Mining threats in high-level biodiversity conservation policies.

Amid a global infrastructure boom, there is increasing recognition of the ecological impacts of the extraction and consumption of construction minerals, mainly processed as concrete, including significant and expanding threats to global biodiversity. We investigated how high-level national and international biodiversity conservation policies address mining threats, with a special focus on construction minerals. We conducted a review and quantified the degree to which threats from mining these minerals are addressed in biodiversity goals and targets under the 2011-2020 and post-2020 biodiversity strategies, national biodiversity strategies and action plans, and the assessments of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services. Mining appeared rarely in national targets but more frequently in national strategies. Yet, in most countries, it was superficially addressed. Coverage of aggregates mining was greater than coverage of limestone mining. We outline 8 key components, tailored for a wide range of actors, to effectively mainstream biodiversity conservation into the extractive, infrastructure, and construction sectors. Actions include improving reporting and monitoring systems, enhancing the evidence base around mining impacts on biodiversity, and modifying the behavior of financial agents and businesses. Implementing these measures could pave the way for a more sustainable approach to construction mineral use and safeguard biodiversity.

Amenazas de la minería a las políticas de alto nivel para la conservación de la biodiversidad Resumen Enmedio del auge global del desarrollo de infraestructura, hay un mayor reconocimiento de los impactos ecológicos de la extracción y consumo de materiales para construcción, procesados predominantemente como concreto. Estos materiales representan amenazas significativas y en expansión para la biodiversidad global. Investigamos cómo son abordadas las amenazas de la minería por las políticas nacionales e internacionales de alto nivel para la conservación de la biodiversidad, con enfoque especial en los minerales para construcción. Realizamos una revisión exhaustiva y cuantificamos el grado en el cual son abordadas las amenazas de la extracción de estos minerales en los objetivos y metas para la biodiversidad bajo estrategias 2011­2020 y post 2020, las estrategias y planes de acción nacionales para la biodiversidad, y las evaluaciones de la Plataforma Intergubernamental Científico­normativa sobre Diversidad Biológica y Servicios de los Ecosistemas. La minería raramente apareció en los objetivos nacionales, pero fue más frecuente en las estrategias nacionales. Sin embargo, fue abordada superficialmente en la mayoría de los países. La cobertura de minería de agregados fue mayor que la cobertura de la minería de caliza. Describimos ocho componentes clave, adaptados para una amplia gama de actores, para incorporar eficazmente la conservación de la biodiversidad en los sectores extractivo, desarrollo de infraestructura y construcción. Las acciones incluyen la mejora de los sistemas de informes y monitoreo, el reforzamiento de la base de evidencias en torno a los impactos de la minería sobre la biodiversidad y la modificación del comportamiento de los agentes financieros y comerciales. La implementación de estas medidas podría allanar el camino para un enfoque más sostenible en el uso de minerales para la construcción y la salvaguarda de la biodiversidad.

Biofunctionalization of surfaces to minimize undesirable effects in cardiovascular assistance devices.

BACKGROUND: The reactivity of blood with non-endothelial surface is a challenge for long-term Ventricular Assist Devices development, usually made with pure titanium, which despite of being inert, low density and high mechanical resistance it does not avoid the thrombogenic responses. Here we tested a modification on the titanium surface with Laser Induced Periodic Surface Structures followed by Diamond Like Carbon (DLC) coating in different thicknesses to customize the wettability profile by changing the surface energy of the titanium. METHODS: Four different surfaces were proposed: (1) Pure Titanium as Reference Material (RM), (2) Textured as Test Sample (TS), (3) Textured with DLC 0.3µm as (TSA) and (4) Textured with 2.4µm DLC as (TSB). A single implant was positioned in the abdominal aorta of Wistar rats and the effects of hemodynamic interaction were evaluated without anticoagulant drugs. RESULTS: After twelve weeks, the implants were extracted and subjected to qualitative analysis by Scanning Electron Microscopy under low vacuum and X-ray Energy Dispersion. The regions that remained in contact with the wall of the aorta showed encapsulation of the endothelial tissue. TSB implants, although superhydrophilic, have proven that the DLC coating inhibits the adhesion of biological material, prevents abrasive wear and delamination, as observed in the TS and TSA implants. Pseudo- neointimal layers were heterogeneously identified in higher concentration on Test Surfaces.

Analysis of durability and replacement of vocal prostheses in total laryngectomy patients at a head and neck surgery referral center.

PURPOSE: The use of tracheoesophageal prostheses has become the gold standard in vocal rehabilitation of patients undergoing total laryngectomy. However, this method also has limitations, such as the need for frequent replacement of prostheses due to leakage or other complications. We have designed a study to access the clinical profile of patients using tracheoesophageal prostheses as vocal rehabilitation after total laryngectomy and to determine the average rate of changes, as well as the main causes of prostheses replacement. METHODS: A retrospective cohort study was performed based on patients who underwent rehabilitation with voice prostheses after total laryngectomy between 2008 and 2017. RESULTS: The sample consisted of 93 patients and 432 vocal prostheses replacement events. The median change of prostheses per patient was 210.25 days, (range 57.33 to 651.50). The most frequent cause of prostheses replacement was leakage through the prostheses, 218 (50.46%). Lower level of education was associated to higher prostheses replacement rate. CONCLUSION: The results of this study show that the median of prostheses durability is higher than that presented in the literature, the main cause of replacement was protheses leakage and that low educational level is associated to higher replacement rate.

Metastatic Melanoma: A Preclinical Model Standardization and Development of a Chitosan-Coated Nanoemulsion Containing Temozolomide to Treat Brain Metastasis.

Melanoma is the most aggressive type of skin cancer. Brain metastasis is the worst scenario in metastatic melanoma and the treatment options for these patients are limited. Temozolomide (TMZ) is a chemotherapy agent used to treat primary central nervous system tumors. Our objective was to develop chitosan-coated nanoemulsion containing temozolomide (CNE-TMZ) for nasal route administration to melanoma brain metastasis treatment. A preclinical model of metastatic brain melanoma was standardized, and the efficiency of the developed formulation was further determined in vitro and in vivo. The nanoemulsion was done by spontaneous emulsification method and the formulation was characterized by size, pH, polydispersity index, and zeta potential. Culture assessments to determine cell viability were done in the A375 human melanoma cell line. To determine the safety of formulation, healthy C57/BL6 mice were treated with a nanoemulsion without TMZ. The model in vivo used B16-F10 cells implanted by stereotaxic surgery in C57/BL6 mice brains. The results demonstrate that the preclinical model used showed to be useful to analyze the efficiency of new candidate drugs to treat melanoma brain metastasis. The chitosan-coated nanoemulsions with TMZ showed the expected physicochemical characteristics and demonstrated safety and efficacy, reducing around 70% the tumor size compared to control mice, and presenting a tendency in mitotic index reduction, becoming an interesting approach to treat melanoma brain metastasis.

Bile acids profile and redox status in healthy infants.

BACKGROUND: At birth, human neonates are more likely to develop cholestasis and oxidative stress due to immaturity or other causes. We aimed to search for a potential association between bile acids profile, redox status, and type of diet in healthy infants. METHODS: A cross-sectional, exploratory study enrolled 2-month-old full-term infants (n = 32). We measured plasma bile acids (total and conjugated), and red blood cell (RBC) oxidative stress biomarkers. The type of diet (breastfeeding, mixed, formula) was used as an independent variable. RESULTS: Plasma total bile acids medium value was 14.80 µmol/L (IQR: 9.25-18.00). The plasma-conjugated chenodeoxycholic acid percentage (CDCA%) correlated significantly and negatively with RBCs membrane-bound hemoglobin percentage (MBH%) (r = -0.635, p < 0.01) and with RBC-oxidized glutathione (r = -0.403, p < 0.05) levels. RBC oxidative stress biomarkers (especially MBH%) were predictors of conjugated CDCA%, and this predictive ability was enhanced when adjusted for the type of diet (MBH, r = 0.452, p < 0.001). CONCLUSIONS: Our data suggest that the bile acid profile might play a role in the regulation of redox status (or vice versa) in early postnatal life. Eventually, the type of diet may have some impact on this process. IMPACT: The conjugated CDCA% in plasma is negatively correlated with biomarkers of RBC oxidative stress in healthy infants. Specific biomarkers of RBC oxidative stress (e.g. MBH, GSH, GSSG) may be promising predictors of conjugated CDCA% in plasma. The type of diet may influence the predictive ability of hit RBC oxidative stress biomarkers (e.g. MBH, GSH, GSSG). Our findings suggest a link between plasma bile acids profile and the RBC redox status in healthy infants, eventually modulated by the type of diet. The recognition of this link may contribute to the development of preventive and therapeutic strategies for neonatal cholestasis.

Psidium cattleianum fruit extract prevents systemic alterations in an animal model of type 2 diabetes mellitus: comparison with metformin effects.

Objective: In this study, we aimed to determine the role of Psidium cattleianum extract (PCE) and compare its effects with those of metformin (Met) in an animal model with type 2 diabetes mellitus (T2DM).Methods: T2DM was induced in rats using a high-fat diet (HFD), followed by a single dose of streptozotocin (STZ). Met and PCE were administered intragastrically once a day throughout the experiment, and their effects on biochemical, inflammatory, oxidative, and histological parameters were evaluated.Results: Met and PCE prevented the increase in serum levels of glucose, total cholesterol (TC), triacylglycerol (TG), very low-density lipoprotein (VLDL) and interleukin-6 (IL-6) induced by T2DM, and restored redox homeostasis in the liver and brain. Met increased the serum levels of anti-inflammatory cytokine and interleukin-10 (IL-10). Furthermore, both treatments restored the liver and pancreas from marked cellular disorganisation, vacuolisation, and necrosis, with PCE being more effective than Met in recovering histological changes.Conclusion: PCE is a promising agent for the prevention of T2DM complications.

Utilization of the ketogenic diet for adults with status epilepticus.

BACKGROUND: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet with therapeutic potential in refractory seizures, both in outpatient and inpatient settings. Successful implementation of KD involves a multifaceted, interdisciplinary approach to address anticipated challenges. We sought to characterize the utilization of KD among healthcare providers caring for adults with status epilepticus (SE). METHODS: We distributed a web-based survey through professional societies, including the American Academy of Neurology (AAN), Neurocritical Care Society (NCS), American Epilepsy Society (AES), Neuro Anesthesia and Critical Care Society (NACCS), and the Academy of Nutrition and Dietetics (AND), and via research contacts. We asked respondents about practice experience and experience using KD as a treatment for SE. Descriptive statistics and Chi-square tests were used to analyze the results. RESULTS: Of 156 respondents, 80% of physicians and 18% of non-physicians reported experience with KD for SE. Anticipated difficulty in achieving ketosis (36.3%), lack of expertise (24.2%), and lack of resources (20.9%) were identified as the most important barriers limiting the utilization of KD. The absence of dietitians (37.1%) or pharmacists (25.7%) support was the most important missing resource. Reasons for stopping KD included perceived ineffectiveness (29.1%), difficulty achieving ketosis (24.6%), and side effects (17.3%). Academic centers had more experience with the use of KD and greater EEG monitoring availability and fewer barriers to its implementation. The need for randomized clinical trials supporting efficacy (36.5%) and better practice guidelines for implementation and maintenance of KD (29.6%) were cited most frequently as factors to increase utilization of KD. CONCLUSION: This study identifies important barriers to the utilization of KD as a treatment for SE despite evidence supporting its efficacy in the appropriate clinical context, namely lack of resources and interdisciplinary support, and lack of established practice guidelines. Our results highlight the need for future research to improve understanding of the efficacy and safety of KD along with better interdisciplinary collaborations to increase its utilization.

Therapeutic potential of blackberry extract in the preventing memory deficits and neurochemical alterations in the cerebral cortex, hippocampus and cerebellum of a rat model with amnesia.

The blackberry (Rubus sp.) is a popular fruit that has a high concentration of phenolic compounds. Pharmacological investigations have demonstrated the important biological activities of the blackberry extract, such as neuroprotective actions. This study aimed to evaluate the effects of blackberry extract on memory and neurochemical parameters in rats subjected to scopolamine (SCO)-induced amnesia. Male rats were divided into five groups: I, control (saline); II, SCO; III, SCO + Rubus sp. (100 mg/kg); IV, SCO + Rubus sp. (200 mg/kg); and V, SCO + donepezil (5 mg/kg). Blackberry extract and donepezil were orally administered for 10 days. On day 11, group I received saline, and groups II, III, IV, and V received SCO (1 mg/kg) intraperitoneally after object recognition behavioral training. Twenty-four hours after the training session, animals were subjected to an object recognition test. Finally, the animals were euthanized, and the cerebral cortex, hippocampus, and cerebellum were collected to evaluate the oxidative stress and acetylcholinesterase (AChE) activity. Rubus sp. extract prevented memory impairment induced by SCO in a manner similar to that of donepezil. Additionally, Rubus sp. extract and donepezil prevented the increase in AChE activity induced by SCO in all the evaluated brain structures. SCO induced oxidative damage in the cerebral cortex, hippocampus, and cerebellum, which was prevented by Rubus sp. and donepezil. Our results suggest that the antioxidant and anticholinesterase activities of Rubus sp. are associated with memory improvement; hence, it can potentially be used for the treatment of neurodegenerative diseases.

Protective Effects of Inosine on Memory Consolidation in a Rat Model of Scopolamine-Induced Cognitive Impairment: Involvement of Cholinergic Signaling, Redox Status, and Ion Pump Activities.

This study investigated the effects of inosine on memory acquisition and consolidation, cholinesterases activities, redox status and Na+, K+-ATPase activity in a rat model of scopolamine-induced cognitive impairment. Adult male rats were divided into four groups: control (saline), scopolamine (1 mg/kg), scopolamine plus inosine (50 mg/kg), and scopolamine plus inosine (100 mg/kg). Inosine was pre-administered for 7 days, intraperitoneally. On day 8, scopolamine was administered pre (memory acquisition protocol) or post training (memory consolidation protocol) on inhibitory avoidance tasks. The animals were subjected to the step-down inhibitory avoidance task 24 hours after the training. Scopolamine induced impairment in the acquisition and consolidation phases; however, inosine was able to prevent only the impairment in memory consolidation. Also, scopolamine increased the activity of acetylcholinesterase and reduced the activity of Na+, K+-ATPase and the treatment with inosine protected against these alterations in consolidation protocol. In the animals treated with scopolamine, inosine improved the redox status by reducing the levels of reactive oxygen species and thiobarbituric acid reactive substances and restoring the activity of the antioxidant enzymes, superoxide dismutase and catalase. Our findings suggest that inosine may offer protection against scopolamine-induced memory consolidation impairment by modulating brain redox status, cholinergic signaling and ion pump activity. This compound may provide an interesting approach in pharmacotherapy and as a prophylactic against neurodegenerative mechanisms involved in Alzheimer's disease.

Blueberry extract as a potential pharmacological tool for preventing depressive-like behavior and neurochemical dysfunctions in mice exposed to lipopolysaccharide.

OBJECTIVE: Major depressive disorder is a debilitating and recurrent psychiatric disorder. Blueberries have several biological properties, including neuroprotective effects, through antioxidant and anti-inflammatory actions. The aim of this study was to evaluate the effect of blueberry extract on depressive-like behavior and lipopolysaccharide (LPS)-induced neurochemical changes. METHODS: Mice were pretreated with vehicle, fluoxetine (20 mg/kg) or blueberry extract (100 or 200 mg/kg) intragastrically for seven days before intraperitoneal LPS (0.83 mg/kg) injection. Twenty-four hours after LPS administration, mice were submitted to behavioral tests. Oxidative stress and neuroinflammatory parameters were evaluated in the cerebral cortex, hippocampus, and striatum. RESULTS: Our data showed that blueberry extract or fluoxetine treatment protected against LPS-induced depressive-like behavior in tail suspension and splash tests (P < 0.05), without changes in locomotor activity (P > 0.05). LPS induced an increase in the levels of reactive oxygen species (P < 0.001), nitrite (P < 0.05) and thiobarbituric acid reactive substances (P < 0.01), as well as a reduction in total sulfhydryl content (P < 0.05) and catalase activity (P < 0.05) in brain structures; blueberry extract restored these alterations (P < 0.05). In addition, blueberry extract attenuated the increase in tumor necrosis factor-alpha (TNF-α) levels induced by LPS administration (P < 0.05). CONCLUSION: This study showed that blueberry extract exerted antidepressant-like effects, protected the brain against oxidative damage, and modulated TNF-α levels induced by LPS.

Ultrasound-Guided Suprazygomatic Nerve Blocks to the Pterygopalatine Fossa: A Safe Procedure.

OBJECTIVES: Large-scale procedural safety data on pterygopalatine fossa nerve blocks (PPFBs) performed via a suprazygomatic, ultrasound-guided approach are lacking, leading to hesitancy surrounding this technique. The aim of this study was to characterize the safety of PPFB. METHODS: This retrospective chart review examined the records of adults who received an ultrasound-guided PPFB between January 1, 2016, and August 30, 2020, at the University of Florida. Indications included surgical procedures and nonsurgical pain. Clinical data describing PPFB were extracted from medical records. Descriptive statistics were calculated for all variables, and quantitative variables were analyzed with the paired t test to detect differences between before and after the procedure. RESULTS: A total of 833 distinct PPFBs were performed on 411 subjects (59% female, mean age 48.5 years). Minor oozing from the injection site was the only reported side effect, in a single subject. Although systolic blood pressure, heart rate, and oxygen saturation were significantly different before and after the procedure (132.3 vs 136.4 mm Hg, P < 0.0001; 78.2 vs 80.8, P = 0.0003; and 97.8% vs 96.3%, P < 0.0001; respectively), mean arterial pressure and diastolic blood pressure were not significantly different (96.2 vs 97.1 mm Hg, P = 0.1545, and 78.2 vs 77.4 mm Hg, P = 0.1314, respectively). Similar results were found within subgroups, including subgroups by sex, race, and indication for PPFB. DISCUSSION: We have not identified clinically significant adverse effects from PPFB performed with an ultrasound-guided suprazygomatic approach in a large cohort in the hospital setting. PPFBs are a safe and well-tolerated pain management strategy; however, prospective multicenter studies are needed.

Immunophenotypic profile of macrophages in generalized pustular psoriasis and deficiency of the interleukin-36 receptor antagonist.

M2 macrophages are copious in generalized pustular psoriasis (GPP). M2 macrophages seem to acquire new skills and share common characteristics in GPP. HAM56 may play a role in attracting immature neutrophils to the inflammatory environment in GPP.

LPS-induced impairment of Na+/K+-ATPase activity: ameliorative effect of tannic acid in mice.

Acetylcholine is an excitatory neurotransmitter that modulates synaptic plasticity and communication, and it is essential for learning and memory processes. This neurotransmitter is hydrolyzed by acetylcholinesterase (AChE), which plays other cellular roles in processes such as inflammation and oxidative stress. Ion pumps, such as Na+/K+-ATPase and Ca2+-ATPase, are highly expressed channels that derive energy for their functions from ATP hydrolysis. Impairment of the cholinergic system and ion pumps is associated with neuropsychiatric diseases. Major depressive disorder (MDD) is an example of a complex disease with high morbidity and a heterogenous etiology. Polyphenols have been investigated for their therapeutic effects, and tannic acid (TA) has been reported to show neuroprotective and antidepressant-like activities. Animal models of depression-like behavior, such as lipopolysaccharide (LPS)-induced models of depression, are useful for investigating the pathophysiology of MDD. In this context, effects of TA were evaluated in an LPS-induced mouse model of depression-like behavior. Animals received TA for 7 days, and on the last day of treatment, LPS (830 µg/kg) was administered intraperitoneally. In vitro exposure of healthy brain to TA decreased the AChE activity. Additionally, this enzyme activity was decreased in cerebral cortex of LPS-treated mice. LPS injection increased the activity of Ca2+-ATPase in the cerebral cortex but decreased the enzyme activity in the hippocampus. LPS administration decreased Na+/K+-ATPase activity in the cerebral cortex, hippocampus, and striatum; however, TA administration prevented these changes. In conclusion, tannins may affect Na+/K+-ATPase and Ca2+-ATPase activities, which is interesting in the context of MDD.

Multitarget Effect of 2-(4-(Methylthio)phenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-4-one in a Scopolamine-Induced Amnesic Rat Model.

Cholinergic system dysfunction, oxidative damage, and alterations in ion pump activity have been associated with memory loss and cognitive deficits in Alzheimer's disease. 1,3-thiazolidin-4-ones have emerged as a class of compounds with potential therapeutic effects due to their potent anticholinesterase activity. Accordingly, this study investigated the effect of the 2-(4-(methylthio)phenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-4-one (DS12) compound on memory, cholinergic and oxidative stress parameters, ion pump activity, and serum biochemical markers in a scopolamine-induced memory deficit model. Male Wistar rats were divided into four groups: I-Control; II-Scopolamine; III-DS12 (5 mg/kg) + scopolamine; and IV-DS12 (10 mg/kg) + scopolamine. The animals from groups III and IV received DS12 diluted in canola oil and administered for 7 days by gavage. On the last day of treatment, scopolamine (1 mg/kg) was administered intraperitoneally (i.p.) 30 min after training in an inhibitory avoidance apparatus. Twenty-four hours after scopolamine administration, the animals were subjected to an inhibitory avoidance test and were thereafter euthanized. Scopolamine induced memory deficits, increased acetylcholinesterase activity and oxidative damage, and decreased Na+/K+-ATPase activity in cerebral cortex and hippocampus. Pretreatment with DS12 prevented these brain alterations. Scopolamine also induced an increase in acetylcholinesterase activity in lymphocytes and whereas butyrylcholinesterase in serum and treatment with DS12 prevented these changes. In animals treated with DS12, no changes were observed in renal and hepatic parameters when compared to the control group. In conclusion, DS12 emerged as an important multitarget compound capable of preventing neurochemical changes associated with memory deficits.

Characterization of macrophage phenotype, redox, and purinergic response upon chronic treatment with methionine and methionine sulfoxide in mice.

Hypermethioninemia is a disorder characterized by high plasma levels of methionine (Met) and its metabolites such as methionine sulfoxide (MetO). Studies have reported associated inflammatory complications, but the mechanisms involved in the pathophysiology of hypermethioninemia are still uncertain. The present study aims to evaluate the effect of chronic administration of Met and/or MetO on phenotypic characteristics of macrophages, in addition to oxidative stress, purinergic system, and inflammatory mediators in macrophages. In this study, Swiss male mice were subcutaneously injected with Met and MetO at concentrations of 0.35-1.2 g/kg body weight and 0.09-0.3 g/kg body weight, respectively, from the 10th-38th day post-birth, while the control group was treated with saline solution. The results revealed that Met and/or MetO induce an M1/classical activation phenotype associated with increased levels of tumor necrosis factor alpha and nitrite, and reduced arginase activity. It was also found that Met and/or MetO alter the activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, as well as the levels of thiol and reactive oxygen species in macrophages. The chronic administration of Met and/or MetO also promotes alteration in the hydrolysis of ATP and ADP, as indicated by the increased activity of ectonucleotidases. These results demonstrate that chronic administration of Met and/or MetO promotes activated pro-inflammatory profile by inducing M1/classical macrophage polarization. Thus, the changes in redox status and purinergic system upon chronic Met and/or MetO exposure may contribute towards better understanding of the alterations consistent with hypermethioninemic patients.

Antidepressant Effect and Modulation of the Redox System Mediated by Tannic Acid on Lipopolysaccharide-Induced Depressive and Inflammatory Changes in Mice.

Depression is an emotional disorder that causes mental and physical changes, and has limited pharmacotherapy. Tannic acid (TA) is a polyphenol with previously described antioxidant and neuroprotective properties. The aim of this study was to evaluate the effects of TA on lipopolysaccharide (LPS)-induced depressive-like behavior, as well as oxidative stress parameters and TNF-α levels in the brains of mice. Animals were pretreated once daily, with TA (30 or 60 mg/kg), fluoxetine (20 mg/kg) or vehicle for 7 days. On the 7th day, the animals received a single injection of LPS (830 µg/kg). After 24 h, open field, forced swimming, tail suspension, and splash tests were conducted. The endotoxin induced depressive-like behavior in these mice and this was attenuated by TA. In the cerebral cortex, hippocampus, and striatum, LPS increased lipid peroxidation and reactive oxygen species production, and this was also prevented by TA administration. TA treatment also prevented a decrease in catalase activity within the striatum. Further, LPS administration caused increased levels of TNF-α in all brain structures, and this was prevented in the cortex by TA treatment. In conclusion, TA shows many neuroprotective properties, with demonstrated antioxidant, anti-inflammatory and antidepressant effects in this animal model of acute depressive-like behavior. Therefore, this compound could provide an alternative therapeutic approach for the treatment of depression.

Inference in road ecology research: what we know versus what we think we know.

Roads and traffic impacts on wildlife populations are well documented. Three major mechanisms can cause them: reduced connectivity, increased mortality and reduced habitat quality. Researchers commonly recommend mitigation based on the mechanism they deem responsible. We reviewed the 2012-2016 literature to evaluate authors' inferences, to determine whether they explicitly acknowledge all possible mechanisms that are consistent with their results. We found 327 negative responses of wildlife to roads, from 307 studies. While most (84%) of these responses were consistent with multiple mechanisms, 60% of authors invoked a single mechanism. This indicates that many authors are over-confident in their inferences, and that the literature does not allow estimation of the relative importance of the mechanisms. We found preferences in authors' discussion of mechanisms. When all three mechanisms were consistent with the response measured, authors were 2.4 and 2.9 times as likely to infer reduced habitat quality compared to reduced connectivity or increased mortality, respectively. When both reduced connectivity and increased mortality were consistent with the response measured, authors were 5.2 times as likely to infer reduced connectivity compared to increased mortality. Given these results, road ecologists and managers are likely over-recommending mitigation for improving habitat quality and connectivity, and under-recommending measures to reduce road-kill.

An adaptive plan for prioritizing road sections for fencing to reduce animal mortality.

Mortality of animals on roads is a critical threat to many wildlife populations and is poised to increase strongly because of ongoing and planned road construction. If these new roads cannot be avoided, effective mitigation measures will be necessary to stop biodiversity decline. Fencing along roads effectively reduces roadkill and is often used in combination with wildlife passages. Because fencing the entire road is not always possible due to financial constraints, high-frequency roadkill areas are often identified to inform the placement of fencing. We devised an adaptive fence-implementation plan to prioritize road sections for fencing. In this framework, areas along roads of high, moderate, and low levels of animal mortality (respectively, roadkill hotspots, warmspots, and coldspots) are identified at multiple scales (i.e., in circles of different diameters [200-2000 m] in which mortality frequency is measured). Fence deployment is based on the relationship between the amount of fencing being added to the road, starting with the strongest roadkill hotspots, and potential reduction in road mortality (displayed in mortality-reduction graphs). We applied our approach to empirical and simulated spatial patterns of wildlife-vehicle collisions. The scale used for analysis affected the number and spatial extent of roadkill hot-, warm-, and coldspots. At fine scales (e.g., 200 m), more hotspots were identified than at coarse scales (e.g., 2000 m), but combined the fine-scale hotspots covered less road and less fencing was needed to reduce road mortality. However, many short fences may be less effective in practice due to a fence-end effect (i.e., animals moving around the fence more easily), resulting in a trade-off between few long and many short fences, which we call the FLOMS (few-long-or-many-short) fences trade-off. Thresholds in the mortality-reduction graphs occurred for some roadkill patterns, but not for others. Thresholds may be useful to consider when determining road-mitigation targets. The existence of thresholds at multiple scales and the FLOMS trade-off have important implications for biodiversity conservation.

Un Plan Adaptativo para la Priorización de Secciones de Carretera para Cercar y Reducir la Mortalidad Animal Resumen La mortalidad de los animales en las carreteras es una amenaza muy importante para las poblaciones silvestres y se pronostica que aumentarán enérgicamente debido a la construcción continua y planeada de carreteras. Si estas nuevas carreteras no pueden evitarse, se necesitarán medidas efectivas de mitigación para detener la declinación de la biodiversidad. El cercado a lo largo de las carreteras reduce efectivamente los atropellamientos y se usa frecuentemente junto con los pasos de fauna. Ya que cercar por completo la carretera no siempre es posible debido a las restricciones financieras, es común identificar las áreas con una frecuencia alta de atropellamientos para que la colocación de cercas esté informada al respecto. Diseñamos un plan adaptativo de implementación de cercas para priorizar las secciones de carretera que requieren ser cercadas. En este marco de trabajo, identificamos las áreas a lo largo de las carreteras con un nivel alto, moderado y bajo de mortalidad animal (respectivamente, puntos calientes, cálidos y fríos de atropellamiento) a diferentes escalas (es decir, en círculos de diferentes diámetros [200-2000 m] dentro de los cuales se mide la frecuencia de la mortalidad). El despliegue de cercas está basado en la relación entre la cantidad de cercas que se van añadiendo a la carretera, iniciando en los puntos calientes de atropellamiento, y la reducción potencial de la mortalidad en la carretera (presentada en gráficas de reducción de la mortalidad). Aplicamos nuestra estrategia a los patrones espaciales empíricos y simulados de las colisiones entre vehículos y animales. La escala utilizada para el análisis afectó al número y a la extensión espacial de los puntos calientes, cálidos y fríos de los atropellamientos. A escalas finas (p. ej.: 200 m), se identificaron más puntos calientes que a escalas más amplias (p. ej.: 2000 m), pero combinadas las escalas finas, los puntos calientes cubrieron una superficie menor de la carretera y se necesitaron menos cercas para reducir la mortalidad. Sin embargo, muchas cercas cortas pueden ser menos efectivas en la práctica debido al efecto de fin de valla (es decir, que los animales se muevan alrededor de la cerca con mayor facilidad), lo que resulta en una compensación entre pocas cercas largas y muchas cercas cortas, que denominamos compensación de cercas FLOMS (pocas-largas-o-muchas-cortas). Los umbrales en las gráficas de reducción de la mortalidad se presentaron para algunos patrones de atropellamiento, pero no para otros. Los umbrales pueden ser útiles para considerar cuando se determinan los objetivos de mitigación para las carreteras. La existencia de los umbrales a escalas múltiples y la compensación de FLOMS tienen implicaciones importantes para la conservación de la biodiversidad.

Development and characterization of CD73-siRNA-loaded nanoemulsion: effect on C6 glioma cells and primary astrocytes.

Introduction: Glioblastoma (GB) is the most common malignant brain tumor and is characterized by high invasiveness, poor prognosis, and limited therapeutic options. Silencing gene expression, through the use of small interfering RNA (siRNA), has been proposed as an alternative to conventional cancer therapy. Here, we evaluated the potential of CD73 as a new therapeutic target, since it is overexpressed in solid tumors and has emerged as a promising target to control GB progression.Methods: A cationic nanoemulsion (NE) as an intravenous siRNA-CD73 delivery system was developed and its effect on C6 glioma cell viability was determined.Results: The nanostructured system was effective in complexing oligonucleotides for delivery to target cells. In addition, we observed that the NE-siRNA-CD73 complex was effective in reducing CD73 protein levels and AMPase activity, which were related to decreased C6 glioma cell viability.Conclusions: These findings indicate the potential of siRNA-CD73-loaded cationic NE as a therapeutic alternative for glioma treatment.

High levels of methionine and methionine sulfoxide: Impact on adenine nucleotide hydrolysis and redox status in platelets and serum of young rats.

We investigated acute and chronic effects administration of methionine (Met) and/or methionine sulfoxide (MetO) on ectonucleotidases and oxidative stress in platelets and serum of young rats. Wistar rats were divided into four groups: control, Met, MetO, and Met + MetO. In acute treatment, the animals received a single subcutaneous injection of amino acid(s) and were euthanized after 1 and 3 hours. In chronic protocol, Met and/or MetO were administered twice a day with an 8-hour interval from the 6th to the 28th day of life. Nucleoside triphosphate phosphohydrolase and 5'-nucleotidase activities were reduced in platelets and serum by Met, MetO, and Met + MetO after 3 hours and 21 days. Adenosine deaminase activity reduced in platelets at 3 hours after MetO and Met + MetO administration and increased after 21 days in animals treated with Met + MetO. Superoxide dismutase and catalase activities decreased in platelets in MetO and Met + MetO groups after 3 hours, while reactive oxygen species (ROS) levels increased in same groups. Catalase activity in platelets decreased in all experimental groups after chronic treatment. Met, MetO, and Met + MetO administration increased plasmatic ROS levels in acute and chronic protocols; glutathione S-transferase activity increased by MetO and Met + MetO administration at 3 hours, and ascorbic acid decreased in all experimental groups in acute and chronic protocols. Thiobarbituric acid reactive substances increased, superoxide dismutase and catalase activities reduced in the Met and/or MetO groups at 3 hours and in chronic treatment. Our data demonstrated that Met and/or MetO induced changes in adenine nucleotide hydrolysis and redox status of platelets and serum, which can be associated with platelet dysfunction in hypermethioninemia.