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α -1 antitrypsin (A1AT) is a 52 kDa acute-phase glycoprotein belonging to the serine protease inhibitor superfamily (SERPIN). It is primarily synthesized by hepatocytes and to a lesser extent by monocytes, macrophages, intestinal epithelial cells, and bronchial epithelial cells. A1AT is encoded by SERPINA1 locus, also known as PI locus, highly polymorphic with at least 100 allelic variants described and responsible for different A1AT serum levels and function. A1AT inhibits a variety of serine proteinases, but its main target is represented by Neutrophil Elastase (NE). However, recent attention has been directed towards its immune-regulatory and homeostatic activities. A1AT exerts immune-regulatory effects on different cell types involved in innate and adaptive immunity. Additionally, it plays a role in metal and lipid metabolism, contributing to homeostasis. An adequate comprehension of these mechanisms could support the use of A1AT augmentation therapy in many disorders characterized by a chronic immune response. The aim of this review is to provide an up-to-date understanding of the molecular mechanisms and regulatory pathways responsible for immune-regulatory and homeostatic activities of A1AT. This knowledge aims to support the use of A1AT in therapeutic applications. Furthermore, the review summarizes the current state of knowledge regarding the application of A1AT in clinical and laboratory settings human and animal models.

The paper aims to enable a comprehensive definition for a Circular Economy (CE) that will support its effective introduction in the building and construction sectors. According to the European Commission (EC), the building sector in 2020 accounted for 40 % of the primary energy demand in the European Union (EU) and 37 % of its greenhouse gas emissions. Thus, the sector can play a crucial role in decarbonisation and hence in achieving a zero-emissions future in response to climate change. A CE aims to harmonise economic growth with environmental protection and is based on the concept of closing the loop with minimal practical waste as in a natural ecosystem. The adoption of CE concepts is therefore seen as a feasible response to climate change through the deployment of more sustainable construction processes that significantly reduce the need for natural resources by maximising recycling and reuse. However, and despite the recognition of the potential of a CE in relation to sustainability issues, the adoption of a CE model within building and construction sectors is challenging because of the wide range of aspects and priorities which are reflected in the diversity of definition resulting in a narrow and limited adoption. There are currently many definitions of CEs as related to building and construction in the literature, creating confusion and preventing effective implementation.The study presented here intends, using a comprehensive literature review as its basis, to define the key domains of a CE on which to align a concise and accurate definition that will enable effective application in the building and construction sectors. The research also aims to identify current research gaps and barriers to contribute to the future of CE research in the building sector and thus drive the implementation of CE projects to mitigate the effects of climate change and support the achievement of the UN Sustainable Development Goals (SDGs) by laying the foundations for a novel and forward-looking approach to circularity based on properly established, defined and understood principles of CEs.

Abstract Tuberculosis (TB) is one of the deadliest infectious disorders in the world. To effectively TB manage, an essential step is to gain insight into the lineage of Mycobacterium tuberculosis (MTB) and the distribution of drug resistance. Although the Campania region is declared a cluster area for the infection, to contribute to the effort to understand TB evolution and transmission, still poorly known, we have generated a dataset of 159 genomes of MTB strains, from Campania region collected during 2018–2021, obtained from the analysis of whole genome sequence. The results show that the most frequent MTB lineage is the 4 according for 129 strains (81.11%). Regarding drug resistance, 139 strains (87.4%) were classified as multi susceptible, while the remaining 20 (12.58%) showed drug resistance. Among the drug-resistance strains, 8 were isoniazid-resistant MTB, 4 multidrug-resistant MTB, while only one was classified as pre-extensively drug-resistant MTB. This dataset expands the existing available knowledge on drug resistance and evolution of MTB, contributing to further TB-related genomics studies to improve the management of this disease.

BAR502, a bile acid analogue, is active as dual FXR/GPBAR1 agonist and represents a promising lead for the treatment of cholestasis and NASH. In this paper we report the synthesis and the biological evaluation of a library of hybrid compounds prepared by combining, through high-yield condensation reaction, some fibrates with BAR502.The activity of the new conjugates was evaluated towards FXR, GPBAR1 and PPARα receptors, employing transactivation or cofactor recruitment assays. Compound 1 resulted as the most promising of the series and was subjected to further pharmacological investigation, together with stability evaluation and cell permeation assessment. We have proved by LCMS analysis that compound 1 is hydrolyzed in mice releasing clofibric acid and BAR505, the oxidized metabolite of BAR502, endowed with retained dual FXR/GPBAR1 activity.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer and the chemotherapies such as gemcitabine/nab-paclitaxel are confronted with intrinsic or acquired resistance. The aim of this study was to investigate mechanisms underlying paclitaxel resistance in PDAC and explore strategies to overcome it. Methods Three paclitaxel (PR) and gemcitabine resistant (GR) PDAC models were established. Transcriptomics and proteomics were used to identify conserved mechanisms of drug resistance. Genetic and pharmacological approaches were used to overcome paclitaxel resistance. Results Upregulation of ABCB1 through locus amplification was identified as a conserved feature unique to PR cells. ABCB1 was not affected in any of the GR models and no cross resistance was observed. The ABCB1 inhibitor verapamil or siRNA-mediated ABCB1 depletion sensitized PR cells to paclitaxel and prevented efflux of ABCB1 substrates in all models. ABCB1 expression was associated with a trend towards shorter survival in patients who had received gemcitabine/nab-paclitaxel treatment. A pharmacological screen identified known and novel kinase inhibitors that attenuate efflux of ABCB1 substrates and sensitize PR PDAC cells to paclitaxel. Conclusion Upregulation of ABCB1 through locus amplification represents a novel, conserved mechanism of PDAC paclitaxel resistance. Kinase inhibitors identified in this study can be further (pre) clinically explored as therapeutic strategies to overcome paclitaxel resistance in PDAC.

The high frequency and complexity of mandibular third molar (M3M) surgery have led several authors to the development of classification systems for better evaluation and management in oral surgery. This study compared the classifications of Juodzabalys and Daugela et al. (JD), Sammartino et al., Chang et al., Jhamb et al., Maglione et al., and Nemsi et al. to understand the concordance between the scores of M3M surgery. Two types of analysis were conducted: the relationship between the M3M and the inferior alveolar nerve (IAN), and the overall difficulty score based on the tooth’s angulation and its spatial position with the adjacent structure. The analysis of the classifications on the relationship between M3M and IAN resulted in a concordance of 26.1%. In the pairwise comparisons, the classifications of Nemsi et al. and Jhamb et al. showed the highest concordance of 59.5%. Analyzing the total scores difficulty, the JD et al., Chang et al., and Sammartino et al. classifications demonstrated a concordance level of 25.5%. A pairwise assessment revealed a higher concordance degree between the classifications of Sammartino et al. and Chang et al. (57.4%). The results highlight the limits in establishing a comprehensive and objective classification for the surgical difficulty of M3M, possibly attributed to variations in the methodology for computing total scores. An objective, automated, and non-operator-dependent classification method for assessing the surgical difficulty of M3M is still needed.

Currently, approximately 70% of new cases of Chagas disease (CD) in Brazil are attributed to oral transmission, particularly through foods such as açaí, bacaba, and sugarcane juice, primarily in the northern and northeastern regions of the country. This underscores the imperative need to control the spread of the disease. The methods utilized to conduct quality control for food associated with outbreaks and to assess the potential for the oral transmission of CD through consuming açaí primarily rely on isolating the parasite or inoculating food into experimental animals, restricting the analyses to major research centers. While there are existing studies in the literature on the detection and quantification of T. cruzi DNA in açaí, the evaluation of parasites’ viability using molecular methods in this type of sample and differentiating between live and dead parasites in açaí pulp remain challenging. Consequently, we developed a molecular methodology based on RT-qPCR for detecting and quantifying viable T. cruzi in açaí pulp samples. This protocol enables the stabilization and preservation of nucleic acids in açaí, along with incorporating an exogenous internal amplification control. The standardization of the RNA extraction method involved a simple and reproducible approach, coupled with a one-step RT-qPCR assay. The assay underwent validation with various T. cruzi DTUs and demonstrated sensitivity in detecting up to 0.1 viable parasite equivalents/mL in açaí samples. Furthermore, we investigated the effectiveness of a bleaching method in eliminating viable parasites in açaí samples contaminated with T. cruzi by comparing the detection of DNA versus RNA. Finally, we validated this methodology using açaí pulp samples positive for T. cruzi DNA, which were collected in a municipality with a history of oral CD outbreaks (Coari-AM). This validation involved comparing the detection and quantification of total versus viable T. cruzi. Collectively, our findings demonstrate the feasibility of this methodology in detecting viable forms of T. cruzi in açaí pulp samples, emerging as a crucial tool for monitoring oral outbreaks of Chagas disease resulting from açaí consumption.

This quantitative study examined the effects of an online synchronous orientation on the final grade of students enrolled in a first-term online class. The multifactor orientation focused on several factors which are thought to contribute to online student success, including organizational skills, goal setting, orientation to the online classroom, and academic support. Six course sections (three treatment and three control) were included in the study. In each of the three treatment sections, students had the option of participating in the orientation during the second week of the term; about half in each section did so. Controlling for course performance at the second week, students who attended the orientation earned significantly higher end-of-term grades, compared to either control students (who were not offered the option of the orientation) or to students who were offered the extra seminar but did not attend it.

Magnusiomyces capitatus (M. capitatus) is an emerging opportunistic yeast in the Mediterranean region typically isolated from immunocompromised patients, usually affected by blood malignancies. We reported a rare case of M. capitatus infection, isolated from a drainage fluid in a patient affected by lung cancer recovered in the University Hospital of Campania “Luigi Vanvitelli”, Naples, Italy. The isolate was identified by phenotypic methods, i.e., Gram and Lactophenol cotton blue (LCB) staining, and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) analysis. We identified M. capitatus on the third day from Sabouraud Dextrose Agar supplemented with chloramphenicol and gentamicin. Antifungal susceptibility test revealed that 5-fluorocytosine was the most active drug against M. capitatus, followed by itraconazole and voriconazole, micafungin, amphotericin B and fluconazole, posaconazole, anidulafungin, and caspofungin. Our data showed the importance of an early cultural and fast microbiology diagnosis based on the characteristic morphologic features observed in Gram-stained smears of blood culture positive bottles, and the validation via MALDI-TOF MS. This dual approach has significant impact in the clinical management of infectious diseases and antibiotic stewardship, by integrating sample processing, fluid handling, and detection for rapid bacterial diagnosis.

Obesity is a pathophysiological condition, dependent on body fat accumulation, that progressively induces systemic oxidative stress/inflammation leading to a set of associated clinical manifestations, including male infertility. CircRNAs, covalently closed RNA molecules, are key regulators of sperm quality. Recently, we have characterized a complete profile of high-fat diet (HFD) spermatic circRNA cargo, predicting paternal circRNA dependent networks (ceRNETs), potentially involved in sperm oxidative stress and motility anomalies. In the current work, using HFD C57BL6/J male mice, orally treated with a mix of bioactive molecules (vitamin C; vitamin B12; vitamin E; selenium-L-methionine; glutathione-GSH) for 4 weeks, a reversion of HFD phenotype was observed. In addition, the functional action of the proposed formulations on circRNA biogenesis was evaluated by assessing the endogenous spermatic FUS-dependent backsplicing machinery and related circRNA cargo. After that, spermatic viability and motility were also analyzed. Paternal ceRNETs, potentially involved in oxidative stress regulation and sperm motility defects, were identified and used to suggest that the beneficial action of the food supplements here conveniently formulated on sperm motility was likely due to the recovery of circRNA profile. Such a hypothesis was, then, verified by an in vitro assay.

Ovarian cancer (OC) is the eighth most common cancer in women. Since screening programs do not exist, it is often diagnosed in advanced stages. Today, the detection of OC is based on clinical examination, transvaginal ultrasound (US), and serum biomarker (Carbohydrate Antigen 125 (CA 125) and Human Epididymis Protein 4 (HE4)) dosage, with a sensitivity of 88% and 95%, respectively, and a specificity of 84% for US and 76% for biomarkers. These methods are clearly not enough, and OC in its early stages is often missed. Many scientists have recently focused their attention on volatile organic compounds (VOCs). These are gaseous molecules, found in the breath, that could provide interesting information on several diseases, including solid tumors. To detect VOCs, an electronic nose was invented by a group of researchers. A similar device, the e-tongue, was later created to detect specific molecules in liquids. For the first time in the literature, we investigated the potential use of the electronic nose and the electronic tongue to detect ovarian cancer not just from breath but also from urine, blood, and plasma samples.

Nowadays, research on plant extracts has attracted increasing interest. The aim of this study was to compare phenolic profile, vitamin C, and carotenoid content, as well as the biological activities of five different rose species, including Rosa canina, R. corymbifera, R. micrantha, R. rubiginosa, and R. rugosa. These species had different morphological characteristics, with R. rugosa showing higher size of flower petals and higher weight of hips. The highest vitamin C content was found in hip extracts of R. rubiginosa and R. rugosa, which also showed the highest carotenoid amount. R. corymbifera showed the highest phenolic content. No significant antimicrobial activity of extracts containing phenolic compounds against different indicator strains could be detected. Cell monolayer integrity was not affected by treatments with the above-mentioned extracts of R. canina, R. micrantha, and R. rugosa at different concentrations for up to 24 h, while those of R. rubiginosa and R. corymbifera affected intestinal permeability at the highest concentration tested. The partial least squares regression analysis generated a predictive model correlating phenolic compounds with cell monolayer integrity, suggesting a relevant role for catechin, quercitrin, and p-coumaric acid. In conclusion, this study highlights how rose hips belonging to different species can have a diverse phenolic profile, differently influencing intestinal monolayer integrity.

Background and Objectives: Acute and chronic injuries are frequent in volleyball. Biomechanics of sport-specific tasks can influence the risk of injury, which is also related to specific court positions. We investigated posture at raster-stereography, balance, and dynamic tasks using inertial motion units to find differences between roles, which can be predictive of a higher risk of injury. Materials and Methods: We cross-sectionally evaluated amateur volleyball athletes. Participants were divided into roles as outside hitters, setters, middle blockers, and opposite hitters. We excluded the “libero” position from our analysis. Results: Sixteen players were included in the analysis. A statistically significant difference was found in left lower limb stiffness among the outside hitter and setter groups. Conclusions: Differences in stiffness might be related to the different training and the different abilities among the two groups. Raster-stereography is extending its indications and should be implemented for non-invasive postural analysis. The use of inertial motion units provides objective measurements of variables that could go unrecognized within a clinical evaluation; its use should be considered in injury preventive programs.

This study introduces a novel hybrid forecasting model for wind power generation. It integrates Artificial Neural Networks, data clustering, and Particle Swarm Optimization algorithms. The methodology employs a systematic framework: initial clustering of weather data via the k-means algorithm, followed by Pearson’s analysis to pinpoint pivotal elements in each cluster. Subsequently, a Multi-Layer Perceptron Artificial Neural Network undergoes training with a Particle Swarm Optimization algorithm, enhancing convergence and minimizing prediction discrepancies. An important focus of this study is to streamline wind forecasting. By judiciously utilizing only sixteen observation points near a wind farm plant, in contrast to the complex global numerical weather prediction systems employed by the European Center Medium Weather Forecast, which rely on thousands of data points, this approach not only enhances forecast accuracy but also significantly simplifies the modeling process. Validation is performed using data from the Italian National Meteorological Centre. Comparative assessments against both a persistence model and actual wind farm data from Southern Italy substantiate the superior performance of the proposed hybrid model. Specifically, the clustered Particle Swarm Optimization-Artificial Neural Network-Wind Forecasting Method demonstrates a noteworthy improvement, with a reduction in mean absolute percentage error of up to 59.47% and a decrease in root mean square error of up to 52.27% when compared to the persistence model.

Abstract Background In older and multimorbid patients, chronic conditions may affect the prognostic validity of computed tomography (CT) findings in COVID-19. This study aims at assessing to which extent CT findings have prognostic implications in COVID-19 older patients. Methods Hospitalized COVID-19 patients aged 60 years or more enrolled in the multicenter, observational and longitudinal GeroCovid study who underwent chest CT were included. Patients were stratified by tertiles of age and pneumonia severity to compare CT findings. Hierarchical clustering based on CT findings was performed to identify CT-related classificatory constructs, if any. The hazard ratio (HR) of mortality was calculated for individual CT findings and for clusters, after adjusting for potential confounders. Results 380 hospitalized COVID-19 patients, with a mean age of 78 (SD:9) years, underwent chest CT scan. Ground glass opacity (GGO), consolidation, and pleural effusion were the three most common CT findings, with GGO prevalence decreasing from younger to older patients and pleural effusion increasing. More severe the pneumonia more prevalent were GGO, consolidation and pleural effusion. HR of mortality was 1.94 (95%CI 1.24–3.06) for pleural effusion and 13 (95%CI 6.41–27) for cluster with a low prevalence of GGO and a high prevalence of pleural effusion (“LH”), respectively. Out of the three CT based clusters, “LH” was the only independent predictor in the multivariable model. Conclusions Pleural effusion qualifies as a distinctive prognostic marker in older COVID-19 patients. Research is needed to verify whether pleural effusion reflects COVID-19 severity or a coexisting chronic condition making the patient at special risk of death. Trial registration ClinicalTrials.gov: NCT04379440

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.