We came, we saw, we cannulated?

Introduction: Despite advances in management of patients with severe acute respiratory distress syndrome (ARDS), mortality due to ARDS still remains high. In patients with refractory gas-exchange abnormalities, extracorporeal membrane oxygenation (ECMO) is considered as salvage therapy that aims to decrease ventilator induced lung injury and provide lung rest. injury and provide lung rest. Methods: We conducted a retrospective study of patients diagnosed with ARDS from October 2010 to September 2012. The aim of the study was to describe the population of patients placed on ECMO for ARDS in our institution. All patients placed on ARDSnet protocol were identified in the electronic patient record. Demographic, laboratory and ventilator data was extracted. Specifically mode of ventilation, use of rescue modalities (which included inhaled epoprostenol, skeletal muscle paralytics and/or use of airway pressure release ventilation (APRV)), Murray score, Oxygenation Index (OI), Alveolar-arterial gradient (A-a) and PaO2/FiO2 ratio (P/F) were tabulated. Survival to hospital discharge was recorded. Results: We identified a total of 149 patients. Of these 87 were managed per ARDSnet protocol, 48 received rescue modalities, and 14 patients were placed on ECMO in addition to rescue therapy after a mean interval of 72 hours. Six of 14 patients were placed on veno-arterial ECMO and the rest on veno-venous ECMO. Table 1 shows the baseline characteristics of these patients. Table 2 depicts the etiology of ARDS among our patient population. Mortality was higher in the ARDS group treated with rescue modalities (other than ECMO) compared to the group placed on ECMO as additional rescue therapy (77% vs. 50%; p = 0.3243). The ECMO group had a survival advantage despite higher A-a gradient, PaO2/Fio2 ratio, Oxygenation Index and Murray Score in the ECMO group (Table 1). Conclusion: Patients with ARDS placed on ECMO had an absolute reduction in mortality of 27% when compared to other rescue modalities. However this did not reach statistical significance due to the small sample size. We believe that ECMO is an important rescue modality in the right clinical setting. Treating physicians should consider ECMO as a treatment modality for severe ARDS patients

The pediatrician's role in the Paideia-Family Health Program in Campinas, Sao Paulo State, Brazil

Brazil is developing a Family Health Program in the Primary Health Care. The Family Health Program's team composition has been criticized as insufficient. One of the criticisms has been about the absence of the pediatrician. This study analyzed the experience of the city of Campinas, Sao Paulo State, which implemented this program with adaptations specifically with the presence of the pediatrician in its 140 teams. Using qualitative methodology and semi-structured interviews, pediatricians and ten family physicians teams were interviewed. The objective was to know their visions about their practice with children's primary health care, the role of each one and about the pediatrician's presence in the team. It was almost an unanimity about the importance of the pediatrician's participation in Primary Health Care, not as a specialty, but because of the improvement of the team's resolubility. Though, the pediatrician's work was considered too focused in the biomedical paradigm and in the office. There is a need for the pediatrician to have more engagement with the psychosocial aspects, the family and territory. It is essential the improvement of the training of pediatricians and family physicians to deal with the complex mission of the primary health care of nowadays.1611479148

Functionalisation of terpenoids at C-4 via organopalladium dimers: cyclopropane formation during oxidation of homoallylic sigma-organopalladium intermediates with lead tetraacetate

The synthesis of new potential adjuvant saponin aglycons was investigated by selective palladium mediated C-H functionalisation of appropriately functionalised derivatives of lanosterol, cholesterol, and friedelin. The desired equatorial aldehyde functionality was successfully introduced into the lanosterol skeleton as expected. Cyclopalladation of a cholesterol derivative proceeded as expected, but during oxidation of the organopalladium intermediate, participation of the adjacent alkene functionality led to stereoselective formation of a cyclopropane and introduction of an acetate group into the steroid backbone at C-6. Further investigation of this unusual cyclopropane formation on a model decalin system confirmed the result, but C-H activation on a related open chain system was prevented by complexation of the alkene functionality to the palladium. (c) 2007 Elsevier Ltd. All rights reserved

Test Smell: A Parasitic Energy Consumer in Software Testing

Traditionally, energy efficiency research has focused on reducing energy consumption at the hardware level and, more recently, in the design and coding phases of the software development life cycle. However, software testing's impact on energy consumption did not receive attention from the research community. Specifically, how test code design quality and test smell (e.g., sub-optimal design and bad practices in test code) impact energy consumption has not been investigated yet. This study examined 12 Apache projects to analyze the association between test smell and its effects on energy consumption in software testing. We conducted a mixed-method empirical analysis from two dimensions; software (data mining in Apache projects) and developers' views (a survey of 62 software practitioners). Our findings show that: 1) test smell is associated with energy consumption in software testing. Specifically smelly part of a test case consumes 10.92\% more energy compared to the non-smelly part. 2) certain test smells are more energy-hungry than others, 3) refactored test cases tend to consume less energy than their smelly counterparts, and 4) most developers lack knowledge about test smells' impact on energy consumption. We conclude the paper with several observations that can direct future research and developments

Human iPSC-Derived Neuronal Model of Tau-A152T Frontotemporal Dementia Reveals Tau-Mediated Mechanisms of Neuronal Vulnerability

Frontotemporal dementia (FTD) and other tauopathies characterized by focal brain neurodegeneration and pathological accumulation of proteins are commonly associated with tau mutations. However, the mechanism of neuronal loss is not fully understood. To identify molecular events associated with tauopathy, we studied induced pluripotent stem cell (iPSC)-derived neurons from individuals carrying the tau-A152T variant. We highlight the potential of in-depth phenotyping of human neuronal cell models for pre-clinical studies and identification of modulators of endogenous tau toxicity. Through a panel of biochemical and cellular assays, A152T neurons showed accumulation, redistribution, and decreased solubility of tau. Upregulation of tau was coupled to enhanced stress-inducible markers and cell vulnerability to proteotoxic, excitotoxic, and mitochondrial stressors, which was rescued upon CRISPR/Cas9-mediated targeting of tau or by pharmacological activation of autophagy. Our findings unmask tau-mediated perturbations of specific pathways associated with neuronal vulnerability, revealing potential early disease biomarkers and therapeutic targets for FTD and other tauopathies

Neural Correlates of Treatment in Adolescents with Bipolar Depression During Response Inhibition

Abstract Objective: Abnormal prefrontal and subcortical activity during cognitive control tasks is identified in non-depressed adolescents with bipolar disorder (BD); however, little is known about the neural correlates of bipolar adolescents in a depressed state (BDd). We aimed to investigate baseline versus after-treatment patterns of neural activity underlying motor response and response inhibition in adolescents with BDd. Methods: In this functional magnetic resonance imaging (fMRI) study, 10 adolescents with BDd relative to 10 age-and sexmatched healthy controls (HC) completed a well-validated go/no go block-design cognitive control task at baseline and after 6 weeks of naturalistic treatment. We used whole-brain analysis and controlled our results for multiple comparisons. Results: There was significant improvement in depression scores (mean change: 57% -28). There was no behavioral difference in BDd baseline versus HC and after treatment. BDd adolescents relative to HC had higher baseline cortical, but not subcortical, neural activity (e.g., bilateral ventrolateral prefrontal during both the go [motor control] and the no go [response inhibition] conditions, and left superior temporal during the no go condition). However, after-treatment activity relative to baseline neural activity during response inhibition was significantly increased in subcortical (e.g., right hippocampus and left thalamus), but not cortical, regions. In addition, at baseline, lower left thalamus activity was correlated with higher depression scores. Conclusions: Adolescents with BDd had baseline prefrontal and temporal hyperactivity underlying motor control and response inhibition that did not change after treatment in contrast to relatively decreased baseline subcortical activity underlying response inhibition associated with the depressive state that was increased after the treatment

Serum profiling by MALDI-TOF mass spectrometry as a diagnostic tool for domoic acid toxicosis in California sea lions

<p>Abstract</p> <p>Background</p> <p>There are currently no reliable markers of acute domoic acid toxicosis (DAT) for California sea lions. We investigated whether patterns of serum peptides could diagnose acute DAT. Serum peptides were analyzed by MALDI-TOF mass spectrometry from 107 sea lions (acute DAT n = 34; non-DAT n = 73). Artificial neural networks (ANN) were trained using MALDI-TOF data. Individual peaks and neural networks were qualified using an independent test set (n = 20).</p> <p>Results</p> <p>No single peak was a good classifier of acute DAT, and ANN models were the best predictors of acute DAT. Performance measures for a single median ANN were: sensitivity, 100%; specificity, 60%; positive predictive value, 71%; negative predictive value, 100%. When 101 ANNs were combined and allowed to vote for the outcome, the performance measures were: sensitivity, 30%; specificity, 100%; positive predictive value, 100%; negative predictive value, 59%.</p> <p>Conclusions</p> <p>These results suggest that MALDI-TOF peptide profiling and neural networks can perform either as a highly sensitive (100% negative predictive value) or a highly specific (100% positive predictive value) diagnostic tool for acute DAT. This also suggests that machine learning directed by populations of predictive models offer the ability to modulate the predictive effort into a specific type of error.</p

The major leucyl aminopeptidase of Trypanosoma cruzi (LAPTc) assembles into a homohexamer and belongs to the M17 family of metallopeptidases

<p>Abstract</p> <p>Background</p> <p>Pathogens depend on peptidase activities to accomplish many physiological processes, including interaction with their hosts, highlighting parasitic peptidases as potential drug targets. In this study, a major leucyl aminopeptidolytic activity was identified in <it>Trypanosoma cruzi</it>, the aetiological agent of Chagas disease.</p> <p>Results</p> <p>The enzyme was isolated from epimastigote forms of the parasite by a two-step chromatographic procedure and associated with a single 330-kDa homohexameric protein as determined by sedimentation velocity and light scattering experiments. Peptide mass fingerprinting identified the enzyme as the predicted <it>T. cruzi </it>aminopeptidase EAN97960. Molecular and enzymatic analysis indicated that this leucyl aminopeptidase of <it>T. cruzi </it>(LAPTc) belongs to the peptidase family M17 or leucyl aminopeptidase family. LAPTc has a strong dependence on neutral pH, is mesophilic and retains its oligomeric form up to 80°C. Conversely, its recombinant form is thermophilic and requires alkaline pH.</p> <p>Conclusions</p> <p>LAPTc is a 330-kDa homohexameric metalloaminopeptidase expressed by all <it>T. cruzi </it>forms and mediates the major parasite leucyl aminopeptidolytic activity. Since biosynthetic pathways for essential amino acids, including leucine, are lacking in <it>T. cruzi</it>, LAPTc could have a function in nutritional supply.</p