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This study investigates the impact of childhood maltreatment (CM) on hypothalamic-pituitary-adrenal (HPA)-axis functioning and on anxiety perception. Moreover, the influence of CM severity and frequency was also explored. In total, 187 participants aged 7-17 were assessed for CM history using validated questionnaires and interviews to be classified according to the criteria of the Tool for Assessing the Severity of Situations in which Children are Vulnerable (TASSCV). Psychopathology was ascertained using the K-SADS-PL5. To assess HPA-axis functioning, salivary cortisol samples were collected throughout a normal day and during an acute psychosocial stressor, the Trier Social Stress Test for children (TSST-C). Subjective anxiety was evaluated using STAI/-C. Youth with a CM history had higher overall diurnal cortisol levels ( = 0.001), blunted cortisol response to acute psychosocial stress ( = 0.002) and greater perceived anxiety ( = 0.003), than those without CM. Specifically, participants exposed to moderate/severe or often/frequent CM showed the greater diurnal cortisol output ( = 0.002; = 0.003), and blunted cortisol response during the TSST-C ( = 0.006; = 0.008). Meanwhile, youth with low CM severity/frequency exhibited a similar cortisol response to those without CM. However, perceived anxiety was higher in those exposed to CM ( < 0.001), regardless of its severity/frequency. Disturbances in HPA-axis functioning are already evident early after CM exposure, while psychological and physiological responses to an acute stressor are dissociated in youth exposed to CM. The dose-response relationship described in this paper highlights the need to comprehensively evaluate CM so that vulnerable children can be identified and assigned to proper interventions.

Introduction: Identifying the complexity of palliative care needs is a key aspect of referral to specialized multidisciplinary early palliative care (EPC) teams. The PALCOM scale is an instrument consisting of five multidimensional assessment domains developed in 2018 and validated in 2023 to identify the level of complexity in patients with advanced cancer. (1) Objectives: The main objective of this study was to determine the degree of instability (likelihood of level change or death), health resource consumption and the survival of patients according to the level of palliative complexity assigned at the baseline visit during a 6-month follow-up. (2) Method: An observational, prospective, multicenter study was conducted using pooled data from the development and validation cohort of the PALCOM scale. The main outcome variables were as follows: (a) instability ratio (IR), defined as the probability of level change or death; (b) emergency department visits; (c) days of hospitalization; (d) hospital death; (e) survival. All the variables were analyzed monthly according to the level of complexity assigned at the baseline visit. (3) Results: A total of 607 patients with advanced cancer were enrolled. According to the PALCOM scale, 20% of patients were classified as low complexity, 50% as medium and 30% as high complexity. The overall IR was 45% in the low complexity group, 68% in the medium complexity group and 78% in the high complexity group (p < 0.001). No significant differences in mean monthly emergency department visits (0.2 visits/ patient/month) were observed between the different levels of complexity. The mean number of days spent in hospital per month was 1.5 in the low complexity group, 1.8 in the medium complexity group and 3.2 in the high complexity group (p < 0.001). The likelihood of in-hospital death was significantly higher in the high complexity group (29%) compared to the medium (16%) and low (8%) complexity groups (p < 0.001). Six-month survival was significantly lower in the high complexity group (24%) compared to the medium (37%) and low (57%) complexity groups (p < 0.001). Conclusion: According to the PALCOM scale, more complex cases are associated with greater instability and use of hospital resources and lower survival. The data also confirm that the PALCOM scale is a consistent and useful tool for describing complexity profiles, targeting referrals to the EPC and managing the intensity of shared care.

Objectives: Key neurobiological factors contribute to vulnerability to nonsuicidal self-injury (NSSI) among adolescents and how they respond to treatment targeted to reduce such behaviors. This study aims to examine differences in intrinsic functional connectivity between adolescents with NSSI and healthy controls (HCs) and to identify baseline connectivity markers that predict improvements in NSSI after psychotherapy. Methods: Adolescents aged 12–17 (n = 24) with repetitive NSSI along with demographically similar HCs (n = 16) underwent resting-state functional MRI scanning after which patients received up to 4 months of psychological treatment. A seed-based approach was used to examine baseline between-group differences in intrinsic functional connectivity of the amygdala and the medial prefrontal cortex (mPFC). Further analyses examined the associations between intrinsic functional connectivity at baseline and improvement in NSSI after psychological treatment. Results: Compared with HCs, adolescents with NSSI showed significantly reduced connectivity between the amygdala and the anterior cingulate cortex, subcallosal cortex, and paracingulate gyrus, as well as between the amygdala and a cluster encompassing the right planum temporale and right insula. Adolescents with NSSI, compared with HCs, also showed reduced connectivity between the mPFC and two clusters: one located in the precentral and postcentral gyri and another in the left insula. After treatment, 50% of patients reported fewer NSSI episodes compared to baseline, which was considered as improvement. Stronger negative amygdala-prefrontal connectivity was associated with greater posttreatment improvement in NSSI. Conclusions: Adolescents with NSSI may have aberrant amygdala and mPFC connectivity compared with HCs. Furthermore, stronger baseline negative amygdala-prefrontal connectivity may predict greater improvement in NSSI after psychological intervention. Given that no prior study has used resting-state functional connectivity to predict response to psychological treatment in adolescents with NSSI, replication of these findings is needed.

This longitudinal study aimed to explore anxiety and depressive symptoms, individual resources, and job demands in a multi-country sample of 612 healthcare workers (HCWs) during the COVID-19 pandemic. Two online surveys were distributed to HCWs in seven countries (Germany, Andorra, Ireland, Spain, Italy, Romania, Iran) during the first (May-October 2020, T1) and the second (February-April 2021, T2) phase of the pandemic, assessing sociodemographic characteristics, contact with COVID-19 patients, anxiety and depressive symptoms, self-compassion, sense of coherence, social support, risk perception, and health and safety at the workplace. HCWs reported a significant increase in depressive and anxiety symptoms. HCWs with high depressive or anxiety symptoms at T1 and T2 reported a history of mental illness and lower self-compassion and sense of coherence over time. Risk perception, self-compassion, sense of coherence, and social support were strong independent predictors of depressive and anxiety symptoms at T2, even after controlling for baseline depressive or anxiety symptoms and sociodemographic variables. These findings pointed out that HCWs during the COVID-19 outbreak experienced a high burden of psychological distress. The mental health and resilience of HCWs should be supported during disease outbreaks by instituting workplace interventions for psychological support.

Introduction: The life experience of patients with advanced cancer and limited life expectancy is unique and profoundly complex, often leading to moral discrepancies among the various individuals involved in decision making. There are no data in the literature on the prevalence of ethical issues in the end-of-life care of patients with advanced cancer. Objectives: The primary objective of this study is to identify the overall and specific prevalence of ethical issues in the end-of-life care process for patients with advanced cancer. Method: We performed a secondary analysis using pooled data from the prospective development and validation cohorts of the PALCOM scale, focusing on the complexity of palliative care needs. This was performed to determine the overall and specific prevalence of ethical issues, describe their evolution over a 6-month follow-up period, and analyze their association with the level of palliative care complexity. Results: A total of 607 patients with advanced cancer and a life expectancy of 6 months or less were included. The consistency in clinical data and the frequencies of the PALCOM scale domains between the development and validation cohorts, conducted in various settings and times, confirmed the reliability of the pooled data sample. Systematic application of the PALCOM scale identified 126 patients (20.7%) who experienced at least one ethical issue. A total of 204 ethical issues (1.6 per patient) were recorded, related to the following: the proportionality of healthcare intervention (15.6%); information (13.0%); research (2.9%); the desire to hasten death (1.8%); and palliative sedation (0.15%). The monthly probability of presenting an ethical issue was significantly higher at the baseline visit (24.0%) compared to the rest of the 6-month follow-up period (14–17%) (p < 0.001). The prevalence of ethical issues was notably higher in patients with greater palliative care complexity as measured by the PALCOM scale: 4.5% in low complexity, 19.5% in medium complexity, and 30.8% in high complexity (p < 0.001). Conclusions: The prevalence of ethical issues in patients with advanced cancer is high. Most of these issues are directly or indirectly related to the preservation of patient autonomy in the decision-making process. The presence of ethical issues is significantly associated with the greater complexity of palliative care needs. In this context, it is crucial for healthcare professionals to strengthen both communication skills and basic competencies to effectively identify, assess, and manage these ethical issues.

PurposeThe main aim of this study was to determine the prevalence of ethical dilemmas in the end-of-life process in advanced cancer patients.MethodsWe carried out a multicenter, cross-sectional, observational, prospective study in a cohort of cancer patients whose life expectancy was ≤ 6 months. We recorded sociodemographic characteristics, diagnosis of cancer, symptom burden, cognitive and functional status, emotional impact, and sociofamilial risk factors. The main outcome measure was the detection of ethical dilemmas, based on the following definition: conflict in decision-making during the end-of-life process that involves the need to choose between morally acceptable opposing options, where none is clearly preferable to another.ResultsWe included 324 patients (mean age, 69 years; 58% men). We identified 117 dilemmas in 90 patients (27.8%). The dilemmas detected were as follows: (a) conflicts of information (adaptive denial, conspiracy of silence, information exceeding patient’s desired limit), 15.7%; (b) discrepancies in proportionality (discussion on futility, rejection of treatment, withdrawal of life support measures), 16.7%; (c) unrealistic expectations about the outcome of clinical trials, 2.5%; and (d) request for euthanasia or medically assisted suicide, 1.2%. We observed a greater prevalence of ethical dilemmas in men, in patients receiving active cancer treatment, and in patients with emotional distress (p < 0.05).ConclusionsThe prevalence of ethical dilemmas during the end-of-life process in cancer patients is relevant. Most dilemmas were associated directly or indirectly with respect for patient autonomy. In this context, the communication skills of the health professionals and advanced care planning take on a key role.

Background: In a patient-centred model of care, referral to early palliative care (EPC) depends on both the prognosis and the complexity of care needs. The PALCOM scale is a 5-domain multidimensional assessment tool developed to identify the level of complexity of palliative care needs of cancer patients. The aim of this study was to validate the PALCOM scale. Patient and methods: We conducted a prospective cohort study of cancer patients to compare the PALCOM scale and expert empirical assessment (EA) of the complexity of palliative care needs. The EA had to categorise patients according to their complexity, considering that medium to high levels required priority attention from specialist EPC teams, while those with low levels could be managed by non-specialist teams. Systematically collected multidimensional variables were recorded in an electronic report form and stratified by level of complexity and rating system (PALCOM scale versus EA). The correlation rank (Kendall’s tau test) and accuracy test (F1-score) between the two rating systems were analysed. ROC curve analysis was used to determine the predictive power of the PALCOM scale. Results: A total of 283 advanced cancer patients were included. There were no significant differences in the frequency of the levels of complexity between the EA and the PALCOM scale (low 22.3–23.7%; medium 57.2–59.0%; high 20.5–17.3%). The prevalence of high symptom burden, severe pain, functional impairment, socio-familial risk, existential/spiritual problems, 6-month mortality and in-hospital death was significantly higher (p < 0.001) at the high complexity levels in both scoring systems. Comparative analysis showed a high correlation rank and accuracy between the two scoring systems (Kendall’s tau test 0.81, F1 score 0.84). The predictive ability of the PALCOM scale was confirmed by an area under the curve in the ROC analysis of 0.907 for high and 0.902 for low complexity. Conclusions: In a patient-centred care model, the identification of complexity is a key point to appropriate referral and management of shared care with EPC teams. The PALCOM scale is a high precision tool for determining the level of complexity of palliative care needs.

It is estimated that 80% of bacterial life exists in the context of a biofilm. This makes biofilms one of the key areas of research for many organisms. In Pseudomonas fluorescens, the initial, transitory adherence to a surface is mediated by the Lap system, which is conserved and functional in many other bacterial species. Within this thesis, three aspects of Lap system function and regulation are explored. Chapter 2 discusses the adhesin LapA and its regulation. It was found that several key structural features of LapA contribute to its function as an adhesin which can alternatively released or retained.Chapter 3 presents work done on proteins from Desulfovibrio vulgaris. Several proteins, found in a genomic context similar to that of the Lap system, are key to biofilm formation in this organism. In this study, some of the key features of this Laplike system have been investigated. The structures and functions of three proteins, DvhD, DvhG and DvhA were and found to be similar in many respects to their predicted Lap system homologs, LapD, LapG and LapA, respectively. DvhG was found to selectively process the N terminus of DvhA. The HD-GYP domain of DvhD in particular was found to be capable of binding c-di-GMP, an important regulator of the Lap system, and possessed a previously uncharacterized binding site. The data obtained about this system suggest that it behaves similarly to the Lap system and represents an important component of biofilm formation in D. vulgaris. Finally, Chapter 4 presents work which explores the ligand binding preferences of diguanylate cyclases (DGCs) in P. fluorescens. The Lap system was shown to be regulated in part by physical interaction between certain DGCs and LapD. This interaction can be enhanced by ligand binding to the DGC. The Cache, or ligand binding, domains of two DGCs were assessed biochemically. The Cache domain from Pfl01_3800 was found to preferentially bind small carboxylic acids and was characterized structurally. This work contributes to our understanding of ligand specificity in Cache domains in general and helped elucidate factors that might enhance biofilm formation in P. fluorescens.

El emprendimiento presenta posibilidades considerables en la revitalización económica del territorio cuando tributa a sus líneas estratégicas y por la incidencia que tiene en los indicadores económicos. El propósito de este trabajo es diseñar una Metodología de Gestión del Conocimiento para el Emprendimiento Territorial. Los resultados de investigación se obtuvieron a partir del año 2012 hasta marzo del 2017 mediante coordinaciones de trabajo entre la Facultad de Economía de la UH y el Centro Universitario Municipal “Simón Bolívar” del Municipio Yaguajay, Provincia de Sancti Spíritus, Cuba, que organizó las actividades realizadas conjuntamente con el gobierno, las organizaciones y base campesina ganadera. El tipo de investigación responde a un paradigma cuali-cuanti, se trabajó con dos grupos: 15 expertos y una muestra compuesta por campesinos ganaderos, actores del Centro Universitario Municipal y del gobierno, en total 157. El resultado es el diseño de una metodología para gestionar el conocimiento que tribute a potenciar el emprendimiento territorial. La novedad radica en que articula la acción de los actores para determinar las necesidades fundamentales de información y formación y las formas colectivas de abordar su satisfacción; incluye la determinación del impacto de los indicadores de capital intelectual en el emprendimiento, la aplicación del Modelo Multiatributo de Ponderación Aditiva Simple para establecer el orden de prioridad de las necesidades de formación e información identificadas y la propuesta de una incubadora como figura de transferencia tecnológica.El diseño constituye una contribución metodológica materializada en siete etapas que refuerzan el vínculo entre el gobierno, la universidad y el emprendimiento.