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Objective: To identify the most effective non-pharmacological measures for pain control in preterm infants in the Neonatal Intensive Care Unit (NICU)., Methods: A Systematic review and network meta-analysis of randomized clinical trials published in English, Portuguese, and Spanish from April 2020 to December 2023. The data sources used were MedLine via PubMed, LILACS, EMBASE, The Cochrane Central Register of Controlled Trials, and Pedro. We performed the risk of bias analysis with Rob 2 and the certainty of the evidence and strength of the recommendation using the Grading of Recommendations Assessment, Development, and Evaluation system. We assessed heterogeneity using the Higgins and Thompson I 2 test, the classification of interventions using the P-score, and inconsistencies using the Direct Evidence Plot., Results: From 210 publications identified, we utilized 12 studies in analysis with 961 preterm infants, and we combined ten studies in network meta-analysis with 716 preterm infants, and 12 combinations of non-pharmacological measures. With moderate confidence, sensory saturation, sugars, non-nutritive sucking, maternal heart sound, lullaby, breast milk odor/taste, magnetic acupuncture, skin-to-skin contact, and facilitated tucking have been shown to reduce pain in preterm infants when compared to no intervention, placebo, proparacaine or standard NICU routine: sensory saturation [SMD 5,25 IC 95%: -8,98; -1,53], sugars [SMD 2,32 IC 95%: -3,86; -0,79], pacifier [SMD 3,74 IC 95%: -7,30; 0,19], and sugars and pacifier SMD [3,88 IC 95% -7,72; -0,04]., Conclusion: Non-pharmacological measures are strongly recommended for pain management in preterm infants in the NICU., Implications for Clinical Practice: The findings of this study have important implications for policy and practice. This is the only systematic review that compared the effectiveness of non-pharmacological measures, thus making it possible to identify which measure presents the best results and could be the first choice in clinical decision making., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Several studies highlighted the complexity of mixing pesticides present in Amazonian aquatic environments today. There is evidence that indicates that ongoing climate change can alter the pattern of pesticide use, increasing the concentration and frequency of pesticide applications. It is known that the combination of thermal and chemical stress can induce interactive effects in aquatic biota, which accentuates cell and molecular damage. However, considering that the effects of climate change go beyond the increase in temperature the objective of this study was to evaluate the effect of climate change scenarios proposed by 6 th IPCC report and a mixture of pesticides on the tambaqui (Colossoma macropomum). The hypothesis of this study is that the negative effects will be accentuated by the combination of an extreme climate changes scenario and a mixture of pesticides. To test the hypothesis, juvenile tambaqui were exposed to a combination of four pesticides (chlorpyrifos, malathion, carbendazim and atrazine) in two scenarios, one that simulates current environmental conditions and another that predicted the environmental scenario for the year 2100. Fish were subjected to the experimental conditions for 96 h. At the end of the experiment, samples of blood, gills, liver, brain, and muscle were obtained for hematological, genotoxic, biochemical, and histopathological analyses. The results demonstrate that environmentally realistic concentrations of pesticides, when mixed, can alter the biochemical responses of tambaqui. The extreme scenario promotes hematological adjustments, but impairs branchial antioxidant enzymes. There is an interaction between the mixture of pesticides and the extreme scenario, accentuating liver tissue damage, which demonstrates that even increased activity of antioxidant and biotransformation enzymes were not sufficient to prevent liver damage., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Drug-release systems have attracted attention over the last few years since they can be used as a substitute for traditional methods of drug delivery. These have the advantage of being directly administered at the treatment site and can maintain the drug at adequate levels for a longer period, thus increasing their efficacy. Starch-based films are interesting candidates for use as matrices for drug release, especially due to starch's non-toxic properties and its biocompatibility. Endophytic fungi are an important source of bioactive molecules, including secondary metabolites such as phenolic compounds with antioxidant activity. In the present study, cassava starch-based films were developed to act as release systems of phenolic compounds with antioxidant activity. The Amazonian endophytic fungus Aspergillus niger MgF2 was cultivated in liquid media, and the fungal extract was obtained by liquid-liquid partition with ethyl acetate. The starch-based films incorporated with the fungal extract were characterized in regards to their physicochemical properties. The release kinetics of the extract from the film and its antioxidant and cytotoxic properties were also evaluated. The films incorporated with the extract presented maximum release after 25 min at 37 °C and pH 6.8. In addition, it was observed that the antioxidant compounds of the fungal extract maintain their activity after being released from the film, and were non-toxic. Therefore, considering the promising physicochemical properties of the extract-incorporated films, and their considerable antioxidant capacity, the films demonstrate great biotechnological potential with diverse applications in the pharmacological and cosmetic industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Different classes of pesticides such as fungicides, herbicides, and insecticides, can induce differential expression of genes that are involved in tumorigenesis events in fish, including the expression of tumor suppressor tp53. The degree and duration of the stressful condition is decisive in defining which tp53-dependent pathway will be activated. Herein we evaluate the target genes expression that participates in the regulation pathway of the tumor suppressor tp53 and in the cancerous processes in tambaqui after exposure to malathion. Our hypothesis is that malathion promotes a gene response that is differentially regulated over time, with positive regulation of tp53 target genes related to the apoptotic pathway and a negative regulation of genes that promote antioxidant responses. The fish were exposed to a sublethal concentration of the insecticide for 6 and 48 h. Liver samples were used to analyze the expression of 11 genes using real-time PCR. Overall, the malathion promoted over time increases in tp53 expression and differential expression of tp53 related genes. The exposure resulted in the activation of damage response related genes, caused a positive expression of atm/atr genes. The pro-apoptotic gene bax was up-regulated and the anti-apoptotic bcl2 was down-regulated. Increased expression of mdm2 and sesn1 in the first hours of exposure and no effect on the antioxidant genes sod2 and gpx1 were also observed. We also witnessed an increase in the expression of the hif-1α gene, with no effect on ras proto-oncogene. The extension of this stressful condition accentuated tp53 transcription, and minimized the levels of mdm2, sens1 and bax; however, it down regulated the levels of bcl2 and the bcl2/bax ratio, which indicates the maintenance of the apoptotic response to the detriment of an antioxidant response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A preservation protocol has not been established for Colossoma macropomum oocytes, and its development may improve the production and breeding programs of this South American fish species. Thus, this study aimed to determine the effect of different methods and protocols for the preservation of C. macropomum oocytes. Seven experiments were conducted throughout the breeding season of this species. The oocytes were collected and stored in sterile conditions. Preserved oocytes were subjected to storage in the following treatments: room temperature (RT, 27 °C), centrifugation followed by ovarian fluid removal (Cen), vacuum (Vac), chilled temperature (ChT), centrifugation and vacuum (CV), vacuum and chilled temperature (VChT), and centrifugation, vacuum, and chilled temperature (CVChT) in dry sterilized plastic containers and plastic bags. Chilled storage was tested at 4 and 13 °C. Fertilization and hatching rates were assessed at 0, 30, 60, 90, and 120 min after stripping (MAS) for preservation protocols. The larval malformation rate was analyzed at 0 and 30 MAS for RT and ChT. Quantitation and identification (by mean of MALDI-TOF MS) of bacteria were performed at 0, 60, 90, and 120 MAS, and scanning electron microscopy (SEM) analyses were carried out at 0, 60, and 90 MAS. The fertilization and hatching rates decreased over preservation time and breeding season. RT samples fertilized at 0, 30, and 60 MAS yielded similar fertilization rates at both the beginning and end of the season. By the end of the season, oocytes from treatment ChT at 13 °C 30 MAS yielded higher fertilization and hatching rates, and a lower percentage of larvae malformation than RT 30 MAS. The treatment ChT at 4 °C triggered low a fertilization rate. The treatments ChT (13 °C) and Cen provided good fertilization rate when used alone and with other approaches, i.e., treatments VChT, CV, and CVChT. The treatment Vac presented inconsistent results, so no conclusion could be made. Bacterial colony counts were low (10-1.6 × 10 5  CFU-mL -1 ), and a total of 18 bacteria species were identified in all batches analyzed; however, the treatments did not influence the number of bacteria. C. macropomum female breeders presented distinct bacteria species in their oocytes and the presence of bacteria did not impair oocyte quality until 120 MAS. Moreover, SEM analyses showed that the micropyle was not occluded during oocyte storage, and ovarian fluid was observed on the surface of chilled oocytes. Therefore, Colossoma macropomum oocytes could be preserved under chilled storage at 13 °C for 30 min throughout its breeding season., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To determine the accuracy of the 5-time stand-to-sit (5TSTS) test for the identification of older adults with reduced gait speed., Design: Cross-sectional study., Setting and Participants: A total of 559 community-dwelling older adults were included in the study, divided into groups of women (n = 465) and men (n = 94)., Methods: 5TSTS and gait speed were assessed. Multiple linear regression analysis with adjustment was performed in order to determine the association between 5TSTS and gait speed, followed by the receiver operating characteristic (ROC) curve for the identification of the usefulness of 5TSTS to discriminate older adults with reduced gait speed. Based on the ROC curve, we identified the area under the curve, the sensitivity, specificity, and cutoff points of the 5TSST. Statistical analyses were made using the SPSS software (version 25.0), and a significance level of 5% (P ≤ .05) was adopted., Results: The 5TSTS showed correlation with gait speed. Additionally, 5TSTS was able to discriminate reduced gait speed with moderate accuracy (P < .05; AUC between 0.7 and 0.8). For women, the cutoff scores for 5TSTS to identify gait speed <0.8 m/s was 14.15 seconds; for gait speed <1.0 m/s, it was 12.67 seconds. For men, the cutoff scores for 5TSTS to identify gait speed <0.8 m/s was 14.67 seconds, and for gait speed <1.0 m/s, it was 13.63 seconds., Conclusion and Implications: The 5TSTS is clinically useful and can be an alternative assessment for discriminating community-dwelling older adults with reduced gait speed, when the gait evaluation is not feasible. The study also suggests different cutoff values for 5TSTS considering the gait speeds <0.8 and <1.0 m/s for older women and men, respectively., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Quinones are plant-derived secondary metabolites that present diverse pharmacological properties, including antibacterial, antifungal, antiviral, anti-inflammatory, antipyretic and anticancer activities. In the present study, we evaluated the cytotoxic effect of a new naphthoquinone 6b,7-dihydro-5H-cyclopenta [b]naphtho [2,1-d]furan-5,6 (9aH)-dione) (CNFD) in different tumor cell lines. CNFD displayed cytotoxic activity against different tumor cell lines, especially in MCF-7 human breast adenocarcinoma cells, which showed IC 50 values of 3.06 and 0.98 μM for 24 and 48 h incubation, respectively. In wound-healing migration assays, CNFD promoted inhibition of cell migration. We have found typical hallmarks of apoptosis, such as cell shrinkage, chromatin condensation, phosphatidylserine exposure, increase of caspases-9 and-3 activation, increase of internucleosomal DNA fragmentation without affecting the cell membrane permeabilization, increase of ROS production, and loss of mitochondrial membrane potential induced by CNFD. Moreover, gene expression experiments indicated that CNFD increased the expression of the genes CDKN1A, FOS, MAX, and RAC1 and decreased the levels of mRNA transcripts of several genes, including CCND1, CDK2, SOS1, RHOA, GRB2, EGFR and KRAS. The CNFD treatment of MCF-7 cells induced the phosphorylation of c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs) and inactivation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). In a study using melanoma cells in a murine model in vivo, CNFD induced a potent anti-tumor activity. Herein, we describe, for the first time, the cytotoxicity and anti-tumor activity of CNFD and sequential mechanisms of apoptosis in MCF-7 cells. CNFD seems to be a promising candidate for anti-tumor therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The plant popularly known as "negramina" (Siparuna guianensis Aubl.), member of the family Siparunaceae produces an essential oil that presents several biological activities reported in literature. Here, the essential oil was obtained by hydrodistillation from fresh leaves collected in the state of Roraima, far north of the Amazon. Chemical composition of the essential oil was characterized by gas chromatography coupled to mass spectrometry (GC-MS) and flame ionization detector (GC-FID). The sesquiterpenoid shyobunone and its derivatives were identified as major compounds in the oil (>40%). The effect of S. guianensis essential oil on the acetylcholinesterase (AChE) activity from Crassostrea rhizophorae, Litopenaeus vannamei and Electrophorus electricus was tested by spectrophotometric assays. The essential oil has been identified as an AChE inhibitor. The mechanism of inhibition was investigated as well as spectrofluorimetric interactions between the essential oil and the enzyme. 1 H NMR titration and molecular docking were also investigated. The spectrophotometric results revealed that shyobunone and its derivatives strongly interact with AChE with a kind of non-competitive inhibition. Interaction studies support the results of enzyme inhibition. Molecular coupling predicted that iso-shyobunone is the strongest ligand, corroborated by fluorescence suppression and 1 H NMR titration results. In conclusion, Siparuna guianensis essential oil can be a new source of shyobunone and derivatives capable to reversibly inhibit AChE showing potential neuroprotective properties to be applied in the treatment of Alzheimer's disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ariá (Goeppertia allouia) is a tuber from the arrowroot's family widely found in the Brazilian Amazon. The tuber has a flavor similar to corn, besides high retrogradation when cooked, differing from other commercial starches. To enhance its added value, the Ariá starch was extracted to evaluate its potential as a food ingredient. The Ariá starch was compared to the commercially available corn and potato starches regarding their physicochemical, thermal, structural, and rheological properties based on the Duncan's test (p-value <0.05). The Ariá starch presented high amylose content (~38% w/w). Furthermore, the X-ray diffraction pattern confirmed its Type-C crystalline structure. The rheological properties showed that the starch gels presented high hardness and retrogradation as other studied starches. Ariá has great potential as a source of starch with low digestibility, increasing the satiety of food products., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Aim: Evaluate the acute effects of non-invasive positive pressure ventilation (NiPPV) during high-intensity exercise on endothelial function in patients with coexisting chronic obstructive pulmonary disease (COPD) and heart failure (HF)., Methods: This is a randomized, double blinded, sham-controlled study involving 14 COPD-HF patients, who underwent a lung function test and Doppler echocardiography. On two different days, patients performed incremental cardiopulmonary exercise testing (CPET) and two constant-work rate tests (80% of CPET peak) receiving Sham or NiPPV (bilevel mode - Astral 150) in a random order until the limit of tolerance (Tlim). Endothelial function was evaluated by flow mediated vasodilation (FMD) at three time points: 1) Baseline; 2) immediately post-exercise with NiPPV; and 3) immediately post-exercise with Sham., Results: Our patients had a mean age of 70 ± 7 years, FEV 1 1.9 ± 0.7 L and LVEF 41 ± 9%. NIPPV resulted in an increased Tlim (NiPPV: 130 ± 29s vs Sham: 98 ± 29s p = 0.015) and SpO 2 (NiPPV: 94.7 ± 3.5% vs Sham: 92.7 ± 5.2% p = 0.03). Also, NiPPV was able to produce a significant increase in FMD (%) (NiPPV: 9.2 ± 3.1 vs Sham: 3.6 ± 0.7, p < 0.05), FMD (mm) (NiPPV: 0.41 ± 0.18 vs Sham: 0.20 ± 0.11, p < 0.05), Blood flow velocity (NiPPV: 33 ± 18 vs Baseline: 20 ± 14, p < 0.05) and Shear Stress (SS) (NiPPV: 72 ± 38 vs Baseline: 43 ± 25, p < 0.05). We found correlation between Tlim vs. ΔSS (p = 0.03; r = 0.57). Univariate-regression analysis revealed that increased SS influenced 32% of Tlim during exercise with NiPPV., Conclusion: NiPPV applied during high-intensity exercise can acutely modulate endothelial function and improve exercise tolerance in COPD-HF patients. In addition, the increase of SS positively influences exercise tolerance., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Carbon nanotubes (CN) have been studied to treat spinal cord injuries because of its electrical properties and nanometric dimensions. This work aims to develop a photopolymerizable hydrogel containing CN functionalized with an anti-inflammatory molecule to be used in situ on spinal cord injuries. The CN functionalization step was done using the drug (formononetin). The nanocomposites were characterized by morphological analysis, FTIR, Raman Spectroscopy, thermal analysis and cytotoxicity assays (MTT and HET-CAM). The nanocomposites were incorporated into gelatin methacryloyl hydrogel and exposed to UV light for photopolymerization. The volume of the formulation and the UV exposition time were also analyzed. The CN characterization showed that formononetin acted as a functionalization agent. The functionalized CN showed safe characteristics and can be incorporated in photocrosslinkable formulation. The UV exposition time for the formulation photopolymerization was compatible with the cell viability and also occurred in the injury site., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Cavernous carotid aneurysms (CCA) represent 2-9% of all intracranial aneurysms. For long considered benign lesions, these entities are unique when it comes to clinical presentation and management. Usually asymptomatic, CCAs can grow and rupture causing different manifestations. The lack of a long-term assessment of both treated and untreated CCAs' natural history justifies why there is no consensus regarding what are the recommended therapeutic measures. While some advocate that an intervention is always necessary, others consider that patients deserve an individualized evaluation., Patients and Methods: We describe our single-institution experience in diagnosis, follow-up, and management of 201 CCAs. In addition, we evaluate the association of giant CCAs with aneurysms in other locations using a Chi-square test., Results: 201 patients had 245 CCAs. 92% of the patients were women. The mean age at diagnosis was 61 years. Concomitant aneurysms were observed in 53.2% of the patients, and the middle cerebral artery was the most affected artery. 66 (30.6%) CCAs were considered "giant", and the follow-up period ranged from 1 to 23 years.The presence of a giant CCA seemed to hinder other aneurysms' formation - RR 0.47 (IC 95% 0.31-0.67), p < 0.0001., Conclusions: CCAs should be individually assessed. A conservative approach ought to be adopted for asymptomatic and oligosymptomatic lesions. Finally, a multidisciplinary team must evaluate the other situations, in order to define whether the microsurgical or the endovascular treatment is better option. Presence of a giant lesion within the cavernous sinus is associated with less occurrence of other aneurysms., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This paper describes a novel robust decentralized control design methodology for a single inductor multiple output (SIMO) DC-DC converter. Based on a nominal multiple input multiple output (MIMO) plant model and performance requirements, a pairing input-output analysis is performed to select the suitable input to control each output aiming to attenuate the loop coupling. Thus, the plant uncertainty limits are selected and expressed in interval form with parameter values of the plant model. A single inductor dual output (SIDO) DC-DC buck converter board is developed for experimental tests. The experimental results show that the proposed methodology can maintain a desirable performance even in the presence of parametric uncertainties. Furthermore, the performance indexes calculated from experimental data show that the proposed methodology outperforms classical MIMO control techniques., (Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.)

Three guaianolide sesquiterpenes, denoted guatterfriesols A-C, and four aporphine alkaloid derivatives were isolated from the stem bark of the Amazonian plant Guatteria friesiana. Thus far, sesquiterpene lactones have not been described in Annonaceae. Structures of the previously undescribed compounds were established by using 1D and 2D NMR spectroscopy in combination with MS. The absolute stereochemistry was assigned via NOE NMR experiments, ECD spectroscopy, and theoretical calculations using the TDDFT approach. Among the isolated compounds, the alkaloid guatterfriesidine showed anti-glycation activity by inhibiting the formation of advanced glycation end-products (AGEs) through the prevention of oxidation in both BSA/methylglyoxal and BSA/fructose systems., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Two derivatives of dillapiole, dillapiole ethyl ether (1KL39-B) and butyl ether-n dillapiole (1KL43-C), were studied for their toxicity and genotoxicity against Aedes albopictus, to help develop new strategies for the control of this potential vector of dengue and other arboviruses, because it is resistant to synthetic insecticides. Eggs and larvae exposed to different concentrations of 1KL39-B (25, 30, 50, 70, and 80μg/mL) and of 1KL43-C (12.5, 20, 25, 30 and 40μg/mL) exhibited toxicity and susceptibility, with 100% mortality. The LC50 was 55.86±1.57μg/mL for 1KL39-B and 25.60±1.24μg/mL for 1KL43-C, while the LC90 was 70.12μg/mL for 1KL39-B and 41.51μg/mL for 1KL43-C. The gradual decrease in oviposition of the females of the G1 to G4 generations was proportional to the increase in concentrations of these compounds, which could be related to the cumulative effect of cell anomalies in neuroblasts and oocytes (P<0.05), including micronuclei, budding, multinucleated cells and nuclear bridges. These findings showed that both 1KL39-B and 1KL43-C can serve as potential alternatives in the control of A. albopictus., (Copyright © 2016. Published by Elsevier B.V.)

In this study, we demonstrate that G-CSF administration triggers distinct kinetics of stem cell-SC mobilization with early raise of hematopoietic-HSC and late increase of mesenchymal-MSC in bone marrow-BM and peripheral blood-PB. The cytokine microenvironment observed following primary cultures showed an overall G-CSF dose-dependent profile with a clear mixed pro-inflammatory/regulatory pattern. Moreover, primary cultures performed at the peak of MSC/HSC ratio, showed distinct cytokine patterns, with higher IL-10, TNF-α and IL-17A observed for BM and enhanced IL-10, IL-2 and IFN-γ for PB harvested cells. Positive correlation was observed between BM-MSC and the levels of TNF-α, IL-10 and IL-17A whereas negative correlation was found between IL-10 and BM-HSC. An opposite association was observed between IL-10 and PB-HSC. Our results support the hypothesis that MSC and HSC harvested from BM and PB display differential functional properties that should be considered when electing the SC sources available for cell therapy applied in clinical protocols., (Copyright © 2014 Elsevier Inc. All rights reserved.)