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Ensuring equity in education is a goal for sustainable development. Among the factors that hinder equity, socioeconomic status (SES) has the highest impact on learning Mathematics. This paper addresses the issue of equity at the secondary school level by proposing an approach based on adopting automatic formative assessment (AFA). Carefully designed mathematical activities with interactive feedback were experimented with a sample of 299 students of grade 8 for a school year. A control group of 257 students learned the same topics using traditional methodologies. Part of the sample belonged to low SES. The learning achievement was assessed through pre-and post-tests to understand if the adoption of AFA impacted learning and whether the results depended on the students' SES. The results show a positive effect of the experimentation (effect size: 0.42). Moreover, the effect size of the experimentation restricted to the low-SES group is high (0.77). In the treatment group, the results do not depend on SES, while in the control group, they do, suggesting that AFA is an equitable approach while traditional instruction risks perpetuating inequalities.

Gene circuits allow cells to carry out complex functions such as the precise regulation of biological metabolic processes. In this study, we combined, in the yeast S. cerevisiae, genetic regulatory elements with the enzymatic reactions of the human CYP2C9 and its redox partner CPR on luciferin substrates and diclofenac. S. cerevisiae cells were permeabilized and used as enzyme bags in order to host these metabolic reactions. We engineered three different (genetic)-enzymatic basic Boolean gates (YES, NOT, and N-IMPLY). In the YES and N-IMPLY gates, human CYP2C9 was expressed under the galactose-inducible GAL1 promoter. The carbon monoxide releasing molecule CORM-401 was used as an input in the NOT and N-IMPLY gates to impair CYP2C9 activity through inhibition of the Fe+2- heme prosthetic group in the active site of the human enzyme. Our study provides a new approach in designing synthetic bio-circuits and optimizing experimental conditions to favor the heterologous expression of human drug metabolic enzymes over their endogenous counterparts. This new approach will help study precise metabolic attributes of human P450s.

SUPPORT TEACHERS AND INCLUSIVE EDUCATION: A STUDY ON ATTITUDES, SELF-EFFICACY, SELF-ASSESSMENT OF KNOWLEDGE AND SKILLS, AND BEHAVIORS IN THE CLASSROOM Abstract This exploratory study analyzes attitudes toward inclusion, self-efficacy in implementing inclusive education, knowledge, and skills for managing pupils with special needs, and behaviors implemented for school inclusion in a sample of 391 support teachers without specialization. The results highlight favorable attitudes towards inclusion but reveal the persistence of beliefs that justify the separation of students with special needs. Teachers report a good level of self-efficacy in inclusion but perceive themselves to be less competent in managing classroom dynamics. Many teachers, while perceiving themselves as skilled in managing relationships with colleagues and planning, perceive gaps in the knowledge and skills needed to implement effective inclusive education. Especially self-efficacy in implementing inclusive education appears to be related to knowledge, skills, and inclusive behaviors. This research suggests the need to strengthen the training of support teachers and promote inclusive behaviors to ensure effective inclusion.

Laccase is a multicopper oxidase enzyme that oxidizes a variety of substrates, including polyphenols and polycyclic aromatic hydrocarbons (PAHs). It catalyzes the four-electron reduction of molecular oxygen that results in the production of water as a by-product. Thus, laccase can play an important role in environmental care. Previously, we have successfully expressed Trametes trogii laccase (TtLcc1) in the yeast Saccharomyces cerevisiae. In this work, we have expressed in yeast another laccase, LacA from Trametes sp. AH28-2, and tested its function on PAHs. Yeast cells engineered to produce the two laccases performed efficient PAH degradation. Both TtLcc1 and LacA led to the construction of spatiotemporal fluorescence-pulse generators when combined with a benzoate/salicylate yeast biosensor in a two-population system. Moreover, laccases returned a visual output signal in yeast synthetic circuits—upon reacting with ABTS (2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid)). Thus, in S. cerevisiae, laccases are a powerful alternative to fluorescent reporter proteins.

Self-assessment, in the education framework, is a methodology that motivates students to play an active role in reviewing their performance. It is defined as "the evaluation or judgment of 'the worth' of one's performance and the identification of one's strengths and weaknesses with a view to improving one's learning outcomes". The goal of this research is to study the relationship between self-assessment and the development and improvement of problem-solving skills in Mathematics. In particular, the investigation focuses on how accurate the students' self-evaluations are when compared to external ones, and if (and how) the accuracy in self-assessment changed among the various processes involved in the problem-solving activity. Participants are grade 11 students (in all 182 participants) in school year 2020/2021 who were asked to solve 8 real-world mathematical problems using an Advanced Computing Environment (ACE). Each problem was assessed by a tutor and self-assessed by students themselves, according to a shared rubric with five indicators: Comprehension of the problematic situation, identification of the solving strategy, development of the solving process, argumentation of the chosen strategy, and appropriate and effective use of the ACE. Through a quantitative analysis, students' self-assessment and tutors' assessment were compared; data were cross-checked with students' answers to a questionnaire. The results show a general correlation between tutor assessment and self-assessment, with a tendency of students to underestimate their performance. Moreover, students were more precise in self-assessing in the indicators: Development of the solving process and use of the ACE, while they had major difficulties in self-assessment for the indicators: Comprehension of the problematic situation and argumentation.

The role of mathematics in several scientific disciplines is undisputed; work and everyday life take great advantage of its application. Nevertheless, students often tend to not particularly like it and to consider it of little interest. It is also believed that only people with a certain attitude are capable of mastering the subject. In consideration of this, we aimed to help science students develop mathematical competences by designing a course specifically oriented to applications and problem solving. We administered our course to students attending the first year of a program in biotechnology, asking them to work with technologies instilling curiosity and interest, thus achieving a better proficiency as a consequence. Two questionnaires, along with access and proficiency data, allowed us to collect information about students' attitudes, beliefs, and activity, which we analyzed by means of descriptive statistics. The promotion of the interaction among learners made them active users of the contents, thus allowing for the adaptation of their learning paths according to their personal necessities, as well as the development of teamwork skills and flexibility. Finally, students recognized the usefulness of the problem-solving approach and the role played by software.

Abstract Background Every year in Italy, influenza affects about 4 million people. Almost 5% of them are hospitalised. During peak illness, enormous pressure is placed on healthcare and economic systems. This study aims to quantify the clinical and economic burden of severe influenza during 5 epidemic seasons (2014–2019) from administrative claims data. Methods Patients hospitalized with a diagnosis of influenza between October 2014, and April 2019, were analyzed. Clinical characteristics and administrative information were retrieved from health-related Administrative Databases (ADs) of 4 Italian Local Health Units (LHUs). The date of first admission was set as the Index Date (ID). A follow-up period of six months after ID was considered to account for complications and re-hospitalizations, while a lookback period (2 years before ID) was set to assess the prevalence of underlying comorbidities. Results Out of 2,333 patients with severe influenza, 44.1% were adults ≥ 65, and 25.6% young individuals aged 0–17. 46.8% had comorbidities (i.e., were at risk), mainly cardiovascular and metabolic diseases (45.3%), and chronic conditions (24.7%). The highest hospitalization rates were among the elderly (≥ 75) and the young individuals (0–17), and were 37.6 and 19.5/100,000 inhabitants/year, respectively. The average hospital stay was 8 days (IQR: 14 − 4). It was higher for older individuals (≥ 65 years, 11 days, [17 − 6]) and for those with comorbidities (9 days, [16 − 6]), p-value

Recent trends have shown that autonomous agents, such as Autonomous Ground Vehicles (AGVs), Unmanned Aerial Vehicles (UAVs), and mobile robots, effectively improve human productivity in solving diverse tasks. However, since these agents are typically powered by portable batteries, they require extremely low power/energy consumption to operate in a long lifespan. To solve this challenge, neuromorphic computing has emerged as a promising solution, where bio-inspired Spiking Neural Networks (SNNs) use spikes from event-based cameras or data conversion pre-processing to perform sparse computations efficiently. However, the studies of SNN deployments for autonomous agents are still at an early stage. Hence, the optimization stages for enabling efficient embodied SNN deployments for autonomous agents have not been defined systematically. Toward this, we propose a novel framework called SNN4Agents that consists of a set of optimization techniques for designing energy-efficient embodied SNNs targeting autonomous agent applications. Our SNN4Agents employs weight quantization, timestep reduction, and attention window reduction to jointly improve the energy efficiency, reduce the memory footprint, optimize the processing latency, while maintaining high accuracy. In the evaluation, we investigate use cases of event-based car recognition, and explore the trade-offs among accuracy, latency, memory, and energy consumption. The experimental results show that our proposed framework can maintain high accuracy (i.e., 84.12% accuracy) with 68.75% memory saving, 3.58x speed-up, and 4.03x energy efficiency improvement as compared to the state-of-the-art work for the NCARS dataset. In this manner, our SNN4Agents framework paves the way toward enabling energy-efficient embodied SNN deployments for autonomous agents.

Abstract Background Recurrent Upper Respiratory Tract Infections (R-URTIs) pose a significant challenge in pediatric healthcare, affecting both children and their families. This study aimed to investigate the prevalence, risk factors, and clinical implications of R-URTI in children aged 0–5 years. Methods This observational study involved a sample of 483 children aged 0–5 years, focusing on establishing a practical and dynamic definition of R-URTI. Family pediatricians prospectively collected socio-demographic information, medical history, and recorded the occurrence of URTI episodes. Children were followed from recruitment until March 2021, predating the COVID-19 outbreak. Results A substantial prevalence of R-URTIs was found, estimating it at 5–10% among this age group. To define R-URTI, a practical and dynamic criterion was proposed: children experiencing a minimum of four URTI episodes, each lasting four days or more, within a six-month period, with intervals of well-being in between. Conclusions The study highlighted that specific risk factors for R-URTI were elusive, suggesting that this condition may affect children regardless of their family or clinical history. Moreover, the study’s stratification by age group and times of observation facilitated patient-specific clinical decision-making. The proposed definition may represent a valuable tool for clinicians in diagnosing and addressing R-URTI cases.

Abstract Background Diagnosis of acute otitis media (AOM) in children can be challenging, given that symptoms are often non-specific or absent, and that the direct observation of the tympanic membrane in its entirety through otoscopy can sometimes be difficult. The aim of this study is to assess the diagnostic concordance in detection of AOM episodes between primary care paediatricians and physicians especially trained in paediatric otoscopy, and to characterize the most misleading elements in diagnostic failure. Methods Consecutive clinical charts of children regularly followed for recurrent AOM (RAOM, i.e.: >3 episodes in 6 months or > 4 episodes in 1 year) at our Otitis Media paediatric outpatient clinic were retrospectively screened, in order to collect any diagnosis of AOM episode (and the related clinical findings/middle ear complaints) performed by primary care paediatricians/emergency room paediatricians. Diagnosis of AOM episode was validated by the same experienced physician (FF) in case of otoscopic relief of a bulging eardrum with at least one of the following: hyperaemia or yellow-like colour. The diagnostic concordance in detection of AOM episodes between primary care/emergency room paediatricians and our internal validator was expressed as the percentage of matching diagnosis. Results One hundred and thirty-four single AOM episodes occurring in 87 children (mean age: 26.9 +/- 18.9 months) were included in the analysis. Diagnostic concordance in detection of AOM episodes between primary care/emergency room paediatricians and our internal validator was reported in 72.4% of cases. The most common pitfall found in our study was the misleading diagnosis of AOM in case of hyperaemic tympanic membrane without bulging (32/37 out of non-validated diagnoses). Conclusions AOM diagnosis still represents a relevant issue among paediatricians in our country, and the presence of tympanic membrane hyperaemia without concomitant bulging can be confusing.

The COVID-19 pandemic has evidenced a need for tools and methodologies to support students' autonomous learning and the formative assessment practices in distance education contexts, especially for students from challenging backgrounds. This paper proposes a conceptualization of Interactive Feedback (IF) for Mathematics, which is a step-by-step interactive process that guides the learner in the resolution of a task after one or more autonomous tentative. This conceptualization is grounded on theories and models of automatic assessment, formative assessment, and feedback. We discuss the effectiveness of the IF for engaging students from low socio-economic contexts in closing the gap between current and reference performance through a didactic experimentation involving 299 Italian students in grade 8. Using quantitative analyses on data from the automatic assessment, we compared the results of the first and last attempts in activities with and without IF, based on algorithmic parameters so that the task changes at every attempt. We found that IF was more effective than other kinds of activities to engage learners in actions aimed at improving their results, and the effects are stronger in low socio-economic contexts.

Background Global food systems in recent years have been impacted by some harsh environmental challenges and excessive anthropogenic activities. The increasing levels of both biotic and abiotic stressors have led to a decline in food production, safety, and quality. This has also contributed to a low crop production rate and difficulty in meeting the requirements of the ever-growing population. Several biotic stresses have developed above natural resistance in crops coupled with alarming contamination rates. In particular, the multiple antibiotic resistance in bacteria and some other plant pathogens has been a hot topic over recent years since the food system is often exposed to contamination at each of the farm-to-fork stages. Therefore, a system that prioritizes the safety, quality, and availability of foods is needed to meet the health and dietary preferences of everyone at every time. Methods This review collected scattered information on food systems and proposes methods for plant disease management. Multiple databases were searched for relevant specialized literature in the field. Particular attention was placed on the genetic methods with special interest in the potentials of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and Cas (CRISPR associated) proteins technology in food systems and security. Results The review reveals the approaches that have been developed to salvage the problem of food insecurity in an attempt to achieve sustainable agriculture. On crop plants, some systems tend towards either enhancing the systemic resistance or engineering resistant varieties against known pathogens. The CRISPR-Cas technology has become a popular tool for engineering desired genes in living organisms. This review discusses its impact and why it should be considered in the sustainable management, availability, and quality of food systems. Some important roles of CRISPR-Cas have been established concerning conventional and earlier genome editing methods for simultaneous modification of different agronomic traits in crops. Conclusion Despite the controversies over the safety of the CRISPR-Cas system, its importance has been evident in the engineering of disease- and drought-resistant crop varieties, the improvement of crop yield, and enhancement of food quality.

Boolean gates, the fundamental components of digital circuits, have been widely investigated in synthetic biology because they permit the fabrication of biosensors and facilitate biocomputing. This study was conducted to design and construct Boolean gates in the yeast Saccharomyces cerevisiae, the main component of which was the RNA interference pathway (RNAi) that is naturally absent from the budding yeast cells. We tested different expression cassettes for the siRNA precursor (a giant hairpin sequence, a DNA fragment—flanked by one or two introns—between convergent promoters or transcribed separately in the sense and antisense directions) and placed different components under the control of the circuit inputs (i.e., the siRNA precursor or proteins such as the Dicer and the Argonaute). We found that RNAi-based logic gates are highly sensitive to promoter leakage and, for this reason, challenging to implement in vivo. Convergent-promoter architecture turned out to be the most reliable solution, even though the overall best performance was achieved with the most difficult design based on the siRNA precursor as a giant hairpin.

Ensuring equity in education is a goal for sustainable development. Among the factors that hinder equity, socioeconomic status (SES) has the highest impact on learning Mathematics. This paper addresses the issue of equity at the secondary school level by proposing an approach based on adopting automatic formative assessment (AFA). Carefully designed mathematical activities with interactive feedback were experimented with a sample of 299 students of grade 8 for a school year. A control group of 257 students learned the same topics using traditional methodologies. Part of the sample belonged to low SES. The learning achievement was assessed through pre-and post-tests to understand if the adoption of AFA impacted learning and whether the results depended on the students’ SES. The results show a positive effect of the experimentation (effect size: 0.42). Moreover, the effect size of the experimentation restricted to the low-SES group is high (0.77). In the treatment group, the results do not depend on SES, while in the control group, they do, suggesting that AFA is an equitable approach while traditional instruction risks perpetuating inequalities.

Abstract Background Children tend to have milder forms of COVID-19 than adults, however post-acute complications have been observed also in the paediatric population. In this study, we compared COVID-19-related outcomes and long-term complications between paediatric and adult patients infected by SARS-CoV-2. Methods The study is based on individuals enrolled from October 2020 to June 2021 in the DECO COVID-19 multicentre prospective study supported by the Italian Ministry of Health (COVID-2020–12371781). We included individuals with RT-PCR -confirmed SARS-CoV-2 infection, who were evaluated in the emergency department and/or admitted to COVID-dedicated wards. The severity of SARS-CoV-2 infection was compared across age groups (children/adolescents aged

Abstract Background Antibiotic overuse in children is a significant public health concern, as it can lead to the emergence and spread of antibiotic-resistant bacteria. Although respiratory infections account for most antibiotic prescriptions in children, many of these infections are viral and do not require antibiotics. In this study, we aimed to investigate the use of antibiotics in children with respiratory infections in a primary care setting and to explore the possible role of fever on antibiotic prescription. Methods We conducted a prospective observational study that evaluated preschool children aged 0–5 years who were assessed by their primary care pediatricians for respiratory infectious diseases between October 2019 and March 2021. The study involved 69 public primary care pediatricians and a total of 678 pediatric episodes for respiratory infections. Results Amoxicillin/clavulanate was the most frequently prescribed drug. Bronchitis accounted for most of inappropriate antibiotic prescriptions (73%). Furthermore, the presence of fever was associated with a ~ 300% increase in the likelihood of prescribing antibiotics for respiratory infections that do not typically require antibiotics. Conclusion Our findings emphasize the need for adherence to international guidelines and recommendations in the primary care of children to reduce unnecessary antibiotic use and prevent the development of antibiotic resistance. This study also underscores the potential relevance of new studies to evaluate antibiotic prescription attitudes in other clinical settings and geographical areas.

Abstract Background Acute pharyngitis is a frequent reason for primary care or emergency unit visits in children. Most available data on pharyngitis management come from primary care studies that demonstrate an underuse of microbiological tests, a tendency to over-prescribe antibiotics and a risk of antimicrobial resistance increase. However, a comprehensive understanding of acute pharyngitis management in emergency units is lacking. This study aimed to investigate the frequency of rapid antigen test use to diagnose acute pharyngitis, as well as other diagnostic approaches, the therapeutic attitude, and follow-up of children with this condition in the emergency units. Methods A multicentric national study was conducted in Italian emergency departments between April and June 2022. Results A total of 107 out of 131 invited units (response rate 82%), participated in the survey. The results showed that half of the units use a scoring system to diagnose pharyngitis, with the McIsaac score being the most commonly used. Most emergency units (56%) were not provided with a rapid antigen diagnostic test by their hospital, but the test was more frequently available in units visiting more than 10,000 children yearly (57% vs 33%, respectively, p = 0.02). Almost half (47%) of the units prescribe antibiotics in children with pharyngitis despite the lack of microbiologically confirmed cases of Group A β-hemolytic streptococcus. Finally, about 25% of units prescribe amoxicillin-clavulanic acid to treat Group A β-hemolytic streptococcus pharyngitis. Conclusions The study sheds light on the approach to pharyngitis in emergency units, providing valuable information to improve the appropriate management of acute pharyngitis in this setting. The routinary provision of rapid antigen tests in the hospitals could enhance the diagnostic and therapeutic approach to pharyngitis.

Rubinstein–Taybi syndrome (RTS) is a rare genetic disorder characterized by intellectual disability, facial dysmorphisms, and enlarged thumbs and halluces. Approximately 55% of RTS cases result from pathogenic variants in the CREBBP gene, with an additional 8% linked to the EP300 gene. Given the close relationship between these two genes and their involvement in epigenomic modulation, RTS is grouped into chromatinopathies. The extensive clinical heterogeneity observed in RTS, coupled with the growing number of disorders involving the epigenetic machinery, poses a challenge to a phenotype-based diagnostic approach for these conditions. Here, we describe the first case of a patient clinically diagnosed with RTS with a CREBBP truncating variant in mosaic form. We also review previously described cases of mosaicism in CREBBP and apply clinical diagnostic guidelines to these patients, confirming the good specificity of the consensus. Nonetheless, these reports raise questions about the potential underdiagnosis of milder cases of RTS. The application of a targeted phenotype-based approach, coupled with high-depth NGS, may enhance the diagnostic yield of whole-exome sequencing (WES) in mild and mosaic conditions.

Group A Streptococcus (GAS) presents a significant global health burden due to its diverse clinical manifestations ranging from mild infections to life-threatening invasive diseases. While historically stable, the incidence of GAS infections declined during the COVID-19 pandemic but resurged following the relaxation of preventive measures. Despite general responsiveness to β-lactam antibiotics, there remains an urgent need for a GAS vaccine due to its substantial global disease burden, particularly in low-resource settings. Vaccine development faces numerous challenges, including the extensive strain diversity, the lack of suitable animal models for testing, potential autoimmune complications, and the need for global distribution, while addressing socioeconomic disparities in vaccine access. Several vaccine candidates are in various stages of development, offering hope for effective prevention strategies in the future.

Abstract Mother-to-child transmission of SARS-CoV-2 has been reported since the onset of the COVID-19 pandemic. We conducted a study to summarize evidence on the risk of mother-to-child transmission in the first 30 days after birth in high-income countries and to evaluate the association between preventive measures and the risk of infection for the neonate. A systematic review and meta-analysis were undertaken following PRISMA guidelines. The National Library of Medicine, Web of Science, and Excerpta Medica databases were screened on February 26, 2022. All prospective observational studies addressing the frequency of infection in infants born to mothers SARS-CoV-2 positive were included. Twenty-six studies were included, reporting data of 2653 mothers with SARS-CoV-2 and 2677 neonates. The proportion meta-analysis pointed out an overall estimate of SARS-CoV-2 infection among infants of 2.3% (95% CI: 1.4–3.2%). Data from studies with (1.4%, 95% CI: 0.8–2) and without (1.3%, 95% CI: 0.0–2.7%) rooming-in provided similar risk of infection. Adopting at least two prevention measures during rooming-in resulted in a rate of mother-to-child infection of 1.0% (95%CI: 0.3–1.7%). The results of this study show a low rate of perinatal infection, support the rooming-in and confirm the effectiveness of preventive measures in reducing the risk of mother-to-child viral transmission.

Abstract Background Unfounded concerns regarding fever are increasingly observed among nurses worldwide. However, no study has so far explored the preferred approach towards pediatric fever among nursing students. Therefore, we aimed to investigate the attitude towards pediatric fever among final-year nursing students. Methods Between February and June 2022, final-year nursing students of 5 Italian university hospitals were asked to answer an online survey on their approach to fever in children. Both quantitative and qualitative methods were utilized. Multiple regression models were employed to explore the existence of moderators on fever conceptions. Results The survey was filled in by 121 nursing students (response rate 50%). Although most students (98%) do not consider discomfort to treat fever in children, only a minority would administer a second dose of the same antipyretic in nonresponsive cases (5.8%) or would alternate antipyretic drugs (13%). Most students would use physical methods to decrease fever (84%) and do not think that fever has mainly beneficial effects in children (72%). The own know-how adequacy on fever was inversely associated (OR 0.33, 95% CI 0.13–0.81) with the beliefs that high fever might lead to brain damage. No further predictive variable was significantly associated with the concern that fever might be associated with brain damage, the advice of physical methods use, and the assumption that fever has mostly positive effects. Discussion This study shows for the first time that misconceptions and inappropriate attitudes towards fever in children are common among final-year nursing students. Nursing students could potentially be ideal candidates for improving fever management within clinical practice and amongst caregivers.

Using digital tools for teaching and learning has become quite common in the latest years: while already before the year 2020 their use had been constantly increasing, the breakout of the COVID-19 pandemic at the beginning of the current decade gave a strong impulse to their diffusion. This phenomenon has become enduring also now that the presence of the virus does no longer constitute an emergency, with a view that certain changes will become essentially permanent. The use of digital tools in teaching brings some advantages, for example by allowing to teach and learn at a distance, but also challenges, since moving from using PCs and other devices for everyday life to using them in educational contexts is less straightforward than expected. In this research, we analyse how students perceived higher education during the transition scenario implied by the pandemic, through a survey delivered to military and civilian students enrolled in security and defence studies, which investigates students feelings while undergoing relevant changes in their educational habits. From the analysis of the questionnaire, it resulted that students had trouble, among other things, relating with teachers and feeling the same intensity of engagement when unable to see them in person. This research is part of the activities of the European project DIGICODE, aimed at the improvement of education quality in security and defence by fostering the correct use of digital tools, and by developing the relative competencies in both students and teachers.

Abstract Background Acute pain is a common symptom in children of all ages, and is associated with a variety of conditions. Despite the availability of guidelines, pain often remains underestimated and undertreated. Paracetamol and ibuprofen are the most commonly used drugs for analgesia in Pediatrics. Multimodal pain management by using a combination of paracetamol and ibuprofen results in greater analgesia. Methods An investigation using the Nominal Group Technique was carried out between May and August 2022. Two open (non-anonymous) questionnaires were consecutively sent to a Board of ten clinicians to understand their opinions on the use of the oral paracetamol and ibuprofen association. Answers were examined in a final meeting where conclusions were drawn. Results The board achieved a final consensus on a better analgesic power of paracetamol and ibuprofen in fixed-dose combination as compared to monotherapy, without compromising safety. Strong consensus was reached on the opinion that the fixed-dose combination of paracetamol and ibuprofen may be a useful option in case of inefficacy of one or other drug as monotherapy, especially in case of headaches, odontalgia, earache, and musculoskeletal pain. The use of the fixed combination may be also considered suitable for postoperative pain management. Conclusions The use of the fixed-dose combination may represent advantage in terms of efficacy and safety, allowing a better control of the dose of both paracetamol and ibuprofen as monotherapy, thus minimizing the risk of incorrect dosage. However, the limited evidence available highlights the need for future well designed studies to better define the advantages of this formulation in the various therapeutic areas.

The bubbly flow of air or steam in subcooled water are investigated here in several test cases, characterized by different pipe sizes, bubble dimensions and flow rates, by means of CFD using a Eulerian-Eulerian approach. The performance of models that differ for the turbulence closure in the continuous phase, as well as for the description of the lift force on the dispersed phase, are compared in detail. When air is considered, the space of the experimental parameters leading to a reasonable performance for the selected models are identified and discussed, while the issues left in the modelling of the concurrent condensation are highlighted for the cases where steam is used.

The consumption of medicinal herbs, in the form of infusions, such as chamomile (Matricaria chamomilla), rosemary (Rosmarinus officinalis), wormwood (Artemisia absinthium), mint (Mentha piperita) and muña-muña (Clinopodium gilliesii) is widespread in the region. The determination of toxic and essential elements is relevant to evaluate their incorporation into the human organism. Although the study of elemental levels in different herbs and their infusions is quite widespread, information on plants from Argentina is scarce. In the present work, Cd, Pb, As, Fe, Cu, Ca, Mg, Na and K were quantified in the five commercially available medicinal herbs and in their infusions by atomic absorption and emission spectrometry. In general, the nutrient levels obtained in the herbs studied followed the sequence: K > Ca > Mg > Fe > Na > Cu while in the infusions the order was: K > Mg > Na > Ca > Fe > Cu. Pb was found in the chamomile and wormwood infusions at levels below 10 µg.L-1, whereas Cd and As were not detected (LOD= 0.07 μg.L-1 and 7 μg.L-1 respectively). The estimated daily intake (EDI) values calculated for the essential elements in the infusions were lower than the recommended daily intake (RDI) levels suggested by the World Health Organization (WHO) and did not provide the diet with significant nutritional values. As for to the toxic elements Pb, Cd and As, the EDI values obtained in the infusions were below the provisional maximum tolerable daily intake (PMTDI), indicating that they do not entail a health risk.

Abstract Background Acute otitis media has become a rare cause of facial palsy in children. A high index of suspicion is essential to achieve the diagnosis and to properly treat this condition to avoid permanent neurological sequelae. Case presentation A case of acute otitis media-related facial nerve palsy in an 18 months-old child is described and a review of the recent literature about the clinical presentation, diagnosis, and management of this condition is performed. Conclusions Facial paralysis is an uncommon complication of acute otitis media that requires appropriate care. As highlighted in our report, the treatment of facial nerve palsy secondary to otitis media should be conservative, using antibiotics and corticosteroids. The role of antiviral is still a matter of debate. Myringotomy and a ventilation tube should be added when spontaneous perforation of the tympanic membrane is not present. More aggressive surgical approach should be considered only when there is no significant improvement.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). Current vaccine strategies for KTRs seem to be unable to provide effective protection against coronavirus disease 2019 (COVID-19), and the occurrence of severe disease in some vaccinated KTRs suggested a lack of immunity. We initially analyzed the antibody response in a group of 32 kidney transplant recipients (KTRs) followed at the nephrology and dialysis unit of the Hospital Pio XI of Desio, ASST-Brianza, Italy. Thus, we studied the differences in antibody levels between subjects who contracted SARS-CoV-2 after the booster (8 individuals) and those who did not contract it (24 individuals). Furthermore, we verified if the antibody response was in any way associated with creatinine and eGFR levels. We observed a significant increase in the antibody response pre-booster compared to post-booster using both a Roche assay and DIAPRO assay. In the latter, through immunotyping, we highlight that the major contribution to this increase is specifically due to IgG S1 IgM S2. We observed a significant increase in IgA S1 and IgA NCP (p = 0.045, 0.02) in the subjects who contracted SARS-CoV-2. We did not find significant associations for the p-value corrected for false discovery rate (FDR) between the antibody response to all assays and creatinine levels. This observation allows us to confirm that patients require additional vaccine boosters due to their immunocompromised status and therapy in order to protect them from infections related to viral variants. This is in line with the data reported in the literature, and it could be worthwhile to deeply explore these phenomena to better understand the role of IgA S1 and IgA NCP antibodies in SARS-CoV-2 infection.

Among CRISPR-Cas systems, type V CRISPR-Cas12c is of significant interest because Cas12c recognizes a very simple PAM (TN) and has the ability to silence gene expression without cleaving the DNA. We studied how new transcription factors for the yeast Saccharomyces cerevisiae can be built on Cas12c. We found that, upon fusion to a strong activation domain, Cas12c is an efficient activator. Its functionality was proved as a component of hybrid Boolean gates, i.e., logic circuits that mix transcriptional and translational control (the latter reached via tetracycline-responsive riboswitches). Moreover, Cas12c activity can be strongly inhibited by the anti-CRISPR AcrVA1 protein. Thus, Cas12c has the potential to be a new tool to control the activation of gene expression within yeast synthetic gene circuits.

The use of anthracycline derivatives was approved for the treatment of a broad spectrum of human tumors (i.e., breast cancer). The need to test these drugs on cancer models has pushed the basic research to apply many types of in vitro assays, and, among them, the study of anthracycline-induced apoptosis was mainly based on the application of flow cytometry protocols. However, the chemical structure of anthracycline derivatives gives them a strong autofluorescence effect that must be considered when flow cytometry is used. Unfortunately, the guidelines on the analysis of anthracycline effects through flow cytometry are lacking. Therefore, in this study, we optimized the flow cytometry detection of doxorubicin and epirubicin-treated breast cancer cells. Their autofluorescence was assessed both by using conventional and imaging flow cytometry; we found that all the channels excited by the 488 nm laser were affected. Anthracycline-induced apoptosis was then measured via flow cytometry using the optimized setting. Consequently, we established a set of recommendations that enable the development of optimized flow cytometry settings when the in vitro assays of anthracycline effects are analyzed, with the final aim to reveal a new perspective on the use of those in vitro tests for the further implementation of precision medicine strategies in cancer.

Abstract Background Bronchiectasis is characterized by neutrophilic inflammation and frequent exacerbations often associated with infections. Lipid mediators play critical roles in the inflammatory response, and the balance between anti-inflammatory and pro-inflammatory mediators could drive to chronic inflammation. The aim of this study was to evaluate the metabolites of docosahexaenoic acid and arachidonic acid in sputum of adults with bronchiectasis defining their associations with clinical data, bacterial load and neutrophil elastase. Methods An observational, cross-sectional study was conducted at the bronchiectasis program of the Policlinico Hospital in Milan, Italy, where patients were enrolled. Active neutrophil elastase was measured by enzyme-linked immunosorbent assay, pro-resolving and pro-inflammatory fatty acid-derived mediators were evaluated by mass spectrometry and respiratory pathogens were assessed by real-time PCR. Analysis were performed on sputum collected during stable state and clinical data were also collected. Results Levels of pro-inflammatory mediators derived from arachidonic acid metabolism showed association with neutrophil elastase, were proportional to Pseudomonas aeruginosa identifications and were linked with radiological gravity index, while the concentrations of pro-resolution mediators derived from docosahexaenoic acid were associated with a better health status, highlighted by the inverse correlation with radiological gravity index, bacterial infections and sputum volume production. Conclusion Pro-inflammatory mediators derived from FA metabolisms are associated with severity of bronchiectasis while DHA-derived metabolites are inversely associated with severity of the disease, which may be used for personized treatment of bronchiectasis.