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Background: Biphenotypic sinonasal sarcoma is a rare low-grade tumor arising from the sinonasal tract, featuring locally aggressive biological behavior, with a tendency to invade the orbit and skull base. There are no defined guidelines of treatment; thus, the management varies among different institutions. The aim of the present study is to provide a modular system of surgical approaches according to the lesion pattern of growth from a literature review. Materials and Methods: A comprehensive and detailed literature review on the PubMed and Embase online electronic databases on biphenotypic sinonasal sarcoma with orbital invasion was conducted. A personal case exhibiting peculiar features was also added. Demographic (patient's sex and age), clinical (presenting symptoms and time to treatment), neuroradiological (anatomical origin and pattern of growth), and treatment (type of treatment, surgical approach, extent of resection, peri- and postoperative complications, and adjuvant therapies) data, as well as clinical outcome, recurrence rates, and overall survival, were analyzed. Results: Thirty-one patients harboring biphenotypic sinonasal sarcoma with orbital invasion were identified. Tumors mainly affected female patients (66.7%) and a middle-aged population (median 55.2 years old). Simultaneous skull base involvement occurred in most cases (80.6%). Surgery was performed in all but one case (97%), as unique treatment (59%) or in association with radio-(23.5%) and/or chemotherapy (5.9%/2.9%), allowing for gross total tumor resection in most cases (66.7%). The endoscopic endonasal approach was the most adopted surgical corridor (51.7%). The local recurrence rate was 19.3%, and only two cases of tumor-related mortality occurred. Conclusions: Surgery is the only curative treatment, with the main goal to restore/improve/arrest progression of clinical manifestations. The endoscopic endonasal route represents the master approach for lesions confined to the midline. Microsurgical transcranial and endoscopic transorbital approaches have a complementary role for addressing the lesion's component with large intracranial extension or affecting the paramedian aspect of the anterior cranial fossa and superior-lateral orbital compartment, respectively. The approach selection should be made case by case according to the tumor pattern of growth.

Irritable bowel syndrome with diarrhea (IBS-D) is the most prevalent subtype of IBS, characterized by chronic gastrointestinal symptoms in the absence of identifiable pathological findings. This study aims to investigate the molecular mechanisms underlying IBS-D using transcriptomic data. By employing causal network inference methods, we identify key transcriptomic modules associated with IBS-D. Utilizing data from public databases and applying advanced computational techniques, we uncover potential biomarkers and therapeutic targets. Our analysis reveals significant molecular alterations that affect cellular functions, offering new insights into the complex pathophysiology of IBS-D. These findings enhance our understanding of the disease and may foster the development of more effective treatments.

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) affecting the gastrointestinal tract that can also cause extra-intestinal complications. Following exposure to the mRNA vaccine BNT162b2 (Pfizer-BioNTech) encoding the SARS-CoV-2 Spike (S) protein, some patients experienced a lack of response to the biological drug Adalimumab and a recrudescence of the disease. In CD patients in progression, resistant to considered biological therapy, an abnormal increase in intestinal permeability was observed, more often with a modulated expression of different proteins such as Aquaporin 8 (AQP8) and in tight junctions (e.g., ZO-1, Claudin1, Claudin2, Occludin), especially during disease flares. The aim of this study is to investigate how the SARS-CoV-2 vaccine could interfere with IBD therapy and contribute to disease exacerbation. We investigated the role of the SARS-CoV-2 Spike protein, transported by extracellular vesicles (EVs), and the impact of various EVs components, namely, exosomes (EXOs) and microvesicles (MVs), in modulating the expression of molecules involved in the exacerbation of CD, which remains unknown.

Conductive polymers, such as polyaniline (PANI), have interesting applications, ranging from flexible electronics, energy storage devices, sensors, antistatic or anticorrosion coatings, etc. However, the full exploitation of conductive polymers still poses a challenge due to their low processability. The use of compatible stabilizers to obtain dispersible and stable colloids is among the possible solutions to overcome such drawbacks. In this work, potato starch was used as a steric stabilizer for the preparation of colloidal polyaniline (emeraldine salt, ES)/starch composites by exploiting the oxidative polymerization of aniline in aqueous solutions with various starch-to-aniline ratios. The polyaniline/starch bio-composites were subjected to structural, spectroscopic, thermal, morphological, and electrochemical analyses. The samples were then tested for their dispersibility/solubility in a range of organic solvents. The results demonstrated the formation of PANI/starch biocomposites with a smaller average size than starch particles, showing improved aqueous dispersion and enhanced solubility in organic solvents. With respect to previously reported PANI-EB (emeraldine base)/starch composites, the novel colloids displayed a lower overall crystallinity, but the conductive nature of PANI-ES enhanced its electrochemical properties, resulting in richer redox chemistry, particularly evident in its oxidation behavior, as observed through cyclic voltammetry. Finally, as proof of the improved processability, the colloids were successfully integrated into a thin polyether sulfone (PES) membrane.

Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients treated with EGFR-tyrosine kinase inhibitors (TKIs) inevitably develop resistance through several biological mechanisms. However, little is known on the molecular mechanisms underlying acquired resistance to suboptimal EGFR-TKI doses, due to pharmacodynamics leading to inadequate drug exposure. To evaluate the effects of suboptimal EGFR-TKI exposure on resistance in NSCLC, we obtained HCC827 and PC9 cell lines resistant to suboptimal fixed and intermittent doses of gefitinib and compared them to cells exposed to higher doses of the drug. We analyzed the differences in terms of EGFR signaling activation and the expression of epithelial-mesenchymal transition (EMT) markers, whole transcriptomes byRNA sequencing, and cell motility. We observed that the exposure to low doses of gefitinib more frequently induced a partial EMT associated with an induced migratory ability, and an enhanced transcription of cancer stem cell markers, particularly in the HCC827 gefitinib-resistant cells. Finally, the HCC827 gefitinib-resistant cells showed increased secretion of the EMT inducer transforming growth factor (TGF)-β1, whose inhibition was able to partially restore gefitinib sensitivity. These data provide evidence that different levels of exposure to EGFR-TKIs in tumor masses might promote different mechanisms of acquired resistance.

Irritable bowel syndrome (IBS) involves low-grade mucosal inflammation. Among the various approaches capable of managing the symptoms, physical activity is still under investigation. Despite its benefits, it promotes oxidative stress and inflammation. Mitochondria impacts gut disorders by releasing damage-associated molecular patterns, such as cell-free mtDNA (cf-mtDNA), which support inflammation. This study evaluated the effects of a 12-week walking program on the cf-mtDNA and DNase in 26 IBS and 17 non-IBS subjects. Pro- and anti-inflammatory cytokines were evaluated by ELISA. Digital droplet PCR was used to quantify cf-mtDNA; DNase activity was assessed using a single radial enzyme diffusion assay. PCR-RFLP was used to genotype DNASE1 rs1053874 SNP. Significantly lower IL-10 levels were found in IBS than in non-IBS individuals. Exercise reduced cf-mtDNA in non-IBS subjects but not in IBS patients. DNase activity did not correlate with the cf-mtDNA levels in IBS patients post-exercise, indicating imbalanced cf-mtDNA clearance. Different rs1053874 SNP frequencies were not found between groups. The study confirms the positive effects of regular moderate-intensity physical activity in healthy subjects and its role in cf-mtDNA release and clearance. Walking alone might not sufficiently reduce subclinical inflammation in IBS, based on imbalanced pro- and anti-inflammatory molecules. Prolonged programs are necessary to investigate their effects on inflammatory markers in IBS.

Natural compounds like flavonoids preserve intestinal mucosal integrity through their antioxidant, anti-inflammatory, and antimicrobial properties. Additionally, some flavonoids show prebiotic abilities, promoting the growth and activity of beneficial gut bacteria. This study investigates the protective impact of Lens culinaris extract (LE), which is abundant in flavonoids, on intestinal mucosal integrity during LPS-induced inflammation. Using Caco-2 cells as a model for the intestinal barrier, the study found that LE did not affect cell viability but played a cytoprotective role in the presence of LPS. LE improved transepithelial electrical resistance (TEER) and tight junction (TJ) protein levels, which are crucial for barrier integrity. It also countered the upregulation of pro-inflammatory genes TRPA1 and TRPV1 induced by LPS and reduced pro-inflammatory markers like TNF-α, NF-κB, IL-1β, and IL-8. Moreover, LE reversed the LPS-induced upregulation of AQP8 and TLR-4 expression. These findings emphasize the potential of natural compounds like LE to regulate the intestinal barrier and reduce inflammation's harmful effects on intestinal cells. More research is required to understand their mechanisms and explore therapeutic applications, especially for gastrointestinal inflammatory conditions.

NOTCH1 PEST domain mutations are often seen in hematopoietic malignancies, including T-cell acute lymphoblastic leukemia (T-ALL), chronic lymphocytic leukemia (CLL), splenic marginal zone lymphoma (SMZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL). These mutations play a key role in the development and progression of lymphoproliferative tumors by increasing the Notch signaling and, consequently, promoting cell proliferation, survival, migration, and suppressing apoptosis. There is currently no specific treatment available for cancers caused by NOTCH1 PEST domain mutations. However, several NOTCH1 inhibitors are in development. Among these, inhibition of the Sarco-endoplasmic Ca 2+ -ATPase (SERCA) showed a greater effect in NOTCH1 -mutated tumors compared to the wild-type ones. One example is CAD204520, a benzimidazole derivative active in T-ALL cells harboring NOTCH1 mutations. In this study, we preclinically assessed the effect of CAD204520 in CLL and MCL models and showed that NOTCH1 PEST domain mutations sensitize cells to the anti-leukemic activity mediated by CAD204520. Additionally, we tested the potential of CAD204520 in combination with the current first-line treatment of CLL, venetoclax, and ibrutinib. CAD204520 enhanced the synergistic effect of this treatment regimen only in samples harboring the NOTCH1 PEST domain mutations, thus supporting a role for Notch inhibition in these tumors. In summary, our work provides strong support for the development of CAD204520 as a novel therapeutic approach also in chronic lymphoproliferative disorders carrying NOTCH1 PEST domain mutations, emerging as a promising molecule for combination treatment in this aggressive subset of patients.

In the last years, several studies demonstrated that low-aggressive (Grade Group (GG) ≤ 2) and high-aggressive (GG ≥ 3) prostate cancers (PCas) have different prognoses and mortality. Therefore, the aim of this study was to develop and externally validate a radiomic model to noninvasively classify low-aggressive and high-aggressive PCas based on biparametric magnetic resonance imaging (bpMRI). To this end, 283 patients were retrospectively enrolled from four centers. Features were extracted from apparent diffusion coefficient (ADC) maps and T2-weighted (T2w) sequences. A cross-validation (CV) strategy was adopted to assess the robustness of several classifiers using two out of the four centers. Then, the best classifier was externally validated using the other two centers. An explanation for the final radiomics signature was provided through Shapley additive explanation (SHAP) values and partial dependence plots (PDP). The best combination was a naïve Bayes classifier trained with ten features that reached promising results, i.e., an area under the receiver operating characteristic (ROC) curve (AUC) of 0.75 and 0.73 in the construction and external validation set, respectively. The findings of our work suggest that our radiomics model could help distinguish between low- and high-aggressive PCa. This noninvasive approach, if further validated and integrated into a clinical decision support system able to automatically detect PCa, could help clinicians managing men with suspicion of PCa.

The aim of this study is to evaluate the predictive role of specific clinical factors for the diagnosis of Multiple Endocrine Neoplasia type-1 (MEN1) and type-4 (MEN4) in patients with an initial diagnosis of gastrointestinal, bronchial, or thymic neuroendocrine tumor (NET)., Methods: Patients referred to the NET Unit between June 2021 and December 2022 with a diagnosis of NET and at least one clinical criterion of suspicion for MEN1 and MEN4 underwent molecular analysis of the MEN1 and CDKN1B genes. Phenotypic criteria were: (1) age ≤ 40 years; (2) NET multifocality; (3) MEN1/4-associated manifestations other than NETs; and (4) endocrine syndrome related to NETs or pituitary/adrenal tumors., Results: A total of 22 patients were studied. In 18 patients (81.8%), the first-level genetic test was negative (Group A), while four patients (25%) were positive for MEN1 (Group B). No patient was positive for MEN4 . In Group A, 10 cases had only one clinical criterion, and three patients met three criteria. In Group B, three patients had three criteria, and one met all criteria., Conclusion: These preliminary data show that a diagnosis of NET in patients with a negative family history is suggestive of MEN1 in the presence of ≥three positive phenotypic criteria, including early age, multifocality, multiple MEN-associated manifestations, and endocrine syndromes. This indication may allow optimization of the diagnosis of MEN in patients with NET.

Colorectal cancer (CRC) is one of the leading causes of mortality for cancer in industrialized countries. The link between diet and CRC is well-known, and presumably CRC is the type of cancer which is most influenced by dietary habits. In Western countries, an inadequate dietary intake of fibers is endemic, and this could be a driving factor in the increase of CRC incidence. Indeed, several epidemiologic studies have elucidated an inverse relationship between daily fiber intake and risk of CRC. Long-term prognosis in CRC survivors is also dependent on dietary fibers. Several pathogenetic mechanisms may be hypothesized. Fibers may interfere with the metabolism of bile acids, which may promote colon carcinogenesis. Further, fibers are often contained in vegetables which, in turn, contain large amounts of antioxidant agents like resveratrol, polyphenols, or phytoestrogens. Moreover, fibers can be digested by commensal flora, thus producing compounds such as butyrate, which exerts an antiproliferative effect. Finally, fibers may modulate gut microbiota, whose composition has shown to be associated with CRC onset. In this regard, dietary interventions based on high-fiber-containing diets are ongoing to prevent CRC development, especially in patients with high potential for this type of tumor. Despite the fact that outcomes are preliminary, encouraging results have been observed.

Several gastrointestinal (GI) tract abnormalities, including visceral hypersensitivity, motility, and intestinal permeability alterations, have been implicated in functional GI disorders (FGIDs). Ion channels play a crucial role in all the functions mentioned above. Hormones and natural molecules modulate these channels and represent targets of drugs and bacterial toxins. Mutations and abnormal functional expression of ion channel subunits can lead to diseases called channelopathies. These channelopathies in gastroenterology are gaining a strong interest, and the evidence of co-relationships is increasing. In this review, we describe the correlation status between channelopathies and FGIDs. Different findings are available. Among others, mutations in the ABCC7 /CFTR gene have been described as a cause of constipation and diarrhea. Mutations of the SCN5A gene are instead associated with irritable bowel syndrome. In contrast, mutations of the TRPV1 and TRPA genes of the transient receptor potential (TRP) superfamily manifest hypersensitivity and visceral pain in sensory nerves. Recently, mice and humans affected by Cantu syndrome (CS), which is associated with the mutations of the KCNJ8 and ABCC9 genes encoding for the Kir6.1 and SUR2 subunits, showed dysfunction of contractility throughout the intestine and death in the mice after the weaning on solid food. The discovery of a correlation between channelopathies and FIGD opens new avenues for discovering new direct drug targets for specific channelopathies, leading to significant implications for diagnosing and treating functional GI diseases.

The Posidonia oceanica meadows represent a fundamental biological indicator for the assessment of the marine ecosystem's state of health. They also play an essential role in the conservation of coastal morphology. The composition, extent, and structure of the meadows are conditioned by the biological characteristics of the plant itself and by the environmental setting, considering the type and nature of the substrate, the geomorphology of the seabed, the hydrodynamics, the depth, the light availability, the sedimentation speed, etc. In this work, we present a methodology for the effective monitoring and mapping of the Posidonia oceanica meadows by means of underwater photogrammetry. To reduce the effect of environmental factors on the underwater images (e.g., the bluish or greenish effects), the workflow is enhanced through the application of two different algorithms. The 3D point cloud obtained using the restored images allowed for a better categorization of a wider area than the one made using the original image elaboration. Therefore, this work aims at presenting a photogrammetric approach for the rapid and reliable characterization of the seabed, with particular reference to the Posidonia coverage.

Early life exposure to Endocrine Disruptor Chemicals (EDCs), such as the organophosphate pesticide Chlorpyrifos (CPF), affects the thyroid activity and dependent process, including the glucose metabolism. The damage of thyroid hormones (THs) as a mechanism of action of CPF is underestimated because the studies rarely consider that TH levels and signaling are customized peripherally. Here, we investigated the impairment of metabolism/signaling of THs and lipid/glucose metabolism in the livers of 6-month-old mice, developmentally and lifelong exposed to 0.1, 1, and 10 mg/kg/die CPF (F1) and their offspring similarly exposed (F2), analyzing the levels of transcripts of the enzymes involved in the metabolism of T3 ( Dio1 ), lipids ( Fasn , Acc1 ), and glucose ( G6pase , Pck1 ). Both processes were altered only in F2 males, affected by hypothyroidism and by a systemic hyperglycemia linked to the activation of gluconeogenesis in mice exposed to 1 and 10 mg/kg/die CPF. Interestingly, we observed an increase in active FOXO1 protein due to a decrease in AKT phosphorylation, despite insulin signaling activation. Experiments in vitro revealed that chronic exposure to CPF affected glucose metabolism via the direct modulation of FOXO1 activity and T3 levels in hepatic cells. In conclusion, we described different sex and intergenerational effects of CPF exposure on the hepatic homeostasis of THs, their signaling, and, finally, glucose metabolism. The data points to FOXO1-T3-glucose signaling as a target of CPF in liver.

The erythroid transcriptional factor Krüppel-like factor 1 (KLF1) is a master regulator of erythropoiesis. Mutations that cause KLF1 haploinsufficiency have been linked to increased fetal hemoglobin (HbF) and hemoglobin A 2 (HbA 2 ) levels with ameliorative effects on the severity of β-thalassemia. With the aim of determining if KLF1 gene variations might play a role in the modulation of β-thalassemia, in this study we screened 17 subjects showing a β-thalassemia-like phenotype with a slight or marked increase in HbA 2 and HbF levels. Overall, seven KLF1 gene variants were identified, of which two were novel. Functional studies were performed in K562 cells to clarify the pathogenic significance of these mutations. Our study confirmed the ameliorative effect on the thalassemia phenotype for some of these variants but also raised the notion that certain mutations may have deteriorating effects by increasing KLF1 expression levels or enhancing its transcriptional activity. Our results indicate that functional studies are required to evaluate the possible effects of KLF1 mutations, particularly in the case of the co-existence of two or more mutations that could differently contribute to KLF1 expression or transcriptional activity and consequently to the thalassemia phenotype.

The literature predominantly advocates subjective perception of disability and pain as an outcome measure for the functional evaluation of patients with low back pain (LBP). Physical outcome measurements are almost completely ignored. In this systematic review, we focused on physical functional measurements that can contribute to the prediction of patients' return to work (RTW) readiness after sick leave or rehabilitation. Searches were conducted in July 2022 without any time limit in the Cochrane Library, PEDro, PubMed and Scopus databases for functional and clinical tests reliable and applicable in clinical practice without demanding equipment. Two independent researchers extracted the data from the included articles in a standardised data collection form, and a third researcher validated the data extraction. No date restriction was applied. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in conducting the review. We found seven original articles, including six with an impact on predicting RTW. We found four fair and three poor original studies fulfilling our criteria. We found the Back Performance Scale (BPS) and back endurance test to be the most promising tests for occupational health service and the clinical practitioner. Radiation of back pain, with or without neurological deficiencies, had some predictive value in terms of RTW, too. The working conditions vary a lot, which causes inconsistency in the studies and in their interpretation. Functional tests could complete the widely used working ability evaluations methods such as the Work Ability Index (WAI) and are worth considering for future research. Overall, more research is needed in this field. The question of when LBP patients can resume everyday activities and work is not possible to determine with functional tests alone. Psychosocial aspects and work demands must be considered. PROSPERO: CRD42022353955. The study was funded by the University of Helsinki.

Although the imbalance of circulating levels of Thyroid Hormones (THs) affects female fertility in vertebrates, its involvement in the promotion of Premature Ovarian Aging (POA) is debated. Therefore, altered synthesis of THs in both thyroid and ovary can be a trait of POA. We investigated the relationship between abnormal TH signaling, dysthyroidism, and POA in evolutionary distant vertebrates: from zebrafish to humans. Ovarian T3 signaling/metabolism was evaluated by measuring T3 levels, T3 responsive transcript, and protein levels along with transcripts governing T3 availability (deiodinases) and signaling (TH receptors) in distinct models of POA depending on genetic background and environmental exposures (e.g., diets, pesticides). Expression levels of well-known ( Amh , Gdf9 , and Inhibins) and novel ( miR143/145 and Gas5 ) biomarkers of POA were assessed. Ovarian dysthyroidism was slightly influenced by genetics since very few differences were found between C57BL/6J and FVB/NJ females. However, diets exacerbated it in a strain-dependent manner. Similar findings were observed in zebrafish and mouse models of POA induced by developmental and long-life exposure to low-dose chlorpyrifos (CPF). Lastly, the T3 decrease in follicular fluids from women affected by diminished ovarian reserve, as well as of the transcripts modulating T3 signaling/availability in the cumulus cells, confirmed ovarian dysthyroidism as a common and evolutionary conserved trait of POA.

Frequently touched surfaces (FTS) that are contaminated with pathogens are one of the main sources of nosocomial infections, which commonly include hospital-acquired and healthcare-associated infections (HAIs). HAIs are considered the most common adverse event that has a significant burden on the public's health worldwide currently. The persistence of pathogens on contaminated surfaces and the transmission of multi-drug resistant (MDR) pathogens by way of healthcare surfaces, which are frequently touched by healthcare workers, visitors, and patients increase the risk of acquiring infectious agents in hospital environments. Moreover, not only in hospitals but also in high-traffic public places, FTS play a major role in the spreading of pathogens. Consequently, attention has been devoted to developing novel and alternative methods to tackle this problem. This study planned to produce and characterize innovative functionalized enameled coated surfaces supplemented with 1% AgNO 3 and 2% AgNO 3 . Thus, the antimicrobial properties of the enamels against relevant nosocomial pathogens including the Gram-positive Staphylococcus aureus and the Gram-negative Escherichia coli and the yeast Candida albicans were assessed using the ISO:22196:2011 norm.

(1) Background: In recent years, the consumption of sprouts, thanks to their high nutritional value, and the presence of bioactive compounds with antioxidant, antiviral and antibacterial properties, is becoming an increasingly widespread habit. Moringa oleifera Lam. (Moringa) seems to be an inexhaustible resource considering that many parts may be used as food or in traditional medicine; on the other hand, Moringa sprouts still lack a proper characterization needing further insights to envisage novel uses and applications. (2) Methods: In this study, a rapid and easy protocol to induce the in vivo and in vitro germination of Moringa seeds has been set up to obtain sprouts and cotyledons to be evaluated for their chemical composition. Moreover, the effects of sprouts developmental stage, type of sowing substrate, and gibberellic acid use on the chemical characteristics of extracts have been evaluated. (3) Results: Moringa seeds have a high germinability, both in in vivo and in vitro conditions. In addition, the extracts obtained have different total phenolic content and antioxidant activity. (4) Conclusions: This research provides a first-line evidence to evaluate Moringa sprouts as future novel functional food or as a valuable source of bioactive compounds.

Background: Residents of a large area in the Veneto Region (Northeastern Italy) were exposed to drinking water contaminated by perfluoroalkyl substances (PFAS) for decades. While exposure to PFAS has been consistently associated with elevated serum lipids, combined exposures to multiple PFASs have been poorly investigated. Utilising different statistical approaches, we examine the association between chemical mixtures and lipid parameters., Methods: Cross-sectional data from the regional health surveillance program (34,633 individuals aged 20-64 years) were used to examine the combined effects of PFAS mixture (Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS)) on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Weighted Quantile Sum (WQS) regression, Quantile-based G-computation (Q-Gcomp) and Bayesian Kernel Machine Regression (BKMR) were used based on their ability to handle highly correlated chemicals., Results: We observed that each quartile increase in the WQS index was associated with an increase in the levels of TC (β: 4.09, 95% CI: 3.47-4.71), HDL-C (β: 1.13, 95% CI: 0.92-1.33) and LDL-C (β: 3.14, 95% CI: 2.65-3.63). Q-Gcomp estimated that a quartile increase in the PFAS mixture was associated with increased TC (ψ: 4.04, 95% CI 3.5-4.58), HDL-C (ψ: 1.07, 95% CI 20.87-1.27) and LDL-C (ψ: 2.71, 95% CI 2.23-3.19). In the BKMR analysis, the effect of PFAS mixture on serum lipids increased significantly when their concentrations were at their 75th percentiles or above, compared to those at their 50th percentile. All methods revealed a major contribution of PFOS and PFNA, although the main exposure was due to PFOA. We found suggestive evidence that associations varied when stratified by gender., Conclusions: The PFAS mixture was positively associated with lipid parameters, regardless of the applied method. Very similar results obtained from the three methods may be attributed to the linear positive association with the outcomes and no interaction between each PFAS.

The advent of trastuzumab has significantly improved the prognosis of HER2-positive (HER2+) breast cancer patients; nevertheless, drug resistance limits its clinical benefit. Anti-HER2 active immunotherapy represents an attractive alternative strategy, but effective immunization needs to overcome the patient's immune tolerance against the self-HER2. Phage display technology, taking advantage of phage intrinsic immunogenicity, permits one to generate effective cancer vaccines able to break immune tolerance to self-antigens. In this study, we demonstrate that both preventive and therapeutic vaccination with M13 bacteriophages, displaying the extracellular (EC) and transmembrane (TM) domains of human HER2 or its Δ16HER2 splice variant on their surface (ECTM and Δ16ECTM phages), delayed mammary tumor onset and reduced tumor growth rate and multiplicity in ∆16HER2 transgenic mice, which are tolerant to human ∆16HER2. This antitumor protection correlated with anti-HER2 antibody production. The molecular mechanisms underlying the anticancer effect of vaccine-elicited anti-HER2 antibodies were analyzed in vitro against BT-474 human breast cancer cells, sensitive or resistant to trastuzumab. Immunoglobulins (IgG) purified from immune sera reduced cell viability mainly by impairing ERK phosphorylation and reactivating retinoblastoma protein function in both trastuzumab-sensitive and -resistant BT-474 cells. In conclusion, we demonstrated that phage-based HER2 vaccines impair mammary cancer onset and progression, opening new perspectives for HER2+ breast cancer treatment.

In December 2021-January 2022 the Veneto region in Italy faced an unprecedented wave of SARS-CoV-2 infections, even though both the vaccine coverage and the number of previously infected individuals keep increasing. In this study we address the protection against the SARS-CoV-2 infection offered by natural immunity and a three-dose regimen through a retrospective study based on Veneto's regional databases. In particular, we compared these protection levels during two distinct periods respectively representative of the Delta (B.1.617.2) and the Omicron (B.1.1.529) variants, in order to investigate and quantify the immunological evasion, especially of the Omicron. For each period we compared the incidence rate of infection among the population with various immunological protections against SARS-CoV-2 and performed a multivariable proportional hazard Cox binomial regression to assess the effectiveness afforded by both forms of active immunization. We found out that a previous SARS-CoV-2 infection (irrespective of its timing) offers 85% (83-87%) and 36% (33-39%) protection against being reinfected by Delta and Omicron, respectively. In addition, we estimated the third dose to be more effective in both periods and to have a minor proportional loss of effectiveness due to the rise of the Omicron variant, with an afforded effectiveness against SARS-CoV-2 Delta and Omicron infection of 97% (96-97%) and 47% (45-48%), respectively. Our findings suggest that viral variant factors may affect any form of active immunization but that receiving a booster vaccination cycle is more effective and less variable than natural immunity in terms of afforded protection against SARS-CoV-2 infections.

Low Back Pain (LBP) is currently the first cause of disability in the world, with a significant socioeconomic burden. Diagnosis and treatment of LBP often involve a multidisciplinary, individualized approach consisting of several outcome measures and imaging data along with emerging technologies. The increased amount of data generated in this process has led to the development of methods related to artificial intelligence (AI), and to computer-aided diagnosis (CAD) in particular, which aim to assist and improve the diagnosis and treatment of LBP. In this manuscript, we have systematically reviewed the available literature on the use of CAD in the diagnosis and treatment of chronic LBP. A systematic research of PubMed, Scopus, and Web of Science electronic databases was performed. The search strategy was set as the combinations of the following keywords: “Artificial Intelligence”, “Machine Learning”, “Deep Learning”, “Neural Network”, “Computer Aided Diagnosis”, “Low Back Pain”, “Lumbar”, “Intervertebral Disc Degeneration”, “Spine Surgery”, etc. The search returned a total of 1536 articles. After duplication removal and evaluation of the abstracts, 1386 were excluded, whereas 93 papers were excluded after full-text examination, taking the number of eligible articles to 57. The main applications of CAD in LBP included classification and regression. Classification is used to identify or categorize a disease, whereas regression is used to produce a numerical output as a quantitative evaluation of some measure. The best performing systems were developed to diagnose degenerative changes of the spine from imaging data, with average accuracy rates >80%. However, notable outcomes were also reported for CAD tools executing different tasks including analysis of clinical, biomechanical, electrophysiological, and functional imaging data. Further studies are needed to better define the role of CAD in LBP care.

We evaluated the effects of cannabidiol (CBD) on seizures and peroxisome proliferator-activated receptor gamma (PPARγ) levels in an animal model of temporal lobe epilepsy (TLE). Adult male Sprague-Dawley rats were continuously monitored by video-electrocorticography up to 10 weeks after an intraperitoneal kainic acid (15 mg/kg) injection. Sixty-seven days after the induction of status epilepticus and the appearance of spontaneous recurrent seizures in all rats, CBD was dissolved in medium-chain triglyceride (MCT) oil and administered subcutaneously at 120 mg/kg (n = 10) or 12 mg/kg (n = 10), twice a day for three days. Similarly, the vehicle was administered to ten epileptic rats. Brain levels of PPARγ immunoreactivity were compared to those of six healthy controls. CBD at 120 mg/kg abolished the seizures in 50% of rats (p = 0.033 vs. pre-treatment, Fisher’s exact test) and reduced total seizure duration (p < 0.05, Tukey Test) and occurrence (p < 0.05). PPARγ levels increased with CBD in the hippocampal CA1 subfield and subiculum (p < 0.05 vs. controls, Holm−Šidák test), but only the highest dose increased the immunoreactivity in the hippocampal CA3 subfield (p < 0.001), perirhinal cortex, and amygdala (p < 0.05). Overall, these results suggest that the antiseizure effects of CBD are associated with upregulation of PPARγ in the hippocampal CA3 region.

In March 2019, the World Health Organization (WHO) recognized the COVID-19 pandemic as a global issue. To reduce the spread of this disease, health safety pathways were implemented worldwide. These extraordinary measures changed people's lifestyles, e.g., by being forced to isolate, and in many cases, to work remotely from home. Low back pain (LBP), the most common cause of disability worldwide, is often a symptom of COVID-19. Moreover, it is often associated with different lifestyle features (type of job, physical activity, body weight). Therefore, the purpose of this systematic review and meta-analysis was to estimate the effect of the COVID-19 lockdown on LBP intensity and prevalence compared with LBP rates before the pandemic. A systematic search was performed on Scopus, PubMed, and Cochrane Central. Overall, eight studies with 2365 patients were included in the analysis. We used the Joanna Briggs Institute (JBI) critical appraisal tool to evaluate the risk of bias: six studies (75%) were at moderate risk of bias and two studies (25%) were at low risk of bias. These studies showed an increase in both the prevalence and intensity of LBP during the COVID-19 lockdown.

The high toxicity of antineoplastic drugs (ADs) makes them dangerous not only for patients, but also for exposed workers. Therefore, the aim of this review was to provide an updated overview of the biological monitoring of occupational AD exposure in order to extrapolate information useful to improve risk assessment and management strategies in workplaces. Several studies demonstrated that remarkable portions of healthcare workers may have traces of these substances or their metabolites in biological fluids, although with some conflicting results. Nurses, directly engaged in AD handling, were the occupational category at higher risk of contamination, although, in some cases, personnel not involved in AD-related tasks also showed quantifiable internal doses. Overall, further research carried out on greater sample sizes appears necessary to gain deeper insight into the variability retrieved in the reported results. This may be important to understand the impact of the extent of ADs use, different handling, procedures, and cleaning practices, spill occurrence, training of the workforce, as well as the adoption of adequate collective and personal protective equipment in affecting the occupational exposure levels. This may support the achievement of the greatest clinical efficiency of such therapies while assuring the health and safety of involved workers.

Background. Skin diseases (e.g., psoriasis and systemic sclerosis) are generally associated with negative psychosocial outcomes. Although different psychological interventions have been used to improve the quality of life of dermatological patients, the effects of the guided written disclosure (GWD) protocol have not been previously examined in these patients. Moreover, little attention has been paid to positive psychology constructs. Methods. This study investigates the effectiveness of GWD on positive and negative functioning in dermatological patients. Pre- and 1-month post-intervention measures included emotion regulation, sense of inner peace, skin-related symptoms and functioning, sense of coherence, and psychological distress. Results. A total of 196 consecutive outpatients were randomly assigned to GWD and active control groups, of whom 60 (30.6%) completed the study and 45 (GWD: n = 24; AC: n = 21) provided complete data. Our results did not show any significant difference between the experimental and control groups in the outcome variables, whereas non-completers reported higher levels of distress, unpleasant skin-related emotions, and lower cognitive reappraisal compared to completers. Conclusions. These findings show a poor compliance, and suggest that expressive writing is not well accepted by patients and is not effective in improving positive and negative psychological functioning in dermatological patients.

(1) Background: The purpose of this review is to study the role of radiomics as a supporting tool in predicting bone disease status, differentiating benign from malignant bone lesions, and characterizing malignant bone lesions. (2) Methods: Two reviewers conducted the literature search independently. Thirteen articles on radiomics as a decision support tool for bone lesions were selected. The quality of the methodology was evaluated according to the radiomics quality score (RQS). (3) Results: All studies were published between 2018 and 2021 and were retrospective in design. Eleven (85%) studies were MRI-based, and two (15%) were CT-based. The sample size was <200 patients for all studies. There is significant heterogeneity in the literature, as evidenced by the relatively low RQS value (average score = 22.6%). There is not a homogeneous protocol used for MRI sequences among the different studies, although the highest predictive ability was always obtained in T2W-FS. Six articles (46%) reported on the potential application of the model in a clinical setting with a decision curve analysis (DCA). (4) Conclusions: Despite the variability in the radiomics method application, the similarity of results and conclusions observed is encouraging. Substantial limits were found; prospective and multicentric studies are needed to affirm the role of radiomics as a supporting tool.

Altered gut-brain communication can contribute to intestinal dysfunctions in the intestinal bowel syndrome. The neuroprotective high-fat, adequate-protein, low-carbohydrate ketogenic diet (KD) modulates the levels of different neurotransmitters and neurotrophins. The aim was to evaluate the effects of KD on levels of 5-HT, the receptors 5-HT 3B and 5-HT 4 , the 5-HT transporter SERT, the neurotrophin BDNF, and its receptor TrkB in the colon and brain of a rat model of irritable bowel syndrome (IBS). Samples from Wistar rats exposed to maternal deprivation as newborns and then fed with a standard diet (IBS-Std) or KD (IBS-KD) for ten weeks were analyzed. As controls, unexposed rats (Ctrl-Std and Ctrl-KD) were studied. IBS-Std rats had a disordered enteric serotoninergic signaling shown by increased mucosal 5-HT content and reduced SERT, 5-HT 3B , and 5-HT 4 levels compared to controls. In the brain, these animals showed up-regulation of the BDNF receptor TrkB as a counteracting response to the stress-induced reduction of the neurotrophin. KD showed a dual effect in improving the altered 5-HT and BDNF systems. It down-regulated the increased mucosal 5-HT without affecting transporter and receptor levels. KD improved brain BDNF levels and established negative feedback, leading to a compensatory downregulation of TrkB to maintain a physiological steady state.

Low back pain represents a significant socioeconomic burden. Several nonsurgical medical treatments have been proposed for the treatment of this disabling condition. Epidural steroid injections (ESIs) are commonly used to treat lumbosacral radicular pain and to avoid surgery. Even though it is still not clear which type of conservative intervention is superior, several studies have proved that ESIs are able to increase patients' quality of life, relieve lumbosacral radicular pain and finally, reduce or delay more invasive interventions, such as spinal surgery. The aim of this narrative review is to analyze the mechanism of action of ESIs in patients affected by low back pain and investigate their current application in treating this widespread pathology.

Chronic low back pain (CLBP) is the most common cause of disability worldwide, affecting about 12% to 30% of the adult population. Psychological factors play an important role in the experience of pain, and may be predictive of pain persistence, disability, and long-term sick leave. The aim of this meta-analysis was to identify and to describe the most common psychological approaches used to treat patients who suffer from CLBP. A systematic search was performed on PubMed/MEDLINE and Cochrane Central. Overall, 16 studies with a total of 1058 patients were included in the analysis. Our results suggest that cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR) interventions are both associated with an improvement in terms of pain intensity and quality of life when singularly compared to usual care. Disability also improved in both groups when compared to usual care. Significant differences in fear-avoidance beliefs were noted in the CBT group compared to usual care. Therefore, psychological factors are related to and influence CLBP. It is crucial to develop curative approaches that take these variables into account. Our findings suggest that CBT and MBSR modify pain-related outcomes and that they could be implemented in clinical practice.

Background: Residents of a large area of north-eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Despite the large amount of evidence in adults of a positive association between serum PFAS and metabolic outcomes, studies focusing on children and adolescents are limited. We evaluated the associations between serum PFAS concentrations that were quantifiable in at least 40% of samples and lipid profile, blood pressure (BP) and body mass index (BMI) in highly exposed adolescents and children., Methods: A cross-sectional analysis was conducted in 6669 adolescents (14-19 years) and 2693 children (8-11 years) enrolled in the health surveillance program of the Veneto Region. Non-fasting blood samples were obtained and analyzed for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was calculated. Systolic and diastolic BP were measured, and BMI z-score accounting for age and sex was estimated. The associations between ln-transformed PFAS (and categorized into quartiles) and continuous outcomes were assessed using generalized additive models. The weighted quantile sum regression approach was used to assess PFAS-mixture effects for each outcome. Analyses were stratified by gender and adjusted for potential confounders., Results: Among adolescents, significant associations were detected between all investigated PFAS and TC, LDL-C, and to a lesser extent HDL-C. Among children, PFOS and PFNA had significant associations with TC, LDL-C and HDL-C, while PFOA and PFHxS had significant associations with HDL-C only. Higher serum concentrations of PFAS, particularly PFOS, were associated with lower BMI z-score. No statistically significant associations were observed between PFAS concentrations and BP. These results were confirmed by the multi-pollutant analysis., Conclusions: Our study supports a consistent association between PFAS concentration and serum lipids, stronger for PFOS and PFNA and with a greater magnitude among children compared to adolescents, and a negative association of PFAS with BMI.

This systematic review and meta-analysis aimed to analyze the effects of workplace interventions (WI) on clinical outcomes related to low back pain (LBP) in a worker population, and to assess socio-economic parameters as participants on sick leave, days of sick leave, and return to work following WI. A systematic literature search was performed to select randomized clinical trials that investigated the effectiveness of WI on return to work, sick leave, and working capacity of workers affected by nonspecific LBP. Fourteen articles were included in the review and meta-analysis. The meta-analysis showed improvements in pain ( p = 0.004), disability ( p = 0.0008), fear-avoidance for psychical activity ( p = 0.004), and quality of life ( p = 0.001 for physical scale and p = 0.03 for mental scale) for patients who underwent WI compared to controls. Moreover, the pain reduction following WI was statistically significant in the healthcare workers' group ( p = 0.005), but not in the other workers' group. The participants on sick leave and the number of days of sick leave decreased in the WI group without statistical significance ( p = 0.85 and p = 0.10, respectively). Finally, LBP recurrence was significantly reduced in the WI group ( p = 0.006). WI led to a significant improvement of clinical outcomes in a workers' population affected by LBP.

(1) Background: Classic Ehlers-Danlos syndrome (cEDS) is a heritable connective tissue disorder characterized by joint hypermobility and skin hyperextensibility with atrophic scarring. Many cEDS individuals carry variants in either the COL5A1 or COL5A2 genes. Mosaicism is relatively common in heritable connective tissue disorders but is rare in EDS. In cEDS, a single example of presumed gonosomal mosaicism for a COL5A1 variant has been published to date. (2) Methods: An 8-year-old girl with cEDS was analyzed by next-generation sequencing (NGS). Segregation was performed by Sanger sequencing in her unaffected parents. In the father, the mosaicism of the variant was further analyzed by targeted NGS and droplet digital PCR (ddPCR) in the blood and by Sanger sequencing in other tissues. (3) Results: The NGS analysis revealed the novel germline heterozygous COL5A1 c.1369G>T, p.(Glu457*) variant in the proband. Sanger chromatogram of the father's blood specimen suggested the presence of a low-level mosaicism for the COL5A1 variant, which was confirmed by NGS and estimated to be 4.8% by ddPCR. The mosaicism was also confirmed by Sanger sequencing in the father's saliva, hair bulbs and nails. (4) Conclusions: We described the second case of cEDS caused by paternal gonosomal mosaicism in COL5A1 . Parental mosaicism could be an issue in cEDS and, therefore, considered for appropriate genetic counseling.

During the COVID-19 pandemic, many countries adopted various non-pharmacological interventions to contain the number of infections. The most often used policy was school closures. We describe the strategy adopted by the Veneto Regional Authority to contain transmission in school settings. This included a detailed school surveillance system, strict contact tracing, and maintaining school attendance with self-monitoring for symptoms whenever possible. All analyzed COVID-19 cases among children, adolescents (0-19 years old), and school staff were registered using a web-based application between 4 January 2021 and 13 June 2021. During the study period, 6272 episodes of infection in schools were identified; 87% were linked to a student index case and 13% to school staff; 69% generated no secondary cases; 24% generated one or two; and only 7% caused more than two. Our data may help to clarify the role of school closures, providing useful input for decisions in the months to come. Good practice in public health management needs tools that provide a real-time interpretation of phenomena like COVID-19 outbreaks. The proposed measures should be easy to adopt and accessible to policymakers.

Chronic Low Back Pain (LBP) is a symptom that may be caused by several diseases, and it is currently the leading cause of disability worldwide. The increased amount of digital images in orthopaedics has led to the development of methods related to artificial intelligence, and to computer vision in particular, which aim to improve diagnosis and treatment of LBP. In this manuscript, we have systematically reviewed the available literature on the use of computer vision in the diagnosis and treatment of LBP. A systematic research of PubMed electronic database was performed. The search strategy was set as the combinations of the following keywords: "Artificial Intelligence", "Feature Extraction", "Segmentation", "Computer Vision", "Machine Learning", "Deep Learning", "Neural Network", "Low Back Pain", "Lumbar". Results: The search returned a total of 558 articles. After careful evaluation of the abstracts, 358 were excluded, whereas 124 papers were excluded after full-text examination, taking the number of eligible articles to 76. The main applications of computer vision in LBP include feature extraction and segmentation, which are usually followed by further tasks. Most recent methods use deep learning models rather than digital image processing techniques. The best performing methods for segmentation of vertebrae, intervertebral discs, spinal canal and lumbar muscles achieve Sørensen-Dice scores greater than 90%, whereas studies focusing on localization and identification of structures collectively showed an accuracy greater than 80%. Future advances in artificial intelligence are expected to increase systems' autonomy and reliability, thus providing even more effective tools for the diagnosis and treatment of LBP.

The aim of our study was to ascertain the prevalence of SARS-CoV-2 infection in the general population during a period of moderate risk, just before Italy started to implement its vaccination campaign. A third-generation antigenic nasal swab sample was collected by a healthcare provider, and all individuals testing positive subsequently had a nasopharyngeal swab for molecular testing; the result was used to calculate the positive predictive value. The population consisted of 4467 asymptomatic adults with a mean age of 46.8 ± 16.00 years. The 62.2% tested for the first time, while 37.8% had previously undergone a mean 2.2 tests for SARS-CoV-2. With 77 of our overall sample reporting they had previously tested positive for COVID-19 and 14 found positive on our screening test, the overall estimated prevalence of the infection was 0.31%. Nine of the 14 cases were confirmed on molecular testing with a PPV of 64.3%. The mean age of the individuals testing positive was 38.1 ± 17.4. Based on the timing of symptom onset, six of the above cases were classified as false negatives, and the adjusted estimated prevalence was 0.34%. Describing levels of infection in a general population seems to be very difficult to achieve, and the universal screening proved hugely expensive particularly in a low-prevalence situation. Anyway, it is only thanks to mass screening efforts that epidemiological data have been collected. This would support the idea that routine screening may have an impact on mitigating the spread of the virus in higher-risk environments, where people come into contact more frequently, as in the workplace.

Nonalcoholic fatty liver disease (NAFLD) is the leading liver chronic disease featuring hepatic steatosis. Mitochondrial β-oxidation participates in the derangement of lipid metabolism at the basis of NAFLD, and mitochondrial oxidative stress contributes to the onset of the disease. We evaluated the presence and effects of mitochondrial oxidative stress in the liver from rats fed a high-fat plus fructose (HF-F) diet inducing NAFLD. Supplementation with dehydroepiandrosterone (DHEA), a multitarget antioxidant, was tested for efficacy in delaying NAFLD. A marked mitochondrial oxidative stress was originated by all diets, as demonstrated by the decrease in Superoxide Dismutase 2 (SOD2) and Peroxiredoxin III (PrxIII) amounts. All diets induced a decrease in mitochondrial DNA content and an increase in its oxidative damage. The diets negatively affected mitochondrial biogenesis as shown by decreased peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α), mitochondrial transcription factor A (TFAM), and the COX-IV subunit from the cytochrome c oxidase complex. The reduced amounts of Beclin-1 and lipidated LC3 II form of the microtubule-associated protein 1 light chain 3 (LC3) unveiled the diet-related autophagy's decrease. The DHEA supplementation did not prevent the diet-induced changes. These results demonstrate the relevance of mitochondrial oxidative stress and the sequential dysfunction of the organelles in an obesogenic diet animal model of NAFLD.

Over the last few years, much attention has been paid to phytocannabinoids derived from Cannabis for their therapeutic potential. Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD) are the most abundant compounds of the Cannabis sativa L. plant. Recently, novel phytocannabinoids, such as cannabidibutol (CBDB) and cannabidiphorol (CBDP), have been discovered. These new molecules exhibit the same terpenophenolic core of CBD and differ only for the length of the alkyl side chain. Roles of CBD homologs in physiological and pathological processes are emerging but the exact molecular mechanisms remain to be fully elucidated. Here, we investigated the biological effects of the newly discovered CBDB or CBDP, compared to the well-known natural and synthetic CBD (nat CBD and syn CBD) in human breast carcinoma cells that express CB receptors. In detail, our data demonstrated that the treatment of cells with the novel phytocannabinoids affects cell viability, increases the production of reactive oxygen species (ROS) and activates cellular pathways related to ROS signaling, as already demonstrated for natural CBD. Moreover, we observed that the biological activity is significantly increased upon combining CBD homologs with drugs that inhibit the activity of enzymes involved in the metabolism of endocannabinoids, such as the monoacylglycerol lipase (MAGL) inhibitor, or with drugs that induces the activation of cellular stress pathways, such as the phorbol ester 12-myristate 13-acetate (PMA).

Due to the COVID-19 pandemic, in December 2020, the Italian government established a second home confinement during the Christmas holidays. These restrictions offered the opportunity to utilize a well-defined model for observing the consequences of lifestyle changes of healthy individuals. This study aimed at estimating in healthy subjects from Southern Italy the physical activity (PA), the presence and the severity of gastrointestinal (GI) symptoms, and the association between the possible worsening of GI health status and the PA levels. An adapted version of the International PA Questionnaire-short form (IPAQ-SF) and the Gastrointestinal Symptom Rating Scale (GSRS) were proposed through Google's online survey platform in three different periods via WhatsApp TM to 499 healthy subjects (62% females) from Apulia (25%), Calabria (37%), and Campania (38%). Our results showed statistically significant changes during the home confinement: reduced energy expenditure (EE) among overweight subjects (-239.82, 95%CI -405.74; -73.89) or those who had high GSRS total score (-1079.54, 95%CI -2027.43; -131.66). An increase in GSRS total score was observed in overweight subjects, reaching statistical significance in those from Campania. Our study supports the importance of PA to reduce health risks, including those related to the possible onset of GI tract diseases.

Thyroid hormone levels are usually genetically determined. Thyrocytes produce a unique set of enzymes that are dedicated to thyroid hormone synthesis. While thyroid transcriptional regulation is well-characterized, post-transcriptional mechanisms have been less investigated. Here, we describe the involvement of ZFP36L2, a protein that stimulates degradation of target mRNAs, in thyroid development and function, by in vivo and in vitro gene targeting in thyrocytes. Thyroid-specific Zfp36l2 -/- females were hypothyroid, with reduced levels of circulating free Thyroxine (cfT4) and Triiodothyronine (cfT3). Their hypothyroidism was due to dyshormonogenesis, already evident one week after weaning, while thyroid development appeared normal. We observed decreases in several thyroid-specific transcripts and proteins, such as Nis and its transcriptional regulators ( Pax8 and Nkx2 .1), and increased apoptosis in Zfp36l2 -/- thyroids. Nis , Pax8, and Nkx2 .1 mRNAs were also reduced in Zfp36l2 knock-out thyrocytes in vitro (L2KO), in which we confirmed the increased apoptosis. Finally, in L2KO cells, we showed an altered response to TSH stimulation regarding both thyroid-specific gene expression and cell proliferation and survival. This result was supported by increases in P21/WAF1 and p-P38MAPK levels. Mechanistically, we confirmed Notch1 as a target of ZFP36L2 in the thyroid since its levels were increased in both in vitro and in vivo models. In both models, the levels of Id4 mRNA, a potential inhibitor of Pax8 activity, were increased. Overall, the data indicate that the regulation of mRNA stability by ZFP36L2 is a mechanism that controls the function and survival of thyrocytes.

Primary brain tumors (PBTs) are some of the most difficult types of cancer to treat, and despite advancements in surgery, chemotherapy and radiotherapy, new strategies for the treatment of PBTs are needed, especially for those with poor prognosis such as inoperable/difficult-to-reach lesions or relapsing disease. In regard to the last point, malignant primary brain tumors remain some of the most lethal types of cancer. Nuclear medicine may provide exciting new weapons and significant contributions in the treatment of PBTs. In this review, we performed literature research in order to highlight the possible role of peptide receptor radionuclide therapy (PRRT) in the treatment of PBTs with radiolabeled molecules that bind with high-affinity transmembrane receptors such as somatostatin receptors (SSTRs), neurokinin type-1 receptor and prostate-specific membrane antigen (PSMA). These receptors are overexpressed in some cancer types such as gliomas, meningiomas, pituitary tumors and medulloblastomas. A comprehensive overview of possible applications in this field will be shown, providing knowledge about benefits, feasibility, developments and limitations of PRRT in this type of tumor, also revealing new advantages in the management of the disease.

Novel parameters in PET imaging, such as volumetric parameters, are gaining interest in the scientific literature, but the role of dopaminergic tumor volume (DTV) and total lesion F-DOPA activity (TLDA) and the correlation between volumetric and SUV-derived parameters are not well defined yet. One hundred and thirty-three patients that underwent 18F-FDOPA imaging for primary brain tumors were included in this retrospective study. SUV-derived indices were calculated (the occipital region was chosen to generate ratios of tumor SUV) and compared with volumetric parameters. Regression models were applied in univariate analysis and lnSUVmax was positively associated with lnDTV (beta 0.42, p = 0.007), the lnSUVmax ratio was positively associated with lnDTV (beta 0.80, p = 0.011), lnSUVmax was positively associated with lnTLDA (beta 1.27, p < 0.0001), and the lnSUVmax ratio was positively associated with lnTLDA (beta 1.87, p < 0.0001). Our study demonstrates that volumetric uptake parameters in 18F-FDOPA PET/CT are easier to assess in primary brain tumors with higher SUV max and SUV max ratios, and supports the emerging role of volumetric parameters in the data interpretation.

Thyroid hormones (THs) regulate many biological processes in vertebrates, including reproduction. Testicular somatic and germ cells are equipped with the arrays of enzymes (deiodinases), transporters, and receptors necessary to locally maintain the optimal level of THs and their signalling, needed for their functions and spermatogenesis. Pesticides, as chlorpyrifos (CPF) and ethylene thiourea (ETU), impair the function of thyroid and testis, affecting male fertility. However, their ability to disarrange testicular T3 (t-T3) metabolism and signalling is poorly considered. Here, a multi-species analysis involving zebrafish and mouse suggests the damage of t-T3 metabolism and signalling as a mechanism of gonadic toxicity of low-doses CPF and ETU. Indeed, the developmental exposure to both compounds reduces Dio2 transcript in both models, as well as in ex-vivo cultures of murine seminiferous tubules, and it is linked to alteration of steroidogenesis and germ cell differentiation. A major impact on spermatogonia was confirmed molecularly by the expression of their markers and morphologically evidenced in zebrafish. The results reveal that in the adopted models, exposure to both pesticides alters the t-T3 metabolism and signalling, affecting the reproductive capability. Our data, together with previous reports suggest zebrafish as an evaluable model in assessing the action of compounds impairing locally T3 signalling.

Tamisolve ® NxG, a well-known non-toxic solvent, was used for poly(vinylidene fluoride) (PVDF) membranes preparation via a non-solvent-induced phase separation (NIPS) procedure with water as a coagulation bath. Preliminary investigations, related to the study of the physical/chemical properties of the solvent, the solubility parameters, the gel transition temperature and the viscosity of the polymer-solvent system, confirmed the power of the solvent to solubilize PVDF polymer for membranes preparation. The role of polyvinylpyrrolidone (PVP) and/or poly(ethylene glycol) (PEG), as pore former agents in the dope solution, was studied along with different polymer concentrations (10 wt%, 15 wt% and 18 wt%). The produced membranes were then characterized in terms of morphology, thickness, porosity, contact angle, atomic force microscopy (AFM) and infrared spectroscopy (ATR-FTIR). Pore size measurements, pore size distribution and water permeability (PWP) tests placed the developed membranes in the ultrafiltration (UF) and microfiltration (MF) range. Finally, PVDF membrane performances were investigated in terms of rejection (%) and permeability recovery ratio (PRR) using methylene blue (MB) in water solution to assess their potential application in separation and purification processes.

The pursuit of sustainability in the field of road asphalt pavements calls for effective decision-making strategies, referring to both the technical and environmental sustainability of the solutions. This study aims to compare the life cycle impacts of several pavement solution alternatives involving, in the binder and base layers, some eco-designed, hot- and cold-produced asphalt mixtures made up of recycled aggregates in substitution for natural filler and commercial recycled polymer pellets for dry mixture modification. The first step focused on the technical and environmental compatibility assessment of the construction and demolition waste (CDW), jet grouting waste (JGW), fly ash (FA), and reclaimed asphalt pavement (RAP). Then, three non-traditional mixtures were designed for the binder layer and three for the base layer and characterized in terms of the stiffness modulus. Asphalt pavement design allowed for the definition of the functional units of Life Cycle Assessment (LCA), which was applied to all of the pavement configurations under analysis in a "from cradle to grave" approach. The LCA results showed that the best performance was reached for the solutions involving a cold, in-place recycled mixture made up of RAP and JGW in the base layer, which lowered all the impact category indicators by 31% on average compared to those of the traditional pavement solution. Further considerations highlighted that the combination of a cold base layer with a hot asphalt mixture made up of CDW or FA in the binder layer also maximized the service life of the pavement solution, providing the best synergistic effect.

Secondary raw materials consist of production waste or material resulting from recycling processes, currently in large quantities, which can be injected back into the economic system as new raw materials. This study proposes jet grouting waste (JGW) as filler for hot and cold asphalt mixtures applied as base layers of road pavements and investigates the physical and mechanical properties. JGW is derived from soil consolidation performed during underground roadway tunnel construction. The research compares three asphalt mixtures: (a) hot mixture containing limestone aggregate-filler (HMA), (b) HMA containing JGW (HMAJ), (c) cold recycled asphalt mixture containing JGW (CRAJ). Leaching tests of JGW and reclaimed asphalt pavement (RAP) were conducted; the best configurations of the three mixtures were determined by using the volumetric method through gyratory compaction. Three mastics with filler-to-binder ratios reflecting those of the asphalt mixtures were investigated through delta ring and ball test and frequency sweep test at 0.05% stress by using a dynamic shear rheometer. The morphology of each mixture was further investigated by scanning electron microscopy. The results showed that CRAJ with 28 days of curing time reached the indirect tensile strength (ITS) of HMA (0.73 MPa) within 14 days and, among all studied mixtures, returned the lowest cumulative strain, which was on average 30% lower than that of HMA and HMAJ. The results of this study have shown that the cold alternative mixture, CRAJ, promotes the reuse of two types of waste, RAP and JGW, as it fully meets the reference Italian Technical Standard and ensures good mixture performance in addition to conserving natural resources.

Low back pain (LBP) is currently the leading cause of disability worldwide and the most common reason for workers' compensation (WC) claims. Studies have demonstrated that receiving WC is associated with a negative prognosis following treatment for a vast range of health conditions. However, the impact of WC on outcomes after spine surgery is still controversial. The aim of this meta-analysis was to systematically review the literature and analyze the impact of compensation status on outcomes after lumbar spine surgery. A systematic search was performed on Medline, Scopus, CINAHL, EMBASE and CENTRAL databases. The review included studies of patients undergoing lumbar spine surgery in which compensation status was reported. Methodological quality was assessed through ROBINS-I and quality of evidence was estimated using the GRADE rating. A total of 26 studies with a total of 2668 patients were included in the analysis. WC patients had higher post-operative pain and disability, as well as lower satisfaction after surgery when compared to those without WC. Furthermore, WC patients demonstrated to have a delayed return to work. According to our results, compensation status is associated with poor outcomes after lumbar spine surgery. Contextualizing post-operative outcomes in clinical and work-related domains helps understand the multifactorial nature of the phenomenon.