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Abstract Background For Attention Deficit/Hyperactivity Disorder (ADHD) youth transitioning from child to adult services, protocols that guide the transition process are essential. While some guidelines are available, they do not always consider the effective workload and scarce resources. In Italy, very few guidelines are currently available, and they do not adhere to common standards, possibly leading to non-uniform use. Methods The present study analyzes 6 protocols collected from the 21 Italian services for ADHD patients that took part in the TransiDEA (Transitioning in Diabetes, Epilepsy, and ADHD patients) Project. The protocols’ content is described, and a comparison with the National Institute for Clinical Health and Excellence (NICE) guidelines is carried out to determine whether the eight NICE fundamental dimensions were present. Results In line with the NICE guidelines, the dimensions addresses in the 6 analyzed documents are: early transition planning (although with variability in age criteria) (6/6), individualized planning (5/6), and the evaluation of transfer needs (5/6). All protocols also foresee joint meetings between child and adult services. The need to include the families is considered by 4 out of 6 protocols, while monitoring (2/6), and training programs (1/6) are less encompassed. In general, a highly heterogeneous picture emerges in terms of quality and quantity of regulations provided. Conclusions While some solid points and core elements are in common with international guidelines, the content’s variability highlights the need to standardize practices. Finally, future protocols should adhere more to the patients’ needs and the resources available to clinicians.

Western equine encephalitis virus (WEEV) is a mosquitoborne virus that reemerged in December 2023 in Argentina and Uruguay, causing a major outbreak. We investigated the outbreak using epidemiologic, entomological, and genomic analyses, focusing on WEEV circulation near the Argentina‒Uruguay border in Rio Grande do Sul state, Brazil. During November 2023‒April 2024, the outbreak in Argentina and Uruguay resulted in 217 human cases, 12 of which were fatal, and 2,548 equine cases. We determined cases on the basis of laboratory and clinical epidemiologic criteria. We characterized 3 fatal equine cases caused by a novel WEEV lineage identified through a nearly complete coding sequence analysis, which we propose as lineage C. Our findings highlight the importance of continued surveillance and equine vaccination to control future WEEV outbreaks in South America.

Background: Invasive fungal infections (IFIs) represent a major cause of morbidity among allogeneic hematopoietic stem cell transplantation (allo-HSCT). Isavuconazole (ISA) is a broad-spectrum triazole with favorable safety profile. Objectives and design: Herein, we evaluate the real life coadministration of ISA and sirolimus in allo-HSCT recipients in a single-center retrospective analysis, describing clinical efficacy, safety, and therapeutic drug monitoring (TDM) of both drugs. Methods: All consecutive allo-HSCT recipients who received the coadministration of ISA and sirolimus for at least 2 weeks between July 2017 and December 2022 were included in this retrospective analysis. TDM was longitudinally performed during treatment. IFIs were classified according to the revised European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus criteria. Results: A total of 51 recipients were included in the analysis. A total of 17 patients received ISA as continuous antifungal treatment for IFI diagnosed before transplant: one patient experienced a probable invasive pulmonary aspergillosis, and one patient switched from ISA to liposomal amphotericin B for a possible IFI. A total of 34 patients started ISA as antifungal therapy for IFI diagnosed after transplant. Sixteen of 34 were treated for a proven/probable breakthrough IFI during mold-active prophylaxis: 6/16 patients died for IFI after a median of 51 days of ISA. Eighteen of 34 started ISA as empirical therapy for a possible IFI: 15/18 patients were alive with resolution of infection after 6 weeks, 1 died for disease progression, and 2 had empirically changed antifungal therapy due to pneumonia progression. Clinical and radiological response rate was 68% after 90 days from IFI diagnosis. No toxicities related to drug–drug interaction have been registered in patients reaching concomitant therapeutic levels of ISA and sirolimus. Conclusion: The coadministration of ISA and sirolimus was safe and feasible in this cohort, confirming favorable clinical efficacy in patients with multiple-drug coadministration.

Abstract Achieving sustainable development is today a basic premise for all companies and governments. The 2030 Agenda has outlined an action plan focused on all areas and interest groups. Achieving economic growth and technological progress, social development, peace, justice, environmental protection, inclusion and prosperity represent the main areas to achieve social change. Furthermore, the circular economy is capable of improving the efficiency of products and resources, and can contribute to this social change, but there is a gap in the literature regarding whether the orientation of the companies in their circular economy strategy can lead to the achievement of the sustainable development goals. The objective of this study is to develop an initial circular economy-sustainable development goals (CE-SDGs) framework that considers the circular economy as the precedent and sustainable development goals as a consequence of implementing a circular economy. With respect to the methodology, the literature linking the relationship between the circular economy and sustainable development goals was reviewed first. A Structural Equation Model with the Partial Least Squares technique was also employed, analyzing two complementary models in enterprises involved in the Social Economy in the Autonomous Community of Extremadura (Spain). Regarding the results obtained, a link has been observed between professional profiles and training in people-oriented activities. The same does not occur for activities oriented toward the planet. Moreover, the existence of corporate reports that obtain data on circular activities is crucial to achieving orientation toward the sustainable development goals, for activities oriented toward both people and the planet. Finally, the results confirm that the existence of barriers and incentives determines the observed results, being aware that the lack of specialized training in human resources always has a significant incidence. Using resource and capability and dynamic capabilities theories, this study contributes with an initial framework by joining two lines of research and analyzing the CE-SDGs link in SE enterprises. Future research and empirical validations could contribute more deeply to the literature. As key recommendations, social economy managers must be committed to introducing circular economy practices to achieve people- and planet-oriented objectives, being proactive in fostering CE-SDGs frameworks.

Abstract Spontaneous abortion is a pregnancy complication characterized by complex and multifactorial etiology. About 5% of childbearing women are globally affected by early pregnancy loss (EPL) and most of them experience recurrence (RPL). Epigenetic mechanisms and controlled inflammation are crucial for pregnancy maintenance and genetic predispositions may increase the risk affecting the maternal–fetal crosstalk. Combined analyses of global methylation, inflammation and inherited predispositions may contribute to define pregnancy loss etiopathogenesis. LINE-1 epigenetic regulation plays crucial roles during embryo implantation, and its hypomethylation has been associated with senescence and several complex diseases. By analysing a group of 230 women who have gone through pregnancy interruption and comparing those experiencing spontaneous EPL (n = 123; RPL, 54.5%) with a group of normal pregnant who underwent to voluntary interruption (VPI, n = 107), the single statistical analysis revealed significant lower (P

Abstract Background The early identification of infants with a risk for neurodevelopmental disorders in the first few years of life is essential for better developmental outcomes. Screenings should be carried out by combining the family pediatricians’ and parents’ perspectives, the two fundamental sources of information on children’s health. The present study has three aims: (a) to test the feasibility of parent-report instruments to detect warning signs in their children’s development; (b) to ascertain whether there is an agreement between the family pediatricians’ (FP) clinical judgments of warning signs and the parental perceptions; (c) to determine whether there is a link between parents’ distress and child development. Methods Within the NASCITA birth cohort, in addition to the family pediatrician’s clinical evaluation with routine tools, the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) was completed by parents to assess the child’s language, social skills, behavior, and sensory areas. Parents were also asked to complete the Parenting Stress Index, Short Form (PSI-SF) to verify the magnitude of stress in the parent-child system. Univariate and multivariate analyses were performed to evaluate the association between child and parental characteristics and the presence of warning signs. Results The follow-up assessment was completed for 435 infants: 69 (15.8%) presented warning signs: 43 in the pediatrician’s assessment and 36 in the M-CHAT-R (10 in both). A total of 16 children (14 with warning signs) received a diagnosis after a specialist evaluation. Being male (OR 2.46, 95%CI: 1.23–4.91) and having sleep disorders (OR 2.43, 95% CI 1.17–5.04) was associated with a greater likelihood of warning signs in the multivariate analysis, while reading aloud was a protective factor (not exposed versus exposed (OR = 3.14; 95% CI 1.60–6.17). For 73 children (18.4%), at least one parent tested positive for PSI-SF. An increased prevalence of parental distress was observed in children with warning signs (OR 2.36, 95% CI 1.27–4.37). Conclusions Integrating physician and parental perspectives during well-child visits and in clinical practice appears feasible and can improve the identification of children at risk of developmental disorders.

The need for faster and more accessible alternatives to laboratory microscopy is driving many innovations throughout the image and data acquisition chain in the biomedical field. Benchtop microscopes are bulky, lack communications capabilities, and require trained personnel for analysis. New technologies, such as compact 3D-printed devices integrated with the Internet of Things (IoT) for data sharing and cloud computing, as well as automated image processing using deep learning algorithms, can address these limitations and enhance the conventional imaging workflow. This review reports on recent advancements in microscope miniaturization, with a focus on emerging technologies such as photoacoustic microscopy and more established approaches like smartphone-based microscopy. The potential applications of IoT in microscopy are examined in detail. Furthermore, this review discusses the evolution of image processing in microscopy, transitioning from traditional to deep learning methods that facilitate image enhancement and data interpretation. Despite numerous advancements in the field, there is a noticeable lack of studies that holistically address the entire microscopy acquisition chain. This review aims to highlight the potential of IoT and artificial intelligence (AI) in combination with portable microscopy, emphasizing the importance of a comprehensive approach to the microscopy acquisition chain, from portability to image analysis.

Farmers’ Markets (FMs) have gained relevance in recent years as increasingly acknowledged to be critical to turn to more equitable food systems, easing agroecological transition, and preserving biocultural heritage. However, the issue of the forms of social and institutional coordination needed to create, organize, manage and promote FMs is a recent topic in the literature, and their governance is still poorly considered. Based on a set of case studies in Tuscany, Italy, this paper intends to contribute to filling this gap by analysing the forms of governance and the role of different stakeholders. The hypothesis is that FMs are social constructions that respond to processes of social and institutional innovation through direct exchanges between producers, consumers and other stakeholders, articulated at both local and non-local level. The aim of the paper is to explore the interactions between stakeholders and the corresponding forms of multi-level governance that emerge. The method for testing the hypotheses is qualitative, through semi-structured interviews to FMs managers and conversations with producers and other stakeholders, conducted between May and August 2022 in Tuscany. The research was complemented by consultation of indirect sources, such as FMs websites and social networks. The results are summarized in the elaboration of a three-dimensional and territorially embedded governance model. The first dimension refers to the management of internal relations between stakeholders within the FM. The second corresponds to the activation of dialogue, negotiation, and agreement with the municipality and other local authorities, and with local farmers’ unions. The third type corresponds to vertical flows between the FMs and extraterritorial bodies, i.e., regional government, regional and national farmers’ unions and other stakeholder associations. It is important to note that at FMs level, processes of hybridization between the different types of governance are established. The article contributes to the analysis of FMs as economic and social constructions and may be useful for establishing comparative frameworks around institutional and collective action dimensions, multi-actor and multilevel studies of governance.

BackgroundCariprazine, a third-generation antipsychotic (TGAs), has demonstrated efficacy in the treatment of schizophrenia with good tolerability profile. Actual real-world literature data are lacking, particularly when exploring its efficacy in the long term. The present study examined the effects of cariprazine treatment on specific psychopathological domains with a particular focus on outcomes and side effects in real-life experience, after a long-term treatment.MethodsThe present 12-month longitudinal naturalistic study included a sample of subjects with a DSM-5-TR diagnosis of schizophrenia, recruited in the outpatients’ psychiatric services of university and community hospitals in Italy, naturally treated with cariprazine. The assessments included: a sociodemographic data sheet, the Structured Clinical Interview for the DSM-5 (SCID-5), the Positive and Negative Symptom Scale (PANSS) and the St. Hans Rating Scale (SHRS). The PANSS was also administered after 6 (T1) and 12 (T2) months of treatment with cariprazine while the SHRS at T1.ResultsThe total sample consisted of 31 patients, 15 males and 16 females. A significant decrease of the PANSS’ subscales, Marder factors and total mean scores emerged at both T1 and T2 with respect to T0. Extrapyramidal symptoms occurred in a minority of patients and in mild or mild/moderate forms: no patient showed moderate forms of psychic/motor akathisia or dystonia, three subjects showed moderate parkinsonism.ConclusionsThis study confirms a good efficacy profile of cariprazine in both positive and negative symptoms in patients with Schizophrenia, combined with a good tolerability profile in extrapyramidal symptoms.

Abstract Background Supporting young ADHD patients in transition to adult services is essential. Yet, the low percentages of successful referrals and the issues reported by patients and clinicians stress the need for further attention to transitioning practices. The present study assessed the transitioning process of Attention-Deficit/Hyperactivity Disorder (ADHD) patients in Child and Adolescent Mental Health Services (CAMHS) and Adult Mental Health Services (AMHS) in the Italian territory. We asked child and adult psychiatrists to report the current state of services and their observations on limitations and possible future matters that must be addressed. Method Seventy-seven centers (42 CAMHS, 35 AMHS) filled in a web-based survey in which they reported the number of ADHD patients, how many transitioning patients they had within the past year, and how they structured transition. Results A fragmented picture emerged from the survey. Lack of resources, training, and communication between services hinder the transition process, and many adult patients remain under CAMHS’ care. While some services have a protocol, there is no structured guidance that can help improve integration and continuity of treatment. Conclusion The observed situation reflects a need for improvement and standard guidelines to enable a successful transition process, considering clinicians' and patients’ necessities.

Background: Liver cancer, particularly hepatocellular carcinoma (HCC), is a significant gastrointestinal disease with a mortality rate as high as nearly 80% within five years. The disease’s pathophysiology involves deranged immune responses and bile acid metabolism, with the gut microbiota (GM) playing a crucial role. Recent research highlights the potential of GM in influencing HCC treatment outcomes, especially regarding immune checkpoint inhibitors (ICIs). However, few patients currently benefit from ICIs due to a lack of effective response biomarkers. Aims and methods: This review aimed to explore the literature on HCC treatment issues, focusing on immune response, bile acid metabolism, and GM dysbiosis. This review included studies from PubMed, Medline, and major gastroenterology and hepatology meetings, using keywords like gut microbiota, immune system, liver cancer, and checkpoint inhibitors. Results: GM dysbiosis significantly impacts immune response and bile acid metabolism, making it a promising biomarker for ICI response. Modulating GM can enhance ICI treatment efficacy, although more research is needed to confirm its direct therapeutic benefits for HCC. Conclusions: GM dysbiosis is integral to liver cancer pathogenesis and treatment response. Its modulation offers promising therapeutic avenues for improving HCC prognosis and response to immunotherapy.

Abstract Aims Ensuring a successful transition to Adult Mental Health Services (AMHS) is fundamental for attention deficit/hyperactivity disorder (ADHD) patients to prevent adverse scenarios in adults (e.g., psychiatric disorders, substance or alcohol abuse). Yet, most European nations do not have appropriate transition guidelines and still fail to adequately support transition processes. This study aims to enquire about the current transition paths in Italy and the perceived experiences of the patients and their clinicians. Methods The present observational study collected 36 interviews with young adults with ADHD who turned 18 between 2017 and 2021. Simultaneously, two questionnaires were filled in by the clinicians (both from paediatric and AMHS) who were involved in their transition paths. These tools collected information about the transition process, the services that cared for the young adults and well-being indicators such as impairment in daily life, employment status and the presence of sentinel events (e.g., critical stage accesses to the emergency room or hospitalizations). Successful and failed referrals were analysed. Results A referral to an AMHS was attempted for 16 young adults (8 before age 18 and 8 when turning 18), and 8 patients (22.2% overall) were successfully taken into the care of the AMHS. Twenty patients were not referred since it was deemed unnecessary (N = 6) or because of the lack of specialized services or compliance (N = 14). At the time of the interview, only nine participants were still under AMHS care. Of eleven individuals with a high need for care (identified by the level of impairment, support needs or sentinel events), five were not followed by a mental health professional at the time of the interview. Conclusions For the majority of ADHD young adults, a transition path was never started or completed. While this is partly due to mild levels of impairment, in many cases it was difficult to find a service that could care for the adult patient. Only one out of four young adults are successfully transferred to AMHS care. Creating or improving evidence-based transition guidelines should be a priority of the public health system to ensure healthcare for as many patients as possible. The results of this study will converge towards the need for recommendations for the transition of services from adolescence to adulthood for young people with ADHD for Italian clinical practice.

A 14-year-old female domestic short-haired cat with a diagnosed diabetes mellitus and acromegaly was presented for lethargy and dysorexia. On clinical presentation, the patient showed hyperglycemia, hyperthermia, dull mentation, and dehydration. With the suspicion of an inflammatory or infectious complication of diabetes, she was hospitalized with constant rate infusion of insulin, and empirical ampicillin sulbactam was started. Blood culture revealed positivity for Yersinia pseudotuberculosis and the septic picture was confirmed by blood analysis, with leukocytosis, neutrophilia, and an increased serum amyloid A concentration. The isolated Y. pseudotuberculosis strain showed susceptibility to every antimicrobial tested. During the second day of hospitalization, the onset of hypoglycemia and hypotension was treated with norepinephrine and glucose in fluid therapy. The cat recovered well and was discharged with insulin and amoxicillin-clavulanate. This is the first case of septicemia associated with Y. pseudotuberculosis in a cat, suspected of developing the infection after contact with natural reservoirs such as rodents or birds. This route of transmission should be highlighted especially in relation to the zoonotic potential of the bacteria.

COVID-19 pandemic waves have hit on our lives with pulmonary and, also, gastrointestinal symptoms. The latter also includes acute liver damage linked to direct SARS-CoV-2 action and/or drug-induced (DILI) in the frame of pre-existing chronic liver disease. We aimed to review literature data regarding liver damage during COVID-19. We conducted a systematic search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials and case series using the following keywords and acronyms and their associations: liver disease, COVID-19, acute liver damage, drug-induced liver injury, antivirals. Acute liver damage due to SARS-CoV-2 infection is common among COVID-19 patients and is generally self-limiting. However, chronic hepatic diseases, such as metabolic-associated fatty liver disease (MAFLD), are associated with a less favorable prognosis, especially when alkaline phosphatases show a significant rise. Pathophysiology of COVID-19 liver damage is multifaceted and helps understand differences in liver derangement among patients. Thus, early recognition, monitoring and treatment of liver damage are crucial in these patients. In the frame of a not-ending pandemic sustained by SARS-CoV-2, it is crucial to recognize acute hepatic decompensation due to the virus and/or drugs used for COVID-19 treatment.

Abstract Background Bloodstream infections are a matter of concern in small animal veterinary practice. Few reports are avaiable, especially regarding the role of opportunistic bacteria in becoming infectious. This report aims to add to the current veterinary literature on two opportunistic bacterial species (Enterococcus hirae and Enterobacter xiangfangensis) associated with bloodstream infections in small animals admitted to the Bologna University Veterinary Hospital. Case presentation In the first case, a 15-year-old, immunocompromised, cardiopathic dog was admitted to the hospital for anorexia and diarrhea. The patient had a history of previous surgery and hospitalization. After three days, hyperthermia, leukopenia and hyperlactatemia were recorded, and blood culture revealed positivity for Enterococcus hirae, identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The patient’s general conditions progressively worsened, and the patient was euthanized. In the second case, a 2-year-old cat with chronic ocular herpesvirus infection and hypertrophic cardiomyopathy was admitted to the hospital for anorexia and hyperthermia. The cat was hospitalized one week before and received antimicrobial treatment for urinary tract infection by Staphylococcus felis. Hypokalemia and lymphopenia were also diagnosed. The patient progressively improved and was discharged after three days. On the same day, blood culture taken at admission revealed positivity for Enterobacter xiangfangensis, identified using MALDI-TOF MS. After five days, the patient returned with neurological symptoms, hypothermia and bradycardia, and was euthanized. Conclusions In small animal veterinary practice, the impact of opportunistic bacterial agents (such as E.hirae and E.xiangfangensis) on bloodstream infections remains unclear. As in human medicine, they can be contracted in every healthcare setting and considered hospital-acquired infections. In this report, we highlighted the threat they pose especially in patients with multiple risk factors. Rapid and accurate diagnostic tools (such as MALDI-TOF MS) could be particularly important for reducing the severity of the infections.

The role of commercial banks and financial institutions has been described as crucial for the circular economy since they are key actors in financing companies and projects. The facilitating potential of some financial instruments managed by the financial sector has not been studied in connection to extending the circular economy in the environmental accounting framework. Particularly, the renting contracts service, which has been associated with more sustainable performance, shows interesting circular characteristics for servitization and the sharing economy. By studying the details of renting contracts of a financial institution over 18 years as a case study in Spain, this research demonstrates how this type of service, applied to vehicles, can render important benefits in terms of use of resources, environmental impact, energy efficiency and reduced carbon emissions. Measuring these quantitative impacts and reporting about them is important from an environmental accounting basis and in the framework of the European Union taxonomy for sustainable finance. The results obtained from the stakeholders’ perspective highlight the pivotal role of existing financial instruments and the need for new metrics for reporting linked to the servitization of the economy as a specific circular issue. This paper contributes to the academic literature by bringing empirical results to a still recent line of research. For practitioners, we provide innovative metrics for circular economy in the financial sector, and for policymakers, this research highlights the wider role of financial institutions in promoting circular economy within the sustainability framework.

This study presents a model to measure Circular Economy (CE) in businesses from the point of view of both the range of activities and the intensity with which they are implemented to close material circles. The scope of CE is analysed from an environmental accounting approach with the aim of knowing the degree of implementation of the CE and increasing our understanding of the relationship between the implementation of CE in firms and environmental management accounting and reporting practices (EMAR) developed. The results of an empirical survey conducted on a sample of Spanish companies will be used to examine environmental accounting and reporting practices that can be related to the implementation and measurement of CE and also to the progress being made by these companies in closing material and resource circles. The principal results show that CE activities are generally adopted without thinking in an integrated view of CE principles. Furthermore, there is a moderate correlation between the level of circularity of companies and the development of EMAR practices. This correlation is higher the greater the number of EMAR practices that have been developed, especially the implementation of environmental management systems or the development of transparency and reporting policies. Although firms are progressively adopting practices related to CE, the lack of specific indicators does not allow firms to specifically account for their effect on the closing of material loops.

Rhythmic breathing is generated by neural circuits located in the brainstem. At its core is the preBötzinger Complex (preBötC), a region of the medulla, necessary for the generation of rhythmic breathing in mammals. The preBötC is comprised of various neuronal populations expressing neurokinin-1 receptors, the cognate G-protein-coupled receptor of the neuropeptide substance P (encoded by the tachykinin precursor 1 or Tac1). Neurokinin-1 receptors are highly expressed in the preBötC and destruction or deletion of neurokinin-1 receptor-expressing preBötC neurons severely impair rhythmic breathing. Although, the application of substance P to the preBötC stimulates breathing in rodents, substance P is also involved in nociception and locomotion in various brain regions, suggesting that Tac1 neurons found in the preBötC may have diverse functional roles. Here, we characterized the role of Tac1-expressing preBötC neurons in the generation of rhythmic breathing in vivo, as well as motor behaviors. Using a cre-lox recombination approach, we injected adeno-associated virus containing the excitatory channelrhodopsin-2 ChETA in the preBötC region of Tac1-cre mice. Employing a combination of histological, optogenetics, respiratory, and behavioral assays, we showed that stimulation of glutamatergic or Tac1 preBötC neurons promoted rhythmic breathing in both anesthetized and freely moving animals, but also triggered locomotion and overcame respiratory depression by opioid drugs. Overall, our study identified a population of excitatory preBötC with major roles in rhythmic breathing and behaviors.

This work reports about preparation of W/Fe co-sputtered layers between tungsten and steel in order to ease their coefficient of thermal expansion mismatch.Iron and tungsten have been gradually co-sputtered on W tiles with real time deposition parameters changing to obtain a graded interlayer: SEM, EDS, XPS, HR-TEM have been used to characterize the W/Fe co-sputtered layer.W tiles co-sputtered with the W/Fe layers have been hot pressed to steel tiles: morphology and mechanical strength have been investigated for joints with and without W/Fe co-sputtered layer.Lap-shear tests in compression at room temperature have been made on hot pressed W/steel joints with and without W/Fe co-sputtered layer, showing a different behaviour.High flux test on joints with and without W/Fe co-sputtered layer are reported and discussed. The mechanical test results of manufactured joints are in good accordance with high heat flux test results, showing that the behaviour of hot-pressed joints with W/Fe co-sputtered layer was slightly worse if compared to joints without co-sputtered layer at the interface.

Background and aim: Antimicrobial resistance (AMR) is a chronic issue of our Westernized society, mainly because of the uncontrolled and improper use of antimicrobials. The coronavirus disease 2019 (COVID-19) pandemic has triggered and expanded AMR diffusion all over the world, and its clinical and therapeutic features have changed. Thus, we aimed to review evidence from the literature on the definition and causative agents of AMR in the frame of the COVID-19 post-pandemic era. Methods: We conducted a search on PubMed and Medline for original articles, reviews, meta-analyses, and case series using the following keywords, their acronyms, and their associations: antibiotics, antimicrobial resistance, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), COVID-19 pandemic, personal protective equipment. Results: AMR had a significant rise in incidence both in in-hospital and outpatient populations (ranging from 5 up to 50%) worldwide, but with a variegated profile according to the germ and microorganism considered. Not only bacteria but also fungi have developed more frequent and diffuse AMR. These findings are explained by the increased use and misuse of antibiotics and preventive measures during the first waves of the SARS-CoV2 pandemic, especially in hospitalized patients. Subsequently, the reduction in and end of the lockdown and the use of personal protective equipment have allowed for the indiscriminate circulation of resistant microorganisms from low-income countries to the rest of the world with the emergence of new multi- and polyresistant organisms. However, there is not a clear association between COVID-19 and AMR changes in the post-pandemic period. Conclusions: AMR in some microorganisms has significantly increased and changed its characteristics during and after the end of the pandemic phase of COVID-19. An integrated supranational monitoring approach to this challenge is warranted in the years to come. In detail, a rational, personalized, and regulated use of antibiotics and antimicrobials is needed.

This paper analyzes the issues related to the establishment of an academic fashion course in our age of complexity. It shows the transition from studies focused on the analysis of the fashion object, with reference to the history of costume and the history of art, to studies focused on the complex of productive, cultural and communicative activities that established the current fashion system. It also shows the correspondence of the course launched at the University of Milan with respect to the so-called “Triple Helix” cultural policy. It therefore refers to the connections among the three poles of the virtuous exchange relationship: first, the university, with its research centers and scientific and educational activities; secondly, the world of work, with the relationship with representatives of companies and various entities in the fashion world, as well as the promotion of internships; finally, the third pole consists of the national and European government and the various initiatives to support innovative aspects and sustainable fashion.

Nanomechanics is a highly developed area of research, given the significant reported changes in material properties at the nanometer scale, requiring the development of new theories to explain the underlying mechanisms. Such theories must be based on measurements that are as accurate as possible, but unfortunately, conventional experimental techniques do not apply to such small components. Here we present a unique new method to control electro-mechanical forces on quasi −1D nanostructures through static electric fields with multiple ways of control of GaAs nanowires’ strain directly on the growth substrate.

Receptor-Interacting serine/threonine-Protein Kinase 1 (RIPK1) emerged as an important driver of inflammation and, consequently, inflammatory pathologies. The enzymatic activity of RIPK1 is known to indirectly promote inflammation by triggering cell death, in the form of apoptosis, necroptosis and pyroptosis. Small molecule Receptor-Interacting serine/threonine-Protein Kinase 1 inhibitors have therefore recently entered clinical trials for the treatment of a subset of inflammatory pathologies. We previously identified GSK2656157 (GSK’157), a supposedly specific inhibitor of protein kinase R (PKR)-like ER kinase (PERK), as a much more potent type II Receptor-Interacting serine/threonine-Protein Kinase 1 inhibitor. We now performed further structural optimisation on the GSK’157 scaffold in order to develop a novel class of more selective Receptor-Interacting serine/threonine-Protein Kinase 1 inhibitors. Based on a structure-activity relationship (SAR) reported in the literature, we anticipated that introducing a substituent on the para-position of the pyridinyl ring would decrease the interaction with PERK. Herein, we report a series of novel GSK’157 analogues with different para-substituents with increased selectivity for Receptor-Interacting serine/threonine-Protein Kinase 1. The optimisation led to UAMC-3861 as the best compound of this series in terms of activity and selectivity for Receptor-Interacting serine/threonine-Protein Kinase 1 over PERK. The most selective compounds were screened in vitro for their ability to inhibit RIPK1-dependent apoptosis and necroptosis. With this work, we successfully synthesised a novel series of potent and selective type II Receptor-Interacting serine/threonine-Protein Kinase 1 inhibitors based on the GSK’157 scaffold.

Opioid medications are the mainstay of pain management but present substantial side-effects such as respiratory depression which can be lethal with overdose. Most opioid drugs, such as fentanyl, act on opioid receptors such as the G-protein-coupled µ-opioid receptors (MOR). G-protein-coupled receptors activate pertussis toxin-sensitive G-proteins to inhibit neuronal activity. Binding of opioid ligands to MOR and subsequent activation G proteins βγ is modulated by regulator of G-protein signaling (RGS). The roles of G-proteins βγ and RGS in MOR-mediated inhibition of the respiratory network are not known. Using rodent models to pharmacologically modulate G-protein signaling, we aim to determine the roles of βγ G-proteins and RGS4. We showed that inhibition of βγ G-proteins using gallein perfused in the brainstem circuits regulating respiratory depression by opioid drugs results in complete reversal of respiratory depression. Blocking of RGS4 using CCG55014 did not change the respiratory depression induced by MOR activation despite co-expression of RGS4 and MORs in the brainstem. Our results suggest that neuronal inhibition by opioid drugs is mediated by G-proteins, but not by RGS4, which supports the concept that βγ G-proteins could be molecular targets to develop opioid overdose antidotes without the risks of re-narcotization often found with highly potent opioid drugs. On the other hand, RGS4 mediates opioid analgesia, but not respiratory depression, and RGS4 may be molecular targets to develop pain therapies without respiratory liability.