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Abstract In the last year, there have been many remarkable articles published in the Italian Journal of Pediatrics. This review highlights papers that can be potentially helpful in healthcare practice among the most cited or accessed papers on the journal website. We have chosen key articles on allergy, analgesics, cardiology, endocrinology, gastroenterology, genetics, global health, infectious diseases, neonatology, neurology and pulmonology. Advances in understanding risk factors, mechanisms, diagnosis, treatment options and prevention of pediatric diseases have been discussed and in the context of the subsequent steps. We think that progresses achieved in 2023 will have a significant impact on the management of diseases in childhood.

Catastrophic antiphospholipid syndrome (CAPS) is a rare clinical form of antiphospholipid syndrome (APS) associated with life-threatening complications due to simultaneous thrombosis that may affect small and large vessels. It may be localized to the venous and/or arteries at the same time, and there are not available guidelines based on randomized clinical trials or large series. We here report a clinical case of CAPS with onset after resolution of oligo-symptomatic infection SARS-CoV-2, that had transient improvement with warfarin after recurrent thromboses occurred despite treatment off-label with low doses of low molecular weight heparin. Furthermore, we tried to trace a line by which a multidisciplinary team may set specific timing to have follow-up because of the high morbidity, mortality, and prolonged time of hospitalization.

The ICH S1B carcinogenicity global testing guideline has been recently revised with a novel addendum that describes a comprehensive integrated Weight of Evidence (WoE) approach to determine the need for a 2-year rat carcinogenicity study. In the present work, experts from different organizations have joined efforts to standardize as much as possible a procedural framework for the integration of evidence associated with the different ICH S1B(R1) WoE criteria. The framework uses a pragmatic consensus procedure for carcinogenicity hazard assessment to facilitate transparent, consistent, and documented decision-making and it discusses best-practices both for the organization of studies and presentation of data in a format suitable for regulatory review. First, it is acknowledged that the six WoE factors described in the addendum form an integrated network of evidence within a holistic assessment framework that is used synergistically to analyze and explain safety signals. Second, the proposed standardized procedure builds upon different considerations related to the primary sources of evidence, mechanistic analysis, alternative methodologies and novel investigative approaches, metabolites, and reliability of the data and other acquired information. Each of the six WoE factors is described highlighting how they can contribute evidence for the overall WoE assessment. A suggested reporting format to summarize the cross-integration of evidence from the different WoE factors is also presented. This work also notes that even if a 2-year rat study is ultimately required, creating a WoE assessment is valuable in understanding the specific factors and levels of human carcinogenic risk better than have been identified previously with the 2-year rat bioassay alone.

Background: Although, in most children with asthma, good symptom control is achieved with a low to moderate dose of inhaled corticosteroids, a small group of patients still experiences frequent symptoms, and even severe exacerbations, impairment of lung function, and reduced quality of life. Some of these subjects with severe asthma require biologic drugs as add-on therapy. In the past decade, numerous monoclonal antibodies have been approved for children or adolescents with severe asthma, in addition to their increasing use in adult asthma. However, the available evidence on how to select the most appropriate biologic based on a single patient’s clinical, functional, and laboratory characteristics is still scant, and is insufficient to guide clinicians in the decision-making process of a personalized treatment. Materials and Methods: We report a case series of four patients with severe eosinophilic asthma treated with mepolizumab, an anti-interleukin-5 monoclonal antibody, and review the existing literature on this treatment in children and adolescents. Results: Our patients, all with blood eosinophilia and elevated fractional exhaled nitric oxide levels, developed poor symptom control despite prolonged treatment with high-dose inhaled corticosteroids plus a second controller, addressing the addition of a biologic drug. In all of them, a 12-month treatment with subcutaneous mepolizumab showed a reduction in the blood eosinophil count and in asthma exacerbations, as well as an improvement on the Asthma Control Test. The results of the literature search focused on the strengths and limitations of the pediatric use of mepolizumab and highlighted the areas worthy of further research. Conclusions: Mepolizumab has proven effective in improving symptom control in pediatric patients with severe asthma. Additional well-powered clinical trials will be helpful in developing evidence-based guidelines regarding biologic drugs in the pediatric population.

Digital technologies are increasingly adopted and developed in living labs, to support and enable co-production processes around wellbeing related public services. This research report presents the case of one of the local laboratories established by the European project NLAB4CIT, in the city of Kaisariani, Greece. In order to enhance community engagement, participatory design methods are applied under an “infrastructuring” notion; the living lab model is reapproached as community infrastructure; and digital tools are understood as civic technologies. The article reports on the initial co-design phases, in order to provide other living labs on digital co-production with an overview on the socio-technical challenges encountered. These challenges concern how community actors can engage in the process of co-production of public services, and how digital technologies can be introduced to this purpose. Strength factors emerge such as the existence of an already active community, the creation of an enduring space of collaboration between researchers and citizens, and a civic approach to technology that makes them accessible and tailored. Open challenges concern the role of the public administration, the extent to which technologies are actually co-designed and co-developed, and some technical issues such as internet accessibility.

IntroductionObesity is the most common nutritional disease in dogs, and is generally managed by caloric restriction. Gut microbiota alteration could represent a predisposing factor for obesity development, which has been associated with a low-grade inflammatory condition and an impaired antioxidant status. Besides, weight loss has been shown to influence the gut microbiota composition and reduce the inflammatory response and oxidative stress.MethodHowever, these insights in canine obesity have not been fully elucidated. The aim of this study was to assess the differences in serum and inflammatory parameters, antioxidant status, fecal microbiota and bacterial metabolites in 16 obese and 15 lean client-owned dogs and how these parameters in obese may be influenced by caloric restriction. First, for 30 days, all dogs received a high-protein, high-fiber diet in amounts to maintain their body weight; later, obese dogs were fed for 180 days the same diet in restricted amounts to promote weight loss.ResultsBefore the introduction of the experimental diet (T0), small differences in fecal microbial populations were detected between obese and lean dogs, but bacterial diversity and main bacterial metabolites did not differ. The fecal Dysbiosis Index (DI) was within the reference range (< 0) in most of dogs of both groups. Compared to lean dogs, obese dogs showed higher serum concentrations of acute-phase proteins, total thyroxine (TT4), and antioxidant capacity. Compared to T0, dietary treatment affected the fecal microbiota of obese dogs, decreasing the abundance of Firmicutes and increasing Bacteroides spp. However, these changes did not significantly affect the DI. The caloric restriction failed to exert significative changes on a large scale on bacterial populations. Consequently, the DI, bacterial diversity indices and metabolites were unaffected in obese dogs. Caloric restriction was not associated with a reduction of inflammatory markers or an improvement of the antioxidant status, while an increase of TT4 has been observed.DiscussionIn summary, the present results underline that canine obesity is associated with chronic inflammation. This study highlights that changes on fecal microbiota of obese dogs induced by the characteristics of the diet should be differentiated from those that are the consequence of the reduced energy intake.

In this paper, we review and connect the three essential conditions needed by the collapse model to achieve a complete and exact formulation, namely the theoretical, the experimental, and the ontological ones. These features correspond to the three parts of the paper. In any empirical science, the first two features are obviously connected but, as is well known, among the different formulations and interpretations of non-relativistic quantum mechanics, only collapse models, as the paper well illustrates with a richness of details, have experimental consequences. Finally, we show that a clarification of the ontological intimations of collapse models is needed for at least three reasons: (1) to respond to the indispensable task of answering the question ’what are collapse models (and in general any physical theory) about?’; (2) to achieve a deeper understanding of their different formulations; (3) to enlarge the panorama of possible readings of a theory, which historically has often played a fundamental heuristic role.

I territori deltizi sono globalmente a rischio per gli effetti dei cambiamenti climatici, delle dinamiche insediative sempre più intense, dell'artificializzazione delle coste. La sfida di affrontare e gestire in maniera più sostenibile e integrata i processi trasformativi dei delta è stata accolta dal CITERlab di UNIFE intrecciando ricerca universitaria, attività didattiche e coinvolgimento di stakeholder e comunità locali, attualmente impegnati nello sviluppo di un “Manifesto per il Delta del Po” per il territorio emiliano-romagnolo.

Current climatc, social and fnancial phenomena have triggered deep modifcatons in cultural landscapes, threatening their fragile territories and the communites that live in them. Nevertheless, they also represent a challenge to fnd a renewed link between forms of human actvity and the producton of landscape in order to understand its future evolutons. This paper deals with this feld of investgaton in the context of the Cinque Terre Natonal Park, in Italy, through scenario planning criteria with the goal of rethinking the heritagelisted system of traditonal terraced agriculture systems as an infrastructural element for a resilient territory. Startng from the Universal Soil Loss Equaton (USLE), it identfes the main territorial factors of uncertainty and accordingly suggests possible interventon categories on the wider scale of the so-called slope units, through 2x2 matrixes. Defning a resilient transformaton program for the environmental system of the Cinque Terre Natonal Park over a twenty-year tme frame means considering adaptability as a key aspect in diferent scenarios that might be generated in the near future.

This contribution, written by an urban designer and an educationist, aims at (re)focusing the attention of the interdisciplinary debate on the active role of children within the public urban realm or – as we could rephrase it – on the potential influences that the city, its structure, regulations and spaces has on children intended as a vulnerable population group. In order to do so, some reflections on the relationship between “the child and the city” are presented, also supported by an original walk-to-school research conducted in the Italian city of Cassino, investigating children's active and independent mobility, and by a conceptual model based on the classification of children's physical activity as either “independent” or “non-independent”. Finally, a discussion on the pivotal role of public spaces is developed, briefly presenting some virtuous project examples.

Intradermal therapy, known as mesotherapy, is a technique used to inject a drug into the surface layer of the skin. In particular, it involves the use of a short needle to deposit the drug in the dermis. The intradermal microdeposit modulates the drug’s kinetics, slowing absorption and prolonging the local mechanism of action. It is successfully applied in the treatment of some forms of localized pain syndromes and other local clinical conditions. It could be suggested when a systemic drug-sparing effect is useful, when other therapies have failed (or cannot be used), and when it can synergize with other pharmacological or nonpharmacological therapies. Despite the lack of randomized clinical trials in some fields of application, a general consensus is also reached in nonpharmacological mechanism of action, the technique execution modalities, the scientific rationale to apply it in some indications, and the usefulness of the informed consent. The Italian Mesotherapy Society proposes this position paper to apply intradermal therapy based on scientific evidence and no longer on personal bias.

Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.

In this paper I will argue in favor of the view that if physics is to become a coherent metaphysics of nature, it needs an interpretation, namely (i) a clear formulation of its ontological/metaphysical claims and (ii) and a precise understanding of how such claims are related to the world of our experience, which is the most important reservoir of traditional, merely aprioristic metaphysical speculations. Such speculations − especially if conducted in full autonomy from physics, or imposed upon it “from the outside” − risk to turn analytic metaphysics into a “rigorous” but fully sterile intellectual game.

In this paper I analyze the difficult question of the truth of mature scientific theories by tackling the problem of the truth of laws. After introducing the main philosophical positions in the field of scientific realism, I discuss and then counter the two main arguments against realism, namely the pessimistic meta-induction and the abstract and idealized character of scientific laws. I conclude by defending the view that well-confirmed physical theories are true only relatively to certain values of the variables that appear in the laws.

In this essay I claim that thought experiments have invariably been very important to inquire into the foundations of natural science (in particolar physics). In particular, they have proved essential to test the stability of allegedly clear but ultimately contradictory concepts, that were nonetheless at the basis of widely shared scientific theories. By quickly reviewing some famous Gedankenexperimenten proposed by Einstein against the completeness of (Bohr’s interpretation of) quantum mechanics, I will try to ask how could they possibly have the critical role that they always had.