Syneresis of self-crowded calcium-alginate hydrogels as a self-driven athermal aging process.

The assembly of biopolymers into a hydrated elastic network often goes along with syneresis, a spontaneous process during which the hydrogel slowly shrinks and releases solvent. The tendency to syneresis of calcium-alginate hydrogels, widely used biocompatible materials, is a hindrance to applications for which dimensional integrity is crucial. Although calcium-induced aggregation of specific block-sequences has been long known as the microscopic process at work in both primary cross-linking and syneresis, the nature of the coupling between these structural events and the global deswelling flow has remained so far elusive. We have tackled this issue within the regime of entangled pregels that yield highly cross-linked, self-crowded hydrogels with stiff networks. Using an original, stopped-flow extrusion experiment, we have unveiled a robust, stretched-exponential kinetics of shrinking, spanning more than six decades of time and quasi-independent of the alginate concentration. A careful analysis of the puzzling dynamical features of syneresis in these gels has led us to propose that due to the network rigidity, the calcium-fueled, random collapse events that drive solvent locally, are not thermally activated but rather controlled by the average poroelastic flow itself, according to a self-sustained mechanism described here for the first time.

Detection of Intermittent Claudication from Smartphone Inertial Data in Community Walks Using Machine Learning Classifiers.

Peripheral arterial disease (PAD) causes blockage of the arteries, altering the blood flow to the lower limbs. This blockage can cause the individual with PAD to feel severe pain in the lower limbs. The main contribution of this research is the discovery of a solution that allows the automatic detection of the onset of claudication based on data analysis from patients' smartphones. For the data-collection procedure, 40 patients were asked to walk with a smartphone on a thirty-meter path, back and forth, for six minutes. Each patient conducted the test twice on two different days. Several machine learning models were compared to detect the onset of claudication on two different datasets. The results suggest that we can identify the onset of claudication using inertial sensors with a best case accuracy of 92.25% for the Extreme Gradient Boosting model.

Adaptation of Lipid Profiling in Depression Disease and Treatment: A Critical Review.

Major depressive disorder (MDD), also called depression, is a serious disease that impairs the quality of life of patients and has a high incidence, affecting approximately 3.8% of the world population. Its diagnosis is very subjective and is not supported by measurable biomarkers mainly due to the lack of biochemical markers. Recently, disturbance of lipid profiling has been recognized in MDD, in animal models of MDD or in depressed patients, which may contribute to unravel the etiology of the disease and find putative new biomarkers, for a diagnosis or for monitoring the disease and therapeutics outcomes. In this review, we provide an overview of current knowledge of lipidomics analysis, both in animal models of MDD (at the brain and plasma level) and in humans (in plasma and serum). Furthermore, studies of lipidomics analyses after antidepressant treatment in rodents (in brain, plasma, and serum), in primates (in the brain) and in humans (in plasma) were reviewed and give evidence that antidepressants seem to counteract the modification seen in lipids in MDD, giving some evidence that certain altered lipid profiles could be useful MDD biomarkers for future precision medicine.

Gene Expression Detects the Factors Influencing the Reproductive Success and the Survival Rates of Paracentrotus lividus Offspring.

The increase in the demand for Paracentrotus lividus roe, a food delicacy, causes increased pressure on its wild stocks. In this scenario, aquaculture facilities will mitigate the effects of anthropogenic pressures on the wild stocks of P. lividus. Consequently, experimental studies should be conducted to enhance techniques to improve efficient aquaculture practices for these animals. Here, we for the first time performed molecular investigations on cultured sea urchins. We aimed at understanding if maternal influences may significantly impact the life of future offspring, and how the culture conditions may impact the development and growth of cultured specimens. Our findings demonstrate that the outcomes of in vitro fertilization of P. lividus are influenced by maternal influences, but these effects are largely determined by culture conditions. In fact, twenty-three genes involved in the response to stress and skeletogenesis, whose expressions were measured by Real Time qPCR, were differently expressed in sea urchins cultured in two experimental conditions, and the results were largely modified in offspring deriving from two groups of females. The findings herein reported will be critical to develop protocols for the larval culture of the most common sea urchin, both for research and industrial production purposes for mass production.

NEGR1 and FGFR2 cooperatively regulate cortical development and core behaviours related to autism disorders in mice.

Autism spectrum disorders are neurodevelopmental conditions with diverse aetiologies, all characterized by common core symptoms such as impaired social skills and communication, as well as repetitive behaviour. Cell adhesion molecules, receptor tyrosine kinases and associated downstream signalling have been strongly implicated in both neurodevelopment and autism spectrum disorders. We found that downregulation of the cell adhesion molecule NEGR1 or the receptor tyrosine kinase fibroblast growth factor receptor 2 (FGFR2) similarly affects neuronal migration and spine density during mouse cortical development in vivo and results in impaired core behaviours related to autism spectrum disorders. Mechanistically, NEGR1 physically interacts with FGFR2 and modulates FGFR2-dependent extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) signalling by decreasing FGFR2 degradation from the plasma membrane. Accordingly, FGFR2 overexpression rescues all defects due to Negr1 knockdown in vivo. Negr1 knockout mice present phenotypes similar to Negr1-downregulated animals. These data indicate that NEGR1 and FGFR2 cooperatively regulate cortical development and suggest a role for defective NEGR1-FGFR2 complex and convergent downstream ERK and AKT signalling in autism spectrum disorders.

Unfolded Protein Response: Cause or Consequence of Lipid and Lipoprotein Metabolism Disturbances?

The liver plays a capital role in the control of whole body energy homeostasis through the metabolization of dietary carbohydrates and lipids. However, under excess macronutrient uptake, those pathways overcharge nucleus-to-endoplasmic reticulum (ER) traffic pathways, leading to luminal overload of unfolded proteins which activates a series of adaptive signaling pathways known as unfolded protein response (UPR). The UPR is a central network mechanism for cellular stress adaptation, however far from a global nonspecific all-or-nothing response. Such a complex signaling network is able to display considerable specificity of responses, with activation of specific signaling branches trimmed for distinct types of stimuli. This makes the UPR a fundamental mechanism underlying metabolic processes and diseases, especially those related to lipid and carbohydrate metabolism. Thus, for a better understanding of the role of UPR on the physiopathology of lipid metabolism disorders, the concepts discussed along this chapter will demonstrate how several metabolic derangements activate UPR components and, in turn, how UPR triggers several metabolic adaptations through its component signaling proteins. This dual role of UPR on lipid metabolism will certainly foment the pursuit of an answer for the question: is UPR cause or consequence of lipid and lipoprotein metabolism disturbances?

Optimizing the use of darbepoetin-α with a split strategy: A concept change
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As erythropoiesis is a continuous process, we hypothesized that a new approach with smaller doses of darbepoetin-α administered more regularly could result in fewer variations of its serum levels and be more effective. In a prevalent hemodialysis population, we evaluated the effects of the darbepoetin splitting in "mini-doses". A 34-month prospective study was performed in a cohort of 110 patients, with a mean age of 66.6 ± 14.2 years, median dialysis vintage of 63.6 months (IQ range: 27 - 86), 46.4% (n = 51) male gender, 36.4% (n = 40) diabetics. In the first 12 months of the study, the usual dose regime for darbepoetin (weekly, every other week, or monthly) was unchanged. In the following 22 months, darbepoetin doses were divided into multiples of 10 µg and administered in the maximum possible number of hemodialysis (HD) sessions. Paired Student's t or Wilcoxon matched-pairs analyses were performed. After darbepoetin splitting, we verified a decrease in its consumption (1.9 ± 1.7 to 1.4 ± 1.6 µg/kg, p < 0.0001) and in the erythropoietin resistance index (8.6 to 6.7 IU/kg/week, p = 0.0001), with stable hemoglobin levels (11.4 ± 0.7 to 11.3 ± 0.6 g/dL, p = 0.02). We also observed an increase in ferritin levels (490 ± 138.2 to 560.7 ± 149.3 µg/L, p < 0.0001) and C-reactive protein (CRP) levels, with no changes in iron doses (2.2 - 3.2 mg/kg, p = 0.24). From these results, we conclude that the splitting of darbepoetin in "mini-doses" is highly effective, potentially allowing a significant decrease in the costs of anemia treatment. Larger and randomized studies are needed to prove the cost-benefit of this new strategy.
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Environmental Enrichment Induces Changes in Long-Term Memory for Social Transmission of Food Preference in Aged Mice through a Mechanism Associated with Epigenetic Processes.

Decline in declarative learning and memory performance is a typical feature of normal aging processes. Exposure of aged animals to an enriched environment (EE) counteracts this decline, an effect correlated with reduction of age-related changes in hippocampal dendritic branching, spine density, neurogenesis, gliogenesis, and neural plasticity, including its epigenetic underpinnings. Declarative memories depend on the medial temporal lobe system, including the hippocampus, for their formation, but, over days to weeks, they become increasingly dependent on other brain regions such as the neocortex and in particular the prefrontal cortex (PFC), a process known as system consolidation. Recently, it has been shown that early tagging of cortical networks is a crucial neurobiological process for remote memory formation and that this tagging involves epigenetic mechanisms in the recipient orbitofrontal (OFC) areas. Whether EE can enhance system consolidation in aged animals has not been tested; in particular, whether the early tagging mechanisms in OFC areas are deficient in aged animals and whether EE can ameliorate them is not known. This study aimed at testing whether EE could affect system consolidation in aged mice using the social transmission of food preference paradigm, which involves an ethologically based form of associative olfactory memory. We found that only EE mice successfully performed the remote memory recall task, showed neuronal activation in OFC, assessed with c-fos immunohistochemistry and early tagging of OFC, assessed with histone H3 acetylation, suggesting a defective system consolidation and early OFC tagging in aged mice which are ameliorated by EE.

Meglumine Antimoniate (Glucantime) Causes Oxidative Stress-Derived DNA Damage in BALB/c Mice Infected by Leishmania (Leishmania) infantum.

Leishmaniasis is a neglected tropical disease caused by >20 species of the protozoan parasite Leishmania Meglumine antimoniate (Glucantime) is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which meglumine antimoniate causes DNA damage was investigated for BALB/c mice infected by Leishmania (Leishmania) infantum and treated with meglumine antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that meglumine antimoniate, as well as L. infantum infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both meglumine antimoniate treatment and L. infantum infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a meglumine antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment.

Evaluation of antitumor activity and cardiac toxicity of a bone-targeted ph-sensitive liposomal formulation in a bone metastasis tumor model in mice.

Chemotherapy for bone tumors is a major challenge because of the inability of therapeutics to penetrate dense bone mineral. We hypothesize that a nanostructured formulation with high affinity for bone could deliver drug to the tumor while minimizing off-target toxicity. Here, we evaluated the efficacy and toxicity of a novel bone-targeted, pH-sensitive liposomal formulation containing doxorubicin in an animal model of bone metastasis. Biodistribution studies with the liposome showed good uptake in tumor, but low accumulation of doxorubicin in the heart. Mice treated with the bone-targeted liposome formulation showed a 70% reduction in tumor volume, compared to 35% reduction for free doxorubicin at the same dose. Both cardiac toxicity and overall mortality were significantly lower for animals treated with the bone-targeted liposomes compared to free drug. Bone-targeted, pH-sensitive, doxorubicin containing liposomes represent a promising approach to selectively delivering doxorubicin to bone tumors while minimizing cardiac toxicity.

ICT-based applications to improve social health and social participation in older adults with dementia. A systematic literature review.

OBJECTIVES: Information and communication technologies (ICT) developers, together with dementia experts have created several technological solutions to improve and facilitate social health and social participation and quality of life of older adults living with dementia. However, there is a need to carry out a systematic literature review that focuses on the validity and efficacy of these new technologies assessing their utility to promote 'social health' and 'active ageing' in people with dementia. METHOD: Searches in electronic databases identified 3824 articles of which 6 met the inclusion criteria and were coded according to their methodological approach, sample sizes, type of outcomes and results. RESULTS: Six papers were identified reporting the use of 10 different interventions with people with dementia. Qualitative studies (four) showed a benefit of the use of technologies to foster social participation in people with dementia. At the same time, barriers to a widespread use of these technologies in this population were identified. A quantitative study and a mixed-method study with quantitative outcomes showed that ICT-based interventions promote more social behaviours than non-technology-based interventions. CONCLUSIONS: In the last years, several technological devices for living independently and fostering social health and social participation in people with dementia have been developed. However, specific outcome measures to assess social health and social participation are needed. Even though the analysed studies provided some evidence-base for the use of technology in this field, there is an urge to develop high quality studies and specific outcome measures.

Early and sustained exposure to high-sucrose diet triggers hippocampal ER stress in young rats.

Early-life environmental insults have been shown to promote long-term development of chronic non-communicable diseases, including metabolic disturbances and mental illnesses. As such, premature consumption of high-sugar foods has been associated to early onset of detrimental outcomes, whereas underlying mechanisms are still poorly understood. In the present study, we sought to investigate whether early and sustained exposure to high-sucrose diet promotes metabolic disturbances that ultimately might anticipate neurological injuries. At postnatal day 21, weaned male rats started to be fed a standard chow (10 % sucrose, CTR) or a high-sucrose diet (25 % sucrose, HSD) for 9 weeks prior to euthanasia at postnatal day 90. HSD did not alter weight gain and feed efficiency between groups, but increased visceral, non-visceral and brown adipose tissue accumulation. HSD rats demonstrated elevated blood glucose levels in both fasting and fed states, which were associated to impaired glucose tolerance. Peripheral insulin sensitivity did not change, whereas hepatic insulin resistance was supported by increased serum triglyceride levels, as well as higher TyG index values. Assessment of hippocampal gene expression showed endoplasmic reticulum (ER) stress pathways were activated in HSD rats, as compared to CTR. HSD rats had overexpression of unfolded protein response sensors, PERK and ATF6; ER chaperone, PDIA2 and apoptosis-related genes, CHOP and Caspase 3; but decreased expression of chaperone GRP78. Finally, HSD rats demonstrated impaired neuromuscular function and anxious behavior, but preserved cognitive parameters. In conclusion, our data indicate that early exposure to HSD promote metabolic disturbances, which disrupt hippocampus homeostasis and might precociously affect its neurobehavioral functions.

High-volume postdilution hemodiafiltration is a feasible option in routine clinical practice.

Hemodiafiltration (HDF) with 20-22 L of substitution fluid is increasingly recognized as associated with significant benefits regarding patient outcome. However, some doubt exists as to whether these high volumes can be achieved in routine clinical practice. A total of 4176 sessions with 366 patients on postdilution HDF were analyzed in this 1-month observational cohort study with prospective data collection. All dialysis machines were equipped with AutoSub plus signal analysis software that automatically and continuously adapts the substitution fluid flow according to the blood flow, blood viscosity, and dialyzer characteristics. Percentages of sessions with different types of vascular access were compared regarding achievement of ≥21 L substitution fluid. Logistic regression analysis was conducted to study the independent relationship of selected variables with achievement of ≥21 L substitution volume. Patient- and dialysis-related variables that showed an association with the convection volume were entered in a multivariable model that included hematocrit up front. Respectively, 87%, 84%, and 33% of routine sessions conducted with fistulas, grafts, and catheters qualified as high-volume HDF. Serum albumin levels ≥4.2 g/dL were positively associated with the achievement of at least 21 L substitution volume. Positive associations were also observed for blood flows in the ranges 350-399 and ≥400 mL/min compared with the reference range (300-350 mL/min), for longer treatment time, for fistula versus catheter, for higher filtration fraction, and for dialysis conducted at the end of the week versus Monday. It can be concluded that implementation and sustainability of high-volume HDF is possible in routine clinical practice for almost all patients treated with fistulas and grafts.

Communicating through humour: A project of stand-up comedy about science.

A study of a project on science stand-up comedy developed in Portugal between 2009 and 2013 is presented, in which thirteen scientists, coordinated by a science communicator and a professional actor, created and presented comedy acts. Eleven of these scientists were asked about their motivations to participate, the process of performance development and the perceived value of the project. Personal motivations were highly important, but professional reasons were also mentioned. Working in a group with the guidance of coordinators, testing and re-writing the texts and gradually gaining confidence on stage were considered fundamental in the development of the shows. Additionally, a questionnaire revealed that the audience, most of whom were young adults, and held a higher education degree, were satisfied with the show. Overall, both participating scientists and audience members considered that stand-up comedy has potential for science communication.

Impact of chronic fluoxetine exposure on zebrafish: From fatty acid profile to behavior.

The consumption of antidepressants, such as fluoxetine, has increased over the years and, as a result, they are increasingly found in aquatic systems. Given the increasing use of zebrafish as an animal model in toxicological studies, this work proposed to evaluate the effects of chronic exposure, for 21 days, to fluoxetine at environmentally relevant concentrations (1, 10, 100, and 1000 ng/L). The behavioral tests performed did not reveal significant effects of fluoxetine. However, oxidative stress and changes in energy metabolism were detected after exposure to the highest concentrations of fluoxetine tested, namely a decrease in glutathione S-transferase (GST) activity (decrease of ca. 31%), increase in catalase (CAT) activity (increase of ca. 71%), and decrease in lactate dehydrogenase (LDH) activity (decrease of ca. 53%). Analysis of the fatty acid profile (FA) revealed a decrease in the omega-3 FA, docosahexaenoic acid (DHA), C22:6 (decrease in relative abundance between 6% and 8% for both the head and body), an increase in omega-6 FA, linoleic acid (LA), C18:2, (increased relative abundance between 8% and 11% in the head and between 5% and 9% in the body), which may suggest changes in the inflammatory state of these organisms. The integrated analysis adopted proved to be useful in detecting subindividual effects of fluoxetine and modes of action in fish.

Atomic Force Microscopy Applied to the Study of Tauopathies.

Atomic force microscopy (AFM) is a scanning probe microscopy technique which has a physical principle, the measurement of interatomic forces between a very thin tip and the surface of a sample, allowing the obtaining of quantitative data at the nanoscale, contributing to the surface study and mechanical characterization. Due to its great versatility, AFM has been used to investigate the structural and nanomechanical properties of several inorganic and biological materials, including neurons affected by tauopathies. Tauopathies are neurodegenerative diseases featured by aggregation of phosphorylated tau protein inside neurons, leading to functional loss and progressive neurotoxicity. In the broad universe of neurodegenerative diseases, tauopathies comprise the most prevalent, with Alzheimer's disease as its main representative. This review highlights the use of AFM as a suitable research technique for the study of cellular damages in tauopathies, even in early stages, allowing elucidation of pathogenic mechanisms of these diseases.

European journalists and the sea: Contexts, motivations, and difficulties.

The media play an important role in informing us about new developments in our understanding of the sea and raising awareness about its sustainability. However, press coverage of marine issues seems to be modest, compared with the importance oceans have in our lives. In this study, we examine science journalists' working contexts, motivations, and difficulties in writing about the sea in Europe. We conducted semi-structured interviews with 26 journalists who write for quality newspapers from 13 European countries. We found that the recent production of press news on marine issues is mainly conditioned by working contexts in newspapers, the personal and professional interests of journalists, and the available resources to write news. More studies are needed to compare our findings, including with other regions outside Europe.

Regional communication and media analysis of aquaculture in Atlantic islands.

The way the media portrays aquaculture-related events can influence how this industry is perceived by the public and affect its success. Since media are an important source of public information, media content analysis has been carried out in several regions of the world. This study aimed to determine which aspects of aquaculture were more exposed and how they were discussed by regional media in the Madeira archipelago, an oceanic group of Portuguese islands. Analysis of aquaculture's media coverage in the two most-read regional newspapers of Madeira was carried out over a 5-year period (2017 to 2021). For each news article, the assessment focused on the geographic scope, the main topics covered, the stakeholders with access to the debate, and the general tone of the article (risk/benefit framework). A total of 297 articles were analyzed. Results indicate the occurrence of trigger events that contributed to a shift in the amount of news published and in the way media framed aquaculture. In general, political and economic issues dominated the coverage, whereas social, environmental, scientific, and landscape matters received less media attention. The voice of the government was predominant throughout the 5 years in analysis and aquaculture was generally framed with a balanced tone, slightly more negative. Open and transparent communication between the stakeholders and the media is fundamental for the sustainable development of the aquaculture industry.

Analyzing causes of urban blight using cognitive mapping and DEMATEL.

Blight is a concept not commonly discussed. However, blight is a problem that exists in the lives of many people, especially if they reside in urban areas. Blight originates whenever properties are neglected, contributing to both a functional and social depreciation process and ultimately leading to uninhabitable dwellings. Despite being blighted, these properties and surrounding neighborhoods often are occupied by families who fail to have sufficient income to afford residences that meet minimum standards or to live in neighborhoods free from drug trafficking and prostitution or other forms of crime. Blight may spread rapidly, thus, experts must, in a timely manner, analyze its causes, which are essential to preventing and mitigating blight problems. The purpose of this study is to seek an understanding of blight and identify its causal factors. The generic methods commonly applied in previous blight research present limitations that this study aims to overcome by using cognitive mapping and the decision making trial and evaluation laboratory (DEMATEL) technique. This dual methodology provides a more transparent and less restrictive approach for analyzing and complying with the dynamics of cause-and-effect relationships among variables. Group debate involving a panel of specialists in this field identified six causation clusters based on the experts' experience and knowledge. The resulting framework and its application were validated both by these specialists and the head of the Territorial and Environmental Assessment and Monitoring Division of Cascais City Council Strategic Planning Department, Portugal.

Morphologic and genic effects of waste pollution on the reproductive physiology of Paracentrotus lividus lmk: a mesocosm experiment.

A considerable amount of coastal contamination is caused by wastes deriving from household and the degradation and the metabolism of plants and animals, even if our attention is commonly focused on industrial pollutants and contaminants. Waste pollutants are mainly represented by highly diluted soluble compounds and particles deriving from dead organisms. This complex combination, consisting of suspended particles and dissolved nutrients, has a significant impact on coastal planktonic and benthic organisms, also playing an active role in the global cycles of carbon. In addition, production practices are nowadays shifting towards recirculated aquaculture systems (RAS) and the genic responses of target organisms to the pollution deriving from animal metabolism are still scarcely addressed by scientific investigations. The reservoir of organic matter dissolved in the seawater is by far the least understood if compared to that on land, cause only a few compounds have been identified and their impacts on animals and plants are poorly understood. The tendency of these compounds to concentrate at interfaces facilitates the absorption of dissolved organic compound (DOC) onto suspended particles. Some DOC components are chemically combined with dissolved metals and form complexes, affecting the chemical properties of the seawater and the life of the coastal biota. In this research, we compared the reproductive performances of the common sea urchin Paracentrotus lividus cultured in open-cycle tanks to those cultured in a recirculating aquaculture system (RAS), where pollution progressively increased during the experiment due to animal escretions. Sea urchins were cultured for 7 months under these two conditions and their gametes were collected. Embryos resulting by in vitro fertilization were analyzed by Real Time qPCR to identify possible effects of pollution-induced stress. The fertility of sea urchins was evaluated, as well as the gonadosomatic indices and the histological features of gonads. Our results indicate that pollution due to excess of nutrients, event at sub-lethal concentrations, may hardly impact the reproductive potential of this key species and that chronic effects of stress are revealed by the analyses of survival rates and gene expression.