Linalool Reduces Virulence and Tolerance to Adverse Conditions of Listeria monocytogenes.

Listeria monocytogenes, a foodborne pathogen causing listeriosis, poses substantial societal, economic, and public health challenges due to its resistance, persistence, and biofilm formation in the food industry. Exploring subinhibitory concentrations of compounds to target virulence inhibition and increase susceptibility to adverse conditions presents a promising strategy to mitigate its impact of L. monocytogenes and unveils new potential applications. Thus, this study aims to explore the effect of linalool on virulence factors of L. monocytogenes and potential use in the reduction in its tolerance to stressful conditions. This action was analysed considering the use of two sub-inhibitory concentrations of linalool, 0.312 and 0.625 mg/mL. We found that even with the lowest tested concentrations, a 65% inhibition of violacein production by Chromobacterium violaceum, 55% inhibition in biofilm formation by L. monocytogenes and 62% reduction on haemolysis caused by this bacterium were observed. In addition to its impact on virulence factors, linalool diminished the tolerance to osmotic stress (up to 4.3 log reduction after 24 h with 12% NaCl), as well as to high (up to 3.8 log reduction after 15 min at 55 °C) and low temperatures (up to 4.6 log reduction after 84 days with 12% NaCl at 4 °C). Thus, this study paves the way to further investigation into the potential utilization of linalool to mitigate the threat posed by L. monocytogenes in the field of food safety and public health.

Preconditioning of MSCs for Acute Neurological Conditions: From Cellular to Functional Impact-A Systematic Review.

This systematic review aims to gather evidence on the mechanisms triggered by diverse preconditioning strategies for mesenchymal stem cells (MSCs) and their impact on their potential to treat ischemic and traumatic injuries affecting the nervous system. The 52 studies included in this review report nine different types of preconditioning, namely, manipulation of oxygen pressure, exposure to chemical substances, lesion mediators or inflammatory factors, usage of ultrasound, magnetic fields or biomechanical forces, and culture in scaffolds or 3D cultures. All these preconditioning strategies were reported to interfere with cellular pathways that influence MSCs' survival and migration, alter MSCs' phenotype, and modulate the secretome and proteome of these cells, among others. The effects on MSCs' phenotype and characteristics influenced MSCs' performance in models of injury, namely by increasing the homing and integration of the cells in the lesioned area and inducing the secretion of growth factors and cytokines. The administration of preconditioned MSCs promoted tissue regeneration, reduced neuroinflammation, and increased angiogenesis and myelinization in rodent models of stroke, traumatic brain injury, and spinal cord injury. These effects were also translated into improved cognitive and motor functions, suggesting an increased therapeutic potential of MSCs after preconditioning. Importantly, none of the studies reported adverse effects or less therapeutic potential with these strategies. Overall, we can conclude that all the preconditioning strategies included in this review can stimulate pathways that relate to the therapeutic effects of MSCs. Thus, it would be interesting to explore whether combining different preconditioning strategies can further boost the reparative effects of MSCs, solving some limitations of MSCs' therapy, namely donor-associated variability.

Aberrant microbiomes are associated with increased antibiotic resistance gene load in hybrid mice.

Antibiotic resistance is a priority public health problem resulting from eco-evolutionary dynamics within microbial communities and their interaction at a mammalian host interface or geographical scale. The links between mammalian host genetics, bacterial gut community, and antimicrobial resistance gene (ARG) content must be better understood in natural populations inhabiting heterogeneous environments. Hybridization, the interbreeding of genetically divergent populations, influences different components of the gut microbial communities. However, its impact on bacterial traits such as antibiotic resistance is unknown. Here, we present that hybridization might shape bacterial communities and ARG occurrence. We used amplicon sequencing to study the gut microbiome and to predict ARG composition in natural populations of house mice (Mus musculus). We compared gastrointestinal bacterial and ARG diversity, composition, and abundance across a gradient of pure and hybrid genotypes in the European House Mouse Hybrid Zone. We observed an increased overall predicted richness of ARG in hybrid mice. We found bacteria-ARG interactions by their co-abundance and detected phenotypes of extreme abundances in hybrid mice at the level of specific bacterial taxa and ARGs, mainly multidrug resistance genes. Our work suggests that mammalian host genetic variation impacts the gut microbiome and chromosomal ARGs. However, it raises further questions on how the mammalian host genetics impact ARGs via microbiome dynamics or environmental covariates.

Silver and Antimicrobial Polymer Nanocomplexes to Enhance Biocidal Effects.

Antimicrobial resistance has become a major problem over the years and threatens to remain in the future, at least until a solution is found. Silver nanoparticles (Ag-NPs) and antimicrobial polymers (APs) are known for their antimicrobial properties and can be considered an alternative approach to fighting resistant microorganisms. Hence, the main goal of this research is to shed some light on the antimicrobial properties of Ag-NPs and APs (chitosan (CH), poly-L-lysine (PLL), ε-poly-L-lysine (ε-PLL), and dopamine (DA)) when used alone and complexed to explore the potential enhancement of the antimicrobial effect of the combination Ag-NPs + Aps. The resultant nanocomplexes were chemically and morphologically characterized by UV-visible spectra, zeta potential, transmission electron microscopy, and Fourier-transform infrared spectroscopy. Moreover, the Ag-NPs, APs, and Ag-NPs + APs nanocomplexes were tested against Gram-positive Staphylococcus aureus (S. aureus) and the Gram-negative Escherichia coli (E. coli) bacteria, as well as the fungi Candida albicans (C. albicans). Overall, the antimicrobial results showed potentiation of the activity of the nanocomplexes with a focus on C. albicans. For the biofilm eradication ability, Ag-NPs and Ag-NPs + DA were able to significantly remove S. aureus preformed biofilm, and Ag-NPs + CH were able to significantly destroy C. albicans biofilm, with both performing better than Ag-NPs alone. Overall, we have proven the successful conjugation of Ag-NPs and APs, with some of these formulations showing potential to be further investigated for the treatment of microbial infections.

Global fine-resolution data on springtail abundance and community structure.

Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.

Reimagining infrastructure for a biodiverse future.

Civil infrastructure will be essential to face the interlinked existential threats of climate change and rising resource demands while ensuring a livable Anthropocene for all. However, conventional infrastructure planning largely neglects the contributions and maintenance of Earth's ecological life support systems, which provide irreplaceable services supporting human well-being. The stability and performance of these services depend on biodiversity, but conventional infrastructure practices, narrowly focused on controlling natural capital, have inadvertently degraded biodiversity while perpetuating social inequities. Here, we envision a new infrastructure paradigm wherein biodiversity and ecosystem services are a central objective of civil engineering. In particular, we reimagine infrastructure practice such that 1) ecosystem integrity and species conservation are explicit objectives from the outset of project planning; 2) infrastructure practices integrate biodiversity into diverse project portfolios along a spectrum from conventional to nature-based solutions and natural habitats; 3) ecosystem functions reinforce and enhance the performance and lifespan of infrastructure assets; and 4) civil engineering promotes environmental justice by counteracting legacies of social inequity in infrastructure development and nature conservation. This vision calls for a fundamental rethinking of the standards, practices, and mission of infrastructure development agencies and a broadening of scope for conservation science. We critically examine the legal and professional precedents for this paradigm shift, as well as the moral and economic imperatives for manifesting equitable infrastructure planning that mainstreams biodiversity and nature's benefits to people. Finally, we set an applied research agenda for supporting this vision and highlight financial, professional, and policy pathways for achieving it.

Evaluation of Bile Salts on the Survival and Modulation of Virulence of Aliarcobacter butzleri.

Aliarcobacter butzleri is a Gram-negative bacterium associated with infections of the gastrointestinal tract and widely distributed in various environments. For successful infection, A. butzleri should be able to tolerate various stresses during gastrointestinal passage, such as bile. Bile represents an antimicrobial host barrier that acts against external noxious agents and consists of a variety of bile salts. The intestinal bile salts act as detergents involved in the antimicrobial host defense; although, on the bacterial side, they could also serve as a signal to activate virulence mechanisms. The aim of this work was to understand the effects of bile salts on the survival and virulence of A. butzleri. In our study, A. butzleri was able to survive in the presence of human physiological concentrations of bile salts. Regarding the virulence features, an increase in cellular hydrophobicity, a decrease in motility and expression of flaA gene, as well as an increase in biofilm formation with a concomitant change in the type of biofilm structure were observed in the presence of sub-inhibitory concentration of bile salts. Concerning adhesion and invasion ability, no significant difference was observed. Overall, the results demonstrated that A. butzleri is able to survive in physiological concentrations of bile salts and that exposure to bile salts could change its virulence mechanisms.

Resveratrol as an Inhibitor of the NorA Efflux Pump and Resistance Modulator in Staphylococcus aureus.

Staphylococcus aureus can exhibit resistance to various antibiotics. Among its resistance mechanisms, the active efflux of antibiotics can be seen as relevant. This study aimed to evaluate the ability of resveratrol to modulate norfloxacin resistance in S. aureus. The antimicrobial activity of resveratrol was assessed using the broth microdilution method to determine the minimum inhibitory concentration (MIC). Then, the modulatory effect of resveratrol was evaluated using the MIC determination for the antibiotic or ethidium bromide in the presence and absence of resveratrol at a sub-MIC level. The MIC of norfloxacin against S. aureus SA1199B (NorA-overexpressing strain) decreased 16-fold when in the presence of resveratrol, with a similar behavior being observed for ethidium bromide. An evaluation of the ethidium bromide accumulation was also performed, showing that in the presence of resveratrol, the SA1199B strain had augmented fluorescence due to the accumulation of ethidium bromide. Altogether, the results suggested that resveratrol may act by inhibiting NorA. These in vitro data were supported by docking results, with interactions between resveratrol and the NorA efflux pump predicted to be favorable. Our findings demonstrated that resveratrol may modulate norfloxacin resistance through the inhibition of NorA, increasing the effectiveness of this antibiotic against S. aureus.

Amplicon sequencing allows differential quantification of closely related parasite species: an example from rodent Coccidia (Eimeria).

BACKGROUND: Quantifying infection intensity is a common goal in parasitological studies. We have previously shown that the amount of parasite DNA in faecal samples can be a biologically meaningful measure of infection intensity, even if it does not agree well with complementary counts of transmission stages (oocysts in the case of Coccidia). Parasite DNA can be quantified at relatively high throughput using quantitative polymerase chain reaction (qPCR), but amplification needs a high specificity and does not simultaneously distinguish between parasite species. Counting of amplified sequence variants (ASVs) from high-throughput marker gene sequencing using a relatively universal primer pair has the potential to distinguish between closely related co-infecting taxa and to uncover the community diversity, thus being both more specific and more open-ended. METHODS: We here compare qPCR to the sequencing-based amplification using standard PCR and a microfluidics-based PCR to quantify the unicellular parasite Eimeria in experimentally infected mice. We use multiple amplicons to differentially quantify Eimeria spp. in a natural house mouse population. RESULTS: We show that sequencing-based quantification has high accuracy. Using a combination of phylogenetic analysis and the co-occurrence network, we distinguish three Eimeria species in naturally infected mice based on multiple marker regions and genes. We investigate geographical and host-related effects on Eimeria spp. community composition and find, as expected, prevalence to be largely explained by sampling locality (farm). Controlling for this effect, the novel approach allowed us to find body condition of mice to be negatively associated with Eimeria spp. abundance. CONCLUSIONS: We conclude that amplicon sequencing provides the underused potential for species distinction and simultaneous quantification of parasites in faecal material. The method allowed us to detect a negative effect of Eimeria infection on the body condition of mice in the natural environment.

Gitelman Syndrome: A Case Report.

Gitelman syndrome is a rare hereditary tubulopathy characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. In this case report, we describe a 21-year-old male who presented with myalgias, asthenia, general muscle weakness, and hypokalemia after receiving oral potassium supplementation for six months. Additional biochemical studies showed hypomagnesemia, metabolic alkalosis, and increased urinary potassium and magnesium excretion. Calcium urinary excretion was within the normal range, but 25-hydroxycholecalciferol levels were low. Systolic arterial hypertension was found, probably reflecting chronic hyperreninemic hyperaldosteronism. Genetic testing for SCL12A3 mutations identified a pathogenic variant in homozygosity, which confirmed the Gitelman syndrome diagnosis. Treatment with chronic potassium and magnesium oral supplementation was started, as well as eplerenone and amiloride, with sustained correction of hypokalemia and hypomagnesemia.

Colloidal copper oxide nanoparticles leading to a biphasic dose-response in growth inhibition of Staphylococcus aureus.

Aim: The dose response in growth inhibition of Staphylococcus aureus treated with colloidal copper oxide nanoparticles (CuO-NP) was evaluated. Methods: An in vitro microbial viability assay was conducted with CuO-NP concentrations spreading over the 0.4-848.0 µg/ml range. The dose-response curve was modeled with a double Hill equation. UV-Visible absorption and photoluminescence spectroscopies allowed tracking concentration-dependent modifications in CuO-NP. Results: Two specific phases separated by the critical concentration of 26.5 µg/ml were observed in the dose-response curve, with each exhibiting proper IC50 parameters, Hill coefficients and relative amplitudes. Spectroscopy techniques reveal the occurrence of a concentration-triggered aggregation of CuO-NP starting from this critical concentration. Conclusion: The findings demonstrate a dose-related change in S. aureus sensitivity to CuO-NP, which probably arises from the aggregation of this agent.

Antibacterial agents are often used to stop the growth of bacteria such as Staphylococcus aureus (S. aureus). Copper oxide nanoparticles (CuO-NP) stand as a promising candidate for this purpose. Generally, the agent´s effectiveness is inspected following a dose-response curve in which de agent´s antibacterial response is plotted against its dose (concentration). In this work, employing an extended mathematical interpretation we were capable of discerning experimentally the existence of two stages of dose-response (biphasic dose-response) in the treatment of S. aureus with CuO-NP. These results in combination with insights from spectroscopic techniques lead to the understanding that the biphasic behavior arises from the aggregation of CuO-NP at high concentrations. Therefore, according to the adopted concentration to treat S. aureus, the agent can behave as a dispersed nanoparticle or as an aggregated nanoparticle. In summary, understanding whether antibacterial agents transform as a function of concentration is important in determining their practical applications.

Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors.

The Notch signaling ligand JAG1 is overexpressed in various aggressive tumors and is associated with poor clinical prognosis. Hence, therapies targeting oncogenic JAG1 hold great potential for the treatment of certain tumors. Here, we report the identification of specific anti-JAG1 single-chain variable fragments (scFvs), one of them endowing chimeric antigen receptor (CAR) T cells with cytotoxicity against JAG1-positive cells. Anti-JAG1 scFvs were identified from human phage display libraries, reformatted into full-length monoclonal antibodies (Abs), and produced in mammalian cells. The characterization of these Abs identified two specific anti-JAG1 Abs (J1.B5 and J1.F1) with nanomolar affinities. Cloning the respective scFv sequences in our second- and third-generation CAR backbones resulted in six anti-JAG1 CAR constructs, which were screened for JAG1-mediated T-cell activation in Jurkat T cells in coculture assays with JAG1-positive cell lines. Studies in primary T cells demonstrated that one CAR harboring the J1.B5 scFv significantly induced effective T-cell activation in the presence of JAG1-positive, but not in JAG1-knockout, cancer cells, and enabled specific killing of JAG1-positive cells. Thus, this new anti-JAG1 scFv represents a promising candidate for the development of cell therapies against JAG1-positive tumors.

Putative Role of an ABC Efflux System in Aliarcobacter butzleri Resistance and Virulence.

Aliarcobacter butzleri is considered a ubiquitous microorganism and emergent pathogen, for which increasing rates of multidrug resistance have been described. In line with this, the present work aimed to evaluate for the first time the contribution of an ABC efflux system, the YbhFSR, in the resistance and virulence of this bacterium. Following the in silico characterization of the YbhFSR transporter, a mutant strain was constructed by inactivating the gene responsible for ATP-binding. After ensuring that the mutation did not have an impact on bacterial growth, the resistance profile of parental and mutant strains to different antimicrobial agents was evaluated. The results suggest that the efflux pump may influence the resistance to benzalkonium chloride, ethidium bromide, and cadmium, and several other compounds were identified as potential substrates. Regarding the evaluation of the accumulation of ethidium bromide, a slight increase was observed for the mutant strain, demonstrating a potential role of the YbhFSR efflux pump in the extrusion of toxic compounds from A. butzleri. Subsequently, the role of this efflux pump on the A. butzleri known virulence properties was evaluated, but no difference was seen among mutant and parental strains for the motility, biofilm formation ability, susceptibility to oxidative stress, or the ability to adhere and invade Caco-2 cells. However, in contrast to the parental strain, the mutant strain showed a resistance to human serum. Overall, the results support the role of efflux pumps in A. butzleri resistance to antimicrobials, highlighting the particular role of the YbhFSR system.

Globally invariant metabolism but density-diversity mismatch in springtails.

Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning.

Chemical composition, antioxidant, and antimicrobial activities of six commercial essential oils.

Essential oils (EOs) and their components extracted from medicinal and aromatic plants are used in several areas, such as perfumery and chemical, cosmetic, food, and pharmaceutical industries. Considering the different applications of EOs, this work aimed to screen the composition and the bioactivities properties of the EOs of Foeniculum vulgare, Helichrysum stoechas, Mentha pulegium, Pinus pinaster, Ruta graveolens, and Thymus mastichina. Gas chromatography-mass spectrometry revealed the presence of different compounds in EOs F. vulgare (12), H. stoechas (27), M. pulegium (8), P. pinaster (24), R. graveolens (8), and T. mastichina (16). All the EOs showed antioxidant activity acting through inhibition of lipid peroxidation, while only two EOs (H. stoechas and M. pulegium) scavenged the free radicals of DPPH. Mentha pulegium and T. mastichina EOs showed the strongest antimicrobial activity. Also, the effect on the fibroblast's viability was directly proportional to the EOs concentration, and the highest cytotoxic effect was registered with R. graveolens EO. The present study revealed significant bioactive properties of different EOs, highlighting M. pulegium and T. mastichina EOs to be considered in further studies for potential use in the food and pharmaceutical industries, due to their antioxidant and antimicrobial properties.

High-frequency repetitive magnetic stimulation rescues ischemia-injured neurons through modulation of glial-derived neurotrophic factor present in the astrocyte's secretome.

Due to its ability to improve the most frequent clinical sequelae left by ischemia, repetitive transcranial magnetic stimulation has been considered a promising therapeutic strategy for stroke. Those improvements are associated with changes in neurons and their synaptic liaisons. However, the hypothesis that this technique modulates astrocytes, potentiating their neuroprotective capabilities, was also raised. This study aims to identify the effects triggered by high-frequency repetitive magnetic stimulation (HF-rMS) on astrocytes that contribute to its neuroprotective effects. Neuron-glia and astrocyte cortical cultures subject to oxygen and glucose deprivation were used as an in vitro model of ischemia. Neuroprotection promoted by HF-rMS was evaluated by analysis of markers of neuronal activity and morphometric analysis of neurons. Glial reactivity was determined by immunocytochemistry. The levels of growth factors in the astrocyte-conditioned medium (CM) were assessed through a Growth Factor Array and glial-derived neurotrophic factor (GDNF) expression was analyzed by RT-PCR and Western blot. Our results show that neurons injured by ischemia can be rescued through the modulation of astrocytes by HF-rMS. This modulation helps to maintain the number and length of neurites and increases the number of neurons expressing ERK1/2 and c-Fos. Analysis of the astrocyte-CM showed that HF-rMS stimulated the release of several trophic factors by astrocytes. Moreover, GDNF was one of the released factors that contributed to the recovery mechanisms triggered by HF-rMS. Our results show that modulation of astrocytes by HF-rMS effectively rescues neurons injured by ischemia and suggest that by targeting astrocytes this approach can also be used to promote neuroprotection in other brain lesions.

Melissa officinalis essential oil as an antimicrobial agent against Listeria monocytogenes in watermelon juice.

The burden of foodborne illness has a negative effect on public health, but also in countries' economy. Melissa officinalis is an aromatic plant known for its biological properties, including antioxidant and antimicrobial effects. This work highlighted M. officinalis essential oil's antioxidant potential and antimicrobial activity against L. monocytogenes, presenting a bactericidal action and being able to inhibit some virulence attributes, such as biofilm formation. The pre-exposure of the bacterium to subinhibitory levels of essential oil (0.125 µL/mL) did not induce high tolerance to stresses (such as high temperature, low pH, osmotic stress and desiccation) or cross-resistance with antibiotics, while not modifying the invasion ability to Caco-2 cells. When applied in food model media (lettuce, chicken and milk) and watermelon juice, the essential oil showed to have antimicrobial activity in a lettuce leaf model medium, further diminishing L. monocytogenes contamination and inhibiting the natural microbiota present in watermelon juice. M. officinalis essential oil shows potential to be used as control of L. monocytogenes in watermelon juice, while increasing the food's microbial shelf life.

Small supernumerary marker chromosomes derived from human chromosome 11.

Introduction: With only 39 reported cases in the literature, carriers of a small supernumerary marker chromosome (sSMC) derived from chromosome 11 represent an extremely rare cytogenomic condition. Methods: Herein, we present a review of reported sSMC(11), add 18 previously unpublished cases, and closely review eight cases classified as 'centromere-near partial trisomy 11' and a further four suited cases from DECIPHER. Results and discussion: Based on these data, we deduced the borders of the pericentric regions associated with clinical symptoms into a range of 2.63 and 0.96 Mb for chromosome 11 short (p) and long (q) arms, respectively. In addition, the minimal pericentric region of chromosome 11 without triplo-sensitive genes was narrowed to positions 47.68 and 60.52 Mb (GRCh37). Furthermore, there are apparent differences in the presentation of signs and symptoms in carriers of larger sSMCs derived from chromosome 11 when the partial trisomy is derived from different chromosome arms. However, the number of informative sSMC(11) cases remains low, with overlapping presentation between p- and q-arm-imbalances. In addition, uniparental disomy (UPD) of 'normal' chromosome 11 needs to be considered in the evaluation of sSMC(11) carriers, as imprinting may be an influencing factor, although no such cases have been reported. Comprehensively, prenatal sSMC(11) cases remain a diagnostic and prognostic challenge.

Endogenous GDNF Is Unable to Halt Dopaminergic Injury Triggered by Microglial Activation.

Overactivation of microglial cells seems to play a crucial role in the degeneration of dopaminergic neurons occurring in Parkinson's disease. We have previously demonstrated that glial cell line-derived neurotrophic factor (GDNF) present in astrocytes secretome modulates microglial responses induced by an inflammatory insult. Therefore, astrocyte-derived soluble factors may include relevant molecular players of therapeutic interest in the control of excessive neuroinflammatory responses. However, in vivo, the control of neuroinflammation is more complex as it depends on the interaction between different types of cells other than microglia and astrocytes. Whether neurons may interfere in the astrocyte-microglia crosstalk, affecting the control of microglial reactivity exerted by astrocytes, is unclear. Therefore, the present work aimed to disclose if the control of microglial responses mediated by astrocyte-derived factors, including GDNF, could be affected by the crosstalk with neurons, impacting GDNF's ability to protect dopaminergic neurons exposed to a pro-inflammatory environment. Also, we aimed to disclose if the protection of dopaminergic neurons by GDNF involves the modulation of microglial cells. Our results show that the neuroprotective effect of GDNF was mediated, at least in part, by a direct action on microglial cells through the GDNF family receptor α-1. However, this protective effect seems to be impaired by other mediators released in response to the neuron-astrocyte crosstalk since neuron-astrocyte secretome, in contrast to astrocytes secretome, was unable to protect dopaminergic neurons from the injury triggered by lipopolysaccharide-activated microglia. Supplementation with exogenous GDNF was needed to afford protection of dopaminergic neurons exposed to the inflammatory environment. In conclusion, our results revealed that dopaminergic protective effects promoted by GDNF involve the control of microglial reactivity. However, endogenous GDNF is insufficient to confer dopaminergic neuron protection against an inflammatory insult. This reinforces the importance of further developing new therapeutic strategies aiming at providing GDNF or enhancing its expression in the brain regions affected by Parkinson's disease.

Clinical Nutrition in Portuguese Gastroenterology Departments: A Multicentric Study.

BACKGROUND: Hospital nutrition is a major public health problem, as up to 50% of hospitalized patients suffer from undernutrition. Adequate nutritional support (NS) decreases morbidity/mortality, shortens the length of stay, and reduces costs. We aimed to evaluate the engagement of Portuguese gastroenterology departments in NS, especially in artificial nutrition (AN). METHODS: Cross-sectional multicentric study, using an online survey sent to 31 Portuguese gastroenterology departments. RESULTS: Nine centers were involved, and all departments were engaged in NS activities. The most performed nutrition technique was endoscopic gastrostomy and not all departments had the expertise to perform all nutrition procedures, namely, endoscopic jejunostomy. Two departments had an AN outpatient clinic. Five centers were involved in hospital nutrition committees. Only four performed systematic nutritional evaluation of every patient on admission. Two departments developed research in the nutrition field. An increase staff and nutrition training were pointed out as suggestions to improve NS. CONCLUSIONS: This study outlines a broad picture of NS/AN in Portuguese gastroenterology departments. Medical nutritional training and increasing nutrition teams' staff may contribute to developing NS/AN. Multidisciplinary management of nutrition-related disorders is of utmost importance, and gastroenterologists are expected to be at the core of hospital nutrition.