Seasonality of viral respiratory infections in Southeast of Brazil: the influence of temperature and air humidity

Viruses are the major cause of lower respiratory tract infections in childhood and the main viruses involved are Human Respiratory Syncytial Virus (HRSV), Human Metapneumovirus (HMPV), Influenzavirus A and B (FLUA and FLUB), Human Parainfluenza Virus 1, 2 and 3 (HPIV1, 2 and 3) and Human Rhinovirus (HRV). The purposes of this study were to detect respiratory viruses in hospitalized children younger than six years and identify the influence of temperature and relative air humidity on the detected viruses. Samples of nasopharyngeal washes were collected from hospitalized children between May/2004 and September/2005. Methods of viral detection were RT-PCR, PCR and HRV amplicons were confirmed by hybridization. Results showed 54% (148/272) of viral positivity. HRSV was detected in 29% (79/272) of the samples; HRV in 23.1% (63/272); HPIV3 in 5.1% (14/272); HMPV in 3.3% (9/272); HPIV1 in 2.9% (8/272); FLUB in 1.4% (4/272), FLUA in 1.1% (3/272), and HPIV2 in 0.3% (1/272). The highest detection rates occurred mainly in the spring 2004 and in the autumn 2005. It was observed that viral respiratory infections tend to increase as the relative air humidity decreases, showing significant association with monthly averages of minimal temperature and minimal relative air humidity. In conclusion, viral respiratory infections vary according to temperature and relative air humidity and viral respiratory infections present major incidences it coldest and driest periods.

Postmortem diagnosis of acute myocardial infarction in patients with acute respiratory failure: demographics, etiologic and pulmonary histologic analysis

OBJECTIVES: Acute respiratory failure is present in 5% of patients with acute myocardial infarction and is responsible for 20% to 30% of the fatal post-acute myocardial infarction. The role of inflammation associated with pulmonary edema as a cause of acute respiratory failure post-acute myocardial infarction remains to be determined. We aimed to describe the demographics, etiologic data and histological pulmonary findings obtained through autopsies of patients who died during the period from 1990 to 2008 due to acute respiratory failure with no diagnosis of acute myocardial infarction during life. METHODS: This study considers 4,223 autopsies of patients who died of acute respiratory failure that was not preceded by any particular diagnosis while they were alive. The diagnosis of acute myocardial infarction was given in 218 (4.63%) patients. The age, sex and major associated diseases were recorded for each patient. Pulmonary histopathology was categorized as follows: diffuse alveolar damage, pulmonary edema, alveolar hemorrhage and lymphoplasmacytic interstitial pneumonia. The odds ratio of acute myocardial infarction associated with specific histopathology was determined by logistic regression. RESULTS: In total, 147 men were included in the study. The mean age at the time of death was 64 years. Pulmonary histopathology revealed pulmonary edema as well as the presence of diffuse alveolar damage in 72.9% of patients. Bacterial bronchopneumonia was present in 11.9% of patients, systemic arterial hypertension in 10.1% and dilated cardiomyopathy in 6.9%. A multivariate analysis demonstrated a significant positive association between acute myocardial infarction with diffuse alveolar damage and pulmonary edema. CONCLUSIONS: For the first time, we demonstrated that in autopsies of patients with acute respiratory failure as the cause of death, 5% were diagnosed with acute myocardial infarction. Pulmonary histology revealed a significant inflammatory response, which has not previously been reported.

Model-based reuse for crosscutting frameworks: assessing reuse and maintenance effort

Abstract Background Over the last years, a number of researchers have investigated how to improve the reuse of crosscutting concerns. New possibilities have emerged with the advent of aspect-oriented programming, and many frameworks were designed considering the abstractions provided by this new paradigm. We call this type of framework Crosscutting Frameworks (CF), as it usually encapsulates a generic and abstract design of one crosscutting concern. However, most of the proposed CFs employ white-box strategies in their reuse process, requiring two mainly technical skills: (i) knowing syntax details of the programming language employed to build the framework and (ii) being aware of the architectural details of the CF and its internal nomenclature. Also, another problem is that the reuse process can only be initiated as soon as the development process reaches the implementation phase, preventing it from starting earlier. Method In order to solve these problems, we present in this paper a model-based approach for reusing CFs which shields application engineers from technical details, letting him/her concentrate on what the framework really needs from the application under development. To support our approach, two models are proposed: the Reuse Requirements Model (RRM) and the Reuse Model (RM). The former must be used to describe the framework structure and the later is in charge of supporting the reuse process. As soon as the application engineer has filled in the RM, the reuse code can be automatically generated. Results We also present here the result of two comparative experiments using two versions of a Persistence CF: the original one, whose reuse process is based on writing code, and the new one, which is model-based. The first experiment evaluated the productivity during the reuse process, and the second one evaluated the effort of maintaining applications developed with both CF versions. The results show the improvement of 97% in the productivity; however little difference was perceived regarding the effort for maintaining the required application. Conclusion By using the approach herein presented, it was possible to conclude the following: (i) it is possible to automate the instantiation of CFs, and (ii) the productivity of developers are improved as long as they use a model-based instantiation approach.

Biphasic positive airway pressure minimizes biological impact on lung tissue in mild acute lung injury independent of etiology

Abstract Introduction Biphasic positive airway pressure (BIVENT) is a partial support mode that employs pressure-controlled, time-cycled ventilation set at two levels of continuous positive airway pressure with unrestricted spontaneous breathing. BIVENT can modulate inspiratory effort by modifying the frequency of controlled breaths. Nevertheless, the optimal amount of inspiratory effort to improve respiratory function while minimizing ventilator-associated lung injury during partial ventilatory assistance has not been determined. Furthermore, it is unclear whether the effects of partial ventilatory support depend on acute lung injury (ALI) etiology. This study aimed to investigate the impact of spontaneous and time-cycled control breaths during BIVENT on the lung and diaphragm in experimental pulmonary (p) and extrapulmonary (exp) ALI. Methods This was a prospective, randomized, controlled experimental study of 60 adult male Wistar rats. Mild ALI was induced by Escherichia coli lipopolysaccharide either intratracheally (ALIp) or intraperitoneally (ALIexp). After 24 hours, animals were anesthetized and further randomized as follows: (1) pressure-controlled ventilation (PCV) with tidal volume (Vt) = 6 ml/kg, respiratory rate = 100 breaths/min, PEEP = 5 cmH2O, and inspiratory-to-expiratory ratio (I:E) = 1:2; or (2) BIVENT with three spontaneous and time-cycled control breath modes (100, 75, and 50 breaths/min). BIVENT was set with two levels of CPAP (Phigh = 10 cmH2O and Plow = 5 cmH2O). Inspiratory time was kept constant (Thigh = 0.3 s). Results BIVENT was associated with reduced markers of inflammation, apoptosis, fibrogenesis, and epithelial and endothelial cell damage in lung tissue in both ALI models when compared to PCV. The inspiratory effort during spontaneous breaths increased during BIVENT-50 in both ALI models. In ALIp, alveolar collapse was higher in BIVENT-100 than PCV, but decreased during BIVENT-50, and diaphragmatic injury was lower during BIVENT-50 compared to PCV and BIVENT-100. In ALIexp, alveolar collapse during BIVENT-100 and BIVENT-75 was comparable to PCV, while decreasing with BIVENT-50, and diaphragmatic injury increased during BIVENT-50. Conclusions In mild ALI, BIVENT had a lower biological impact on lung tissue compared to PCV. In contrast, the response of atelectasis and diaphragmatic injury to BIVENT differed according to the rate of spontaneous/controlled breaths and ALI etiology.

Human respiratory syncytial virus N, P and M protein interactions in HEK-293T cells

Characterization of Human Respiratory Syncytial Virus (HRSV) protein interactions with host cell components is crucial to devise antiviral strategies. Viral nucleoprotein, phosphoprotein and matrix protein genes were optimized for human codon usage and cloned into expression vectors. HEK-293T cells were transfected with these vectors, viral proteins were immunoprecipitated, and co-immunoprecipitated cellular proteins were identified through mass spectrometry. Cell proteins identified with higher confidence scores were probed in the immunoprecipitation using specific antibodies. The results indicate that nucleoprotein interacts with arginine methyl-transferase, methylosome protein and Hsp70. Phosphoprotein interacts with Hsp70 and tropomysin, and matrix with tropomysin and nucleophosmin. Additionally, we performed immunoprecipitation of these cellular proteins in cells infected with HRSV, followed by detection of co-immunoprecipitated viral proteins. The results indicate that these interactions also occur in the context of viral infection, and their potential contribution for a HRSV replication model is discussed.

Proline dehydrogenase regulates redox state and respiratory metabolism in Trypanosoma Cruzi

Over the past three decades, L-proline has become recognized as an important metabolite for trypanosomatids. It is involved in a number of key processes, including energy metabolism, resistance to oxidative and nutritional stress and osmoregulation. In addition, this amino acid supports critical parasite life cycle processes by acting as an energy source, thus enabling host-cell invasion by the parasite and subsequent parasite differentiation. In this paper, we demonstrate that L-proline is oxidized to Δ(1)-pyrroline-5-carboxylate (P5C) by the enzyme proline dehydrogenase (TcPRODH, E.C. 1.5.99.8) localized in Trypanosoma cruzi mitochondria. When expressed in its active form in Escherichia coli, TcPRODH exhibits a Km of 16.58±1.69 µM and a Vmax of 66±2 nmol/min mg. Furthermore, we demonstrate that TcPRODH is a FAD-dependent dimeric state protein. TcPRODH mRNA and protein expression are strongly upregulated in the intracellular epimastigote, a stage which requires an external supply of proline. In addition, when Saccharomyces cerevisiae null mutants for this gene (PUT1) were complemented with the TcPRODH gene, diminished free intracellular proline levels and an enhanced sensitivity to oxidative stress in comparison to the null mutant were observed, supporting the hypothesis that free proline accumulation constitutes a defense against oxidative imbalance. Finally, we show that proline oxidation increases cytochrome c oxidase activity in mitochondrial vesicles. Overall, these results demonstrate that TcPRODH is involved in proline-dependant cytoprotection during periods of oxidative imbalance and also shed light on the participation of proline in energy metabolism, which drives critical processes of the T. cruzi life cycle.

Formaldehyde inhalation reduces respiratory mechanics in a rat model with allergic lung inflammation by altering the nitric oxide/cyclooxygenase-derived products relationship

Bronchial hyperresponsiveness is a hallmark of asthma and many factors modulate bronchoconstriction episodes. A potential correlation of formaldehyde (FA) inhalation and asthma has been observed; however, the exact role of FA remains controversial. We investigated the effects of FA inhalation on Ovalbumin (OVA) sensitisation using a parameter of respiratory mechanics. The involvement of nitric oxide (NO) and cyclooxygenase-derived products were also evaluated. The rats were submitted, or not, to FA inhalation (1%, 90 min/day, 3 days) and were OVA-sensitised and challenged 14 days later. Our data showed that previous FA exposure in allergic rats reduced bronchial responsiveness, respiratory resistance (Rrs) and elastance (Ers) to methacholine. FA exposure in allergic rats also increased the iNOS gene expression and reduced COX-1. L-NAME treatment exacerbated the bronchial hyporesponsiveness and did not modify the Ers and Rrs, while Indomethacin partially reversed all of the parameters studied. The L-NAME and Indomethacin treatments reduced leukotriene B4 levels while they increased thromboxane B2 and prostaglandin E2. In conclusion, FA exposure prior to OVA sensitisation reduces the respiratory mechanics and the interaction of NO and PGE2 may be representing a compensatory mechanism in order to protect the lung from bronchoconstriction effects.

Variability of neurally-adjusted ventilatory assist (nava) compared to pressure support ventilation (psv) during the weaning phase of mechanical ventilation.

Rationale: NAVA is an assisted ventilatory mode that uses the electrical activity of the diaphragm (Edi) to trigger and cycle the ventilator, and to offer inspiratory assistance in proportion to patient effort. Since Edi varies from breath to breath, airway pressure and tidal volume also vary according to the patient's breathing pattern. Our objective was to compare the variability of NAVA with PSV in mechanically ventilated patients during the weaning phase. Methods: We analyzed the data collected for a clinical trial that compares PSV and NAVA during spontaneous breathing trials using PSV, with PS of 5 cmH2O, and NAVA, with Nava level titrated to generate a peak airway pressure equivalent to PSV of 5 cmH2O (NCT01137271). We captured flow, airway pressure and Edi at 100Hz from the ventilator using a dedicated software (Servo Tracker v2, Maquet, Sweden), and processed the cycles using a MatLab (Mathworks, USA) code. The code automatically detects the tidal volume (Vt), respiratory rate (RR), Edi and Airway pressure (Paw) on a breath-by-breath basis for each ventilatory mode. We also calculated the coefficient of variation (standard deviation, SD, divided by the mean). Results: We analyzed data from eleven patients. The mean Vt was similar on both modes (370 ±70 for Nava and 347± 77 for PSV), the RR was 26±6 for Nava and 26±7 or PSV. Paw was higher for Nava than for PSV (14±1 vs 11±0.4, p=0.0033), and Edi was similar for both modes (12±8 for Nava and 11±6 for PSV). The variability of the respiratory pattern, assessed with the coefficient of variation, was larger for Nava than for PSV for the Vt ( 23%±1% vs 15%±1%, p=0.03) and Paw (17%±1% vs 1% ±0.1%, p=0.0033), but not for RR (21% ±1% vs 16% ±8%, p=0.050) or Edi (33%±14% vs 39% ±16%,p=0.07). Conclusion: The variability of the breathing pattern is high during spontaneous breathing trials independent of the ventilatory mode. This variability results in variability of airway pressure and tidal volume, which are higher on Nava than on PSV. Our results suggest that Nava better reflects the normal variability of the breathing pattern during assisted mechanical ventilation.

Potential respiration is a better respiratory predictor than biomass in young Artemia salina

[EN] These experiments test whether respiration can be predicted better from biomass or from potential respiration, a measurement of the mitochondrial and microsomal respiratory electron transport systems. For nearly a century Kleiber's law or a similar precursor have argued the importance of biomass in predicting respiration. In the last decade, a version of the Metabolic Theory of Ecology has elaborated on Kleiber's Law adding emphasis to the importance of biomass in predicting respiration. We argue that Kleiber's law works because biomass packages mitochondria and microsomal electron transport complexes. On a scale of five orders of magnitude we have shown previously that potential respiration predicts respiration aswell as biomass inmarine zooplankton. Here, using cultures of the branchiopod, Artemia salina and on a scale of less than 2 orders of magnitude,we investigated the power of biomass and potential respiration in predicting respiration.We measured biomass, respiration and potential respiration in Artemia grown in different ways and found that potential respiration (Ф) could predict respiration (R), both in μlO2h−1 (R=0.924Φ+0.062, r2=0.976), but biomass (as mg dry mass) could not (R=27.02DM+8.857, r2=0.128). Furthermore the R/Ф ratio appeared independent of age and differences in the food source.

Behavior of respiratory metabolism and pyridine nucleotide levels in Oxyrrhis marina during starvation

Máster en Oceanografía