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Abstract University students have to handle crucial challenges for their future lives, such as succeeding in academic studies and finding attachment figures. These processes could potentially involve their well-being and mental health, with possible sociocultural differences based on the country of study. In order to explore such potential differences, a cross-sectional, multi-center survey was performed involving students from the University of Torino (Italy), Sevilla (Spain), and Lusòfona (Portugal). The survey, conducted from May to November 2023, investigated students’ demographic and educational details, socioeconomic status, social support, mental health, academic environment, perceived COVID-19 pandemic impact, and future plans. Demographic profiles showed a predominance of female participants and straight sexual orientation, followed by bisexuality. Italian students showed the lowest levels of mental well-being and the highest rates of mental problems (anxiety and depression) and suicidal risk across the three countries despite the relatively similar profiles of social support. The prevalence of the students’ confidence in their professional future is higher in Spain than in Italy and Portugal. This study provides a comprehensive examination of university students’ mental health and well-being in three Southern European countries, addressing the major mental health challenges among university students and offering valuable insights for public health purposes.

Abstract Background The COVID-19-pandemic has had a profound impact on the lives of adolescents worldwide. This study examined the subjective perception of the COVID-19 pandemic measures and its association with mental health and well-being (i.e., loneliness, life satisfaction and multiple health complaints) among 13- and 15-years-old adolescents from 22 countries. Methods Data from the cross-national Health Behaviour in School-aged Children (HBSC) 2021/22 study were used from representative samples of 22 countries (N = 67,544; 51.9% girls). The self-perceived impact of COVID-19 measure comprised 10 items asking about the impact on several dimensions of adolescent lives (e.g., relationships with family and friends, health, or eating behaviours). Measures of loneliness, multiple health complaints, and life satisfaction were included as indicators of mental health and well-being. A non-parametric multilevel latent class analysis considering individual and country-levels was conducted to identify classes of self-perceived impact of the COVID-19 measures. Multilevel logistic regression models adjusted by age and socioeconomic status were applied to assess the association between COVID-19 measure impact classes and mental health. Results Three classes were identified on individual level encompassing a neutral (51%), positive (31%), or negative (18%) perception of COVID-19 measures. A third of the adolescents reported a positive impact of the pandemic measures. The distribution of classes was heterogeneous within and across countries. Within the positive COVID-19 measure impact class, social relationships were the most important dimension, whereas mental health problems were mostly represented within the negative COVID-19 measure impact class. Girls with a negative perception of pandemic measures showed higher levels of loneliness and multiple health complaints and lower life satisfaction. 15-year-old adolescents and those with a low socioeconomic status reported higher levels of loneliness and lower life satisfaction. Conclusions The majority of adolescents perceived the pandemic measures as neutral or positive. Girls, 15-year-old adolescents, and those with low socioeconomic status were at higher risk of suffering from pandemic measures and associated problems of loneliness, multiple health complaints, and low life satisfaction. We conclude that adolescent’s mental health and well-being should be considered in the decision-making process by ensuring that the unique challenges of adolescents are adequately addressed in policies.

Adverse Childhood Experiences (ACEs) refer to early life stress events, including abuse, neglect, and other psychosocial childhood traumas that can have long-lasting effects on a wide range of physiological functions. ACEs provoke sex-specific effects, whereas women have been shown to display a strong positive correlation with obesity and cardiometabolic disease. Notably, rodent models of chronic behavioral stress during postnatal life recapitulate several effects of ACEs in a sex-specific fashion. In this review, we will discuss the potential mechanisms uncovered by models of early life stress that may explain the greater susceptibility of females to obesity and metabolic risk compared with their male counterparts. We highlight the early life stress-induced neuroendocrine shaping of the adrenal-adipose tissue axis as a primary event conferring sex-dependent heightened sensitivity to obesity.

IntroductionVaccination practice is a well-known individual protective measure for biological risk in healthcare. During the COVID-19 pandemic vaccine hesitancy has grown among healthcare workers (HCWs). The study aims to investigate how vaccine hesitancy influences the psychological burden experienced by healthcare workers.MethodsThis study aimed to explore attitudes of HCWs in acceptance or refusal of vaccinations related to the risk of psychological impairment (PI) and describe the associated occupational factors, during the seasonal flu/COVID-19 vaccination campaign of 2022–2023. 302 HCWs were enrolled in the study. A questionnaire was self-administered, including two scales on the risk of psychological impairment (Psychological Injury Risk Indicator, PIRI) and vaccine hesitancy (Adult Vaccine Hesitancy Scale, AVHS).ResultsPIRI scores revealed that 29.8% of participants were at risk of PI. Differences in sex, age, occupational seniority, professional category, and night shifts were found between HCWs at risk of PI and those not at risk. Females registered a four-fold higher risk than males (85.6% vs. 14.4%, χ2 = 4.450, p

Abstract Background Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling. Methods Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification. Results The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition. Conclusions Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.

Research on creative organizations often questions how artistic practices can be squared within the rational decision-making of economic thinking. This paper examines how the relational language, or conversation, between artistic and economic rationales unfolds for creative entrepreneurs. Through ethnographic work with a designer-entrepreneur, this paper presents a fine-grained analysis of the conversation the designer cultivates between artistic and economic rationales through work practices. We contribute to the literature about artistic and economic rationales at work, and more specifically to the concept of conversation. First, we show that high levels of conversing make way for low levels of conversing and vice versa. In the studio, the designer’s engagement with either rationale varies as the creative process progresses. Second, on a more global dynamic, we demonstrate the conversation is continuous. It relies on its variations, which ensure the balance between rationales in the long run. We also contribute to the field of creative entrepreneurship research. We identify here one type of creative entrepreneur, with what we call a ‘small is beautiful’ attitude. Far from the mythical figure of the entrepreneur, this unconventional entrepreneur aims for sustainable use of creative resources rather than growth at all costs.

ABSTRACTIntratumoral bacteria flexibly contribute to cellular and molecular tumor heterogeneity for supporting cancer recurrence through poorly understood mechanisms. Using spatial metabolomic profiling technologies and 16SrRNA sequencing, we herein report that right-sided colorectal tumors are predominantly populated with Colibactin-producing Escherichia coli (CoPEC) that are locally establishing a high-glycerophospholipid microenvironment with lowered immunogenicity. It coincided with a reduced infiltration of CD8+ T lymphocytes that produce the cytotoxic cytokines IFN-γ where invading bacteria have been geolocated. Mechanistically, the accumulation of lipid droplets in infected cancer cells relied on the production of colibactin as a measure to limit genotoxic stress to some extent. Such heightened phosphatidylcholine remodeling by the enzyme of the Land’s cycle supplied CoPEC-infected cancer cells with sufficient energy for sustaining cell survival in response to chemotherapies. This accords with the lowered overall survival of colorectal patients at stage III-IV who were colonized by CoPEC when compared to patients at stage I-II. Accordingly, the sensitivity of CoPEC-infected cancer cells to chemotherapies was restored upon treatment with an acyl-CoA synthetase inhibitor. By contrast, such metabolic dysregulation leading to chemoresistance was not observed in human colon cancer cells that were infected with the mutant strain that did not produce colibactin (11G5∆ClbQ). This work revealed that CoPEC locally supports an energy trade-off lipid overload within tumors for lowering tumor immunogenicity. This may pave the way for improving chemoresistance and subsequently outcome of CRC patients who are colonized by CoPEC.

ABSTRACTHuman colorectal cancers (CRCs) are readily colonized by colibactin-producing E. coli (CoPEC). CoPEC induces DNA double-strand breaks, DNA mutations, genomic instability, and cellular senescence. Infected cells produce a senescence-associated secretory phenotype (SASP), which is involved in the increase in tumorigenesis observed in CRC mouse models infected with CoPEC. This study investigated whether CoPEC, and the SASP derived from CoPEC-infected cells, impacted chemotherapeutic resistance. Human intestinal epithelial cells were infected with the CoPEC clinical 11G5 strain or with its isogenic mutant, which is unable to produce colibactin. Chemotherapeutic resistance was assessed in vitro and in a xenograft mouse model. Expressions of cancer stem cell (CSC) markers in infected cells were investigated. Data were validated using a CRC mouse model and human clinical samples. Both 11G5-infected cells, and uninfected cells incubated with the SASP produced by 11G5-infected cells exhibited an increased resistance to chemotherapeutic drugs in vitro and in vivo. This finding correlated with the induction of the epithelial to mesenchymal transition (EMT), which led to the emergence of cells exhibiting CSC features. They grew on ultra-low attachment plates, formed colonies in soft agar, and overexpressed several CSC markers (e.g. CD133, OCT-3/4, and NANOG). In agreement with these results, murine and human CRC biopsies colonized with CoPEC exhibited higher expression levels of OCT-3/4 and NANOG than biopsies devoid of CoPEC. Conclusion: CoPEC might aggravate CRCs by inducing the emergence of cancer stem cells that are highly resistant to chemotherapy.

ObjectivesSocial media has become integrated into adolescents’ lives and influences body image perceptions. Our study examined four patterns of social media use (SMU): non-active, active, intensive, and problematic. We hypothesised that intensive SMU and problematic SMU would be associated with negative body image (negative subjective body weight) and over/underestimated body weight congruence, compared to non-active and active SMU. In addition, we expect these associations to be stronger for girls.MethodsData from 190,892 respondents aged 11, 13, and 15 from 42 countries involved in the Health Behaviour in School-aged Children study were analysed.ResultsFindings revealed higher rates of intensive or problematic SMU among adolescents who perceived themselves as too fat or too thin. Two-level regression analyses showed intensive and problematic SMU as more likely to perceive themselves as too fat or too thin than active users. The association was significant among intensive and problematic girl social media users, whereas, among boys, the relationship was only significant for problematic users.ConclusionOur findings highlight the importance of assessing SMU patterns to evaluate associations with body image.

Abstract Background Safe pet feeding practices and food bowl hygiene measures are important for minimising the risk of microbiological contaminations in the domestic environment. This study compares the practices reported by dog and cat caregivers, and investigates whether cleaning method, feed type or bowl material affects the microbiological contamination of dog food bowls. Results Data from 351 dog caregivers and 186 cat caregivers were collected via an online survey. The majority of dogs (70.7%) were fed twice daily, whereas cats (43%) were mostly fed ad libitum. The most common material for dog food bowls was metal (67.1%) versus plastic (38.1%) and metal (37.6%) for cats. Dog food bowls were most frequently cleaned after each meal (35.7%); whereas for cats, 21.5% were cleaned after each meal, 22.7% once a day and 19.3% 2–3 times a week. Total mesophilic aerobic bacteria counts (TMABc), Enterobacteriaceae counts and pathogenic bacteria (Salmonella spp., Campylobacter spp., Verotoxigenic E. coli [VTEC]) were assessed for 96 dog food bowls. TMABc were higher in metal vs. plastic bowls (p

IntroductionCrohn’s disease (CD) is a chronic inflammatory bowel disease, of which the etiology involves genetic, environmental and microbial factors. Adherent-invasive Escherichia coli (AIEC) and polymorphisms in autophagy-related genes have been implicated in CD etiology. Autophagy is a key process for the maintenance of cellular homeostasis, which allows the degradation of damaged cytoplasmic components and pathogens via lysosome. We have shown that a functional autophagy is necessary for AIEC clearance. Here, we aimed at identifying the autophagy receptor(s) responsible to target AIEC to autophagy for degradation.MethodsThe levels of autophagy receptors p62, NDP52, NBR1, TAX1BP1 and Optineurin were knocked down in human intestinal epithelial cells T84 using siRNAs. The NDP52 knock-out (KO) and p62 KO HeLa cells, as well as NDP52 KO HeLa cells expressing the wild-type NDP52 or the mutated NDP52Val248Ala protein were used.Results and discussionWe showed that, among the tested autophagy receptors (p62, NDP52, NBR1, TAX1BP1 and Optineurin), diminished expression of p62 or NDP52 increased the number of the clinical AIEC LF82 strain inside epithelial cells. This was associated with increased pro-inflammatory cytokine production. Moreover, p62 or NDP52 directly colocalized with AIEC LF82 and LC3, an autophagy marker. As the NDP52Val248Ala polymorphism has been associated with increased CD susceptibility, we investigated its impact on AIEC control. However, in HeLa cell and under our experimental condition, no effect of this polymorphism neither on AIEC LF82 intracellular number nor on pro-inflammatory cytokine production was observed. Together, our results suggest that p62 and NDP52 act as autophagy receptors for AIEC recognition, controlling AIEC intracellular replication and inflammation.

Abstract Metastatic uveal melanomas are highly resistant to all existing treatments. To address this critical issue, we performed a kinome‐wide CRISPR‐Cas9 knockout screen, which revealed the LKB1‐SIK2 module in restraining uveal melanoma tumorigenesis. Functionally, LKB1 loss enhances proliferation and survival through SIK2 inhibition and upregulation of the sodium/calcium (Na+/Ca2+) exchanger SLC8A1. This signaling cascade promotes increased levels of intracellular calcium and mitochondrial reactive oxygen species, two hallmarks of cancer. We further demonstrate that combination of an SLC8A1 inhibitor and a mitochondria‐targeted antioxidant promotes enhanced cell death efficacy in LKB1‐ and SIK2‐negative uveal melanoma cells compared to control cells. Our study also identified an LKB1‐loss gene signature for the survival prognostic of patients with uveal melanoma that may be also predictive of response to the therapy combination. Our data thus identify not only metabolic vulnerabilities but also new prognostic markers, thereby providing a therapeutic strategy for particular subtypes of metastatic uveal melanoma.

In recent years, due to the large Romanian community present in Italy, the retail of foods coming from Eastern Europe has increased. The most common type of violation detected in these foods consists of incorrect labeling and species-replacement frauds. In this paper, the compliance of labels of 43 ethnic processed food coming from Eastern Europe and commercialized in Italy was evaluated by means of PCR and Sanger sequencing. Our data revealed 33% of non-compliant labels in samples containing swine, ruminants, and avian ingredients. These results demonstrate that PCR can be easily used for the identification of species in highly processed products, proving to be a rapid, effective, and economic method. On the other hand, samples reporting fish as ingredients highlighted the ineffectiveness of the applied sequencing protocol, due to the low informative property of targeted fragments or to the lack of consensus sequences in the case of uncommon species.

Research on elders’ acceptance of virtual technologies is much needed. Here we studied the user experience of elders (N = 10, mean age = 88.2 years) during virtual biking, an exergame where participants pedal on a cycle ergometer and wear a Head-Mounted Display that provides them an immersive experience of a bike ride. We tested the effects of augmented gaze on user experience. Augmented gaze is a condition in which horizontal head turns yield amplified visual shifts, which is assumed to facilitate visual exploration. User experience was measured by asking participants to rate satisfaction, motivation, sense of presence and sense of safety. We found a very good acceptance of virtual biking and no signs of negative effects of augmented gaze. These preliminary observations suggest that augmented gaze may be a viable optimization of elders’ experience with certain virtual reality applications.

The goal of this research was to create an antibacterial formulation from Scinus areira essential oil (EO) that could spread in water. To achieve this, we developed liposomal formulations of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) or DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) that encapsulated the EO. In addition, we utilized the EO as a reducing and stabilizing agent to synthesize silver nanoparticles (AgNPs). The nanoformulations were characterized by determining their size and zeta potential. In the case of liposomal formulations, chemical composition, and encapsulation efficiency were also determined. Furthermore, antimicrobial activity studies against Gram-positive and Gram-negative model bacteria were carried out for both kinds of formulations. The results obtained showed the successful encapsulation of the S. areira EO in multilamellar liposomes of phosphatidylcholine with high efficiency. DPPC liposomes have proven to be a better encapsulation system, retaining more monoterpenes from the EO and therefore presenting antimicrobial activity against S. aureus with an minimal inhibitory concentration (MIC) value of 3 mg/mL of EO. On the other hand, it was also possible to obtain AgNPs by using S. areira EO, which showed antimicrobial activity against S. aureus and E. coli at low concentrations of EO, with MIC values of 6.68 µg/mL and 3.4 µg/mL of silver, respectively. The data obtained will contribute to enhancing the biotechnological value of natural products derived from native plant species in Argentina. This will be achieved through the generation of novel formulations with antibacterial activity and potential bioavailability.

Digital soil mapping (DSM) is commonly conducted using input soil attributes derived from laboratory analyses of geographically referenced samples. Field observations are often abundant and can offer a dense source of soil data that has the potential to enhance DSM predictions. However, they are not widely used due to to concerns about subjectivity and data quality. This study investigates the usefulness of hand-feel soil texture (HFST) data for DSM. We processed HFST data obtained from forest soils in France from two inventory campaigns: (i) HFST determination from systematic 1 km2 grid observations in France utilizing a specialized soil texture triangle, and (ii) HFST observations from soil survey samples, using a different texture triangle. Both sets of HFST data were used as input soil variables, with the same covariates, for predicting topsoil texture In a sizable, forested area through a DSM method. By employing independent sampling and laboratory soil analyses in selected areas, we uncovered measurement bias in one of the datasets. However, intriguingly, these biased observations identified subtle yet highly specific and unexpected patterns of sands in terraces due to alluvial deposits along small rivers. Thus, field soil observations, even if they are biased, should not be dismissed solely based on their overall predictive performance. It is essential to carefully examine predicted maps and covariates to determine whether patterns may have pedological and/or lithological origins and if they are pertinent for enhancing DSM predictions, enhancing soil process understanding, and meeting the requirements of end users. Numerous HFST are available worldwide, these datasets are usually disregarded for DSM. Here we contend that efforts should be put in recovering these data, and their potential for enhancing DSM and deepening our understanding of soil processes.

Recent data showed that prenatal alcohol exposure (PAE) impairs the “placenta–brain” axis controlling fetal brain angiogenesis in human and preclinical models. Placental growth factor (PlGF) has been identified as a proangiogenic messenger between these two organs. CD146, a partner of the VEGFR-1/2 signalosome, is involved in placental angiogenesis and exists as a soluble circulating form. The aim of the present study was to investigate whether placental CD146 may contribute to brain vascular defects described in fetal alcohol spectrum disorder. At a physiological level, quantitative reverse transcription polymerase chain reaction experiments performed in human placenta showed that CD146 is expressed in developing villi and that membrane and soluble forms of CD146 are differentially expressed from the first trimester to term. In the mouse placenta, a similar expression pattern of CD146 was found. CD146 immunoreactivity was detected in the labyrinth zone and colocalized with CD31-positive endothelial cells. Significant amounts of soluble CD146 were quantified by ELISA in fetal blood, and the levels decreased after birth. In the fetal brain, the membrane form of CD146 was the majority and colocalized with microvessels. At a pathophysiological level, PAE induced marked dysregulation of CD146 expression. The soluble form of CD146 decreased in both placenta and fetal blood, whereas it increased in the fetal brain. Similarly, the expression of several members of the CD146 signalosome, such as VEGFR2 and PSEN, was differentially impaired between the two organs by PAE. At a functional level, targeted repression of placental CD146 by in utero electroporation (IUE) of CRISPR/Cas9 lentiviral plasmids resulted in (i) a decrease in cortical vessel density, (ii) a loss of radial vascular organization, and (iii) a reduced density of oligodendrocytes. Statistical analysis showed that the more the vasculature was impaired, the more the cortical oligodendrocyte density was reduced. Altogether, these data support that placental CD146 contributes to the proangiogenic “placenta–brain” axis and that placental CD146 dysfunction contributes to the cortical oligo-vascular development. Soluble CD146 would represent a promising placental biomarker candidate representative of alcohol-induced neurovascular defects in neonates, as recently suggested by PlGF (patents WO2016207253 and WO2018100143).

Radionuclide contamination is a serious health issue caused by nuclear experiments and plant accidents, as seen for the Chernobyl and Fukushima nuclear plants. Italy has been especially interested in northwestern alpine regions, as have several other nations. The aim of this work was to indagate 134Cs and 137Cs contamination in wild boars, which were considered bioindicators sampled in the Chisone/Germanasca Valley and the Pellice Valley districts (Piedmont, Italy) in two hunting seasons (2014 and 2016). In the 2014 season, only the livers of the animals (n = 48) were sampled, whereas in 2016, five different anatomical sampling sites were sampled for each animal (n = 16). The analyses were conducted in an accredited laboratory (Agenzia Regionale per la Protezione dell'Ambiente-ARPA) by the aid of an HPGe detector (Ortec) with a relative efficiency of 50%. In general, the contamination levels registered in 2014 were under the detection limit for 134Cs and low for 137Cs (Chisone/Germanasca valley: min: 0.0, max: 23.9 median 11.0 Bq/kg vs Pellice valley: min 0, max: 31.7, median: 9.6 Bq/kg) and no health concern can be supposed. In the first-year samples, the liver showed a negative correlation between age and contamination level. In the second year of sampling, low levels were confirmed (min: 3.1 Bq/kg, max: 113.3; median 17.7 Bq/kg). Multiple sampling from the same animal showed that the diaphragm (median = 27.7 Bq/kg) kidney (27.4) and tongue (27.6) were more contaminated than the liver (17.7) and spleen (15.3). Moreover, a linear mixed model revealed a negative organ-by-age interaction, meaning that interorgan differences in contamination level were greater in younger (5-11 months) than in older (18-36 months) animals. Different feeding habits can be the explanation. Our paper shows that muscle sites (diaphragm and tongue) can be useful for radionuclide pollution surveillance in wild boar populations and that younger animals show more interorgan variability in contamination levels than older animals. More investigations are needed to confirm this correlation and to fulfill the request for more data to achieve better risk assessment.

Background We have previously reported that male mice exposed to maternal separation and early weaning (MSEW), a model of early life stress, show sympathetic activation and increased blood pressure in response to a chronic high‐fat diet. The goal of this study was to investigate the contribution of the renin–angiotensin–aldosterone system to the mechanism by which MSEW increases blood pressure and vasomotor sympathetic tone in obese male mice. Methods and Results Mice were exposed to MSEW during postnatal life. Undisturbed litters served as controls. At weaning, both control and MSEW offspring were placed on a low‐fat diet or a high‐fat diet for 20 weeks. Angiotensin peptides in serum were similar in control and MSEW mice regardless of the diet. However, a high‐fat diet induced a similar increase in angiotensinogen levels in serum, renal cortex, liver, and fat in both control and MSEW mice. No evidence of renin–angiotensin system activation was found in adipose tissue and renal cortex. After chronic treatment with enalapril (2.5 mg/kg per day, drinking water, 7 days), an angiotensin‐converting enzyme inhibitor that does not cross the blood–brain barrier, induced a similar reduction in blood pressure in both groups, while the vasomotor sympathetic tone remained increased in obese MSEW mice. In addition, acute boluses of angiotensin II (1, 10, 50 μg/kg s.c.) exerted a similar pressor response in MSEW and control mice before and after enalapril treatment. Conclusions Overall, elevated blood pressure and vasomotor sympathetic tone remained exacerbated in MSEW mice compared with controls after the peripheral inhibition of angiotensin‐converting enzyme, suggesting a mechanism independent of angiotensin II.

Introduction: There are no clear indications for the best choice of anti-seizure medications to control brain tumor related epilepsy. In vitro studies have shown an antitumoral effect of Levetiracetam and Lacosamide on glioblastoma IDH-wild type. Research question: This study investigates whether the use of levetiracetam and/or lacosamide impacts survival rates. The secondary aim was to evaluate the efficacy of both ASMs in controlling seizures. Materials and methods: In this observational retrospective single-cohort study, patients underwent chemoradiation protocol after GBM surgery. They were grouped as follows: (1) use of levetiracetam, (2) use of lacosamide, (3) simultaneous use of levetiracetam and lacosamide, (4) no ASM usage. Survival curves were plotted using the Kaplan-Meier method coupled with a log-rank test for difference assesments. To evaluate the pharmacological efficacy of post-operative seizure control, a negative binomial regression was conducted. Results: The study included 272 patients, 174 of which underwent adjuvant chemoradiation treatment. Patients without ASM therapy had a non-significant longer median OS (compared to the other groups (log-rank = 0.37). The IRR of seizure relapse was 2.57 (p = 0.007) times higher in lacosamide users, and MGMT promoter methylation demonstrated a protective effect against postoperative seizure onset (p = 0.05), regardless of the aforementioned confounding factors. Discussion and conclusions: In patients diagnosed with GBM IDH-WT undergoing chemoradiation therapy, the use of levetiracetam or lacosamide for controlling BTRE does not seem to modify survival. Lacosamide users exhibited a higher IRR of postoperative seizures compared to levetiracetam users, and MGMT promoter methylation appears to be a protective factor.

ABSTRACTColorectal cancer (CRC) patients are frequently colonized by colibactin-producing Escherichia coli (CoPEC) (>40%), which enhances tumorigenesis in mouse models of CRC. We observed that 50% of CoPEC also contains the cnf1 gene, which encodes cytotoxic necrotizing factor-1 (CNF1), an enhancer of the eukaryotic cell cycle. The impact of its co-occurrence with colibactin (Clb) has not yet been investigated. We evaluated the impact of CNF1 on colorectal tumorigenesis using human colonic epithelial HT-29 cells and CRC-susceptible ApcMin/+ mice inoculated with the CoPEC 21F8 clinical strain (Clb+Cnf+) or 21F8 isogenic mutants (Clb+Cnf-, Clb-Cnf+ and Clb-Cnf-). Infection with the Clb+Cnf- strain induced higher levels of inflammatory cytokines and senescence markers both in vitro and in vivo compared to those induced by infection with the Clb+Cnf+ strain. In contrast, the Clb+Cnf- and Clb+Cnf+ strains generated similar levels of DNA damage in HT-29 cells and in colonic murine tissues. Furthermore, the ApcMin/+ mice inoculated with the Clb+Cnf- strain developed significantly more tumors than the mice inoculated with the Clb+Cnf+ strain or the isogenic mutants, and the composition of their microbiota was changed. Finally, rectal administration of the CNF1 protein in ApcMin/+ mice inoculated with the Clb+Cnf- strain significantly decreased tumorigenesis and inflammation. Overall, this study provides evidence that CNF1 decreases the carcinogenic effects of CoPEC in ApcMin/+ mice by decreasing CoPEC-induced cellular senescence and inflammation.

Abstract Background Serum anti-Mullerian hormone (AMH) is currently considered the best marker of ovarian reserve and of ovarian responsiveness to gonadotropins in in-vitro fertilization (IVF). AMH assay, however, is not available in all IVF Units and is quite expensive, a reason that limits its use in developing countries. The aim of this study is to assess whether the "ovarian sensitivity index" precisely reflects AMH so that this index may be used as a surrogate for AMH in prediction of ovarian response during an IVF cycle. Methods AMH serum levels were measured in 61 patients undergoing IVF with a "long" stimulation protocol including the GnRH agonist buserelin and recombinant follicle-stimulating hormone (rFSH). Patients were divided into four subgroups according to the percentile of serum AMH and their ovarian stimulation was prospectively followed. Ovarian sensitivity index (OSI) was calculated dividing the total administered FSH dose by the number of retrieved oocytes. Results AMH and OSI show a highly significant negative correlation (r = -0.67; p = 0.0001) that is stronger than the one between AMH and the total number of retrieved oocytes and than the one between AMH and the total FSH dose. Conclusions OSI reflects quite satisfactory the AMH level and may be proposed as a surrogate of AMH assay in predicting ovarian responsiveness to FSH in IVF. Being very easy to calculate and costless, its use could be proposed where AMH measurement is not available or in developing countries where limiting costs is of primary importance.

Abstract Objective The aim of this prospective cross sectional study was to evaluate the cranial structure and condylar asymmetry of adult patients with rheumatoid arthritis (RA) diagnosed after 25 years of age compared to a healthy adult control group. Methods Eighteen adult patients (57.4 ± 11.4 years) with RA were compared with a control group. Cephalometric analysis and the Habets method for the calculation of the condylar asymmetry were used. The main cephalometric data investigated were focused on the diagnosis of hyperdivergent cranial structure (NSL/ML, NL/ML), backwards rotation of the mandible (Fh/ML), short vertical ramus (Ar:Go), steep mandibular plane (ML/Oc). Results The cephalometric data considered were not significantly different in the RA vs controls except for the steepness of the occlusal plane (NL/Oc), which was steeper in the patients group (P