The incorporation of alpha-tocopherol and functional doses of phytosterol esters during cheesemaking does not affect DNA or mRNA dynamics of Streptococcus thermophilus and Lactococcus lactis throughout and after the end of ripening

Tocopherols and phytosterols are lipid-soluble molecules which have been widely used in the food industry. Nevertheless, the influence of these compounds on the performance of starter lactic acid bacteria (SLAB) in fermented foods has received little attention. Here, we assessed the behavior of Streptococcus thermophilus and Lactococcus lactis during the ripening of a functional Port Salut light cheese elaborated with these SLAB and with alpha-tocopherol and phytosterol esters as bioactive molecules. Functional and control cheeses were manufactured at an industrial plant and sampled at 7, 21, 40, 60 and 90 days after elaboration for real-time quantitative PCR (qPCR) or reverse transcription-qPCR (RT-qPCR) experiments. Target DNA and mRNA from both SLAB were detected after 90 days of elaboration in both functional and control cheeses, supporting their potential role in generating flavor metabolites. Furthermore, here we showed for the first time that the addition of alpha-tocopherol and functional doses of phytosterols did not affect DNA or mRNA dynamics of these SLAB during cheesemaking, throughout and after the end of ripening. Therefore, our results support the use of cheese manufactured with both S. thermophilus and L. lactis as an optimal delivery system for these beneficial bioactive compounds.Fil: Pega, Juan Franco. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Pérez, Carolina Daiana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Rizzo, Sergio Anibal. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; ArgentinaFil: Rossetti, Luciana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; ArgentinaFil: Diaz, G.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; ArgentinaFil: Ruzal, Sandra Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nanni, M.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; ArgentinaFil: Descalzo, Adriana Maria. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; Argentina. Centre de Coopération Internationale en Recherche Agronomique pour le Développerment; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Assessment of the Possible Reuse of Extractive Waste Coming from Abandoned Mine Sites: Case Study in Gorno, Italy

Supply of resources, a growing population, and environmental pollution are some of the main challenges facing the contemporary world. The rapid development of mining activities has produced huge amounts of waste. This waste, found in abandoned mine sites, provides the potential opportunity of extracting raw material. The current study, therefore, focuses on testing the validation of a shared methodology to recover extractive waste from abandoned mines, and applies this methodology to a case study in Gorno, northwest Italy. The methods focused on: (1) analyzing the impact of tailings and fine fraction of waste rock (<2 mm) on plants (Cress - Lepidium Sativum) to assess usability of both as soil additive, and (2) recovering raw materials from tailings and coarse fraction (>2 mm) of waste rock, by means of dressing methods like wet shaking table and froth flotation. The results indicated that the fine fraction of waste rock and tailings did not have detrimental effects on seed germination; however, there was marked decrease in plant growth. As for the recovery of raw materials, the coarse waste rock samples, crushed to <0.5 mm, produced a recovery of Cd, Ga, and Zn—as much as 66%, 56%, and 64%, respectively—using the wet shaking table. The same samples when crushed to 0.063–0.16 mm and used for froth flotation produced a recovery of Cd, Ga, and Zn of up to 61%, 72%, and 47%, respectively. The flotation experiment on tailings showed a recovery of Cd, Ga and Zn at pH 7 of 33%, 6% and 29% respectively. The present investigation highlights the methodologies used for extracting raw materials from extractive waste

Early polytherapy for benzodiazepine-refractory status epilepticus.

The transition from single seizures to status epilepticus (SE) is associated with malaptive trafficking of synaptic gamma-aminobutyric acid (GABAA) and glutamate receptors. The receptor trafficking hypothesis proposes that these changes are key events in the development of pharmacoresistance to antiepileptic drugs (AEDs) during SE, and that blocking their expression will help control drug-refractory SE (RSE). We tested this hypothesis in a model of SE induced by very high-dose lithium and pilocarpine (RSE), and in a model of SE induced by sc soman. Both models are refractory to benzodiazepines when treated 40 min after seizure onset. Our treatments aimed to correct the loss of inhibition because of SE-associated internalization of synaptic GABAA receptors (GABAAR), using an allosteric GABAAR modulator, sometimes supplemented by an AED acting at a nonbenzodiazepine site. At the same time, we reduced excitation because of increased synaptic localization of NMDA and AMPA (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate) receptors (NMDAR, AMPAR (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, N-methyl-D-aspartate receptors)) with an NMDAR channel blocker, since AMPAR changes are NMDAR-dependent. Treatment of RSE with combinations of the GABAAR allosteric modulators midazolam or diazepam and the NMDAR antagonists dizocilpine or ketamine terminated RSE unresponsive to high-dose monotherapy. It also reduced RSE-associated neuronal injury, spatial memory deficits, and the occurrence of spontaneous recurrent seizures (SRS), tested several weeks after SE. Treatment of soman-induced SE also reduced seizures, behavioral deficits, and epileptogenesis. Addition of an AED further improved seizure outcome in both models. Three-dimensional isobolograms demonstrated positive cooperativity between midazolam, ketamine, and valproate, without any interaction between the toxicity of these drugs, so that the therapeutic index was increased by combination therapy. The midazolam-ketamine-valproate combination based on the receptor trafficking hypothesis was far more effective in stopping RSE than the midazolam-fosphenytoin-valproate combination inspired from clinical guidelines for the treatment of SE. Furthermore, sequential administration of midazolam, ketamine, and valproate was far less effective than simultaneous treatment with the same drugs at the same dose. These data suggest that treatment of RSE should be based at least in part on its pathophysiology. The search for a better treatment should focus on the cause of pharmacoresistance, which is loss of synaptic GABAAR and gain of synaptic glutamate receptors. Both need to be treated. Monotherapy addresses only half the problem. Improved pharmacokinetics will not help pharmacoresistance because of loss of receptors. Waiting for one drug to fail before giving the second drugs gives pharmacoresistance time to develop. Future clinical trials should consider treating both the failure of inhibition and the runaway excitation which characterize RSE, and should include an early polytherapy arm. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures"

Rational polytherapy in the treatment of cholinergic seizures.

The initiation and maintenance phases of cholinergic status epilepticus (SE) are associated with maladaptive trafficking of synaptic GABAA and glutamate receptors. The resulting pharmacoresistance reflects a decrease in synaptic GABAA receptors and increase in NMDA and AMPA receptors, which tilt the balance between inhibition and excitation in favor of the latter. If these changes are important to the pathophysiology of SE, both should be treated, and blocking their consequences should have therapeutic potential. We used a model of benzodiazepine-refractory SE (RSE) (Tetz et al., 2006) and a model of soman-induced SE to test this hypothesis. Treatment of RSE with combinations of the GABAAR agonists midazolam or diazepam and the NMDAR antagonists MK-801 or ketamine terminated RSE unresponsive to high-dose monotherapy with benzodiazepines, ketamine or other antiepileptic drugs (AEDs). It also reduced RSE-associated neuronal injury, spatial memory deficits and the occurrence of spontaneous recurrent seizures (SRS), tested several weeks after SE. Treatment of sc soman-induced SE similarly showed much greater reduction of EEG power by a combination of midazolam with ketamine, compared to midazolam monotherapy. When treating late (40 min after seizure onset), there may not be enough synaptic GABAAR left to be able to restore inhibition with maximal GABAAR stimulation, and further benefit is derived from the addition of an AED which increases inhibition or reduces excitation by a non-GABAergic mechanism. The midazolam-ketamine-valproate combination is effective in terminating RSE. 3-D isobolograms demonstrate positive cooperativity between midazolam, ketamine and valproate, without any interaction between the toxicity of these drugs, so that the therapeutic index is increased by combination therapy between GABAAR agonist, NMDAR antagonist and selective AEDs. We compared this drug combination based on the receptor trafficking hypothesis to treatments based on clinical practice. The midazolam-ketamine-valproate combination is far more effective in stopping RSE than the midazolam-fosphenytoin-valproate combination inspired from clinical guidelines. Furthermore, sequential administration of midazolam, ketamine and valproate is far less effective than simultaneous treatment with the same drugs at the same dose. These data suggest that we should re-evaluate our traditional treatment of RSE, and that treatment should be based on pathophysiology. The search for a better drug has to deal with the fact that most monotherapy leaves half the problem untreated. The search for a better benzodiazepine should acknowledge the main cause of pharmacoresistance, which is loss of synaptic GABAAR. Future clinical trials should consider treating both the failure of inhibition and the runaway excitation which characterize RSE, and should include an early polytherapy arm

Landfill mining from extractive waste facilities: The importance of a correct site characterisation and evaluation of the potentialities. A case study from Italy

Raw materials (RM) and critical raw materials (CRM; EC, 2017) supply is essential to both the maintenance and development of the EU economy as its industries rely on a steady RM supply. Thus, securing a sustainable RM and CRM supply and their circular use in the economy is of importance at EU level and beyond (Blengini et al., 2017, Coulomb et al., 2015, Vidal-Legaz et al., 2016). Furthermore, the developments of clean technologies coupled with economic growth exacerbate the short and long-term demand and needs (Blagoeva et al., 2016, Pavel and Tzimas, 2016). For example, Habib and Wenzel (2014) reported that the necessary supply Nd and Dy will grow from 10.0 Gg to 54.5 Gg and 0.5 Gg to 4.95 Gg respectively from 2010 to 2050

Uvulopalatopharyngoplasty and barbed reposition pharyngoplasty with and without hyoid suspension for obstructive sleep apnea hypopnea syndrome: A comparison of long-term functional results

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common condition; when conservative approaches are not effective, surgical techniques aimed at reducing the airway obstruction effect are used. This retrospective study aimed at comparing the functional outcomes in patients with OSAHS undergoing uvulopalatopharyngoplasty (UPPP) according to Fairbanks and barbed reposition pharyngoplasty (BRP) according to Mantovani, with or without hyoid suspension (HS). One-hundred twenty-two consecutive OSAHS patients who underwent surgical treatment were included in the study. Patients were divided into 4 groups; all patients underwent preoperative and postoperative polysomnography (PSG) with apnea/hypopnea index (AHI) and oxygen desaturation index (ODI) evaluation, and Epworth Sleepiness Scale (ESS) evaluation. The results were analyzed according to the different surgical procedures, in relation to the preoperative PSG and anthropometric data. A significant reduction was observed at 18-month follow-up for patients in BRP group for BMI (p = 0.004), ESS (p < 0.0001), ODI (p < 0.0001), and AHI (p < 0.0001). Risk factors for poor postoperative AHI reduction were evaluated; preoperative AHI was the strongest independent protective factor, while preoperative ODI was the strongest risk factor. The association of HS with UPPP or BRP showed significant results in terms of higher postoperative AHI reduction only when associated to UPPP (p < 0.0001). This study showed that the BRP technique was more effective compared to UPPP for patients with OSAHS. The association of HS showed greater benefits in UPPP compared to BRP.  Randomized prospective trials with longer follow-up are necessary to confirm our results and formulate a more accurate indication of the optimal therapeutic strategy