Publications by authors named "Pedro Mendes"

137 Publications

Teaching point-of-care transfontanellar ultrasound for pediatricians and medical students.

J Pediatr (Rio J) 2021 Mar 10. Epub 2021 Mar 10.

Universidade Federal de Juiz de Fora (UFJF), Programa de Pós-graduação em Saúde Brasileira, Juiz de Fora, MG, Brazil; Universidade Federal de Juiz de Fora (UFJF), Departamento de Nefrologia, Juiz de Fora, MG, Brazil.

Objectives: The authors aim to evaluate the "point-of-care" transfontanellar ultrasound (TU) as an extension to pediatric physical examination and suggest a TU teaching protocol.

Methods: The students were randomly divided into two groups, group A (12 participants) and group B (15 participants). The first group only received theoretical training, while the second group received theoretical and practical training. A third group, group C, included 15 pediatricians and interns who also received theoretical and practical training. All the participants underwent multiple-choice testing before and after a four-hour short course on TU. Six months later, another evaluation was performed to analyze the retained knowledge. Furthermore, a questionnaire based on the Likert scale was administered to evaluate satisfaction.

Results: The cognitive evaluation (maximum score=10 points) before and after training increased in group A from 4,0±1,04 to 7,5±1,2 (p<0.001) and, 6 months later, to 6,5±1,16 (p<0.003); in group B from 3,8±1,24 to 8,8±1,01 (p<0.001) and, 6 months later, to 8,46±0,91 (p<0.001); and in group C from 6,0±0,75 to 9,0±0,75 (p<0.001) and, 6 months later, to 8,8±0,77 (p<0.001). The average satisfaction estimated by the Likert scale was over 80% for all questions.

Conclusion: Cognitive assessment before and after classes and training reveals progress in learning, with knowledge retention in 6 months. Theoretical-practical courses are well accepted.
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http://dx.doi.org/10.1016/j.jped.2021.01.006DOI Listing
March 2021

Agent Based Models of Polymicrobial Biofilms and the Microbiome-A Review.

Microorganisms 2021 Feb 17;9(2). Epub 2021 Feb 17.

Department of Oral Health and Diagnostic Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.

The human microbiome has been a focus of intense study in recent years. Most of the living organisms comprising the microbiome exist in the form of biofilms on mucosal surfaces lining our digestive, respiratory, and genito-urinary tracts. While health-associated microbiota contribute to digestion, provide essential nutrients, and protect us from pathogens, disturbances due to illness or medical interventions contribute to infections, some that can be fatal. Myriad biological processes influence the make-up of the microbiota, for example: growth, division, death, and production of extracellular polymers (EPS), and metabolites. Inter-species interactions include competition, inhibition, and symbiosis. Computational models are becoming widely used to better understand these interactions. Agent-based modeling is a particularly useful computational approach to implement the various complex interactions in microbial communities when appropriately combined with an experimental approach. In these models, each cell is represented as an autonomous agent with its own set of rules, with different rules for each species. In this review, we will discuss innovations in agent-based modeling of biofilms and the microbiota in the past five years from the biological and mathematical perspectives and discuss how agent-based models can be further utilized to enhance our comprehension of the complex world of polymicrobial biofilms and the microbiome.
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http://dx.doi.org/10.3390/microorganisms9020417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922883PMC
February 2021

Chronic Pulmonary Aspergillosis and the Effect of Corticosteroids.

Arch Bronconeumol 2021 Jan 28. Epub 2021 Jan 28.

Serviço de Cirurgia Cardiotorácica do Hospital Central do Funchal, Portugal.

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http://dx.doi.org/10.1016/j.arbres.2020.12.033DOI Listing
January 2021

Computational strategies to combat COVID-19: useful tools to accelerate SARS-CoV-2 and coronavirus research.

Brief Bioinform 2021 03;22(2):642-663

Philipps-University Marburg, Germany.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need for fast detection, understanding and treatment of COVID-19. To control the ongoing COVID-19 pandemic, it is of utmost importance to get insight into the evolution and pathogenesis of the virus. In this review, we cover bioinformatics workflows and tools for the routine detection of SARS-CoV-2 infection, the reliable analysis of sequencing data, the tracking of the COVID-19 pandemic and evaluation of containment measures, the study of coronavirus evolution, the discovery of potential drug targets and development of therapeutic strategies. For each tool, we briefly describe its use case and how it advances research specifically for SARS-CoV-2. All tools are free to use and available online, either through web applications or public code repositories. Contact:evbc@unj-jena.de.
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http://dx.doi.org/10.1093/bib/bbaa232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665365PMC
March 2021

Neuromuscular blockade and airway management during endotracheal intubation in Brazilian intensive care units: a national survey.

Rev Bras Ter Intensiva 2020 Jul-Sep;32(3):433-438

Disciplina de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo - São Paulo (SP), Brasil.

Objective: To describe the use of neuromuscular blockade as well as other practices among Brazilian physicians in adult intensive care units.

Methods: An online national survey was designed and administered to Brazilian intensivists. Questions were selected using the Delphi method and assessed physicians' demographic data, intensive care unit characteristics, practices regarding airway management, use of neuromuscular blockade and sedation during endotracheal intubation in the intensive care unit. As a secondary outcome, we applied a multivariate analysis to evaluate factors associated with the use of neuromuscular blockade.

Results: Five hundred sixty-five intensivists from all Brazilian regions responded to the questionnaire. The majority of respondents were male (65%), with a mean age of 38 ( 8.4 years, and 58.5% had a board certification in critical care. Only 40.7% of the intensivists reported the use of neuromuscular blockade during all or in more than 75% of endotracheal intubations. In the multivariate analysis, the number of intubations performed monthly and physician specialization in anesthesiology were directly associated with frequent use of neuromuscular blockade. Etomidate and ketamine were more commonly used in the clinical situation of hypotension and shock, while propofol and midazolam were more commonly prescribed in the situation of clinical stability.

Conclusion: The reported use of neuromuscular blockade was low among intensivists, and sedative drugs were chosen in accordance with patient hemodynamic stability. These results may help the design of future studies regarding airway management in Brazil.
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http://dx.doi.org/10.5935/0103-507X.20200073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595723PMC
February 2020

Telemedicine in COPD: An Overview by Topics.

COPD 2020 10 7;17(5):601-617. Epub 2020 Sep 7.

Pulmonology Department, Central Hospital of Funchal, Portugal.

COPD is a major cause of morbidity and mortality worldwide and carries a huge and growing economic and social burden. Telemedicine might allow the care of patients with limited access to health services and improve their self-management. During the COVID-19 pandemic, patient's safety represents one of the main reasons why we might use these tools to manage our patients. The authors conducted a literature search in MEDLINE database. The retrieval form of the Medical Subject Headings (Mesh) was ((Telemedicine OR Tele-rehabilitation OR Telemonitoring OR mHealth OR Ehealth OR Telehealth) AND COPD). We only included systematic reviews, reviews, meta-analysis, clinical trials and randomized-control trials, in the English language, with the selected search items in title or abstract, and published from January 1st 2015 to 31st May 2020 ( = 56). There was a positive tendency toward benefits in tele-rehabilitation, health-education and self-management, early detection of COPD exacerbations, psychosocial support and smoking cessation, but the heterogeneity of clinical trials and reviews limits the extent to which this value can be understood. Telemonitoring interventions and cost-effectiveness had contradictory results. The literature on teleconsultation was scarce during this period. The non-inferiority tendency of telemedicine programmes comparing to conventional COPD management seems an opportunity to deliver quality healthcare to COPD patients, with a guarantee of patient's safety, especially during the COVID-19 outbreak.
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http://dx.doi.org/10.1080/15412555.2020.1815182DOI Listing
October 2020

Characteristics and outcomes of patients with COVID-19 admitted to the ICU in a university hospital in São Paulo, Brazil - study protocol.

Clinics (Sao Paulo) 2020 26;75:e2294. Epub 2020 Aug 26.

Divisao de Pneumologia, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.

Objectives: We designed a cohort study to describe characteristics and outcomes of patients with coronavirus disease (COVID-19) admitted to the intensive care unit (ICU) in the largest public hospital in Sao Paulo, Brazil, as Latin America becomes the epicenter of the pandemic.

Methods: This is the protocol for a study being conducted at an academic hospital in Brazil with 300 adult ICU beds dedicated to COVID-19 patients. We will include adult patients admitted to the ICU with suspected or confirmed COVID-19 during the study period. The main outcome is ICU survival at 28 days. Data will be collected prospectively and retrospectively by trained investigators from the hospital's electronic medical records, using an electronic data capture tool. We will collect data on demographics, comorbidities, severity of disease, and laboratorial test results at admission. Information on the need for advanced life support and ventilator parameters will be collected during ICU stay. Patients will be followed up for 28 days in the ICU and 60 days in the hospital. We will plot Kaplan-Meier curves to estimate ICU and hospital survival and perform survival analysis using the Cox proportional hazards model to identify the main risk factors for mortality. ClinicalTrials.gov: NCT04378582.

Results: We expect to include a large sample of patients with COVID-19 admitted to the ICU and to be able to provide data on admission characteristics, use of advanced life support, ICU survival at 28 days, and hospital survival at 60 days.

Conclusions: This study will provide epidemiological data about critically ill patients with COVID-19 in Brazil, which could inform health policy and resource allocation in low- and middle-income countries.
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http://dx.doi.org/10.6061/clinics/2020/e2294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442378PMC
September 2020

Trends in clinical profiles, organ support use and outcomes of patients with cancer requiring unplanned ICU admission: a multicenter cohort study.

Intensive Care Med 2021 Feb 7;47(2):170-179. Epub 2020 Aug 7.

Department of Critical Care and Graduate Program in Translational Medicine, D'Or Institute for Research and Education, Rio de Janeiro, Brazil.

Purpose: To describe trends in outcomes of cancer patients with unplanned admissions to intensive-care units (ICU) according to cancer type, organ support use, and performance status (PS) over an 8-year period.

Methods: We retrospectively analyzed prospectively collected data from all cancer patients admitted to 92 medical-surgical ICUs from July/2011 to June/2019. We assessed trends in mortality through a Bayesian hierarchical model adjusted for relevant clinical confounders and whether there was a reduction in ICU length-of-stay (LOS) over time using a competing risk model.

Results: 32,096 patients (8.7% of all ICU admissions; solid tumors, 90%; hematological malignancies, 10%) were studied. Bed/days use by cancer patients increased up to more than 30% during the period. Overall adjusted mortality decreased by 9.2% [95% credible interval (CI), 13.1-5.6%]. The largest reductions in mortality occurred in patients without need for organ support (9.6%) and in those with need for mechanical ventilation (MV) only (11%). Smallest reductions occurred in patients requiring MV, vasopressors, and dialysis (3.9%) simultaneously. Survival gains over time decreased as PS worsened. Lung cancer patients had the lowest decrease in mortality. Each year was associated with a lower sub-hazard for ICU death [SHR 0.93 (0.91-0.94)] and a higher chance of being discharged alive from the ICU earlier [SHR 1.01 (1-1.01)].

Conclusion: Outcomes in critically ill cancer patients improved in the past 8 years, with reductions in both mortality and ICU LOS, suggesting improvements in overall care. However, outcomes remained poor in patients with lung cancer, requiring multiple organ support and compromised PS.
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http://dx.doi.org/10.1007/s00134-020-06184-2DOI Listing
February 2021

Long-term outcome of adjustable transobturator male system for stress urinary incontinence in the Iberian multicentre study.

Neurourol Urodyn 2020 08 4;39(6):1737-1745. Epub 2020 Jun 4.

Department of Urology, Centro Hospitalar São João, Oporto, Portugal.

Aim: The aim of this study is to evaluate long-term durability and effectiveness of the adjustable transobturator male system (ATOMS).

Materials And Methods: The retrospective multicenter Iberian ATOMS study (n = 215) was updated to evaluate long-term continence status, complications, explants, and secondary treatments. Mean follow-up from surgery to March 2020 was 60.6 ± 18.4 months (range, 39-91). Eleven patients deceased of an unrelated causes. Kaplan-Meier curves were performed to evaluate device durability and incontinence free of recurrence interval. The multivariate analysis defined the population at risk of device explant.

Results: A total of 155 patients were dry at the last follow-up visit (72.1%); 99 (46%) used no pads and 56 (26%) used a security pad/day with urine loss less than 10 mL; 96% of dry patients after adjustment remained free of incontinence 1 year later, 93.6% 2 years later, 91.1% 3 years later, 89.2% 5 years later, and 86.7% 8 years later. Complications during follow-up occurred in 43 of 215 (20%). In total, 25 (11.6%) devices were explanted and causes were inefficacy 11 (44%), inefficacy and pain 3 (12%), port erosion 10 (40%), and wound infection 1 (4%). The secondary implant was performed in 11 (5.1%) cases, 6 artificial urinary sphincter and 5 repeated ATOMS. Time to explant was associated to complications (P < .0001), baseline stress urinary incontinence (SUI) severity (P = .01), and former irradiation (P = .03). Multivariate analysis revealed complications (hazard ratio [HR] = 8.71; 3.83-19.82), baseline SUI severity (>5 compared to 1-2 pads/day; HR = 14.9; 1.87-125), and irradiation before ATOMS (HR = 2.26; 1.02-5.18) predicted earlier ATOMS explant. Three cases received radiation after implant without complication.

Conclusions: ATOMS device is efficacious and safe in the long term. Determinants for device explant include complications, baseline severity of incontinence, and previous irradiation. Currently, the durability of the device after 5 years is reassuring.
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http://dx.doi.org/10.1002/nau.24410DOI Listing
August 2020

Adherence to a stress ulcer prophylaxis protocol by critically ill patients: a prospective cohort study.

Rev Bras Ter Intensiva 2020 Mar 8;32(1):37-42. Epub 2020 May 8.

Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.

Objective: To evaluate adherence to the stress ulcer prophylaxis protocol in critically ill patients at a tertiary university hospital.

Methods: In this prospective cohort study, we included all adult patients admitted to the medical and surgical intensive care units of an academic tertiary hospital. Our sole exclusion criterion was upper gastrointestinal bleeding at intensive care unit admission. We collected baseline variables and stress ulcer prophylaxis indications according to the institutional protocol and use of prophylaxis. Our primary outcome was adherence to the stress ulcer prophylaxis protocol. Secondary outcomes were appropriate use of stress ulcer prophylaxis, upper gastrointestinal bleeding incidence and factors associated with appropriate use of stress ulcer prophylaxis.

Results: Two hundred thirty-four patients were enrolled from July 2nd through July 31st, 2018. Patients were 52 ± 20 years old, 125 (53%) were surgical patients, and the mean SAPS 3 was 52 ± 20. In the longitudinal follow-up, 1499 patient-days were studied; 1069 patient-days had stress ulcer prophylaxis indications, and 777 patient-days contained prophylaxis use (73% stress ulcer prophylaxis protocol adherence). Of the 430 patient-days without stress ulcer prophylaxis indications, 242 involved prophylaxis (56% inappropriate stress ulcer prophylaxis use). The overall appropriate use of stress ulcer prophylaxis was 64%. Factors associated with proper stress ulcer prophylaxis prescription were mechanical ventilation OR 2.13 (95%CI 1.64 - 2.75) and coagulopathy OR 2.77 (95%CI 1.66 - 4.60). The upper gastrointestinal bleeding incidence was 12.8%.

Conclusion: Adherence to the stress ulcer prophylaxis protocol was low and inappropriate use of stress ulcer prophylaxis was frequent in this cohort of critically ill patients.
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http://dx.doi.org/10.5935/0103-507x.20200007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206951PMC
March 2020

Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in adult patients: a systematic review and meta-analysis.

Rev Bras Ter Intensiva 2019 Oct-Dec;31(4):548-554

Unidade de Terapia Intensiva, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo - São Paulo (SP), Brasil.

Objective: The evidence of improved survival with the use of extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome is still uncertain.

Methods: This systematic review and meta-analysis was registered in the PROSPERO database with the number CRD-42018098618. We performed a structured search of Medline, Lilacs, and ScienceDirect for randomized controlled trials evaluating the use of ECMO associated with (ultra)protective mechanical ventilation for severe acute respiratory failure in adult patients. We used the Cochrane risk of bias tool to evaluate the quality of the evidence. Our primary objective was to evaluate the effect of ECMO on the last reported mortality. Secondary outcomes were treatment failure, hospital length of stay and the need for renal replacement therapy in both groups.

Results: Two randomized controlled studies were included in the meta-analysis, comprising 429 patients, of whom 214 were supported with ECMO. The most common reason for acute respiratory failure was pneumonia (60% - 65%). Respiratory ECMO support was associated with a reduction in last reported mortality and treatment failure with risk ratios (RR: 0.76; 95%CI 0.61 - 0.95 and RR: 0.68; 95%CI 0.55 - 0.85, respectively). Extracorporeal membrane oxygenation reduced the need for renal replacement therapy, with a RR of 0.88 (95%CI 0.77 - 0.99). Intensive care unit and hospital lengths of stay were longer in ECMO-supported patients, with an additional P50th 14.84 (P25th - P75th: 12.49 - 17.18) and P50th 29.80 (P25th - P75th: 26.04 - 33.56] days, respectively.

Conclusion: Respiratory ECMO support in severe acute respiratory distress syndrome patients is associated with a reduced mortality rate and a reduced need for renal replacement therapy but a substantial increase in the lengths of stay in the intensive care unit and hospital. Our results may help bedside decision-making regarding ECMO initiation in patients with severe respiratory distress syndrome.
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http://dx.doi.org/10.5935/0103-507X.20190077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008998PMC
July 2020

Word frequency effects on judgments of learning: More than just beliefs.

J Gen Psychol 2021 Apr-Jun;148(2):124-148. Epub 2019 Dec 27.

University of Minho.

Judgments of learning (JOLs) are usually higher for high-frequency words than for low-frequency words, which has been attributed to beliefs about how word frequency affects memory. The main goal of the present study was to explore if identifying word frequency as a relevant cue is necessary for it to affect JOLs. The idea is that for one to base judgments in beliefs of how a variable affects memory, one must first consider that variable. In Experiments 1 and 2, participants studied a list of high- and low-frequency words, made immediate JOLs, and answered questions aimed at identifying the cues used to make those JOLs. The results showed that identifying word frequency as a cue was not necessary for effects on JOLs to occur, suggesting that some participants could not have used beliefs about how word frequency affects memory when making JOLs. In Experiment 3, we measured processing fluency of high- and low-frequency words through a lexical decision task. Participants identified high-frequency words quicker than low-frequency words, suggesting the former to be more fluently processed. In Experiment 4, we explored if response times in a lexical decision task mediated the effect of word frequency on JOLs. Results showed a significant mediation of 8-13%, depending on the analysis technique. We argue that theory-driven processes do not fully account for word frequency effects on JOLs.
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http://dx.doi.org/10.1080/00221309.2019.1706073DOI Listing
December 2019

Data Management in Computational Systems Biology: Exploring Standards, Tools, Databases, and Packaging Best Practices.

Methods Mol Biol 2019 ;2049:285-314

School of Computer Science, University of Manchester, Manchester, UK.

Computational systems biology involves integrating heterogeneous datasets in order to generate models. These models can assist with understanding and prediction of biological phenomena. Generating datasets and integrating them into models involves a wide range of scientific expertise. As a result these datasets are often collected by one set of researchers, and exchanged with others researchers for constructing the models. For this process to run smoothly the data and models must be FAIR-findable, accessible, interoperable, and reusable. In order for data and models to be FAIR they must be structured in consistent and predictable ways, and described sufficiently for other researchers to understand them. Furthermore, these data and models must be shared with other researchers, with appropriately controlled sharing permissions, before and after publication. In this chapter we explore the different data and model standards that assist with structuring, describing, and sharing. We also highlight the popular standards and sharing databases within computational systems biology.
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http://dx.doi.org/10.1007/978-1-4939-9736-7_17DOI Listing
June 2020

ModelBricks-modules for reproducible modeling improving model annotation and provenance.

NPJ Syst Biol Appl 2019 8;5:37. Epub 2019 Oct 8.

1Center for Cell Analysis and Modeling, UConn Health, Farmington, CT USA.

Most computational models in biology are built and intended for "single-use"; the lack of appropriate annotation creates models where the assumptions are unknown, and model elements are not uniquely identified. Simply recreating a simulation result from a publication can be daunting; expanding models to new and more complex situations is a herculean task. As a result, new models are almost always created anew, repeating literature searches for kinetic parameters, initial conditions and modeling specifics. It is akin to building a brick house starting with a pile of clay. Here we discuss a concept for building annotated, reusable models, by starting with small well-annotated modules we call ModelBricks. Curated ModelBricks, accessible through an open database, could be used to construct new models that will inherit ModelBricks annotations and thus be easier to understand and reuse. Key features of ModelBricks include reliance on a commonly used standard language (SBML), rule-based specification describing species as a collection of uniquely identifiable molecules, association with model specific numerical parameters, and more common annotations. Physical bricks can vary substantively; likewise, to be useful the structure of ModelBricks must be highly flexible-it should encapsulate mechanisms from single reactions to multiple reactions in a complex process. Ultimately, a modeler would be able to construct large models by using multiple ModelBricks, preserving annotations and provenance of model elements, resulting in a highly annotated model. We envision the library of ModelBricks to rapidly grow from community contributions. Persistent citable references will incentivize model creators to contribute new ModelBricks.
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http://dx.doi.org/10.1038/s41540-019-0114-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783478PMC
April 2020

Multisite rate control analysis identifies ribosomal scanning as the sole high-capacity/low-flux-control step in mRNA translation.

FEBS J 2020 03 4;287(5):925-940. Epub 2019 Oct 4.

Warwick Integrative Synthetic Biology Centre [WISB] and School of Life Sciences, University of Warwick, Coventry, UK.

Control of complex intracellular pathways such as protein synthesis is critical to organism survival, but is poorly understood. Translation of a reading frame in eukaryotic mRNA is preceded by a scanning process in which a subset of translation factors helps guide ribosomes to the start codon. Here, we perform comparative analysis of the control status of this scanning step that sits between recruitment of the small ribosomal subunit to the m GpppG-capped 5'end of mRNA and of the control exerted by downstream phases of polypeptide initiation, elongation and termination. We have utilized a detailed predictive model as guidance for designing quantitative experimental interrogation of control in the yeast translation initiation pathway. We have built a synthetic orthogonal copper-responsive regulatory promoter (P ) that is used here together with the tet07 regulatory system in a novel dual-site in vivo rate control analysis strategy. Combining this two-site strategy with calibrated mass spectrometry to determine translation factor abundance values, we have tested model-based predictions of rate control properties of the in vivo system. We conclude from the results that the components of the translation machinery that promote scanning collectively function as a low-flux-control system with a capacity to transfer ribosomes into the core process of polypeptide production that exceeds the respective capacities of the steps of polypeptide initiation, elongation and termination. In contrast, the step immediately prior to scanning, that is, ribosome recruitment via the mRNA 5' cap-binding complex, is a high-flux-control step.
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http://dx.doi.org/10.1111/febs.15059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054134PMC
March 2020

Oxygen delivery, carbon dioxide removal, energy transfer to lungs and pulmonary hypertension behavior during venous-venous extracorporeal membrane oxygenation support: a mathematical modeling approach.

Rev Bras Ter Intensiva 2019 May 13;31(2):113-121. Epub 2019 May 13.

Unidade de Terapia Intensiva, Disciplina de Emergências Clínicas; Departamento de Clínica Médica; Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo - São Paulo (SP), Brasil.

Objective: To describe (1) the energy transfer from the ventilator to the lungs, (2) the match between venous-venous extracorporeal membrane oxygenation (ECMO) oxygen transfer and patient oxygen consumption (VO2), (3) carbon dioxide removal with ECMO, and (4) the potential effect of systemic venous oxygenation on pulmonary artery pressure.

Methods: Mathematical modeling approach with hypothetical scenarios using computer simulation.

Results: The transition from protective ventilation to ultraprotective ventilation in a patient with severe acute respiratory distress syndrome and a static respiratory compliance of 20mL/cm H2O reduced the energy transfer from the ventilator to the lungs from 35.3 to 2.6 joules/minute. A hypothetical patient, hyperdynamic and slightly anemic with VO2 = 200mL/minute, can reach an arterial oxygen saturation of 80%, while maintaining the match between the oxygen transfer by ECMO and the VO2 of the patient. Carbon dioxide is easily removed, and normal PaCO2 is easily reached. Venous blood oxygenation through the ECMO circuit may drive the PO2 stimulus of pulmonary hypoxic vasoconstriction to normal values.

Conclusion: Ultraprotective ventilation largely reduces the energy transfer from the ventilator to the lungs. Severe hypoxemia on venous-venous-ECMO support may occur despite the matching between the oxygen transfer by ECMO and the VO2 of the patient. The normal range of PaCO2 is easy to reach. Venous-venous-ECMO support potentially relieves hypoxic pulmonary vasoconstriction.
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http://dx.doi.org/10.5935/0103-507X.20190018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649222PMC
May 2019

First Population-Based Screening of Abdominal Aortic Aneurysm in Portugal.

Ann Vasc Surg 2019 Aug 22;59:48-53. Epub 2019 Feb 22.

Departamento de Cirurgia e Fisiologia, Unidade de Investigação Cardiovascular, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.

Background: The incidence of abdominal aortic aneurysm (AAA) repairs in Portugal is one of the lowest mentioned in the literature. This phenomenon can be justified either by a low prevalence of the disease or by its low detection rate. To date, the prevalence of the pathology is unknown. The objective of the study was to estimate the prevalence of AAA and its associated risk factors, in men aged ≥65 years and to evaluate the population's disease awareness.

Methods: All males aged ≥65 years registered in a Portuguese primary health care unit were invited to participate. The abdominal aorta was measured by ultrasound (inner to inner method). Concomitant risk factors and patient's AAA awareness were also assessed. An aortic diameter >30 mm was considered aneurysmatic.

Results: Nine hundred thirty-three patients were invited for the screening. Of these, 715 participated in the study (participation rate of 76.6%). The AAA prevalence in this sample was 2.1%. Eighty-five percent of the evaluated patients had never heard of the disease before. The mean age of the assessed population was 72.3 years; Multiple logistic regression analysis showed a positive association between AAA and history of smoking (odds ratio [OR] 8.8, P = 0.037) and history of dyslipidemia (OR 9.6, P = 0.035). A negative association was found between diabetes and AAA (OR 0.33, P = 0.045).

Conclusions: The found prevalence shows that a significant number of potentially fatal AAAs remains to be diagnosed in Portugal. These results highlight the need for an effective program of AAA detection in Portugal. The lack of awareness in the Portuguese population for this pathology should also prompt reflexion.
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http://dx.doi.org/10.1016/j.avsg.2018.12.091DOI Listing
August 2019

Factors associated with renal Doppler resistive index in critically ill patients: a prospective cohort study.

Ann Intensive Care 2019 Jan 31;9(1):23. Epub 2019 Jan 31.

Emergency Medicine Discipline, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Av Enéas de Carvalho Aguiar 255 Sala 5023, São Paulo, SP, Postal Code: 05403-000, Brazil.

Background: The renal Doppler resistive index (renal RI) is a noninvasive tool that has been used to assess renal perfusion in the intensive care unit (ICU) setting. However, many parameters have been described as influential on the values of renal RI. Therefore, we proposed this study to evaluate the variables that could impact renal RI in critically ill patients.

Methods: A prospective observational study was performed in a 14-bed medical-surgical adult ICU. All consecutive patients admitted to the ICU during the study period were evaluated for eligibility. Renal RI was performed daily until the third day after ICU admission, death, or renal replacement therapy (RRT) requirement. Clinical and blood test data were collected throughout this period. Acute kidney injury (AKI) reversibility was categorized as transient (normalization of renal function within 3 days of AKI onset) or persistent (non-resolution of AKI within 3 days of onset or need for RRT). A linear mixed model was applied to evaluate the factors that could influence renal RI.

Results: Eighty-three consecutive patients were included. Of these, 65% were male and 50.6% were medical admissions. Mean SAPS 3 was 47 ± 16. Renal RI was significantly different between no-AKI (0.64 ± 0.06), transient AKI (0.64 ± 0.07), and persistent AKI groups (0.70 ± 0.08, p < 0.01). Variables associated with renal RI variations were mean arterial pressure, lactate, age, and persistent AKI (p < 0.05). No association between serum chloride and renal RI was observed (p = 0.868).

Conclusions: Mean arterial pressure, lactate, age, and type of AKI might influence renal RI in critically ill patients.
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http://dx.doi.org/10.1186/s13613-019-0500-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355884PMC
January 2019

A computational model to understand mouse iron physiology and disease.

PLoS Comput Biol 2019 01 4;15(1):e1006680. Epub 2019 Jan 4.

Center for Quantitative Medicine and Department of Cell Biology, University of Connecticut School of Medicine, Farmington, Connecticut, United States of America.

It is well known that iron is an essential element for life but is toxic when in excess or in certain forms. Accordingly there are many diseases that result directly from either lack or excess of iron. Yet many molecular and physiological aspects of iron regulation have only been discovered recently and others are still elusive. There is still no good quantitative and dynamic description of iron absorption, distribution, storage and mobilization that agrees with the wide array of phenotypes presented in several iron-related diseases. The present work addresses this issue by developing a mathematical model of iron distribution in mice calibrated with ferrokinetic data and subsequently validated against data from mouse models of iron disorders, such as hemochromatosis, β-thalassemia, atransferrinemia and anemia of inflammation. To adequately fit the ferrokinetic data required inclusion of the following mechanisms: a) transferrin-mediated iron delivery to tissues, b) induction of hepcidin by transferrin-bound iron, c) ferroportin-dependent iron export regulated by hepcidin, d) erythropoietin regulation of erythropoiesis, and e) liver uptake of NTBI. The utility of the model to simulate disease interventions was demonstrated by using it to investigate the outcome of different schedules of transferrin treatment in β-thalassemia.
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http://dx.doi.org/10.1371/journal.pcbi.1006680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334977PMC
January 2019

Career Termination of Portuguese Elite Football Players: Comparison between the Last Three Decades.

Sports (Basel) 2018 Nov 28;6(4). Epub 2018 Nov 28.

Department of Sport Sciences, Universidade da Beira Interior, 6201-001 Covilhã, Portugal.

The aim of this study was to explore the process of career termination of elite soccer players, comparing the quality and the resources to support career termination over the last three decades. To this end, was developed a questionnaire defined by four sections: (a) biographical data, (b) athletic career, (c) quality of career termination and (d) available resources at the moment of career termination. Ninety male former elite Portuguese soccer players participated in this study. The results highlighted a decrease in the length of athletic career as football players and an increase in the number of years as youth players over the last 30 years. The results also revealed that the quality of career termination was difficult. The analysis of resources for career termination revealed an increase in a high level of education over the years. Despite the evolution in the level athletes' education in the last three decades, the athletic career termination remained difficult and it was reported that they did not plan their career termination. In line with previous studies, the results highlight that the lack of plans for career termination is one of the most important factors that constrain the quality of career transition.
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http://dx.doi.org/10.3390/sports6040155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315626PMC
November 2018

Gastrointestinal iron excretion and reversal of iron excess in a mouse model of inherited iron excess.

Haematologica 2019 04 8;104(4):678-689. Epub 2018 Nov 8.

Department of Pathology and Laboratory Medicine, Brown University, Providence, RI

The current paradigm in the field of mammalian iron biology states that body iron levels are determined by dietary iron absorption, not by iron excretion. Iron absorption is a highly regulated process influenced by iron levels and other factors. Iron excretion is believed to occur at a basal rate irrespective of iron levels and is associated with processes such as turnover of intestinal epithelium, blood loss, and exfoliation of dead skin. Here we explore iron excretion in a mouse model of iron excess due to inherited transferrin deficiency. Iron excess in this model is attributed to impaired regulation of iron absorption leading to excessive dietary iron uptake. Pharmacological correction of transferrin deficiency not only normalized iron absorption rates and halted progression of iron excess but also reversed body iron excess. Transferrin treatment did not alter the half-life of Fe in mutant mice. Fe-based studies indicated that most iron was excreted via the gastrointestinal tract and suggested that iron-loaded mutant mice had increased rates of iron excretion. Direct measurement of urinary iron levels agreed with Fe-based predictions that urinary iron levels were increased in untreated mutant mice. Fecal ferritin levels were also increased in mutant mice relative to wild-type mice. Overall, these data suggest that mice have a significant capacity for iron excretion. We propose that further investigation into iron excretion is warranted in this and other models of perturbed iron homeostasis, as pharmacological targeting of iron excretion may represent a novel means of treatment for diseases of iron excess.
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http://dx.doi.org/10.3324/haematol.2018.198382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442972PMC
April 2019

Characterization of patients transported with extracorporeal respiratory and/or cardiovascular support in the State of São Paulo, Brazil.

Rev Bras Ter Intensiva 2018 Jul-Sept;30(3):317-326

Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo - São Paulo (SP), Brasil.

Objective: To characterize the transport of severely ill patients with extracorporeal respiratory or cardiovascular support.

Methods: A series of 18 patients in the state of São Paulo, Brazil is described. All patients were consecutively evaluated by a multidisciplinary team at the hospital of origin. The patients were rescued, and extracorporeal membrane oxygenation support was provided on site. The patients were then transported to referral hospitals for extracorporeal membrane oxygenation support. Data were retrieved from a prospectively collected database.

Results: From 2011 to 2017, 18 patients aged 29 (25 - 31) years with a SAPS 3 of 84 (68 - 92) and main primary diagnosis of leptospirosis and influenza A (H1N1) virus were transported to three referral hospitals in São Paulo. A median distance of 39 (15 - 82) km was traveled on each rescue mission during a period of 360 (308 - 431) min. A median of one (0 - 2) nurse, three (2 - 3) physicians, and one (0 - 1) physical therapist was present per rescue. Seventeen rescues were made by ambulance, and one rescue was made by helicopter. The observed complications were interruption in the energy supply to the pump in two cases (11%) and oxygen saturation < 70% in two cases. Thirteen patients (72%) survived and were discharged from the hospital. Among the nonsurvivors, there were two cases of brain death, two cases of multiple organ dysfunction syndrome, and one case of irreversible pulmonary fibrosis.

Conclusions: Transportation with extracorporeal support occurred without serious complications, and the hospital survival rate was high.
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http://dx.doi.org/10.5935/0103-507X.20180052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180471PMC
December 2018

Reproducible Research Using Biomodels.

Authors:
Pedro Mendes

Bull Math Biol 2018 12 6;80(12):3081-3087. Epub 2018 Sep 6.

Center for Quantitative Medicine and Department of Cell Biology, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.

Like other types of computational research, modeling and simulation of biological processes (biomodels) is still largely communicated without sufficient detail to allow independent reproduction of results. But reproducibility in this area of research could easily be achieved by making use of existing resources, such as supplying models in standard formats and depositing code, models, and results in public repositories.
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http://dx.doi.org/10.1007/s11538-018-0498-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234049PMC
December 2018

An important role for periplasmic storage in Pseudomonas aeruginosa copper homeostasis revealed by a combined experimental and computational modeling study.

Mol Microbiol 2018 11 16;110(3):357-369. Epub 2018 Sep 16.

Center for Quantitative Medicine and Department of Cell Biology, University of Connecticut School of Medicine, 263 Farmington Av, Farmington, CT, 06030, USA.

Biological systems require precise copper homeostasis enabling metallation of cuproproteins while preventing metal toxicity. In bacteria, sensing, transport, and storage molecules act in coordination to fulfill these roles. However, there is not yet a kinetic schema explaining the system integration. Here, we report a model emerging from experimental and computational approaches that describes the dynamics of copper distribution in Pseudomonas aeruginosa. Based on copper uptake experiments, a minimal kinetic model describes well the copper distribution in the wild-type bacteria but is unable to explain the behavior of the mutant strain lacking CopA1, a key Cu efflux ATPase. The model was expanded through an iterative hypothesis-driven approach, arriving to a mechanism that considers the induction of compartmental pools and the parallel function of CopA and Cus efflux systems. Model simulations support the presence of a periplasmic copper storage with a crucial role under dyshomeostasis conditions in P. aeruginosa. Importantly, the model predicts not only the interplay of periplasmic and cytoplasmic pools but also the existence of a threshold in the concentration of external copper beyond which cells lose their ability to control copper levels.
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http://dx.doi.org/10.1111/mmi.14086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207460PMC
November 2018

An Overview of Network-Based and -Free Approaches for Stochastic Simulation of Biochemical Systems.

Computation (Basel) 2018 Mar 31;6(1). Epub 2018 Jan 31.

Center for Quantitative Medicine and Department of Cell Biology, University of Connecticut School of Medicine, 263 Farmington Av., Farmington, CT 06030-6033, USA.

Stochastic simulation has been widely used to model the dynamics of biochemical reaction networks. Several algorithms have been proposed that are exact solutions of the chemical master equation, following the work of Gillespie. These stochastic simulation approaches can be broadly classified into two categories: network-based and -free simulation. The network-based approach requires that the full network of reactions be established at the start, while the network-free approach is based on reaction rules that encode classes of reactions, and by applying rule transformations, it generates reaction events as they are needed without ever having to derive the entire network. In this study, we compare the efficiency and limitations of several available implementations of these two approaches. The results allow for an informed selection of the implementation and methodology for specific biochemical modeling applications.
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http://dx.doi.org/10.3390/computation6010009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013266PMC
March 2018

ANALYSIS OF SURGICAL SITE INFECTIONS IN PEDIATRIC PATIENTS AFTER ORTHOPEDIC SURGERY: A CASE-CONTROL STUDY.

Rev Paul Pediatr 2017 Jan-Mar;35(1):18-24

Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira - Fundação Oswaldo Cruz - Ministério da Saúde, Rio de Janeiro, RJ, Brasil.

Objectives: To describe the rate of surgical site infections in children undergoing orthopedic surgery in centers of excellence and analyze the patients' profiles.

Methods: Medical records of pediatric patients undergoing orthopedic surgery in the Jamil Haddad National Institute of Traumatology and Orthopedics from January 2012 to December 2013 were analyzed and monitored for one year. Patients diagnosed with surgical site infection were matched with patients without infection by age, date of admission, field of orthopedic surgery and type of surgical procedure. Patient, surgical and follow-up variables were examined. Descriptive, bivariate and correspondence analyses were performed to evaluate the patients' profiles.

Results: 347 surgeries and 10 surgical site infections (2.88%) were identified. There was association of infections with age - odds ratio (OR) 11.5 (confidence interval - 95%CI 1.41-94.9) -, implant - OR 7.3 (95%CI 1.46-36.3) -, preoperative period - OR 9.8 (95%CI 1.83-53.0), and length of hospitalization - OR 20.6 (95%CI 3.7-114.2). The correspondence analysis correlated the infection and preoperative period, weight, weight Z-score, age, implant, type of surgical procedure, and length of hospitalization. Average time to diagnosis of infection occurred 26.5±111.46 days after surgery.

Conclusions: The rate of surgical site infection was 2.88%, while higher in children over 24 months of age who underwent surgical implant procedures and had longer preoperative periods and lengths of hospitalization. This study identified variables for the epidemiological surveillance of these events in children. Available databases and appropriate analysis methods are essential to monitor and improve the quality of care offered to the pediatric population.
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http://dx.doi.org/10.1590/1984-0462/;2017;35;1;00011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417805PMC
June 2018

Solid and aqueous magnetoliposomes as nanocarriers for a new potential drug active against breast cancer.

Colloids Surf B Biointerfaces 2017 Oct 8;158:460-468. Epub 2017 Jul 8.

Centre of Physics (CFUM), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; QuantaLab, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal. Electronic address:

Iron oxide nanoparticles, with diameters around 12nm, were synthesized by coprecipitation method. The magnetic properties indicate a superparamagnetic behavior with a coercive field of 9.7Oe and a blocking temperature of 118K. Both aqueous and solid magnetoliposomes containing magnetite nanoparticles have sizes below 150nm, suitable for biomedical applications. Interaction between both types of magnetoliposomes and models of biological membranes was proven. A new antitumor compound, a diarylurea derivative of thienopyridine, active against breast cancer, was incorporated in both aqueous and solid magnetoliposomes, being mainly located in the lipid membrane. A promising application of these magnetoliposomes in oncology is anticipated, allowing a combined therapeutic approach, using both chemotherapy and magnetic hyperthermia.
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http://dx.doi.org/10.1016/j.colsurfb.2017.07.015DOI Listing
October 2017

biochem4j: Integrated and extensible biochemical knowledge through graph databases.

PLoS One 2017 14;12(7):e0179130. Epub 2017 Jul 14.

Manchester Centre for Synthetic Biology of Fine and Specialty Chemicals (SYNBIOCHEM), Manchester Institute of Biotechnology, The University of Manchester, Manchester, United Kingdom.

Biologists and biochemists have at their disposal a number of excellent, publicly available data resources such as UniProt, KEGG, and NCBI Taxonomy, which catalogue biological entities. Despite the usefulness of these resources, they remain fundamentally unconnected. While links may appear between entries across these databases, users are typically only able to follow such links by manual browsing or through specialised workflows. Although many of the resources provide web-service interfaces for computational access, performing federated queries across databases remains a non-trivial but essential activity in interdisciplinary systems and synthetic biology programmes. What is needed are integrated repositories to catalogue both biological entities and-crucially-the relationships between them. Such a resource should be extensible, such that newly discovered relationships-for example, those between novel, synthetic enzymes and non-natural products-can be added over time. With the introduction of graph databases, the barrier to the rapid generation, extension and querying of such a resource has been lowered considerably. With a particular focus on metabolic engineering as an illustrative application domain, biochem4j, freely available at http://biochem4j.org, is introduced to provide an integrated, queryable database that warehouses chemical, reaction, enzyme and taxonomic data from a range of reliable resources. The biochem4j framework establishes a starting point for the flexible integration and exploitation of an ever-wider range of biological data sources, from public databases to laboratory-specific experimental datasets, for the benefit of systems biologists, biosystems engineers and the wider community of molecular biologists and biological chemists.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179130PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510799PMC
September 2017

COPASI and its applications in biotechnology.

J Biotechnol 2017 Nov 24;261:215-220. Epub 2017 Jun 24.

BioQuant/COS, Heidelberg University, Heidelberg, Germany.

COPASI is software used for the creation, modification, simulation and computational analysis of kinetic models in various fields. It is open-source, available for all major platforms and provides a user-friendly graphical user interface, but is also controllable via the command line and scripting languages. These are likely reasons for its wide acceptance. We begin this review with a short introduction describing the general approaches and techniques used in computational modeling in the biosciences. Next we introduce the COPASI package, and its capabilities, before looking at typical applications of COPASI in biotechnology.
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http://dx.doi.org/10.1016/j.jbiotec.2017.06.1200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623632PMC
November 2017