To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory ...flows in endotoxic shock.
Animal experimental study.
University translational research laboratory.
Fifteen Landrace pigs.
Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance.
Hypotension was significantly shorter in i-NE group (7.5 min 5.5-22.0 min vs 49.3 min 29.5-60.0 min; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively).
In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.
The aim of this work was to evaluate the influence of partial replacement of maize flour by sub-valuated whole grain flours on the interactions and spatial distribution of the main components of ...extruded snacks. Non-destructive, fast spectroscopic and microscopic complementary tools were employed. All blends (composed by maize + 25% of pearl millet, red sorghum, quinoa or hairless canary seed) presented lower carbohydrate and lipid contents and higher protein, ash and dietary fiber levels than the control maize extrudates. These compositional changes were reflected in FT-MIR and FT-Raman spectra which also allowed detecting modifications at molecular level, such as protein agglomeration, amylose-lipids complexes formation and surface exposure of carotenoids. Tridimensional distribution and spatial arrangements of the main components in the extruded samples were studied through CLSM and XPS. These properties are related to quality aspects such as lipid oxidation sensitivity and textural properties. The combined FT-MIR, FT-Raman, CLSM and XPS were helpful tools to understand thermo-mechanical modifications of starch, proteins and lipids as a consequence of the extrusion process.
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•Whole grain flours addition improved nutritional profile of maize-based extrudates.•FT-IR/Raman showed starch amorphization and proteins in random coil conformations.•Extrusion caused the formation of amylose-lipids complexes and protein agglomerates.•CLSM/XPS revealed potential lipid oxidation susceptibility of extrudates.
This paper aimed to build a predictive model through an empirical study to examine the influence of environmental awareness (EA) on attitude (ATT) and perceived behavioral control (PBC), as well as ...to determine the influence of the three variables of the theory of planned behavior (TPB) on willingness to pay (WP) for green products in the Peruvian market.
A total of 405 Peruvian consumers were surveyed. Most of them were between the ages of 18 and 30 and single. To test the hypotheses, partial least squares (PLS-SEM) were used using the SamrtPls4 software. The results show the significant positive effect of EA on ATT and PBC. The positive and significant effect of ATT, SN, and PBC on WP was also tested A total of 405 Peruvian consumers were surveyed. Most of them were between 18 and 30 years old and single. To test the hypotheses, partial least squares (PLS-SEM) was used using SamrtPls4 software.
The results show the positive and significant effect of AD on ATT and PBC. The positive and significant effect of ATT, SN and PBC on WP was also tested.
The research provides antecedents that allow evaluation of the possibility that companies and governments adjust the dissemination strategies and related public policies regarding the impact of environmentally responsible behavior in order to contribute to the development of environmental awareness as a variable that promotes the disposition of consumers to pay for environmentally friendly products.
Melanoma is an aggressive cancer that utilizes multiple signaling pathways, including those that involve oncogenes, proto-oncogenes, and tumor suppressors. It has been suggested that melanoma ...formation requires cross-talk of the PI3K/Akt/mTOR and Ras-ERK pathways. This pathway cross-talk has been associated with aggressiveness, drug resistance, and metastasis; thus, simultaneous targeting of components of the different pathways involved in melanoma may aid in therapy. We have previously reported that bacterial cyclodipeptides (CDPs) are cytotoxic to HeLa cells and inhibit Akt phosphorylation. Here, we show that CDPs decreased melanoma size and tumor formation in a subcutaneous xenografted mouse melanoma model. In fact, CDPs accelerated death of B16-F0 murine melanoma cells. In mice, antitumor effect was improved by treatment with CDPs using cyclodextrins as drug vehicle. In tumors, CDPs caused nuclear fragmentation and changed the expression of the Bcl-2 and Ki67 apoptotic markers and promoted restoration of hyperactivation of the PI3K/Akt/mTOR pathway. Additionally, elements of several signaling pathways such as the Ras-ERK, PI3K/JNK/PKA, p27Kip1/CDK1/survivin, MAPK, HIF-1, epithelial–mesenchymal transition, and cancer stem cell pathways were also modified by treatment of xenografted melanoma mice with CDPs. The findings indicate that the multiple signaling pathways implicated in aggressiveness of the murine B16-F0 melanoma line are targeted by the bacterial CDPs. Molecular modeling of CDPs with protein kinases involved in neoplastic processes suggested that these compounds could indeed interact with the active site of the enzymes. The results suggest that CDPs may be considered as potential antineoplastic drugs, interfering with multiple pathways involved in tumor formation and progression.
Waxy corn starch (amylopectin) and three of its chemical derivatives: acetylated cross‐linked (ACLS), oxidized (OS), and octenyl‐succinylated (OSA), were used together with additives such as Tween ...80, sorbitol, and beeswax suspension or safflower oil to test their effect on film‐forming solutions (FFS) and films. The objectives of this study were the starch structure characterization, and its correlation with rheological properties of FFS and solubility, opacity, and water vapor permeability (WVP) of the produced films. Analysis of starch structure, rheological characterization, and films micrographs revealed that the starches contained predominantly low MW amylopectin molecules and film properties depended on their ability to reorganize. Additionally, the interaction among groups introduced in modified starches or with additive molecules can hinder or promote starch reorganization, resulting in films with increased or reduced WVP, solubility and transparency properties. Films were obtained by casting and showed a thickness less than 41 µm. Films prepared with OS and beeswax exhibited the best reorganizing capacity of FFS, resulting in less soluble (30.0 ± 1.6%), highly transparent (23.2 ± 3.3 UA × nm) and less permeable films (0.485 ± 0.016 g · mm · m−2 · h−1 · kPa−1). On the other hand, ACLS showed an opposite trend which was attributed to a more open film structure. These results contribute to understand the molecular interactions of waxy starch molecules in FFS which may be useful to design tailored coatings.
The current pandemic generated by SARS-CoV-2 has led to mass vaccination with different biologics that have shown wide variations among human populations according to the origin and formulation of ...the vaccine. Studies evaluating the response in individuals with a natural infection before vaccination have been limited to antibody titer analysis and evaluating a few humoral and cellular response markers, showing a more rapid and intense humoral response than individuals without prior infection. However, the basis of these differences has not been explored in depth. In the present work, we analyzed a group of pro and anti-inflammatory cytokines, antibody titers, and cell populations in peripheral blood of individuals with previous SARS-CoV-2 infection using BNT162b2 biologic. Our results suggest that higher antibody concentration in individuals with an earlier disease could be generated by higher production of plasma cells to the detriment of the presence of memory B cells in the bloodstream, which could be related to the high baseline expression of cytokines (IL-6 and IL-10) before vaccination.
The fish's immune response is affected by different factors, including a wide range of environmental conditions that can also disrupt or promote changes in the host-pathogen interactions. How ...environmental conditions modulate the salmon genome during parasitism is poorly understood here. This study aimed to explore the environmental influence on the Salmo salar transcriptome and methylome infected with the sea louse Caligus rogercresseyi. Atlantic salmon were experimentally infected with lice at two temperatures (8 and 16 °C) and salinity conditions (32 and 26PSU). Fish tissues were collected from the infected Atlantic salmon for reduced representation bisulfite sequencing (RRBS) and whole transcriptome sequencing (RNA-seq) analysis. The parasitic load was highly divergent in the evaluated environmental conditions, where the lowest lice abundance was observed in fish infected at 8 °C/26PSU. Notably, transcriptome profile differences were statistically associated with the number of alternative splicing events in fish exposed to low temperature/salinity conditions. Furthermore, the temperature significantly affected the methylation level, where high values of differential methylation regions were observed at 16 °C. Also, the association between expression levels of spliced transcripts and their methylation levels was determined, revealing significant correlations with Ferroptosis and TLR KEEG pathways. This study supports the relevance of the environmental conditions during host-parasite interactions in marine ecosystems. The discovery of alternative splicing transcripts associated with DMRs is also discussed as a novel player in fish biology.
•Atlantic salmon transcriptome and methylome are modulated during sea lice infestation.•Transcriptional differences among environmental conditions are also associated with alternative splicing events.•The parasitic load was highly divergent in the evaluated environmental conditions.•The environmental conditions affect the host-parasite interactions in marine ecosystems.
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