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Abstract Background Despite advances in pain management, cancer-related pain remains a critical issue for many patients. In recent years, there has been a growing interest in the use of fascial plane blocks, such as the Erector Spinae Plane Block (ESPB), for managing chronic pain, including in the oncology field. We conducted a systematic review to synthetize existing evidence on the use of ESPB for cancer pain management. Methods We selected studies published between January 2016 to April 2024. A systematic search in Pubmed and Embase databases was performed. The search strategy included the following keywords and/or MeSH terms according to the controlled vocabulary of the databases sought: ((erector spinae plane block) OR (ESP block) OR (ESPB) AND ((cancer pain). We considered eligible Randomized, nonrandomized studies, case series and case reports reporting data on the use of ESPB in patients with cancer pain. Results The search revealed 34 studies. Among these, we found one RCT, three retrospective studies, two case series, and 28 case reports for a total of 135 patients. Studies included described the use of ESPB for the management of various types of cancer pain across different conditions, including chronic thoracic cancer-related pain, abdominal visceral pain and pain related to bone metastases. Single-shot ESPB was performed in 26 studies while continuous ESPB and the use of a peripheral nerve catheter for continuous analgesia were described in 8 studies. Neurolytic ESPB was performed in 6 studies for a total of 10 patients There was a high clinical heterogeneity in terms of technique, drugs, and use of adjuvants. The lack of comparators was a major flaw, together with the low level of evidence in the majority of the included studies. Conclusions The evidence supporting the use of ESPB for cancer pain management is currently scarce, heterogeneous, and of low quality. To better understand its potential and provide robust clinical guidance, future research needs to focus on rigorous comparative studies, standardization of techniques and larger sample sizes.

Periodic observations made on two 800-plus-year-old Quercus pubescens trees in the Madonie Mountains (Sicily) revealed the presence of two saprotroph and occasionally weak parasite fungi. The basiodiomycetes Laetiporus sulphureus and Pseudoinonotus dryadeus were identified by combining morphological and observation of microscopic characters with molecular analysis. The two mushrooms fall in the so-named category of “medicinal mushrooms” showing many properties such as antioxidant, antimicrobial, anticancer, cytotoxic, hypoglycemic and anti-inflammatory. Actions are proposed to safeguard old trees and, simultaneously, preserve ex situ the wood-decay fungi of potential medicinal interest.

Abstract We propose a new approach of jet-based event reconstruction that aims to optimally exploit correlations between the products of a hadronic multi-pronged decay across all Lorentz boost regimes. The new approach utilizes clustered small-radius jets as seeds to define unconventional jets, referred to as PAIReD jets. The constituents of these jets are subsequently used as inputs to machine learning-based algorithms to identify the flavor content of the jet. We demonstrate that this approach achieves higher efficiencies in the reconstruction of signal events containing heavy-flavor jets compared to other event reconstruction strategies at all Lorentz boost regimes. Classifiers trained on PAIReD jets also have significantly better background rejections compared to those based on traditional event reconstruction approaches using small-radius jets at low Lorentz boost regimes. The combined effect of a higher signal reconstruction efficiency and better classification performance results in a two to four times stronger rejection of light-flavor jets compared to conventional strategies at low Lorentz-boosts, and rejection rates similar to classifiers based on large-radius multi-pronged jets at high Lorentz-boost regimes.

This paper deals with the basidiomycete Pleurotus nebrodensis, one of the rare examples of endemic fungi in Italy and Europe. After clarifying the taxonomy of this taxon, including a comparison with a species from China misidentified as “Pleurotus nebrodensis”, we describe the characteristics of its natural habitat, and provide a new morphological description and information on its pilot-scale cultivation, current conservation status according to IUCN criteria and conservation strategies. New ITS region sequences were deposited in GenBank. Furthermore, the antibacterial and anti-cancer properties of P. nebrodensis are mentioned, making it a potential medicinal mushroom. Finally, a critical analysis, on a phylogenetic basis, of the Italian production of substrates inoculated with “P. nebrodensis” strains is also included.

Wilson’s disease (WD) is a biallelic disease-causing variant in the ATP7B gene on chromosome 13q14.3 that results in copper accumulation in many organs, particularly the liver and brain. The phenotypic spectrum is wide and symptoms at onset can be heterogeneous. We describe two Sicilian siblings, a young man and his elder sister, both compound heterozygous for the variants c.1286-2A>G and c.2668G>A (p.Val890Met) in the ATB7B gene. The male patient presented with liver cirrhosis, which quickly progressed to end-stage liver disease (Child–Pugh score = C10), while his sister had moderate steatotic liver disease (SLD). Our findings highlight that SLD may not always be related to obesity in overweight patients, especially when there are other potential risk factors such as a family history of chronic liver disease, or the persistence of high transaminase despite the adoption of adequate dietary and pharmacological intervention. Screening for conditions such as WD could identify patients at risk of developing SLD and avoid delays in diagnosis. Phenotypic variability in WD is considerable; therefore, further studies are needed to identify which WD patients have a greater risk of developing SLD and determine factors that can predict the severity of the disease.

IntroductionStatistical shape analysis (SSA) with clustering is often used to objectively define and categorise anatomical shape variations. However, studies until now have often focused on simplified anatomical reconstructions, despite the complexity of studied anatomies. This work aims to provide insights on the anatomical detail preservation required for SSA of highly diverse and complex anatomies, with particular focus on the left atrial appendage (LAA). This anatomical region is clinically relevant as the location of almost all left atrial thrombi forming during atrial fibrillation (AF). Moreover, its highly patient-specific complex architecture makes its clinical classification especially subjective.MethodsPreliminary LAA meshes were automatically detected after robust image selection and wider left atrial segmentation. Following registration, four additional LAA mesh datasets were created as reductions of the preliminary dataset, with surface reconstruction based on reduced sample point densities. Utilising SSA model parameters determined to optimally represent the preliminary dataset, SSA model performance for the four simplified datasets was calculated. A representative simplified dataset was selected, and clustering analysis and performance were evaluated (compared to clinical labels) between the original trabeculated LAA anatomy and the representative simplification.ResultsAs expected, simplified anatomies have better SSA evaluation scores (compactness, specificity and generalisation), corresponding to simpler LAA shape representation. However, oversimplification of shapes may noticeably affect 3D model output due to differences in geometric correspondence. Furthermore, even minor simplification may affect LAA shape clustering, where the adjusted mutual information (AMI) score of the clustered trabeculated dataset was 0.67, in comparison to 0.12 for the simplified dataset.DiscussionThis study suggests that greater anatomical preservation for complex and diverse LAA morphologies, currently neglected, may be more useful for shape categorisation via clustering analyses.

Abstract Background Mental health (MH) is extremely relevant when referring to people living with a chronic disease, such as people living with HIV (PLWH). In fact – although life expectancy and quality have increased since the advent of antiretroviral therapy (ART) – PLWH carry a high incidence of mental disorders, and this burden has been exacerbated during the COVID-19 pandemic. In this scenario, UNAIDS has set new objectives for 2025, such as the linkage of at least 90% of PLWH to people-centered, context-specific MH services. Aim of this study was to determine the prevalence of MD in PLWH followed at the Clinic of Infectious Diseases of the University of Bari, Italy. Methods From January 10th to September 10th, 2022, all PLWH patients accessing our outpatient clinic were offered the following standardized tools: HAM-A for anxiety, BDI-II for depression, PC-PTSD-5 for post-traumatic stress disorder, CAGE-AID for alcohol-drug abuse. Factors associated with testing positive to the four MD were explored with a multivariable logistic regression model. Results 578 out of 1110 HIV-patients agreed to receive MH screening, with 141 (24.4%) people resulting positive to at least one MH disorder. HAM-A was positive in 15.8% (n = 91), BDI-II in 18% (n = 104), PC-PTSD-5 in 5% (n = 29) and CAGE in 6.1% (n = 35). The multivariable logistic regression showed a higher probability of being diagnosed with anxiety, depression and post-traumatic stress disorder for PLWH who reported severe stigma, social isolation, psychological deterioration during the COVID-19 pandemic and for those receiving a dolutegravir (DTG)-based regimen. Moreover, history of drug use (OR 1.13; [95% CE 1.06–4.35]), family stigma (2.42 [1.65–3.94]) and social isolation (2.72 [1.55;4.84]) were found to be associated to higher risk for substance use disorder. Conclusions In this study, stigma was a strong predictor for being diagnosed of a MH disorder among PLWH. Also, the possible role of dolutegravir as a risk factor for the onset of MH disorders should be considered in clinical practice, and MH of patients receiving DTG-containing regimens should be constantly monitored.

Abstract Remdesivir (RDV) was the first Food and Drug Administration (FDA)-approved medication for COVID-19, with discordant data on efficacy in reducing mortality risk and disease progression. In the context of a dynamic and rapidly changing pandemic landscape, the utilization of real-world evidence is of utmost importance. The objective of this study is to evaluate the impact of RDV on patients who have been admitted to two university referral hospitals in Italy due to COVID-19. All patients older than 18 years and hospitalized at two different universities (Bari and Palermo) were enrolled in this study. To minimize the effect of potential confounders, we used propensity score matching with one case (Remdesivir) and one control that never experienced this kind of intervention during hospitalization. Mortality was the primary outcome of our investigation, and it was recorded using death certificates and/or medical records. Severe COVID-19 was defined as admission to the intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. After using propensity score matching, 365 patients taking Remdesivir and 365 controls were included. No significant differences emerged between the two groups in terms of mean age and percentage of females, while patients taking Remdesivir were less frequently active smokers (p

Abstract In recent years, there has been a growing awareness of the limitations and risks associated with the overreliance on opioids in various surgical procedures, including cardiothoracic surgery. This shift on pain management toward reducing reliance on opioids, together with need to improve patient outcomes, alleviate suffering, gain early mobilization after surgery, reduce hospital stay, and improve patient satisfaction and functional recovery, has led to the development and widespread implementation of enhanced recovery after surgery (ERAS) protocols. In this context, fascial plane blocks are emerging as part of a multimodal analgesic in cardiac surgery and as alternatives to conventional neuraxial blocks for thoracic surgery, and there is a growing body of evidence suggesting their effectiveness and safety in providing pain relief for these procedures. In this review, we discuss the most common fascial plane block techniques used in the field of cardiothoracic surgery, offering a comprehensive overview of regional anesthesia techniques and presenting the latest evidence on the use of chest wall plane blocks specifically in this surgical setting.

Introduction: Vaccines are the most cost-effective and straightforward intervention against severe infectious diseases. However, in Europe and in Italy, paediatric vaccination coverage for certain vaccines remains suboptimal, with considerable regional differences in Italy. Vaccine coverage varies significantly due to socio-economic and organisational factors. Aim of this study was to assess the influence of the Deprivation Index, the density of General Practitioners and General Paediatricians per inhabitants on the coverage of both mandatory and non-mandatory paediatric vaccinations across local health authorities and health districts in the Campania Region for birth cohorts from 2001 to 2015. Materials and methods: Population-based, ecological time series analysis focusing on the Campania Region, most populous region in the south of Italy. Vaccination coverage data were extracted from the regional immunization database, whilst information on the Deprivation Index and number of primary care doctors and primary care paediatricians per local health district were extracted from public health records. Univariate descriptive statistics were employed to describe study characteristics, as appropriate, whilst and mixed-effect linear regression models were employed to assess the associations between variables of interest and vaccination coverage. Results: Overall vaccination coverage has generally increased, except for the MMR vaccine, which showed coverage fluctuations. An increase in the Deprivation Index, indicative of less favourable socio-economic conditions, was associated with decreased vaccination coverage in the 24-month age group for some mandatory vaccines (DTaP: Coef −0.97, 95% CI −1.77 | −0.17; Poliomyelitis: Coef −0.98, 95% CI −1.78 | −0.17; Hepatitis B: Coef −0.90, 95% CI −1.71 | −0.10). Moreover, areas with a greater density of General Paediatricians per inhabitants saw increased coverage for Haemophilus influenzae type b in the 6-year age group (Coef 9.78, 95% CI 1.00 | 18.56). Conclusions: It is necessary to target public health policies to address vaccination inequalities. These efforts should include expanding vaccination campaigns, enhancing catch-up programs, and increase resource allocation in primary care settings to facilitate the role of General Practitioners and Paediatricians in fostering awareness and adherence.

We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic DSF (De Simone formulation) in improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because the low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and DSF treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. Methods: We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria). Patients were randomized into two groups: group A (n = 64) was treated with rifaximin (seven days per month for three months) followed by DSF, and group B (n = 60) was treated with a placebo. By the end of the intervention, 68.7% and 62.5% of patients from group A reported improved NIH-CPSI (National Institute of Health’s Chronic Prostatitis Symptom Index) and IBS-SSS (Irritable Bowel Syndrome Severity Scoring System) scores, respectively, compared to only 3.3% and 5% of the placebo group. Group A patients also had significantly lower mean seminal plasma levels of IL-6 (11.3 vs. 32.4 pg/mL) and significantly higher mean levels of IL-10 (7.9 vs. 4.4 pg/mL) relative to baseline, whereas the levels of IL-6 and IL-10 did not change in the placebo group. Conclusions: The combined treatment with rifaximin and DSF appears to represent the optimal approach for addressing a syndrome such as irritable bowel syndrome (IBS-D plus), which frequently co-occurs with prostatitis (IIIa prostatitis). This approach is particularly beneficial in cases where the symptoms are not always clearly delineated, the etiology is multifactorial, and the diagnosis is multilevel.

Type-2 diabetes affects an increasing percentage of the world’s population and its control through dietary management, involving the consumption of health-promoting foods or their derived supplements, is a common strategy. Several mushroom species have been demonstrated to be endowed with antidiabetic properties, resulting from their ability in improving insulin sensitivity and production, or inhibiting the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase. This study aimed to investigate for the first time the hypoglycemic properties of the edible mushroom Leccinum scabrum (Bull.) Gray. Mushroom extracts were prepared through the microwave-assisted extraction (MAE) technique using green solvents with different polarity degrees. The inhibition activity of all the obtained extracts on both α-glucosidase and α-amylase was evaluated and the highest activity was observed for the EtOAc extract which showed an IC50 value about 60-fold lower than the reference compound 1-deoxynojirimycin (DNJ) on α-glucosidase (0.42 ± 0.02 and 25.4 ± 0.6 µg/mL, respectively). As expected on the basis of the literature data concerning both α-glucosidase and α-amylase inhibition, a milder inhibition activity on pancreatic α-amylase was observed. Preliminary in vivo tests on Drosophila melanogaster carried out on the most active obtained extract (EtOAc) confirmed the in vitro observed hypoglycemic activity. Finally, the EtOAc extract metabolic profile was determined through GC-MS and HRMS analyses.

The road alignment design relies on the knowledge of vehicle dynamics variables. However, it assumes that drivers faithfully follow the lane axis on straights and curves. Deviating from this assumption leads to unexpected outcomes and can significantly impact users’ safety. In this context, vehicle speed and longitudinal acceleration play a crucial role as key references in the international standards. They provide insights into critical driving aspects; therefore, it is essential to thoroughly analyze their real trends. Broad data collection campaigns should derive synthetic indicators in order to highlight eventual significant deviations between the ideal and real dynamics. To achieve this objective, the authors propose some indexes deduced during an experimental study with a Sim-Easy driving simulator, by AVSimulation. Importantly, these indicators can be freely applied in real driving scenarios without limitations. These indexes were tested on four different horizontal curves and proved effective in identifying relevant characteristics related to longitudinal acceleration and speed. Looking ahead, by analyzing similar data for numerous driving contexts on real roads, infrastructure managers could use this methodology to identify those sections with increased vulnerability for users’ safety. Moreover, the collected data from sensors, processed using these indicators, can be filtered and transmitted to users (via ADAS tools) while driving on a specific road to provide timely warnings about potential difficulties. The indicators control the physical variable (acceleration or speed) on a certain geometric element with reference to what is prescribed by the standard. For example, the acceleration indicators are normalized with respect to a threshold value while for speed indexes, the result depends on the difference between the end control points of the geometrical element. In both cases, international regulations report prescribed or recommended reference values, so the analyst is immediately aware of any critical issues in the maneuver.

Abstract Heart valve disease is a major cause of mortality and morbidity worldwide with no effective medical therapy and no ideal valve substitute emulating the extremely sophisticated functions of a living heart valve. These functions influence survival and quality of life. This has stimulated extensive attempts at tissue engineering “living” heart valves. These attempts utilised combinations of allogeneic/ autologous cells and biological scaffolds with practical, regulatory, and ethical issues. In situ regeneration depends on scaffolds that attract, house and instruct cells and promote connective tissue formation. We describe a surgical, tissue-engineered, anatomically precise, novel off-the-shelf, acellular, synthetic scaffold inducing a rapid process of morphogenesis involving relevant cell types, extracellular matrix, regulatory elements including nerves and humoral components. This process relies on specific material characteristics, design and “morphodynamism”.

Abstract Introduction Bloodstream infections (BSI) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are associated with high mortality with limited treatment. The aim of this study is to compare effectiveness and safety of colistin-based versus cefiderocol-based therapies for CRAB-BSI. Methods This is a retrospective observational study enrolling patients with monomicrobial CRAB-BSIs treated with colistin or cefiderocol from 1 January 2020, to 31 December 2022. The 30-day all-cause mortality rate was the primary outcome. A Cox regression analysis was performed to identify factors independently associated with mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. Results Overall 118 patients were enrolled, 75 (63%) and 43 (37%) treated with colistin- and cefiderocol-based regimens. The median (q1–q3) age was 70 (62–79) years; 70 (59%) patients were men. The 30-day all-cause mortality was 52%, significantly lower in the cefiderocol group (40% vs 59%, p = 0.045). By performing a Cox regression model, age (aHR = 1.03, 95% CI 1.00–1.05), septic shock (aHR = 1.93, 95% CI 1.05–3.53), and delayed targeted therapy (aHR = 2.42, 95% CI 1.11–5.25) were independent predictors of mortality, while cefiderocol-based therapy was protective (aHR = 0.49, 95% CI 0.25–0.93). The IPTW-adjusted Cox analysis confirmed the protective effect of cefiderocol (aHR = 0.53, 95% CI 0.27–0.98). Conclusions Cefiderocol may be a valuable treatment option for CRAB-BSI, especially in the current context of limited treatment options.

Abstract In respiratory infections, anemia is both a consequence of acute inflammation and a predictor of poor clinical outcomes. There are few studies investigating the role of anemia in COVID-19, suggesting a potential role in predicting disease severity. In this study, we aimed to assess the association between the presence of anemia at admission and incidence of severe disease and death in patients hospitalized for COVID-19. Data from all adult patients admitted for COVID-19 in University Hospital “P. Giaccone” Palermo, and University Hospital of Bari, Italy, were retrospectively collected from 1st of September 2020 to 31 August 2022. The association between anemia (defined as Hb

Mild cognitive impairment (MCI) is a significant concern as it is a risk factor for AD progression, and early detection is vital in order to delay dementia onset and enable potential therapeutic interventions. Olfactory impairment is recognized as a predictive biomarker in neurodegenerative processes. The aims of this study were to explore the degree of entorhinal cortical atrophy (ERICA) and the severity of MCI symptoms; to analyze magnetic resonance imaging (MRI) results for the entorhinal cortex, parahippocampal gyrus, peri entorhinal cortex, and the cerebellar tentorium; and to perform a comprehensive neuropsychological and psychophysical assessment. The main results highlighted that in our sample—multidomain amnesic MCI patients with hyposmic symptomatology—we found that ERICA scores were associated with the severity of anxiety symptomatology. One possible hypothesis to explain this observation is that anxiety may contribute to neurodegenerative processes by inducing chronic stress and inflammation. Future research should consider the longitudinal development of neuropsychological scores, anxiety disorders, and brain atrophy to determine their potential predictive value for MCI progression. These findings suggest the importance of psychological factors in MCI progression and the utility of neuropsychological assessment alongside neuroimaging techniques for early detection and follow-up in MCI patients.

Inversion of the left atrial appendage is a rare phenomenon, which may occur during the de-airing maneuvers associated to routinely performed surgery procedures, such as cardiopulmonary bypass or left ventricular assist device implantation. In this case, the body of the inverted appendage can obstruct the mitral valve leading to severe complications. The mechanisms are still poorly known, and more specific studies are needed to better understand its causes and identify mitigating strategies. The current study attempts to gain a better comprehension of the conditions and the factors favourable to left atrial appendage inversion. Four patient specific appendage morphologies, obtained from computerised tomography and representative of the main typologies commonly used for the appendage classification (chicken wing, cactus, cauliflower, and windsock), were used for the study. The numerical models were subjected to the same loading pattern, made of subsequent different pressure curves.Results show that the morphologies invert and recover their original anatomical configuration at different pressure loads, indicating that their tendency to invert is associated to their specific morphological features. Moreover, the analysis highlights that, although restoring the physiological left atrium pressure is not sufficient to induce appendage recovery, pressures well below the ventricular ones can induce the return to the natural configuration.All models recovered the anatomical configuration at pressures well below the ventricular pressure (about 100 mmHg), suggesting that basic trans-catheter maneuvers, e.g. producing temporary mitral regurgitation, could be attempted to correct the appendage configuration, prior to opt for more invasive surgical approaches.

IntroductionDespite proven efficacy, HPV vaccination coverage is still suboptimal. Factors influencing vaccination uptake are education attainment, socio-economic position, and knowledge about HPV. This study aimed to assess HPV vaccination uptake and its correlates among medical students and identify logistic-organizational barriers, knowledge, and attitudes with regard towards HPV vaccination to improve current public health vaccination strategies. Medical students, with their acquired biological knowledge, were selected as a low-risk groups for HPV vaccination uptake. This cross-sectional study was conducted using a validated questionnaire.MethodsStudents in their the first 3 years of study students were preferentially invited. Eventually, the invitation was extended to every medical student. Logistic multivariable regression was used to assess determinants of HPV vaccination uptake. Additional analysis explored determinants of knowledge of and attitude toward HPV vaccination. Finally, a sensitive analysis was conducted to further assess the effect of knowledge and attitude on the HPV vaccination rate.ResultsA total of 882 medical students participated, with 74.5% enrolled in the first 3 years of their training. HPV vaccination uptake was 55.5%, ranging from 78.5% for females to 16.5% for males. Male sex and increasing age were consistently associated with a lower vaccination uptake (males sex: OR 0.03, CI 0.02–0.05; age: OR 0.77, CI 0.68–0.88), whereasilst progress in their academic career was associated with a to higher likelihood of being vaccinated (6th year: OR 3.45, CI 1.24–9.57). These associations were confirmed when considering the knowledge of and attitude towards HPV. Additionally also, an active outreach from healthcare institutions was associated with a higher likelihood of receiving HPV vaccination (OR 1.70, CI 1.09–2.65.ConclusionHPV vaccination in medical students was higher than in the general population; however, it was still suboptimal. An active and up-to-date call strategy and extending the free-of-charge offer are essential measures for to improvinge vaccination uptake. The findings support the need to improve public health strategies and increase awareness and knowledge ofregarding HPV vaccination.

IntroductionIn Europe, there is still suboptimal tetanus, diphtheria, and acellular pertussis (Tdap) booster coverage. This study aimed to assess coverage status, knowledge, and attitude on Tdap vaccination in healthcare workers (HcWs) of the University Hospital “Federico II” in Naples, Southern Italy, in 2022, to improve current vaccination strategies.MethodsA cross-sectional study was conducted using a validated anonymous questionnaire. Knowledge and attitude were measured as scores. Multivariable logistic and linear regression models were employed to identify correlates of Tdap booster and knowledge and attitude toward the vaccination, as appropriate. Models were controlled for age, sex, profession, department, and job seniority.ResultsA total of 206 questionnaires were administered among HcWs, and 143 (69.4%) were medical doctors. In total, 71 (34.47%) HcWs received the Tdap booster. Those who have worked 5–9 years at the hospital had a 78% lower likelihood of being vaccinated with the Tdap booster (5–9 years—OR: 0.22, CI: 0.06 | 0.85) as compared with newly hired HcWs. No differences in the average knowledge score were found. Other healthcare workers had a lower attitude as compared to medical doctors (Other—Coef. −2.15; CI: −4.14 | −0.15) and, as compared with those who worked in a clinical department, those who worked in a diagnostic–therapeutic department or medical management had 3.1 and 2.0 lower attitude scores, on average, respectively (diagnostic–therapeutic—Coef. −3.12, CI: −5.13 | −1.12; public health—Coef. −1.98, CI: −3.41 | −0.56).DiscussionThe study findings support the necessity to implement public health strategies and improve knowledge and attitude toward vaccinations and specifically highlight the importance of Tdap booster every 10 years as a prevention tool to protect high-risk populations.

The design of road geometry is based on a rather elementary assumption that the user strictly follows the lane axis. Based on this hypothesis, the ideal trend of some factors related to the driver’s performance, such as steering angle and speed, can be derived to optimize the most appropriate design choices. In practice, driving behavior differs from the assumed one and produces trends in these variables, which are very different from the ideal functions. The purpose of this research is therefore to propose synthetic performance indicators useful for highlighting the real characteristics of users’ driving behavior during road travel. Toward this aim, some driving experiments along four different curves in a simulated environment were studied in order to evidence possible criticisms. The proposed indicators showed a remarkable ability to represent and synthesize even very complex performance function trends. The proposed performance indicators can have multiple uses, such as, for example, in statistical analyses—which are generally carried out at a later stage—or constitute sufficient information to guide the decisions of infrastructure managers. In the long term, in a “smart road” perspective, they can be used by road administrators for information exchange among users (with each other and with the infrastructure) to improve road operation and safety.

Abstract The aims of this study were to characterize new SARS-CoV-2 genomes sampled all over Italy and to reconstruct the origin and the evolutionary dynamics in Italy and Europe between February and June 2020. The cluster analysis showed only small clusters including

Abstract Nutritional and environmental factors had been reporting in the progression of hepatocellular carcinoma (HCC). In this study, we focused our intervention in the correlation between the folate status and the progression of HCC in patients with chronic virus C (HCV) infection. Nine-eight patients, HCV positive with HCC and one hundred of patients with HCV positive liver cirrhosis (LC) and one hundred patients with HCV positive chronic hepatitis (CHC) and one hundred control subjects were enrolled. The viremia for hepatitis C patients (HCV) was determined by HCV RNA with polymerase chain reaction. HCV was confirmed by HCV RNA or a positive anti-HCV test with chronic liver disease. The comparison of folate serum levels in HCC patients vs Liver Cirrhosis (LC) patients showed a significant decrease of 1.16 ng/ml P = 0.0006 (95% CI-1.925 to − 0.395), in HCC patients versus CHC a decrease of 1.40 ng/ml P

Nowadays, many wireless applications require the exchange of electromagnetic waves through propagation environments that look like to stratified media to some extent. This may concern both natural scenarios, e.g., air/vegetation/ground, and artificial structures, like meta-materials, photonic devices, solar cells or systems-on-chip. The characterization of the layered propagation channel is therefore important for the design and deployment of effective devices and systems. To this aim, the Dyadic Green Function method has been often leveraged, although its use is usually limited to simple sources, like short dipoles or current elements. Furthermore, it seems unsuited to assess the dispersive properties of the channel, which are known to become important when high data-rate must be conveyed. In this paper, a ray-based approach to propagation inside layers is proposed. As the layered environment can be quite reverberating, a great number of rays may be needed, to the extent that the corresponding computational burden might be hardly afforded by general purpose ray tracing tools. Therefore, the ray tracing engine here presented is specifically conceived for the layered case, and mostly relies on analytical formulation. The accuracy of the model is checked against measurement carried out at chip scale at optical frequency, as a reference study case.

IntroductionTuberculosis (TB) remains an unresolved global health problem and vulnerable groups such as migrants remain the most affected with a higher risk of worse outcomes. The aim of this study was to evaluate clinical features, outcomes, and adverse events in migrant and native Italian patients admitted to three Italian hospitals in Southern Italy in order to assess differences and targeted strategies.MethodsWe performed a retrospective study on TB patients admitted between January 1, 2013, and December 31, 2021, in three Apulia hospitals. Two logistic regression models were used, with the dependent variables being (I) unsuccessful treatment (died, loss to follow-up, and failed treatment) and (II) adverse events.ResultsWe enrolled 543 consecutive patients admitted at three Italian hospitals with a diagnosis of TB during the study period, of them 323 (59.5%) were migrants and 220 Italian patients. The treatment success rate in the migrant group was 44.9% (137/305), while in the non-migrant group was 97.1% (203/209). Independent factors of unsuccess treatment (death, failure or loss to follow up) were: migrant status (O.R. = 11.31; 95% CI 9.72–14.23), being male (O.R. = 4.63; 95% CI 2.16–6.10), homelessness (O.R. = 3.23; 95% CI 2.58–4.54), having a MDR (Multidrug-resistant) (O.R = 6.44; 95% CI 4.74–8.23), diagnostic delay (O.R. = 3.55; 95% CI 1.98–5.67), and length of hospitalization (O.R. = 3.43; 95% CI 1.88–5.87). While, age >65 ys (O.R. = 3.11; 95% CI 1.42–4.76), presence of extrapulmonary TB (O.R. = 1.51; 95% CI 1.31–2.18), monoresistance (O.R. = 1.45; 95% CI 1.25–3.14) and MDR pattern (O.R. = 2.44; 95% CI 1.74–5.03) resulted associated with adverse events.ConclusionMigrant population is at high risk of unsuccessful treatment (death, loss to follow-up, and treatment failure). Policies targeted specifically to this group are needed to really impact and improve their health status and also to contain the TB burden.

In this paper a novel model, based on the smoothed particle hydrodynamics (SPH) method, is proposed to simulate thrombus formation. This describes the main phases of the coagulative cascade through the balance of four biochemical species and three type of platelets. SPH particles can switch from fluid to solid phase when specific biochemical and physical conditions are satisfied. The interaction between blood and the forming blood clot is easily handled by an innovative monolithic FSI approach. Fluid-solid coupling is modelled by introducing elastic binds between solid particles, without requiring detention and management of the interface between the two media. The proposed model is able to realistically reproduce the thromboembolic process, as confirmed by the comparison of numerical results with experimental data available in the literature.

Neonatal encephalopathy is a relatively common clinical condition which results in serious consequences including death, cerebral palsy, epilepsy and other cognitive, developmental and behavioral problems. In 1966 some researchers found that many cases of congenital lesions of the cerebral cortex, basal ganglia and other suprasegmental structures showed symptoms and signs many months after birth. Currently, many children with non-perinatal neurological history present later in infancy with neurological abnormalities, usually hemiparesis, that is attributable to remote focal infarction on neuroimaging. Although intrapartum asphyxia accounts for less the 10% of cases of cerebral palsy, it represents a leading claim in obstetric malpractice litigation. So, in confirmed cases of neonatal encephalopathy, the likelihood that it was determined by an acute intrapartum or peripartum event should be determined. ACOG Task Force on Neonatal Encephalopathy recommended a multidimensional assessment process for neonatal encephalopathy and defined diagnostic criteria. On the other hand, there is growing evidence that ischemic perinatal stroke is the leading known cause of hemiplegic cerebral palsy, with an incidence of 1:3000 live births or more. Object of this paper is to report 3 cases series affected by ischemic perinatal stroke and review the classification and diagnostic criteria of both neonatal and ischemic perinatal stroke, with the aim of speculate that IPS due to perinatal hypoxia could lead to cerebral palsy also without evidences of neonatal encephalopathy close to birth and increase litigation for obstetric malpractice.

Beer is one of the oldest and most popular alcoholic beverages and is currently consumed worldwide. The various components used in the brewing process have a physiological impact on the consumer and current research aims to improve its technological and functional properties through the addition of natural compounds (plants or mushrooms). In this work, the addition of two different amounts (5 and 10 g/L) of Pleurotus eryngii var. eryngii in powder form added at different production stages (PRE and POST alcoholic fermentation) showed the improvement in yeast viability during the alcoholic fermentation, increased the alcoholic content, and improved the sensorial profile. Regarding the organoleptic profile in the experimental samples, cocoa/chocolate and mushroom aromas were found and the samples PRE10 and POST5 received the best ratings with respect to all evaluated parameters.

Oral capillaroscopy is a critical and non-invasive technique used to evaluate microcirculation. Its ability to observe small vessels in vivo has generated significant interest in the field. Capillaroscopy serves as an essential tool for diagnosing and prognosing various pathologies, with anatomic–pathological lesions playing a crucial role in their progression. Despite its importance, the utilization of videocapillaroscopy in the oral cavity encounters limitations due to the acquisition setup, encompassing spatial and temporal resolutions of the video camera, objective magnification, and physical probe dimensions. Moreover, the operator’s influence during the acquisition process, particularly how the probe is maneuvered, further affects its effectiveness. This study aims to address these challenges and improve data reliability by developing a computerized support system for microcirculation analysis. The designed system performs stabilization, enhancement and automatic segmentation of capillaries in oral mucosal video sequences. The stabilization phase was performed by means of a method based on the coupling of seed points in a classification process. The enhancement process implemented was based on the temporal analysis of the capillaroscopic frames. Finally, an automatic segmentation phase of the capillaries was implemented with the additional objective of quantitatively assessing the signal improvement achieved through the developed techniques. Specifically, transfer learning of the renowned U-net deep network was implemented for this purpose. The proposed method underwent testing on a database with ground truth obtained from expert manual segmentation. The obtained results demonstrate an achieved Jaccard index of 90.1% and an accuracy of 96.2%, highlighting the effectiveness of the developed techniques in oral capillaroscopy. In conclusion, these promising outcomes encourage the utilization of this method to assist in the diagnosis and monitoring of conditions that impact microcirculation, such as rheumatologic or cardiovascular disorders.

The Italian SIAPEC-AIT 2014 classification, the 2017 Bethesda System for Reporting Thyroid Cytology (TBSRTC), the 2016 UK Royal College of Pathologists (RCPath) thyroid reporting system, and the 2019 Japanese reporting system for thyroid aspiration cytology (JRSTAC2019) represent the most widely used reporting systems among clinicians and pathologists for the purpose of cytologically diagnosing, estimating the potential risk of malignancy (ROM), and defining the most appropriate treatment for a patient with a thyroid nodule. Although all the systems use overlapping diagnostic categories and morphologic criteria, they differ on the basis of the criteria for inclusion in the cytologic categories, which may, in turn, affect the ROM of a given category and the clinical management of the patient, particularly with regard to the “indeterminate” categories. The aim of this review is to analyze the main differences that emerge between the systems and to propose possible solutions for a comprehensive reporting system that integrates and harmonizes all the criteria of the Italian classification and the Bethesda system, also taking into account the impact that the new tumor entity NIFTP (non-invasive follicular tumor with papillary-like nuclear features) that has, in many instances, replaced the non-invasive form of the follicular variant of papillary carcinoma, has had on the modification of malignancy risks.

To date, the molecular mechanisms that underline aggressiveness and resistance to tyrosine kinase inhibitors in some thyroid carcinomas (TCs) are not known yet. We report the case of a young patient with a metastatic poorly differentiated (PDTC) and follicular thyroid carcinoma (FTC) refractory to conventional therapies and to Sorafenib. The patient, despite an initial partial response, died of progressive disease 21 months after diagnosis. The genetic analysis performed on the primary tumor and on lymph nodes and distant metastases allowed to identify a frameshift mutation (p.P248Tfs*5) in the PTEN gene, never described in TC. This mutation was present in the primary tumor and, with a lower allelic frequency, in metastases diagnosed after treatment with Sorafenib. Mutations in TP53 (p.C135Y and c.920-2A>G previously detected in anaplastic carcinomas and p.M133R never found in TC) were also detected in the primary tissue together with a mono-allelic expression of the p.C135Y mutant at RNA level. At metastatic sites level, we found only the TP53 splicing mutation c.920-2A>G. The presence of defects in mismatch repair (MMR) proteins and genomic instability was also evaluated. The primary tumor showed a partial expression of MMR proteins together with a strong genomic instability. In conclusion, we demonstrated that the rare combination of somatic PTEN and TP53 mutations in a patient with a metastatic FTC, together with the presence of tumor heterogeneity and genomic instability, might be associated with a high tumor aggressiveness and resistance to treatments.

The neurofibromatosis-1 gene (NF1) was initially characterized because its germline mutation is responsible for an inherited syndromic disease predisposing tumor development, in particular neurofibromas but also various malignancies. Recently, large-scale tumor sequencing efforts have demonstrated NF1 as one of the most frequently mutated genes in human cancer, being mutated in approximately 5–10% of all tumors, especially in malignant peripheral nerve sheath tumors and different skin tumors. NF1 acts as a tumor suppressor gene that encodes neurofibromin, a large protein that controls neoplastic transformation through several molecular mechanisms. On the other hand, neurofibromin loss due to NF1 biallelic inactivation induces tumorigenic hyperactivation of Ras and mTOR signaling pathways. Moreover, neurofibromin controls actin cytoskeleton structure and the metaphase–anaphase transition. Consequently, neurofibromin deficiency favors cell mobility and proliferation as well as chromosomal instability and aneuploidy, respectively. Growing evidence supports the role of oxidative stress in NF1-related tumorigenesis. Neurofibromin loss induces oxidative stress both directly and through Ras and mTOR signaling activation. Notably, innovative therapeutic approaches explore drug combinations that further increase reactive oxygen species to boost the oxidative unbalance of NF1-altered cancer cells. In our paper, we review NF1-related tumors and their pathogenesis, highlighting the twofold contribution of oxidative stress, both tumorigenic and therapeutic.

The Water-Cooled Lead Lithium (WCLL) Breeding Blanket (BB) is one of the two BB concept candidates to be selected as the driver blanket for the EU DEMO fusion reactor. In this regard, the development of a sound architecture of the WCLL Central Outboard Blanket (COB) Segment, ensuring the fulfilment of the thermal and structural design requirements, is one of the main goals of the EUROfusion consortium. To this purpose, an exploratory research campaign has been launched to preliminarily investigate the thermo-mechanical performances of the Bottom Cap (BC) region of the WCLL COB segment because of its peculiarities making its design different from the other regions. The assessment has been carried out considering the nominal BB operating conditions, the Normal Operation (NO) scenario, as well as a steady-state scenario derived from the in-box LOCA accident, the Over-Pressurization (OP) scenario. Starting from the reference geometric layout of the WCLL COB BC region, a first set of analyses has been launched in order to evaluate its structural performances under a previously calculated thermal field and to select potential geometric improvements. Then, the analysis of a complete BC region was conducted from both the thermal and structural standpoints, evaluating its structural behaviour in compliance with the RCC-MRx code. Finally, after some iterations and geometric updates, a promising geometric layout of the BC region has been obtained even though some criticalities still persist in the internal Stiffening Plates and First Wall. However, the obtained results clearly showed that the proposed layout is worthy to be further assessed to achieve a robust enough configuration. The work has been performed following a theoretical-numerical approach based on the Finite Element Method (FEM) and adopting the quoted Ansys commercial FEM code.

Seeds are specialized plant organs that carry, nurture, and protect plant offspring. Developmental coordination between the three genetically distinct seed tissues (the embryo, endosperm, and seed coat) is crucial for seed viability. In this study, we explore the relationship between the TFs AtHB25 and ICE1. Previous results identified ICE1 as a target gene of AtHB25. In seeds, a lack of ICE1 (ice1-2) suppresses the enhanced seed longevity and impermeability of the overexpressing mutant athb25-1D, but surprisingly, seed coat lipid polyester deposition is not affected, as shown by the double-mutant athb25-1D ice1-2 seeds. zou-4, another mutant lacking the transcriptional program for proper endosperm maturation and for which the endosperm persists, also presents a high sensitivity to seed aging. Analysis of gso1, gso2, and tws1-4 mutants revealed that a loss of embryo cuticle integrity does not underlie the seed-aging sensitivity of ice1-2 and zou-4. However, scanning electron microscopy revealed the presence of multiple fractures in the seed coats of the ice1 and zou mutants. Thus, this study highlights the importance of both seed coat composition and integrity in ensuring longevity and demonstrates that these parameters depend on multiple factors.

Abstract In spite of machine learning has been successfully used in a wide range of healthcare applications, there are several parameters that could influence the performance of a machine learning system. One of the big issues for a machine learning algorithm is related to imbalanced dataset. An imbalanced dataset occurs when the distribution of data is not uniform. This makes harder the implementation of accurate models. In this paper, intelligent models are implemented to predict the hematocrit level of blood starting from visible spectral data. The aim of this work is to show the effects of two balancing techniques (SMOTE and SMOTE+ENN) on the imbalanced dataset of blood spectra. Four different machine learning systems are fitted with imbalanced and balanced datasets and their performances are compared showing an improvement, in terms of accuracy, due to the use of balancing.

Cyclists are a vulnerable group of road users, especially when no separate infrastructure for cyclists is provided. Then,road factors such as distance and altitude differences can indirectly affect cyclists' safety. Therefore, the authors proposed a procedure based on the geometric characteristics of the road that can determine riding difficulties for cyclists. The proposed procedure can be used both by the public authorities whomanage cyclists' safety and as a method of classifying the road network for cycling. The proposed procedure, based on the use of pattern recognition techniques, analysesdata from a sample of nine riders who travelled on rural roads within the Municipality of Messina (Italy) to classify the roads according to their cycling difficulty. For each rider, duration, distance, road slope, altitude difference and spent calories have been measured and analysed.The collected data wereused for the development of a model capable of predicting the cyclist’s physical effort as a function of the road alignment itself. Knowing the effort required to cycle along a route can contribute to a more complete assessment of road classification, commonly defined according to motor vehicles. Moreover, it may constitute a measure determining the safety of cycling by encouraging cyclists to travel along roads compatible with their physical abilities.

BackgroundA large majority of thrombi causing ischemic complications under atrial fibrillation (AF) originate in the left atrial appendage (LAA), an anatomical structure departing from the left atrium, characterized by a large morphological variability between individuals. This work analyses the hemodynamics simulated for different patient-specific models of LAA by means of computational fluid–structure interaction studies, modeling the effect of the changes in contractility and shape resulting from AF.MethodsThree operating conditions were analyzed: sinus rhythm, acute atrial fibrillation, and chronic atrial fibrillation. These were simulated on four patient-specific LAA morphologies, each associated with one of the main morphological variants identified from the common classification: chicken wing, cactus, windsock, and cauliflower. Active contractility of the wall muscle was calibrated on the basis of clinical evaluations of the filling and emptying volumes, and boundary conditions were imposed on the fluid to replicate physiological and pathological atrial pressures, typical of the various operating conditions.ResultsThe LAA volume and shear strain rates were analyzed over time and space for the different models. Globally, under AF conditions, all models were well aligned in terms of shear strain rate values and predicted levels of risk. Regions of low shear rate, typically associated with a higher risk of a clot, appeared to be promoted by sudden bends and focused at the trabecule and the lobes. These become substantially more pronounced and extended with AF, especially under acute conditions.ConclusionThis work clarifies the role of active and passive contraction on the healthy hemodynamics in the LAA, analyzing the hemodynamic effect of AF that promotes clot formation. The study indicates that local LAA topological features are more directly associated with a thromboembolic risk than the global shape of the appendage, suggesting that more effective classification criteria should be identified.

In this work, we analyze the effects of the presence of waveguides in a wireless on-chip optical channel, which act as obstacles for the rays composing the propagating signal. The analysis has been performed numerically by using the FDTD method, and the simulation results have been validated by the experimental characterization. This work focuses on the relationship between the received signal and the position of the obstacles on the circuit plane in a multilayered channel made of heterogeneous dielectric cladding. We show how the crossing waveguide perturbates the received power and we provide ad hoc guidelines for the best topological choices allowing to mitigate losses. Moreover, with a good agreement between numerical and experimental results, amounting to a variation of less than 1 dB, we have demonstrated that the effects of this perturbation in real chips can be predicted. The results of this analysis, as well as increasing the level of knowledge of on-chip optical wireless links, allow a better comprehension and control of unbound optical signals within the optical chip environment.

Functionality of a square used for ferry boats boarding has repercussions on safety and comfort of users, as well as on the efficiency of maritime transport. Inadequate use of the infrastructure causes driving errors followed by corrective manoeuvres, loss of time and potential accidents with consequences for community and the maritime transport compa-ny. The wide diversification of traffic components and payment methods are generally managed through a traditional horizontal and vertical signage system that does not refer to any current legislation. Therefore, the purpose of this research is to investigate driver's behaviour and the interaction that takes place between the latter and the environ-mental context. In particular, the authors focused on the study of the driver’s workload in a simulated environment, considering a users' sample and different driving scenarios inside the boarding area, concerning traffic conditions (isolated vehicle or presence of disturbing vehicles) and signs position. All this, in order to evaluate whether any change in a virtual context could bring real benefits to drivers, before being transferred to the real context. The results obtained, in terms of subjective workload and performance measures, have made it possible to judge the different solutions proposed in a simulated environment through synthetic indices referring to the entire boarding place or at certain parts of it. In this way, the manager can decide to change the circulation of the entire square or only some aspects of detail, such as some signals, in the event that they manifest an evident difficulty in the transfer of infor-mation. The use of the simulated environment allows greater speed in identifying the best solution, lower costs (avoid-ing the creation of a critical configuration for circulation) and greater user safety, since risky manoeuvres are identi-fied and corrected by the simulator. The proposed procedure can be used by managers for a correct arrangement of the signs, for the purpose of correctly directing the flows and maximizing the flow rate disposed of.

Background: The once-daily oral combination of daclatasvir (DCV) and sofosbuvir (SOF), with or without ribavirin (RBV), is effective and well tolerated in patients with hepatitis C virus (HCV). However, further field-practice studies are necessary to investigate the effectiveness and safety of the DCV+SOF combination in diverse subpopulations of patients with HCV, including those who are more challenging to treat such as patients with a genotype 3 (G3) infection. The aim of this retrospective, multicenter, field-practice study was to investigate the therapeutic efficacy and safety of the oral combination of DCV and SOF, with or without RBV (DCV+SOF±RBV), in a large unselected cohort of patients with chronic HCV infection (CHC). Patients and methods: Consecutive patients received DCV+SOF±RBV for 12 or 24 weeks. The efficacy endpoint was sustained virological response at 12 weeks after the end of treatment (SVR12). Safety factors were also considered. Results: A total of 620 patients were included in this study; the predominant genotype was G3 (55.3%). Of the total sample, 248 (40%) patients were treated with DCV+SOF+RBV and 372 (60%) did not receive RBV. The majority of patients assessed at week 12 (98%, 596/608) achieved SVR12. Among G3 patients, 98.8% (335/339) achieved SVR12. The most common adverse event was elevated bilirubin (30.6%), recorded in 4.9% of cases as a grade 3–4 adverse event. Conclusion: This study shows the high pan-genotypic effectiveness and safety of the DCV+SOF±RBV combination in a large, unselected sample of CHC patients with G1–4, including a wide proportion of G3 CHC patients.

Abstract Background Portal vein thrombosis (PVT) occurs frequently in hepatocellular carcinoma (HCC) and is often diagnosed in the course of a routine patient evaluation and surveillance for liver cancer. The purpose of this study is to investigate the relationship between folate status and portal vein thrombosis. Methods HCC with PVT patients were 78, HCC without PVT were 60 and control subjects were 70 randomly selected. We evaluate serum and red blood cellular folate, homocysteine, alpha fetal protein cholesterol, triglycerides, prothrombin time. Results HCC patients with PVT showed lower levels of serum folate, respect HCC patients without PVT, with an average difference of 1.6 nmol/l p

Abstract Background Papillary thyroid cancer (PTC) is the most frequent endocrine tumor. Radioiodine (RAI) treatment is highly effective in these tumors, but up to 60% of metastatic cases become RAI-refractory. Scanty data are available on either the molecular pattern of radioiodine refractory papillary thyroid cancers (PTC) or the mechanisms responsible for RAI resistance. Methods We analyzed the molecular profile and gene/miRNA expression in primary PTCs, synchronous and RAI-refractory lymph node metastases (LNMs) in correlation to RAI avidity or refractoriness. We classified patients as RAI+/D+ (RAI uptake/disease persistence), RAI−/D+ (absent RAI uptake/disease persistence), and RAI+/D- (RAI uptake/disease remission), and analyzed the molecular and gene/miRNA profiles, and the expression of thyroid differentiation (TD) related genes. Results A different molecular profile according to the RAI class was observed: BRAF V600E cases were more frequent in RAI−/D+ (P = 0.032), and fusion genes in RAI+/D+ cases. RAI+/D- patients were less frequently pTERT mutations positive, and more frequently wild type for the tested mutations/fusions. Expression profiles clearly distinguished PTC from normal thyroid. On the other hand, in refractory cases (RAI+/D+ and RAI−/D+) no distinctive PTC expression patterns were associated with either tissue type, or RAI uptake, but with the driving lesion and BRAF−/RAS-like subtype. Primary tumors and RAI-refractory LNMs with BRAF V600E mutation display transcriptome similarity suggesting that RAI minimally affects the expression profiles of RAI-refractory metastases. Molecular profiles associated with the expression of TPO, SLC26A4 and TD genes, that were found more downregulated in BRAF V600E than in gene fusions tumors. Conclusions The present data indicate a different molecular profile in RAI-avid and RAI-refractory metastatic PTCs. Moreover, BRAF V600E tumors displayed reduced differentiation and intrinsic RAI refractoriness, while PTCs with fusion oncogenes are RAI-avid but persistent, suggesting different oncogene-driven mechanisms leading to RAI refractoriness.

Abstract Background Wilson disease (WD) is an Autosomal-Recessive disorder due to mutations of ATP7B gene on chromosome 13q14.3. Inadequate protein function leads to low ceruloplasmin blood levels and copper accumulation in liver, basal ganglia and chornea. Main clinical manifestations are hypertransaminasemia, tremors, dysarthria, dystonia and psychiatric symptoms. The phenotypic variability in WD is considerable and its onset can be heterogeneous: the most common type in childhood is the hepatic involvement, followed by the neurological one or others. The presence of a genotype-phenotype correlation has not yet been fully demonstrated. The phenotypic variability may be explained by the intervention of other modifier genes regulating copper metabolism in the presence of mutations ATP7B. Case presentation A streaking phenotypic variability was observed in two Sicilian sisters carrying the same genotype for ATB7B gene [c.3207C > A / c.3904-2A > G]. Although both started to present signs at age 10 years, onset was characterized by neurological signs in the first (tremors, motor incoordination, language and cognitive impairment), while liver involvement has been the only sign in the other. They started the same chelation therapy. After a 20-year follow-up the former is severely affected (MRI evidence of basal ganglia copper deposits and hyperchogenic liver, thrombocytopenia), while the latter presents only a moderate liver enlargement. In literature, the splice mutation c.3904-2A > G is also reported in Egypt population, associated with acute liver failure or chronic hepatic disease, and it could be typical of Mediterranean area, not being reported in other geographical zones. Conclusion Based on our clinical experience in Eastern Sicily, there is a considerable phenotypic variability in WD, even in the presence of an identical genotype. The mutation c.3904-2A > G could be associated with this phenotypic variability in Mediterranean population, but further studies should be conducted. This condition could be explained by the intervention of modifier genes regulating copper metabolism in the presence of defective ATP7B protein function. Further investigations on their role by Next Generation Sequencing or Whole Exome Analysis might have a profound impact on patients’ management and in particular on therapy.

Preliminary archaeological investigations between Naples and Cancello on the Naples-Bari railway track in October 2014, brought a necropolis to the light that can be dated between the Late Copper Age and the Early Bronze Age. The archeological investigations made it possible to fill an important archaeological gap in Campania as the transition from the Copper Age to the Bronze Age is difficult to document in this area. Thanks to the discovery of the necropolis of Gaudello it has been possible to identify an occupation of the territory by a cultural group that gives life to a very peculiar vascular production which can be read as a full hybridization between Laterza pottery shapes and Bell Beaker and Cetina decorations. Globular shapes are created, with a cap or with a “S”-profile with decorations similar to “dragged comb ware”. Likewise it is highlighted how the people who occupied the Acerra territory, near the Clanis river, were absorptive for external influences and participated in exchange circuits thanks to which inside the tombs halberds and pins from the Cetina aspect and Bell Beaker horizon are found. In this necropolis from the assimilation of the Bell Beaker and Cetina elements arises a real form of “hybridisation”, not enclosable in a typological facies, but which can be defined as a cultural horizon where more types of influences coming from more areas are mixed. The legacy of the previous Laterza horizon is lost, abandoning the material production that was rooted with it, showing, instead, a high degree of absorption of external influences that become an autonomous interpretation and mixture of new models from which arises a different production, related to different cultural matrices. A vast basin of syncretism is created where different elements merge, generating mixtures, interactions and associations between heterogeneous characters that are reworked and taken over by people who decided to use these traits within their own funeral areas.

Background: The COVID-19 pandemic has undone years of progress in providing essential TB services and controlling the TB burden. Italy, a low TB burden country, has an incidence of 7.1 cases per 100,000 people. To control the TB spreading in Italy is critical to investigate the characteristics of patients with the worst outcomes and the highest risk of adverse events related to antituberculosis therapy. Therefore, we conducted a large retrospective study in TB patients admitted to the Clinic of Infectious Diseases University of Bari, Italy, in order to describe the clinical presentation and the factors associated with adverse events and outcomes. Methods: We retrospectively evaluated the patients admitted to the Clinic of Infectious Diseases from January 2013 to 15 December 2021. We stratified our cohort into two groups:

Novel effective therapeutic strategies are needed to treat brain neurodegenerative diseases and to improve the quality of life of patients affected by Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic Lateral sclerosis (ALS) as well as other brain conditions. At present no effective treatment options are available; current therapeutics for neurodegenerative diseases (NDs) improve cognitive symptoms only transiently and in a minor number of patients. Further, most of the amyloid-based phase III clinical trials recently failed in AD, in spite of promising preclinical and phase I-II clinical trials, further pinpointing the need for a better knowledge of the early mechanisms of disease as well as of more effective routes of drug administration. In fact, beyond common pathological events and molecular substrates, each of these diseases preferentially affect defined subpopulations of neurons in specific neuronal circuits (selective neuronal vulnerability), leading to the typical age-related clinical profile. In this perspective, key to successful drug discovery is a robust and reproducible biological validation of potential new molecular targets together with a concomitant set up of protocols/tools for efficient and targeted brain delivery to a specific area of interest. Here we propose and discuss Focused UltraSound aided drug administration as a specific and novel technical approach to achieve optimal concentration of the drug at the target area of interest. We will focus on drug delivery to the brain through the nasal route coupled to FUS as a promising approach to achieve neuroprotection and rescue of cognitive decline in several NDs.