β-lactam dosing in critical patients: a narrative review of optimal efficacy and the prevention of resistance and toxicity

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time β-lactam antibiotic dose adjustments according to the patient's condition are critical. The continuous infusion of β-lactams and the therapeutic monitoring of their concentration have both been proposed to improve their efficacy, but strong data to support their use are still lacking. The knowledge of the pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further increase the dosing conundrum. Recent data have emerged linking overexposure to β-lactams to central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition, it is well recognized that β-lactam exposure facilitates resistance selection and that correct dosing can help to overcome it. In this review, we discuss recent data regarding real-time β-lactam antibiotic dose adjustment, options in special populations, and the impacts on mitochondria and the microbiome.info:eu-repo/semantics/publishedVersio

Comparing AHP and ELECTRE I for prioritizing software requirements

Requirement prioritization is a process that allows selection of the “key” candidate requirements, the ones that are the most important for the construction of quality and cost-controlled software. Requirement prioritization brings certain issues and challenges related with the different stakeholders involved in the project, as well as with the prioritization techniques used, which differ in procedures, criteria and metrics. This manuscript compares two multi-criteria decision methods (MCDM), AHP and ELECTRE I, seeking to justify which one is the most feasible in the requirement prioritization process of a real-world case study. To accomplish this aim, several criteria were used to compare the applicability and performance of both MCDMs. In order to reflect reality as close as possible, several stakeholders, including software professionals directly related to the case study, were involved. The results confirm the intuition that ELECTRE I is more easily applicable than AHP. ELECTRE I is subject to fewer mistakes in comparisons of the requirements than the AHP method, as these are carried out differently. In fact, due to its inherent complexity, AHP becomes even impractical in software projects with a large number of requirements

The PREPIT project : Pregraduate Research Program Impact & Trajectories : a work in progress

Introduction: The GAPIC – Gabinete de Apoio à Investigação Científica, Tecnológica e Inovação (Scientific Research, Technology and Innovation Support Office) of Faculdade de Medicina da Universidade de Lisboa (FMUL) is celebrating its 30th anniversary. During the past 30 years, GAPIC has developed several initiatives to promote and disseminate scientific research, mostly among undergraduate students and young graduates. These initiatives have been fundamental in the career path of young students and have had an increase impact in the future of society and the quality of life of its citizens. To assess the impact of GAPIC Programs in terms of gains in knowledge, skills and attitudes; barriers and opportunities; scientific production and professional trajectories of undergraduate students who participated in the GAPIC scientific research projects from 1997/98 to 2014/2015, the PREPIT Project is being developed with the collaboration of the FMUL´s library team. Two primary objectives were defined: i) Evaluate scientific productivity indicators of participants in GAPIC undergraduate programs in short and long term (study A); ii) Characterize the perspectives of participants in GAPIC undergraduate programs on the importance and impact of these (study B). Secondary objectives are: i) Identify predictors of scientific productivity indicators of these participants in short and long term (study A); ii) Characterize professional and academic trajectories among participants and identify predictors of these trajectories (study B). As a work in progress, only preliminary results are presented. Methods: Study Design1: two-component observational study: cohort, retrospective, bibliometric (study A) and cross-sectional, by electronic survey (study B). Population: all undergraduate students accepted to the GAPIC “Education for Science” program (or equivalent) from 1997/98 to 2014/2015. Data Collection and Instruments: i) data collection for the bibliometric cohort study (study A): academic year/GAPIC program; number of participations; demographic data; project description; ORCID iD. The definition of scientific profiles will be done through WoS and Scopus bibliometric data. Data will be exported to Excel and analyzed through SPSS. For data collection by electronic survey (study B) SurveyMonkey platform will be used. The survey will include closed, single and multiple choice questions, with Likert2 items. A modified Dillmman methodology3 with 3 reminders will be used and the survey will be open for 4 weeks. Study B protocol will be submitted to the Ethics Committee. Results and discussion: Based on author name and ORCID iD search, by now we have collected preliminary bibliometric data from 553 students involved in 387 GAPIC projects. As this is a work in progress more results will be available soon after the distribution and analysis of the electronic survey results. At the end of the project we aim to achieve all the proposed objectives, to gain an in-depth understanding of the impact and relevance of integrating research in all stages of medical education and positively contribute to support future research training interventions.info:eu-repo/semantics/publishedVersio

Future without delirium: not quite there yet but we can start by prescribing touch

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.The recently published article by Kotfs et al. “The future of intensive care: delirium should no longer be an issue”, brought us great interest and although we agree with the authors’ perspective this is still far from being reality. Despite delirium increase report as an adverse event, it is often faced on daily practice as a patient’s “weakness” or an inevitability due to acute illness that we fail to avoid. Tis perspective precludes multidisciplinary team effort from targeting the modifiable components of delirium mentioned in the paper.info:eu-repo/semantics/publishedVersio

Curcumin and 10-undecenoic acid as natural quorum sensing inhibitors of LuxS/AI-2 of Bacillus subtilis and LasI/LasR of Pseudomonas aeruginosa

The quorum sensing (QS) system is related to cell-to-cell communication as a function of population density, which regulates several physiological functions including biofilm formation and virulence gene expression. QS inhibitors have emerged as a promising strategy to tackle virulence and biofilm development. Among a wide variety of phytochemicals, many of them have been described as QS inhibitors. Driven by their promising clues, this study aimed to identify active phytochemicals against LuxS/autoinducer-2 (AI-2) (as the universal QS system) from Bacillus subtilis and LasI/LasR (as a specific QS system) of Pseudomonas aeruginosa, through in silico analysis followed by in vitro validation. The optimized virtual screening protocols were applied to screen a phytochemical database containing 3479 drug-like compounds. The most promising phytochemicals were curcumin, pioglitazone hydrochloride, and 10-undecenoic acid. In vitro analysis corroborated the QS inhibitory activity of curcumin and 10-undecenoic acid, however, pioglitazone hydrochloride showed no relevant effect. Inhibitory effects on LuxS/AI-2 QS system triggered reduction of 33-77% by curcumin (at 1.25-5 mu g/mL) and 36-64% by 10-undecenoic acid (at 12.5-50 mu g/mL). Inhibition of LasI/LasR QS system was 21% by curcumin (at 200 mu g/mL) and 10-54% by 10-undecenoic acid (at 15.625-250 mu g/mL). In conclusion, in silico analysis allowed the identification of curcumin and, for the first time, 10-undecenoic acid (showing low cost, high availability, and low toxicity) as alternatives to counteract bacterial pathogenicity and virulence, avoiding the imposition of selective pressure usually related to classic industrial disinfection and antibiotics therapy

Síndrome de Austrian: descrição de uma entidade excepcionalmente rara e mortal

Austrian Syndrome is the rare combination of a triad of endocarditis, meningitis, and pneumonia in the context of pneumococcal infection. Due to the involvement of several anatomical sites, the Austrian syndrome has a high mortality. Importantly, endocarditis is usually not considered during pneumococcal infection. We present a case of Austrian syndrome in a previously healthy 67-year-old woman. She featured with mental state alteration, respiratory failure, and shock, and was diagnosed with ceftriaxone-sensitive pneumococcal bacteremia, meningitis, and pneumonia. A transesophageal echocardiogram revealed vegetation of the mitral valve. Despite an improvement in her medical condition, she remained in a coma and died due to neurological complications. Even though the major cause of mortality in Austrian syndrome is cardiac involvement, meningitis is also linked with high morbidity and eventually death. We emphasize the relevance of an early diagnosis of the triad in order to decrease the very high mortality associated with this syndrome.A síndrome de Austrian é uma entidade extremamente rara, pautada por meningite, endocardite e pneumonia secundárias a doença pneumocócica invasiva. Devido à expressão multissistêmica, a mortalidade associada é elevada. Particularmente, a manifestação como endocardite é muitas vezes clinicamente insuspeita, carecendo de elevado índice de suspeita. Apresenta-se um caso de síndrome de Austrian numa doente do sexo feminino, 67 anos, previamente saudável. Clinicamente, apresentava coma, insuficiência respiratória e choque, tendo sido diagnosticada pneumonia e meningite, e com bacteremia a Streptococcus pneumoniae. Ecocardiograma transesofágico evidenciou uma vegetação na válvula mitral. Apesar da regressão do quadro respiratório, persistiu um quadro de coma, acabando a doente por morrer. Apesar da principal causa de morte descrita na síndrome de Austrian estar relacionada com complicações de endocardite, apresenta-se um caso único de apresentação e morte por meningite. Com poucos casos descritos mundialmente, sublinha-se a necessidade de um diagnóstico precoce desta tríade, motivo pelo qual relatamos o caso descrito

Phototriggering of neuroactive amino acids from 5,6-benzocoumarinyl conjugates

Uncaging of several neuroactive amino acids, namely β-alanine, tyrosine, 3,4-dihydroxyphenylalanine (DOPA) and glutamic acid from the corresponding 5,6-benzocoumarinyl conjugates was carried out by irradiation at different wavelengths and in different solvent systems. The release of the various amino acids was faster in ACN/HEPES buffer mixtures and for the tyrosine conjugate, an increase in the photolysis reaction rates and the quantitative uncaging of the amino acid was associated with increasing water content in the solvent mixture.Fundação para a Ciência e a Tecnologia (FCT) - REDE/1517/RMN/2005Fundo Europeu de Desenvolvimento Regional (FEDER) - POCI 201

Influência das propriedades reológicas do sangue em microcanal com contração simétrica

Neste trabalho recorreu-se à Dinâmica de Fluidos Computacional para simular escoamentos nãonewtonianos em microcanais com estenose simétrica. Para descrever o comportamento não-newtoniano do sangue utilizou-se o modelo de Carreau sendo os resultados obtidos considerando este modelo comparados com os obtidos para fluido newtoniano, o que permitiu avaliar o impacto das propriedades não-newtonianas nos escoamentos estudados

Comparative study of polyaromatic and polyheteroaromatic fluorescent photocleavable protecting groups

Fluorescent conjugates of N-benzyloxycarbonyl protected gamma-aminobutyric acid were prepared by coupling to its C-terminus several polyheteroaromatic, based on the oxobenzopyran skeleton (trivially known as coumarin) and polyaromatic labels, such as naphthalene and pyrene. Photophysical properties were evaluated, as well as their behaviour towards photocleavage by irradiation in MeOH/HEPES buffer solution (80:20), in a photochemical reactor at different wavelengths (254, 300, 350 and 419 nm), followed by HPLC/UV monitoring.Thanks are due to the Foundation for Science and Technology (Portugal) for financial support through project PTDC/QUI/69607/2006 and a Ph.D. grant to M.J.G.F. (SFRH/BD/36695/2007)

Aportaciones desde la biomecánica de la natación de competición

A natação é uma modalidade individual, cíclica e fechada, pelo que, no respectivo quadro de factores determinantes do sucesso competitivo, a optimização do gesto técnico desempenha um papel determinante.info:eu-repo/semantics/publishedVersio