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Abstract Background A systematic examination of low-dose CT (LDCT) scan, beside lung nodules, may disclose the presence of undiagnosed diseases, improving the efficacy and the cost/efficacy of these programs. The study was aimed at evaluating the association between LDCT scan findings and non-oncologic and oncologic diseases. Methods The LDCT scan of participants to the “Un Respiro per la vita”® lung cancer screening program were checked and abnormal findings, beside lung nodules, recorded. First admission to the acute care because of cardiovascular (CD), respiratory (RD) and oncological diseases (OD) in the following three years were retrieved. The association of LDCT scan abnormal findings with CD, RD and OD was assessed through univariable and multivariable logistic regression models. Results Mean age of 746 participants was 62 years (SD:5), 62% were male. 11 (1.5%) received a diagnosis of lung cancer. 16.1% participants were admitted to the acute care in the following three years: 8.6% for CD, 4.3% for RD and 5.2% for OD. Valve calcification (OR 2.02, p:0.02) and mucus plugs (OR 3.37, p:0.04) were positively associated with CD, while sub-pleural fibrosis had a protective role (OR 0.47, p:0.01). Lung nodules > 8 mm (OR 5.54, p:

Students face a wealth of challenges in college for example a lack of support, sometimes making it difficult to persevere. However, in an academic environment that teaches grit and fosters growth, students can learn to persist. Those who believe intelligence is fixed and cannot be changed exert less effort to succeed. Students who persevere when faced with challenges and adversity seem to have what Angela Duckworth calls, grit. This is the idea behind a growth mindset in learning according to Dweck (1999, 2007, 2010) and Duckworth, Peterson, Matthews, and Kelly (2007). Grit can be defined as "…passion and perseverance for long-term goals…" ("Frontiers In Psychology," 2014). One grit effect study was conducted in collaboration with the U.S. Army and the University of Pennsylvania to create predictors of retention. The purpose of this present work is to explore researched competencies related to persistence in reaching academic goals, review literature in grit and growth mindset related to learning and persistence, and examine what educators can do to foster grit and a growth mindset. Recommendations for increasing persistence and grit in college students will be provided.

Abstract Molecular markers are suggested to improve the diagnostic and prognostic accuracy in patients with coronary artery disease (CAD) beyond current clinical scores based on age, gender, symptoms and traditional risk factors. In this context, plasma lipids are emerging as predictors of both plaque composition and risk of future events. We aim to identify plasma lipid biomarkers associated to CAD indexes of stenosis severity, plaque lipid content and a comprensive score of CAD extent and its risk. We used a simple high performance liquid chromatography-tandem mass spectrometry method to identify 69 plasma lipids in 132 subjects referred to Coronary Computed Tomography Angiography (CCTA) for suspected CAD, all under statin treatment. Patients were stratified in groups using three different CCTA-based annotations: CTA-risk score, lipid plaque prevalence (LPP) ratio and the coronary artery disease-reporting and data system (CAD-RADS). We identified a common set of lipid biomarkers composed of 7 sphingomyelins and 3 phosphatidylethanolamines, which discriminates between high risk CAD patients and controls regardless of the CAD annotations used (CTA score, LPP ratio, or CAD-RADS). These results highlight the potential of circulating lipids as biomarkers of stenosis severity, non calcified plaque composition and overall plaque risk of events.

Photocrosslinked hydrogels, such as methacrylate‐modified gelatin (gelMA) and hyaluronic acid (HAMA), are widely utilized as tissue engineering scaffolds and/or drug delivery vehicles, but lack a suitable means for noninvasive, longitudinal monitoring of surgical placement, biodegradation, and drug release. Therefore, a novel photopolymerizable X‐ray contrast agent, methacrylate‐modified gold nanoparticles (AuMA NPs), is developed to enable covalent‐linking to methacrylate‐modified hydrogels (gelMA and HAMA) in one‐step during photocrosslinking and noninvasive monitoring by X‐ray micro‐computed tomography (micro‐CT). Hydrogels exhibit a linear increase in X‐ray attenuation with increased Au NP concentration to enable quantitative imaging by contrast‐enhanced micro‐CT. The enzymatic and hydrolytic degradation kinetics of gelMA‐Au NP hydrogels are longitudinally monitored by micro‐CT for up to 1 month in vitro, yielding results that are consistent with concurrent measurements by optical spectroscopy and gravimetric analysis. Importantly, AuMA NPs do not disrupt the hydrogel network, rheology, mechanical properties, and hydrolytic stability compared with gelMA alone. GelMA‐Au NP hydrogels are thus able to be bioprinted into well‐defined 3D architectures supporting endothelial cell viability and growth. Overall, AuMA NPs enable the preparation of both conventional photopolymerized hydrogels and bioprinted scaffolds with tunable X‐ray contrast for noninvasive, longitudinal monitoring of placement, degradation, and NP release by micro‐CT.

A recurring question concerning Trypanosoma cruzi DNA detection/quantification is related to the fact that DNA amplification, by itself, does not differentiate between viable or dead parasites. On the other hand, RNA can be considered a potential molecular marker of pathogens viability. Herein, we developed a quantitative real-time PCR with reverse Transcription (RT-qPCR) to quantify viable T. cruzi in artificially infected Rhodnius prolixus whilst evaluating differences between DNA and mRNA quantification along the insect midgut during 5, 9, 15 and 29 days after feeding. The RT-qPCR presented an improved performance with linearities ranging from 107 to 102 parasites equivalents and 3 to 0.0032 intestine unit equivalents, and efficiencies of 100.3% and 102.8% for both T. cruzi and triatomine targets, respectively. Comparing both RT-qPCR and qPCR, we confirmed that RNA is faster degraded, no longer being detected at day 1 after parasite lysis, while DNA detection was stable, with no decrease in parasite load over the days, even after parasite lysis. We also observed statistical differences between the quantification of the parasite load by DNA and by RNA on day 15 after feeding of experimentally infected R. prolixus. When assessing different portions of the digestive tract, by RT-qPCR, we could detect a statistically significant reduction in the parasite amount in the anterior midgut. Oppositely, there was a statistically significant increase of the parasite load in the hindgut. In conclusion, for this study parasite's viability in R. prolixus digestive tract were assessed targeting T. cruzi mRNA. In addition, differences between DNA and RNA detection observed herein, raise the possibility that RNA is a potential molecular viability marker, which could contribute to understanding the dynamics of the parasite infection in invertebrate hosts.

Score-based diffusion models are a class of generative models whose dynamics is described by stochastic differential equations that map noise into data. While recent works have started to lay down a theoretical foundation for these models, a detailed understanding of the role of the diffusion time T is still lacking. Current best practice advocates for a large T to ensure that the forward dynamics brings the diffusion sufficiently close to a known and simple noise distribution; however, a smaller value of T should be preferred for a better approximation of the score-matching objective and higher computational efficiency. Starting from a variational interpretation of diffusion models, in this work we quantify this trade-off and suggest a new method to improve quality and efficiency of both training and sampling, by adopting smaller diffusion times. Indeed, we show how an auxiliary model can be used to bridge the gap between the ideal and the simulated forward dynamics, followed by a standard reverse diffusion process. Empirical results support our analysis; for image data, our method is competitive with regard to the state of the art, according to standard sample quality metrics and log-likelihood.

Hospitalized patients with respiratory failure due to SARS-CoV-2 pneumonia are at increased risk of malnutrition and related mortality. The predictive value of the Mini-Nutritional Assessment short form (MNA-sf®), hand-grip strength (HGS), and bioelectrical impedance analysis (BIA) was determined with respect to in-hospital mortality or endotracheal intubation. The study included 101 patients admitted to a sub-intensive care unit from November 2021 to April 2022. The discriminative capacity of MNA-sf, HGS, and body composition parameters (skeletal mass index and phase angle) was assessed computing the area under the receiver operating characteristic curves (AUC). Analyses were stratified by age groups (

Compounds featuring a 1,2,4-oxadiazole core have been recently identified as a new chemotype of farnesoid X receptor (FXR) antagonists. With the aim to expand this class of compounds and to understand the building blocks necessary to maintain the antagonistic activity, we describe herein the synthesis, the pharmacological evaluation, and the in vitro pharmacokinetic properties of a novel series of 1,2,4-oxadiazole derivatives decorated on the nitrogen of the piperidine ring with different N-alkyl and N-aryl side chains. In vitro pharmacological evaluation showed compounds 5 and 11 as the first examples of nonsteroidal dual FXR/Pregnane X receptor (PXR) modulators. In HepG2 cells, these compounds modulated PXR- and FXR-regulated genes, resulting in interesting leads in the treatment of inflammatory disorders. Moreover, molecular docking studies supported the experimental results, disclosing the ligand binding mode and allowing rationalization of the activities of compounds 5 and 11.

The remarkable biological activities of oregano essential oils (EOs) have recently prompted a host of studies aimed at exploring their potential innovative applications in the food and pharmaceutical industries. The chemical composition and biological activities of EOs from two Origanum vulgare genotypes, widely cultivated in Sicily and not previously studied for their biological properties, were characterized. Plants of the two genotypes, belonging to the carvacrol (CAR) and thymol (THY) chemotypes and grown in different cultivation environments, were considered for this study. The chemical profiles, including the determination of enantiomeric distribution, of the EOs, obtained by hydrodistillation from dried leaves and flowers, were investigated by GC–MS. Biological activity was evaluated as antimicrobial properties against different pathogen indicator strains, while intestinal barrier integrity, reduction in pathogen adhesion and anti-inflammatory actions were assayed in the intestinal Caco-2 cell line. The chemical profile of the CAR genotype was less complex and characterized by higher levels of the most active compound, i.e., carvacrol, when compared to the THY genotype. The enantiomeric distribution of chiral constituents did not vary across genotypes, while being markedly different from that observed in Origanum vulgare genotypes from other geographical origins. In general, all EOs showed high antimicrobial activity, both in vitro and in a food matrix challenge test. Representative EOs from the two genotypes resulted not altering epithelial monolayer sealing only for concentrations lower than 0.02%, were able to reduce the adhesion of selected pathogens, but did not exert relevant anti-inflammatory effects. These results suggest their potential use as control agents against a wide spectrum of foodborne pathogens.

(1) Background: Chagas disease is the main neglected tropical disease in America. It is estimated that around 6 million people are currently infected with the parasite in Latin America, and 25 million live in endemic areas with active transmission. The disease causes an estimated economic loss of USD 24 billion dollars annually, with a loss of 75,200 working years per year of life; it is responsible for around ~12,000 deaths annually. Although Mexico is an endemic country that recorded 10,186 new cases of Chagas disease during the period of 1990–2017, few studies have evaluated the genetic diversity of genes that could be involved in the prophylaxis and/or diagnosis of the parasite. One of the possible candidates proposed as a vaccine target is the 24 kDa trypomastigote excretory–secretory protein, Tc24, whose protection is linked to the stimulation of T. cruzi-specific CD8+ immune responses. (2) Methods: The aim of the present study was to evaluate the fine-scale genetic diversity and structure of Tc24 in T. cruzi isolates from Mexico, and to compare them with other populations reported in the Americas with the aim to reconsider the potential role of Tc24 as a key candidate for the prophylaxis and improvement of the diagnosis of Chagas disease in Mexico. (3) Results: Of the 25 Mexican isolates analysed, 48% (12) were recovered from humans and 24% (6) recovered from Triatoma barberi and Triatoma dimidiata. Phylogenetic inferences revealed a polytomy in the T. cruzi clade with two defined subgroups, one formed by all sequences of the DTU I and the other formed by DTU II–VI; both subgroups had high branch support. Genetic population analysis detected a single (monomorphic) haplotype of TcI throughout the entire distribution across both Mexico and South America. This information was supported by Nei’s pairwise distances, where the sequences of TcI showed no genetic differences. (4) Conclusions: Given that both previous studies and the findings of the present work confirmed that TcI is the only genotype detected from human isolates obtained from various states of Mexico, and that there is no significant genetic variability in any of them, it is possible to propose the development of in silico strategies for the production of antigens that optimise the diagnosis of Chagas disease, such as quantitative ELISA methods that use this region of Tc24.

The biological activities of dietary bioactive polysaccharides have been largely explored. Studies on the immunomodulating effects of oligosaccharides and polysaccharides have shown that they are able to modulate innate immunity. Prebiotics are a class of poorly digested carbohydrates that are mainly produced from dietary fibers, which are carbohydrate polymers with ten or more monomeric units as defined by the Codex Alimentarius Commission in 2009. Considering the capacity of prebiotics in reducing gut inflammation, the aim of this study was to investigate the anti-inflammatory activity of galactooligosaccharide (Bimuno® GOS) in an in vitro model of ulcerative colitis (UC)-like inflamed intestinal cells. Differentiated Caco-2 cells were exposed to 2 % dextran-sulfate-sodium salt (DSS) to induce inflammation, and then with different concentrations of Bimuno GOS (1–1,000 μg/ml). Cell monolayer permeability, tight- and adherent junction protein distribution, pro-inflammatory cytokine secretion, and NF-kB cascade were assessed. Bimuno GOS at different concentrations, while not affecting cell monolayer permeability, was shown to counteract UC-like intestinal inflammatory responses and damages induced by DSS. Indeed, Bimuno GOS was able to counteract the detrimental effects of DSS on cell permeability, determined by transepithelial electrical resistance, phenol red apparent permeability, and tight- and adherent junction protein distribution. Furthermore, Bimuno GOS inhibited the DSS-induced NF-kB nuclear translocation and pro-inflammatory cytokine secretion. Further analyses showed that Bimuno GOS was able to revert the expression levels of most of the proteins involved in the NF-kB cascade to control levels. Thus, the prebiotic Bimuno GOS can be a safe and effective way to modulate the gut inflammatory state through NF-kB pathway modulation, and could possibly further improve efficacy in inducing remission of UC.

Abstract Background and aims Reduced sleep quality is common in advanced age. Poor sleep quality is associated with adverse outcomes, chiefly cardiovascular, in young and middle-aged subjects, possibly because of its association with metabolic syndrome (MetS). However, the correlates of sleep quality in oldest populations are unknown. We evaluated the association of sleep quality with MetS in a cohort of subjects aged 90+. Methods and results We analysed data of 343 subjects aged 90+ living in the Mugello area (Tuscany, Italy). Quality of sleep was assessed using the Pittsburgh Sleep Quality Assessment Index (PSQI). Good quality of sleep was defined by a PSQI score .050). However, an increasing number of MetS components was associated with increasing probability of good quality of sleep (P for trend = .002), and of PSQI below the median (P for trend = .007). Generalized Additive Model analysis documented no smoothing function suggestive of nonlinear association between PSQI and MetS. Conclusion Our results confirm a high prevalence of poor sleep quality in oldest age; however, in these subjects, MetS seems to be associated with better sleep quality. Additional larger, dedicated studies are required to confirm our results, and, if so, to identify the subsystems involved and the potential therapeutic implications of such an association.

Abstract This article presents an in-depth analysis and comparison of two computer science degree offerings, viz., the Bologna BSc in Information Systems and Computer Engineering, offered by the Instituto Superior Técnico of the University of Lisbon, Portugal, and the BSc in Computer Science offered by the Pontifical Catholic University of Rio de Janeiro, Brazil. The analysis is based on the student transcripts collected from the academic systems of both institutions over circa one decade. The article starts with a description of the degrees and global statistics of the student population considered. Then, it presents a comparative analysis of the curricula, which focuses on how close students follow the recommended curricula, based on data visualization techniques and academic performance indexes. The indexes indicated a mismatch between the semesters that the curricula recommend for the courses and the semesters that students enroll in those courses. Furthermore, a visualization of course advances and delays indicated that a significant fraction of the students failed in the semester that the curricula recommend for the courses. The article moves on to present a comparative analysis of student performance in individual courses, and then applies a technique borrowed from Market Basket Analysis to investigate student performance in multiple courses that are taken in the same semester. The analysis pointed out sets of courses, at both degrees, that students are struggling with, when they take the courses in the same semester. Finally, the article summarizes the lessons learned, which invite academic administrators to reflect on the weaknesses and strengths of each degree analyzed. Specifically, the analysis suggests that the curricula should be reorganized to avoid that students take certain courses together, not because of conceptual reasons, but because students frequently fail if they do so. Some of these patterns are common to both degrees.

Class II malocclusions are the most frequent within the Italian population. Normally, these malocclusions are caused by a reduction in a mandibular component whose functional stimulus is still very much cause for debate. The negative effect of all types of Class II functional appliances is in the proclination of the lower incisors, which, in subjects whose incisors are already labially inclined, must be checked at all times to avoid serious consequences to these elements. In this case study, a girl aged 14 years and 5 months presented with Class II malocclusion, 2nd division with a convex profile and a visibly retruded chin. The lower incisors presented a marked proclination (−1/Go-Gn ini = 107.7°) in a brachyfacial patient. To avoid further inclination of the lower incisors a Herbst appliance was mounted in two separate sittings. The first part of the appliance including the tubes was mounted to the upper jaw allowing the vestibularisation of the upper incisors in order to increase the overjet. Once this was obtained the lower part of the appliance was mounted together with the telescopic arms associated with two temporary anchorage devices (TADs) in positions 36–37 and 46–47, and an anterior section 33–43 with distal loop to which two double metallic ligatures were anchored at the TADs to contrast the negative effect of the appliance. At the end of the first functional phase, the treatment was refined using MBK fixed therapy to finish the case. The orthodontic therapy led to a visible improvement of the profile and the achievement of a first-class dental–skeletal result on both sides. From the cephalometric evaluation carried out immediately after the Herbst appliance treatment at time T1 and at the end of the orthodontic therapy T2 it was possible to verify a slight increase in the inclination of the lower incisors (−1/Go-Gn fin = 108°). In conclusion, it can be said that the use of the skeletal anchorage avoided, in this case, the proclination effect in the lower incisors due to the use of a Herbst appliance.

The human body contains a very complex and dynamic ecosystem of bacteria. The bacteriome interacts with the host bi-directionally, and changes in either factor impact the entire system. It has long been known that chronic airway diseases are associated with disturbances in the lung bacteriome. However, less is known about the role of gut bacteriome in the most common respiratory diseases. Here, we aim to summarise the evidence concerning the role of the intestinal bacteriome in the pathogenesis and disease course of bronchial asthma, chronic obstructive pulmonary disease, and obstructive sleep apnea. Furthermore, we discuss the consequences of an altered gut bacteriome on the most common comorbidities of these lung diseases. Lastly, we also reflect on the therapeutic potential of influencing the gut microbiome to improve disease outcomes.

Triatoma melanica is a sylvatic vector species in Brazil. In We aimed to characterize the Trypanosoma cruzi discrete typing units (DTUs), the parasitic loads, and the blood meal sources of insects collected in rocky outcrops in rural areas in the state of Minas Gerais. An optical microscope (OM) and kDNA-PCR were used to examine natural infection by T. cruzi, and positive samples were genotyped by conventional multilocus PCR. Quantification of the T. cruzi load was performed using qPCR, and the blood meal sources were identified by Sanger sequencing the 12S rRNA gene. A total of 141 T. melanica were captured. Of these, ~55% (61/111) and ~91% (63/69) were positive by OM and KDNA-PCR, respectively. We genotyped ~89% (56/63) of the T. cruzi-positive triatomines, with TcI (~55%, 31/56) being the most prevalent DTU, followed by TcIII (~20%, 11/56) and TcII (~7%, 4/56). Only TcI+TcIII mixed infections were detected in 10 (~18%) specimens. A wide range of variation in the parasitic loads of T. melanica was observed, with an overall median value of 104 parasites/intestine, with females having higher T. cruzi loads than N2, N4, and N5. TcII showed lower parasitic loads compared to TcI and TcIII. The OM positive diagnosis odds ratio between T. cruzi infection when the parasite load is 107 compared to 103 was approximately 29.1. The most frequent blood meal source was Kerodon rupestris (~58%), followed by Thrichomys apereoides (~18%), Wiedomys cerradensis (~8%), Galactis cuja (~8%) and Gallus gallus (~8%). Our findings characterize biological and epidemiological aspects of the sylvatic population of T. melanica in the study area, highlighting the need to extend surveillance and control to this vector.

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is a serious public health problem. Current treatment is restricted to two drugs, benznidazole and nifurtimox, displaying serious efficacy and safety drawbacks. Nucleoside analogues represent a promising alternative as protozoans do not biosynthesize purines and rely on purine salvage from the hosts. Protozoan transporters often present different substrate specificities from mammalian transporters, justifying the exploration of nucleoside analogues as therapeutic agents. Previous reports identified nucleosides with potent trypanocidal activity; therefore, two 7-derivatized tubercidins (FH11706, FH10714) and a 3′-deoxytubercidin (FH8513) were assayed against T. cruzi. They were highly potent and selective, and the uptake of the tubercidin analogues appeared to be mediated by the nucleoside transporter TcrNT2. At 10 μM, the analogues reduced parasitemia >90% in 2D and 3D cardiac cultures. The washout assays showed that FH10714 sterilized the infected cultures. Given orally, the compounds did not induce noticeable mouse toxicity (50 mg/kg), suppressed the parasitemia of T. cruzi-infected Swiss mice (25 mg/kg, 5 days) and presented DNA amplification below the limit of detection. These findings justify further studies with longer treatment regimens, as well as evaluations in combination with nitro drugs, aiming to identify more effective and safer therapies for Chagas disease.

Second cheese whey (SCW) derived from buffalo milk is the main by-product of the mozzarella cheese dairy industry. The objective of this study was to develop a membrane-based purification procedure to obtain specific fractions from SCW and assess their biological and applicative potential. Special interest was paid to the proteins and newly identified health-promoting compounds that could be recovered and used as value-added products in different sectors of food and pharmaceutical industries. SCW has been treated, sequentially, with microfiltration (MF), ultrafiltration (UF), and nanofiltration (NF) membranes giving the possibility to obtain three different fractions, namely retentates recovered on 100 and 10 kDa (R100 and R10) and a nanofiltration retentate (RNF). These retentates were compared for their ability to preserve human keratinocytes from dehydration, to form protein-based films by casting, and finally they were used for probiotic cultivations as the main substrate. Results showed that Lactobacillus rhamnosus could grow without any further additional nutrient up to 2.2 ± 0.3 × 109 CFU/mL in the RNF medium. Dehydration tests on HaCat cells proved R100 as the most efficient fraction in preserving cell viability from this specific stress. R10, after diafiltrations, formed transparent films with improved features when glycerol was added as a plasticizer.

Staphylococcus aureus (S. aureus) represents an important pathogen of clinical relevance, causing a wide variety of symptoms. The broad distribution of multidrug-resistant strains necessarily demands new antibacterial agents for the treatment of S. aureus infections. The aim of this study was to assess the antibacterial activity of plant-derived compounds, pure 4,5″-dihydroxy-anthraquinone-2-carboxylic acid (Rhein), against standard and clinical isolated S. aureus strains. The hemolysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were used to determine the cytotoxicity on human erythrocytes and bronchial epithelial cells after treatment with Rhein. The antibacterial effect was assessed via disk diffusion test, broth microdilution methods, time-killing assays and live–dead evaluation (50–0.39 µg/mL). Rhein effect on the hemolytic activity of α-toxin and catalase were estimated. Moreover, crystal violet (CV) assay evaluated its impact on biofilm biomass. The compound exhibited 50% cytotoxic concentration (CC50) and 50% hemolysis concentration (EC50) of 43.6 and >50 µg/mL, respectively. The minimum inhibitory concentration (MIC) of Rhein was 12.5 µg/mL for all tested strains, exerting bacteriostatic action. MIC and sub-MIC concentrations of Rhein significantly reduced hemolytic and catalase activities, impairing the major virulence factors of S. aureus strains. Rhein also reduced biofilm biomass in a dose-dependent manner, reaching rates of about 50% eradication at a dose of 50 µg/mL. These findings suggest that Rhein could represent a promising therapeutic option for the treatment of S. aureus infections.

BDDE (1,4-butanediol-diglycidylether)-crosslinked hyaluronan (HA) hydrogels are widely used for dermo-aesthetic purposes. The rheology and stability of the gels under physiological conditions greatly affect their clinical indications and outcomes. To date, no studies investigating how these features are related to the chemistry of the polymeric network have been reported. Here, four available HA-BDDE hydrogels were studied to determine how and to what extent their rheology and stability with respect to enzymatic hydrolysis relate to the type and degree of HA structural modification. 1H-/13C-NMR analyses were associated for the quantification of the “true” HA chemical derivatization level, discriminating between HA that was effectively crosslinked by BDDE, and branched HA with BDDE that was anchored on one side. The rheology was measured conventionally and during hydration in a physiological medium. Sensitivity to bovine testicular hyaluronidase was quantified. The correlation between NMR data and gel rheology/stability was evaluated. The study indicated that (1) the gels greatly differed in the amounts of branched, crosslinked, and overall modified HA, with most of the HA being branched; (2) unexpectedly, the conventionally measured rheological properties did not correlate with the chemical data; (3) the gels’ ranking in terms of rheology was greatly affected by hydration; (4) the rheology of the hydrated gels was quantitatively correlated with the amount of crosslinked HA, whereas the correlations with the total HA modification level and with the degree of branched HA were less significant; (5) increasing HA derivatization/crosslinking over 9/3 mol% did not enhance the stability with respect to hyaluronidases. These results broaden our knowledge of these gels and provide valuable information for improving their design and characterization.

Cannabis sativa L. is a plant belonging to the Cannabaceae family, cultivated for its psychoactive cannabinoid (Δ9-THC) concentration or for its fiber and nutrient content in industrial use. Industrial hemp shows a low Δ9-THC level and is a valuable source of phytochemicals, mainly represented by cannabinoids, flavones, terpenes, and alkaloids, with health-promoting effects. In the present study, we investigated the phytochemical composition of leaves of the industrial hemp cultivar Futura 75, a monoecious cultivar commercially used for food preparations or cosmetic purposes. Leaves are generally discarded, and represent waste products. We analyzed the methanol extract of Futura 75 leaves by HPLC and NMR spectroscopy and the essential oil by GC-MS. In addition, in order to compare the chemical constituents, we prepared the water infusion. One new cannabinoid derivative (1) and seven known components, namely, cannabidiol (2), cannabidiolic acid (3), β-cannabispirol (4), β-cannabispirol (5), canniprene (6), cannabiripsol (7), and cannflavin B (8) were identified. The content of CBD was highest in all preparations. In addition, we present the outcomes of a computational study focused on elucidating the role of 2α-hydroxy-Δ3,7-cannabitriol (1), CBD (2), and CBDA (3) in inflammation and thrombogenesis.

This data article associated with the manuscript “A high glucose levels is associated with decreased aspirin-mediated acetylation of platelet cyclooxygenase (COX)-1 at serine 529: a pilot study” (Finamore et al., 2018) refers to the shotgun proteomics approach carried out on platelet protein extracts from diabetic patients and healthy controls. Platelet proteins were in vitro incubated with 500 µM aspirin for 30 min at 37 °C to enhance the acetylation process. After protein digestion with trypsin, DDA data were acquired on a Thermo QExactive plus using 3 technical replicate injections per sample. Here, we were able to elucidate the preferential sites of aspirin-induced acetylation on a significant fraction of the platelet proteome and to quantify the impact of diabetes on the effect of aspirin on several platelet proteins. Data are available via ProteomeXchange with identifier PXD011582.

In Brazil, orally acquired T. cruzi infection has become the most relevant transmission mechanisms from public health perspective. Around 70% of new Chagas disease cases have been associated with consumption of contaminated food or beverages. Açai (Euterpe oleracea and Euterpe precatoria) is currently one of the most commercialized Amazonian fruits in the Brazilian and international markets. Therefore, it has become important to incorporate in the production process some procedures to measure out effective hygiene and product quality control required by global market. Molecular methods have been developed for rapid detection and quantification of T. cruzi DNA in several biological samples, including food matrices, for epidemiological investigation of Chagas disease and food quality control. However, a high-performance molecular methodology since DNA extraction until detection and quantification of T. cruzi DNA in açai berry pulp is still needed. Herein, a simple DNA extraction methodology was standardized from the supernatant of açai berry pulp stabilized in a 6M Guanidine-HCl/0.2M EDTA buffer. In addition, a multiplex real time qPCR assay, targeting T. cruzi DNA and an Exogenous Internal Positive Control was developed and validated, using reference from all T. cruzi DTUs and commercial samples of açai pulp, from an endemic municipality with previous history of oral Chagas disease outbreak. Thus, a high-sensitivity qPCR assay, that could detect up to 0.01 parasite equivalents/mL in açai, was reached. As of the 45 commercial samples analyzed, 9 (20%) were positive for T. cruzi. This high-sensitive, fast, and easy-to-use molecular assay is compatible with most of the laboratories involved in the investigations of oral Chagas disease outbreaks, representing an important tool to the epidemiology, control, and surveillance of Chagas disease.

Microbial biofilms pose a serious threat to patients requiring medical devices (MDs). Prolonged periods of implantation carry a high risk of device-related infections (DRIs). Patients with DRIs often have negative outcomes following the failure of antibiotic treatment. Resistant DRIs are mainly due to the MDs contamination by bacteria producing biofilm. The present study aimed to detect biofilm formation among MD bacterial isolates and to explore their antibiotic resistance profile. The study was conducted on 76 MDs, collected at University Hospital of Campania “Luigi Vanvitelli,” between October 2019 and September 2020. Identification of isolates and antibiotic susceptibility testing were performed using Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and Phoenix Becton Dickinson, respectively. Biofilm-forming abilities were assessed using the tissue culture plate (TCP) method. Among the 94 MDs isolated strains, 42.7% were Gram-positive, 40.3% Gram-negative, and 17% Candida species. Among 78 bacterial strains, 43.6% were non-biofilm producers while 56.4% produced biofilms. All biofilm producing isolates were sensitive to a limited spectrum of antibiotic classes. All moderate and strong biofilm producers and 81% of weak biofilm producers were Multidrug Resistance (MDR) strains. In contrast, among non-biofilm producers, only 11.8% were classified as MDR strains. Our results highlighted that Sulfamides and Glycopeptides for the major Gram-positive strains and Fluoroquinolones, Carbapenems, and Aminoglycosides for the most represented Gram-negative isolates could be the most suitable therapeutic choice for most biofilm-DRIs.

(1) Background: Plantar fasciitis (PF) is the most common cause of heel pain in adults. Extracorporeal shockwave therapy (ESWT) is a minimally invasive treatments commonly used for treating PF. Our aim is to provide a complete overview of which treatments have been compared to ESWT, with a focus on the modalities that have been used. (2) Methods: A thorough search of the literature was performed on Medline via Pubmed, Cochrane Database of Systematic Reviews (CDSR) of the Cochrane Library and Physiotherapy Evidence Databases (PEDro) up to 18 November 2021. In the study were included only systematic reviews and meta-analysis in English language, published from 2010 to date. (3) Results: A total of 14 systematic reviews and meta-analysis were included in the umbrella review. A total of eight studies compared the efficacy of ESWT treatment with placebo, three studies compared ESWT with another therapy (two studies compared ESWT and corticosteroids, one study ESWT and ultrasound therapy), and three studies had more than one comparison. (4) Conclusions: When compared to placebo, ESWT demonstrated to be effective. More randomized trials with specific comparisons between different types and intensity of SW are needed to obtain more precise information on SW effectiveness.

The non-professional sport environment is a grey zone not as widely assessed as that of elite athletes. The purpose of this research was to investigate the dietary supplementation habits and the nutrition knowledge on sport (NKS) in a sample of gym users. The level of adequacy of NKS was set at ≥60% of correct answers. Almost half (46.4%) of respondents stated they used food supplements, in particular multivitamins (31.0%), amino acid pills (29.5%), minerals (29.1%), and protein powders (28.7%). Supplements were used to increase muscle mass (36.9%) and to repair muscle (35.1%). Gym trainers were the preferred source of information on the use of supplements, especially in males (84%). The NKS correct response rate was 57.1% and the proportion of respondents with a sufficient level of NKS was 47.3%. The prevalence of correct answers was highest in males (61.5%) and for respondents with the highest educational attainment levels (44.5% and 53%). This study demonstrated that non-professional sportsmen do not have sufficient knowledge of nutrition and that the gym environment does not facilitate the circulation of the correct information on the role of supplementation. Considering the importance of nutrition for sportsmen, it is necessary to put in place actions aimed at increasing the knowledge of nutrition of gym users and their trainers.

O artigo avalia as relações intersetoriais que se estabelecem entre os fluxos da água e as atividades econômicas da economia brasileira. Para isso, foi construído um modelo insumo-produto ecológico que incorpora um vetor ambiental de fluxos físicos do uso e do consumo de água em cada setor. Os indicadores de encadeamentos setoriais evidenciaram que o setor eletricidade estimula fortemente o uso de água no país e o setor agropecuário, o maior consumo de água. Verificou-se que pouco mais de um terço da água consumida pelas atividades econômicas do país são exportadas, principalmente por meio da agropecuária de exportação que responde por 88,79% da “água virtual”.

The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus (SARS)-CoV-2. In light of the urgent need to identify novel approaches to be used in the emergency phase, we have embarked on an exploratory campaign aimed at repurposing natural substances and clinically available drugs as potential anti-SARS-CoV2-2 agents by targeting viral proteins. Here we report on a strategy based on the virtual screening of druggable pockets located in the central β-sheet core of the SARS-CoV-2 Spike's protein receptor binding domain (RBD). By combining an in silico approach and molecular in vitro testing we have been able to identify several triterpenoid/steroidal agents that inhibit interaction of the Spike RBD with the carboxypeptidase domain of the Angiotensin Converting Enzyme (ACE2). In detail, we provide evidence that potential binding sites exist in the RBD of the SARS CoV-2 Spike protein and that occupancy of these pockets reduces the ability of the RBD to bind to the ACE2 consensus in vitro. Naturally occurring and clinically available triterpenoids such as glycyrrhetinic and oleanolic acids, as well as primary and secondary bile acids and their amidated derivatives such as glyco-ursodeoxycholic acid and semi-synthetic derivatives such as obeticholic acid reduces the RBD/ACE2 binding. In aggregate, these results might help to define novel approaches to COVID-19 based on SARS-CoV-2 entry inhibitors.

Glioblastoma multiforme (GBM) is one of the most aggressive types of brain cancer, characterized by rapid progression, resistance to treatments, and low survival rates; the development of a targeted treatment for this disease is still today an unattained objective. Among the different strategies developed in the latest few years for the targeted delivery of nanotherapeutics, homotypic membrane-membrane recognition is one of the most promising and efficient. In this work, we present an innovative drug-loaded nanocarrier with improved targeting properties based on the homotypic recognition of GBM cells. The developed nanoplatform consists of boron nitride nanotubes (BNNTs) loaded with doxorubicin (Dox) and coated with cell membranes (CM) extracted from GBM cells (Dox-CM-BNNTs). We demonstrated as Dox-CM-BNNTs are able to specifically target and kill GBM cells in vitro, leaving unaffected healthy brain cells, upon successful crossing an in vitro blood-brain barrier model. The excellent targeting performances of the nanoplatform can be ascribed to the protein component of the membrane coating, and proteomic analysis of differently expressed membrane proteins present on the CM of GBM cells and of healthy astrocytes allowed the identification of potential candidates involved in the process of homotypic cancer cell recognition.

We investigated the efficacy of different probiotics and bacteria used in dairy products to prevent the development of obesity and ameliorate established obesity in C57BL/6J mice fed a high fat diet (HFD). For the preventive efficacy, Lactobacillus rhamnosus GG, L. acidophilus LA1/K8, a mixture of Bifidobacterium lactis Bi1, B. breve Bbr8 and B. breve BL10 (B. mix), or a mixture of L. bulgaricus Lb2 and S. termophilus Z57 were given to mice before (2 weeks) and together with HFD (12 weeks). B. mix was selected for its anti-obesity activity and assessed in established obesity by feeding mice the HFD for 24 weeks and B. mix for the last 12 weeks. We found that B. mix was able to both prevent and ameliorate established obesity by reducing weight gain, adipose tissue fat accumulation, adipocyte size, and macrophage and CD4+ T cell infiltration, improving lipid profile and regulating leptin and cytokine secretion.

Panaiotis Finamore,1 Claudio Pedone,1 Simone Scarlata,1 Alessandra Di Paolo,1 Simone Grasso,2 Marco Santonico,2 Giorgio Pennazza,2 Raffaele Antonelli Incalzi1 1Unit of Geriatrics, Campus Bio-Medico di Roma University, Rome, Italy; 2Unit of Electronics for Sensor Systems, Campus Bio-Medico di Roma University, Rome, Italy Aim: Six-minute walking test distance (6MWD) and body mass index, obstruction, dyspnea and exercise (BODE) index are measures of functional status in COPD patients, but require space, time and patient’s compliance. Exhaled volatile organic compounds (VOCs) analysis via electronic nose is a quick and easy method that has already been used to discriminate COPD phenotypes. The aim of this study is to evaluate whether VOCs analysis can predict functional status and its variation over time in COPD patients.Methods: A monocentric prospective study with 1 year of follow-up was carried out. All patients underwent pulmonary function tests, arterial gas analysis, bioimpedance analysis, 6-minute walking test, and VOCs collection. Exhaled breath was collected with Pneumopipe® and analyzed using BIONOTE electronic nose. Outcomes prediction was performed by k-fold cross-validated partial least square discriminant analysis: accuracy, sensitivity and specificity as well as Cohen’s kappa for agreement were calculated.Results: We enrolled 63 patients, 60.3% men, with a mean age of 71 (SD: 8) years, median BODE index of 1 (interquartile range: 0–3) and mean 6MWD normalized by squared height (n6MWD) of 133.5 (SD: 42) m/m2. The BIONOTE predicted baseline BODE score (dichotomized as BODE score

Abstract Background Several cases of food-borne acute Chagas disease (ACD) have been reported in the Brazilian Amazon so far. Up to 2004, the occurrence of ACD by oral transmission, associated with food consumption, was rare. Recent cases of ACD in Brazil have been attributed to the consumption of juice from the açai palm containing reservoir animals or insect vectors waste, infected with Trypanosoma cruzi. This study aimed to determine the T. cruzi contamination rate and to genotype the parasite in food samples prepared from açai, which are commercialized in Rio de Janeiro and the Pará States in Brazil. Methods The amplificability of DNA extracted from açai samples, and T. cruzi and Triatominae detection were performed by conventional PCR. Molecular characterization was done by multilocus PCR analysis, to determine the parasite discrete type units (DTUs) based on the size of PCR products in agarose gels, using the intergenic region of the spliced leader (SL), 24 Sα rDNA and nuclear fragment A10 as targets. Results From the 140 samples of açai-based products analyzed, T. cruzi DNA was detected in 14 samples (10%); triatomine DNA was detected in one of these 14 samples. The parasite genotyping demonstrated that food samples containing açai showed a mixture of T. cruzi DTUs with TcIII, TcV and TcI prevailing. Conclusions In this study, the molecular detection and identification of T. cruzi from açai-based manufactured food samples, was performed for the first time. Although parasite DNA is a marker of possible contamination during food manufacturing, our findings do not indicate that açai is a source of Chagas disease via oral transmission per se, as live parasites were not investigated. Nevertheless, a molecular approach could be a powerful tool in the epidemiological investigation of outbreaks, supporting previous evidence that açai-based food can be contaminated with T. cruzi. Furthermore, both food quality control and assessment of good manufacturing practices involving açai-based products can be improved, assuring the safety of açai products.

Waste reduction and reuse is a crucial target of current research efforts. In this respect, the present study was focused on providing an example of local investment in a simple process configuration that converts whey into value-added compounds and allows recovery of a clean water stream. In particular, buffalo milk whey obtained during mozzarella manufacturing was ultrafiltered in-house on spiral membrane modules (20 kDa), and the two obtained fractions, namely the retentate and the permeate, provided by the dairy factory, were further processed during this work. The use of an additional nanofiltration step allowed the recovery of high-quality water to be reused in the production cycle (machine rinsing water within the facility) and/or in agriculture, also reducing disposal costs and the environmental impact. The ultrafiltration retentate, on the other hand, was spray-dried and the powder obtained was used as the main substrate for the cultivation of Lactobacillus fermentum, a widely studied probiotic with anti-inflammatory, immunomodulatory and cholesterol-lowering properties. In addition, the same sample was tested in vitro on a human keratinocytes model. Resuspended concentrated whey powder improved cell reparation rate in scratch assays, assisted through time-lapse video-microscopy. Overall these data support the potential of buffalo whey as a source of biologically active components and recyclable water in the frame of a local circular economy approach.

Natural products have been the main source of bioactive molecules for centuries. We tested the biological profile of two metabolites extracted from Gentiana lutea L. by means of computational techniques and in vitro assays. The two molecules (loganic acid and gentiopicroside) were tested in silico using an innovative technique, named Inverse Virtual Screening (IVS), to highlight putative partners among a panel of proteins involved in inflammation and cancer events. A positive binding with cyclooxygenase-2 (COX-2), alpha-1-antichymotrypsin, and alpha-1-acid glycoprotein emerged from the computational experiments and the outcomes from the promising interaction with COX-2 were confirmed by Western blot, highlighting the reliability of IVS in the field of the natural products.