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Background: We tested whether the tendency to worry could affect psychological responses to quarantine by capitalizing on the opportunity of having collected data before the COVID-19 outbreak on measures of worry, anxiety, and trait mindfulness in a group of university students. Methods: Twenty-five participants completed self-report measures assessing worry (Penn State Worry Questionnaire, PSWQ), anxiety (Anxiety Sensitivity Index, ASI-3), and trait mindfulness (Mindful Attention Awareness Scale, MAAS) at T0 (pre-lockdown, 4 November 2019&ndash, 17 February 2020) and T1 (at the end of lockdown, 26 April&ndash, 30 April 2020). We compared assessments at the two time points in the whole sample and in high and low worriers (defined at T0 by scores on PSWQ respectively above and below 1.5 SD from mean of the Italian normative sample). Outcomes: High worriers showed at T1 a significant increase of anxiety sensitivity and fear of mental health in comparison to low worriers. Moreover, in the whole sample, at T1 trait mindfulness was inversely related to worry and fear of mental health. Interpretation: A valuable approach to support individuals experiencing anxiety related to the COVID-19 outbreak could be represented by mindfulness-based interventions improving the ability to focus attention and awareness on the present moment.

The importance of rhinosinusitis finally reached pediatricians' attention a few years ago, and it has now been demonstrated that it is medically important and has a considerable socioeconomic impact in childhood. These guidelines, which have been prepared with and approved by many Italian Scientific Societies, are based on the most recent findings in the fields of clinical symptoms, imaging and microbiology tests for the diagnosis of acute rhinosinusitis, and efficacy evidence concerning antibiotic treatment and non-antibiotic adjuvant treatment. A Pubmed search using the key words "sinusitis", "rhinosinusitis", "child" and "antibiotic treatment", and the limits "human studies" and "English language", led to the selection of more than 2,700 articles published between 1966 and 2007. These guidelines are based on the 125 that were considered truly relevant and reflect the most widely shared positions concerning the diagnosis and treatment of acute, subacute and recurrent rhinosinusitis in children.

Bacillus Calmette-Guerin (BCG) vaccine is still the only vaccine approved for the prevention of tuberculosis (TB), and is widely used in highly endemic countries, where all newborns receive a single intradermal dose immediately after birth; however, the recommendations concerning its use in Europe vary widely from country to country. This document describes the recommendations of a group of Italian scientific societies concerning its pediatric use in Italy, the persistence of the protection it provides, its safety, its interference with tuberculin skin test (TST) responses, and the children who should be vaccinated. The experts conclude that BCG vaccination provides a good level of protection against tuberculous meningitis and disseminated forms, and a fair level of protection against pulmonary disease; the protective effective lasts at least 10 years, and revaccination offers no advantages over a single administration. The vaccine is safe in immunocompetent subjects, and affects the response to a TST for at least 6 y On the basis of these observations, we recommend its use in Italy in all TST-negative immunocompetent newborns and breastfeeding infants aged

Background Discrepancies in the management of pharyngitis in children have been reported in Europe and the United States, and recommendations concerning the use of clinical scores, rapid antigen diagnostic tests (RADTs) or throat cultures, and the indications for antibiotic treatment largely differ. Objective This article summarizes the Italian guidelines on the management of pharyngitis in children issued by the National Institute of Health. Methods A multidisciplinary panel of experts (the Guidelines Development Group) developed and used a set of key questions to conduct a systematic review of the literature. Relevant publications in English were identified through a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception through April 30, 2011. Final recommendations were scaled according to the Italian National Guidelines Program grading. Results Eighteen clinical questions were defined, and 44 recommendations were issued. None of the available scoring systems is sufficiently accurate to identify group A β-hemolytic streptococci (GABHS) pharyngitis in settings with low prevalence for rheumatic disease. RADT should be performed by trained personnel in every child with a history and signs/symptoms suggestive of GABHS pharyngitis. RADT is not recommended in children with a McIsaac score of 0 or 1 with ≥2 signs/symptoms suggestive of viral infection. Backup culture in children with negative RADT result is not recommended. Culture test with antibiotic susceptibility assay should be performed exclusively for epidemiologic purposes. Streptococcal antibody titers are of no value in diagnosing acute pharyngitis. Antibiotic therapy is recommended in microbiologically documented GABHS pharyngitis. Because penicillin V is not available in Italy, amoxicillin (50 mg/kg/d in 2–3 doses orally) for 10 days is the first choice of treatment. In noncompliant cases, benzathine penicillin may be administered. Although not routinely recommended due to the high cost and wide spectrum of activity, a 5-day course with a second-generation cephalosporin may be used in noncompliant cases. Macrolides should be limited to children with demonstrated type I hypersensitivity to penicillin. Ibuprofen or paracetamol is recommended for relief of pain or fever associated with discomfort. Because the carrier state is not associated with increased risk of suppurative complications and risk of GABHS transmission to contacts is minimal, the carrier state should never be investigated and treated. Recommendations for the management of suppurative complications are given. Conclusions This guideline provides a comprehensive, evidence based, tool for the diagnosis and therapy of acute pharyngitis in children.

The aims of this investigation are: 1) to assess the function of the hepatocyte in transplanted porcine liver, immediately after reperfusion, by monitoring both LFTs and the MEGX levels; 2) to search for correlation between MEGX and LFTS, in an effort to evaluate the metabolic mechanisms occurring in the early liver transplantation revascularization phase. The MEGX test was found to be less than 50 micrograms/ml in all the recipients and all the LFTS tested have been reported to be out the normal range. Furthermore our data has shown a statistically significant correlationship between the MEGX values and those of alkaline phosphatase and prothrombin and a highly significant correlationship with cholinesterase.

Adequate and balanced nutrition is essential to promote optimal child growth and a long and healthy life. After breastfeeding, the second step is the introduction of complementary feeding (CF), a process that typically covers the period from 6 to 24 months of age. This process is, however, still highly controversial, as it is heavily influenced by socio-cultural choices, as well as by the availability of specific local foods, by family traditions, and pediatrician beliefs. The Società Italiana di Pediatria Preventiva e Sociale (SIPPS) together with the Federazione Italiana Medici Pediatri (FIMP), the Società Italiana per lo Sviluppo e le Origine della Salute e delle Malattie (SIDOHaD), and the Società Italiana di Nutrizione Pediatrica (SINUPE) have developed evidence-based recommendations for CF, given the importance of nutrition in the first 1000 days of life in influencing even long-term health outcomes. This paper includes 38 recommendations, all of them strictly evidence-based and overall addressed to developed countries. The recommendations in question cover several topics such as the appropriate age for the introduction of CF, the most appropriate quantitative and qualitative modalities to be chosen, and the relationship between CF and the development of Non-Communicable Diseases (NCDs) later in life.

The tuning of the structural batteries for various applications of transportation is an ambitious target. The pollutant emission and mostly the process for battery recycling and recovery are peculiar aspects to consider for new designs. The goal is to reduce the weight. In this frame, taking into account that the traditional battery packs do not contribute to the structural performance, it is worth to underline the solution of the structural batteries allows to increase the mechanical properties as they are integrated into the primary structure. The paper establishes the response of a composite structural battery model subjected to low-velocity impact tests. The process used to manufacture the structural battery model is described, and the experimental activities are performed by a customized drop tower and finally replicated numerically by explicit code to enhance the comprehension of the structural dynamics. Differences with respect to a carbon fiber laminate are highlighted both for the force released at the impact and dart displacement, for the same levels of energy.

Electric or hybrid electric propulsion systems have received a great deal of attention in recent years in various branches of transportation including aviation. Europe is committed to the ambitious goals of reducing CO2 emissions by 75%, NOx emissions by 90% and perceived noise by two-thirds by the year 2050 compared to the average new aircraft of the year 2000. The main barrier of the electric propulsion is bound to the battery limits in terms of energy and power densities, thus determining a relevant negative impact on payload or aircraft size. It is possible to design and fly an electrically propelled aircraft, as testified by some existing examples, both prototypical and production models, in the categories of ultralight and general aviation aircraft. A novel technology, which allows the electrification process toward heavier categories of aircraft, is constituted by structural batteries. These are similar in structure to carbon fiber composites, where the matrix features dielectric characteristics, making the structure capable of storing electric energy while retaining the capability to withstand mechanical loads. Despite that, it raises relevant issues concerning aircraft sizing procedures that need to be conceived considering the specific characteristics of such multifunctional technology. This research work aims to evaluate the potential benefits the structural batteries have on the fuel burn for a 11-seater commuter aircraft. According to the envisaged technologies (structural batteries), this work will focus on the determination of the best hybridization factors determining the energy requirements for the typical mission of a commuter aircraft.

Introduction Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9Is) were associated with a risk of neurocognitive adverse drug reactions (ADRs). Objective We aimed to investigate the occurrence of neuropsychiatric ADRs related to PCSK9Is. Methods We analyzed Individual Case Safety Reports (ICSRs) sent through the European pharmacovigilance database that reported alirocumab or evolocumab as the suspected drug and at least one neurological or psychiatric ADR. The reporting odds ratio (ROR) was computed to compare the probability of reporting ICSRs with neuropsychiatric ADRs between alirocumab, evolocumab and statins. Results Overall, 2041 ICSRs with alirocumab and/or evolocumab as the suspected drug described the occurrence of neuropsychiatric ADRs. The most reported preferred terms for both drugs were headache, insomnia and depression. No difference between alirocumab and evolocumab was observed for the RORs of ICSRs with ADRs belonging to the System Organ Classes (SOCs) ‘Nervous system disorders’ or ‘Psychiatric disorders’ (ROR 1.02, 95% confidence interval 0.91–1.14; and 1.12, 95% CI 0.94–1.34, respectively), while evolocumab and alirocumab had a higher reporting probability of ICSRs with ADRs belonging to the SOC ‘Nervous system disorders’ compared with atorvastatin and fluvastatin. A lower reporting probability was instead found for ICSRs with ADRs belonging to the SOC ‘Psychiatric disorders’ for evolocumab and alirocumab versus simvastatin, pravastatin and rosuvastatin. Conclusion Our results demonstrated that 22.7% of all ICSRs reporting alirocumab or evolocumab as suspect drugs described the occurrence of neuropsychiatric ADRs. The ROR showed that evolocumab and alirocumab had a higher reporting probability of neurological ADRs compared with statins. Further data from real-life contexts are needed. Electronic supplementary material The online version of this article (10.1007/s40264-020-01021-3) contains supplementary material, which is available to authorized users.

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs. Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs. Supplementary Information The online version contains supplementary material available at 10.1186/s13052-021-01150-0.

Background In 2019, a multidisciplinary panel of experts from eight Italian scientific paediatric societies developed a consensus document for the use of inhaled corticosteroids in the management and prevention of the most common paediatric airways disorders. The aim is to provide healthcare providers with a multidisciplinary document including indications useful in the clinical practice. The consensus document was intended to be addressed to paediatricians who work in the Paediatric Divisions, the Primary Care Services and the Emergency Departments, as well as to Residents or PhD students, paediatric nurses and specialists or consultants in paediatric pulmonology, allergy, infectious diseases, and ear, nose, and throat medicine. Methods Clinical questions identifying Population, Intervention(s), Comparison and Outcome(s) were addressed by methodologists and a general agreement on the topics and the strength of the recommendations (according to the GRADE system) was obtained following the Delphi method. The literature selection included secondary sources such as evidence-based guidelines and systematic reviews and was integrated with primary studies subsequently published. Results The expert panel provided a number of recommendations on the use of inhaled corticosteroids in preschool wheezing, bronchial asthma, allergic and non-allergic rhinitis, acute and chronic rhinosinusitis, adenoid hypertrophy, laryngitis and laryngospasm. Conclusions We provided a multidisciplinary update on the current recommendations for the management and prevention of the most common paediatric airways disorders requiring inhaled corticosteroids, in order to share useful indications, identify gaps in knowledge and drive future research.

The renin-angiotensin-aldosterone system (RAAS) firstly considered as a cardiovascular circulating hormonal system, it is now accepted as a local tissue system that works synergistically or independently with the circulating one. Evidence states that tissue RAAS locally generates mediators with regulatory homeostatic functions, thus contributing, at some extent, to organ dysfunction or disease. Specifically, RAAS can be divided into the traditional RAAS pathway (or classic RAAS) mediated by angiotensin II (AII), and the non-classic RAAS pathway mediated by angiotensin 1–7. Both pathways operate in the heart and lung. In the heart, the classic RAAS plays a role in both hemodynamics and tissue remodeling associated with cardiomyocyte and endothelial dysfunction, leading to progressive functional impairment. Moreover, the local classic RAAS may predispose the onset of atrial fibrillation through different biological mechanisms involving inflammation, accumulation of epicardial adipose tissue, and electrical cardiac remodeling. In the lung, the classic RAAS regulates cell proliferation, immune-inflammatory response, hypoxia, and angiogenesis, contributing to lung injury and different pulmonary diseases (including COVID-19). Instead, the local non-classic RAAS counteracts the classic RAAS effects exerting a protective action on both heart and lung. Moreover, the non-classic RAAS, through the angiotensin-converting enzyme 2 (ACE2), mediates the entry of the etiological agent of COVID-19 (SARS-CoV-2) into cells. This may cause a reduction in ACE2 and an imbalance between angiotensins in favor of AII that may be responsible for the lung and heart damage. Drugs blocking the classic RAAS (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) are well known to exert a cardiovascular benefit. They are recently under evaluation for COVID-19 for their ability to block AII-induced lung injury altogether with drugs stimulating the non-classic RAAS. Herein, we discuss the available evidence on the role of RAAS in the heart and lung, summarizing all clinical data related to the use of drugs acting either by blocking the classic RAAS or stimulating the non-classic RAAS.

Gliflozins are a novel class of oral anti-diabetic drugs, acting as inhibitors of sodium-glucose co-transporters (SGLTs) through the proximal convoluted tubules (PCT) and intestinal epithelium. The sodium-glucose co-transporters 2 (SGLT2) are mainly expressed in S1 and S2 segments of the proximal convoluted tubule in the kidneys. Clinical guidelines recommend their use especially in Type 2 Diabetes mellitus (T2DM) patients with vascular complications and/or heart failure highlighting the importance of sodium-glucose co-transporter 2 inhibitors (SGLT2i) pleiotropic effects. Interestingly, cognitive decline is a widely recognized complication of T2DM and, in addition, to clarify its pathophysiology, there is an urgent need to understand how and if diabetes therapies can control diabetes-related cognitive dysfunction. At the time, although SGLT2 proteins are present in the Central Nervous System (CNS), the SGLT2i effects on cognitive impairments remain partly unknown. In pre-clinical studies, SGLT2i ameliorates cognitive dysfunction in obese and T2DM mice, reducing oxidative stress, neuroinflammation and improving neuronal plasticity and mitochondrial brain pathway. In addition, SGLT2i could bring back mTOR to a physiological state of activation, stopping neurodegenerative diseases' onset or progression. Instead, clinical studies on T2DM-related cognitive dysfunction treated by SGLT2i are much more limited. For these reasons, further studies are needed to better elucidate if SGLT2i therapy can affect T2DM-related cognitive decline. In this scenario, this review aims to summarize the state of knowledge on the role of SGLT2i in T2DM-related cognitive dysfunction and stimulate new clinical trials.

Despite several innovative medicines gaining worldwide approval in recent years, there are still therapeutic areas for which unsatisfied therapeutic needs persist. For example, high unmet clinical need was observed in patients diagnosed with type 2 diabetes mellitus and hemophilia, as well as in specific age groups, such as the pediatric population. Given the urgent need to improve the therapy of clinical conditions for which unmet clinical need is established, clinical testing, and approval of new medicines are increasingly being carried out through accelerated authorization procedures. Starting from 1992, the Food and Drug Administration and the European Medicines Agency have supported the so-called Early Access Programs (EAPs). Such procedures, which can be based on incomplete clinical data, allow an accelerated marketing authorization for innovative medicines. The growth in pharmaceutical research has also resulted in the development of novel therapeutic approaches, such as biotech drugs and advanced therapy medicinal products, including new monoclonal antibodies for the treatment of asthma, antisense oligonucleotides for the treatment of Duchenne muscular dystrophy and spinal muscular atrophy, and new anticancer drugs that act on genetic biomarkers rather than any specific type of cancer. Even though EAPs and novel therapeutic approaches have brought huge benefits for public health, their implementation is limited by several challenges, including the high risk of safety-related label changes for medicines authorized through the accelerated procedure, the high costs, and the reimbursement and access concerns. In this context, regulatory agencies should provide the best conditions for the implementation of the described new tools.