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The asialoglycoprotein receptor 1 (ASGR1), a multivalent carbohydrate-binding receptor that primarily is responsible for recognizing and eliminating circulating glycoproteins with exposed galactose (Gal) or N-acetylgalactosamine (GalNAc) as terminal glycan residues, has been implicated in modulating the lipid metabolism and reducing cardiovascular disease burden. In this study, we investigated the impact of ASGR1 deficiency (ASGR1 -/-) on atherosclerosis by evaluating its effects on plaque formation, lipid metabolism, circulating immunoinflammatory response, and circulating N-glycome under the hypercholesterolemic condition in ApoE-deficient mice. After 16 weeks of a western-type diet, ApoE -/- /ASGR1 -/- mice presented lower plasma cholesterol and triglyceride levels compared to ApoE -/- . This was associated with reduced atherosclerotic plaque area and necrotic core formation. Interestingly, ApoE -/- /ASGR1 -/- mice showed increased levels of circulating immune cells, increased AST/ALT ratio, and no changes in the N-glycome profile and liver morphology. The liver of ApoE -/- /ASGR1 -/- mice, however, presented alterations in the metabolism of lipids, xenobiotics, and bile secretion, indicating broader alterations in liver homeostasis beyond lipids. These data suggest that improvements in circulating lipid metabolism and atherosclerosis in ASGR1 deficiency is paralleled by a deterioration of liver injury. These findings point to the need for additional evaluation before considering ASGR1 as a pharmacological target for dyslipidemia and cardiovascular disorders., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Microbial electrochemical technologies represent innovative approaches to contaminated soil and groundwater remediation and provide a flexible framework for removing organic and inorganic contaminants by integrating electrochemical and biological techniques. To simulate in situ microbial electrochemical treatment of groundwater plumes, this study investigates Cr(VI) reduction within a bioelectrochemical continuous flow (BECF) system equipped with soil-buried electrodes, comparing it to abiotic and open-circuit controls. Continuous-flow systems were tested with two chromium-contaminated solutions (20-50 mg Cr(VI)/L). Additional nutrients, buffers, or organic substrates were introduced during the tests in the systems. With an initial Cr(VI) concentration of 20 mg/L, 1.00 mg Cr(VI)/(L day) bioelectrochemical removal rate in the BECF system was observed, corresponding to 99.5% removal within nine days. At the end of the test with 50 mg Cr(VI)/L (156 days), the residual Cr(VI) dissolved concentration was two orders of magnitude lower than that in the open circuit control, achieving 99.9% bioelectrochemical removal in the BECF. Bacteria belonging to the orders Solirubrobacteriales, Gaiellales, Bacillales, Gemmatimonadales, and Propionibacteriales characterized the bacterial communities identified in soil samples; differently, Burkholderiales, Mycobacteriales, Cytophagales, Rhizobiales, and Caulobacterales characterized the planktonic bacterial communities. The complexity of the microbial community structure suggests the involvement of different microorganisms and strategies in the bioelectrochemical removal of chromium. In the absence of organic carbon, microbial electrochemical removal of hexavalent chromium was found to be the most efficient way to remove Cr(VI), and it may represent an innovative and sustainable approach for soil and groundwater remediation. Integr Environ Assess Manag 2024;20:2033-2049. © 2024 The Author(s). Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)., (© 2024 The Author(s). Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).)

Background: In Italy, knee osteoarthritis (KOA) accounts for over 5 million prevalent cases and requires long-term multidisciplinary management. The most frequent KOA symptom is pain. The aim of the survey is to provide a national overview of the current management of moderate-to-severe pain associated with KOA from both clinicians' and patients' perspectives., Methods: An exploratory qualitative survey was conducted in Italy between July and October 2023. The survey participants were members of four national scientific societies and two patient associations who were invited to participate via email and given an online questionnaire. Questions included a mix of single and multiple responses and scalar items., Results: In total, 1473 clinicians and 150 patients with KOA completed the questionnaire. Patients rated knee pain as both the most burdensome symptom and the most frequent reason for treatment dissatisfaction and seeking consultation. One in two patients declared that they were unsatisfied/little satisfied with the current prescribed analgesic treatments. The clinicians surveyed preferentially prescribed intra-articular hyaluronic acid, oral non-steroidal anti-inflammatory drugs/paracetamol, non-pharmacological intervention, and intra-articular corticosteroids. The clinicians' selection of analgesic therapy often failed to adequately meet patients' expectations for pain relief., Conclusions: Our findings highlight the current unmet needs of patients with KOA in Italy and call for new approaches to effectively optimize the management of KOA-associated pain.

Background: In Italy, Diagnosis-Related Groups (DRGs) have been adopted for hospital services reimbursement. In some Italian regions, nurse staffing allocation is purely volume-based, with different minutes/patient/day categories determined by the type of hospital ward. The Information System of Nursing Performance (SIPI) is a valid and reliable tool assessing nursing care complexity as an indicator of the actual nursing care demand. Evidence is lacking about the ability of current resource allocation methods to account for the nursing care demand., Objective: To evaluate the association between (1) DRG rates and nursing care complexity and (2) hospital ward categories of nurse staffing and nursing care complexity., Methods: All patients discharged from the medical department of an Italian hospital over a data collection period were eligible. To assess the association between nursing care complexity (SIPI) and DRGs, the distribution of the DRG rate (median and first-third quartile) was compared for cases with high or low complexity. To evaluate the association between nursing care complexity (SIPI) and nurse staffing, the frequency of high complexity within nurse staffing categories (120/180/240 min/patient/day) was compared. Because the sample was very large, methods of statistical inference were not applied, and only descriptive measures were reported., Results: 6872 hospitalizations were included. The median DRG rate for high and low complexity admissions were very similar (EUR 3536 and EUR 3285, respectively). The proportion of admissions with high complexity decreased for wards with higher staffing allocation rates., Conclusion: DRG reimbursement and the nurse staffing allocation systems were ineffective in accounting for nursing care complexity. The SIPI could help identify areas requiring more financial and staffing resources for nursing care.

Background: In Italy, longstanding limitations in the existing reporting system of the inpatient rehabilitation activities have been reported. The Hospital Discharge form (HDF) primarily uses ICD codes that inadequately capture the functional status and rehabilitation needs of patients, impacting equity of care and service evaluation. Therefore, the Italian Ministry of Health (IMH) launched an initiative aimed at developing a new reporting system to be specifically adopted in the inpatient rehabilitation setting., Methods: A working group (WG), lead by representatives of IMH, was established in 2019. It included members of scientific societies and professional associations in rehabilitation, administrators, policy makers, and other experts. Representatives of the Associations of Patients and Families were also consulted. The WG submitted the new version of the HDF to the political decision makers in early 2020. It includes detailed data on patients' functional levels before and after rehabilitation, and the complexity of clinical conditions. In using the ICD codes, priority is given to functional diagnoses., Results: In 2023, after a period of interruption due to the COVID-19 pandemic, a Ministry of Health Decree sanctioned the adoption of the new reporting system nationwide after a one-year trial period, starting on January 2024., Conclusions: The new HDF is expected to improve data collection, reduce local and regional disparities, allow better comparison of the performances of the structures, and ultimately enhance the quality and outcomes of rehabilitation care across the country. The Italian Society of Physical and Rehabilitation Medicine (SIMFER) gave an important contribution in the development of the system.

Objectives: To determine features and frequency of ultrasound (US)-detected tenosynovitis in ankles with clinically active disease and to investigate whether its detection may affect the achievement of inactive disease in patients with new-onset juvenile idiopathic arthritis (JIA)., Methods: The study included children with new-onset JIA and clinically active disease of the ankle. Based on US, patients were stratified as having isolated arthritis or as having tenosynovitis irrespective of the presence of concomitant arthritis in the ankle. Estimation of patients who were able to achieve clinically inactive disease 6 months after starting treatment was assessed by the Kaplan-Meier method. Cox model was used to calculate hazard ratio (HR) and 95% confidence interval (CI). Reliability of US was tested using kappa statistic., Results: Forty-five patients were recruited. On US, tenosynovitis of the ankle was detected in 28 patients (62.2%); isolated arthritis was found in 17 patients (37.8%). The medial and lateral tendon compartments were the tendon sites most frequently inflamed. Patients with tenosynovitis had similar likelihood of those without tenosynovitis to achieve clinically inactive disease (60.7% and 58.8%, respectively; HR 1.12, 95%CI:0.51-2.45). In the subanalysis excluding patients who were given biologics, the probability of experiencing inactive disease was slightly higher for patients with tenosynovitis compared to those without (64.7% and 54.5%, respectively; HR 1.56, 95%CI: 0.58-4.24). The rate of US reliability was high., Conclusions: US-detected tenosynovitis is frequent in ankles with clinical arthritis at JIA onset but does not impair the chance of achieving clinically inactive disease in the early disease phase.

Introduction: The role of uric acid (UA) and Hyper Uricemia (HU) in cardiac rehabilitation (CR) patients have been very little studied., Aim: To evaluate the prevalence of HU and if it is associated to the functional improvement obtained or the left ventricular Ejection Fraction (EF) in CR patients after Acute or Chronic Coronary Syndrome (ACS and CCS respectively)., Methods: We enrol 411 patients (62.4 ± 10.2 years; males 79.8%) enrolled in the CR program at Niguarda Hospital (Milan) from January 2012 to May 2023. HU was defined both as the classic cut-off (> 6 for females, > 7 mg/dL for males) and with the newly identified one by the URRAH study (> 5.1 for females, > 5.6 mg/dL for males). All patients performed a 6MWT and an echocardiography at the beginning and at the end of CR program., Results: Mean UA values were within the normal range (5.6 ± 1.4 mg/dL) with 19.5% (classic cut-off) HU patients with an increase to 47.4% with the newer one. Linear regression analysis showed no role for UA in determining functional improvement, while UA and hyperuricemia (classic cut-off) were associated to admission and discharge EF. The same was not with the URRAH cut-off., Conclusions: HU is as frequent in CR patients as in those with ACS and CCS. UA didn't correlate with functional recovery while it is associated with admission and discharge EF as also is for HU (classic cut-off). Whit the URRAH cut-off HU prevalence increases significantly, however, it doesn't show any significant association with EF., (© 2024. The Author(s).)

Background: Activation of brown adipose tissue (BAT) has gained attention due to its ability to dissipate energy and counteract cardiometabolic diseases (CMDs)., Methods: This study investigated the consequences of cold exposure on the BAT and liver proteomes of an established CMD mouse model based on LDL receptor-deficient (LdlrKO) mice fed a high-fat, high-sucrose, high-cholesterol diet for 16 weeks. We analyzed energy metabolism in vivo and performed untargeted proteomics on BAT and liver of LdlrKO mice maintained at 22 °C or 5 °C for 7 days., Results: We identified several dysregulated pathways, miRNAs, and transcription factors in BAT and liver of cold-exposed Ldlrko mice that have not been previously described in this context. Networks of regulatory interactions based on shared downstream targets and analysis of ligand-receptor pairs identified fibrinogen alpha chain (FGA) and fibronectin 1 (FN1) as potential crosstalk factors between BAT and liver in response to cold exposure. Importantly, genetic variations in the genes encoding FGA and FN1 have been associated with cardiometabolic-related phenotypes and traits in humans., Discussion: This study describes the key factors, pathways, and regulatory networks involved in the crosstalk between BAT and the liver in a cold-exposed CMD mouse model. These findings may provide a basis for future studies aimed at testing whether molecular mediators, as well as regulatory and signaling mechanisms involved in tissue adaption upon cold exposure, could represent a target in cardiometabolic disorders., (© 2024. The Author(s).)

Background: Red raspberry (Rubus idaeus L.) is an important nectar source for honey production in some specific habitats as well as an important crop, so the definition of the features of this kind of honey is noteworthy. However, due to its rarity on the market, red raspberry honey is poorly characterized. The aim of this work was the phytochemical characterization of honey containing red raspberry from different geographical origins, through melissopalynological analyses concurrently with untargeted metabolomics achieved with different chromatographic techniques coupled to mass spectrometry: solid-phase micro-extraction/gas chromatography/mass spectrometry (SPME-GC-MS) and high-performance liquid chromatography/Orbitrap mass spectrometry (HPLC-Orbitrap)., Results: Only 4 out of the 12 samples involved in the study contained raspberry pollen as dominant pollen, although these honeys did not group in the hierarchical cluster analysis nor in the classical multidimensional scaling analyses used for data evaluation. The first result was the detection of mislabelling in two samples, which contained raspberry pollen only as minor or important minor pollen. Of the 188 compounds identified by HPLC-Orbitrap and of the 260 identified by SPME-GC-MS, 87 and 31 compounds were present in all samples, respectively. The structurally related compounds nicotinaldehyde and nicotinamide, nicotinic acid and nicotinyl alcohol were present in 100% of the samples and correlated with R. idaeus pollen count (r > 0.60, Pearson's correlation analysis)., Conclusion: This study reveals important aspects about the characterization of red raspberry honey and could give new insights on bee diet and preferences, since niacin compounds resulted interestingly to be related to the presence of red raspberry pollen. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The metabolic contribution of the small intestine (SI) is still unclear despite recent studies investigating the involvement of single cells in regional differences. Using untargeted proteomics, we identified regional characteristics of the three intestinal tracts of C57BL/6J mice and found that proteins abundant in the mouse ileum correlated with the high ileal expression of the corresponding genes in humans. In the SI of C57BL/6J mice, we also detected an increasing abundance of lysosomal acid lipase (LAL), which is responsible for degrading triacylglycerols and cholesteryl esters within the lysosome. LAL deficiency in patients and mice leads to lipid accumulation, gastrointestinal disturbances, and malabsorption. We previously demonstrated that macrophages massively infiltrated the SI of Lal-deficient (KO) mice, especially in the duodenum. Using untargeted proteomics (ProteomeXchange repository, data identifier PXD048378), we revealed a general inflammatory response and a common lipid-associated macrophage phenotype in all three intestinal segments of Lal KO mice, accompanied by a higher expression of GPNMB and concentrations of circulating sTREM2. However, only duodenal macrophages activated a metabolic switch from lipids to other pathways, which were downregulated in the jejunum and ileum of Lal KO mice. Our results provide new insights into the process of absorption in control mice and possible novel markers of LAL-D and/or systemic inflammation in LAL-D.

Introduction: To introduce a drug to the market, it's not mandatory for it to be more effective and safer than the current treatment for the same condition. Consequently, head-to-head studies between the two best treatments for the same condition are not required, and this could result in a lack of information for patients, clinicians, and decision-makers. This study aims to evaluate the presence of head-to-head studies among the drugs used for the treatment of non-small cell lung cancer (NSCLC)., Methods: Taking into account the National Comprehensive Cancer Network (NCCN) guidelines updated to 2022, which list all available treatments for each NSCLC subtype, the search engine Pubmed and the platform clinicaltrials.gov were consulted to find all completed and ongoing head-to-head studies among various treatments for NSCLC., Results: Among the anti-EGFR (epidermal growth factor receptor) drugs, 7 studies were found, with 6 completed and 5 registrational for drug commercialisation. No completed study to date has compared osimertinib and afatinib. For anti-ALK (anaplastic lymphoma kinase) drugs, 7 studies were found, with 5 completed. Alectinib, brigatinib, and lorlatinib have no completed comparison studies, but all were compared with crizotinib. Among various immunotherapy-based regimens, 5 studies were found, with only 1 completed. Therapeutic regimens based on pembrolizumab, atezolizumab, or the combination of nivolumab/ipilimumab have not been compared in studies published to date., Conclusion: There are few head-to-head studies comparing treatments for NSCLC; there are no such studies between the latest generation of drugs. Consequently, ambiguous areas exist due to the lack of comparative studies among the available evidence, preventing the clinician's choice of the most effective treatment and risking the patient receiving suboptimal therapy. Simultaneously, the price of the drug cannot be determined correctly, relying only on indirect evaluations from different trials. To dispel this uncertainty, it would be desirable to initiate a process that brings together the demands derived from clinical practice and clinical research to provide clinicians and patients with the best possible evidence., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cutin, one of the main structural components of tomato peels, is a waxy biopolymer rich in hydroxylated fatty acids. In this study, 10,16-dihydroxyhexadecanoic acid (10,16-diHHDA) was extracted and isolated from tomato peels and exploited to develop fully crosslinked polyesters as potential candidates for replacing fossil-based metal protective coatings. A preliminary screening was conducted to select the base formulation, and then a design of experiments (DoE) was used as a methodology to identify the optimal composition to develop a suitable coating material. Different formulations containing 10,16-diHHDA and other biorefinery monomers, including 2,5-furandicarboxylic acid, were considered. To this end, all polyesters were characterized through differential scanning calorimetry (DSC) and gel content measurements to determine their T g value and crosslinking efficiency. Compositions exhibiting the best trade-off between T g value, chemical resistance, and sufficiently high 10,16-diHHDA content between 39 and 48 wt.% were used to prepare model coatings that were characterized for assessing their wettability, scratch hardness, chemical resistance, and adhesion to metal substrates. These polyester coatings showed a T g in the range of 45-55 °C, a hydrophobic behavior with a water contact angle of around 100°, a good solvent resistance (>100 MEK double rubs), and an adhesion strength to steel higher than 2 MPa. The results obtained confirmed the potential of cutin-based resins as coatings for metal protection, meeting the requirements for ensuring physicochemical properties of the final product, as well as for optimizing the valorization of such an abundant agri-food waste as tomato peels.

This review investigates the relationship between pediatric obstructive sleep apnea, often associated with adenotonsillar hypertrophy, and cardiovascular health, particularly pulmonary hypertension. We conducted a comprehensive literature search using electronic databases, including Medline Pub-Med, Scopus, and the Web of Science. The study analyzed a total of 230 articles and screened 48 articles, with 20 included in the final analysis, involving 2429 children. The PRISMA flowchart visually illustrates the selection process, and the ROBINS-E and -I tools help ensure the reliability and validity of the evidence produced by these studies. These studies explored various aspects, including the severity of obstructive sleep apnea, cardiac anomalies, cardiac stress markers, risk factors for pulmonary hypertension, and the impact of adenoidectomy and tonsillectomy on cardiac function. The research found that adenotonsillar hypertrophy and obstructive sleep apnea are significant risk factors for cardiovascular complications, especially pulmonary hypertension, in children. Adenoidectomy and tonsillectomy may provide effective treatments. Following adenoidectomy in relation to obstructive sleep apnea, there appears to be a reduction in mean pulmonary artery pressure during echocardiographic examination. However, the efficacy of these procedures can vary based on the severity of obstructive sleep apnea and individual cardiac conditions. The study also identified concerns regarding data bias. The authors emphasize the need for well-designed clinical studies, including both healthy patients with adenotonsillar hypertrophy and vulnerable children with genetic disorders, to ensure that clinical decisions are based on solid scientific evidence.

Background: Asialoglycoprotein receptor 1 (ASGR1), primarily expressed on hepatocytes, promotes the clearance and the degradation of glycoproteins, including lipoproteins, from the circulation. In humans, loss-of-function variants of ASGR1 are associated with a favorable metabolic profile and reduced incidence of cardiovascular diseases. The molecular mechanisms by which ASGR1 could affect the onset of metabolic syndrome and obesity are unclear. Therefore, here we investigated the contribution of ASGR1 in the development of metabolic syndrome and obesity., Methods: ASGR1 deficient mice (ASGR1 -/- ) were subjected to a high-fat diet (45% Kcal from fat) for 20 weeks. The systemic metabolic profile, hepatic and visceral adipose tissue were characterized for metabolic and structural alterations, as well as for immune cells infiltration., Results: ASGR1 -/- mice present a hypertrophic adipose tissue with 41% increase in fat accumulation in visceral adipose tissue (VAT), alongside with alteration in lipid metabolic pathways. Intriguingly, ASGR1 -/- mice exhibit a comparable response to an acute glucose and insulin challenge in circulation, coupled with notably decreased in circulating cholesterol levels. Although the liver of ASGR1 -/- have similar lipid accumulation to the WT mice, they present elevated levels of liver inflammation and a decrease in mitochondrial function., Conclusion: ASGR1 deficiency impacts energetic homeostasis during obesity leading to improved plasma lipid levels but increased VAT lipid accumulation and liver damage., (© 2024. The Author(s).)

Rhus coriaria L. (Anacardiaceae), also known as Sumac, is commonly used as a spice, flavoring agent, and as a traditional medicinal herb. This includes also the traditional use for treating asthma, catarrh, and common colds. The accumulating evidence supports its cardioprotective, antidiabetic, neuroprotective, anticancer, gastroprotective, antibacterial, anti-inflammatory, antiviral, antioxidant, and respiratory effects. However, there are no previous studies that have shown its effects and mechanism in the airway smooth muscle tone, and therefore, the aim of our study was to investigate the in vitro pharmacological action of R. coriaria L. extract (RCE) on the rat isolated tracheal and bronchial preparations by exploring its relaxant activity and mechanism of action. The direct relaxant effect of RCE (0.1-0.7 mg/mL) was tested in the rat bronchi and trachea rings precontracted by carbachol (CCh). In addition, the pretreatment with RCE (1 mg/mL) was tested on the bronchial and tracheal reactivity induced by CCh, potassium chloride (KCl), or CaCl 2 . In addition, the cyclooxygenase inhibitor indomethacin and the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME), respectively, were used for exploring the mechanisms of RCE-induced relaxation and reduction of reactivity. Our findings demonstrated that RCE induced a concentration-dependent relaxation and a significant reduction of reactivity, significantly reduced with either indomethacin or L-NAME. In addition, RCE decreased the responsiveness to KCl and affected the extracellular Ca 2+ -induced contraction in the tissues with added CCh or KCl in Ca 2+ -free Krebs-Henseleit solution. In summary, we have shown that RCE displayed relaxant activities in the in vitro airway smooth muscles, and the possible mechanisms seems to involve the prostaglandin, nitric oxide, and Ca 2+ pathways. Taken together, our findings indicate the potential role of RCE in the treatment of respiratory diseases with limited airflow, or obstructive respiratory diseases, and could justify its traditional use in the respiratory diseases.

The asialoglycoprotein receptor (ASGPR) and the mannose receptor C-type 1 (MRC1) are well known for their selective recognition and clearance of circulating glycoproteins. Terminal galactose and N-Acetylgalactosamine are recognized by ASGPR, while terminal mannose, fucose, and N-Acetylglucosamine are recognized by MRC1. The effects of ASGPR and MRC1 deficiency on the N-glycosylation of individual circulating proteins have been studied. However, the impact on the homeostasis of the major plasma glycoproteins is debated and their glycosylation has not been mapped with high molecular resolution in this context. Therefore, we evaluated the total plasma N-glycome and plasma proteome of ASGR1 and MRC1 deficient mice. ASGPR deficiency resulted in an increase in O-acetylation of sialic acids accompanied by higher levels of apolipoprotein D, haptoglobin, and vitronectin. MRC1 deficiency decreased fucosylation without affecting the abundance of the major circulating glycoproteins. Our findings confirm that concentrations and N-glycosylation of the major plasma proteins are tightly controlled and further suggest that glycan-binding receptors have redundancy, allowing compensation for the loss of one major clearance receptor., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Adenotonsillar hypertrophy has been well-acknowledged as the primary instigator of sleep-disordered breathing in the pediatric population. This condition spans a spectrum, from typical age-related growth that the immune system influences to persistent pathological hypertrophy. Reduction in air spaces, metabolic changes, neurobehavioral alterations, and chronic inflammation characterizes the latter form. As the go-to treatment, adenotonsillectomy has proven effective. However, it is not a guarantee for all patients, leaving us without reliable predictors of treatment success. Evidence suggests a connection between adenotonsillar hypertrophy and specific oral breathing patterns resulting from craniofacial development. This finding implies an intricate interdependence between the two, hinting at a self-sustaining vicious cycle that persists without proper intervention. The theories regarding the relationship between craniofacial conformation and sleep-disordered breathing have given rise to intriguing perspectives. In particular, the "gracilization theory" and the "gravitational hypothesis" have provided fascinating insights into the complex interaction between craniofacial conformation and SDB. Further investigation is crucial to unraveling the underlying pathophysiological mechanisms behind this relationship. It is also vital to explore the risk factors linked to adenotonsillectomy failure, study the long-term effects of adenotonsillar hypertrophy on craniofacial growth, and devise innovative diagnostic techniques to detect upper airway compromise early. Moreover, to assess their efficacy, we must delve into novel therapeutic approaches for cases that do not respond to traditional treatment, including positional therapy and orofacial myofunctional therapy. Though complex and unpredictable, these challenges promise to enhance our understanding and treatment of adenotonsillar hypertrophy and its related complications in children. By taking on this task, we can pave the way for more effective and targeted interventions, ultimately improving affected individuals' well-being and quality of life.

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration., Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020. The trial's primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020, the results of which were reported previously. Secondary endpoints (data cut-off Jan 31, 2022) included the outcomes of patients to immunotherapy based on vaccine administration, for which the final results are reported herein. A propensity score matching by age, sex, performance status, primary tumour site, comorbidities, and smoking habits was planned for the present analysis. Only patients with available data for these variables were included. The outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease-control rate (DCR)., Findings: The original study population consisted of 1188 evaluable patients. After a propensity score matching, 1004 patients were considered (502 vaccinated and 502 unvaccinated), and 986 of them were evaluable for overall survival (OS). At the median follow-up of 20 months, the influenza vaccination demonstrated a favourable impact on the outcome receiving ICI in terms of median OS [27.0 months (CI 19.5-34.6) in vaccinated vs. 20.9 months (16.6-25.2) in unvaccinated, p = 0.003], median progression-free survival [12.5 months (CI 10.4-14.6) vs. 9.6 months (CI 7.9-11.4), p = 0.049], and disease-control rate (74.7% vs. 66.5%, p = 0.005). The multivariable analyses confirmed the favourable impact of influenza vaccination in terms of OS (HR 0.75, 95% C.I. 0.62-0.92; p = 0.005) and DCR (OR 1.47, 95% C.I. 1.11-1.96; p = 0.007)., Interpretation: The INVIDIa-2 study results suggest a favourable immunological impact of influenza vaccination on the outcome of cancer patients receiving ICI immunotherapy, further encouraging the vaccine recommendation in this population and supporting translational investigations about the possible synergy between antiviral and antitumour immunity., Funding: The Federation of Italian Cooperative Oncology Groups (FICOG), Roche S.p.A., and Seqirus., Competing Interests: The Federation of Italian Cooperative Oncology Groups (FICOG) received funding for the present study from Roche S.p.A. and Seqirus, and outside the present research from Astra Zeneca, Bristol-Myers Squibb (BMS), and Sanofi. MB received funding for the present study from Roche S.p.A. and Seqirus (through FICOG as Institution, no personal fees). She also received, outside the current work: research funding from Pfizer and Novartis (through Institutions); honoraria as a speaker at scientific events (personal fees) by BMS, MSD, IPSEN, Novartis, Astra Zeneca, Pierre Fabre, and Pfizer; as a consultant for advisory role (personal fees) by IPSEN, Novartis, Sanofi, Pierre-Fabre, and Merck; personal fees for copyright transfer by Sciclone Pharmaceuticals, Pierre-Fabre, MSD, IPSEN, Pfizer, and Sanofi. AC received speakers fees/grant consultancies from Astrazeneca, BMS, MSD, EISAI, IQVIA, and OncoC4. UDG has served as a consultant for Astellas, Bayer, BMS, Ipsen, Janssen, Novartis, Pfizer, Sanofi, and Pharmamar; he received research funding from AstraZeneca, Roche, and Sanofi; and received travel funds from BMS, Ipsen, Janssen, Pfizer, and Roche during the conduct of the study. MDM reports personal fees from Bristol Myers Squibb, personal fees from Merck Sharp & Dohme, personal fees from AstraZeneca, personal fees from Janssen, personal fees from Astellas, personal fees from Pfizer, personal fees from Eisai, personal fees from Takeda, grants from Tesaro GSK, outside the submitted work. SB received honoraria as a speaker at scientific events and in advisory role by BMS, Pfizer; MSD, Ipsen, Roche S.p.A., Eli-Lilly, AstraZeneca, and Novartis; he also received research funding from Novartis. VS participated, with personal fees, to advisory boards and speaker's bureaus for Roche S.p.A. SC declared his role in an international board for Eli Lilly international. AR declares Advisory Board activity for Bristol, Pfizer, Bayer, and Kyowa Kirin, and speaker honorarium from Roche Diagnostics. PAZ reports outside the submitted work personal fees for advisory role, speaker engagements and travel and accommodation expenses from Merck Sharp & Dohme (MSD), Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, AstraZeneca, Roche, and Bayer. MS received honoraria for advisory role from Janssen, and travel and accommodation expenses from Janssen, IPSEN, BMS, Astellas, and Pfizer. ER had a role as consultant for MSD, Novartis, Pierre Fabre, Immunocore and Pfizer. FG received personal fees from Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, MSD, BMS, Pierre Fabre, Novartis, Merck, Takeda, Bayer, Novartis, and AMGEN for consulting activity; from Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, BMS, AMGEN, MSD, Celgene, and Pierre Fabre for speakers bureaus. GG declares speaker and advisory fees from MSD; Travels and Accommodations from AstraZeneca. DaS declares honoraria for advisory board from Astellas, Janssen, Bayer, Novartis, Astra-Zeneca, MSD, BMS, Roche. FM received personal fees for advisory role by Roche, MSD, Takeda, Novartis, Sanofi. RRS received travel grants from AIOM and CIPOMO, and declares memberships in AIOM, CIPOMO, ESMO, ASCO and Rotary Club. SP received honoraria as a speaker from Roche, Astra Zeneca, MSD, and GSK. DG received honoraria as a speaker from Amgen. MR received honoraria as speaker/consultant by MSD, Astra Zeneca, Bristol-MyersSquibb (BMS), Novartis, and Pfizer. All the cited competing interests were outside the current work and not related to the content of our manuscript if not differently specified. All remaining authors have declared no conflicts of interest., (© 2023 The Authors.)

The rapid spread of SARS-CoV-2 worldwide has triggered intense activity in the field of biotechnology, leading to the development and regulatory approval of multiple COVID-19 vaccines in less than 1 year while raising sustained scrutiny as to the ethical issues associated with this process. This article pursues a twofold objective. First, it reconstructs and provides a thorough overview of the different steps, from clinical trial design to regulatory procedures, underpinning the "fast-tracking" of COVID-19 vaccine R&D and approval. Second, drawing on a review of published literature, the article identifies, outlines, and analyzes the most ethically challenging aspects related to such process, including concerns around vaccine safety, issues in study design, the enrollment of study participants, and the challenges in obtaining valid informed consent. By scrutinizing relevant aspects of COVID-19 vaccine development and regulatory processes leading to market authorization, this article ultimately aims to provide a comprehensive overview of the regulatory and ethical issues underpinning the roll-out of this key pandemic-containment technology worldwide., (© 2023 The Authors. Bioethics published by John Wiley & Sons Ltd.)

Background: Emerging Technologies (ETs) have recently acquired great relevance in elderly care. The exceptional experience with SARS-CoV-2 pandemic has emphasized the usefulness of ETs in the assistance and remote monitoring of older adults. Technological devices have also contributed to the preservation of social interactions, thus reducing isolation and loneliness. The general purpose of this work is to provide a comprehensive and updated overview of the technologies currently employed in elderly care. This objective was achieved firstly, by mapping and classifying the ETs currently available on the market and, secondly, by assessing the impact of such ETs on elderly care, exploring the ethical values promoted, as well as potential ethical threats., Methods: An in-depth search was carried out on Google search engine, by using specific keywords (e.g. technology, monitoring techniques, ambient intelligence; elderly, older adults; care and assistance). Three hundred and twenty-eight technologies were originally identified. Then, based on a predetermined set of inclusion-exclusion criteria, two hundreds and twenty-two technologies were selected., Results: A comprehensive database was elaborated, where the two hundred and twenty-two ETs selected were classified as follows: category; developmental stage; companies and/or partners; functions; location of development; time of development; impact on elderly care; target; website. From an in-depth qualitative analysis, some ethically-related contents and themes emerged, namely: questions related to safety, independence and active aging, connectedness, empowerment and dignity, cost and efficiency. Although not reported by developers, a close analysis of website contents highlights that positive values are often associated with potential risks, notably privacy threats, deception, dehumanization of care., Conclusions: Research findings may ultimately lead to a better understanding of the impact of ETs on elderly people., (© 2023. The Author(s).)

Polylactic acid (PLA) is one of the most important biopolymers employed on the market due to its good mechanical strength and barrier properties. On the other hand, this material presents a rather low flexibility, limiting its employment. The valorization of bio-based agro-food waste for the modification of bioplastics is a highly appealing approach for the replacement of petrol-based materials. The aim of this work is to employ cutin fatty acids derived from a biopolymer (i.e., cutin), present in waste tomato peels and its bio-based derivatives as new plasticizers to enhance PLA flexibility. In particular, pure 10,16-dihydroxy hexadecanoic acid was extracted and isolated from tomato peels and then functionalized to give the desired compounds. All the molecules developed in this study were characterized by NMR and ESI-MS. Blends at different concentrations (10, 20, 30, and 40% w / w ) the flexibility (T g measurements with differential scanning calorimetry-DSC) of the final material. Furthermore, the physical behavior of two blends obtained by mechanical mixing of PLA and 16-methoxy,16-oxohexadecane-1,7-diyl diacetate was investigated through thermal and tensile tests. The data collected by DSC show a lowering in the T g of all the blends of PLA with functionalized fatty acids, in comparison with pure PLA. Lastly, the tensile tests highlighted how PLA blended with 16-methoxy,16-oxohexadecane-1,7-diyl diacetate (20% w / w ) can efficiently enhance its flexibility.

Prostate cancer (PCa) represents the fifth cause of cancer death in men. Currently, chemotherapeutic agents for the treatment of cancers, including PCa, mainly inhibit tumor growth by apoptosis induction. However, defects in apoptotic cellular responses frequently lead to drug resistance, which is the main cause of chemotherapy failure. For this reason, trigger non-apoptotic cell death might represent an alternative approach to prevent drug resistance in cancer. Several agents, including natural compounds, have been shown to induce necroptosis in human cancer cells. In this study we evaluated the involvement of necroptosis in anticancer activity of delta-tocotrienol (δ-TT) in PCa cells (DU145 and PC3). Combination therapy is one tool used to overcome therapeutic resistance and drug toxicity. Evaluating the combined effect of δ-TT and docetaxel (DTX), we found that δ-TT potentiates DTX cytotoxicity in DU145 cells. Moreover, δ-TT induces cell death in DU145 cells that have developed DTX resistance (DU-DXR) activating necroptosis. Taken together, obtained data indicate the ability of δ-TT to induce necroptosis in both DU145, PC3 and DU-DXR cell lines. Furthermore, the ability of δ-TT to induce necroptotic cell death may represent a promising therapeutical approach to overcome DTX chemoresistance in PCa.