Search

Abstract Background The COVID-19 pandemic has had an unparalleled impact, precipitating not only direct threats to physical health but also widespread economic and psychological challenges. This study aims to explore the dynamics of coping behaviour and psychological distress (PD) across different phases of the pandemic within an adult general population sample, spanning Austria and Italy. Methods An online questionnaire-based panel study was conducted between 2020 and 2023 including three measurements. We collected data on sociodemographic variables, coping responses (Brief COPE), and PD (Brief-Symptom-Checklist). Statistical analyses were conducted within a linear-mixed-model framework. Multiple imputation and sensitivity analysis were applied to validate the results obtained by complete case analysis. Results The study follows 824 participants and reveals a marginal decrease in overall PD from the first to the second follow-up, particularly in clinically relevant phobic anxiety (35.6% and 34.5% to 25.4%). Most coping behaviours exhibited stable mean-levels with intra-individual variability across the study period. Maladaptive coping strategies were consistently linked to increased PD, whereas adaptive strategies were associated with decreased PD. Conclusion Our findings underscore the complex nature of coping behaviours and PD during and after the pandemic, suggesting that while mean-levels of PD and coping responses remained relatively stable, most coping strategies were subject to intra-individual change. Maladaptive strategies were associated with increased PD, pinpointing to the need for interventions that establish the foundation for adaptive coping mechanisms and promote their application. Further research should explore the reciprocal influences of mental health on coping behaviour, incorporating interventional designs to unravel the nuances of these relationships.

Aim: Individual experiences shape perceptions of illness. Post-Soviet migrants have different expectations of chronic disease treatment than German patients. This study aimed to delve into perceptions of diabetes mellitus, a topic of increasing importance in global migration. Design: Qualitative, semi-structured interviews were conducted with 26 post-Soviet migrants with diabetes and three Russian-speaking diabetes counselors, mainly recruited through a snowball system. Methods: The research data were analyzed using a hermeneutic approach. The categories of the common-sense self-regulation model and developed subcategories were scrutinized by means of content analysis, ensuring a comprehensive understanding of the data. Results: The perception of diabetes mellitus varied depending on the country where the diagnosis was made. This included the individual recording of symptoms, the expected time course, and the allocation of different competencies. Opportunities for access to the local healthcare system in the former Soviet Union influenced these expectations. Conclusion: The study's findings underscore the importance of healthcare access in the country of origin and the patient's knowledge of diabetes mellitus in shaping their perception and treatment. These factors, influenced by the social environment and the patient's level of education, continue to play a role even after immigration to Germany.

Abstract Vegetable tannins are environmentally friendly tanning agents. However, they generally impart a dark colour to the tanned leather and highly contribute to the organic load in wastewaters. In this study, we employed a purification protocol separately on chestnut tannin (CT) and sulfited quebracho tannin (QT) to obtain the purified fractions (PCT and PQT). These samples were characterised by GPC, 1H NMR, 13C NMR, FT-IR, and HPLC–DAD techniques and applied for tanning tests. Through the purification process, non-tannin components and smaller molecules such as gallic acid, glucopyranose, and catechin were effectively removed from CT and QT, which consequently led to the reduced moisture content, pH value, and lighter colour of purified fractions. The crust leathers processed with PCT and PQT showed desirable light shades. Moreover, the organic loads in PCT and PQT tanning wastewater were reduced by 13.5% and 19.1%, respectively, when compared to those in traditional CT and QT tanning wastewater. Additionally, the physical and mechanical characteristics of crust leathers processed with PCT and PQT were comparable to those processed with CT and QT. Thus, purification of vegetable tannins may serve as a feasible strategy for producing light-colored vegetable-tanned leather while minimizing organic pollutant discharge during the vegetable tanning process. Graphical Abstract

This paper pilots a method of testing the learning effects of a role-playing simulation of negotiations over the Nile basin. Players negotiate how to apply general principles from international law, such as sharing water equitably and avoiding significant harm, to specific circumstances of the river basin. Students are presented with a set of factual statements about the basin and surveyed before and after play as to which facts will be (were) most important in negotiations. Surveys of 75 participating graduate students show interesting patterns: (1) a shift from emphasis on managing risks to exploiting cooperative opportunities; (2) change in the value orientation of the statements students consider most important, with development-oriented values increasing and environment-oriented values decreasing; and (3) change in the dimensions of power students consider most salient, including an increased appreciation for the institutional and knowledge-related elements of power and a de-emphasis on the structural aspects of power. Before-and-after surveying offers an alternative to the more common methods of learning assessment, based on knowledge acquisition or student satisfaction, while discussion of the survey results with students allows for a richer, more reflective learning experience.

Abstract General Practitioners (GPs) play a key role in the early detection and management of depression and in preventing suicide risk. They are often the first healthcare professionals that people in crisis contact. However, their effectiveness can be limited by several barriers, including the lack of specific training and appropriate tools. The EAAD-Best project aims to fill these gaps through its iFightDepression tool, an online tool designed to support patients, psychologists, psychiatrists, and GPs in managing depression and preventing suicide. This article examines the implementation of the iFightDepression platform in Italy, assessing its impact on the empowerment of GPs in the fight against depression. Through a qualitative and quantitative analysis of the data collected by the project, the ‘unmet need’ of GPs’ in Italy regarding their specific training in mental health is highlighted. The response of 2,068 Italian GPs in just 7 months after the start of the iFD project is an expression of GPs’ engagement to work against depression and for suicide risk prevention.

Abstract Colorectal cancer (CRC) is a global health concern, and the incidence of early onset (EO) CRC, has an upward trend. This study delves into the genomic landscape of EO-CRC, specifically focusing on pediatric (PED) and young adult (YA) patients, comparing them with adult (AD) CRC. In this retrospective monocentric investigation, we performed targeted next-generation sequencing to compare the mutational profile of 38 EO-CRCs patients (eight PED and 30 YA) to those of a ‘control group’ consisting of 56 AD-CRCs. Our findings reveal distinct molecular profiles in EO-CRC, notably in the WNT and PI3K-AKT pathways. In pediatrics, we observed a significantly higher frequency of RNF43 mutations, whereas APC mutations were more prevalent in adult cases. These observations suggest age-related differences in the activation of the WNT pathway. Pathway and copy number variation analysis reveal that AD-CRC and YA-CRC have more similarities than the pediatric patients. PED shows a peculiar profile with CDK6 amplification and the enrichment of lysine degradation pathway. These findings may open doors for personalized therapies, such as PI3K-AKT pathway inhibitors or CDK6 inhibitors for pediatric patients. Additionally, the distinct molecular signatures of EO-CRC underscore the need for age-specific treatment strategies and precision medicine. This study emphasizes the importance of comprehensive molecular investigations in EO-CRCs, which can potentially improve diagnostic accuracy, prognosis, and therapeutic decisions for these patients. Collaboration between the pediatric and adult oncology community is fundamental to improve oncological outcomes for this rare and challenging pediatric tumor.

Background: Ascites is common in advanced gastrointestinal cancers with peritoneal metastases (PM) and negatively impacts patient survival. No study to date has specifically evaluated the relationship between ascites, PM and survival outcomes in metastatic colorectal cancer (mCRC) and metastatic gastric cancer (mGC). Objectives: This study aims to investigate and elucidate the relationship between malignant ascites, PM and survival outcomes in both mCRC and mGC patients. Design: This is a retrospective analysis of prospectively collected clinical trial data of mCRC and mGC patients with PM. Methods: We performed two pooled analyses, firstly of two Italian randomized trials enrolling patients with mCRC eligible for systemic therapy (TRIBE2; VALENTINO), and secondly of gastric cancer and peritoneal metastasis (GCPM) patients who underwent bi-directional therapeutic treatment comprising systemic and peritoneal-directed therapies. Results: Of 900 mCRC patients, 39 (4.3%) had PM with malignant ascites. Compared to the group without PM, median progression-free and overall survival were significantly inferior in the ascites group (hazard ratio (HR) for progression-free survival (PFS) 1.68, 95% confidence interval (CI): 1.21–2.35, p = 0.007; HR for overall survival (OS) 2.14, 95% CI: 1.57–3.01, p

BackgroundChildhood obesity has become a significant public health concern over the past 2 decades, posing multifactorial challenges, including modifiable factors like dietary habits, physical activity, screen time, and sleeping habits. Prevention efforts require a comprehensive approach comprising educational interventions, collaboration among multidisciplinary teams, and community engagement. Since schools play a central role in children's lives, they are the ideal setting for promoting healthy habits. ObjectiveThe LIVELY (Multidimensional School-Based and Family-Involved Interventions to Promote a Healthy and Sustainable Lifestyle) study will assess the prevalence of overweight and obesity in primary school children and identify contributing factors within families. Additionally, it aims to implement and evaluate a multidimensional, multidisciplinary intervention to foster a sustainable and healthy lifestyle, ultimately working toward preventing obesity in school-aged children. MethodsDuring the school year, each class will be individually involved in a multidimensional educational intervention covering the topics of healthy, sustainable nutrition and lifestyle. Children will also participate in a multimedia lab where they will create an animated cartoon. The lectures will engage them through various methods, including direct instructions, games, and drawing activities, to stimulate and enhance their learning and involvement. ResultsData collection began in October 2023 and will last until the end of October 2024. A sample of 227 children from 14 classes was included in the study. The mean age was 8.9 (SD 1.2) years, and 48% (n=110) were males. Among the overall sample, 18.1% (n=41; 95% CI 13.7%-23.7%) were overweight, while 5.3% (n=12; 95% CI 3%-9%) had obesity. Males had a higher prevalence of obesity than females (9.1%, n=10 vs 1.7%, n=3, P=.03, respectively). Otherwise, the prevalence of central obesity was similar between the two (P=.329). Data analysis and the presentation of the complete results will be available after the end of 2024. ConclusionsThe study could lead to the structuring of an educational intervention model in school settings aimed at preventing childhood obesity. Moreover, it could help raise awareness of childhood obesity and help prevent this public health issue. Trial RegistrationClinicalTrials.gov NCT05966051; https://clinicaltrials.gov/study/NCT05966051 International Registered Report Identifier (IRRID)DERR1-10.2196/57509

Abstract Background The identification and staging of Alzheimer’s Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD. Methods One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses. Results Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI. Conclusions Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD.

Abstract Malignant bile duct obstruction is typically treated by biliary stenting, which however increases the risk of bacterial infections. Here, we analyzed the microbial content of the biliary stents from 56 patients finding widespread microbial colonization. Seventeen of 36 prevalent stent species are common oral microbiome members, associate with disease conditions when present in the gut, and include dozens of biofilm- and antimicrobial resistance-related genes. This work provides an overview of the microbial communities populating the stents.

Abstract Background Primary progressive aphasia (PPA) diagnostic criteria underestimate the complex presentation of semantic (sv) and logopenic (lv) variants, in which symptoms partially overlap, and mixed clinical presentation (mixed-PPA) and heterogenous profile (lvPPA +) are frequent. Conceptualization of similarities and differences of these clinical conditions is still scarce. Methods Lexical, semantic, phonological, and working memory errors from nine language tasks of sixty-seven PPA were analyzed using Profile Analysis based on Multidimensional Scaling, which allowed us to create a distributed representation of patients’ linguistic performance in a shared space. Patients had been studied with [18F] FDG-PET. Correlations were performed between metabolic and behavioral data. Results Patients’ profiles were distributed across a continuum. All PPA, but two, presented a lexical retrieval impairment, in terms of reduced production of verbs and nouns. svPPA patients occupied a fairly clumped space along the continuum, showing a preponderant semantic deficit, which correlated to fusiform gyrus hypometabolism, while only few presented working memory deficits. Adjacently, lvPPA + presented a semantic impairment combined with phonological deficits, which correlated with metabolism in the anterior fusiform gyrus and posterior middle temporal gyrus. Starting from the shared phonological deficit side, a large portion of the space was occupied by all lvPPA, showing a combination of phonological, lexical, and working memory deficits, with the latter correlating with posterior temporo-parietal hypometabolism. Mixed PPA did not show unique profile, distributing across the space. Discussion Different clinical PPA entities exist but overlaps are frequent. Identifying shared and unique clinical markers is critical for research and clinical practice. Further research is needed to identify the role of genetic and pathological factors in such distribution, including also higher sample size of less represented groups.

IntroductionThis study was conducted on the occasion of the parricide in Bolzano (South Tyrol, Italy) in January 2021. The psychological impact of parricide on the general population and on mental health professionals has scarcely been investigated to the present day. Studies on stigmatization show differences between various groups. The aim was to analyze the emotional reactions to the parricide and the stigmatization of persons with mental disorders in the South Tyrolian population.MethodsIn September 2022, 121 mental health professionals of the Department of Psychiatry in Bolzano were surveyed using an online questionnaire. In addition, from January to March 2023, the general population of South Tyrol was invited to take part in the survey through an online-link and was divided into three groups: 267 persons with mental health problems, 855 relatives and 1,019 persons with no direct or indirect contact to people with mental problems. The validated Reported and Intended Behavior Scale (RIBS) was used together with questions on the emotional reactions to the parricide and the perceived dangerousness of psychiatric patients. Descriptive statistics, one-way Anovas as well as regressions were carried out.Results and discussionAll groups experienced sadness the most. Relatives experienced more sadness and anger than the other groups. Over 80% of the professionals stated that psychiatric patients were not at greater risk of committing parricide. The population with no contact rated the risk higher than those affected and had the lowest level of openness (RIBS). There were no differences between genders, but there were age differences, with younger people being more stigmatizing. The results suggest that personal contact, appropriate information, and education are associated with less stigmatization.

Desde hace años, se puede observar una tendencia en el derecho comparado de atribuirles responsabilidad (penal o administrativa) a los entes colectivos por los delitos que han cometido sus integrantes si se cumplen ciertos requisitos. Esta tendencia se ha extendido también en Latinoamérica. En este trabajo, se analiza cómo se regula la responsabilidad de las personas jurídicas en Perú y Argentina. Aunque ambas legislaciones cuentan con aspectos similares, difieren en algunas cuestiones importantes, comenzando por la propia naturaleza jurídica de esta responsabilidad corporativa. Mientras que en Argentina se regula la responsabilidad penal de las personas jurídicas, en Perú se establece un régimen de responsabilidad administrativa de las personas jurídicas por los delitos cometidos por sus miembros.

Este trabajo analiza una cuestión que ha dado lugar a un intenso debate en la doctrina y que ha tenido mucha repercusión en la jurisprudencia. Se trata de la posible exclusión de las sociedades pantalla del ámbito subjetivo de aplicación del régimen de responsabilidad «penal» de las personas jurídicas previsto en los arts. 31 bis y ss. CP. Aunque gran parte de los autores, la Fiscalía General del Estado y el Tribunal Supremo consideran que estos preceptos no deben aplicarse a dichas sociedades, esta interpretación no ha estado exenta de críticas por su aparente contradicción con lo dispuesto en los arts. 31 quinquies.2 y 66 bis.2.ª.b) CP. En este texto se adopta una postura que procura dotar de coherencia a esta regulación ante el problema que presentan las sociedades pantalla.

Abstract Background Pancreatic cancer (PC) first‐line therapy often consists of polychemotherapy regimens, but choosing a second‐line therapy after disease progression, especially following first‐line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab‐paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions. Methods The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice. Results AG was well‐tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression‐free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second‐line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first‐line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first‐line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second‐line OS and PFS. Conclusions This study represents the largest real‐world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first‐line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first‐line therapy.

Lysosomal Ca2+ signaling is emerging as a crucial regulator of endothelial Ca2+ dynamics. Ca2+ release from the acidic vesicles in response to extracellular stimulation is usually promoted via Two Pore Channels (TPCs) and is amplified by endoplasmic reticulum (ER)-embedded inositol-1,3,4-trisphosphate (InsP3) receptors and ryanodine receptors. Emerging evidence suggests that sub-cellular Ca2+ signals in vascular endothelial cells can also be generated by the Transient Receptor Potential Mucolipin 1 channel (TRPML1) channel, which controls vesicle trafficking, autophagy and gene expression. Herein, we adopted a multidisciplinary approach, including live cell imaging, pharmacological manipulation, and gene targeting, revealing that TRPML1 protein is expressed and triggers global Ca2+ signals in the human brain microvascular endothelial cell line, hCMEC/D3. The direct stimulation of TRPML1 with both the synthetic agonist, ML-SA1, and the endogenous ligand phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) induced a significant increase in [Ca2+]i, that was reduced by pharmacological blockade and genetic silencing of TRPML1. In addition, TRPML1-mediated lysosomal Ca2+ release was sustained both by lysosomal Ca2+ release and ER Ca2+- release through inositol-1,4,5-trisphophate receptors and store-operated Ca2+ entry. Notably, interfering with TRPML1-mediated lysosomal Ca2+ mobilization led to a decrease in the free ER Ca2+ concentration. Imaging of DAF-FM fluorescence revealed that TRPML1 stimulation could also induce a significant Ca2+-dependent increase in nitric oxide concentration. Finally, the pharmacological and genetic blockade of TRPML1 impaired ATP-induced intracellular Ca2+ release and NO production. These findings, therefore, shed novel light on the mechanisms whereby the lysosomal Ca2+ store can shape endothelial Ca2+ signaling and Ca2+-dependent functions in vascular endothelial cells.