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Abstract Background When patients do not speak the same language as their doctors, they face poorer medical outcomes, decreased doctor-patient trust, and a diminished desire to seek medical care. It has been well established that interpretation is an essential part of an accessible healthcare system, but effective use of such language services relies on both the interpreters themselves and the healthcare teams working with them. This study presents an interdisciplinary examination of the motivations of undergraduate student medical interpreters, a group which serves as a bridge between these roles. While not full-time interpreters, they receive official training and spend time serving patients in local clinics. Further, for those who aspire to careers in medicine, interpreting provides invaluable exposure to the medical field and early professional know-how. Methods Semi-structured individual interviews with undergraduate student interpreters were conducted to describe this multifaceted educational experience. A thematic analysis framework was employed to understand how and why they volunteer their time to interpret. Results Motivations of student interpreters were found to fall under three general categories: (1) personal identity, or connection to family, language, and their career aspirations; (2) community engagement, or the opportunity to make a direct impact on patients at an early stage; and (3) pre-professional experience, both in general and specifically in healthcare. Each of these contributes to the view of a student medical interpreter as a unique contributor to language equity in medicine, as they provide language services in the short-term as well as set themselves up to be linguistically and culturally competent providers in the long-term. Conclusions A greater understanding of student motivations adds to knowledge about language mediation and validates the utility of students in this role, encouraging the development of more student interpreter programs. Particularly in communities with high proportions of non-English speakers, these students can contribute to making medical care as inclusive and accessible as possible.

Genomic screened homeobox 1 (Gsx1 or Gsh1) is a neurogenic transcription factor required for the generation of excitatory and inhibitory interneurons during spinal cord development. In the adult, lentivirus (LV) mediated Gsx1 expression promotes neural regeneration and functional locomotor recovery in a mouse model of lateral hemisection spinal cord injury (SCI). The LV delivery method is clinically unsafe due to insertional mutations to the host DNA. In addition, the most common clinical case of SCI is contusion/compression. In this study, we identify that adeno-associated virus serotype 6 (AAV6) preferentially infects neural stem/progenitor cells (NSPCs) in the injured spinal cord. Using a rat model of contusion SCI, we demonstrate that AAV6 mediated Gsx1 expression promotes neurogenesis, increases the number of neuroblasts/immature neurons, restores excitatory/inhibitory neuron balance and serotonergic neuronal activity through the lesion core, and promotes locomotor functional recovery. Our findings support that AAV6 preferentially targets NSPCs for gene delivery and confirmed Gsx1 efficacy in clinically relevant rat model of contusion SCI.

Antimalarial resistance to the first-line partner drug piperaquine (PPQ) threatens the effectiveness of artemisinin-based combination therapy. In vitro piperaquine resistance is characterized by incomplete growth inhibition, i.e. increased parasite growth at higher drug concentrations. However, the 50% inhibitory concentrations (IC50) remain relatively stable across parasite lines. Measuring parasite viability of a drug-resistant Cambodian Plasmodium falciparum isolate in a parasite reduction ratio (PRR) assay helped to better understand the resistance phenotype towards PPQ. In this parasite isolate, incomplete growth inhibition translated to only a 2.5-fold increase in IC50 but a dramatic decrease of parasite killing in the PRR assay. Hence, this pilot study reveals the potential of in vitro parasite viability assays as an important, additional tool when it comes to guiding decision-making in preclinical drug development and post approval. To the best of our knowledge, this is the first time that a compound was tested against a drug-resistant parasite in the in vitro PRR assay.

Biofumigation was proposed as an alternative to synthetic pesticides for the disinfection of agricultural soils, in view of the biocidal effect of isothiocyanates (ITCs) released by some vegetal species, like Brassicaceae. However, biofumigation also presents limitations; thus, a novel and viable alternative could be the direct introduction of ITCs into agricultural soils as components loaded into biodegradable hydrogels. Thus, in this work, ITCs-based microemulsions were developed, which can be loaded into porous polymer-based hydrogel beads based on sodium alginate (ALG) or sodium carboxymethyl cellulose (CMC). Three ITCs (ethyl, phenyl, and allyl isothiocyanate) and three different surfactants (sodium dodecylsulfate, Brij 35, and Tween 80) were considered. The optimal system was characterized with attenuated ATR-FTIR spectroscopy and differential scanning calorimetry to study how the microemulsion/gels interaction affects the gel properties, such as the equilibrium water content or free water index. Finally, loading and release profiles were studied by means of UV–Vis spectrophotometry. It was found that CMC hydrogel beads showed a slightly more efficient profile of micelles’ release in water with respect to ALG beads. For this reason, and due to the enhanced contribution of Fe(III) to their biocidal properties, CMC-based hydrogels are the most promising in view of the application on real agricultural soils.

Olive leaves are a rich source of polyphenols with healthful properties and represent one of the most abundant waste products of olive oil production. The aims of this study were to explore the phenolic composition of olive leaves from the three main Tuscan cultivars (Leccino, Moraiolo and Frantoio) collected in Siena and Grosseto provinces and to investigate the possible use of these compounds as varietal and geographic origin markers. Discriminant factorial analysis (DFA) was used for distinguishing between different cultivars and locations. Apigenin and caffeoyl-secologanoside showed significant differences between cultivars. DFA showed that ligstroside, apigenin and luteolin have the most influence in determining the differences between sites, whereas total polyphenols, olacein and hydroxytyrosol acetate allowed for separation between leaves from the same province. The results of the present study indicate that concentrations of phenolic compounds, measured through high-resolution mass spectrometry, can be used as a marker for both the cultivar and of geographical origin of olive leaves, and possibly of olive-related products, as well as across small geographic scales (less than 50 km distance between sites).

Oxygen minimum zones (OMZs), due to their large volumes of perennially deoxygenated waters, are critical regions for understanding how the interplay between anaerobic and aerobic nitrogen (N) cycling microbial pathways affects the marine N budget. Here, we present a suite of measurements of the most significant OMZ N cycling rates, which all involve nitrite (NO2-) as a product, reactant, or intermediate, in the eastern tropical North Pacific (ETNP) OMZ. These measurements and comparisons to data from previously published OMZ cruises present additional evidence that NO3- reduction is the predominant OMZ N flux, followed by NO2- oxidation back to NO3-. The combined rates of both of these N recycling processes were observed to be much greater (up to nearly 200 times) than the combined rates of the N loss processes of anammox and denitrification, especially in waters near the anoxic–oxic interface. We also show that NO2- oxidation can occur when O2 is maintained near 1 nM by a continuous-purge system, NO2- oxidation and O2 measurements that further strengthen the case for truly anaerobic NO2- oxidation. We also evaluate the possibility that NO2- dismutation provides the oxidative power for anaerobic NO2- oxidation. The partitioning of N loss between anammox and denitrification differed widely from stoichiometric predictions of at most 29 % anammox; in fact, N loss rates at many depths were entirely due to anammox. Our new NO3- reduction, NO2- oxidation, dismutation, and N loss data shed light on many open questions in OMZ N cycling research, especially the possibility of truly anaerobic NO2- oxidation.

Coral reef health depends on an intricate relationship among the coral animal, photosynthetic algae, and a complex microbial community. The holobiont can impact the nutrient balance of their hosts amid an otherwise oligotrophic environment, including by cycling physiologically important nitrogen compounds. Here we use 15N-tracer experiments to produce the first simultaneous measurements of ammonium oxidation, nitrate reduction, and nitrous oxide (N2O) production among five iconic species of reef-building corals (Acropora palmata, Diploria labyrinthiformis, Orbicella faveolata, Porites astreoides, and Porites porites) in the highly protected Jardines de la Reina reefs of Cuba. Nitrate reduction is present in most species, but ammonium oxidation is low potentially due to photoinhibition and assimilatory competition. Coral-associated rates of N2O production indicate a widespread potential for denitrification, especially among D. labyrinthiformis, at rates of ~1 nmol cm-2 d-1. In contrast, A. palmata displays minimal active nitrogen metabolism. Enhanced rates of nitrate reduction and N2O production are observed coincident with dark net respiration periods. Genomes of bacterial cultures isolated from multiple coral species confirm that microorganisms with the ability to respire nitrate anaerobically to either dinitrogen gas or ammonium exist within the holobiont. This confirmation of anaerobic nitrogen metabolisms by coral-associated microorganisms sheds new light on coral and reef productivity.

Flaxseed lignans frequently feature in the literature. However, much remains to be discovered about the mechanisms underlying their functional and therapeutic properties. Furthermore, it is necessary to identify systems for lignan production and detoxification that are sustainable, cost-effective, easy to use, and scale up. These systems can address the needs of the nutraceutical, cosmetic, and pharmaceutical sectors and lead to competitive commercial products. This review analyzes the biological effects of lignans as anticancer, antioxidants, and modulators of estrogen activity. It also focuses on the most recent articles on lignan extraction methods that are sustainable and suitable as products for human consumption. Furthermore, the most up-to-date and relevant patents for lignan recovery are examined. The search and selection methodology for articles and patents was conducted using the most popular bibliographic and patent databases (e.g., Scopus, Pubmed, Espacenet). To the best of our knowledge, this is the first overview that details the patented technologies developed in the flaxseed lignans area in the last 10 years.

Abstract Severe COVID-19 infection results in significant immune dysregulation resulting from excessive recruitment and activation of neutrophils. The aim of this study was to confirm feasibility, initial safety and detect signal of efficacy of a non-propriety device delivered using an intermittent extra-corporeal system (LMOD) allowing leucocytes modulation in the setting of Severe COVID-19 infection. Twelve patients were recruited. Inclusion criteria were > 18 years age, confirmed COVID-19, acute respiratory distress syndrome requiring mechanical support and hypotension requiring vasopressor support. Primary end point was vasopressor requirements (expressed as epinephrine dose equivalents) and principle secondary endpoints related to safety, ability to deliver the therapy and markers of inflammation assessed over five days after treatment initiation. LMOD treatment appeared safe, defined by hemodynamic stability and no evidence of white cell number depletion from blood. We demonstrated a significant decrease in vasopressor doses (−37%, p = 0.02) in patients receiving LMOD therapy (despite these patients having to tolerate an additional extracorporeal intermittent therapy). Vasopressor requirements unchanged/increasing in control group (+ 10%, p = 0.48). Although much about the use of this therapy in the setting of severe COVID-19 infection remains to be defined (e.g. optimal dose and duration), this preliminary study supports the further evaluation of this novel extracorporeal approach.

Abstract A novel and miniaturized Marchand balun is proposed using two quarter‐wave edge coupled transmission line and two complementary split‐ring resonators (CSRR) unit cell in the ground plane. These coupled lines are joined with the help of an uncoupled microstrip line. The short circuit and open circuit terminations are assigned at the specified ports. Two rectangular shaped CSRR cells improve the circuit performance. A step impedance technique has been applied at the balanced ports to enhance the bandwidth. This proposed design produces a fractional bandwidth of 18.75% at the centre frequency with a maximum magnitude and phase imbalance of 0.56 dB and 0.85°. This design occupies a total circuit area of 0.515 λg (30.72 mm) × 0.279λg (16.63 mm). The circuit has been designed at 2.4 GHz centre frequency using low‐cost FR4 substrate material. The simulated and measured results are in acceptable accord in terms of magnitude and phase response.

Behavioral disorders affect millions of people worldwide. Hypertension contributes to both the development and progression of brain damage and cognitive dysfunction and could represent the most powerful modifiable risk factor for cerebral vessel dysfunction and consequent behavioral impairment. Tomato contains antioxidants and bioactive molecules that might play an important role in the prevention of cardiovascular and brain diseases. The effects of the combined gel and serum from Lycopersicum esculentum L. var. “Camone” tomatoes and those of purified tomato glycoalkaloids (tomatine) and an antihypertensive drug (captopril) were investigated in male spontaneously hypertensive rats (SHRs) and compared with normotensive Wistar Kyoto (WKY) rats. Body weight, systolic blood pressure, behavioral parameters, as well as brain susceptibility to oxidative stress and brain cytokine contents, were assessed. Treating hypertensive rats with tomato gel/serum or captopril for four weeks caused a significant reduction in blood pressure, decreased locomotor activity and increased grooming behavior; the last two parameters were also significantly affected by tomatine treatment. Brain slices obtained from hypertensive rats treated with tomato gel/serum were more resistant to oxidative stress and contained lower levels of inflammatory cytokines than vehicle-treated ones. In contrast, tomatine treatment had no effect. In conclusion, the tomato-derived gel/serum can be considered a dietary supplement able to drive in vivo blood pressure towards healthier values and also control some central effects such as behavior and brain oxidative stress.

In a preferential looking paradigm, we studied how children's looking behavior and pupillary response were modulated by the degree of phonological mismatch between the correct label of a target referent and its manipulated form. We manipulated degree of mismatch by introducing one or more featural changes to the target label. Both looking behavior and pupillary response were sensitive to degree of mismatch, corroborating previous studies that found differential responses in one or the other measure. Using time-course analyses, we present for the first time results demonstrating full separability among conditions (detecting difference not only between one vs. more, but also between two and three featural changes). Furthermore, the correct labels and small featural changes were associated with stable target preference, while large featural changes were associated with oscillating looking behavior, suggesting significant shifts in looking preference over time. These findings further support and extend the notion that early words are represented in great detail, containing subphonemic information.

Extracellular vesicles (EVs) are cell-derived membrane structures that are formed by budding from the plasma membrane or originate from the endosomal system. These microparticles (100 nm–100 µm) or nanoparticles (>100 nm) can transport complex cargos to other cells and, thus, provide communication and intercellular regulation. Various cells, such as hepatocytes, liver sinusoidal endothelial cells (LSECs) or hepatic stellate cells (HSCs), secrete and take up EVs in the healthy liver, and the amount, size and content of these vesicles are markedly altered under pathophysiological conditions. A comprehensive knowledge of the modified EV-related processes is very important, as they are of great value as biomarkers or therapeutic targets. In this review, we summarize the latest knowledge on hepatic EVs and the role they play in the homeostatic processes in the healthy liver. In addition, we discuss the characteristic changes of EVs and their potential exacerbating or ameliorating effects in certain liver diseases, such as non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), drug induced liver injury (DILI), autoimmune hepatitis (AIH), hepatocarcinoma (HCC) and viral hepatitis.

A giant bezoar fulfilling the stomach, the duodenum and the jejunum for about 60–70 cm was found in a young girl with autism spectrum disorder, admitted for acute abdominal pain. At initial radiological evaluation an intestinal ilea-ileal intussusception was diagnosed but a computed tomography showed hypointense material with a chambered aspect likely due to accidental ingestion of exogenous material. The presence of a giant bezoar was endoscopically confirmed and the patient underwent surgery for its manual removal.

ImportanceAccurate monitoring of core body temperature is integral to targeted temperature management (TTM) following cardiac arrest. However, there are no reliable non-invasive methods for monitoring temperature during TTM.ObjectivesWe compared the accuracy and precision of a novel non-invasive Zero-Heat-Flux Thermometer (SpotOn™) to a standard invasive esophageal probe in a cohort of patients undergoing TTM post-cardiac arrest.Design, Setting, and ParticipantsWe prospectively enrolled 20 patients undergoing post-cardiac arrest care in the intensive care units at the London Health Sciences Centre in London, Canada. A SpotOn™ probe was applied on each patient's forehead, while an esophageal temperature probe was inserted, and both temperature readings were recorded at 1-min intervals for the duration of TTM.Main outcomes and MeasuresWe compared the SpotOn™ and esophageal monitors using the Bland–Altman analysis and the Pearson correlation, with accuracy set as a primary outcome. Secondary outcomes included precision and correlation. Bias exceeding 0.1°C and limits of agreement exceeding 0.5°C were considered clinically important.ResultsSixteen (80%) of patients had complete data used in the final analysis. The median (interquartile range) duration of recording was 38 (12–56) h. Compared to the esophageal probe, SpotOn™ had a bias of 0.06 ± 0.45°C and 95% limits of agreement of −0.83 to 0.95°C. The Pearson correlation coefficient was 0.97 (95% confidence interval 0.9663–0.9678), with a two-tailed p < 0.0001.Conclusion and RelevanceThe SpotOn™ is an accurate method that may enable non-invasive monitoring of core body temperature during TTM, although its precision is slightly worse than the predefined 0.5°C when compared to invasive esophageal probe.

The Authors consider that as a mid-term storage technology (from some hours to some days), small/medium size CAES systems (1–10 MW) might be efficiently and profitably used for off-grid and self-consumption applications as well as for the provision of ancillary services on the lower grid levels. A crucial aspect related to the feasibility of the system concerns with the availability of efficient and affordable air expanders. For typical applications, suitable values for pressure at the air expander inlet range from 40 to 60 bar. Since such values are comparable with those featuring industrial steam turbines, an interesting option to reduce development efforts and costs is to take as a reference the common steam turbine engineering practice. The goal of the present paper is to explore the possibility of using existing modules developed by industrial steam turbines manufacturers to assemble the air expander. On the basis of available information, a possible arrangement for an air turbine has been set up and modeled. Results show a loss of performance in terms of efficiency in respect to steam operations. Nevertheless, the performance level in a really wide range of operation can be considered more than satisfactory. Therefore, the use of industrial steam turbines technology might be considered of interest for the intended applications. Keywords: Compressed Air Energy Storage (CAES), Industrial steam turbines, Turbomachinery modeling, Air expander

Abstract Background Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. Chronic exposure to intermittent hemodialysis may be a source of added stress to the cardiovascular system; intradialytic hypotension is a common complication of hemodialysis, and repeated events may lead to hemodynamic stress and ischemic injuries. Administration of non-pneumatic compression stockings to the lower limbs has demonstrated hemodynamic stabilizing effects in other settings and may provide similar benefits in the kidney disease population. Therefore, we conducted this pilot study assessing the feasibility and tolerability of the application of non-pneumatic compression stockings to patients with kidney disease. We also assessed the changes in hemodynamic measurements following the application of the compression stockings to explore the biological feasibility of this being an effective intervention for intradialytic hypotension. Methods Fifteen individuals were enrolled in the study (5 healthy, 5 chronic kidney disease patients, and 5 dialysis patients). Outcomes including hemodynamic parameters such as cardiac output, peripheral vascular resistance, and blood pressure were measured using continuous pulse wave analysis. Changes in global longitudinal strain were measured via echocardiography. These outcome measurements were made before and after the application of compression stockings. Results All study participants tolerated the compression garments well and without complication. Hemodynamic response to lower body compression caused varying effects on cardiac output, mean arterial pressure and global longitudinal strain. Some individuals saw large improvements in hemodynamic parameters while in others the opposite effect was observed. No consistent response was elicited. Conclusions Application of compression stockings to patients with renal dysfunction is well-tolerated. However, significant variations in hemodynamic outcomes exist, and may be a barrier for larger scale trials without prior identification of specific patient characteristics indicating likely benefit from the application of external compression. Trial registration ClinicalTrials.gov, Identifier: NCT02915627, Registration Date: Sept 27, 2016.

Biocompatible nanocarriers can be obtained by lipid extraction from natural sources such as algal biomasses, which accumulate different lipid classes depending on the employed culture media. Lipid aggregates can be distinguished according to supramolecular architecture into lamellar and nonlamellar structures. This distinction is mainly influenced by the lipid class and molecular packing parameter, which determine the possible values of interfacial curvature and thus the supramolecular symmetries that can be obtained. The nanosystems prepared from bio-sources are able to self-assemble into different compartmentalized structures due to their complex composition. They also present the advantage of increased carrier-target biocompatibility and are suitable to encapsulate and vehiculate poorly water-soluble compounds, e.g., natural antioxidants. Their functional properties stem from the interplay of several parameters. Following previous work, here the functionality of two series of structurally distinct lipid nanocarriers, namely liposomes and cubosomes deriving from algal biomasses with different lipid composition, is characterized. In the view of their possible use as pharmaceutical or nutraceutical formulations, both types of nanovectors were loaded with three well-known antioxidants, i.e., curcumin, α-tocopherol and piperine, and their carrier efficacy was compared considering their different structures. Firstly, carrier stability in biorelevant conditions was assessed by simulating a gastrointestinal tract model. Then, by using an integrated chemical and pharmacological approach, the functionality in terms of encapsulation efficiency, cargo bioaccessibility and kinetics of antioxidant capacity by UV-Visible spectroscopy was evaluated. Subsequently, in vitro cytotoxicity and viability tests after administration to model cell lines were performed. As a consequence of this investigation, it is possible to conclude that nanovectors from algal lipids, i.e., cubosomes and liposomes, can be efficient delivery agents for lipophilic antioxidants, being able to preserve and enhance their activity toward different targets while promoting sustained release.

Background: Moderate therapeutic hypothermia (TH) is a well-recognized cardio-protective strategy. The instillation of fluid into the peritoneum provides an opportunity to deliver moderate hypothermia as primary prevention against cardiovascular events. We aimed to to investigate both cardiac perfusion consequences (overall blood flow and detailed assessment of perfusion heterogeneity) and subsequently simulate the associated arrhythmic risk for patients undergoing peritoneal dialysis (PD) induced TH.Methods: Patients underwent high resolution myocardial perfusion scanning using high resolution 256 slice CT scanning, at rest and with adenosine stress. The first visit using the patient's usual PD regimen, on the second visit the same regime was utilized but with cooled peritoneal dialysate at 32°C. Myocardial blood flow (MBF) was quantified from generated perfusion maps, reconstructed in 3D. MBF heterogeneity was assessed by fractal dimension (FD) measurement on the 3D left ventricular reconstruction. Arrhythmogenicity was quantified from a sophisticated computational simulation using a multi-scale human 3D ventricle wedge electrophysiological computational model.Results: We studied 7 PD patients, mean age of 60 ± 7 and mean vintage dialysis of 23.6 ± 17.6 months. There were no significant different in overall segmental MBF between normothermic condition (NT) and TH. MBF heterogeneity was significantly decreased (−14%, p = 0.03) at rest and after stress (−14%, p = 0.03) when cooling was applied. Computational simulation showed that TH allowed a normalization of action potential, QT duration and T wave.Conclusion: TH-PD results in moderate hypothermia leading to a reduction in perfusion heterogeneity and simulated risk of non-terminating malignant ventricular arrhythmias.

Coffea arabica L. leaves represent a viable alternative to the canonical matrices used for preparation of beverages, such as tea leaves and grounded coffee beans. Coffee leaves infusions are rich in antioxidant phenolic compounds and have a lower concentration of caffeine. Due to increasing interest in this field, a complete study of the bioactive compounds as chlorogenic acids, xanthones and alkaloids is noteworthy. C. arabica leaves were subjected to ultrasound-assisted extraction, and the extracts were studied via nuclear magnetic resonance spectroscopy (NMR) and chromatographic techniques coupled with mass spectrometry (HPLC-MSn) to identify and quantify the secondary metabolites profile through an untargeted data dependent approach. A quantitative analysis was performed for the major components—chlorogenic acids, mangiferin, caffeine and trigonelline—via HPLC-MS in Single Ion Monitoring (SIM) mode. In total, 39 compounds were identified. The presence of these bioactive compounds proved the strong potential of C. arabica leaves as functional food and as an alternative to classic infused beverages.

Consumption of cereals (and particularly ancient cereals) is considered the base of a healthy diet, and all current dietary guidelines have cereals at the bottom of the nutrition pyramid. Together with cereals, legumes are an excellent source of nutrients and nutraceuticals. The effects of agroindustrial pretreatments (flaking and precooking processes) on the antioxidant potential of flours from ancient cereals and legumes were studied. The extraction of free hydrophilic phenolic compounds was carried out in a hydroalcoholic solvent mixture via an ultrasound-assisted process. Furthermore, the solid residue was successively hydrolyzed by an alkaline solution to extract the bound phenolic fraction. Both free and bound extracted fractions were then quantitatively characterized for total polyphenolic and flavonoid contents, and the antioxidant potential was determined by carrying out the ABTS and DPPH radical scavenging assays, expressing the results (in both cases) as the Trolox equivalent antioxidant capacity (TEAC/ABTS and TEAC/DPPH, respectively). The samples were also extracted in organic apolar solvents (acetone or water-saturated iso-butanol) to quantitatively characterize lipophilic antioxidant compounds and pigments. A discussion on the comparison of these analytical parameters of flours obtained from raw, flaked, and precooked cereals and legumes is reported revealing that (i) phenolic compounds are mainly present in the post-hydrolysis extract (bound fraction), (ii) the precooking process significantly reduced the concentration of antioxidants, (iii) the flaking process slightly increased the phenolic content, (iv) legumes were less influenced by pretreatments, suggesting the possibility of using legumes to enrich cereal foods.

Controlled/living radical polymerization (CLRP) techniques are widely utilized to synthesize advanced and controlled synthetic polymers for chemical and biological applications. While automation has long stood as a high‐throughput (HTP) research tool to increase productivity as well as synthetic/analytical reliability and precision, oxygen intolerance of CLRP has limited the widespread adoption of these systems. Recently, however, oxygen‐tolerant CLRP techniques, such as oxygen‐tolerant photoinduced electron/energy transfer–reversible addition–fragmentation chain transfer (PET–RAFT), enzyme degassing of RAFT (Enz‐RAFT), and atom‐transfer radical polymerization (ATRP), have emerged. Herein, the use of a Hamilton MLSTARlet liquid handling robot for automating CLRP reactions is demonstrated. Synthesis processes are developed using Python and used to automate reagent handling, dispensing sequences, and synthesis steps required to create homopolymers, random heteropolymers, and block copolymers in 96‐well plates, as well as postpolymerization modifications. Using this approach, the synergy between highly customizable liquid handling robotics and oxygen‐tolerant CLRP to automate advanced polymer synthesis for HTP and combinatorial polymer research is demonstrated.

Abstract Background 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) is a widely used entactogenic drug known to impair cognitive functions on the long-run. Both hippocampal and frontal cortical regions have well established roles in behavior, memory formation and other cognitive tasks and damage of these regions is associated with altered behavior and cognitive functions frequently described in otherwise healthy MDMA users. Meanwhile, in post-traumatic stress disorder (PTSD) patients seem to benefit from therapeutic application of the drug, where damage in hippocampal cue extinction may play a role. The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the consequences of a single dose of MDMA (15 mg/kg) 3 weeks earlier. Results The number of differentially expressed genes in the hippocampus, frontal cortex and the dorsal raphe were 481, 155, and 15, respectively. Gene set enrichment analysis of the microarray data revealed reduced expression of ‘memory’ and ‘cognition’, ‘dendrite development’ and ‘regulation of synaptic plasticity’ gene sets in the hippocampus, parallel to the downregulation of CaMK II subunits, glutamate-, CB1 cannabinoid- and EphA4, EphA5, EphA6 receptors. Downregulated gene sets in the frontal cortex were related to protein synthesis, chromatin organization, transmembrane transport processes, while ‘dendrite development’, ‘regulation of synaptic plasticity’ and ‘positive regulation of synapse assembly’ gene sets were upregulated besides elevated levels of a CaMK II subunit and NMDA2B glutamate receptor. Changes in the dorsal raphe region were mild and in most cases not significant. Conclusion The present data raise the possibility of new synapse formation / synaptic reorganization in the frontal cortex 3 weeks after a single neurotoxic dose of MDMA. In contrast, a prolonged depression of new neurite formation in the hippocampus is proposed by downregulations of members in long-term potentiation pathway and synaptic plasticity emphasizing the particular vulnerability of this brain region and proposing a mechanism responsible for cognitive problems in healthy individuals. At the same time, these results underpin benefits of MDMA in PTSD, where the drug may help memory extinction.

Hyaluronic acid (HA) and chitosan (CH) are biopolymers that are widely used in many biomedical applications and for cosmetic purposes. Their chemical properties are fundamental to them working as drug delivery systems and improving their synergistic effects. In this work, two different protocols were used to obtain zwitterionic liposomes coated with either hyaluronic acid or chitosan. Specifically, the methodologies used to perform vesicle preparation were chosen by taking into account the specific chemical properties of these two polysaccharides. In the case of chitosan, liposomes were first synthesized and then coated, whereas the coating of hyaluronic acid was achieved through lipidic film hydration in an HA aqueous solution. The size and the zeta-potential of the polysaccharide-coated liposomes were determined by dynamic light scattering (DLS). This approach allowed coated liposomes to be obtained with hydrodynamic diameters of 264.4 ± 12.5 and 450.3 ± 16.7 nm for HA- and CH-coated liposomes, respectively. The chemical characterization of the coated liposomal systems was obtained by surface infrared (ATR-FTIR) and nuclear magnetic resonance (NMR) spectroscopies. In particular, the presence of polysaccharides was confirmed by the bands assigned to amides and saccharides being in the 1500–1700 cm−1 and 800–1100 cm−1 regions, respectively. This approach allowed confirmation of the efficiency of the coating processes, evidencing the presence of HA or CH at the liposomal surface. These data were also supported by time-of-flight secondary ion mass spectrometry (ToF-SIMS), which provided specific assessments of surface (3–5 nm deep) composition and structure of the polysaccharide-coated liposomes. In this work, the synthesis and the physical chemistry characterization of coated liposomes with HA or CH represent an important step in improving the pharmacological properties of drug delivery systems.

Prunus persica L. is one of the most important fruit crops in European production, after grapes, apples, oranges and watermelons. Most varieties are rich in secondary metabolites, showing antioxidant properties for human health. The purpose of this study was to develop a chemical analysis methodology, which involves the use of different analytical-instrumental techniques to deepen the knowledge related to the profile of metabolites present in selected cultivars of peaches and nectarines cultivated in the Mediterranean area (Southern Italy). The comparative study was conducted by choosing yellow-fleshed peaches (RomeStar, ZeeLady) and yellow-fleshed nectarines (Nectaross, Venus) from two geographical areas (Piana di Sibari and Piana di Metaponto), and by determining the chemical parameters for the flesh and skin that allow for identification of any distinctive varietal and/or geographical characteristics. A combined analytical and chemometric approach was used, trough rheological, thermogravimetric (TGA), chromatographic (HPLC-ESI-MS), spectroscopic (UV-Vis, ATR-FTIR, NMR) and spectrometric (ToF-SIMS) analysis. This approach allowed us to identify the characterizing parameters for the analysis of a plant matrix so that the developed methodology could define an easily exportable and extendable model for the characterization of other types of vegetable matrices.

Analytical determinations for selected parameters in grapes/wines help planning technology treatments in the vineyards and cellars, improving the quality of final products and preserving consumers’ health. The study first reports a comparative analysis for selected parameters on juice, must, and wines at alcoholic and malolactic fermentation stages, from 2013 harvest and refined bottled wines from 2010–2012 and 2015 vintages. This was considered preliminary to the main goal of the work that consisted of testing if the contents of certain antioxidant principles were influenced or not by additions of copper(II) and/or selected fermentation yeasts. Particular attention was devoted to antioxidant molecule contents: total polyphenols, anthocyanins, trans-resveratrol, and quercetin. Selected samples were then analyzed in absence and in presence excess Cu(II)-sulfate (5 mgCu/L) and/or yeast derivatives to evaluate possible effects on antioxidant concentrations. The total polyphenols contents in untreated wine samples were as high as 3334 ± 60 mg (gallic acid)/L and averaged 2883 ± 299 mg/L (wines 2010–2013 and 2015). In particular, high contents of quercetin and quercetin glucoside were found in Sangiovese/Canaiolo/Colorino (harvest 2015) wine, being 21 ± 2 and 3.0 ± 0.2 mg/L, respectively. Even resveratrol had high concentrations in 100% Sangiovese wine (1.3 ± 0.1 mg/L, harvest 2015; 2.6 ± 0.3 mg/L, harvest 2010). Interestingly, no significant effect was revealed by Cu(II) and/or yeast derivatives on antioxidant contents for wine matrixes. In fact, determinations (validated through the standard addition methods) of trans-resveratrol for untreated Sangiovese wines (1.18 ± 0.09 mg/L) and for wines treated with excess Cu(II) and excess Cu(II) plus excess yeasts mixtures (1.24 ± 0.09 mg/L and 1.22 ± 0.05 mg/L) did not differ significantly.

The active ingredient of ecstasy, ±3,4-methylenedioxymethamphetamine (MDMA), in addition to its initial reinforcing effects, induces selective and non-selective brain damage. Evidences suggest that the hippocampus (HC), a central region for cognition, may be especially vulnerable to impairments on the long-run, nevertheless, transcription factors that may precede and regulate such chronic changes remained uninvestigated in this region. In the current study, we used gene-set enrichment analysis (GSEA) to reveal possible transcription factor candidates responsible for enhanced vulnerability of HC after MDMA administration. Dark Agouti rats were intraperitoneally injected with saline or 15 mg/kg MDMA. Three weeks later HC gene expression was measured by Illumina whole-genome beadarrays and GSEA was performed with MSigDB transcription factor sets. The number of significantly altered genes on the genome level (significance < 0.001) in up/downregulated sets was also counted. MDMA upregulated one, and downregulated 13 gene sets in the HC of rats, compared to controls, including Pax4, Pitx2, FoxJ2, FoxO1, Oct1, Sp3, AP3, FoxO4, and vitamin D receptor (VDR)-regulated sets (q-value

Quercetin is a poorly water-soluble flavonoid with many benefits to human health. Besides the natural food resources that may provide Quercetin, the interest in delivery systems that could enhance its bioavailability in the human body has seen growth in recent years. Promising delivery system candidates are represented by Solid Lipid Nanoparticles (SLNs) which are composed of well-tolerated compounds and provide a relatively high encapsulation efficiency and suitable controlled release. In this study, Quercetin-loaded and negatively charged Solid Lipid Nanoparticles were synthesized based on a coacervation method, using stearic acid as a core lipid and Arabic Gum as a stabilizer. Samples were qualitatively characterized by Dynamic light scattering (DLS), Zeta Potential, Surface infrared spectroscopy (FTIR-ATR), and Time of flight secondary ion mass spectrometry (ToF-SIMS). Encapsulation efficiency, drug release, and antioxidant effect against ABTS•+ were evaluated in vitro by UV–VIS spectrophotometry.

The intake of tomato glycoalkaloids can exert beneficial effects on human health. For this reason, methods for a rapid quantification of these compounds are required. Most of the methods for α-tomatine and dehydrotomatine quantification are based on chromatographic techniques. However, these techniques require complex and time-consuming sample pre-treatments. In this work, HPLC-ESI-QqQ-MS/MS was used as reference method. Subsequently, multiple linear regression (MLR) and partial least squares regression (PLSR) were employed to create two calibration models for the prediction of the tomatine content from thermogravimetric (TGA) and attenuated total reflectance (ATR) infrared spectroscopy (IR) analyses. These two fast techniques were proven to be suitable and effective in alkaloid quantification (R2 = 0.998 and 0.840, respectively), achieving low errors (0.11 and 0.27%, respectively) with the reference technique.