of 11.5% (4.2–19.7) compared to 24.3% (6.3–34.3) in PSV (p = 0.033).\ud
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Conclusions\ud
NAVA reduces patient-ventilator asynchrony index and generates a respiratory pattern similar to PSV during SBTs. Patients considered ready for mechanical ventilation liberation may be submitted to an SBT in NAVA using the same objective criteria used for SBTs in PSV.\ud
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Trial registration\ud
ClinicalTrials.gov (\ud
NCT01337271\ud
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), registered April 12, 2011.This study was funded by FAPESP (project number 2011/20225–1), a government funding agency in Brazil. The grants are provided to cover the costs of the study, not for salary or personal benefit for any of the authors. The funding agency had no participation in study design, data interpretation, or manuscript writing
A systematic comparative evaluation of biclustering techniques
No full textAbstract\ud
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Background\ud
Biclustering techniques are capable of simultaneously clustering rows and columns of a data matrix. These techniques became very popular for the analysis of gene expression data, since a gene can take part of multiple biological pathways which in turn can be active only under specific experimental conditions. Several biclustering algorithms have been developed in the past recent years. In order to provide guidance regarding their choice, a few comparative studies were conducted and reported in the literature. In these studies, however, the performances of the methods were evaluated through external measures that have more recently been shown to have undesirable properties. Furthermore, they considered a limited number of algorithms and datasets.\ud
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Results\ud
We conducted a broader comparative study involving seventeen algorithms, which were run on three synthetic data collections and two real data collections with a more representative number of datasets. For the experiments with synthetic data, five different experimental scenarios were studied: different levels of noise, different numbers of implanted biclusters, different levels of symmetric bicluster overlap, different levels of asymmetric bicluster overlap and different bicluster sizes, for which the results were assessed with more suitable external measures. For the experiments with real datasets, the results were assessed by gene set enrichment and clustering accuracy.\ud
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Conclusions\ud
We observed that each algorithm achieved satisfactory results in part of the biclustering tasks in which they were investigated. The choice of the best algorithm for some application thus depends on the task at hand and the types of patterns that one wants to detect.This research was funded by the São Paulo Research Foundation (FAPESP)\ud
(grants #2014/08840-0 and #2013/18698-4) and the Brazilian National\ud
Research Council (CNPq) (grant #304137/2013-8)
Nephroselmis viridis (Nephroselmidophyceae, Chlorophyta), a new record for the Atlantic Ocean based on molecular phylogeny and ultrastructure
No full textAbstract\ud
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Nephroselmis is composed by unicellular nanoplanktonic organisms, occurring predominantly in marine environments. Currently, 14 species are taxonomically accepted. Nephroselmis viridis was described in 2011 and strains were isolated from Indic and Pacific Oceans. Since then, it was not recorded in other places. A strain was isolated from coastal waters of Brazil by micropipetting and washing, and cultivated in f/2 medium for morphological observations (light, confocal, SEM and TEM) and molecular phylogeny inferences (maximum likelihood and Bayesian). The cells are asymmetrical, have two unequal flagella, one cup-shaped chloroplast with an eyespot, and a large starch covered pyrenoid. Chloroplast thylakoids intrude into the pyrenoid and organic scales cover all cell body and flagella. Molecular phylogeny (18S rRNA) clustered the isolated strain with other Nephroselmis viridis sequences, and the species is the sister of the N. olivacea, the type species of the genus. Morphology and molecular phylogeny corroborate the strain identification, and it is the first time this species is recorded in Brazil and in the Atlantic Ocean.FAPESP (2010/50 187-1), and CNPq scholarships to KMFL (163070/2013-0),\ud
and to MCO (301491/2013-5)
Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a paradoxical manifestation associated with deficiency of antigen-specific regulatory T-cells?
No full textAbstract\ud
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Background\ud
Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients. This case report illustrates the challenges in diagnosing and managing leprosy and its reactional states in a transplant recipient.\ud
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Case presentation\ud
A 53-year-old man presented 34 months after a successful renal transplantation a borderline-tuberculoid leprosy with signs of mild type 1 upgrading reaction (T1R). Cutaneous manifestations were atypical, and diagnosis was only made when granulomatous neuritis was found in a cutaneous biopsy. He was successfully treated with the WHO recommended multidrug therapy (MDT: rifampicin, dapsone and clofazimine). However he developed a severe T1R immediately after completion of the MDT but no signs of allograft rejection. T1R results from flare-ups of the host T-helper-1 cell-mediated immune response against Mycobacterium leprae antigens in patients with immunologically unstable, borderline forms of leprosy and has been considered an inflammatory syndrome in many aspects similar to the immune reconstitution inflammatory syndromes (IRS). The T1R was successfully treated by increasing the prednisone dose without modifying the other immunosuppressive drugs used for preventing allograft rejection. Immunological study revealed that the patient had a profound depletion of both in situ and circulating regulatory T-cells and lack of expansion of the Tregs upon M. leprae stimulation compared to T1R leprosy patients without iatrogenic immunosuppression.\ud
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Conclusions\ud
Our case report highlights that leprosy, especially in the transplant setting, requires a high degree of clinical suspicion and the contribution of histopathology. It also suggests that the development of upgrading inflammatory syndromes such as T1R can occur despite the sustained immunosuppressors regimen for preventing graft rejection. Our hypothesis is that the well-known deleterious effects of these immunosuppressors on pathogen-induced regulatory T-cells contributed to the immunedysregulation and development T1R.This work was supported by Fundação de Amparo a Pesquisa do Estado de\ud
São Paulo grants #2014/15286–0 and 2016/08730-6. APV received a PhD\ud
fellowship from Coordenadoria de Aperfeiçoamento de Pessoal de Ensino\ud
Superior. GB and AJSD are senior researchers from Conselho Nacional de\ud
Pesquisa Científica
Comparative transcriptome analysis reveals different strategies for degradation of steam-exploded sugarcane bagasse by Aspergillus niger and Trichoderma reesei
No full textAbstract\ud
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Background\ud
Second generation (2G) ethanol is produced by breaking down lignocellulosic biomass into fermentable sugars. In Brazil, sugarcane bagasse has been proposed as the lignocellulosic residue for this biofuel production. The enzymatic cocktails for the degradation of biomass-derived polysaccharides are mostly produced by fungi, such as Aspergillus niger and Trichoderma reesei. However, it is not yet fully understood how these microorganisms degrade plant biomass. In order to identify transcriptomic changes during steam-exploded bagasse (SEB) breakdown, we conducted a RNA-seq comparative transcriptome profiling of both fungi growing on SEB as carbon source.\ud
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Results\ud
Particular attention was focused on CAZymes, sugar transporters, transcription factors (TFs) and other proteins related to lignocellulose degradation. Although genes coding for the main enzymes involved in biomass deconstruction were expressed by both fungal strains since the beginning of the growth in SEB, significant differences were found in their expression profiles. The expression of these enzymes is mainly regulated at the transcription level, and A. niger and T. reesei also showed differences in TFs content and in their expression. Several sugar transporters that were induced in both fungal strains could be new players on biomass degradation besides their role in sugar uptake. Interestingly, our findings revealed that in both strains several genes that code for proteins of unknown function and pro-oxidant, antioxidant, and detoxification enzymes were induced during growth in SEB as carbon source, but their specific roles on lignocellulose degradation remain to be elucidated.\ud
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Conclusions\ud
This is the first report of a time-course experiment monitoring the degradation of pretreated bagasse by two important fungi using the RNA-seq technology. It was possible to identify a set of genes that might be applied in several biotechnology fields. The data suggest that these two microorganisms employ different strategies for biomass breakdown. This knowledge can be exploited for the rational design of enzymatic cocktails and 2G ethanol production improvement.This work received funding from Fundação de Amparo à Pesquisa do Estado\ud
de São Paulo (FAPESP, 2011/08945-9 and 2014/11766-7). GPB, CCS, ESS, RACS\ud
hold FAPESP scholarships (2015/08222-8, 2013/09541-4, 2014/11733-1, 2014/\ud
15799-7, respectively). GKZ and RMMTSD were granted scholarships from\ud
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and\ud
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)\ud
scholarships, respectively
Adherence to precautions for preventing the transmission of microorganisms in primary health care: a qualitative study
No full textAbstract\ud
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Background\ud
Health care associated infections (HAIs) are a source of concern worldwide. No health service in any country can be considered HAI risk-free. However, there is scarcity of data on the risks to which both patients and health workers are subject in non-hospital settings. The aim of this study was to identify issues that determine the adherence of professionals to precautions for preventing transmission of microorganisms in primary health care.\ud
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Method\ud
This was a qualitative study, using focus groups of primary health care staff, in two Brazilian municipalities. The data were analysed using content analysis.\ud
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Results\ud
Four focus groups were conducted with 20 professionals (11 community health workers, 5 nursing assistants and 4 nurses), and the analysed content was organized into four thematic categories. These categories are: low risk perception, weaknesses in knowledge, insufficient in-service training and infrastructure limitations.\ud
Participants expressed their weaknesses in knowledge of standard and transmission based precautions, mainly for hand hygiene and tuberculosis. A lack of appropriate resources and standardization in sharps disposal management was also highlighted by the participants.\ud
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Conclusion\ud
The study points out the need to provide in-service training for professionals on the transmission of microorganisms in primary health care to ensure adequate level of risk perception and knowledge. Further recommendations include investment to improve infrastructure to facilitate adherence to precautions and to minimize the risk of disease transmission for both patients and health care workers.This research received grant from São Paulo Research Foundation (FAPESP).\ud
Grant 2013/22559–0 and 2014/08663
Transcript expression plasticity as a response to alternative larval host plants in the speciation process of corn and rice strains of Spodoptera frugiperda
No full textAbstract\ud
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Background\ud
Our main purpose was to evaluate the expression of plastic and evolved genes involved in ecological speciation in the noctuid moth Spodoptera frugiperda, the fall armyworm (FAW); and to demonstrate how host plants might influence lineage differentiation in this polyphagous insect. FAW is an important pest of several crops worldwide, and it is differentiated into host plant-related strains, corn (CS) and rice strains (RS). RNA-Seq and transcriptome characterization were applied to evaluate unbiased genetic expression differences in larvae from the two strains, fed on primary (corn) and alternative (rice) host plants. We consider that genes that are differently regulated by the same FAW strain, as a response to different hosts, are “plastic”. Otherwise, differences in gene expression between the two strains fed on the same host are considered constitutive differences.\ud
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Results\ud
Individual performance parameters (larval and pupal weight) varied among conditions (strains vs. hosts). A total of 3657 contigs was related to plastic response, and 2395 contigs were differentially regulated in the two strains feeding on preferential and alternative hosts (constitutive contigs). Three molecular functions were present in all comparisons, both down- and up-regulated: oxidoreductase activity, metal-ion binding, and hydrolase activity.\ud
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Conclusions\ud
Metabolization of foreign chemicals is among the key functions involved in the phenotypic variation of FAW strains. From an agricultural perspective, high plasticity in families of detoxifying genes indicates the capacity for a rapid response to control compounds such as insecticides.This work was supported by Fundação de Amparo à Pesquisa do Estado de\ud
São Paulo (Fapesp, process 2012/16266–7). Analyzes were performed in the\ud
Thunder Computer Cluster funded by Fapesp (process 2011/00417–3).\ud
AF and CO are recipients of Brazilian CNPq fellowships
Effects of high-frequency transcranial magnetic stimulation on functional performance in individuals with incomplete spinal cord injury: study protocol for a randomized controlled trial
No full textAbstract\ud
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Background\ud
Repetitive transcranial magnetic stimulation (rTMS) has been investigated as a new tool in neurological rehabilitation of individuals with spinal cord injury (SCI). However, due to the inconsistent results regarding the effects of rTMS in people with SCI, a randomized controlled double-blind crossover trial is needed to clarify the clinical utility and to assess the effect size of rTMS intervention in this population. Therefore, this paper describes a study protocol designed to investigate whether the use of rTMS can improve the motor and sensory function, as well as reduce spasticity in patients with incomplete SCI.\ud
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Methods\ud
A double-blind randomized sham-controlled crossover trial will be performed by enrolling 20 individuals with incomplete SCI. Patients who are at least six months post incomplete SCI (aged 18–60 years) will be recruited through referral by medical practitioners or therapists. Individuals will be randomly assigned to either group 1 or group 2 in a 1:1 ratio, with ten individuals in each group. The rTMS protocol will include ten sessions of high-frequency rTMS (5 Hz) over the bilateral lower-limb motor area positioned at the vertex (Cz). Clinical evaluations will be performed at baseline and after rTMS active and sham.\ud
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Discussion\ud
rTMS has produced positive results in treating individuals with physical impairments; thus, it might be promising in the SCI population. The results of this study may provide new insights to motor rehabilitation thereby contributing towards the better usage of rTMS in the SCI population.\ud
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Trial registration\ud
ClinicalTrials.gov, \ud
NCT02899637. Registered on 25 August 2016.The last author (FHM) is currently supported by a research grant from FAPESP\ud
#2015/13096-1 (Foundation of Support for Research of São Paulo State), which\ud
covered the publication costs of this paper.The fisrt author (AVLA) holds a\ud
scholarship from a government agency in Brazil, in charge of promoting high\ud
standards for postgraduate courses (Coordination for Higher Education Staff\ud
Development - CAPES). The financial sponsors will play no role in the design,\ud
execution, analysis and interpretation of data, or writing of the stud
Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil
No full textAbstract\ud
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Background\ud
Non-structural 5A protein (NS5A) resistance-associated substitutions (RASs) have been identified in patients infected with hepatitis C virus (HCV), even prior to exposure to direct-acting antiviral agents (DAAs). Selection for these variants occurs rapidly during treatment and, in some cases, leads to antiviral treatment failure. DAAs are currently the standard of care for hepatitis C treatment in many parts of the world. Nevertheless, in Brazil, the prevalence of pre-existing NS5A RASs is largely unknown. In this study, we evaluated the frequency of naturally occurring NS5A RASs in Brazilian patients infected with HCV as either a monoinfection or coinfection with human immunodeficiency virus (HIV).\ud
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Methods\ud
Direct Sanger sequencing of the NS5A region was performed in 257 DAA-naïve patients chronically infected with HCV (156 monoinfected with HCV and 101 coinfected with HIV/HCV).\ud
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Results\ud
The frequencies of specific RASs in monoinfected patients were 14.6% for HCV GT-1a (M28 V and Q30H/R), 6.0% for GT-1b (L31F/V and Y93H), and 22.6% for GT-3a (A30K and Y93H). For HIV/HCV-coinfected patients, the frequencies of RAS were 3.9% for GT-1a (M28 T and Q30H/R), and 11.1% for GT-1b (Y93H); no RASs were found in GT-3a sequences.\ud
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Conclusions\ud
Substitutions that may confer resistance to NS5A inhibitors exist at baseline in Brazilian DAA-naïve patients infected with HCV GT-1a, −1b, and -3a. Standardization of RAS definitions is needed to improve resistance analyses and to facilitate comparisons of substitutions reported across studies worldwide. Therapeutic strategies should be optimized to efficiently prevent DAA treatment failure due to selection for RASs, especially in difficult-to-cure patients.This study was supported by grant 443,152/2014–4 from CNPq, 2011/50633–4 from the São Paulo Research Foundation (FAPESP) and the Alves de Queiroz Family Fund for Research. João Renato Rebello Pinho and Maria Cassia Mendes Correa received a fellowship from CNPq (Bolsista de Produtividade)
Estimating the prevalence of infectious diseases from under-reported age-dependent compulsorily notification databases
No full textAbstract\ud
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Background\ud
National or local laws, norms or regulations (sometimes and in some countries) require medical providers to report notifiable diseases to public health authorities. Reporting, however, is almost always incomplete. This is due to a variety of reasons, ranging from not recognizing the diseased to failures in the technical or administrative steps leading to the final official register in the disease notification system. The reported fraction varies from 9 to 99% and is strongly associated with the disease being reported.\ud
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Methods\ud
In this paper we propose a method to approximately estimate the full prevalence (and any other variable or parameter related to transmission intensity) of infectious diseases. The model assumes incomplete notification of incidence and allows the estimation of the non-notified number of infections and it is illustrated by the case of hepatitis C in Brazil. The method has the advantage that it can be corrected iteratively by comparing its findings with empirical results.\ud
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Results\ud
The application of the model for the case of hepatitis C in Brazil resulted in a prevalence of notified cases that varied between 163,902 and 169,382 cases; a prevalence of non-notified cases that varied between 1,433,638 and 1,446,771; and a total prevalence of infections that varied between 1,597,540 and 1,616,153 cases.\ud
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Conclusions\ud
We conclude that the model proposed can be useful for estimation of the actual magnitude of endemic states of infectious diseases, particularly for those where the number of notified cases is only the tip of the iceberg. In addition, the method can be applied to other situations, such as the well-known underreported incidence of criminality (for example rape), among others.This work was partially funded by LIM01-HCFMUSP, CNPq, Brazilian Ministry of Health (Grant TED 27/2015) and FAPESP.\ud
DG is grateful to the Leverhulme Trust for support from a Leverhulme Research Fellowship (RF-2015-88) and the British\ud
Council, Malaysia for funding from the Dengue Tech Challenge (Application Reference DTC 16022). EM and DG are\ud
grateful to the Science Without Borders Program for a Special Visiting Fellowship (CNPq grant 30098/2014-7)