Analgesic interpatient variability of remifentanil assessed through pupillary dilation reflex

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Pupillary pain index correlates with postoperative pain scores in neurosurgical patients

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Pupillary pain index correlates in increasing concentrations of remifentanil

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Synthesis and screening of antibacterial activity of 2,4,5-tri(hetero)arylimidazoles based on thieno[3,2-b]thiophene

After the discovery of antibiotics, efforts were made to develop new drugs in order to treat infections caused by a wide range of bacterial strains. With the use of antibiotics for decades, bacteria have adapted, so that resistant strains have emerged. Moreover, the uncontrolled and abusive use of antibiotics has increased, which aggravates the emergence of new resistant strains. The emergence of multidrug resistant (MDR) bacteria has quickly become a worldwide health problem, so new strategies must be developed in order to control MDR bacteria, namely the rational development of new drugs. Imidazole derivatives have several biological activities, including antibacterial activity. In this sense, efforts have been made to develop imidazole-based compounds, because they present higher curative effect than other antibiotics used in clinical practice, lower toxicity and less side effects.1 With this in mind, we report the synthesis of two 2,4,5-tri(hetero)arylimidazoles 3a-b based on thieno[3,2-b]thiophene heterocyclic spacer (Figure 1), through the Radziszewski reaction2 and their characterization by 1H and 13C NMR, UV-Vis absorption and fluorescence spectroscopies. In addition, a screening for antibacterial activity with the synthetized imidazole derivatives against Bacillus subtilis was carried out, using the agar diffusion technique. The results showed the inhibition of Bacillus subtilis proliferation, suggesting antibacterial activity. Therefore, these new imidazole derivatives have the potential for the development of new antibacterial drugs.Thanks are due to Fundação para a Ciência e Tecnologia (FCT) and FEDER (European Fund for Regional Development)-COMPETE-QRENEU for financial support through the Chemistry Research Centre of the University of Minho (UID/QUI/00686/2020). This work was also supported by the “Contrato-Programa” UIDB/04050/2020 funded by national funds through the FCT I.P. Thanks are also due to FCT for financial support to the Portuguese NMR network (PTNMR, Bruker Avance III – Univ. Minho).info:eu-repo/semantics/publishedVersio

Identification of genomic loci associated with genotypic and phenotypic variation among Pseudomonas aeruginosa clinical isolates from pneumonia

In this work, a genotype-phenotype survey of a highly diversified Pseudomonas aeruginosa collection was conducted, aiming to detail pathogen-associated scenarios that clinicians face nowadays. Genetic relation based on RAPD-PCR of 705 isolates, retrieved from 424 patients and several clinical contexts, reported an almost isolate-specific molecular-pattern. Pneumonia-associated isolates HB13 and HB15, clustered in the same RAPD-PCR group, were selected to evaluate the genomic background underlying their contrasting antibiotic resistance and virulence. The HB13 genome harbors antibiotic-inactivating enzymes-coding genes (e.g. aac(3)-Ia, arr, blaVIM-2) and single-nucleotide variations (SNVs) in antibiotic targets, likely accounting for its pan-resistance, whereas HB15 susceptibility correlated to predicted dysfunctional alleles. Isolate HB13 showed the unprecedented rhl-cluster absence and variations in other pathogen competitiveness contributors. Conversely, HB15 genome comprises exoenzyme-coding genes and SNVs linked to increased virulence. Secretome analysis identified signatures features with unknown function as potential novel pathogenic (e.g. a MATE-protein in HB13, a protease in HB15) and antibiotic resistance (a HlyD-like secretion protein in HB13) determinants. Detection of active prophages, proteases (including protease IV and alkaline metalloproteinase), a porin and a peptidase in HB15 highlights the secreted arsenal likely essential for its virulent behavior. The presented phenotype-genome association will contribute to the current knowledge on Pseudomonas aeruginosa pathogenomics.This work was supported by the strategic programme UID/BIA/0050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through FCT I.P., by ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) and through a PhD grant (SFRH/BD/98558/2013) attributed to C.S.M. The facility for Biological Mass Spectrometry Isabel Moura was funded by Proteomass Scientific Society. H.M.S. is funded by the FCT 2015 Investigator Program (IF/00007/2015)

The neural correlates of obsessive-compulsive disorder: a multimodal perspective

Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric conditions. An extensive body of the literature has described some of the neurobiological mechanisms underlying the core manifestations of the disorder. Nevertheless, most reports have focused on individual modalities of structural/functional brain alterations, mainly through targeted approaches, thus possibly precluding the power of unbiased exploratory approaches. Eighty subjects (40 OCD and 40 healthy controls) participated in a multimodal magnetic resonance imaging (MRI) investigation, integrating structural and functional data. Voxel-based morphometry analysis was conducted to compare between-group volumetric differences. The whole-brain functional connectome, derived from resting-state functional connectivity (FC), was analyzed with the network-based statistic methodology. Results from structural and functional analysis were integrated in mediation models. OCD patients revealed volumetric reductions in the right superior temporal sulcus. Patients had significantly decreased FC in two distinct subnetworks: the first, involving the orbitofrontal cortex, temporal poles and the subgenual anterior cingulate cortex; the second, comprising the lingual and postcentral gyri. On the opposite, a network formed by connections between thalamic and occipital regions had significantly increased FC in patients. Integrative models revealed direct and indirect associations between volumetric alterations and FC networks. This study suggests that OCD patients display alterations in brain structure and FC, involving complex networks of brain regions. Furthermore, we provided evidence for direct and indirect associations between structural and functional alterations representing complex patterns of interactions between separate brain regions, which may be of upmost relevance for explaining the pathophysiology of the disorder

Modeling reservoir surface temperatures for regional and global climate models: A multi-model study on the inflow and level variation effects

UIDB/04292/2020 KI-853/13 KI-853- 16 UIDB/04292/2020The complexity of the state-of-the-art climate models requires high computational resources and imposes rather simplified parameterization of inland waters. The effect of lakes and reservoirs on the local and regional climate is commonly parameterized in regional or global climate modeling as a function of surface water temperature estimated by atmosphere-coupled one-dimensional lake models. The latter typically neglect one of the major transport mechanisms specific to artificial reservoirs: heat and mass advection due to inflows and outflows. Incorporation of these essentially two-dimensional processes into lake parameterizations requires a trade-off between computational efficiency and physical soundness, which is addressed in this study. We evaluated the performance of the two most used lake parameterization schemes and a machine-learning approach on high-resolution historical water temperature records from 24 reservoirs. Simulations were also performed at both variable and constant water level to explore the thermal structure differences between lakes and reservoirs. Our results highlight the need to include anthropogenic inflow and outflow controls in regional and global climate models. Our findings also highlight the efficiency of the machine-learning approach, which may overperform process-based physical models in both accuracy and computational requirements if applied to reservoirs with long-term observations available. Overall, results suggest that the combined use of process-based physical models and machine-learning models will considerably improve the modeling of air-lake heat and moisture fluxes. A relationship between mean water retention times and the importance of inflows and outflows is established: reservoirs with a retention time shorter than ĝ1/4g100gd, if simulated without inflow and outflow effects, tend to exhibit a statistically significant deviation in the computed surface temperatures regardless of their morphological characteristics.publishersversionpublishe

Cardiovascular responses to passive static flexibility exercises are influenced by the stretched muscle mass and the Valsalva maneuver

BACKGROUND: The respiratory pattern is often modified or even blocked during flexibility exercises, but little is known about the cardiovascular response to concomitant stretching and the Valsalva maneuver (VM) in healthy subjects. OBJECTIVES: This study evaluated the heart rate (HR), systolic blood pressure (SBP), and rate-pressure product (RPP) during and after large and small muscle group flexibility exercises performed simultaneously with the VM. METHODS: Asymptomatic volunteers (N = 22) with the following characteristics were recruited: age, 22 ± 3 years; weight, 73 ± 6 kg; height, 175 ± 5 cm; HR at rest, 66 ± 9 BPM; and SBP at rest, 113 ± 10 mmHg. They performed two exercises: four sets of passive static stretching for 30 s of the dorsi-flexion (DF) of the gastrocnemius and the hip flexion (HF) of the ischio-tibialis. The exercises were performed with (V+) or without (V-) the VM in a counterbalanced order. The SBP and HR were measured, and the RPP was calculated before the exercise session, at the end of each set, and during a 30-min post-exercise recovery period. RESULTS: The within-group comparisons showed that only the SBP and RPP increased throughout the sets (p<0.05), but no post-exercise hypotension was detected. The between-group comparisons showed that greater SBP increases were related to the VM and to a larger stretched muscle mass. Differences for a given set were identified for the HR (the HFV+ and HFV- values were higher than the DFV+ and DFV- values by approximately 12 BPM), SBP (the HFV+ value was higher than the DFV+ and DFV- values by approximately 12 to 15 mmHg), and RPP (the HFV+ value was higher than the HFV- value by approximately 2000 mmHGxBPM, and the HFV+ value was higher than the DFV+ and DFV- values by approximately 4000 mmHGxBPM). CONCLUSION: Both the stretched muscle mass and the VM influence acute cardiovascular responses to multiple-set passive stretching exercise sessions

Adipocyte proteome and secretome influence inflammatory and hormone pathways in glioma

Gliomas represent the most common primary malignant brain tumors in adults, with an extremely poor prognosis. Among several risk factors, lifestyle was also recently identified as a major risk factor for the development of primary glioma. In the present study, we explore the relationship between obesity and glioma in a cellular model. Thus, we have study the influence of adipocytes secretome on glioma cell line GL261. Using the 3T3-L1 adipocyte cell line, and its conditioned medium (adipokines-enriched medium), we showed that adipocyte-released factors relate with glioma angiogenic, growth, hormones and metabolic behavior by MALDI-TOF-MS and proteomic array analysis. In a first view, STI1, hnRNPs and PGK1 are under expressed on CGl. Similarly, both carbonic anhydrase and aldose reductase are even suppressed in glioma cells that grown under adipokines-enriched environment. Contrariwise, RFC1, KIF5C, ANXA2, N-RAP and RACK1 are overexpressed in GL261 cell the in the presence of the adipokines-enriched medium. We further identified the factors that are released by adipocyte cells, and revealed that several pro-inflammatory and angiogenic factors, such as IL-6, IL-11, LIF, PAI-1, TNF-α, endocan, HGF, VEGF IGF-I, were secreted to the medium into a high extent, whereas TIMP-1 and SerpinE1 were under expressed on CGl. This study discloses an interesting in vitro model for the study of glioma biology under a "obesity" environment, that can be explored for the understanding of cancer cells biology, for the search of biomarkers, prognostic markers and therapeutic approaches.info:eu-repo/semantics/publishedVersio