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Abstract Vaccinia virus (VACV) was used for smallpox eradication, but its ultimate origin remains unknown. The genetic relationships among vaccine stocks are also poorly understood. We analyzed 63 vaccine strains with different origin, as well horsepox virus (HPXV). Results indicated the genetic diversity of VACV is intermediate between variola and cowpox viruses, and that mutation contributed more than recombination to VACV evolution. STRUCTURE identified 9 contributing subpopulations and showed that the lowest drift was experienced by the ancestry components of Tian Tan and HPXV/Mütter/Mulford genomes. Subpopulations that experienced very strong drift include those that contributed the ancestry of MVA and IHD-W, in good agreement with the very long passage history of these vaccines. Another highly drifted population contributed the full ancestry of viruses sampled from human/cattle infections in Brazil and, partially, to IOC clones, strongly suggesting that the recurrent infections in Brazil derive from the spillback of IOC to the feral state.

O carcinoma de células escamosas (CCE) é um tumor maligno dos queratinócitos, de baixa capacidade metastática, sendo considerado a neoplasia cutânea mais comum em cães de pelagem branca. Objetiva-se com o presente trabalho, relatar os aspectos gerais do CCE, o diagnóstico e o tratamento, com base em um relato de caso de um canino que foi submetido a uma amputação de dígito, em decorrência de um CCE.

Frequency resolved optical gating is the core method for characterising ultra-fast optical pulses. Here, the authors use zero-index nonlinearities to largely enhance key performances and enable simultaneous second and third harmonic measurements.

Abstract Background Healthcare workers represent one of the most affected categories by the adverse effects of the COVID-19 pandemic on mental health. Excessive stress and anxiety are critical factors that could compromise work performance. Besides, high levels of stress and anxiety may have long-term physical and psychological consequences. Recent studies investigated virtual reality to reduce stress and anxiety among healthcare workers during the COVID-19 pandemic. However, the proposed virtual reality interventions have important limitations related to their location (i.e., research lab and hospitals) and content (i.e., virtual experiences only for relaxation). Within this context, this randomized controlled trial aims to investigate the efficacy and acceptability of a brief home-based virtual reality training for managing stress and anxiety during the COVID-19 crisis in a sample of Italian healthcare workers. Methods The study is a randomized controlled trial. It includes two groups of 30 individuals recruited from healthcare workers: (1) the experimental group and (2) the control group. Participants in the experimental group will receive a training consisting of three home sessions performed in a week. In each session, participants will try through an immersive virtual reality standalone system (i.e., Oculus Quest 2) a virtual psychoeducation experience on stress and anxiety (i.e., MIND-VR). Subsequently, they will try the virtual relaxation content (i.e., The Secret Garden). The control group will receive no training and will be reassessed one week and one month after the initial evaluation. Discussion If the proposed brief home-based virtual reality training will result helpful and easy to use, it could become an empirically assessed viable option for protecting healthcare workers’ mental health both during the COVID-19 pandemic and once it will be over. Furthermore, the intervention might be easily adapted for other categories of people who need support in managing stress and anxiety. Trial registration ClinicalTrials.gov NCT04611399 .

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Nel luglio 2022 un importante raccolta di carte di Orio Vergani e dei figli Guido e Leonardo è stata donata dai suoi nipoti ad Apice (Archivi della Parola, dell’Immagine e della Comunicazione Editoriale), istituzione dell’Università degli Studi di Milano. La donazione costituisce un’importante occasione di studio e approfondimento dell’attività del grande giornalista, attivo in moltissimi campi (reportage, fotogiornalismo e letteratura, ma anche critica letteraria e d’arte, editoria, pittura, cinema, radio, pubblicità, enogastronomia), come dimostra il ritratto a tutto tondo di Vergani qui proposto sulla base di materiali inediti, ampiamente citati.

Introduction The closure of forensic psychiatric hospitals and the conversion to a residential model of care based on secure residential units in the community (REMS) has made Italy the first and only country in the world to have followed the principles of the deinstitutionalization movement. Following the reform, several management issues have emerged, such as the creation of long waiting lists for admission to REMS. Improper hospitalization in Acute Psychiatric Units (SPDC) has often been used to address this issue. In addition, the handover of inmates’ care to Mental Health Departments (DSMD’s) has posed further challenges. To date, the field has received little attention from international literature. Objectives Description and analysis of a sample of offender inpatients hospitalized in an acute psychiatric unit. Methods We conducted a retrospective study including male offenders admitted to the SPDC of San Gerardo Hospital (ASST Monza), between January 2007 and September 2022. Data analysis was performed by using SPSS. Results 120 male offenders were included for a total of 204 admissions. 98 offenders (81.7%) were hospitalized once. We observed an absolute (N=1; N=30) and percentage (0.2%;12%) increase in the number of hospitalized offenders per year during the time period under study. Jail was the main provenance in the sample (46.6%), followed by residential care facilities (27%) and the psychiatric observation unit (ROP) of Monza’s jail (10.8%). The two most prevalent diagnoses were personality disorders (37.5%) and psychosis (39.2%). In addition, 66 subjects (55%) had a history of substance abuse. The average duration of hospitalization was 19.45 days; it increased to 77 days for inpatients waiting to be transferred to REMS. Hetero-aggressive behavior as the reason for admission was associated with longer hospitalization (p=0.031), while attempted suicide correlated to shorter hospital stay (p=0.032). Out of the 55 offenders who attempted suicide, 41 came from jail (74.5%). Finally, longer hospitalizations were associated with an increased number of adverse events (p=0.001). Conclusions Psychiatric hospitalizations of offenders have increased over the last years. This population tends to require longer hospital stays (regional average of SPDC hospitalization in Lombardy: 14 days), which are even lengthier for inpatients destined to REMS. Longer hospitalizations exert a large burden on DSMD’s and impact the general health of patients, exposing them to a higher risk of adverse events. Further studies are needed to confirm our findings and to develop better strategies for the management and care of offender patients. Disclosure of Interest None Declared

Introduction Depression is a severe mental disorder with an estimated 3.8% of the population affected, representing a leading cause of disability worldwide. Being linked to reduced quality of life and individual functioning, medical morbidity and mortality, depression has a huge social and economic impact. A wide range of potentially modifiable factors for depression has been identified. Among these, social factors (e.g. support/engagement) appear to play a major role in the emergence and severity of depression. Objectives We aimed at providing a quantitative synthesis of the consistency and magnitude of the association between measures of social connection and depression. Social connection included both quantitative (i.e. existence/absence of social relationships) and functional (i.e. support provided) measures of social relationships, as well as measures focusing on social inequalities related to participation in community spaces/activities (i.e. social discrimination). Methods We searched PubMed, PsycINFO, Cochrane Library and EMBASE. The strength of the association between exposure factors (social measures) and depression was extracted and equivalent odds ratios were computed to compare the strength of the effect sizes among meta-analyses. The quality of each review was assessed using AMSTAR-2. Results As a result of the selection process 47 studies were included in the umbrella review. Social support was found to have a protective role on depression, with an observed moderate/strong effect in peripartum population and a weaker effect in clinical populations (e.g. AIDS/HIV patients). A moderate association between stigma/discrimination and depression emerged in clinical populations (e.g. epilepsy, mental illness, post-stroke), while a weaker effect was found in (ethnic) minorities. There are still few studies quantitatively investigating the link between depression and other social measures (e.g. community connectedness). Conclusions Our findings align with the literature on social connection and mental health, confirming the role of social determinants in the emergence and severity of depression, particularly in the case of vulnerable populations. Social factors emerge as important modifiable targets in the context of depression prevention. Efforts to counteract disconnection at the societal and individual levels and to reduce stigma should be central to an effective depression prevention agenda. Disclosure of Interest None Declared

Introduction Intellectual Developmental Disorder (IDD) is diagnosed with cognitive and adaptive behaviour evaluations. There is increasing evidence of a high prevalence of psychiatric disorders comorbid with IDD. The relationship between specific cognitive dysfunctions and psychiatric vulnerability may provide the basis for a paradigm shift from “intellectually below average IQ” to “neuropsychological characterization”. Objectives 1) reassessing an IDD sample in cognitive profile and psychiatric comorbidities 2) investigating the correlations between specific cognitive dysfunctions and specific psychiatric diagnoses in IDD. Methods 120 individuals with IDD from 3 Italian facilities were consecutively evaluated, one group with mild IDD, using WAIS-IV or Leiter-3, TMT, Stroop and TOL tests, after which a professional caregiver did individual interviews (Vineland Adaptive Behavior Scale-II, SPAIDD-G, and STA-DI) to evaluate the patient adaptive behaviour, psychiatric comorbidities and presence of ASD. The second group (more severe IDD), was evaluated only with professional caregiver assessment tools. Results 90 males and 30 females, mean age 57 years, institutionalized for a mean period of 36.44 years. 52% had no education, 19% a middle school diploma. IDD diagnoses: borderline 3%, mild 16%, moderate 11%, moderate-severe 4%, severe 59%, profound 0%.11% comorbid ASD diagnosis, 29% with ASD after diagnostic re-assessment (STA-DI). 89% physical comorbidities, 58% psychiatric comorbidities, 56% psychoses (Fig. 1). Psychiatric comorbidities re-assessment (SPAIDD-G) identified a significant number of disorders (Fig. 2), despite the medical records showed a low prevalence of psychiatric diagnoses. The consistent quantity of psychotropic drugs prescribed in the sample, possibly reflects the real prevalence of psychopathology. Pearson correlations (p

Introduction According to DSM V, substance-induced psychotic disorder is a mental health condition in which the onset of psychotic symptoms can be traced to the use of a psychotropic substance. The pathogenesis of this disease is still poorly understood; current literature traces its causes back to genetic predisposition and early traumatic events (i.e. child abuse). Objectives The present study aims to identify specific clinical features and biochemical markers which could be addressed as predictors for the long-term prognosis of this disease. Moreover, we aim to identify specific correlations between the clinical phenotype and the underlying substance abuse, in order to allow the early start of a tailored treatment. Methods Between 2020 and 2022 we recruited 218 patients referring to the Policlinico Hospital in Milan and the San Gerardo Hospital in Monza, Italy. All the patients were diagnosed with substance induced psychotic disorder: 31 reported alcohol abuse (14,2%), 71 psichostimulants (32,6%), 116 cannabis, (53,2%). For each patients, we collected demographic data, medical records and a comprehensive psychometric assessment (GAF, PANSS, BPRS, Modified Sad Person Scale-MOAS). Furthermore, we collected a blood sample for dosing Na+, K+, Na+/K+, hemogram with formula and platelets, glucose , urea, creatinine, uric acid, transaminases, γGT, bilirubin, plasma proteins, albumin, LDH, CPK, PCHE, cholesterol, HDL, LDL, Tg, TSH. Results Chi squared test (χ²) has been used to compare qualitative variables between the 3 subgrous (alcohol-, psychostimulants- and cannabis-induced psychotic syndromes) (fig.1). One way ANOVA test has been used to compare quantitative variables between the same 3 subgroups (fig.2). After removing one of the subgropus (alcohol-induced psychotic symptoms), the same analysis have been repeated. Significant variables have been included in a binary logistic regression model in order to confirm their validity as predictors for cannabis- and psychostimulants-induced psychotic disorders (fig 3). Finally we performed Omnibus test and Hosmer-Lemeshow test in order to verify the validity of these regression models. Image: Image 2: Image 3: Conclusions For each considered subgroups, we indentified the following features. Alcohol induced psychotic syndrome: higher age of onset and age of hospital admission, higher cholesterol and hurea levels, , high comorbidity with medical conditions anxiety/depression, low social functioning, higher suicidal risk;, higher hospitalization rate. Cannabis induced psychotic syndrome: higher hemoglobin and albumin levels, more severe psychiatric symtoms (BPRS), higher smoking rates. Psychostimulants induced psychotic syndrome: higher multi-drug abuse risk. We could assume that according to this consideration the treatment protocols for each of these subgroups should be tailored according to their specific features. Disclosure of Interest None Declared

Introduction Bipolar Disorder (BD) is a frequent psychiatric disorder, which can be associated with high disability. Psychotic symptoms occur in more than half of bipolar patients and are associated with an unfavorable course of the disorder (Chakrabarti et al. World J Psychiatry 2022; 12(9) 1204-1232). Objectives The aim of this study is therefore to identify clinical and biological markers able to discriminate between BD patients with (BD-PS) and without lifetime psychotic symptoms (BD-NPS) to facilitate early diagnosis and to implement a target clinical management of these patients. Methods We recruited 665 patients consecutively hospitalized for BD at Fondazione IRCCS Policlinico (Milan) and at San Gerardo Hospital (Monza). Data were obtained through a screening of the clinical charts and blood analyses conducted during the hospitalization. Patients were assessed by psychometric scales. The two groups (BD-PS and BD-NPS) were compared by t tests for quantitative variables and χ2 tests for qualitative ones. Variables that resulted to be significant in univariate analyses were inserted in binary logistic models with the presence of psychotic symptoms as dependent variable. Results Among the total sample, 64.5% of patients were affected by BD-PS while 35.5% by BD-NPS. The final binary logistic regression model showed that, compared to patients with BD-NPS, those with BD-PS had a longer duration of hospitalization (p=0.007) and were more frequently hospitalized for a manic episode (p=0.001). In addition, subjects with BD-PS had a lower score on the current Global Assessment of Functioning (GAF) (t = 3.157; p = 0.002) and were more frequently males (χ² = 4.061; p = 0.044; OR = 1.399). With regard to biological variables, patients with BD-PS, compared to the counterpart, had a higher Neutrophile to Lymphocyte Ratio (NLR) (t = 2.776; p = 0.006), lower levels of Gamma-Glutamyl Transferase (γGT) (t = 2.249; p = 0.026), higher total bilirubin (t = 2.348; p = 0.019) and creatine phosphokinase (CPK) (t=2.807; p = 0.005), lower total cholesterol (t = 2.369; p = 0.018) and triglycerides (t = 2.554; p = 0.013). Conclusions Our data appear to be in line with the literature, especially with respect to the occurrence of psychotic symptoms mainly in manic episodes and their association with greater clinical severity, longer hospitalization and worse outcome (Altamura et al. Aust N Z J Psychiatry 2019; 53(8) 772-781). From a biological point of view, it seems important to emphasize that patients with lifetime psychotic symptoms presented a higher NLR, revealing more prominent low-grade inflammation in these patients than the counterpart. These data confirm the possibility of using NLR as biomarker of severity in bipolar patients, as proposed previously by other authors (Kulacaoglu et al. Nord J Psychiatry 2022). Future multi-center study have to confirm the results of the present study. Disclosure of Interest None Declared

Narcissistic personality disorder is characterized by self-absorption, grandiosity, exploitation of others and lack of empathy. People with that disorder may switch from an overt form, mainly with grandiosity, to a covert presentation, with fears, hypersensitivity and dependence from others. Empathy represents a key point in detecting people affected by narcissistic personality disorder because, even if it is described as reduced, it plays a fundamental role in exploitation and manipulation. A systematic search of Literature without any language or time restriction, was performed combining thesaurus and free-search indexing terms related to Narcissistic personality disorder and empathy and produced 531 results. Fifty-two papers that analyzed possible issues in the empathic attitude of people with narcissistic personality disorder were included in this narrative review. Empathy is the capability of understating and feeling others emotions. It is not a unitary construct and can be distinguished in cognitive and affective. It might be channeled into prosocial and antisocial behaviors. A crucial trait identified in narcissistic empathy is affective dissonance that is closely related to rivalry as part of the dark tetrad (narcissism, machiavellianism, psychopathy, and sadism). Subjects affected by narcissistic personality disorder show greater impairment in affective aspects while their cognitive part of empathy appears preserved. Saving at least the cognitive aspects of empathy may contribute to therapeutic improvement of affective aspects.

Background Cardiac adrenergic receptor gene polymorphisms have the potential to influence risk of developing ventricular fibrillation (VF) during ST‐segment‐elevation myocardial infarction, but no previous study has comprehensively investigated those most likely to alter norepinephrine release, signal transduction, or biased signaling. Methods and Results In a case–control study, we recruited 953 patients with ST‐segment‐elevation myocardial infarction without previous cardiac history, 477 with primary VF, and 476 controls without VF, and genotyped them for ADRB1 Arg389Gly and Ser49Gly, ADRB2 Gln27Glu and Gly16Arg, and ADRA2C Ins322‐325Del. Within each minor allele‐containing genotype, haplotype, or 2‐genotype combination, patients with incident VF were compared with non‐VF controls by odds ratios (OR) of variant frequencies referenced against major allele homozygotes. Of 156 investigated genetic constructs, 19 (12.2%) exhibited significantly (P

This paper presents the development of a multi-user, collaborative virtual reality environment for training electricians to work on the electric power distribution network. Typically, traditional trainings in this field have lots of constraints and don’t allow learners to experience a wide set of different equipment that is installed in the network nor bad weather conditions and the different risk analysis that should be performed. With the proposed virtual reality environment, learners will be able to practice several realistic conditions without risking themselves.

Cumulative effects are crucial for applications of laser filaments, such as for the remote transfer of energy and the control of electric discharges. Up to now, studies of cumulative effects in the air of high‐repetition‐rate pulse trains have been performed at lower rates than 10 kHz. Herein, the nonlinear effects associated with short plasma filaments produced by pulses of moderate energy (0.4 mJ per pulse) and repetition rates up to 100 kHz are experimentally characterized. With increasing repetition rate, a decrease in absorption, fluorescence emission, and breakdown voltage and concurrently an increase in peak intensity and third‐harmonic‐generation efficiency are observed. Hydrodynamic simulations of the heated gas show that the observed decreases are directly related to a quasi‐stationary state of reduced gas density in the filament. However, further investigations are required to fully understand the physics underpinning the observed sharp reduction of the breakdown voltage at 100 kHz repetition rates. The results may prove relevant for energy and information delivery applications by laser‐induced air waveguide or electric discharge and lightning control.

Team-based learning is a powerful collaborative learning technique that can be used effectively in a principles of economics course, although its implementation can be costly for instructors and students alike. The author suggests a series of strategies that can result in a much smoother transition to a fully collaborative classroom. The author also highlights some unexpected benefits of team-based learning.

In a globalised economy, metropolises seem to have an ‘extra gear’ compared to smaller urban centres: they attract the most skilled businesses, drive innovation in many fields and can count on material and immaterial assets that foster greater resilience to adverse events of various kinds. Against the dynamism of metropolises, which evolutionary paths do medium-sized cities (MSCs) follow? This paper focuses on the case of Northern Italy and explores employment trends between 2012 and 2020 in 189 MSCs with a population of between 20,000 and 200,000 inhabitants. The evolutionary trajectories of these cities and their varying specialisations are investigated over a period marked by a moderate recovery of the Italian economy following the Great Recession and by a further setback caused by the COVID-19 pandemic. In general, in terms of employment performance, the 189 cities in question were less dynamic than the metropolises, but it is nevertheless necessary to look at their individual circumstances in detail. Furthermore, this work shows significant differences between the MSCs of the Northwest and Northeast in terms of evolutionary trajectories and specialisation profiles. The most problematic situations also relate to cities with a hub status in the wider context and do not only concentrate where a production structure is present that is linked to industry.

Severe forms of Anorexia Nervosa (AN) are characterized by medical complications, psychiatric comorbidity, and high mortality. This study investigated potential associations between clinical/biological factors and the severity of AN, measured by the Body Mass Index (BMI). Red and white blood cells, hemoglobin, platelets, iron, vitamins D and B12, folate, and total cholesterol were measured in a mixed sample of 78 inpatients and outpatients. Linear regressions and one-way analyses of variance (ANOVAs) were carried out to evaluate the relationship between BMI and clinical/biochemical variables. BMI was significantly lower in hospitalized patients (F = 4.662; p = 0.034) and in those under pharmacological treatment (F = 5.733; p = 0.019) or poly-therapy (F = 5.635; p = 0.021). Higher vitamin B12 (β = −0.556, p < 0.001), total cholesterol (β = −0.320, p = 0.027), and later age at onset (with a trend towards significance) (β = −0.376, p = 0.058) were associated with a lower BMI. Increased total cholesterol and vitamin B12, later age at onset, current pharmacological treatment, and poly-therapy might be distinctive in patients with a lower BMI. In clinical practice, these findings may contribute to the early identification of AN patients at higher risk of developing complicated or chronic forms of the disorder. Further studies on larger samples are needed to identify potential predictive factors of AN severity in the framework of precision medicine.

The anti-hyperglycemic drug glibenclamide (Glb) might represent an interesting therapeutic option in human neurodegenerative diseases because of its anti-inflammatory activity and its ability to downregulate activation of the NLRP3 inflammasome. Bi-functionalized liposomes that can cross the blood–brain barrier (BBB) may be used to release Glb into the central nervous system (CNS), overcoming its poor solubility and bioavailability. Here, we analyzed in vitro the effect of Glb-loaded nanovectors (GNVs) and Glb itself on NLRP3 inflammasome activation using a lipopolysaccharide- and nigericine-activated THP-1 cell model. Apoptosis-associated speck-like protein containing a CARD (ASC) aggregation and NLRP3-related cytokine (IL-1β, caspase 1, and IL-18) production and gene expression, as well as the concentration of miR-223-3p and miR-7-1-5p, known to modulate the NLRP3 inflammasome, were evaluated in all conditions. Results showed that both GNVs and Glb reduced significantly ASC-speck oligomerization, transcription and translation of NLRP3, as well as the secretion of caspase 1 and IL-1β (p < 0.05 for all). Unexpectedly, GNVs/Glb significantly suppressed miR-223-3p and upregulated miR-7-1-5p expression (p < 0.01). These preliminary results thus suggest that GNVs, similarly to Glb, are able to dampen NLRP3 inflammasome activation, inflammatory cytokine release, and modulate miR-223-3p/miR-7-1-5p. Although the mechanisms underlying the complex relation among these elements remain to be further investigated, these results can open new roads to the use of GNVs as a novel strategy to reduce inflammasome activation in disease and rehabilitation.

Ryegrass is one such cereal that has been underutilized in human nutrition despite its high nutritional and functional value due to the presence of phytochemicals and dietary fibers. Exploiting ryegrass for human consumption is an exciting option, especially for countries that do not produce wheat, as it is easily adaptable and overgrows, making it economically viable. This study evaluated the nutritional content of γ-aminobutyric acid and bioactive compounds (total soluble phenolic compounds) and the physicochemical and technological properties of partially substituting maize flour (MF) with sprouted whole ryegrass flour (SR) in developing extrusion-cooked breakfast cereals. A completely randomized design with substitutions ranging from 0 to 20% of MF with SR was employed as the experimental strategy (p < 0.05). Partial incorporation of SR increased the content of γ-aminobutyric acid and total soluble phenolic compounds. Using sprouted grains can adversely affect the technological quality of extruded foods, mainly due to the activation of the amylolytic enzymes. Still, ryegrass, with its high dietary fiber and low lipid content, mitigates these negative effects. Consequently, breakfast cereals containing 4 and 8% SR exhibited better physicochemical properties when compared to SR12, SR16, SR20, and USR10, presenting reduced hardness and increased crispness, and were similar to SR0. These results are promising for ryegrass and suggest that combining the age-old sprouting process with extrusion can enhance the nutritional quality and bioactive compound content of cereal-based breakfast products while maintaining some technological parameters, especially crispiness, expansion index, water solubility index, and firmness, which are considered satisfactory.

Tendon injuries caused by overuse or age-related deterioration are frequent. Incomplete knowledge of somatic tendon cell biology and their progenitors has hindered interventions for the effective repair of injured tendons. Here, we sought to compare and contrast distinct tendon-derived cell populations: type I and II tendon stem cells (TSCs) and tenocytes (TNCs). Porcine type I and II TSCs were isolated via the enzymatic digestion of distinct membranes (paratenon and endotenon, respectively), while tenocytes were isolated through an explant method. Resultant cell populations were characterized by morphology, differentiation, molecular, flow cytometry, and immunofluorescence analysis. Cells were isolated, cultured, and evaluated in two alternate oxygen concentrations (physiological (2%) and air (21%)) to determine the role of oxygen in cell biology determination within this relatively avascular tissue. The different cell populations demonstrated distinct proliferative potential, morphology, and transcript levels (both for tenogenic and stem cell markers). In contrast, all tendon-derived cell populations displayed multipotent differentiation potential and immunophenotypes (positive for CD90 and CD44). Type II TSCs emerged as the most promising tendon-derived cell population for expansion, given their enhanced proliferative potential, multipotency, and maintenance of a tenogenic profile at early and late passage. Moreover, in all cases, physoxia promoted the enhanced proliferation and maintenance of a tenogenic profile. These observations help shed light on the biological mechanisms of tendon cells, with the potential to aid in the development of novel therapeutic approaches for tendon disorders.

Hyperglycemia associated with prediabetes (PD) alters NLRP3 inflammasome activity and related interleukins, yet no study has evaluated the expression of the NLRP3 inflammasome complex and related interleukins in individuals with a PD condition that did or did not develop type 2 diabetes mellitus (T2DM). This study investigated the effect of 6 months of lifestyle modification on the expression of the NLRP3 inflammasome and related interleukins (1α, 1β, 18, 33 and 37) in the sera of individuals with a PD condition that did or did not develop T2DM. This interventional study included 67 Saudi adults (mean age = 41.9 ± 8.0 years, mean BMI = 33.2 ± 5.5 kg/m2). Overnight-fasting serum samples were collected at baseline and at the 6-month follow-up. Serum levels of NLRP3, capsase-1 and related ILs were analyzed at both visits using commercially available immunoassay kits. Results showed that IL-1α increased in the PD group that developed T2DM (p = 0.046), IL-33 decreased in the PD group that reverted to normal (p < 0.001) and NLRP3 decreased in the PD group that remained PD (p = 0.01). Results also showed a positive over-time correlation between NLRP3 and both IL-1α and IL-33 (p < 0.001 and p = 0.028, respectively). In conclusion, glycemic control favorably altered NLRP3 inflammasome complex activity, and lifestyle modification in PD individuals is crucial in reversing harmful metabolic and inflammatory phenotypes.

Autism spectrum disorders (ASD) can present with different onset and timing of symptom development; children may manifest symptoms early in their first year of life, i.e., early onset (EO-ASD), or may lose already achieved skills during their second year of life, thus showing a regressive-type onset (RO-ASD). It is still controversial whether regression represents a neurobiological subtype of ASD, resulting from distinct genetic and environmental causes. We focused this study on the 25 kD synaptosomal-associated protein (SNAP-25) gene involved in both post-synaptic formation and adhesion and considered a key player in the pathogenesis of ASD. To this end, four single nucleotide polymorphisms (SNPs) of the SNAP-25 gene, rs363050, rs363039, rs363043, and rs1051312, already known to be involved in neurodevelopmental and psychiatric disorders, were analyzed in a cohort of 69 children with EO-ASD and 58 children with RO-ASD. Both the rs363039 G allele and GG genotype were significantly more frequently carried by patients with EO-ASD than those with RO-ASD and healthy controls (HC). On the contrary, the rs1051312 T allele and TT genotype were more frequent in individuals with RO-ASD than those with EO-ASD and HC. Thus, two different SNAP-25 alleles/genotypes seem to discriminate between EO-ASD and RO-ASD. Notably, rs1051312 is located in the 3′ untranslated region (UTR) of the gene and is the target of microRNA (miRNA) regulation, suggesting a possible epigenetic role in the onset of regressive autism. These SNPs, by discriminating two different onset patterns, may represent diagnostic biomarkers of ASD and may provide insight into the different biological mechanisms towards the development of better tailored therapeutic and rehabilitative approaches.

In the field of contaminated site remediation, risk analyses can be carried out by the use of appropriate mathematical models, based on simplified hypotheses of real sites. The possibility to have shared and accurate analytical methods is an important challenge for both routine laboratories and supervisory institutions. Although official methods (e.g., APH2009) are already available, they are lacking in some aspects, such as applicability to all the different sampling and analysis media and ease of use in routine analysis. Here, we report our recent advances in the implementation of an empirical method for hydrocarbon speciation in an air matrix, previously developed by the authors and published in 2015. The validation results led to a coefficient of variation (CV%) between 10–15% for the hydrocarbon fractions investigated (C5-C8 aliphatic, C9-C12 aliphatic, C9-C10 aromatic and C11-C12 aromatic) and recovery of ≤20%, in agreement with the required characteristics for the analytical methods. Several real samples were analyzed by the proposed method and the results were compared to those obtained by the official approach. The comparison led to an average bias (that is, the difference between the results from the developed method and those from the conventional one) of about 10%, confirming that the innovative approach is robust, accurate and can be applied to all the analytical media used for air sampling, such as soil gas.

Background: Subjects with intellectual disability (ID) are vulnerable to experience psychiatric disorders. The present authors performed a systematic review and meta-analysis to estimate the prevalence of co-occurring psychiatric disorders, excluding co-occurring autism spectrum disorders, in subjects with intellectual disability. Method: The present authors performed a random-effects meta-analysis of the prevalence of psychiatric disorders in adults and adolescents with intellectual disability. Results: Twenty-two studies were included. The pooled prevalence of any co-occurring psychiatric disorders in intellectual disability was 33.6% (95% CI: 25.2%-43.1%) with high heterogeneity but no publication bias. Prevalence was lower in population-based studies, in studies that used ICD criteria for the psychopathology and in studies with low risk of bias. The prevalence was higher in mild, moderate and severe intellectual disability than in profound intellectual disability. Conclusions: Psychiatric disorders are common in subjects with intellectual disability, and the present authors found that clinical and methodological moderators affect the pooled prevalence.

Since the start of the COVID-19 outbreak, more than four million people have died of this disease. Given its ability to provide a precise response, mass spectrometry-based proteomics could represent a useful tool to study this pathology. To this end, an untargeted nLC-ESI-MS/MS-based method to characterise SARS-CoV-2 proteins, including possible variants, and investigate human saliva and plasma proteome in a single analysis was developed for further application in patients. Four SARS-CoV-2 recombinant proteins, three (S1–S2–RBD) belonging to the spike glycoprotein (S) and one corresponding to the nucleoprotein (N), were prepared and analysed with nLC-UHRTOF by injecting decreasing amounts to establish the limit of detection (LOD) of the method. This was determined as 10 pg for all the components of the S protein and for N (71 amol and 213 amol, respectively). Various viral inactivation strategies plus deglycosylation and digestion approaches were then tested in saliva and plasma spiked with different quantities of SARS-CoV-2 recombinant proteins. The limit of characterisation (LOC) in saliva for the N and S proteins was observed at 100 pg (coverage of 20% and 3%, respectively); instead, in plasma, it was 33 pg for N and 330 pg for the S protein, with a coverage of 4% for both. About 300 and 800 human proteins were identified in plasma and saliva, respectively, including several key effectors and pathways that are known to be altered in COVID-19 patients. In conclusion, this approach allows SARS-CoV-2 proteins and the human proteome to be simultaneously explored, both for plasma and saliva, showing a high relevant potential for retrospective studies aimed at investigating possible virus variants and for patient stratification.

El objetivo de este artículo es reflexionar acerca de las relaciones entre los feminismos y el discurso punitivo a partir del análisis de la legislación penal en materia de violencia de género, el sentimiento de inseguridad de las mujeres, y las cifras oficiales en cuanto a violencia de género y prisionalización.

Background: The internet has acquired a fundamental role nowadays, also in the medical field, for example to obtain information about disease or take part in forums/chats to share experience. This study describes how a group of adolescent and young adult [AYA) patients with cancer used the web to find information, confirmation of what they have been told by doctors and parents, and find support. Methods: A questionnaire was developed to investigate: the perceptions of the type of support received from healthcare professionals or in the social environment, the use made of internet, and what motivated them (information, support, sharing), the perceived outcomes of internet searches (reliability, consistency, and usefulness). The questionnaire was administered online between September and November 2021 to patients>15 years who were receiving treatments at our Pediatric Oncology Unit, and to patients who had completed treatments no more than two years previously. Results: The questionnaire was proposed to 42 patients and answered by 41 of them (age 14–29 years, median 19). Respondents identified doctors/nurses and family members as their primary sources of information and support. Internet was used by our patients mainly for entertainment and socializing, and only to a much smaller degree to find information about their disease. Information was considered reliable and useful in a minority of cases. Conclusions: In our specific setting, AYA patients did not see the web as being crucial to understanding and coping with their disease. It is nonetheless important for healthcare professionals to consider the increasing role of internet.

Immersive Virtual Reality technology has recently gained significant attention and is expanding its applications to various fields. It also has many advantages in education, as it allows to both simplify the explanation of complex topics through their visualization, and explore lost or unreachable environments. To evaluate the impact of immersive experiences on learning outcomes we developed an educational experience that lets users visit an ancient Roman Domus and provides information about daily life in Roman times. We designed a between-subjects data collection to investigate learning ratio, user experience, and cybersickness of participants through anonymous questionnaires. We collected 76 responses of participants (18–35 y.o.) divided into three conditions: a Immersive Virtual Reality experience, a slide-based lecture and a 2D desktop-based experience. Our results show that the virtual reality experience is considered more engaging and as effective as more traditional 2D and slide-based experiences in terms of learning.

ObjectivesMonitoring of SARS-CoV-2 spread and vaccination strategies have relied on antibody (Ab) status as a correlate of protection. We used QuantiFERON™ (QFN) and Activation-Induced Marker (AIM) assays to measure memory T-cell reactivity in unvaccinated individuals with prior documented symptomatic infection (late convalescents) and fully vaccinated asymptomatic donors (vaccinees).MethodsTwenty-two convalescents and 13 vaccinees were enrolled. Serum anti-SARS-CoV-2 S1 and N Abs were measured using chemiluminescent immunoassays. QFN was performed following instructions and interferon-gamma (IFN-γ) measured by ELISA. AIM was performed on aliquots of antigen-stimulated samples from QFN tubes. SARS-CoV-2-specific memory CD4+CD25+CD134+, CD4+CD69+CD137+ and CD8+CD69+CD137+ T-cell frequencies were measured by flow cytometry.ResultsIn convalescents, substantial agreement was observed between QFN and AIM assays. IFN-γ concentrations and AIM+ (CD69+CD137+) CD4+ T-cell frequencies correlated with each other, with Ab levels and AIM+ CD8+ T-cell frequencies, whereas AIM+ (CD25+CD134+) CD4+ T-cell frequencies correlated with age. AIM+ CD4+ T-cell frequencies increased with time since infection, whereas AIM+ CD8+ T-cell expansion was greater after recent reinfection. QFN-reactivity and anti-S1 titers were lower, whereas anti-N titers were higher, and no statistical difference in AIM-reactivity and Ab positivity emerged compared to vaccinees.ConclusionsAlbeit on a limited sample size, we confirm that coordinated, cellular and humoral responses are detectable in convalescents up to 2 years after prior infection. Combining QFN with AIM may enhance detection of naturally acquired memory responses and help stratify virus-exposed individuals in T helper 1-type (TH1)-reactive (QFNpos AIMpos Abshigh), non-TH1-reactive (QFNneg AIMpos Abshigh/low), and pauci-reactive (QFNneg AIMneg Abslow).

This study aimed to explore the perception and sensory acceptance of Purple Maize (PM) breakfast cereals by a Brazilian panel. The extrudates were elaborated using 25%, 50%, 75%, and 100% PM in a commercial yellow corn base. A total of 117 consumers evaluated samples through an acceptability test (nine-point hedonic scale) followed by CATA questions (35 descriptive terms) and a market research questionnaire. The cereals formulated with 50% and 75% PM had the best scores (6) in color, aroma, texture, and overall liking during the acceptability test. Based on the penalty-lift analysis, Brazilian consumers' most important drivers of preference were the attractive color, crispy texture, and the natural and innovative purple color. In contrast, hard texture and brown color drivers negatively impacted the scores. In the market research, consumers indicated that they could eat the product both as a breakfast cereal and as a snack during the day; Likewise, they highlighted the possible health benefits, the innovative color, and the use of exotic raw materials as the best characteristics of the product. Therefore, using 50% PM or more allows for obtaining sustainable and nutritious breakfast cereals with characteristics of color, flavor, and texture well accepted by Brazilian consumers.

SNAP-25 protein is a key protein of the SNARE complex that is involved in synaptic vesicles fusion with plasma membranes and neurotransmitter release, playing a fundamental role in neural plasticity. Recently the concentration of three specific miRNAs-miR-27b-3p, miR-181a-5p and miR-23a-3p -was found to be associated with a specific SNAP-25 polymorphism (rs363050). in silico analysis showed that all the three miRNAs target SNAP-25, but the effect of the interaction between these miRNAs and the 3'UTR of SNAP-25 mRNA is currently unknown. For this reason, we verified in vitro whether miR-27b-3p, miR-181a-5p and miR-23a-3p modulate SNAP-25 gene and protein expression. Initial experiments using miRNAs-co-transfected Vero cells and SNAP-25 3'UTR luciferase reporter plasmids showed that miR-181a-5p (p≤0.01) and miR-23a-3p (p

IntroductionChronic lung allograft dysfunction (CLAD) is the main cause of the reduced survival of lung transplanted (LTx) patients. The possible role of immune checkpoint molecules in establishing tolerance has been scarcely investigated in the setting of lung transplantation.MethodsWe conducted a retrospective, observational pilot study on a consecutive series of transbronchial cryobiopsies (TCB) obtained from 24 patients during LTx follow-up focusing on PD-1, one of the most investigated immune checkpoint molecules.ResultsResults showed that PD-1-expressing T lymphocytes were present in all TCB with a histological diagnosis of acute rejection (AR; 9/9), but not in most (11/15) of the TCB not resulting in a diagnosis of AR (p=0.0006). Notably, the presence of PD-1-expressing T lymphocytes in TCB resulted in a 10-times higher risk of developing chronic lung allograft dysfunction (CLAD), the main cause of the reduced survival of lung transplanted patients, thus being associated with a clearly worst clinical outcome.DiscussionResults of this pilot study indicate a central role of PD-1 in the development of AR and its evolution towards CLAD and suggest that the evaluation of PD-1-expressing lymphocytes in TCB could offer a prognostic advantage in monitoring the onset of AR in patients who underwent lung transplantation.

The early differential diagnosis of Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), is challenging because of an overlap of clinical features and the lack of reliable biomarkers. Neural-derived extracellular vesicles (NDEVs) isolated from blood provide a window into the brain's biochemistry and may assist in distinguishing between PD and APS. We verified in a case-control study whether oligomeric α-Synuclein and Tau aggregates isolated from NDEVs could allow the differential diagnosis of these conditions.Blood sampling and clinical data, including disease duration, motor severity, global cognition, and levodopa equivalent daily dose (LEDD), were collected from patients with a diagnosis of either PD (n = 70), PSP (n = 21), or CBD (n = 19). NDEVs were isolated from serum by immunocapture using an antibody against the neuronal surface marker L1CAM; oligomeric α-Synuclein and aggregated Tau were measured by ELISA.NDEVs analyses showed that oligomeric α-Synuclein is significantly augmented in PD compared to APS, whereas Tau aggregates are significantly increased in APS compared to PD (p