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Abstract In the past decade, organic mixed ion-electron conductors have been successfully adopted in innovative bioelectronic, neuromorphic, and electro-optical technologies, as well as in multiple energy harvesting and printed electronics applications. However, despite the intense research efforts devoted to these materials, organic mixed conductors have not yet found application in electronic/photonic devices operating in key regions of the electromagnetic spectrum, such as the microwave (>5 GHz) and terahertz (0.1-10 THz) ranges. A possible reason for this technological gap is the widespread notion that organic electronic materials are unsuitable for high-frequency applications. In this work, we demonstrate for the first time the utility of high-performance polymer mixed conductors as electro-active tuning layers in reconfigurable terahertz metasurfaces, achieving modulation performances comparable with state-of-the-art inorganic and 2D semiconductors. Through time-domain terahertz spectroscopy, we show that the large conductivity modulations of these polymers, until now probed only at very low frequencies, are effectively preserved in the terahertz range, leading to optimal metadevice reconfigurability. Finally, we leverage the unique processability of organic materials to develop fully direct-written electrically tuneable metasurfaces onto both rigid and flexible substrates, opening new opportunities for the mass-scale realization of flexible and light-weight terahertz optics with unique mechanical characteristics and environmental footprint.

Abstract We investigated the relationship between the degree of alveolarization and ultrasound-assessed lung aeration in a validated preterm rabbit model of experimental bronchopulmonary dysplasia (BPD). Lung ultrasound findings were heterogeneously abnormal and consisted of zones with interstitial, interstitial-alveolar or consolidated patterns. The median radial alveolar count was 10.1 [8.4–11.5], 7.8 [6.1–9] and 7.3 [1.8–10.1] in rabbits with interstitial, interstitial-alveolar or consolidated ultrasound pattern, respectively (overall p = 0.036). Alveolar count and lung ultrasound score were significantly correlated (ρ = − 0.044 (95%CI: − 1; − 0.143), p = 0.009; τ-b = − 0.362 (95%CI: − 0.6; − 0.1), p = 0.017).

Abstract Background Juvenile sudden cardiac death (SCD) remains unexplained in approximately 40% of cases, leading to a significant emotional burden for the victims’ families and society. Comprehensive investigations are essential to uncover its elusive causes and enable cascade family screening. This study aimed to enhance the identification of likely causative variants in juvenile SCD cases (age ≤ 50 years), particularly when autopsy findings are inconclusive. Results Autopsy revealed diagnostic structural abnormalities in 46%, non-diagnostic findings in 23%, and structurally normal hearts in 31% of cases. Whole-exome sequencing (WES), refined through a customized virtual gene panel was used to identify variants. These variants were then evaluated using a multidisciplinary approach and a structured variant prioritization scheme. Our extended approach identified likely causative variants in 69% of cases, outperforming the diagnostic yields of both the cardio panel and standard susceptibility gene analysis (50% and 16%, respectively). The extended cardio panel achieved an 80% diagnostic yield in cases with structurally normal hearts, demonstrating its efficacy in challenging scenarios. Notably, half of the positive cases harboured a single variant, while the remainder had two or more variants. Conclusion This study highlights the efficacy of a multidisciplinary approach employing WES and a tailored virtual gene panel to elucidate the aetiology of juvenile SCD. The findings support the expansion of genetic testing using tailored gene panels and prioritization schemes as part of routine autopsy evaluations to improve the identification of causative variants and potentially facilitate early diagnosis in first-degree relatives.

ABSTRACT Objective: To assess whether post-discharge telemonitoring reduces hospital readmission in patients participating in the diabetes care program. Methods: This retrospective cohort study was conducted from June 2021 to December 2022 and included patients who were enrolled in the Diabetes Program under a hyperglycemia treatment protocol and eligible for post-discharge telemonitoring. The variables included age, sex, diagnosis, hospital stay, LACE Score, and readmission rate. Results: Among 165 patients who underwent telemonitoring, significant differences emerged in hospital readmission rates between those with and without telemonitoring (p=0.015), with a 15.4% lower readmission rate in the telemonitoring group (95%CI= 3.0-27.9%). Subgroup analyses revealed higher readmission rates in men without telemonitoring (15.2% difference; 95%CI= 0.4-30.0%; p=0.045), and in age groups ≤60 and ≥75 years without telemonitoring (24.2% difference; 95%CI= 4.5-43.9%; p=0.016 for ≤60 years; 37.1% difference; 95%CI= 9.9% to 64.2%; p=0.007 for ≥75 years). Additionally, patients with prolonged hospital stays (>7 days) without telemonitoring had higher readmission rates (19.5% difference; 95%CI= 4.5%-34.5%; p=0.011). Conclusion: This study suggests that post-discharge telemonitoring can effectively lower hospital readmission rates in diabetes management programs, potentially offering improved health outcomes, cost savings, and enhanced healthcare delivery to patients.

BackgroundChildhood obesity has become a significant public health concern over the past 2 decades, posing multifactorial challenges, including modifiable factors like dietary habits, physical activity, screen time, and sleeping habits. Prevention efforts require a comprehensive approach comprising educational interventions, collaboration among multidisciplinary teams, and community engagement. Since schools play a central role in children's lives, they are the ideal setting for promoting healthy habits. ObjectiveThe LIVELY (Multidimensional School-Based and Family-Involved Interventions to Promote a Healthy and Sustainable Lifestyle) study will assess the prevalence of overweight and obesity in primary school children and identify contributing factors within families. Additionally, it aims to implement and evaluate a multidimensional, multidisciplinary intervention to foster a sustainable and healthy lifestyle, ultimately working toward preventing obesity in school-aged children. MethodsDuring the school year, each class will be individually involved in a multidimensional educational intervention covering the topics of healthy, sustainable nutrition and lifestyle. Children will also participate in a multimedia lab where they will create an animated cartoon. The lectures will engage them through various methods, including direct instructions, games, and drawing activities, to stimulate and enhance their learning and involvement. ResultsData collection began in October 2023 and will last until the end of October 2024. A sample of 227 children from 14 classes was included in the study. The mean age was 8.9 (SD 1.2) years, and 48% (n=110) were males. Among the overall sample, 18.1% (n=41; 95% CI 13.7%-23.7%) were overweight, while 5.3% (n=12; 95% CI 3%-9%) had obesity. Males had a higher prevalence of obesity than females (9.1%, n=10 vs 1.7%, n=3, P=.03, respectively). Otherwise, the prevalence of central obesity was similar between the two (P=.329). Data analysis and the presentation of the complete results will be available after the end of 2024. ConclusionsThe study could lead to the structuring of an educational intervention model in school settings aimed at preventing childhood obesity. Moreover, it could help raise awareness of childhood obesity and help prevent this public health issue. Trial RegistrationClinicalTrials.gov NCT05966051; https://clinicaltrials.gov/study/NCT05966051 International Registered Report Identifier (IRRID)DERR1-10.2196/57509

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is linked to high mortality, primarily through an intense inflammatory response. Diacerein has emerged as a potential therapy for COVID-19 due to its potential impact in decreasing the inflammasome activation and coronavirus replication. This study aims to explore diacerein’s influence in inhibiting both viral replication and the inflammatory response after SARS-CoV-2 infection.MethodsHuman peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteers and infected in vitro with SARS-CoV-2. Additionally, we carried out a pilot randomized, double-blind, placebo-controlled study with 14 participants allocated to diacerein (n = 7) or placebo (n = 7) therapies every 12 h for 10 days. The primary endpoint was change in plasma markers of inflammasome activation (NLRP3, caspase-1, and gasdermin-D).ResultsIn vitro protocols have shown that rhein, diacerein’s primary metabolite, decreased IL-1β secretion caused by SARS-CoV-2 infection in human PBMCs (p < 0.05), and suppressed viral replication when administered either before or after the virus incubation (p < 0.05). This later effect was, at least partially, attributed to its inhibitory effect on 3-chymotrypsin-like protease (SARS-CoV-2 3CLpro) and papain-like protease in the SARS-CoV-2 (SARS-CoV-2 PLpro) virus and in the phosphorylation of proteins related cytoskeleton network (p < 0.05). Diacerein-treated COVID-19 patients presented a smaller area under the curve for NLRP3, caspase-1 and GSDM-D measured on days 2, 5, and 10 after hospitalization compared to those receiving a placebo (p < 0.05).ConclusionThe indicated mechanisms of action of diacerein/rhein can reduce viral replication and mitigate the inflammatory response related to SARS-CoV-2. These findings are preliminary and require confirmation in clinical trials.

BackgroundDespite the extensive use of antibiotics and the growing challenge of antimicrobial resistance, there has been a lack of substantial initiatives aimed at diminishing the prevalence of infections in nursing homes and enhancing the detection of urinary tract infections (UTIs). ObjectiveThis study aims to systematize and enhance efforts to prevent health care–associated infections, mainly UTIs and reduce antibiotic inappropriateness by implementing a multifaceted intervention targeting health care professionals in nursing homes. MethodsA before-and-after intervention study carried out in a minimum of 10 nursing homes in each of the 8 European participating countries (Denmark, Greece, Hungary, Lithuania, Poland, Slovakia, Slovenia, and Spain). A team of 4 professionals consisting of nurses, doctors, health care assistants, or health care helpers are actively involved in each nursing home. Over the initial 3-month period, professionals in each nursing home are registering information on UTIs as well as infection and prevention control measures by means of the Audit Project Odense method. The audit will be repeated after implementing a multifaceted intervention. The intervention will consist of feedback and discussion of the results from the first registration, training on the implementation of infection and prevention control techniques provided by experts, appropriateness of the diagnostic approach and antibiotic prescribing for UTIs, and provision of information materials on infection control and antimicrobial stewardship targeted to staff, residents, and relatives. We will compare the pre- and postintervention audit results using chi-square test for prescription appropriateness and Student t test for implemented hygiene elements. ResultsA total of 109 nursing homes have participated in the pilot study and the first registration audit. The results of the first audit registration are expected to be published in autumn of 2024. The final results will be published by the end of 2025. ConclusionsThis is a European Union–funded project aimed at contributing to the battle against antimicrobial resistance through improvement of the quality of management of common infections based on evidence-based interventions tailored to the nursing home setting and a diverse range of professionals. We expect the intervention to result in a significant increase in the number of hygiene activities implemented by health care providers and residents. Additionally, we anticipate a marked reduction in the number of inappropriately managed UTIs, as well as a substantial decrease in the overall incidence of infections following the intervention. International Registered Report Identifier (IRRID)DERR1-10.2196/60099

We detected Mayaro virus (MAYV) in 3.4% (28/822) of febrile patients tested during 2018–2021 from Roraima State, Brazil. We also isolated MAYV strains and confirmed that these cases were caused by genotype D. Improved surveillance is needed to better determine the burden of MAYV in the Amazon Region.

The return-to-play process' characteristics can vary by injury and sport type but are typically composed of phases of different durations, training targets, and intensities that gradually increase the physiological and mechanical load. In team sports, contact drills are a necessary part of the last phases of this process, and they should be planned using the optimal mechanical load. The present study investigated the external load and kinetic recovery in U19 soccer players performing 6vs6 and 3vs3 small-sided games. A global positioning system (GPS) measured external load metrics. The rate of perceived exertion (RPE) was registered at the end. Total quality of recovery (TQR) was collected at the beginning of the training session and after 24 h. Moreover, before and after the small-sided games (SSGs) and at 24 h, delayed-onset muscle soreness (DOMS) of the legs, sprinting time, and vertical jump height (CMJ) were collected. 6vs6 presented higher values in total distance low-, moderate-, high, and very-high-speed distance, and maximum speed (p < 0.05). However, 3vs3 showed higher number of sprints, acceleration, and deceleration at different intensities. Furthermore, no difference was shown in RPE. The effect of fatigue on sprint seems greater for 6vs6, showing an impairment persistent at 24 h (p < 0.05). Moreover, CMJ height was impaired after 6vs6 and at 24 h (p < 0.05) but did not change after 3vs3 (p > 0.05). DOMS values after SSGs and at 24 h were higher than baseline for both conditions (p < 0.05), while TQR decreased at 24 h in both conditions (p < 0.05). Based on our results, it seems that 6vs6, leading to a greater high-speed running distance, might cause a training load that needs more time to recover. This point may be crucial in a return-to-play process, especially when hamstring muscles are involved.

Abstract Background The endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphisms, able to affect eNOS activity, were associated with cardiometabolic risk features and prevalence of coronary artery disease (CAD). Aim To investigate the association of eNOS Glu298Asp gene polymorphism, cardiometabolic profile, obstructive CAD and inducible myocardial ischemia in patients with suspected stable CAD. Methods A total of 506 patients (314 males; mean age 62 ± 9 years) referred for suspected CAD was enrolled. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible myocardial ischemia and 436 patients underwent non-invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD. Clinical characteristics and blood samples were collected for each patient. Results In the whole population, 49.6% of patients were homozygous for the Glu298 genotype (Glu/Glu), 40.9% heterozygotes (Glu/Asp) and 9.5% homozygous for the 298Asp genotype (Asp/Asp). Obstructive CAD was documented in 178/436 (40.8%) patients undergoing coronary angiography while myocardial ischemia in 160/325 (49.2%) patients undergoing stress testing. Patients with eNOS Asp genotype (Glu/Asp + Asp/Asp) had no significant differences in clinical risk factors and in circulating markers. Independent predictors of obstructive CAD were age, gender, obesity, and low HDL-C. Independent predictors of myocardial ischemia were gender, obesity, low HDL-C and Asp genotype. In the subpopulation in which both stress tests and coronary angiography were performed, the Asp genotype remained associated with increased myocardial ischemia risk after adjustment for obstructive CAD. Conclusion In this population, low-HDL cholesterol was the only cardiometabolic risk determinant of obstructive CAD. The eNOS Glu298Asp gene polymorphism was significantly associated with inducible myocardial ischemia independently of other risk factors and presence of obstructive CAD.

Abstract Pancreatic cancer, ranking as the third factor in cancer‐related deaths, necessitates enhanced diagnostic measures through early detection. In response, SiMoT‐Single‐molecule with a large Transistor multiplexing array, achieving a Technology Readiness Level of 5, is proposed for a timely identification of pancreatic cancer precursor cysts and is benchmarked against the commercially available chemiluminescent immunoassay SIMOA (Single molecule array) SP‐X System. A cohort of 39 samples, comprising 33 cyst fluids and 6 blood plasma specimens, undergoes detailed examination with both technologies. The SiMoT array targets oncoproteins MUC1 and CD55, and oncogene KRAS, while the SIMOA SP‐X planar technology exclusively focuses on MUC1 and CD55. Employing Principal Component Analysis (PCA) for multivariate data processing, the SiMoT array demonstrates effective discrimination of malignant/pre‐invasive high‐grade or potentially malignant low‐grade pancreatic cysts from benign non‐mucinous cysts. Conversely, PCA analysis applied to SIMOA assay reveals less effective differentiation ability among the three cyst classes. Notably, SiMoT unique capability of concurrently analyzing protein and genetic markers with the threshold of one single molecule in 0.1 mL positions it as a comprehensive and reliable diagnostic tool. The electronic response generated by the SiMoT array facilitates direct digital data communication, suggesting potential applications in the development of field‐deployable liquid biopsy.

Notre article va essayer de mettre à profit les études sur le populisme à travers la valorisation du rôle des médias et des stratégies discursives utilisées par le candidat du parti Reconquête ! Éric Zemmour. Plus particulièrement, nous avons mis en lumière la valeur que l’Histoire de France joue dans la perspective subjective et personnelle du candidat. En parcourant les allocutions de sa campagne électorale pour l’élection présidentielle de 2022, nous avons détecté des postures énonciatives et des stratégies argumentatives permettant au porte‑parole de Reconquête ! de créer son « égo‑histoire ». Ainsi, le discours politique d’Éric Zemmour se construit de manière régulière entre l’Histoire de France/des Français et son histoire personnelle : Éric Zemmour fait miroiter les étapes de sa vie privée et professionnelle (fils de parents « migrants », écolier, banlieusard, journaliste, essayiste, homme politique) dans les grandes étapes de l’histoire française.

Dual-energy CT (DECT) is an innovative technology that is increasingly widespread in clinical practice. DECT allows for tissue characterization beyond that of conventional CT as imaging is performed using different energy spectra that can help differentiate tissues based on their specific attenuation properties at different X-ray energies. The most employed post-processing applications of DECT include virtual monoenergetic images (VMIs), iodine density maps, virtual non-contrast images (VNC), and virtual non-calcium (VNCa) for bone marrow edema (BME) detection. The diverse array of images obtained through DECT acquisitions offers numerous benefits, including enhanced lesion detection and characterization, precise determination of material composition, decreased iodine dose, and reduced artifacts. These versatile applications play an increasingly significant role in tumor assessment and oncologic imaging, encompassing the diagnosis of primary tumors, local and metastatic staging, post-therapy evaluation, and complication management. This article provides a comprehensive review of the principal applications and post-processing techniques of DECT, with a specific focus on its utility in managing oncologic patients.

Introduction: The hemogram and hemogram-derivative ratios (HDRs) are becoming markers of the severity and mortality of COVID-19. We evaluated the hemograms and serial weekly HDRs [neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), neutrophil-platelet ratio (NPR) and systemic immune-inflammatory index (SII)] in the survivors and non-survivors of COVID-19. Methods: We retrospectively reviewed the medical notes and serial hemograms of real-time reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 adults hospitalized from April 2020 to March 2021 from the time of diagnosis to the 3rd week of diagnosis. Results: Of the 320 adults, 257 (80.3%) were survivors and had a lower mean age than the non-survivors (57.73 vs. 64.65 years, p < 0.001). At diagnosis, the non-survivors had lower hematocrit (p = 0.021), and lymphocyte (p = 0.002) and basophil (p = 0.049) counts and the hematocrit showed a p-value (Is this what you meant???) of 0.021); higher NLR (p < 0.001), PLR (p = 0.047), NPR (p = 0.022) and SII (p = 0.022). Using general linear models, the survivors and non-survivors showed significant variations with weekly lymphocyte count (p < 0.001), neutrophil count (p = 0.005), NLR (p = 0.009), MLR (p = 0.010) and PLR (p = 0.035). All HDRs remained higher in the non-survivors in the 2nd week and 3rd week of diagnosis and the HDRs were higher in the intubated patients than in the non-intubated patients. The NLR and SII were more efficient predictors of mortality in COVID-19 patients. Conclusions: This study shows that serial lymphocyte and neutrophil counts, NLR, PLR, MLR, NPR and SII could serve as good and easily accessible markers of severity and predictors of outcomes in COVID-19 patients and should be used for the monitoring of treatment response.

Abstract This paper is a literature review of the intersection field between Artificial Intelligence (AI) and Customer Experience (CX). We analyzed and synthesized the most recent and prominent literature on the subject, providing an overview of the state of the art, through articles found in the Scopus database. Among the main findings, it is noteworthy that this intersection appears as an interdisciplinary topic of interest in the fields of Computer Science, Business and Management, and Engineering. Additionally, studies often examine conversational agents such as chatbots and voicebots, as well as machine learning prediction models and recommendation systems as a way to improve the Customer Experience. The most common sectors in the review are tourism, banking and e-commerce. Other segments and technologies appear less and may be underrepresented, thus a scope for future research agenda. Despite the existing literature, it is observed that there is still substantial space for expansion and exploration, especially considering the emergence of new generative Artificial Intelligence models.

In this work, naphthalenediimide (NDI) derivatives are widely studied for their semiconducting properties and the influence of the side-chain length on the crystal packing is reported, along with the thermal properties of three core-chlorinated NDIs with different fluoroalkyl side-chain lengths (CF3-NDI, C3F7-NDI and C4F9-NDI). The introduction of fluorinated substituents at the imide nitrogen and addition of strong electron-withdrawing groups at the NDI core are used to improve the NDI derivatives air stability. The new compound, CF3-NDI, was deeply analyzed and compared to the well-known C3F7-NDI and C4F9-NDI, leading to the discovery and solution of two different crystal phases, form α and solvate form, and a solid solution of CF3-NDI and CF3-NDI-OH, formed by the decomposition in DMSO.

IntroductionMaster athletes are examples of successful aging. It is not clear whether it is the competitive-oriented training or just the amount of total regular exercise that reduces the age-related decline in physiological functions. We aimed to compare health-related parameters in competitive (C) and physically active older adults (A) that performed the same weekly physical activity (PA) amount.MethodsSeventeen C and 17 A were matched for age (8 and 9 male participants under and over 70 years old respectively, for both groups) and weekly PA amount (GPAQ). Body composition, leg and arm maximal strength, balance and reaction time were measured; moreover, leg and arm exercise efficiency, estimated VO2max, and VO2/HR relationships were evaluated. Perception of life and sleep quality was also assessed through specific questionnaires (SF-36 and PSQI). The effect of group (C vs. A), age (U70 vs. O70) and their interaction was examined through a Two-Way ANOVA test.ResultsC dedicated more time to vigorous PA compared to A (p = 0.03), while less to moderate daily work (p 0.05), while balance reduced in A O70. Estimated VO2max was higher for C in leg cycling (p = 0.05) and remained constant across ages (all p > 0.05). VO2/HR relationship, life and sleep quality did not differ for groups and ages.ConclusionsRegular physical exercise of about 6,000 METs/week seems to have a beneficial effect on health-related parameters, both in non-structured and competitive PA, when compared to sedentary behaviour. However, the older adults engaged in competitive training exhibit further advantages: better body composition, higher arm and leg muscle strength, and higher leg VO2max. This study highlights the importance of encouraging active lifestyles for maintaining long-term health, high levels of life quality perception and reducing age-related decline. However, vigorous training suitability needs to be verified by a team of PA specialists.

BackgroundAdequate energy and nutrient intakes in athletes contribute to optimal performance and recovery, decrease the risk of injury, and help preserve athletes’ health. The Mediterranean diet (MD) is considered suitable for covering the nutritional needs of athletes, while contributing to improve eating habits. The aim of the present study was to investigate the energy and nutrient intakes of semi-professional female soccer players and their adherence to the MD, during the competitive season.MethodsA cross-sectional observational study was conducted on twenty-three female soccer players, who were invited to fill in a 3-day food diary twice, one month apart, to assess their energy and nutrient intakes and a validated questionnaire (MEDI-LITE) to evaluate their adherence to MD. Exercise energy expenditure during three training and match-play days was monitored by GPS.ResultsOn average, the participants consumed 1,981 kcal/day, with 44% of their energy deriving from carbohydrates, 21% from protein, and 34% from fat; the mean MD adherence score was 10.1 ± 1.8, corresponding to a good MD adherence. A substantial percentage of athletes were at risk of insufficient nutrient intakes for vitamin D (100%), iodine (87%), potassium (87%), vitamin E (39%), iron and zinc (17 and 30%, respectively).ConclusionThe evaluation of the dietary intake in female soccer players showed energy deficiency in relation to training level, mainly due to the insufficient intake of carbohydrates, and micronutrient deficiencies. The technical staff should promote adequate consumption of starchy foods in female athletes and emphasize the importance of a proper distribution of energy intake among different eating occasions, including snacks. Periodic monitoring of the nutritional status of micronutrients (vitamin D and some minerals) could help reduce deficiency risk. Over all, nutrition education to improve eating habits of athletes seems worthy of attention, in order to preserve athletes’ health and performance.

A critical step of pre-mRNA splicing is the recruitment of U2 snRNP to the branch point sequence of an intron. U2 snRNP conformation changes extensively during branch helix formation, and several RNA-dependent ATPases are implicated in the process. However, the molecular mechanisms involved remain to be fully dissected. We took advantage of the differential nucleotide triphosphates requirements for DExD/H-box enzymes to probe their contributions to in vitro spliceosome assembly. Both ATP and GTP hydrolysis support the formation of A-complex, indicating the activity of a DEAH-enzyme because DEAD-enzymes are selective for ATP. We immunodepleted DHX15 to assess its involvement, and although splicing efficiency decreases with reduced DHX15, A-complex accumulation incongruently increases. DHX15 depletion also results in the persistence of the atypical ATP-independent interaction between U2 snRNP and a minimal substrate that is otherwise destabilized in the presence of either ATP or GTP. These results lead us to hypothesize that DHX15 plays a quality control function in U2 snRNP's engagement with an intron. In efforts to identify the RNA target of DHX15, we determined that an extended polypyrimidine tract is not necessary for disruption of the atypical interaction between U2 snRNP and the minimal substrate. We also examined U2 snRNA by RNase H digestion and identified nucleotides in the branch binding region that become accessible with both ATP and GTP hydrolysis, again implicating a DEAH-enzyme. Together, our results demonstrate that multiple ATP-dependent rearrangements are likely involved in U2 snRNP addition to the spliceosome and that DHX15 may have an expanded role in maintaining splicing fidelity.

SARS-CoV-2 can induce vascular dysfunction and thrombotic events in patients with severe COVID-19; however, the cellular and molecular mechanisms behind these effects remain largely unknown. In this study, we used a combination of experimental and in silico approaches to investigate the role of PC in vascular and thrombotic events in COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the publicly available Gene Expression Omnibus (GEO) repository. In addition, HUVECs were treated with inactive protein C before exposure to SARS-CoV-2 infection or a severe COVID-19 serum. An RT-qPCR array containing 84 related genes was used, and the candidate genes obtained were evaluated. Activated protein C levels were measured using an ELISA kit. We identified at the single-cell level the expression of several pro-inflammatory and pro-coagulation genes in endothelial cells from the patients with COVID-19. Furthermore, we demonstrated that exposure to SARS-CoV-2 promoted transcriptional changes in HUVECs that were partly reversed by the activated protein C pretreatment. We also observed that the serum of severe COVID-19 had a significant amount of activated protein C that could protect endothelial cells from serum-induced activation. In conclusion, activated protein C protects endothelial cells from pro-inflammatory and pro-coagulant effects during exposure to the SARS-CoV-2 virus.

RESUMO Descrever a elaboração de uma estratégia educativa com potencial de criar um espaço de diálogo entre adolescentes, profissionais da saúde e educadores. O trabalho foi realizado em quatro escolas públicas do município de Belo Horizonte (MG), Participaram 67 alunos matriculados no oitavo ano do Ensino Fundamental, quatro professores e 6 profissionais de saúde de unidades básicas próximas às escolas. Na primeira etapa, os alunos responderam a um questionário semiestruturado e, a seguir, participaram de oficinas psicossociais. O estudo chama atenção para a potencialidade das estratégias educativas pautadas no diálogo, no vínculo, na escuta e no acolhimento, para que os adolescentes encontrem espaços de conversação que possibilitem a construção do conhecimento sobre sua saúde sexual, afetiva e reprodutiva, garantindo, assim, que eles possam exercer a sexualidade de maneira mais segura, responsável e consciente.

Abstract Background Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. Methods The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science – comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. Discussion Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines.

This study investigated how a standard could become reality-based in a workplace where certain types of deviations are not permitted, such as a radiopharmaceutical production unit. Compliance with standards is necessary to ensure the safety of individuals who manufacture such substances as well as the security of patients receiving treatment. In this qualitative case study, an ergonomic analysis of work (also known as activity analysis) was performed, with noncompliance recorded in internal audits as a starting point: the lack of double-checking in radiopharmaceutical synthesis cassette assembly. Field observations and self-confrontation interviews with workers from a production unit were conducted to analyze the activities. Although a double-check did not occur, the radiopharmaceutical synthesis operator apparently developed another risk control strategy, focusing his attention to the equipment assembly details, which necessitated continuous control and verification actions to ensure that there were no problems at this stage of production. A multilevel approach was used to demonstrate how the safety and quality of production processes based on standard compliance only become effective and adherent to the activity after resolving various conflicts at work, including control systems (external and internal audits), work collectives, the contradiction of the activity itself, and the discussion of singular situations arising daily. This study contributes to the discussion on workplace safety considering standardization and advances the discussion on changing perspectives regarding rule compliance.

The present volume Immersions and Dives: From the Environment to Virtual Reality of the journal AN-ICON: Studies in Environmental Images is divided into two issues, each one dedicated to a specific thematic analysis, originated by the same conceptual core. The volume reflects on the concept of immersivity, which has become increasingly prominent in many different fields, including contemporary art. The constant reference to immersive experience is redefining the boundaries of artistic practice and fruition, highlighting the complex relationships between art, environments, and human perception.

Objective Protein–energy malnutrition and the subsequent muscle wasting (sarcopenia) are common ageing complications. It is knowing to be also associated with dementia. Our programme will test the cytoprotective functions of vitamin E combined with the cortisol-lowering effect of chocolate polyphenols (PP), in combination with muscle anabolic effect of adequate dietary protein intake and physical exercise to prevent the age-dependent decline of muscle mass and its key underpinning mechanisms including mitochondrial function, and nutrient metabolism in muscle in the elderly.Methods and analysis In 2020, a 6-month double-blind randomised controlled trial in 75 predementia older people was launched to prevent muscle mass loss, in respond to the ‘Joint Programming Initiative A healthy diet for a healthy life’. In the run-in phase, participants will be stabilised on a protein-rich diet (0.9–1.0 g protein/kg ideal body weight/day) and physical exercise programme (high-intensity interval training specifically developed for these subjects). Subsequently, they will be randomised into three groups (1:1:1). The study arms will have a similar isocaloric diet and follow a similar physical exercise programme. Control group (n=25) will maintain the baseline diet; intervention groups will consume either 30 g/day of dark chocolate containing 500 mg total PP (corresponding to 60 mg epicatechin) and 100 mg vitamin E (as RRR-alpha-tocopherol) (n=25); or the high polyphenol chocolate without additional vitamin E (n=25). Muscle mass will be the primary endpoint. Other outcomes are neurocognitive status and previously identified biomolecular indices of frailty in predementia patients. Muscle biopsies will be collected to assess myocyte contraction and mitochondrial metabolism. Blood and plasma samples will be analysed for laboratory endpoints including nutrition metabolism and omics.Ethics and dissemination All the ethical and regulatory approvals have been obtained by the ethical committees of the Azienda Ospedaliera Universitaria Integrata of Verona with respect to scientific content and compliance with applicable research and human subjects’ regulation. Given the broader interest of the society toward undernutrition in the elderly, we identify four main target audiences for our research activity: national and local health systems, both internal and external to the project; targeted population (the elderly); general public; and academia. These activities include scientific workshops, public health awareness campaigns, project dedicated website and publication is scientific peer-review journals.Trial registration number NCT05343611.

The Coping Power Program is an evidence-based intervention for children identified to be at risk for developing externalizing behavioral problems. The Coping Power Program has been adapted to universally prevent behavioral problems in school-aged children. This study sought to test the efficacy of this adaptation, the Coping Power Universal program, on preschoolers' behavioral difficulties and pre-academic skills. Teachers delivered the intervention in their classes. The study included a sample of Italian children (N = 250, 125 boys) with a mean age of 4.50 years (SD = 0.50) at the beginning of the study. Classrooms of these children were randomly assigned to receive either the intervention or the Italian preschool standard curriculum. Measures included a questionnaire and objective and standardized measures for numerical intelligence and metaphonological skills delivered by a psychologist to the preschoolers. Classes in which teachers applied the Coping Power Universal program showed lower problematic behaviors and higher pre-academic skills than those in which teachers followed the standard curriculum only. Although further studies are still needed, the current findings showed that the Coping Power Universal program can be adapted for preschoolers with good results. Implications for practice, methodological limitations, and directions for future research are reviewed.