Riboflavin-LSD1 axis participates in the in vivo tumor-associated macrophage morphology in human colorectal liver metastases.

Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME). In colorectal liver metastasis (CLM), TAM morphology correlates with prognosis, with smaller TAMs (S-TAMs) conferring a more favorable prognosis than larger TAMs (L-TAMs). However, the metabolic profile of in vivo human TAM populations remains unknown. Multiparametric flow cytometry was used to freshly isolate S- and L-TAMs from surgically resected CLM patients (n = 14S-, 14L-TAMs). Mass spectrometry-based metabolomics analyses were implemented for the metabolic characterization of TAM populations. Gene expression analysis and protein activity were used to support the biochemical effects of the enzyme-substrate link between riboflavin and (lysine-specific demethylase 1A, LSD1) with TAM morphologies. L-TAMs were characterized by a positive correlation and a strong association between riboflavin and TAM morphologies. Riboflavin in both L-TAMs and in-vitro M2 polarized macrophages modulates LSD1 protein expression and activity. The inflammatory stimuli promoted by TNFα induced the increased expression of riboflavin transporter SLC52A3 and LSD1 in M2 macrophages. The modulation of the riboflavin-LSD1 axis represents a potential target for reprogramming TAM subtypes, paving the way for promising anti-tumor therapeutic strategies.

Stress management: how does the academic staff cope with it? a cross-sectional study at the university of Udine.

BACKGROUND: Increasing work-related stress in academia can have an impact on physical and mental health. The aim of this study was to analyse the coping strategies of staff employed at the University of Udine and to verify whether sociodemographic data, professional position, and the presence of anxiety or depression symptoms are related to the use of different coping strategies. METHODS: We conducted a cross-sectional study between June and December 2020 using the Brief COPE questionnaire. We correlated coping strategies with professional position, sociodemographic data, and the presence of anxiety or depressive symptoms measured with the Patient Health Questionnaire-9 and the General Anxiety Disorder-7. RESULTS: A total of 366 people participated in the study, including 109 junior academics, 146 senior academics, and 111 administrative staff (response rate 23.6%). The three most frequently used coping strategies in terms of approach coping style were planning (6.77 ± 1.41), active coping (6.58 ± 1.45) and acceptance (6.23 ± 1.44). Women were more likely than men to report using approach and avoidant coping strategies (p < 0.001). Positive reframing and religion were most commonly used by administrative staff (p < 0.05), in contrast to junior academics, who were more likely to use substances and self-blame (p < 0.05). Anxiety was found to correlate with self-blame (OR 1.94) as a coping strategy, while depression was associated with venting (OR 2.83), self-blame (OR 3.27), and humor (OR 3.02). CONCLUSION: Identifying profiles of coping strategies can help higher education institutions to implement support strategies for the academic community, ultimately promoting healthier lives and more effective teaching and research. Our study has shown that women and junior academics among staff at the Udine University would benefit from a tailored health promotion intervention that encourages the use of approach coping styles to reduce their risk of developing anxiety and depressive symptoms.

Are adverse events related to the completeness of clinical records? Results from a retrospective records review using the Global Trigger Tool.

Clinical record (CR) is a tool for recording details about the patient and the most commonly used source of information for detecting adverse events (AEs). Its completeness is an indicator of the quality of care provided and may provide clues for improving professional practice. The primary aim of this study was to estimate the prevalence of AEs. The secondary aims were to determine the completeness of CRs and to examine the relationship between the two variables. We retrospectively reviewed randomly selected CRs of patients discharged from the Academic Hospital of Udine (Italy) in the departments of general surgery, internal medicine, and obstetrics between July and September 2020. Evaluation was performed using the Global Trigger Tool and a checklist to evaluate the completeness of CRs. The relationship between the occurrence of AEs and the completeness of CRs was analyzed using nonparametric tests. A binomial logistic regression analysis was also performed. We reviewed 291 CRs and identified 368 triggers and 56 AEs. Among them, 16.2% of hospitalizations were affected by at least one AE, with a higher percentage in general surgery. The most common AEs were surgical injuries (42.6%; 24) and care related (26.8%; 15). A significant positive correlation was found between the length of hospital stay and the number of AEs. The average completeness of CRs was 72.9% and was lower in general surgery. The decrease in CR completeness correlated with the increase in the total number of AEs (R = -0.14; P = .017), although this was not confirmed by regression analysis by individual departments. Our results seem to suggest that completeness of CRs may benefit patient safety, so ongoing education and involvement of health professionals are needed to maintain professional adherence to CRs.

SARS-CoV-2 transmission by asymptomatic healthcare workers positive to screening swab: an Italian study.

BACKGROUND: SARS-CoV-2 spreads primarily through respiratory droplets of symptomatic individuals. With respect to asymptomatic individuals, there are conflicting results in the literature and a lack of studies specifically examining transmission in healthcare settings. METHODS: The aim of this retrospective study, conducted in a northeastern Italian region, was to estimate the contagiousness of asymptomatic healthcare workers (HCWs) who tested positive for SARS-CoV-2. Asymptomatic HCWs who tested positive for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (rRT-PCR) at a regular screening nasopharyngeal or oropharyngeal swab between 1 February 2020 and 15 September 2020 were considered index cases. Contacts who were at high risk of infection and had follow-up swabs were included. Contacts were considered infected if they had a positive follow-up swab and/or symptoms associated with COVID-19 confirmed by a positive test within 14 days of exposure. Information was taken from records previously collected to identify contacts. Infectivity was estimated using the attack rate (AR) with a 95% confidence interval (95% CI). RESULTS: Thirty-eight asymptomatic HCWs who were positive at the screening swab and 778 contacts were identified. Contacts included 63.8% of colleagues, 25.6% of patients, 7.7% of family members and 3.0% of other contacts. Seven contacts tested positive for SARS-CoV-2 (AR: 0.91%, 95% CI: 0.89-0.93). Five of them were family members (AR: 8.3%), one was a colleague (0.2%) and one was a contact of other type (4.2%). CONCLUSIONS: Viral spread by asymptomatic HCWs was less than in other settings. Identification of risk factors for transmission and reliable indicators of infectivity would be important to prioritize preventive measures.

Gaps and Future Challenges of Italian Apps for Pregnancy and Postnatal Care: Systematic Search on App Stores.

BACKGROUND: Despite the availability of thousands of health apps worldwide, when considering those addressing children's first 1000 days of life, most apps fail to consider the continuity between the prenatal and postnatal stages, and their joint impact on maternal and child health. The reliability, quality, and effectiveness of these apps are largely unknown, and the provided content seems questionable in terms of completeness, updating, and trustworthiness. OBJECTIVE: This study evaluates available Italian pregnancy and postnatal care apps to highlight the main gaps to be overcome and the resulting future challenges to be met in this mobile health-related field. METHODS: A systematic search was conducted on the Apple App Store and Google Play Store, and basic information was collected for all identified apps. After deduplication and further selection based on the exclusion criteria, an in-depth analysis of each app was performed by two researchers independently. A 71-item six-domain questionnaire about the desirable features of apps was used to assess information, functionalities, and technical features, while the Mobile Application Rating Scale (MARS) was employed for app quality evaluation. RESULTS: From an initial sample of 684 apps, 22 were deeply analyzed. Most apps did not fulfill the expectations, as just one achieved 50% of all desirable aspects. Postnatal care and counselling for both the mother and child was the least accomplished domain. Moreover, the quality of app information was generally rated more negatively than the quality of their functionality and esthetic features. The lacking aspects were information about methods for postpartum family planning and birth spacing (1/22, 5%) and immunization (2/22, 9%). CONCLUSIONS: The identified gaps could serve as a basis for designing and implementing increasingly high-quality, targeted, and effective apps for pregnancy and postnatal health care, which provide comprehensive, reliable, and evidence-based information, as well as appropriate esthetic and functional characteristics, with relevant implications in terms of maternal and newborn health prevention and promotion.

Fattori che influenzano lo screening nutrizionale nei pazienti ricoverati in ospedali per acuti: un'indagine di prevalenza regionale (2017).

BACKGROUND: the prevalence of malnutrition among hospitalized patients varies between 19.8% and 50%, with approximately 31% of all hospital patients considered malnourished or at nutritional risk, both in European and in Italian hospitals. Nutritional screening is necessary to identify nutrition-related problems, but it is not largely performed at the admission or during hospitalization. OBJECTIVES: to identify factors associated with the probability of performing nutritional screening during hospitalization and to describe BMI among inpatients in acute facilities of Friuli Venezia Giulia (FVG) Region (Northern Italy). DESIGN: point prevalence survey. SETTING AND PARTICIPANTS: the study was conducted in all the 18 hospitals of the FVG regional healthcare system; 58 trained surveyors collected data from 2nd to 30th October 2017. MAIN OUTCOME MEASURES: weight and height, presence of parenteral and enteral nutrition data of 2,553 patients were collected. RESULTS: BMI was determinable for 77.2% of people under study. Negative predictors for BMI screening were: spoke hospital (p<0.001), age over 65 years (p=0.005), both 'ultimately fatal' (p<0.001) and 'rapidly fatal' (p<0.001) McCabe score, presence of minimally invasive surgery (p=0.02); major surgery was a positive predictor (p<0.001). Prevalence of parenteral and enteral nutrition prescription was 4.0% and 3.6%, respectively; statistical differences were found according to care units and McCabe score (p<0.001). CONCLUSIONS: globally, BMI for inpatients in the surveyed hospitals is often assessed, but more investigations are needed to understand the reasons why the reported differences exist.

Rapid automated diagnosis of primary hepatic tumour by mass spectrometry and artificial intelligence.

BACKGROUND AND AIMS: Complete surgical resection with negative margin is one of the pillars in treatment of liver tumours. However, current techniques for intra-operative assessment of tumour resection margins are time-consuming and empirical. Mass spectrometry (MS) combined with artificial intelligence (AI) is useful for classifying tissues and provides valuable prognostic information. The aim of this study was to develop a MS-based system for rapid and objective liver cancer identification and classification. METHODS: A large dataset derived from 222 patients with hepatocellular carcinoma (HCC, 117 tumours and 105 non-tumours) and 96 patients with mass-forming cholangiocarcinoma (MFCCC, 50 tumours and 46 non-tumours) were analysed by Probe Electrospray Ionization (PESI) MS. AI by means of support vector machine (SVM) and random forest (RF) algorithms was employed. For each classifier, sensitivity, specificity and accuracy were calculated. RESULTS: The overall diagnostic accuracy exceeded 94% in both the AI algorithms. For identification of HCC vs non-tumour tissue, RF was the best, with 98.2% accuracy, 97.4% sensitivity and 99% specificity. For MFCCC vs non-tumour tissue, both algorithms gave 99.0% accuracy, 98% sensitivity and 100% specificity. CONCLUSIONS: The herein reported MS-based system, combined with AI, permits liver cancer identification with high accuracy. Its bench-top size, minimal sample preparation and short working time are the main advantages. From diagnostics to therapeutics, it has the potential to influence the decision-making process in real-time with the ultimate aim of improving cancer patient cure.

Absences from work among healthcare workers: are they related to influenza shot adherence?

BACKGROUND: The coverage for influenza vaccination among healthcare workers (HCWs) is inadequate in many countries despite strong recommendations; is there evidence that influenza vaccination is effective in preventing absenteeism? Aim of the study is to evaluate the influenza vaccination coverage and its effects on absences from work among HCWs of an Italian academic healthcare trust during the 2017-2018 influenza season. METHODS: We performed a retrospective study to identify predictive characteristics for vaccination, and a retrospective cohort study to establish the effect of vaccination on absences among the vaccinated and non-vaccinated cohorts between December 2017 and May 2018. Overall absence rates over the whole observation period and sub-rates over 14-days intervals were calculated; then comparison between the two groups were conducted applying Chi-square test. RESULTS: Influenza vaccination coverage among 4419 HCWs was 14.5%. Age, university degree, medical care area and physician profile were positively associated with vaccine uptake. Globally during influenza season non-vaccinated HCWs lost 2.47/100 person-days of work compared to 1.92/100 person-days of work among vaccinated HCWs (p < 0.001); significant differences in absences rates resulted when focusing on the influenza epidemic peak. CONCLUSIONS: Factors predicting influenza uptake among HCWs were male sex, working within medical care area and being a physician. Absenteeism among HCWs resulted to be negatively correlated with vaccination against influenza. These findings add evidence to the urgent need to implement better influenza vaccination strategies towards HCWs to tackle vaccine hesitancy among professionals.

Correlation Between eHealth Literacy and Health Literacy Using the eHealth Literacy Scale and Real-Life Experiences in the Health Sector as a Proxy Measure of Functional Health Literacy: Cross-Sectional Web-Based Survey.

BACKGROUND: The eHealth Literacy Scale (eHEALS) is a tool for the self-assessment of perceived comfort and skills in using the internet as a source for health-related information. Although evidence exists of the reliability and construct and structural validity of the scale, there is a lack of evidence in relation to what is proposed by Norman and Skinner in their theoretical lily model of eHealth literacy; in particular it is not clear whether having a higher level of health literacy can positively influence electronic health (eHealth) literacy as measured by the eHEALS. OBJECTIVE: Our study aim was to assess whether real-life experiences from studying or working in the health field, as a proxy of higher functional health literacy, correlate with self-referred eHealth literacy as measured by the eHEALS. METHODS: A Web-based survey was conducted among adults living in Northeast Italy using an Italian version of the eHEALS (IT-eHEALS). In order to be able to measure the effect of higher functional health literacy on eHealth literacy, we divided our sample into two groups, respectively characterized by studying or working experience in the health sector and by lack thereof. Mean differences between eHEALS were calculated using t test and effect size evaluated using Cohen d. To ensure the validity of the IT-eHEALS, we evaluated its psychometric properties (internal consistency and dimensionality) and construct validity (by evaluating its correlation with respondents age, gender, educational attainment, self-rated health, use of internet for health-related purposes, and working status). RESULTS: A total of 868 respondents that completed the IT-eHEALS were included for analysis, of which 259 had working or studying experience in the health field. Mean (SD) eHEALS total score was 28.2 (6.2) for the whole sample, with statistically significant differences (P<.001) between the two groups, with the higher health literate group scoring significantly better (31.9 (5.9) vs 26.7 (5.6), respectively), with a standardized mean difference (Cohen d) of 0.9. Interestingly, we found a weak, yet significant, correlation between eHealth literacy and respondent characteristics for the higher health literate group only, as measured by positive Spearman correlation coefficients for age (0.11, P=.001), educational attainment (0.19, P=.002) and self-rated health (0.14, P=.024). Also, in line with current literature, correlation of eHEALS score with frequency of internet use for health-related purposes was significant for both groups (0.32, P<.001 and 0.15, P<.001 for higher and lower health literacy group, respectively). In our study we could not find any difference related to gender, while a significant difference for working status was only present when considering the sample as a whole (P=.03). CONCLUSIONS: Our study demonstrates a sizeable effect of higher levels of functional health literacy on the eHEALS score, corroborating what was initially proposed by Norman and Skinner in the lily model of eHealth literacy.

Protection of Brain Injury by Amniotic Mesenchymal Stromal Cell-Secreted Metabolites.

OBJECTIVES: To define the features of human amniotic mesenchymal stromal cell secretome and its protective properties in experimental models of acute brain injury. DESIGN: Prospective experimental study. SETTING: Laboratory research. SUBJECTS: C57Bl/6 mice. INTERVENTIONS: Mice subjected to sham or traumatic brain injury by controlled cortical impact received human amniotic mesenchymal stromal cells or phosphate-buffered saline infused intracerebroventricularly or intravenously 24 hours after injury. Organotypic cortical brain slices exposed to ischemic injury by oxygen-glucose deprivation were treated with human amniotic mesenchymal stromal cells or with their secretome (conditioned medium) in a transwell system. MEASUREMENTS AND MAIN RESULTS: Traumatic brain injured mice receiving human amniotic mesenchymal stromal cells intravenously or intracerebroventricularly showed early and lasting functional and anatomical brain protection. cortical slices injured by oxigen-glucose deprivation and treated with human amniotic mesenchymal stromal cells or conditioned medium showed comparable protective effects (neuronal rescue, promotion of M2 microglia polarization, induction of trophic factors) indicating that the exposure of human amniotic mesenchymal stromal cells to the injured tissue is not necessary for the release of bioactive factors. Using sequential size-exclusion and gel-filtration chromatography, we identified a conditioned medium subfraction, which specifically displays these highly protective properties and we found that this fraction was rich in bioactive molecules with molecular weight smaller than 700 Da. Quantitative RNA analysis and mass spectrometry-based peptidomics showed that the active factors are not proteins or RNAs. The metabolomic profiling of six metabolic classes identified a list of molecules whose abundance was selectively elevated in the active conditioned medium fraction. CONCLUSIONS: Human amniotic mesenchymal stromal cell-secreted factors protect the brain after acute injury. Importantly, a fraction rich in metabolites, and containing neither proteic nor ribonucleic molecules was protective. This study indicates the profiling of protective factors that could be useful in cell-free therapeutic approaches for acute brain injury.

Vaccination: Adherence and Hesitancy among Pregnant Women for COVID-19, Pertussis, and Influenza Vaccines.

In the realm of antenatal care, vaccinations serve as a cornerstone, crucial for safeguarding the health of both the mother and the fetus, while also extending protection to the newborn against communicable diseases. Nevertheless, vaccine adherence among pregnant women remains very low. The aim of our study was to evaluate the uptake of vaccines (influence, pertussis, and COVID-19) among women during pregnancy and to understand pregnant women's knowledge of vaccines and the diseases they protect against. The purpose was to investigate the reasons why pregnant women chose not to be vaccinated and to develop effective strategies for informing them about the importance of vaccination for both maternal and fetal safety. A prospective observational study was conducted in the Department of Obstetrics and Gynaecology, "Ospedale Santa Maria della Misericordia" in Udine, from 1 December 2021 to 30 June 2022. During this period, a self-completed paper questionnaire was administered to women at the end of pregnancy or during the puerperium. A total of 161 questionnaires were collected. Higher educational level was found to be significantly associated with influenza vaccination uptake (p = 0.037, OR = 2.18, 95% CI 1.05-4.51). Similarly, for pertussis vaccination, adherence was mainly associated with higher educational level (p = 0.014, OR = 2.83, 95% CI 1.24-6.47), but also with Italian nationality (p = 0.003, OR = 3.36, 95% CI 1.56-8.43) and pregnancy attended by a midwife or private gynecologist (p = 0.028, OR = 0.39, 95% CI 0.17-0.90). Regarding the COVID-19 vaccine, the only factor positively influencing uptake was Italian nationality (p = 0.044, OR = 2.66, 95% CI 1.03-6.91). Women's fear that vaccines would endanger the fetus appeared to be the most important reason for refusing vaccinations. Simultaneously, patients also exhibited a desire to receive more information about maternal vaccination, particularly from their general physician or gynecologist. For this reason, it is imperative to enhance maternal vaccination counselling, making it a routine step in prenatal care from the first antenatal visit until the postpartum period.

Sexually transmitted infections and the HPV-related burden: evolution of Italian epidemiology and policy.

Sexually transmitted infections (STIs) are a major public health problem worldwide, with a high prevalence between the ages of 15 and 25 in most Western countries. High notification rates of chlamydia, gonorrhea, and syphilis are reported in the WHO European Region, with differences between countries. In Italy, the total number of STIs alerts increased by 18% from 2020 to 2021. HPV is the most common sexually transmitted infection; globally one in seven women is infected by this virus, and certain sexual behaviors are important risk factors for HPV-related cancers, particularly cervical cancer (CC), anogenital cancers and cancers of the head and neck. The burden of CC is relevant worldwide, in particular in Europe CC is the third leading cause of cancer-related deaths in women aged 15-44. This HPV-related tumor is preventable through a combined strategy of vaccination and screening for precursor lesions. In Italy, the coverage of organized screening varies from region to region and the average HPV vaccination rate is still far from the expected optimal threshold of 95% at the age of 12. To address the challenges of health promotion and HPV prevention, priority actions are needed such as: promoting education and information at every level, from schools to healthcare professionals. In Italy, education of adolescents on sexual and reproductive health, still remains critical, regionally inhomogeneous and much lower than in other European countries. Equitable measures need to be taken, and schools are an important place for health promotion activities.

The Role of Pharmacists in Counteracting Vaccine Hesitancy: Effectiveness of the 2019 Carnia Project in Improving Adherence to Influenza Vaccination among Target Population.

Vaccine hesitancy has been included among the top ten threats to global health by the World Health Organization. Pharmacists can play a pivotal role in removing the individual barrier to vaccination, because of the relationship of trust they have with citizens and their ease of access. The aim of this study was to examine the impact of a pharmacy-based intervention to support the 2019 influenza vaccination campaign conducted in the Carnia district through one-to-one counseling. We analyzed data collected by pharmacists between 22 October 2019 and 20 January 2020, and trends in vaccination adherence in the context of the Local Health Authority and the entire province of Udine since 2016. The results showed that 77.2% of people who had not received an influenza vaccination in the previous year changed their minds about vaccination after receiving counseling. The pharmacy-based intervention improved influenza vaccination adherence in the target district (+13.4%), even when compared to the neighboring district of Gemona or considering the data in the broader local and provincial context, and this effect was particularly pronounced among those aged 65 to 74 years (p < 0.01). Considering these findings, pharmacies should be more effectively involved in the provision of public health services aimed at improving accessibility, timeliness, and equity.

Transcriptomic and metabolomic changes might predict frailty in SAMP8 mice.

Frailty is a geriatric, multi-dimensional syndrome that reflects multisystem physiological change and is a transversal measure of reduced resilience to negative events. It is characterized by weakness, frequent falls, cognitive decline, increased hospitalization and dead and represents a risk factor for the development of Alzheimer's disease (AD). The fact that frailty is recognized as a reversible condition encourages the identification of earlier biomarkers to timely predict and prevent its occurrence. SAMP8 (Senescence-Accelerated Mouse Prone-8) mice represent the most appropriate preclinical model to this aim and were used in this study to carry transcriptional and metabolic analyses in the brain and plasma, respectively, upon a characterization at cognitive, motor, structural, and neuropathological level at 2.5, 6, and 9 months of age. At 2.5 months, SAMP8 mice started displaying memory deficits, muscle weakness, and motor impairment. Functional alterations were associated with a neurodevelopmental deficiency associated with reduced neuronal density and glial cell loss. Through transcriptomics, we identified specific genetic signatures well distinguishing SAMP8 mice at 6 months, whereas plasma metabolomics allowed to segregate SAMP8 mice from SAMR1 already at 2.5 months of age by detecting constitutively lower levels of acylcarnitines and lipids in SAMP8 at all ages investigated correlating with functional deficits and neuropathological signs. Our findings suggest that specific genetic alterations at central level, as well as metabolomic changes in plasma, might allow to early assess a frail condition leading to dementia development, which paves the foundation for future investigation in a clinical setting.

Applying the Participatory Slow Design Approach to a mHealth Application for Family Caregivers in Pediatric Ear, Nose, and Throat Surgery.

Pediatric ear, nose, and throat (ENT) surgery is very common, and its outcomes may improve with family education. In this regard, mobile health (mHealth) applications (apps), which are on the rise due to digital transformation, can be beneficial in healthcare. This study outlines the user-centered design and development of a mHealth app (version 5.15.0) to support family caregivers during the perioperative process of pediatric ENT surgery. Conducted over two years in an Italian maternal and child health hospital (January 2020-May 2022), the study employed a participatory design method based on the Information System Research (ISR) framework and guided by the principles of Slow Medicine. Utilizing the Relevance, Rigor, and Design cycles of the ISR framework, the mHealth app's content, functionalities, and technical features were defined and developed. A committee of fifteen experts guided the process with input from 25 family caregivers and 24 healthcare providers enrolled in the study. The mHealth app content was structured around five crucial educational moments characterizing the ENT perioperative period, providing evidence-based information on surgical procedures, strategies for preparing children for hospitalization and surgery, pain management, and post-discharge care. The mHealth app featured a function that sends customized notifications to guide caregivers at specific perioperative stages. The development of mHealth apps by implementing a rigorous, participatory, and Slow design process can foster accessible and family-centered information and care in the field of maternal and child health and beyond.

Integrating metabolic profiling of pancreatic juice with transcriptomic analysis of pancreatic cancer tissue identifies distinct clinical subgroups.

Introduction: Metabolic reprogramming is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC). A pancreatic juice (PJ) metabolic signature has been reported to be prognostic of oncological outcome for PDAC. Integration of PJ profiling with transcriptomic and spatial characterization of the tumor microenvironment would help in identifying PDACs with peculiar vulnerabilities. Methods: We performed a transcriptomic analysis of 26 PDAC samples grouped into 3 metabolic clusters (M_CL) according to their PJ metabolic profile. We analyzed molecular subtypes and transcriptional differences. Validation was performed by multidimensional imaging on tumor slides. Results: Pancreatic juice metabolic profiling was associated with PDAC transcriptomic molecular subtypes (p=0.004). Tumors identified as M_CL1 exhibited a non-squamous molecular phenotype and demonstrated longer survival. Enrichment analysis revealed the upregulation of immune genes and pathways in M_CL1 samples compared to M_CL2, the group with worse prognosis, a difference confirmed by immunofluorescence on tissue slides. Enrichment analysis of 39 immune signatures by xCell confirmed decreased immune signatures in M_CL2 compared to M_CL1 and allowed a stratification of patients associated with longer survival. Discussion: PJ metabolic fingerprints reflect PDAC molecular subtypes and the immune microenvironment, confirming PJ as a promising source of biomarkers for personalized therapy.

Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells.

MR1T cells are a recently found class of T cells that recognize antigens presented by the major histocompatibility complex-I-related molecule MR1 in the absence of microbial infection. The nature of the self-antigens that stimulate MR1T cells remains unclear, hampering our understanding of their physiological role and therapeutic potential. By combining genetic, pharmacological, and biochemical approaches, we found that carbonyl stress and changes in nucleobase metabolism in target cells promote MR1T cell activation. Stimulatory compounds formed by carbonyl adducts of nucleobases were detected within MR1 molecules produced by tumor cells, and their abundance and antigenicity were enhanced by drugs that induce carbonyl accumulation. Our data reveal carbonyl-nucleobase adducts as MR1T cell antigens. Recognizing cells under carbonyl stress allows MR1T cells to monitor cellular metabolic changes with physiological and therapeutic implications.

Inhibitory effect of natural anti-inflammatory compounds on cytokines released by chronic venous disease patient-derived endothelial cells.

Large vein endothelium plays important roles in clinical diseases such as chronic venous disease (CVD) and thrombosis; thus to characterize CVD vein endothelial cells (VEC) has a strategic role in identifying specific therapeutic targets. On these bases we evaluated the effect of the natural anti-inflammatory compounds α-Lipoic acid and Ginkgoselect phytosome on cytokines/chemokines released by CVD patient-derived VEC. For this purpose, we characterized the levels of a panel of cytokines/chemokines (n = 31) in CVD patients' plasma compared to healthy controls and their release by VEC purified from the same patients, in unstimulated and TNF-α stimulated conditions. Among the cytokines/chemokines released by VEC, which recapitulated the systemic profile (IL-8, TNF-α, GM-CSF, INF- α2, G-CSF, MIP-1ß, VEGF, EGF, Eotaxin, MCP-1, CXCL10, PDGF, and RANTES), we identified those targeted by ex vivo treatment with α-Lipoic acid and/or Ginkgoselect phytosome (GM-CSF, G-CSF, CXCL10, PDGF, and RANTES). Finally, by investigating the intracellular pathways involved in promoting the VEC release of cytokines/chemokines, which are targeted by natural anti-inflammatory compounds, we documented that αLipoic acid significantly counteracted TNF-α-induced NF-κB and p38/MAPK activation while the effects of Ginkgo biloba appeared to be predominantly mediated by Akt. Our data provide new insights into the molecular mechanisms of CVD pathogenesis, highlighting new potential therapeutic targets.

Psychological impact of COVID-19 on healthcare leaders: a cross-sectional survey in Friuli-Venezia Giulia, Italy.

INTRODUCTION: Although several studies highlighted the psychological burden of 2019 coronavirus disease (COVID-19) pandemic, no data are available regarding professionals leading healthcare organisations. This study aims to assess the psychological impact of COVID-19 on healthcare leaders (HeLs), along with the leadership skills and coping strategies needed for successful leadership. METHODS: A cross-sectional survey was conducted in Friuli-Venezia Giulia (Italy) between October and November 2020. We assessed the presence of depressive symptoms (DS), anxiety symptoms (AS), perceived stress (PS) and insomnia using internationally validated tools. Coping strategies and skills needed to overcome the crisis were examined, along with the most challenging phases. RESULTS: A total of 48 HeLs participated. The prevalence of DS and AS was 14.6% and 12.5%, respectively. Moderate and severe insomnia was found in 12.5% and 6.3% of them, respectively. Leaders showed moderate (45.8%) and high 4,2%) level of PS. The two most challenging phases were recognised in early recognition (45.2%) and peak phase (31.0%). Concerning healthcare leaders' skills required to manage with pandemic, the most reported were communication (35.1%) and decision-making (25.5%). CONCLUSION: The high level of PS, insomnia, DS and AS experienced by healthcare leaders shows the COVID-19 pandemic's psychological impact. The two most challenging phases identified enhances the importance of public health surveillance and monitoring systems, and communication appeared a critical success skill for healthcare leaders. Given the key role these professional play in addressing the current crisis in healthcare organisations, their mental health and well-being deserve greater attention.