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Skin is the forestage for a series of many-sided functions of tumor necrosis factor-alpha (TNF-α), a proinflammatory cytokine with staggering versatility and sizable implications for tissue homeostasis, immune responses, angiogenesis, apoptosis, local and systemic inflammation. An aberrant TNF-α-mediated crosstalk has been linked to the pathogenesis of acute and chronic skin inflammatory diseases, and indeed, TNF-α dysregulation can contribute to the development and progression of psoriasis, vitiligo, local damage following exposition to ultraviolet light radiations, cutaneous lupus erythematosus, and acne vulgaris. Therapies that target TNF-α are conspicuously used in the treatment of different skin disorders, aiming to modulate the in vivo immune functions triggered by many cutaneous cells, including keratinocytes, mast cells, or Langerhans cells, and reduce inflammation taking place within the skin. Herein, we focus on the key relationships between TNF-α and distinct skin non-neoplastic inflammatory or physiologic conditions, showing that a natural induction of TNF-α may have a protective significance but that TNF-α overproduction may be harmful or even lethal. Many questions remain unraveled in the therapeutic practice, and caution should be exercised due to eventual backlashes exerted by TNF-α in maintaining skin health or in provoking skin disease.

ObjectivesRecent studies supported coagulation involvement in multiple sclerosis, an inflammatory-demyelinating and degenerative disease of the central nervous system. The main objectives of this observational study were to identify the most specific pro-coagulative/vascular factors for multiple sclerosis pathogenesis and to correlate them with brain hemodynamic abnormalities.MethodsWe compared i) serum/plasma levels of complement(C)/coagulation/vascular factors, viral/microbiological assays, fat-soluble vitamins and lymphocyte count among people with multiple sclerosis sampled in a clinical remission (n=30; 23F/7M, 40 ± 8.14 years) or a relapse (n=30; 24F/6M, age 41 ± 10.74 years) and age/sex-matched controls (n=30; 23F/7M, 40 ± 8.38 years); ii) brain hemodynamic metrics at dynamic susceptibility contrast-enhanced 3T-MRI during relapse and remission, and iii) laboratory data with MRI perfusion metrics and clinical features of people with multiple sclerosis. Two models by Partial Least Squares Discriminant Analysis were performed using two groups as input: (1) multiple sclerosis vs. controls, and (2) relapsing vs. remitting multiple sclerosis.ResultsCompared to controls, multiple sclerosis patients had a higher Body-Mass-Index, Protein-C and activated-C9; and a lower activated-C4. Levels of Tissue-Factor, Tie-2 and P-Selectin/CD62P were lower in relapse compared to remission and HC, whereas Angiopoietin-I was higher in relapsing vs. remitting multiple sclerosis. A lower number of total lymphocytes was found in relapsing multiple sclerosis vs. remitting multiple sclerosis and controls. Cerebral-Blood-Volume was lower in normal-appearing white matter and left caudatum while Cerebral-Blood-Flow was inferior in bilateral putamen in relapsing versus remitting multiple sclerosis. The mean-transit-time of gadolinium-enhancing lesions negatively correlated with Tissue-Factor. The top-5 discriminating variables for model (1) were: EBV-EBNA-1 IgG, Body-Mass-Index, Protein-C, activated-C4 and Tissue-Factor whereas for model (2) were: Tissue-Factor, Angiopoietin-I, MCHC, Vitamin A and T-CD3.ConclusionTissue-factor was one of the top-5 variables in the models discriminating either multiple sclerosis from controls or multiple sclerosis relapse from remission and correlated with mean-transit-time of gadolinium-enhancing lesions. Tissue-factor appears a promising pro-coagulative/vascular biomarker and a possible therapeutic target in relapsing-remitting multiple sclerosis.Clinical trial registrationClinicalTrials.gov, identifier NCT04380220.

This study aimed to confirm the factor structure of the Italian version of the Hare Psychopathy Checklist: Youth Version (PCL:YV) in a sample of adolescents with criminal convictions. The sample was comprised of 116 adolescent boys aged 12-18 years. In addition to PCL:YV, the Structured Assessment of Violence Risk in Youth (SAVRY) and the MMPI-A were used. Confirmatory Factor Analyses (CFA) were performed; the final solution was a four-factors model with correlated latent factors. The internal consistency of each factor was acceptably high. Moreover, as expected, positive and high correlations with SAVRY scores, and a negative association with the SAVRY protective indicator, were found. The factor structure of the Italian PCL:YV specifically tested in this study with adolescents with criminal convictions, has confirmed that the Italian PCL:YV can be a suitable tool for the assessment of psychopathy dimensions among adolescents with criminal convictions in Italy., Author(s): Ugo Sabatello [sup.1] , Laura D'Antuono [sup.2] , Paolo Iliceto [sup.3] , Simona Stefanile [sup.4] [sup.5] , Fiorenzo Laghi [sup.6] Author Affiliations: (1) grid.7841.a, Department of Pediatrics and Child [...]

Inflammation and inflammasomes have been proposed as important regulators of the host–microorganism interaction, playing a key role in morbidity and mortality due to the coronavirus disease 2019 (COVID-19) in subjects with chronic conditions and compromised immune system. The inflammasome consists of a multiprotein complex that finely regulates the activation of caspase-1 and the production and secretion of potent pro-inflammatory cytokines such as IL-1β and IL-18. The pyrin containing NOD (nucleotide-binding oligomerization domain) like receptor (NLRP) is a family of intracellular receptors, sensing patterns associated to pathogens or danger signals and NLRP3 inflammasome is the most deeply analyzed for its involvement in the innate and adaptive immune system as well as its contribution to several autoinflammatory and autoimmune diseases. It is highly expressed in leukocytes and up-regulated in sentinel cells upon inflammatory stimuli. NLRP3 expression has also been reported in B and T lymphocytes, in epithelial cells of oral and genital mucosa, in specific parenchymal cells as cardiomyocytes, and keratinocytes, and chondrocytes. It is well known that a dysregulated activation of the inflammasome is involved in the pathogenesis of different disorders that share the common red line of inflammation in their pathogenetic fingerprint. Here, we review the potential roles of the NLRP3 inflammasome in cardiovascular events, liver damage, pulmonary diseases, and in that wide range of systemic inflammatory syndromes named as a cytokine storm.

Coronavirus disease 2019 (COVID-19) results in higher risks of hospitalization or death in older patients and those with multiple comorbidities, including malignancies. Patients with cancer have greater risks of COVID-19 onset and worse prognosis. This excess is mainly explained by thrombotic complications. Indeed, an imbalance in the equilibrium between clot formation and bleeding, increased activation of coagulation, and endothelial dysfunction characterize both COVID-19 patients and those with cancer. With this review, we provide a summary of the pathological mechanisms of coagulation and thrombotic manifestations in these patients and discuss the possible therapeutic implications of these phenomena.

Skin is the forestage for a series of many-sided functions of tumor necrosis factor-alpha (TNF-α), a proinflammatory cytokine with staggering versatility and sizable implications for tissue homeostasis, immune responses, angiogenesis, apoptosis, local and systemic inflammation. An aberrant TNF-α-mediated crosstalk has been linked to the pathogenesis of acute and chronic skin inflammatory diseases, and indeed, TNF-α dysregulation can contribute to the development and progression of psoriasis, vitiligo, local damage following exposition to ultraviolet light radiations, cutaneous lupus erythematosus, and acne vulgaris. Therapies that target TNF-α are conspicuously used in the treatment of different skin disorders, aiming to modulate the in vivo immune functions triggered by many cutaneous cells, including keratinocytes, mast cells, or Langerhans cells, and reduce inflammation taking place within the skin. Herein, we focus on the key relationships between TNF-α and distinct skin non-neoplastic inflammatory or physiologic conditions, showing that a natural induction of TNF-α may have a protective significance but that TNF-α overproduction may be harmful or even lethal. Many questions remain unraveled in the therapeutic practice, and caution should be exercised due to eventual backlashes exerted by TNF-α in maintaining skin health or in provoking skin disease. [ABSTRACT FROM AUTHOR]

Prolonged B cells stimulation due to the Hepatitis C virus (HCV) can result in autoimmunity, stigmatized by rising levels of cryoglobulins (CGs), the rheumatoid factor (RF), and free light chains (FLC) of immunoglobulins (Ig) associated with a range of symptoms, from their absence to severe cryoglobulinemic vasculitis and lymphoma. Here, we aimed to identify an immunological signature for the earliest stages of vasculitis when cryoprecipitate is still not detectable. We firstly analyzed the IgG subclasses, FLC, and RF in 120 HCV-RNA-positive patients divided into four groups according to the type of cryoprecipitate and symptoms: 30 asymptomatic without cryoprecipitate (No Cryo), 30 with vasculitis symptoms but without CGs that we supposed were circulating but still not detectable (Circulating), 30 type II and 30 type III mixed cryoglobulinemia (Cryo II and Cryo III, respectively). Our results revealed that patients with supposed circulating CGs displayed a pattern of serological parameters that closely resembled Cryo II and Cryo III, with a stronger similarity to Cryo II. Accordingly, we analyzed the groups of Circulating and Cryo II for their immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements, finding a similar mixed distribution of monoclonal, oligoclonal, and polyclonal responses compared to a control group of ten HCV-RNA-negative patients recovered from infection, who displayed a 100% polyclonal response. Our results strengthened the hypothesis that circulating CGs are the origin of symptoms in HCV-RNA-positive patients without cryoprecipitate and demonstrated that an analysis of clonal IGH and TCR rearrangements is the best option for the early diagnosis of extrahepatic complications.

Among the activities planned for the MUSAS Project, the digital reconstruction of the underwater sites constitutes a particular challenge, requiring strong cooperation between archaeologists and technicians. The case of the Villa dei Pisoni in Baiae, one of the richest in the Phlaegrean territory, is particularly interesting: the architectural remains, already documented in the 1980s and now inserted in one of the diving spots of the Underwater Park of Baiae, are disseminated on a huge surface, including quays, thermal complexes, a fishpond, and a large, luxurious viridarium. The effort required for the digital reconstruction of the ancient villa improved the previous knowledge and the lack of documentation even in a well-known site. In this paper, we will retrace the long path from the 3D reconstruction of the archaeological remains to the virtual architectural model of the villa, the numerous challenges, doubts, and uncertainties in the creation of the original spaces, and the support offered by the ancient sources, both literary and iconographic, in solving archaeological problems.

Hepatocellular carcinoma (HCC) represents a worldwide health matter with a major care burden, high prevalence, and poor prognosis. Its pathogenesis mainly varies depending on the underlying etiological factors, although it develops from liver cirrhosis in the majority of cases. This review summarizes the role of the most interesting soluble factors as biomarkers for early diagnosis and as recommended targets for treatment in accordance with the new challenges in precision medicine. In the premalignant environment, inflammatory cells release a wide range of cytokines, chemokines, growth factors, prostaglandins, and proangiogenic factors, making the liver environment more suitable for hepatocyte tumor progression that starts from acquired genetic mutations. A complex interaction of pro-inflammatory (IL-6, TNF-α) and anti-inflammatory cytokines (TGF-α and -β), pro-angiogenic molecules (including the Angiopoietins, HGF, PECAM-1, HIF-1α, VEGF), different transcription factors (NF-kB, STAT-3), and their signaling pathways are involved in the development of HCC. Since cytokines are expressed and released during the different stages of HCC progression, their measurement, by different available methods, can provide in-depth information on the identification and management of HCC.

Bevacizumab is an anti-angiogenic monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF) that induces the proliferation and migration of vascular endothelial cells thus, promoting vasculogenesis. Bevacizumab inhibits cancer angiogenesis, which is fundamental for either tumor development, exponential growth, or metastatic spread by supplying nutrients and oxygen. We report a new possible adverse event of bevacizumab, a Cerebral Amyloid Angiopathy-Related Inflammation (CAARI), in a 72-year-old woman with metastatic cervical cancer. After six cycles every three weeks of chemotherapy (cisplatin, paclitaxel, bevacizumab) and following two maintenance bevacizumab administrations, the patient presented a worsening confusional state. The MRI scan showed bilateral asymmetric temporo-parieto-occipital hyperintensity with numerous cortical microbleeds indicative of a CAARI. After stopping bevacizumab treatment, steroid therapy was administered resulting in rapid clinical improvement. The subsequent neurological and oncological follow-up was negative for recurrence. The patient was a heterozygote carrier for apolipoprotein-E ε4 that increases the risk of sporadic Cerebral Amyloid Angiopathy (CAA), which is characterized by beta-amyloid accumulation and fibrinoid necrosis in cerebral vasculature leading to micro/macrohemorrhages and dementia. Moreover, CAA is present in 30% of people aged over 60 years without dementia. In the brains of CAA patients, there is a proinflammatory state with cerebrovascular endothelial cell alteration and elevated levels of either adhesion molecules or inflammatory interleukins that increase the blood–brain barrier permeability. Moreover, CAARI is an inflammatory form of CAA. Inhibition of VEGF, which has anti-apoptotic, anti-inflammatory, and pro-survival effects on endothelial cells, impairs their regenerative capacity and increases expression of proinflammatory genes leading to weakened supporting layers of blood vessels and, hence, to damaged vascular integrity. In our patient, bevacizumab administration may have further increased permeability of cerebral microvasculature likely impaired by an underlying, asymptomatic CAA. To our knowledge, this is the first case reporting on the development of probable CAARI during bevacizumab treatment, which should alert the clinicians in case of neurological symptom onset in older patients under anti-angiogenic therapy.

CH50 is a screening assay for the activation of the classical complement pathway, the immunoglobulins-mediated one, activated in several inflammatory diseases. Adult growth hormone deficiency (aGHD) is recognized as a chronic inflammatory condition, although poorly evaluated under the profile of inflammatory biomarkers. The aim of this case-control observational study is to analyze CH50 and immunoglobulins G (IgG) subclasses production in aGHD, comparing this condition to healthy controls.38 subjects were included and divided as follows: aGHD (n = 18, 6 females and 12 males); healthy controls (n = 20, 10 females and 10 males). GHD was diagnosed with dynamic test using Growth Hormone-Releasing Hormone (GHRH 50 μg i.v. + arginine 0,5 g/Kg), with a peak GH response < 9 μg/L when BMI was 30 kg/m2. The two groups were evaluated for hormonal and metabolic parameters, CH50 and IgG subtypes.IgG1 and IgG2 were significantly higher in controls than in aGHD, while IgG3 and IgG4 showed a trend to higher levels in controls, although not significant. Furthermore, CH50 levels were significantly higher in aGHD.These data substantiate the hypothesis of a dyscrasia in IgG subclasses production in aGHD. As IgG levels decrease, CH50 levels do not.

IntroductionMultiple sclerosis (MS) is a demyelinating disease of the central nervous system with an underlying immune-mediated and inflammatory pathogenesis. Innate immunity, in addition to the adaptive immune system, plays a relevant role in MS pathogenesis. It represents the immediate non-specific defense against infections through the intrinsic effector mechanism “immunothrombosis” linking inflammation and coagulation. Moreover, decreased cerebral blood volume (CBV), cerebral blood flow (CBF), and prolonged mean transit time (MTT) have been widely demonstrated by MRI in MS patients. We hypothesized that coagulation/complement and platelet activation during MS relapse, likely during viral infections, could be related to CBF decrease. Our specific aims are to evaluate whether there are differences in serum/plasma levels of coagulation/complement factors between relapsing-remitting (RR) MS patients (RRMS) in relapse and those in remission and healthy controls as well as to assess whether brain hemodynamic changes detected by MRI occur in relapse compared with remission. This will allow us to correlate coagulation status with perfusion and demographic/clinical features in MS patients.Materials and MethodsThis is a multi-center, prospective, controlled study. RRMS patients (1° group: 30 patients in relapse; 2° group: 30 patients in remission) and age/sex-matched controls (3° group: 30 subjects) will be enrolled in the study. Patients and controls will be tested for either coagulation/complement (C3, C4, C4a, C9, PT, aPTT, fibrinogen, factor II, VIII, and X, D-dimer, antithrombin, protein C, protein S, von-Willebrand factor), soluble markers of endothelial damage (thrombomodulin, Endothelial Protein C Receptor), antiphospholipid antibodies, lupus anticoagulant, complete blood count, viral serological assays, or microRNA microarray. Patients will undergo dynamic susceptibility contrast-enhanced MRI using a 3.0-T scanner to evaluate CBF, CBV, MTT, lesion number, and volume.Statistical AnalysisANOVA and unpaired t-tests will be used. The level of significance was set at p ≤ 0.05.DiscussionIdentifying a link between activation of coagulation/complement system and cerebral hypoperfusion could improve the identification of novel molecular and/or imaging biomarkers and targets, leading to the development of new effective therapeutic strategies in MS.Clinical Trial RegistrationClinicaltrials.gov, identifier NCT04380220.

This study aimed to examine the association between positive (self-kindness, common humanity, and mindfulness) and negative (isolation, self-judgment, and over-identification) components of self-compassion, and both body dissatisfaction and acceptance of cosmetic surgery among women, through the mediation (for the negative components) of internalization and physical appearance comparison. The participants were 220 young Italian women aged 19–31 (M = 21) years, who completed a questionnaire assessing the variables of interest. Path analysis indicated that higher mindfulness was directly linked to lower acceptance of cosmetic surgery. Mindfulness presented the strongest link with cosmetic surgery, as it was directly associated with acceptance of cosmetic surgery for both social and interpersonal motivations and with consideration of undergoing some cosmetic procedures. Common humanity and self-kindness were related to acceptance of cosmetic surgery for social reasons. Over-identification seemed to be associated with body dissatisfaction and acceptance of cosmetic surgery both directly and indirectly through internalization and physical appearance comparison. Self-judgment and isolation did not present a significant association with either body dissatisfaction or acceptance of cosmetic surgery. These findings confirm that psychological assessment of women who are interested in cosmetic surgery is highly recommended. Interventions should not consider self-compassion as a whole, but they should rather focus on some of its components. The role of over-identification seems to be especially pivotal, as higher scores on this dimension are linked to higher levels of body dissatisfaction and greater acceptance of cosmetic surgery.

The present cross-sectional study aimed to clarify the relationships among specific facets of dispositional mindfulness, psychological well-being, and emotional distress. To understand the relationships among these variables is crucial in order to expand the knowledge of the processes underlying mindfulness effects and to develop effective interventions. The participants (119 Italian males and females; mean age = 29 years) completed self-report questionnaires assessing mindfulness (i.e., observing, describing, acting with awareness, non-judging of inner experience, non-reactivity to inner experience), emotional distress, and psychological well-being. Path analysis revealed that each facet of mindfulness played a unique role in influencing emotional suffering. In line with our prediction, no significant correlation emerged between the observing facet and either psychological well-being or emotional distress. Both the capacity to describe inner events and to act with awareness had an indirect effect on emotional distress, which was fully mediated by the perception of psychological well-being. On the other hand, the capacity for non-reacting to emotions and thoughts directly influenced emotional distress. Interestingly, non-judging inner events showed both a direct and indirect effect on the outcome variable. These findings confirmed the significant role of psychological well-being in mediating the relationship between some facets of mindfulness and emotional distress. Moreover, different mindfulness abilities play specific roles in reducing emotional distress, so mindfulness should be considered as a multidimensional construct., Author(s): Duccio Baroni [sup.1] , Amanda Nerini [sup.1] , Camilla Matera [sup.2] , Cristina Stefanile [sup.1] Author Affiliations: (Aff1) 0000 0004 1757 2304, grid.8404.8, Department of Health Sciences - Section [...]

The ongoing outbreak of coronavirus disease 2019 (COVID-19), which impairs the functionality of several organs, represents a major threat to human health. One of the hardest challenges in the fight against COVID-19 is the development of wide-scale, effective, and rapid laboratory tests to control disease severity, progression, and possible sudden worsening. Monitoring patients in real-time is highly demanded in this pandemic era when physicians need reliable and quantitative tools to prioritize patients’ access to intensive care departments. In this regard, salivary biomarkers are extremely promising, as they allow for the fast and non-invasive collection of specimens and can be repeated multiple times. Methods: We compare salivary levels of immunoglobulin A subclasses (IgA1 and IgA2) and free light chains (kFLC and λFLC) in a cohort of 29 SARS-CoV-2 patients and 21 healthy subjects. Results: We found that each biomarker differs significantly between the two groups, with p-values ranging from 10−8 to 10−4. A Receiving Operator Curve analysis shows that λFLC level is the best-suited candidate to discriminate the two groups (AUC = 0.96), with an accuracy of 0.94 (0.87–1.00 95% CI), a precision of 0.91 (0.81–1.00 95% CI), a sensitivity of 1.00 (0.96–1.00 95% CI), and a specificity of 0.86 (0.70–1.00 95% CI). Conclusion: These results suggest λFLC as an ideal indicator of patient conditions. This hypothesis is strengthened by the consideration that the λFLC half-life (approximately 6 h) is significantly shorter than the IgA one (21 days), thus confirming the potential of λFLC for effectively monitoring patients’ fluctuation in real-time.

Having a lean and athletic physique is increasingly important for Italian men. The purpose of this cross-sectional study was to analyze the relationship between men’s dissatisfaction with muscularity and well-being, conceptualized in terms of the realization of one’s true potential and the experience of purpose or meaning in life (i.e., eudaimonic well-being), considering also the role of sexual orientation and peer influence. Participants (385 Italian men with a mean age of 28.61 years, SD = 9.65) completed a questionnaire assessing the variables of interest. Path analysis indicated that sexual orientation was linked to eudaimonic well-being via muscularity dissatisfaction. Teasing about muscularity predicted men’s eudaimonic well-being both directly and via muscularity dissatisfaction. Peer attributions and appearance conversations predicted well-being through the mediation of athletic internalization and body dissatisfaction. Peer attributions, but not appearance conversations, were also directly linked to well-being. To improve broad aspects of men’s well-being, prevention and treatment programs should be directed to increase men’s ability to resist different forms of pressure, including that of their peers. These kinds of programs could be especially useful for gay men, who are more likely to experience body dissatisfaction and, in turn, poor psychological functioning.

This research aims to evaluate the amount of vertical ground movements during Roman times inside the archaeological area of Portus Julius (Gulf of Pozzuoli) using high-precision surveys on the most reliable archaeological sea-level markers. Measuring the submersion of ancient floors, structural elements belonging to a former fish tank, and several roman pilae, two different relative sea levels (RSLs), related to the beginning and the end of the first century BCE, respectively, −4.7/−5.20 m and −3.10 m MSL (mean sea level), were detected. A photogrammetric survey was carried out in order to produce a 3D model of the fish tank. The results in terms of the RSL variations have enabled us to reconstruct a morpho-evolution of the ancient coastal sector during the last 2.1 kyBP. At the beginning of the first century BCE, the area was characterized by a sheltered gulf with numerous maritime villae located along the coast. In 37 BCE, the construction of the military harbour of Portus Julius strongly modified the paleogeography of the sector, which was also affected by a prevailing subsidence at least until the end of the first century BCE (year 12 BCE), when the port was converted into a commercial hub.

La presenza di gentes di provenienza italica nella popolazione dell’antica Lucentum costituisce un argomento di discussione fondamentale all’interno dello studio della romanizzazione del territorio. L’analisi delle testimonianze epigrafiche e il confronto con la Penisola Italiana permette di identificare queste famiglie, riconoscendo possibili aree di provenienza nella Campania e nell’area appenninica: si riconosce così che, al di là del Fulvius Asclas Pompeianus tradizionalmente considerato di Pompei (e sulla cui origine si può forse ancora discutere), altri individui menzionati nell’epigrafia alicantina mostrano stretti legami con le loro terre di provenienza.

This study investigated the psychometric properties of the Humor Styles Questionnaire (HSQ) and the relation between humor and psychological well-being within the context of Italy. A total of 293 (178 females, 115 males) Italian high school and undergraduate university students – whose ages ranged from 14 to 25 years – completed the Italian versions of the HSQ and the Ryff’s Psychological Well-Being scales (RPWB). The HSQ scale reliabilities were generally acceptable, and intercorrelations among the scales were rather low; the confirmatory factor analysis supported the four-factor structure. Males reported significantly more use of Aggressive humor than did females; no differences were found between adolescents and young adults in the use of humor styles. Affiliative and Self-enhancing humor styles were positively associated with the six dimensions of the RPWB, whereas Self-defeating humor was negatively correlated with the RPWB scales. SEM analysis showed a significant and positive relationship between humor as measured by the HSQ and psychological well-being as assessed by the RPWB. Overall, the findings supported the theoretical structure and usefulness of the HSQ in an Italian context and the differential role of humor components in the various dimensions of psychological well-being.