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Purpose: HEV is an emerging pathogen in Europe and was previously shown to be hyperendemic in areas of Abruzzo and Lazio, Central Italy. No systematic analysis of the HEV strains responsible for human infections over several years in Central Italy has previously been reported. Aim of the study was the molecular characterization of HEV from autochthonous hepatitis E cases occurred in Abruzzo and Lazio between 2015 and 2023., Methods: Samples from 118 cases collected as part of virological surveillance in Abruzzo and Lazio from 2015 to 2023 were subjected to HEV sequencing and phylogenetic analysis., Results: The main observed subtype was 3f, followed by 3c and 3e. The annual subtype distribution was quite stable over the observation period, but 3f cases tended to concentrate in winter/early spring whereas 3e cases in summer. Phylogenetic clusters of highly related sequences (a) highlighted unrecognized "point source outbreaks", (b) provided molecular support to temporally and/or geographically linked cases and (c) provided evidence for transmission of identical/highly related strains up to months/years following their first detection., Conclusions: The data provide an overview of the HEV strains responsible for human infections over eight years in Central Italy. The observed subtype distribution appears to agree better with the subtype distribution reported in Italy in pigs rather than in geographically matched wild boars, suggesting pig and its derivate food was a more frequent source of infection than wild boar in Abruzzo and Lazio. Molecular characterization is essential to recognize "point source outbreaks" and to monitor HEV circulation., (© 2024. The Author(s).)

Background: Ceruloplasmin (Cp) is the most important serum copper transport protein playing a key role in the binding of iron to transferrin. It is a positive acute-phase response protein and the first-level diagnostic marker for Wilson disease and aceruloplasminemia. However, standardization of Cp measurement has not been successful, and assay specific reference levels of Cp are required., Methods: From May 2019 to July 2022, we enrolled 1706 consecutive healthy Italian blood donors (1285 men and 421 women, 18 to 65 years) to identify the reference intervals of serum Cp through quantile regression and evaluate the relationship of Cp with age, sex, iron, and metabolic status through linear regression., Results: We found that mean serum Cp was influenced by sex and slightly by age. The lower reference Cp value rose slightly with increasing age in both men and women. The upper reference value increased, reaching a plateau of about 25 mg/dL around 25 years in men, while in women it initially increased to around 45 mg/dL in young adults to fall sharply below 30 mg/dL for adults after their fifties., Conclusions: We showed that the normal reference curves of serum Cp vary according to sex in a large population of healthy adults. While the lower reference values did not appear to be influenced by age and sex, the upper ones differed according to sex and age showing a particularly high variability in women, possibly reflecting different hormonal status., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Mental disorders with body-centered symptoms, such as somatic, eating, and body dysmorphic disorders, present difficulties in psychotherapy because psychological suffering is manifested in the body rather than expressed verbally. The present study illustrates a single case multi-method investigation sensitive to detecting characteristic change manifestations in the treatment of these disorders. We investigated a treatment of a patient with body dysmorphic disorder. Computerized linguistic measures were applied to 86 sessions to assess changes in symbolic processing; out of the 86 sessions, 40 were analyzed to calculate the proportion of speech focused on bodily symptoms versus on relationships. Changes in personality were assessed using the SWAP-200 on nine sessions from different treatment stages. Measures of linguistic style, speech content, and personality showed marked changes over the treatment. The patient manifested schizoid and schizotypal personality traits that decreased over time, along with an increase in personality high-functioning dimension. The patient's ability to translate his emotional experience into words steadily increased, switching the primary focus of narratives from bodily symptoms to relationships. A multimethod assessment of the treatment of body dysmorphic disorder shows that improvement in personality functioning is accompanied by a shift from a focus on bodily experiences to a focus on relationships.

Digital transformation has become a cornerstone of innovation in pharmaceutical research and development (R&D). Pharmaceutical companies now have an imperative to embrace transformation, including mid-sized and small-sized companies despite resource limitations that do not allow economies of scale compared with larger organizations. This article describes the journey undertaken by Chiesi to develop an efficient framework to drive digital transformation along its R&D value chain with the objective of building and refreshing a clear roadmap and relevant priorities, together with identifying and enabling new digital capabilities and skills within R&D, defining tools and processes that will guide Chiesi activities in the space up to mid-long term. This work has led so far to five main achievements, which align with the steps in the framework: a strategically aligned roadmap with key focus areas for digital transformation and a dedicated team to lead the effort; a common language for data across the R&D value chain; an internal mindset that's open to innovation and participation in key external networks and consortia; a set of quick-win use cases for the new framework; and a defined set of Key Performance Indicators (KPIs) and monitoring tools for digital transformation. The work presented here demonstrates that R&D digital transformation should represent an ongoing process to enable cross-functional collaboration and integration within complex corporate environments that face an ever-growing volume of diverse data, to efficiently support business needs, and to ensure a positive impact on patient care., (© 2024. The Author(s).)

Objectives: to describe prevalence of disability in the population of the Agency for Health Protection of Milan (ATS Milan), integrating current administrative healthcare, socio-healthcare, and social data; to classify disability with a diagnosis into a predominant structural and functional category according to the International Classification of Functioning, Disability and Health (ICF), supplementing it with additional levels of detail., Design: retrospective observational study., Setting and Participants: subjects residing in the territory of ATS Milan in the years from 2018 to 2022.  Main outcomes measures: prevalence of disability in the population of ATS Milan from 2018 to 2022; average annual costs since disability diagnosis of the entire population and stratified by the most common ICF classifications., Results: the prevalence of disability ranges from 5.8% in 2018 to 8.4% in 2022. In general, women have a higher prevalence than men. However, there are significant differences in the gender distribution depending on the considered age group. The main disabilities (32.2%) affect the structures of the nervous system and mental functions, followed by disabilities identified solely by major prosthetic devices (9.4%) and sensory disabilities with alterations in sensory functions with the presence of a major device (5.2%). Analysis of average total annual per capita costs shows an upward trend with increasing years since the diagnosis., Conclusions: the definition of standardized tools, such as the selection from several available healthcare data provided by service suppliers, can be helpful in obtaining reliable data on the prevalence of disability in the population. This evidence can be useful in planning public health interventions to address the needs of this population. The work developed by ATS Milan has been carried out in alignment with the activities outlined in Mission 5 of the National Recovery and Resilience Plan (PNRR), in particular for the reform of disability legislation, which foresees the definition of standardized tools for the in-depth study of the epidemiological aspects of the phenomenon.

The negative impact of the COVID-19 pandemic on mental health has been widely demonstrated; however, few studies have investigated the psychological processes involved in this impact, including core beliefs violation, meaning-making disruption, interpersonal support, or one's relational functioning. This study explored the mental health of 215 Italian adolescents during the COVID-19 pandemic and the subsequent outbreak of the Russian-Ukrainian war. By administering a set of questionnaires, several cognitive and emotional variables were investigated, including core belief violation, meaning attribution to the pandemic and war, attachment, and emotion regulation, social media addiction, and relationships with significant others and teachers. We conducted some descriptive, mean difference, correlational, and predictive analyses that revealed a significant association between core belief violation caused by war and pandemic, ability to integrate war and pandemic within personal meaning universe, the relational support received, and mental health. The relationship with teachers during these challenging periods improved significantly according to the respondents' opinion, becoming both more authoritative and empathic. This study offers insights into what cognitive and relational processes are useful to intervene on to reduce the distress of adolescents who are facing significant moments of crisis due to events that challenge their cognitive and emotional balance.

Viral fusion proteins facilitate cellular infection by fusing viral and cellular membranes, which involves dramatic transitions from their pre- to postfusion conformations. These proteins are among the most protective viral immunogens, but they are metastable which often makes them intractable as subunit vaccine targets. Adapting a natural enzymatic reaction, we harness the structural rigidity that targeted dityrosine crosslinks impart to covalently stabilize fusion proteins in their native conformations. We show that the prefusion conformation of respiratory syncytial virus fusion protein can be stabilized with two engineered dityrosine crosslinks (DT-preF), markedly improving its stability and shelf-life. Furthermore, it has 11X greater potency as compared with the DS-Cav1 stabilized prefusion F protein in immunogenicity studies and overcomes immunosenescence in mice with simply a high-dose formulation on alum., (© 2024. The Author(s).)

Alpha-mannosidosis (MIM #248500) is an ultra-rare autosomal recessive lysosomal storage disease with multi-system involvement and a wide phenotypic spectrum. Information on long-term outcomes remains poor. We present the long-term outcomes (median, 19 years) of nine patients with alpha-mannosidosis, three females and six males, followed at a single center. The findings of the nine patients were collected from medical records and reported as mean ± SD or median, and range. The age of onset of the first symptoms ranged from 0-1 to 10 years. The diagnostic delay ranged from 2 to 22 years (median= 11 years). Coarse face, hearing, heart valves, joints, gait, language, dysarthria, psychiatric symptoms, I.Q., MRI, walking disabilities, orthopedic disturbances and surgeries showed a slow worsening over the decades. Our patients showed a slowly worsening progressive outcome over the decades. Psychiatric symptoms were present in 100% of our population and improved with the appropriate pharmacological intervention. This aspect requires attention when following up on these patients. Our description of the long-term evolution of alpha-mannosidosis patients may provide basic knowledge for understanding the effects of specific treatments., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Haemochromatosis (HC) encompasses a range of genetic disorders. HFE-HC is by far the most common in adults, while non-HFE types are rare due to mutations of HJV, HAMP, TFR2 and gain-of-function mutations of SLC40A1. HC is often unknown to paediatricians as it is usually asymptomatic in childhood. We report clinical and biochemical data from 24 paediatric cases of HC (10 cases of HFE-, 5 TFR2-, 9 HJV-HC), with a median follow-up of 9.6 years. Unlike in the adult population, non-HFE-HC constitutes 58% (14/24) of the population in our series. Transferrin saturation was significantly higher in TFR2- and HJV-HC compared to HFE-HC, and serum ferritin and LIC were higher in HJV-HC compared to TFR2- and HFE-HC. Most HFE-HC subjects had relatively low ferritin and LIC at the time of diagnosis, so therapy could be postponed for most of them after the age of 18. Our results confirm that HJV-HC is a severe form already in childhood, emphasizing the importance of early diagnosis and treatment to avoid the development of organ damage and reduce morbidity and mortality. Although phlebotomies were tolerated by most patients, oral iron chelators could be a valid option in early-onset HC., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)