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Plastic represents 60-80% of litter in the ocean. Degradation of plastic to small fragments leads to the formation of microplastics (MPs <5 mm) and nanoplastics (NPs <1 µm). One of the most widely used and representative plastics found in the ocean is polystyrene (PS). Among marine organisms, the immune system of bivalves is recognized as suitable to assess nanomaterial toxicity. Hemocyte subpopulations [R1 (large granular cells), R2 (small semi-granular cells) and R3 (small agranular or hyaline cells)] of Mytilus galloprovincialis are specialized in particular tasks and functions. The authors propose to examine the effects of different sizes (50 nm, 100 nm and 1 μm) PS NPs on the different immune cells of mussels when they were exposed to (1 and 10 mg·L−1) of PS NPs. The most noteworthy results found in this work are: (i) 1 µm PS NPs provoked higher immunological responses with respect to 50 and 100 nm PS NPs, possibly related to the higher stability in size and shape in hemolymph serum, (ii) the R1 subpopulation was the most affected with respect to R2 and R3 concerning immunological responses and (iii) an increase in the release of toxic radicals, apoptotic signals, tracking of lysosomes and a decrease in phagocytic activity was found in R1.

Hippocampal neurogenesis has widely been linked to memory and learning performance. New neurons generated from neural stem cells (NSC) within the dentate gyrus of the hippocampus (DG) integrate in hippocampal circuitry participating in memory tasks. Several neurological and neuropsychiatric disorders show cognitive impairment together with a reduction in DG neurogenesis. Growth factors secreted within the DG promote neurogenesis. Protein kinases of the protein kinase C (PKC) family facilitate the release of several of these growth factors, highlighting the role of PKC isozymes as key target molecules for the development of drugs that induce hippocampal neurogenesis. PKC activating diterpenes have been shown to facilitate NSC proliferation in neurogenic niches when injected intracerebroventricularly. We show in here that long-term administration of diterpene ER272 promotes neurogenesis in the subventricular zone and in the DG of mice, affecting neuroblasts differentiation and neuronal maturation. A concomitant improvement in learning and spatial memory tasks performance can be observed. Insights into the mechanism of action reveal that this compound facilitates classical PKCα activation and promotes transforming growth factor alpha (TGFα) and, to a lesser extent, neuregulin release. Our results highlight the role of this molecule in the development of pharmacological drugs to treat neurological and neuropsychiatric disorders associated with memory loss and a deficient neurogenesis.

The ability of aquatic organisms to sense the surrounding environment chemically and interpret such signals correctly is crucial for their ecological niche and survival. Although it is an oversimplification of the ecological interactions, we could consider that a significant part of the decisions taken by organisms are, to some extent, chemically driven. Accordingly, chemical contamination might interfere in the way organisms behave and interact with the environment. Just as any environmental factor, contamination can make a habitat less attractive or even unsuitable to accommodate life, conditioning to some degree the decision of organisms to stay in, or move from, an ecosystem. If we consider that contamination is not always spatially homogeneous and that many organisms can avoid it, the ability of contaminants to repel organisms should also be of concern. Thus, in this critical review, we have discussed the dual role of contamination: toxicity (disruption of the physiological and behavioral homeostasis) vs. repellency (contamination-driven changes in spatial distribution/habitat selection). The discussion is centered on methodologies (forced exposure against non-forced multi-compartmented exposure systems) and conceptual improvements (individual stress due to the toxic effects caused by a continuous exposure against contamination-driven spatial distribution). Finally, we propose an approach in which Stress and Landscape Ecology could be integrated with each other to improve our understanding of the threat contaminants represent to aquatic ecosystems.

The use of non-forced multi-compartmented exposure systems has gained importance in the assessment of the contamination-driven spatial avoidance response. This new paradigm of exposure makes it possible to assess how contaminants fragment habitats, interfering in the spatial distribution and species’ habitat selection processes. In this approach, organisms are exposed to a chemically heterogeneous scenario (a gradient or patches of contamination) and the response is focused on identifying the contamination levels considered aversive for organisms. Despite the interesting results that have been recently published, the use of this approach in ecotoxicological risk studies is still incipient. The current review aims to show the sensitivity of spatial avoidance in non-forced exposure systems in comparison with the traditional endpoints used in ecotoxicology under forced exposure. To do this, we have used the sensitivity profile by biological groups (SPBG) to offer an overview of the highly sensitive biological groups and the species sensitive distribution (SSD) to estimate the hazard concentration for 5% of the species (HC5). Three chemically different compounds were selected for this review: copper, glyphosate, and Ag-NPs. The results show that contamination-driven spatial avoidance is a very sensitive endpoint that could be integrated as a complementary tool to ecotoxicological studies in order to provide an overview of the level of repellence of contaminants. This repellence is a clear example of how contamination might fragment ecosystems, prevent connectivity among populations and condition the distribution of biodiversity.

Sea surface partial pressure of CO2 (pCO2) was measured continuously in a transect of the North Atlantic subtropical gyre between Santo Domingo, Dominican Republic (18.1° N, 68.5° W) and Vigo, Spain (41.9° N, 11.8° W) during spring 2011. Additional biogeochemical and physical variables measured to identify factors controlling the surface pCO2 were analyzed in discrete samples collected at 16 sites along the transect at the surface and to a depth of 200 m. Sea surface pCO2 varied between 309 and 662 μatm, and showed differences between the western and eastern subtropical gyre. The subtropical gyre acted as a net CO2 sink, with a mean flux of −5.5 ± 2.2 mmol m−2 day−1. The eastern part of the transect, close to the North Atlantic Iberian upwelling off the Galician coast, was a CO2 source with an average flux of 33.5 ± 9.0 mmol m−2 day−1. Our results highlight the importance of making more surface pCO2 observations in the area located east of the Azores Islands since air-sea CO2 fluxes there are poorly studied.

In the last few decades, there has been a growing interest in understanding the behavior of personal care products (PCPs) in the aquatic environment. In this regard, the aim of this study is to estimate the accumulation and effects of four PCPs within the clam Ruditapes philippinarum . The PCPs selected were triclosan, OTNE, benzophenone-3, and octocrylene. A progressive uptake was observed and maximum concentrations in tissues were reached at the end of the exposure phase, up to levels of 0.68 µg g −1 , 24 µg g −1 , 0.81 µg g −1 , and 1.52 µg g −1 for OTNE, BP-3, OC, and TCS, respectively. After the PCP post-exposure period, the removal percentages were higher than 65%. The estimated logarithm bioconcentration factor ranged from 3.34 to 2.93, in concordance with the lipophobicity of each substance. No lethal effects were found although significant changes were observed for ethoxyresorufin O-demethylase activity, glutathione S-transferase activity, lipid peroxidation, and DNA damage.

Purpose To compare pain incidence and changes in pain scores with fentanyl versus placebo as pre-emptive treatment during turning and 30 min post-turning in mechanically ventilated critically ill patients. Methods We performed a randomized, double-blind, parallel-group, placebo-controlled clinical trial in the intensive care unit of a university hospital. Seventy-five mechanically ventilated patients were randomized to an intervention group (fentanyl) or a control group (placebo). Patients in the intervention group received 1 µg/kg (medical patients) or 1.5 µg/kg (surgical patients) of fentanyl 10 min before turning. Pain indicators were assessed using the behavioral pain scale. Safety was assessed by determining the frequency and severity of pre-defined adverse events. Pain was evaluated at rest (T0), at turn start and end (T1 and T2) and at 5, 15 and 30 min post-turning (T3, T4 and T5). Results The two groups had similar baseline characteristics. The area under the curve for BPS values was significantly smaller in the fentanyl group than in the control group [median and interquartile range (IQR): 132 (108–150) vs. 147 (125–180); p  = 0.016, respectively]. Nineteen non-serious adverse events were recorded in 14 patients, with no significant between-group differences (23 % fentanyl group vs. 14 % control group; p  = 0.381). Conclusions These results suggest an intravenous bolus of fentanyl of 1 µg/kg for medical patients or 1.5 µg/kg for surgical patients reduces the incidence of turning-associated pain in critically ill patients on mechanical ventilation. ClinicalTrials.gov: NCT 01950000.

Although calcineurin inhibitors are very effective as immunosuppressants in organ transplantation, complete graft acceptance remains as a challenge. Transfer of genes with immunosuppressant functions could contribute to improving the clinical evolution of transplantation. In this sense, hydrodynamic injection has proven very efficacious for liver gene transfer. In the present work, the hIL-10 gene was hydrofected ‘ex vivo’ to pig livers during the bench surgery stage, to circumvent the cardiovascular limitations of the procedure, in a model of porcine orthotopic transplantation with a 10-day follow-up. We used IL-10 because human and porcine proteins can be differentially quantified and for its immunomodulatory pleiotropic functions. Safety (biochemical parameters and histology), expression efficacy (RNA transcription and blood protein expression), and acute inflammatory response (cytokines panel) of the procedure were evaluated. The procedure proved safe as no change in biochemical parameters was observed in treated animals, and human IL-10 was efficaciously expressed, with stationary plasma protein levels over 20 pg/mL during the follow-up. Most studied cytokines showed increments (interferon-α, IFN-α; interleukin-1β, IL-1β; tumor necrosis factor α, TNFα; interleukin-6, IL-6; interleukin-8, IL-8; interleukin-4, IL-4; and transforming growth factor-β, TGF-β) in treated animals, without deleterious effects on tissue. Collectively, the results support the potential clinical interest in this gene therapy model that would require further longer-term dose–response studies to be confirmed.

The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.