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The aim of the study was to compare the analgesic efficacy of butorphanol and lidocaine, alone or in combination, in calves undergoing surgical repair of umbilical hernia. The study was conducted in 60 calves of different breeds. Xylazine 0.3 mg/kg was administered intramuscularly to all animals in the study. The animals were then divided into three groups (n = 20) that received different treatments with lidocaine at 4.5 mg/kg and butorphanol at 0.02 mg/kg. The L group received lidocaine both by infiltration of the surgical planes and intraperitoneally, the B group received butorphanol both by infiltration of the surgical planes and intraperitoneally, and finally the LB group received lidocaine by infiltration of the surgical planes and butorphanol intraperitoneally. Heart and respiratory rates, haemoglobin oxygen saturation, non-invasive blood pressure and temperature were recorded during surgery. Response to the surgical stimulus was scored on a cumulative numerical scale that included percentage changes in HR, RR and SAP. Postoperative pain was assessed by three independent observers, blinded to treatment, using the UNESP-Botucatu Unidimensional Composite Pain Scale (UNESP-Botucatu UCPS-IV) for the assessment of postoperative pain in cattle. The course of physiological variables was appropriate for patients under anaesthesia. No subject required rescue intraoperative analgesia. In group L, 4 subjects at 40 m and 5 subjects at 50 m required postoperative rescue analgesia. Both butorphanol alone and the combination of butorphanol and lidocaine showed excellent intraoperative and postoperative scores. Furthermore, this combination did not cause any cardiopulmonary or other adverse effects. Based on the results of this study, both butorphanol alone and the co-administration of butorphanol and lidocaine administered locally proved to be safe and effective in providing adequate and long-lasting analgesia in calves, helping to reduce postoperative discomfort and maintaining adequate animal welfare.

The emergence of vaccinomics and system vaccinology represents a transformative shift in immunization strategies, advocating for personalized vaccines tailored to individual genetic and immunological profiles. Integrating insights from genomics, transcriptomics, proteomics, and immunology, personalized vaccines offer the promise of enhanced efficacy and safety, revolutionizing the field of vaccinology. However, the development of personalized vaccines presents multifaceted challenges, including technical, ethical, economic, and regulatory considerations. Addressing these challenges is essential to ensure equitable access and safety of personalized vaccination strategies. Despite these hurdles, the potential of personalized vaccines to optimize responses and mitigate disease burden underscores the significance of ongoing research and collaboration in advancing precision medicine in immunization.

Lava tubes are powerful heat insulators, allowing lava to practically keep the initial temperature and travel longer distances than when freely flowing on the ground surface. It is thus extremely important to recognize how, when and where these structures form within a lava flow field for hazard assessment purposes, in order to plan possible interventions should a lava flow approach inhabited areas. Often being formed within thick and complex lava flow fields, lava tubes are difficult to detect, study and explore. In this study, we analyse the 1792–93 Etna lava flow field emplaced on a steep slope (>4°) which comprises several lava tubes located at different distances from the eruptive fissure, at different levels within the lava flow field, and showing various inner morphologies, with peculiar inner features related to their maturity and eruptive history. Our aim is to verify whether it is possible to connect the underground features with features observed on the lava flow surface in order to reconstruct the extension of the tube network and unravel the genetic processes. Our results show that, in the studied lava flow field, a clear correspondence is possible between shallow tubes emplaced late during the lava flow field growth and surface textures. In addition, vertical and horizontal tube capture is very widespread, and might be the primary process for lava tube persistence and long life. Our results might be applicable to other lava tubes on Earth and other rocky planets.

Food protein-induced enteropathy (FPE) belongs to non-IgE gastrointestinal mediated food allergies. FPE is a syndrome characterized by diarrhea, weight loss and failure to thrive in young infants. Cow milk is the culprit food that most frequently causes FPE. The prevalence of FPE has not been fully estimated, but it is relatively rare. The diagnosis is based on the clinical manifestations and histological findings through colonoscopy. Laboratory tests are somewhat helpful in the diagnosis, although there are no disease-specific findings. Allergy testing for food specific IgE is not routinely recommended. The cornerstone of the management of FPE is the removal of culprit food from the diet. FPE is usually a transient condition that resolves in most cases by 1–2 years of life. This review addresses the latest findings on FPE, including a practical guide to assist pediatricians treating children with FPE.

Oral squamous cell carcinoma (OSCC) is an aggressive disease whose incomplete biological comprehension contributes to the inappropriate clinical management and poor prognosis. Thus, the identification of new promising molecular targets to treat OSCC is of paramount importance. Ferroptosis is a regulated cell death caused by the iron-dependent accumulation of reactive oxygen species and the consequent oxidative damage of lipid membranes. Over the last five years, a growing number of studies has reported that OSCC is sensitive to ferroptosis induction and that ferroptosis inducers exert a remarkable antitumor effect in OSCC, even in those displaying low response to common approaches, such as chemotherapy and radiotherapy. In addition, as ferroptosis is considered an immunogenic cell death, it may modulate the immune response against OSCC. In this review, we summarize the so far identified ferroptosis regulatory mechanisms and prognostic models based on ferroptosis-related genes in OSCC. In addition, we discuss the perspective of inducing ferroptosis as a novel strategy to directly treat OSCC or, alternatively, to improve sensitivity to other approaches. Finally, we integrate data emerging from the research studies, reviewed here, through in silico analysis and we provide a novel personal perspective on the potential interconnection between ferroptosis and autophagy in OSCC.

Objective: Smoking is the cause of numerous oral pathologies. The aim of the study was to evaluate the effect of smoking traditional cigarettes, e-cigarettes, and heat-not-burn products on the content of salivary cytokines, chemokines, and growth factors in healthy young adults.Design: Three groups of twenty-five smokers each as well as a control group matched in terms of age, gender, and oral status were enrolled in the study. In unstimulated saliva collected from study groups and participants from the control group, the concentrations of cytokines, chemokines, and growth factors were assessed by Bio-Plex® Multiplex System.Results: We demonstrated that smoking traditional cigarettes is responsible for increasing the level of IFN-γ compared to non-smokers and new smoking devices users in unstimulated saliva in the initial period of addiction. Furthermore, e-cigarettes and heat-not-burn products appear to have a similar mechanism of affecting the immune response system of unstimulated saliva, leading to inhibition of the local inflammatory response in the oral cavity.Conclusion: Smoking traditional cigarettes as well as e-cigarettes and heat-not-burn products is responsible for changes of the local immune response in saliva. Further research is necessary to fill the gap in knowledge on the effect of new smoking devices on the oral cavity immune system.

ObjectiveThe prevalence of anxiety and depression in patients diagnosed with Alopecia Areata (AA) is very high and this significant burden of psychological symptoms threatens the Health-Related Quality of Life (HRQoL) of affected patients. Indeed, AA often does not produce significant physical symptoms, but it nonetheless disrupts many areas of mental health. Clinical assessment of disease severity may not reliably predict patient's HRQoL, nor may it predict the patient's perception of illness. For this reason, considerable effort has been made to apply and develop measures that consider patient's perception and assess the HRQoL of individuals affected by AA. The aim of this multicentric study was to provide the Italian version of the Skindex-16AA and to evaluate its psychometric properties in a clinical sample of consecutive patients with moderate-to-severe AA.MethodsThis is a longitudinal, multicenter, observational study. Patients returned for follow-up visits at 4-, 12-, and 24-weeks. The analyses of the current work aimed to confirm the factorial structure of the Skindex-16AA. In the case of non-fit, an alternative structure for the model was proposed, using an Exploratory Graph Analysis and the Bayesian approach.ResultsThe sample was composed of 106 patients with AA. Alopecia Universalis was the most frequently diagnosed type of alopecia at all time points. The analyses on the Skindex-16AA revealed that a two-factor structure with eight items fit the data best (Bayesian Posterior Predictive Checking using 95% Confidence Interval for the Difference Between the Observed and the Replicated Chi-Square values = −6.246/56.395, Posterior Predictive P-value = 0.06), and reported satisfactory psychometric properties (i.e., internal consistency and convergent validity).ConclusionThe Skindex-8AA demonstrated optimal psychometric properties (i.e., convergent and construct validity, and test-retest reliability) measured in a sample of patients with AA, that may suggest that it is an appropriate tool to measure the HRQoL in AA patients. However, further studies are needed in order to confirm and tested other psychometric features of this tool.

Potential traumatic events, such as breast cancer, can influence autobiographical memory (AM), interrupting the continuity of narrative identity. AM is based on a hierarchical search across different levels of specificity that are indexed from top to bottom when a memory is retrieved. In the breast cancer field, non-specific AMs are an observed clinical phenomenon. In particular, breast cancer survivors report issues related to self-defining memories (SDMs), specific and significant AMs that evoke strong emotions and sensory details at the time of memory. SDMs are linked to life goals and facilitate adaptation to critical experiences, preserving the continuity of identity. This study explored the narrative identity integration process of breast cancer survivors, analyzing themes, specificity, and integrative meaning in SDMs. Ten women participated in an online group support program centered on the integration of AMs linked to the cancer journey. Participants were asked to assess their body image perceptions, filling out an online survey three times, in which they had to report three SDMs each time. A reflexive thematic analysis of the SDMs identified three main themes: the onset of breast cancer; the labeling of negative emotions, and changes in the body. The results indicated inhibited retrieval of specific episodes, fostering a progressive failure in memory characterization and the concurrent meaning-making process. Participants struggled with connecting the memories to insights regarding their self and life, as well as relating the memories to external conditions and other individuals. Further studies might examine the impact of these difficulties on the psychological adjustment of BC long-term survivors. They could also explore cognitive reconstruction by reframing the memories and re-evaluating their traumatic meanings.

IntroductionAnnual influenza and COVID-19 vaccinations are effective tools for reducing the disease burden. The goals of the present cross-sectional survey were to investigate attitudes and behaviors toward the simultaneous vaccination against seasonal influenza and COVID-19 and the factors associated.MethodsQuestionnaires were self-administered or researcher-administered between October 2023 and February 2024 in an immunization center in the southern part of Italy.ResultsAll 151 subjects eligible for influenza and COVID-19 vaccinations who attended the center agreed to participate. A total of 59.9% of respondents received concurrent seasonal influenza and COVID-19 vaccinations. Those who perceived that the simultaneous vaccination was safer and those who have been infected by SARS-CoV-2 fewer times were more likely to have simultaneously received both vaccinations. Regarding the reasons reported, half of the sample stated that the simultaneous vaccination was safe and that they were adequately informed. This was more likely indicated by the respondents who had received at least four doses of the COVID-19 vaccination. Among those who had not received the simultaneous vaccination, 70.7% and 29.3% had received only seasonal influenza and COVID-19.ConclusionEducational health communication campaigns are necessary to improve compliance with simultaneous administration of seasonal influenza and COVID-19 vaccinations and to increase the unsatisfactory coverage.

The thyroid gland regulates most of the physiological processes. Environmental factors, including climate change, pollution, nutritional changes, and exposure to chemicals, have been recognized to impact thyroid function and health. Thyroid disorders and cancer have increased in the last decade, the latter increasing by 1.1% annually, suggesting that environmental contaminants must play a role. This narrative review explores current knowledge on the relationships among environmental factors and thyroid gland anatomy and function, reporting recent data, mechanisms, and gaps through which environmental factors act. Global warming changes thyroid function, and living in both iodine-poor areas and volcanic regions can represent a threat to thyroid function and can favor cancers because of low iodine intake and exposure to heavy metals and radon. Areas with high nitrate and nitrite concentrations in water and soil also negatively affect thyroid function. Air pollution, particularly particulate matter in outdoor air, can worsen thyroid function and can be carcinogenic. Environmental exposure to endocrine-disrupting chemicals can alter thyroid function in many ways, as some chemicals can mimic and/or disrupt thyroid hormone synthesis, release, and action on target tissues, such as bisphenols, phthalates, perchlorate, and per- and poly-fluoroalkyl substances. When discussing diet and nutrition, there is recent evidence of microbiome-associated changes, and an elevated consumption of animal fat would be associated with an increased production of thyroid autoantibodies. There is some evidence of negative effects of microplastics. Finally, infectious diseases can significantly affect thyroid function; recently, lessons have been learned from the SARS-CoV-2 pandemic. Understanding how environmental factors and contaminants influence thyroid function is crucial for developing preventive strategies and policies to guarantee appropriate development and healthy metabolism in the new generations and for preventing thyroid disease and cancer in adults and the elderly. However, there are many gaps in understanding that warrant further research.

ObjectivesTo evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA).MethodsA total of 40 pediatric patients, 20 (50%) with JIA and 20 (50%) healthy control subjects, were studied, and performed the renal function on 24-h collection and the 24-h ambulatory blood pressure monitoring (ABPM). Moreover, we compared renal function and blood pressure trends between the groups of JIA patients with different disease activities.ResultsNo statistically significant differences were observed between patients with JIA and healthy children in terms of glomerular filtration rate (GFR), fractional excretion of sodium (FENa), tubular reabsorption of phosphate (TRP), and calcium-creatinine urine ratio (CaU/CrU). In contrast, we observed significantly higher values in JIA patients than in controls for the presence of hematuria (p

PurposeThis study aimed to investigate the effects of ejaculatory abstinence on sperm parameters.MethodsThis analysis was registered in PROSPERO (CRD42023472124). We performed a search on PubMed using the following text terms: ((“sperm parameters” OR “sperm analysis” [Mesh]) AND (“sperm DNA fragmentation” OR “DNA fragmentation” [Mesh]) AND (“sexual abstinence” [Mesh] OR “abstinence”)) and an advanced search in Scopus using the terms (“sperm parameters” OR “sperm parameters” OR “DNA fragmentation”) AND (“abstinence”). The sperm parameters that were investigated were sperm volume, total sperm motility, progressive sperm motility, sperm concentration, sperm morphology, and sperm DNA fragmentation (SDF). A two-day cut-off as a “short” or “long” abstinence period has been defined.ResultsThirteen studies published between 2013 and 2022 were included in this meta-analysis. A total of 2,315 patients, ranging from 6 to 836 from each cohort, were enrolled in the study. We showed that longer abstinence time was associated with greater sperm concentration (mean difference [MD]: 8.19; p

ObjectiveInflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF.MethodsThe risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still’s disease patients and Behçet’s disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression.Results580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet’s disease patients and 497 Still’s disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still’s disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet’s disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (β1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (β1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (β1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (β1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (β1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (β1 = 2.089, 95% CI. 0.7-3.5, p=0.002).ConclusionsThe risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Human Embryonic Kidney cells (HEK293) are a popular host for recombinant protein expression and production in the biotechnological industry. This has driven within both, the scientific and the engineering communities, the search for strategies to increase their protein productivity. The present work is inserted into this search exploring the impact of adding sodium acetate (NaAc) into a batch culture of HEK293 cells. We monitored, as a function of time, the cell density, many external metabolites, and the supernatant concentration of the heterologous extra-cellular domain ECD-Her1 protein, a protein used to produce a candidate prostate cancer vaccine. We observed that by adding different concentrations of NaAc (0, 4, 6 and 8 mM), the production of ECD-Her1 protein increases consistently with increasing concentration, whereas the carrying capacity of the medium decreases. To understand these results we exploited a combination of experimental and computational techniques. Metabolic Flux Analysis (MFA) was used to infer intracellular metabolic fluxes from the concentration of external metabolites. Moreover, we measured independently the extracellular acidification rate and oxygen consumption rate of the cells. Both approaches support the idea that the addition of NaAc to the culture has a significant impact on the metabolism of the HEK293 cells and that, if properly tuned, enhances the productivity of the heterologous ECD-Her1 protein.

BackgroundVaccination in pregnancy offers protection to the mother and the newborn. In Italy, influenza, pertussis, and COVID-19 vaccinations are recommended in pregnancy, but vaccination coverage is still far from the National Immunization Plan goals. We aimed to assess knowledge and attitude on maternal immunization in two groups of Italian women, in pregnancy and in reproductive age (non pregnant).MethodsA cross sectional study on Italian childbearing age women gathering information on their knowledge on maternal immunization and attitudes to receiving influenza and pertussis vaccines in pregnancy was carried out at the University of Rome Tor Vergata, between September 2019 and February 2020. Logistic and multinomial regressions were chosen as statistical tests for our analysis.Results1,031 women participated in the survey by answering the questionnaire. Out of these, 553 (53.6%) women were pregnant, and 478 (46.4%) were in the reproductive age. 37% (204/553) of pregnant women and 41% (198/476) of non pregnant women are aware of the existence of an immunization plan for pregnant women in Italy. The group with age between 20 and 30, for both pregnant women and women in the reproductive age, has a better knowledge of vaccination in pregnancy. Working status is a variable associated with more awareness about vaccination during pregnancy only for pregnant women (OR = 2.34, p

Maca is a traditional Andean crop used as a nutraceutical for the fertility-enhancing properties that are linked with antioxidant activity. The aim of this study was to evaluate, for the first time, the potential beneficial effects of oral Maca (Lepidium meyenii or Lepidium peruvianum) supplementation in improving reproductive performance in male dogs. Forty-eight male dogs of different breeds were enrolled in the study, fed the same maintenance diet, and exposed to the same environmental conditions. The subjects were divided into four groups of 12 dogs each: Subfertile treatment group, Subfertile control group, Normofertile treatment group, and Normofertile control group. The dogs in the treatment groups received Lepidium meyenii in their diet in a capsule formulation [75 mg/kg Maca extract 10:1, thickening agent (hydroxypropyl methylcellulose), ground rice], while the control groups received placebo capsule (starch). For each subject included in the study, the spermiogram was analyzed at three time points of the sperm cycle: at day 0 (T0), day 31 (T31), and day 62 (T62). Dietary supplementation with Maca in subfertile subjects resulted in a significant increase in ejaculate volume and total sperm count compared to the control group. This increase was also observed in normofertile subjects in the treatment group. In addition, total and progressive motility as well as sperm morphology were significantly improved in the groups treated with Maca compared to the control groups. The results thus highlight, for the first time, the potential efficacy of supplementation with 75 mg/kg of Maca extract daily in improving semen quality in dogs.

IntroductionAntarctic Porifera have gained increasing interest as hosts of diversified associated microbial communities that could provide interesting insights on the holobiome system and its relation with environmental parameters.MethodsThe Antarctic demosponge species Haliclona dancoi and Haliclona scotti were targeted for the determination of persistent organic pollutant (i. e., polychlorobiphenyls, PCBs, and polycyclic aromatic hydrocarbons, PAHs) and trace metal concentrations, along with the characterization of the associated prokaryotic communities by the 16S rRNA next generation sequencing, to evaluate possible relationships between pollutant accumulation (e.g., as a stress factor) and prokaryotic community composition in Antarctic sponges. To the best of our knowledge, this approach has been never applied before.ResultsNotably, both chemical and microbiological data on H. scotti (a quite rare species in the Ross Sea) are here reported for the first time, as well as the determination of PAHs in Antarctic Porifera. Both sponge species generally contained higher amounts of pollutants than the surrounding sediment and seawater, thus demonstrating their accumulation capability. The structure of the associated prokaryotic communities, even if differing at order and genus levels between the two sponge species, was dominated by Proteobacteria and Bacteroidota (with Archaea abundances that were negligible) and appeared in sharp contrast to communities inhabiting the bulk environment.DiscussionsResults suggested that some bacterial groups associated with H. dancoi and H. scotti were significantly (positively or negatively) correlated to the occurrence of certain contaminants.

IntroductionDuring the COVID-19 pandemic, adherence to wearing face mask and washing hands procedures and achieving high COVID-19 vaccine coverage among healthcare workers (HCWs) were essential to minimize morbidity and possible death and limit the transmission of the virus. The objectives of the cross-sectional survey were to explore the influence of COVID-19 on the use of preventive measures and vaccination willingness among HCWs in the southern part of Italy and the associated factors.MethodsThe survey was carried out from 15 June 2023 to 15 July 2023 among 521 HCWs who worked in three randomly selected public hospitals. All data were collected through a self-administered questionnaire.ResultsHCWs had a positive change in the use of preventive measures if they did not often/always use them before the pandemic, but they are using in the current epidemiologic context and they were willing to use in a future epidemic situation. A positive change in the adherence to face mask-wearing (24.6%) was more likely among those with at least 5 years of university degree, nurses/midwives, and who had worked in COVID-19 wards. A positive change in alcohol-based hand rubbing (3.1%) was more likely in HCWs in Emergency/Critical/Infectious Diseases wards compared with medical wards. HCWs who were more likely to believe that the COVID-19 vaccine should be mandatory for them (58.1%) had at least 5 years of university degree, in Emergency/Critical/Infectious Diseases wards compared with surgical and medical wards, had received more than three doses of this vaccine, were more concerned to get infected during their activity, and had received information from scientific journals. HCWs more willing to receive the COVID-19 vaccine every year (39.8%) were males, physicians, those in Emergency/Critical/Infectious Diseases wards compared with medical wards, who had received more than three doses of this vaccine, who believed that this vaccine should be mandatory for HCWs, and who needed additional information.DiscussionThe survey showed that the COVID-19 pandemic had an impact on the use of preventive measures among HCWs, not necessarily for the improvement or increase. Educational messages on the importance of these measures regarding the promotion and recommendation of the vaccine need to be investigated and applied among HCWs in order to reduce vaccination gaps and the spread of the infection.

The aim of this study was to evaluate the effect of oral cannabidiol (CBD) administration in addition to a conventional analgesic protocol on the clinical signs of 20 horses with mild joint osteoarthritis. The horses were randomly assigned to either the control group (C group) or the cannabidiol group (CBD group). Both groups were treated with phenylbutazone for 5 days. The CBD group received 0.03 mg/kg cannabidiol in hemp oil orally once daily for 14 days in addition to phenylbutazone treatment. All subjects were monitored for clinical parameters, oxidative status and blood counts. Pain and quality of life were also assessed using the Horse Chronic Pain Scale (HCPS). The CBD group showed a significant reduction in heart rate, respiratory rate, white blood cell count and oxidative stress (malondialdehyde lipid peroxidation). A significant reduction in HCPS scores was seen in both groups. Lower scores were recorded in the CBD group (3 med; range: 2/4) than in the C group (7 med; range: 4/10). The addition of a cannabidiol-based product to an analgesic protocol was well tolerated and showed positive effects on the treated subjects, improving their quality of life and pain relief.

This case report describes the treatment of an adult female patient with a history of periodontitis (Stage 3 -Grade B) and presenting significant crowding in both maxillary and mandibular arches. After periodontal stabilization, the patient underwent orthodontic treatment with clear aligners (CAT) for less than one year. CAT provided an effective quantitative and qualitative control of the forces applied to resolve the malocclusion. This case report provides a detailed description of the clinical strategy and features associated with the clear aligners system which were considered ideal tools for treating periodontal patients during the decisional workflow. The orthodontic treatment goals have been successfully achieved considering functional, periodontal, and aesthetic expectations. Several characteristics of clear aligners could support the recurrence of this orthodontic system for treating patients with a history of periodontitis or at risk of periodontal damage.

Systemic autoinflammatory diseases (SAIDs) are disorders of innate immunity, which are characterized by unprovoked recurrent flares of systemic inflammation often characterized by fever associated with clinical manifestations mainly involving the musculoskeletal, mucocutaneous, gastrointestinal, and nervous systems. Several conditions also present with varied, sometimes prominent, involvement of the vascular system, with features of vasculitis characterized by variable target vessel involvement and organ damage. Here, we report a systematic review of vasculitis and vasculopathy associated with inborn errors of immunity.

BackgroundConsolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented.MethodsA total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy.ResultsPreclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p

Assessing chemical safety is essential to evaluate the potential risks of chemical exposure to human health and the environment. Traditional methods relying on animal testing are being replaced by 3R (reduction, refinement, and replacement) principle-based alternatives, mainly depending on in vitro test methods and the Adverse Outcome Pathway framework. However, these approaches often focus on the properties of the compound, missing the broader chemical-biological interaction perspective. Currently, the lack of comprehensive molecular characterization of the in vitro test system results in limited real-world representation and contextualization of the toxicological effect under study. Leveraging omics data strengthens the understanding of the responses of different biological systems, emphasizing holistic chemical-biological interactions when developing in vitro methods. Here, we discuss the relevance of meticulous test system characterization on two safety assessment relevant scenarios and how omics-based, data-driven approaches can improve the future generation of alternative methods.

IntroductionIn Italy, since December 2022, the COVID-19 vaccination has been extended to children aged 6 months–4 years with conditions of fragility and to those healthy at the request of the parent. The purposes of the cross-sectional survey were to determine the willingness and hesitancy of the parents/guardians to have their healthy children vaccinated against COVID-19.MethodsThe survey was performed among 389 parents/guardians with a child aged 6 months–4 years randomly selected from seven kindergartens and eight nursery schools in the geographic area of Naples, Italy.ResultsOnly 10.5% were very concerned about the risk of infection, and the mean values regarding the perceived utility and safety of the COVID-19 vaccine were 3.3 and 3.2, respectively. Only 13.7% of participants were willing to consent to vaccinate the selected child against COVID-19, while 20.1% were uncertain and 66.2% did not intend. Parents/guardians of older children, those who received information about the COVID-19 vaccine from physicians or pediatricians, those who believed that the COVID-19 vaccine was useful, and those with lower hesitancy regarding the COVID-19 vaccine were more willing to vaccinate their child. The mean Parent Attitudes About Childhood Vaccines (PACV-5) score was 5.6, with 33.1% of respondents who were identified as highly hesitant toward COVID-19 vaccination (score ≥ 7). Parents/guardians with a lower perceived safety of the COVID-19 vaccine were more likely to be highly hesitant.DiscussionThe findings reveal the need to improve community-based education campaigns and effective promotion of the COVID-19 vaccination to increase willingness and address parental safety concerns.

The growing threats posed by wildfires in Southern Europe are calling for the development of comprehensive and sound management and risk assessment strategies. In this work, we present the application of wildfire simulation modeling based on the minimum travel time (MTT) algorithm to assess fine-scale (100-m resolution) wildfire hazard, transmission, and exposure to communities in the Italy-France Maritime cooperation area (Sardinia, Corsica, Tuscany, Liguria and Provence-Alpes-Côte d’Azur), which cover about 72,000 km2 of land. We simulated thousands of wildfires considering the current landscape and characterized and measured fine-scale wildfire risk factors and profiles by taking into account historical fire regimes, fuels, winds and fuel moisture conditions associated with the occurrence of the largest wildfires (>100 ha) that affected the study area in the last 20 years. Individual fires were simulated at 100-m resolution, consistent with the input files. Modeled annual burn probability and ignition probability revealed that Sardinia was the Region most affected by wildfires. The wildfire simulation outputs were then combined with main land uses and building footprint locations to characterize wildfire transmission and exposure to communities, and were summarized for main vegetation types and Regions. This study presents a cross-boundary and standardized approach based on wildfire spread modeling to analyze and quantify wildfire risk profiles in Southern Europe. The stochastic wildfire modeling systems we implemented used harmonized sets of data for a vast, fire-prone Mediterranean area, where previous similar studies were conducted at coarser resolutions and covered lower extent of lands. The approach presented in this work can be used as a reference pillar for the development and implementation of a common wildfire risk monitoring, management, and governance plan in the study area. The methods and findings of this study can be replicated in neighboring Mediterranean and other regions threatened by wildfires.

The ever-growing production of nano-enabled products has generated the need for dedicated risk assessment strategies that ensure safety for humans and the environment. Transdisciplinary approaches are needed to support the development of new technologies while respecting environmental limits, as also highlighted by the EU Green Deal Chemicals Strategy for Sustainability and its safe and sustainable by design (SSbD) framework. The One Health concept offers a holistic multiscale approach for the assessment of nanosafety. However, toxicology is not yet capable of explaining the interaction between chemicals and biological systems at the multiscale level and in the context of the One Health framework. Furthermore, there is a disconnect between chemical safety assessment, epidemiology, and other fields of biology that, if unified, would enable the adoption of the One Health model. The development of mechanistic toxicology and the generation of omics data has provided important biological knowledge of the response of individual biological systems to nanomaterials (NMs). On the other hand, epigenetic data have the potential to inform on interspecies mechanisms of adaptation. These data types, however, need to be linked to concepts that support their intuitive interpretation. Adverse Outcome Pathways (AOPs) represent an evolving framework to anchor existing knowledge to chemical risk assessment. In this perspective, we discuss the possibility of integrating multi-level toxicogenomics data, including toxicoepigenetic insights, into the AOP framework. We anticipate that this new direction of toxicogenomics can support the development of One Health models applicable to groups of chemicals and to multiple species in the tree of life.

A large constellation of hitherto unexplained symptoms including inability to burp, gurgling noises from the chest and lower neck, abdominal bloating, flatulence, painful hiccups and emetophobia was defined as Retrograde Cricopharyngeus Dysfunction (R-CPD) in 2019. First choice treatment of R-CPD involves injection of botulinum toxin into the cricopharyngeus muscle under local or general anesthesia. This treatment has been found to be effective in the vast majority of subjects, with limited adverse events and prolonged therapeutic effects. Notwithstanding, R-CPD is still a poorly understood and underestimated disease, and a specific therapeutic dosage range of botulinum toxin (BT) has not been yet established. In this report, we describe the first case of R-CPD diagnosed in Italy, successfully treated with unilateral, anesthesia-free injection of 10 units of onabotulinum toxin into the cricopharyngeus muscle, representing the lowest dose reported to date.

BackgroundIn Italy, on December 2022, COVID-19 vaccination was recommended for children aged 6 months-4 years with frail conditions and for those healthy. The purposes of the survey were to understand parental willingness and hesitancy toward COVID-19 vaccination of children with frail conditions in Italy and related influencing factors.MethodsA cross-sectional survey was performed among 445 parents with a child aged 6 months-4 years with frail conditions who attended a teaching hospital and a public hospital randomly selected in the city of Naples, Italy.ResultsAlmost one third (29.9%) were willing to vaccinate their frail children against COVID-19, whereas 21.3% were uncertain, and 48.8% did not intend to vaccinate. Parents with a higher level of perception that the vaccine is useful and safe and those who had received information by pediatrician were more likely to be willing to vaccinate their child. The mean Parent Attitudes About Childhood Vaccines (PACV-5) score was 3.4, with 13.5% of parents high-hesitant for the COVID-19 vaccination for their child. Parents with a higher COVID-19 vaccine-related safety concerns, those who have delayed at least one shot of a recommended vaccine for their child, and those who did not have received at least three doses of the vaccine against SARS-CoV-2 were more likely to be high-hesitant.ConclusionThe survey findings have important implications for designing interventions to increase willingness and to reduce hesitancy for COVID-19 vaccine among parents of frail children aged 6 months-4 years in Italy.

Humans play an interconnecting role in social-ecological systems (SES), they are part of these systems and act as agents of their destruction and regulation. This study aims to provide an analytical framework, which combines the concept of SES with the concept of tipping dynamics. As a result, we propose an analytical framework describing relevant dynamics and feedbacks within SES based on two matrixes: the “tipping matrix” and the “cross-impact matrix.” We take the Southwestern Amazon as an example for tropical regions at large and apply the proposed analytical framework to identify key underlying sub-systems within the study region: the soil ecosystem, the household livelihood system, the regional social system, and the regional climate system, which are interconnected through a network of feedbacks. We consider these sub-systems as tipping elements (TE), which when put under stress, can cross a tipping point (TP), resulting in a qualitative and potentially irreversible change of the respective TE. By systematically assessing linkages and feedbacks within and between TEs, our proposed analytical framework can provide an entry point for empirically assessing tipping point dynamics such as “tipping cascades,” which means that the crossing of a TP in one TE may force the tipping of another TE. Policy implications: The proposed joint description of the structure and dynamics within and across SES in respect to characteristics of tipping point dynamics promotes a better understanding of human-nature interactions and critical linkages within regional SES that may be used for effectively informing and directing empirical tipping point assessments, monitoring or intervention purposes. Thereby, the framework can inform policy-making for enhancing the resilience of regional SES.

IntroductionThis paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet’s disease (BD).MethodsThe project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry.ResultsRespondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet’s Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0–30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1–50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range – 1.8–4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p

IntroductionOur research group and others demonstrated the implication of the human endogenous retroviruses (HERVs) in SARS-CoV-2 infection and their association with disease progression, suggesting HERVs as contributing factors in COVID-19 immunopathology. To identify early predictive biomarkers of the COVID-19 severity, we analyzed the expression of HERVs and inflammatory mediators in SARS-CoV-2-positive and -negative nasopharyngeal/oropharyngeal swabs with respect to biochemical parameters and clinical outcome.MethodsResiduals of swab samples (20 SARS-CoV-2-negative and 43 SARS-CoV-2-positive) were collected during the first wave of the pandemic and expression levels of HERVs and inflammatory mediators were analyzed by qRT-Real time PCR.ResultsThe results obtained show that infection with SARS-CoV-2 resulted in a general increase in the expression of HERVs and mediators of the immune response. In particular, SARS-CoV-2 infection is associated with increased expression of HERV-K and HERV-W, IL-1β, IL-6, IL-17, TNF-α, MCP-1, INF-γ, TLR-3, and TLR-7, while lower levels of IL-10, IFN-α, IFN-β, and TLR-4 were found in individuals who underwent hospitalization. Moreover, higher expression of HERV-W, IL-1β, IL-6, IFN-α, and IFN-β reflected the respiratory outcome of patients during hospitalization. Interestingly, a machine learning model was able to classify hospitalized vs not hospitalized patients with good accuracy based on the expression levels of HERV-K, HERV-W, IL-6, TNF-a, TLR-3, TLR-7, and the N gene of SARS-CoV-2. These latest biomarkers also correlated with parameters of coagulation and inflammation.DiscussionOverall, the present results suggest HERVs as contributing elements in COVID-19 and early genomic biomarkers to predict COVID-19 severity and disease outcome.

IntroductionCarfilzomib, a potent, irreversible, selective proteasome inhibitor has demonstrated consistent results in relapsed/refractory multiple myeloma (RRMM) combined with lenalidomide and dexamethasone (KRd). No prospective studies are yet available that analyzed the efficacy of the KRd combination.MethodsHerein, we report a multicenter prospective observational study on 85 patients who were treated with KRd combination as the second or third line of treatment, according to standard practice.ResultsThe median age was 61 years; high-risk cytogenetic was found in 26% and renal impairment (estimated glomerular filtration rate (eGFR)

Recent phase II pilot clinical trials suggested that tauro-urso-deoxycholic acid (TUDCA) might slow functional decline and increase survival in patients with amyotrophic lateral sclerosis (ALS). We performed a multivariate analysis of the original TUDCA cohort to better define the treatment effect and allow comparability with other trials. Linear regression slope analysis showed statistical differences in the decline rate, favoring the active treatment arm (p-value < 0.01; −0.262 for the TUDCA group and −0.388 for the placebo group). Mean survival time, estimated by the Kaplan–Meier analysis, showed a 1-month difference, favoring active treatment (log-rank test p-value = 0.092). Cox regression analysis demonstrated that placebo treatment was associated with a higher risk of death (p-value = 0.055). These data further support the disease-modifying effect of TUDCA monotherapy and raise the question of what could be the additional effect of combining TUDCA with sodium phenylbutyrate.

IntroductionThe impairment of the sense of smell is often related to chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP, CRSsNP). CRSwNP is a frequent condition that drastically worsens the quality of life of those affected; it has a higher prevalence than CRSsNP. CRSwNP patients experience severe loss of smell with earlier presentation and are more likely to experience recurrence of their symptoms, often requiring revision surgery.MethodsThe present study performed a multicentric data collection, enrolling 811 patients with CRS divided according to the inflammatory endotype (Type 2 and non-Type 2). All patients were referred for nasal endoscopy for the assessment of nasal polyposis using nasal polyp score (NPS); Sniffin’ Sticks olfactory test were performed to measure olfactory function, and SNOT-22 (22-item sinonasal outcome test) questionnaire was used to assess patients’ quality of life; allergic status was evaluated with skin prick test and nasal cytology completed the evaluation when available.ResultsData showed that Type 2 inflammation is more common than non-type 2 (656 patients versus 155) and patients suffer from worse quality of life and nasal polyp score. Moreover, 86.1% of patients with Type 2 CRSwNP were affected by a dysfunction of the sense of smell while it involved a lesser percentage of non-Type 2 patients. Indeed, these data give us new information about type-2 inflammation patients’ characteristics.DiscussionThe present study confirms that olfactory function weights on patients’ QoL and it represents an important therapeutic goal that can also improve patients’ compliance when achieved. In a future – and present – perspective of rhinological precision medicine, an impairment of the sense of smell could help the clinician to characterize patients better and to choose the best treatment available.

Malnutrition is a common condition in cancer patients which is usually associated with functional limitations, as well as increased morbidity and mortality. Based on the support of the young sections of Italian Association of Medical Oncology (AIOM), Italian Association of Radiotherapy and Clinical Oncology (AIRO) and Italian Society of Surgical Oncology (SICO) merged into the NutriOnc Research Group, we performed a multidisciplinary national survey with the aim to define the awareness of nutritional issues among healthcare professionals delivering anticancer care. The questionnaire was organized in four sections, as follows: Knowledge and practices regarding Nutritional Management of cancer patients; Timing of screening and assessment of Nutritional Status; Nutritional Treatment and prescription criteria; Immunonutrition and educational topics. The modules focused on esophagogastric, hepato-bilio-pancreatic and colorectal malignancies. Overall, 215 physicians completed the survey. As regards the management of Nutritional Status of cancer patients, many responders adopted the ERAS program (49.3%), while a consistent number of professionals did not follow a specific validated nutritional care protocol (41.8%), mainly due to lack of educational courses (14.5%) and financial support (15.3%). Nearly all the included institutions had a multidisciplinary team (92%) to finalize the treatment decision-making. Cancer patients routinely underwent nutritional screening according to 57.2% of interviewed physicians. The timing of nutritional assessment was at diagnosis (37.8%), before surgery (25.9%), after surgery (16.7%), before radiochemotherapy (13.5%) and after radiochemotherapy (7%). Most of the responders reported that nutritional status was assessed throughout the duration of cancer treatments (55.6%). An important gap between current delivery and need of nutritional assessment persists. The development of specific and defined care protocols and the adherence to these tools may be the key to improving nutritional support management in clinical practice.

Graphical representations are ubiquitous in the learning and teaching of science, technology, engineering, and mathematics (STEM). However, these materials are often not accessible to the over 547,000 students in the United States with blindness and significant visual impairment, creating barriers to pursuing STEM educational and career pathways. Furthermore, even when such materials are made available to visually impaired students, access is likely through literalized modes (e.g., braille, verbal description), which is problematic as these approaches (1) do not directly convey spatial information and (2) are different from the graphic-based materials used by students without visual impairment. The purpose of this study was to design and evaluate a universally accessible system for communicating graphical representations in STEM classes. By combining a multisensory vibro-audio interface and an app running on consumer mobile hardware, the system is meant to work equally well for all students, irrespective of their visual status. We report the design of the experimental system and the results of an experiment where we compared learning performance with the system to traditional (visual or tactile) diagrams for sighted participants (n = 20) and visually impaired participants (n = 9) respectively. While the experimental multimodal diagrammatic system (MDS) did result in significant learning gains for both groups of participants, the results also revealed no statistically significant differences in the capacity for learning from graphical information across both comparison groups. Likewise, there were no statistically significant differences in the capacity for learning from graphical information between the stimuli presented through the experimental system and the traditional (visual or tactile) diagram control conditions, across either participant group. These findings suggest that both groups were able to learn graphical information from the experimental system as well as traditional diagram presentation materials. This learning modality was supported without the need for conversion of the diagrams to make them accessible for participants who required tactile materials. The system also provided additional multisensory information for sighted participants to interpret and answer questions about the diagrams. Findings are interpreted in terms of new universal design principles for producing multisensory graphical representations that would be accessible to all learners.

BackgroundThyroid hormones (TH) play multiple effects on glucose metabolism. Some recent studies carried out in adult patients suggested an association between altered sensitivity to TH and type 2 diabetes, obesity, and metabolic syndrome. No studies are currently available on the presence of altered sensitivity to the action of TH in youths with prediabetes.ObjectiveTo evaluate the relationship between sensitivity to TH and impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or glycosylated hemoglobin (HbA1c) ≥ 5.7% in youths with overweight/obesity (OW/OB).Materials and methodsThis cross-sectional study included 805 Caucasian youths with OW or OB (aged 6-18 years) recruited at seven Italian centers for the care of OW/OB. Individuals with TH out of the normal range of TH in each center were excluded. The fT3/fT4 ratio was evaluated to assess peripheral sensitivity, while TSH index (TSHI), Thyrotroph T4 Resistance Index (TT4RI), Thyroid Feedback Quantile-based Index (TFQI) and Parametric TFQI were calculated to assess central sensitivity.ResultsYouths with IGT (n =72) showed higher levels of TSH (3.08 ± 0.98 vs 2.68 ± 0.98 mIU/L, P =0.001), TSHI (3.06 ± 0.51 vs 2.85 ± 0.53, P =0.001), TT4RI (46.00 ± 17.87 vs 38.65 ± 16.27, P

Minimal/measurable residual disease (MRD) monitoring is progressively changing the management of hematologic malignancies. The possibility of detecting the persistence/reappearance of disease in patients in apparent clinical remission offers a refined risk stratification and a treatment decision making tool. Several molecular techniques are employed to monitor MRD, from conventional real-time quantitative polymerase chain reaction (RQ-PCR) to next generation sequencing and digital droplet PCR (ddPCR), in different tissues or compartments through the detection of fusion genes, immunoglobulin and T-cell receptor gene rearrangements or disease-specific mutations. RQ-PCR is still the gold standard for MRD analysis despite some limitations. ddPCR, considered the third-generation PCR, yields a direct, absolute, and accurate detection and quantification of low-abundance nucleic acids. In the setting of MRD monitoring it carries the major advantage of not requiring a reference standard curve built with the diagnostic sample dilution and of allowing to reduce the number of samples below the quantitative range. At present, the broad use of ddPCR to monitor MRD in the clinical practice is limited by the lack of international guidelines. Its application within clinical trials is nonetheless progressively growing both in acute lymphoblastic leukemia as well as in chronic lymphocytic leukemia and non-Hodgkin lymphomas. The aim of this review is to summarize the accumulating data on the use of ddPCR for MRD monitoring in chronic lymphoid malignancies and to highlight how this new technique is likely to enter into the clinical practice.

BackgroundThis present survey sought to investigate the level of knowledge and the attitudes pertaining the monkeypox (mpox) virus infection among a sample of health care workers (HCWs) in Italy, as well as the possible role of different factors on these outcomes.MethodsThe cross-sectional survey was performed from July through October, 2022 at four randomly selected hospitals located in Southern Italy.ResultsThe questionnaire was completed by 421 HCWs, for an overall 59% response rate. Less than two-thirds were able to define the disease and the correct answer of the transmission mechanisms ranged from 22.8% for contact with contaminated objects to 75.8% through close contact with body fluids. Only 4% and 12.8% indicated HCWs and elderly/frail/people with underlying immune deficiencies as risk groups. The mean overall score of the knowledge assessment on mpox was 3.4 (0–9). The multivariate logistic regression analysis showed that HCWs with a lower number of years of working experience and those who had acquired information about mpox from scientific journals were more likely to have a higher level of knowledge. The average score of the perception of the severity of the disease was 6.3. A similar score with a value of 6.1 has been observed for the statement that mpox is a serious problem for the population. Regarding the level of concern about contracting mpox, the mean score was 5.1. Only 10.5% reported that they feel that this disease can be prevented, with an overall mean score of 6.5. Almost all HCWs reported that they are still living as usual, with no modification of their behavior for fear of contracting the mpox. The results of the multivariate logistic regression model showed that women, HCWs with a higher level of knowledge about mpox, and those who needed additional information about mpox were more likely to have a higher level of perception of the severity of the disease.ConclusionThis survey has demonstrated that HCWs had an unsatisfactory level of knowledge toward mpox and only nearly half showed positive attitudes. Strategic health training programs should be made so that knowledge can be acquired.

ObjectiveTo evaluate the potential role of Streptococcus salivarius K12 (SSK12) in controlling febrile flares in patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Further aims were to assess the impact of SSK12 on (i) flare duration, (ii) variation in the degree of the highest body temperature during flares, (iii) steroid-sparing effect, and (iv) change of PFAPA accompanying symptoms before and after SSK12 introduction.Patients and methodsThe medical charts from 85 pediatric patients with PFAPA syndrome (49 males and 36 females) enrolled in the AIDA registry and treated with SSK12 for a median period of 6.00 ± 7.00 months in the period between September 2017 and May 2022 were examined. Children recruited had a median time of disease duration of 19.00 ± 28.00 months.ResultsThe number of febrile flares significantly decreased comparing the 12 months before [median (IQR), 13.00 (6.00)] and after SSK12 initiation [median (IQR), 5.50 (8.00), p < 0.001]. The duration of fever was significantly reduced from 4.00 (2.00) days to 2.00 (2.00) days [p < 0.001]. Similarly, the highest temperature in°C was found significantly lower in the last follow-up assessment [median (IQR), 39.00 (1.00)] compared to the period prior to SSK12 start [median (IQR), 40.00 (1.00), p < 0.001]. Steroid load (mg/year) of betamethasone (or any equivalent steroid) significantly decreased between 12 months before treatment with SSK12 [median (IQR), 5.00 (8.00) mg/year] and the last follow-up visit [median (IQR), 2.00 (4.00) mg/year, p < 0.001]. The number of patients experiencing symptoms including pharyngitis/tonsillitis (p < 0.001), oral aphthae (p < 0.001) and cervical lymphadenopathy (p < 0.001) significantly decreased following SSK12.ConclusionSSK12 prophylaxis given for at least 6.00 months was found to reduce febrile flares of PFAPA syndrome: in particular, it halved the total number per year of fever flares, shortened the duration of the single febrile episode, lowered body temperature by 1°C in the febrile flare, provided a steroid-sparing effect, and significantly reduced the accompanying symptoms related to the syndrome.

In this work, a 3D environment obtained using fibrin scaffold and two cell populations, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), and primary skeletal muscle cells (SkMs), was assembled. Peripheral blood mononuclear cells (PBMCs) fraction obtained after blood filtration with HemaTrate® filter was then added to the 3D culture system to explore their influence on myogenesis. The best cell ratio into a 3D fibrin hydrogel was 1:1 (BM-MSCs plus SkMs:PBMCs) when cultured in a perfusion bioreactor; indeed, excellent viability and myogenic event induction were observed. Myogenic genes were significantly overexpressed when cultured with PBMCs, such as MyoD1 of 118-fold at day 14 and Desmin 6-fold at day 21. Desmin and Myosin Heavy Chain were also detected at protein level by immunostaining along the culture. Moreover, the presence of PBMCs in 3D culture induced a significant downregulation of pro-inflammatory cytokine gene expression, such as IL6. This smart biomimetic environment can be an excellent tool for investigation of cellular crosstalk and PBMC influence on myogenic processes.

Despite hundreds of RNA modifications described to date, only RNA editing results in a change in the nucleotide sequence of RNA molecules compared to the genome. In mammals, two kinds of RNA editing have been described so far, adenosine to inosine (A-to-I) and cytidine to uridine (C-to-U) editing. Recent improvements in RNA sequencing technologies have led to the discovery of a continuously growing number of editing sites. These methods are powerful but not error-free, making routine validation of newly-described editing sites necessary. During one of these validations on DDX58 mRNA, along with A-to-I RNA editing sites, we encountered putative U-to-C editing. These U-to-C edits were present in several cell lines and appeared regulated in response to specific environmental stimuli. The same findings were also observed for the human long intergenic non-coding RNA p21 (hLincRNA-p21). A more in-depth analysis revealed that putative U-to-C edits result from A-to-I editing on overlapping antisense RNAs that are transcribed from the same loci. Such editing events, occurring on overlapping genes transcribed in opposite directions, have recently been demonstrated to be immunogenic and have been linked with autoimmune and immune-related diseases. Our findings, also confirmed by deep transcriptome data, demonstrate that such loci can be recognized simply through the presence of A-to-I and U-to-C mismatches within the same locus, reflective A-to-I editing both in the sense-oriented transcript and in the cis-natural antisense transcript (cis-NAT), implying that such clusters could be a mark of functionally relevant ADAR1 editing events.

Treatment of acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) is difficult in older patients with comorbidities and high-risk disease factors. Venetoclax, the first-in-class Bcl-2 inhibitor, has proven efficacy and safety in combination with azacytidine for treatment of high-risk myeloid diseases. In this single-center real-life retrospective study, a total of 27 consecutive patients treated with azacytidine plus venetoclax were included, and clinical outcomes, hematological improvements, and biomarkers of responsiveness to therapy were compared to those observed in an historical cohort of 95 consecutive patients treated with azacytidine as single agent. Azacytidine plus venetoclax was effective and safe in older and frail AML and high-risk MDS patients, with median overall survival of 22.3 months, higher than that reported in phase III trial (14.7 months), and higher than that of historical cohort (5.94 months). Progression-free survival was higher in patients treated with the drug combination compared to those treated with azacytidine as single agent (p = 0.0065). Clinical benefits might increase when azacytidine and venetoclax are administered as upfront therapy (p = 0.0500). We showed that Tim-3 expression could be a promising therapeutic target in refractory/relapsed patients, and galectin-9 a biomarker of responsiveness to therapy. Moreover, patients treated with azacytidine and venetoclax displayed a higher overall survival regardless the presence of negative prognostic markers at diagnosis (e.g., increased WT1 copies and/or normalized blast count). These encouraging results in a real-world setting supported efficacy and safety of azacytidine plus venetoclax as upfront therapy in AML and high-risk MDS, with clinical outcomes comparable to those of clinical trials when an appropriate venetoclax management with bone marrow assessment at every first, second, fourth, and eighth cycle, and dose adjustments for toxicities are performed.

The precious coral Corallium rubrum (Linnaeus, 1758) is a charismatic Mediterranean species. A recent large-scale investigation along the Italian coast highlighted its widespread occurrence at mesophotic and upper bathyal depths, especially on coralligenous and bathyal vertical hardgrounds. The lack of morphometric data limited the considerations on the structure and health status of the populations, fundamental to identify the most vulnerable sites and the correct management actions. For this reason, a ROV dataset, consisting of 624 dives carried out between 40 m and 1825 m in the Ligurian Sea, Tyrrhenian Sea, and Sicily Channel, was analysed to extrapolate quantitative data to describe the populations. Ten random frames were obtained from each of the 170 sites hosting red coral. Density, height, and entanglement were evaluated for about 15700 colonies counted in the frames. The densest populations were mainly found between 40 m and 80 m, with a clear latitudinal density decrease. The mesophotic populations were characterized by both scattered and densely aggregated colonies, while the bathyal ones were dominated by sparse colonies. This study identified 17 major coral areas based on the geographic proximity of the sites hosting red coral and their topographic and oceanographic affinity. The size-frequency distribution of the heights was skewed towards the smaller classes in almost all populations, with a modal class between 2 cm and 4 cm. This study depicted a stress situation of the populations throughout the entire study area, which could be correlated also to the long-term harvesting pressure carried out in the basins. Two additional sources of direct mortality were pointed out in this study. Entanglement to artisanal and recreational fishing gear interested about 18% of the recorded colonies, mainly at mesophotic depths. Almost all populations suffered from mechanical entanglement, with the highest percentages in the Ligurian Sea and Sicilian areas. This study also highlighted a massive occurrence of recent deep mortality events, mainly along the eastern and southern coast of Sardinia and in the Campanian Archipelago. Thirty sites with extensive patches of dead colonies still in place were reported from 70 m to around 200 m, but their formation remains unclear.

IntroductionDLK1 gene is considered a molecular gatekeeper of adipogenesis. DLK1 mutations have been reported as a cause of central precocious puberty associated with obesity and metabolic syndrome with undetectable DLK1 serum levels. We investigated the association between DLK1 circulating levels with clinical and biochemical parameters in obese adolescents and healthy controls.MethodsSixty-five obese adolescents and 40 controls were enrolled and underwent a complete clinical examination and biochemical assessment for glucose homeostasis and DLK1 plasma levels.ResultsWe observed lower DLK1 levels in cases compared to controls. Moreover, we found a negative correlation between DLK1 and HOMA-IR and a direct correlation with insulin-sensitivity index.DiscussionOur findings suggest that DLK1 might be involved in metabolic derangement in obese children.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is evolving,the newly emerged Omicron variant being the dominant strain worldwide, and this has raised concerns about vaccine efficacy. The purposes of this survey were to examine the extent to which healthcare workers (HCWs) intend to receive a second booster dose of the COVID-19 vaccine and the factors that influence their willingness to accept it.MethodsThe study was conducted among HCWs who were randomly selected from four public hospitals in the Campania region, Southern Italy.ResultsA total of 496 HCWs answered the questionnaire (a response rate of 61.2%). Among the respondents, 20.8% indicated a score of 10, using a 10-point Likert-type scale, regarding the usefulness of a second COVID-19 vaccine booster dose. Physicians, HCWs who believed that COVID-19 was a severe disease, and those who have acquired information about the second booster dose from scientific journals were more likely to have this positive attitude. Slightly more than half of HCWs self-reported willingness to receive a second booster dose. Respondents who believe that HCWs are at higher risk of being infected by SARS-CoV-2, those who have a higher belief that COVID-19 is a severe disease, and those who have a higher belief that a second booster dose is useful were more willing to receive a second booster dose. The main reasons for those who had a positive intention were to protect their family members and patients, whereas, the main reasons for not getting vaccinated or for uncertainty were that the dose does not offer protection against the emerging variants and the fear of its side effects. HCWs of younger age, physicians, those who have a higher belief that a second booster dose is useful, and those who were willing to receive a second booster dose were more likely to recommend the booster dose to their patients.ConclusionThis study's findings highlight the necessity for designing and implementing educational interventions for improving second booster dose uptake and beliefs among HCWs and their capacity to recommend the vaccine to the patients.