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Mutations in the methyl‐CpG‐binding protein 2 (MeCP2) are associated with Rett syndrome and other neurological disorders. MeCP2 represses transcription mainly by recruiting various co‐repressor complexes. Recently, MeCP2 phosphorylation at Ser 80, Ser 229 and Ser 421 was shown to occur in the brain and modulate MeCP2 silencing activities. However, the kinases directly responsible for this are largely unknown. Here, we identify the homeodomain‐interacting protein kinase 2 (HIPK2) as a kinase that binds MeCP2 and phosphorylates it at Ser 80 in vitro and in vivo . HIPK2 modulates cell proliferation and apoptosis, and the neurological defects of Hipk2 ‐null mice indicate its role in proper brain functions. We show that MeCP2 cooperates with HIPK2 in induction of apoptosis and that Ser 80 phosphorylation is required together with the DNA binding of MeCP2. These data are, to our knowledge, the first that describe a kinase associating with MeCP2, causing its specific phosphorylation in vivo and, furthermore, they reinforce the role of MeCP2 in regulating cell growth. Rett syndrome is a severe neurological disorder caused by mutations in the gene MECP2. Bracaglia and colleagues now identify the kinase HIPK2 as capable of specifically phosphorylating MeCP2 protein at Serine 80 in vivo. They show that MeCP2 cooperates with HIPK2 to induce apoptosis, providing insight into the function of this disease‐associated protein.

La construcción de identidad personal es un proceso evolutivo. Escasas investigaciones estudian este proceso en la infancia. El objetivo de esta investigación es describir la construcción de identidad personal de niños y adolescentes entre 6 y 18 años, desde un enfoque constructivista evolutivo. Se realiza un análisis temático de narrativas autobiográficas escritas por 119 niños y adolescentes. Los resultados se organizaron en torno a tres dimensiones de la identidad personal: unidad de identidad, integración de identidad, integración con otros; observándose que desde la infancia hay un reconocimiento personal, luego se integran diferentes eventos vitales significativos y en la adolescencia se complejiza su construcción, incorporando mayor reflexión y aspectos ideológicos. Se discuten implicancias para favorecer un desarrollo adaptativo de la identidad en todas las edades, validando diversidad de opciones.

(analytical)Construction of personal identity is a developmental process. Few research investigates this process in children. The research objective is to describe the personal identity construction of children and adolescents between 6 and 18 years old, from a developmental constructivist approach. Thematic analysis of autobiographical narratives written by 119 children and adolescents is performed. Results were organized around the three personal identity dimensions: unity of self, integration of self and integration with others. Results show from childhood there is a personal recognition, then different significant life events are integrated, and in adolescense this construction becomes more complex, integrating more reflection and ideological aspects. Implications are discussed to promote an adaptive development of identity through lifespam, validating a diversity of options. Keywords: Personal Identity, personal image, narrative, child development, children, constructivism, Piaget. (analítico)La construcción de identidad personal es un proceso evolutivo. Escasas investigaciones estudian este proceso en la infancia. El objetivo de esta investigación es describir la construcción de identidad personal de niños y adolescentes entre 6 y 18 años, desde un enfoque constructivista evolutivo. Se realiza un análisis temático de narrativas autobiográficas escritas por 119 niños y adolescentes. Los resultados se organizaron en torno a tres dimensiones de la identidad personal: unidad de identidad, integración de identidad, integración con otros; observándose que desde la infancia hay un reconocimiento personal, luego se integran diferentes eventos vitales significativos y en la adolescencia se complejiza su construcción, incorporando mayor reflexión y aspectos ideológicos. Se discuten implicancias para favorecer un desarrollo adaptativo de la identidad en todas las edades, validando diversidad de opciones. Palabras clave: Identidad personal, imagen personal, narrativa, desarrollo del niño, niños, constructivismo, Piaget. (analítico)A construção da identidade pessoal é um processo evolutivo. Poucas pesquisas investigam esse processo na infância. O objetivo desta pesquisa é descrever a construção da identidade pessoal de crianças e adolescentes entre 6 e 18 anos, a partir de uma abordagem construtivista evolutiva. É realizada uma análise temática das narrativas autobiográficas escritas por 119 crianças e adolescentes. Os resultados foram organizados em torno de três dimensões da identidade pessoal: unidade deidentidade, integração de identidade, integração com os outros; e mostram que desde a infância há um reconhecimento pessoal, logo diversos acontecimentos significativos da vida são integrados, e na adolescência sua construção torna-se mais complexa, incorporando mais reflexão e aspectos ideológicos. As implicações para promover o desenvolvimento adaptativo da identidade em todasas idades são discutidas, validando a diversidade de opções. Palavras-chave: Identidade pessoal, si-mesmo, narrativas, desenvolvimento, crianças, Construtivismo, Piaget.

La construcción de identidad personal es un proceso evolutivo. Escasas investigaciones estudian este proceso en la infancia. El objetivo de esta investigación es describir la construcción de identidad personal de niños y adolescentes entre 6 y 18 años, desde un enfoque constructivista evolutivo. Se realiza un análisis temático de narrativas autobiográficas escritas por 119 niños y adolescentes. Los resultados se organizaron en torno a tres dimensiones de la identidad personal: unidad de identidad, integración de identidad, integración con otros; observándose que desde la infancia hay un reconocimiento personal, luego se integran diferentes eventos vitales significativos y en la adolescencia se complejiza su construcción, incorporando mayor reflexión y aspectos ideológicos. Se discuten implicancias para favorecer un desarrollo adaptativo de la identidad en todas las edades, validando diversidad de opciones.

Background The COVID-19 pandemic and related measures have negatively impacted mental health worldwide. The main objective of the present longitudinal study was to investigate mental health in people living in Tyrol (Austria) and South Tyrol (Italy) during the COVID-19 pandemic and to report the prevalence of psychological distress among individuals with versus those without pre-existing mental health disorders (MHD) in the long-term (summer 2020–winter 2022). Here, we specifically focus on the relevance of spirituality and perceived social support in this regard. Methods 161 individuals who had been diagnosed with MHD and 446 reference subjects participated in this online survey. Electronic data capture was conducted using the Computer-based Health Evaluation System and included both sociodemographic and clinical aspects as well as standardized questionnaires on psychological distress, spirituality, and the perception of social support. Results The prevalence of psychological distress was significantly higher in individuals with MHD (36.6% vs. 12.3%) and remained unchanged among both groups over time. At baseline, the perception of social support was significantly higher in healthy control subjects, whereas the two groups were comparable in regards of the subjective relevance of faith. Reference subjects indicated significantly higher spiritual well-being in terms of the sense of meaning in life and peacefulness, which mediated in large part the between-group difference of psychological distress at follow-up. Notably, both faith and the perception of social support did not prove to be relevant in this context. Conclusions These findings point to a consistently high prevalence of psychological distress among people suffering from MHD and underscore the prominent role of meaning in life and peacefulness as a protective factor in times of crisis. Therapeutic strategies that specifically target spirituality may have a beneficial impact on mental health.

Introduction Early risk stratification in the emergency department (ED) is vital to reduce time to effective treatment in high-risk patients and to improve patient flow. Yet, there is a lack of investigations evaluating the incremental usefulness of multiple biomarkers measured upon admission from distinct biological pathways for predicting fatal outcome and high initial treatment urgency in unselected ED patients in a multicenter and multinational setting. Method We included consecutive, adult, medical patients seeking ED care into this observational, cohort study in Switzerland, France and the USA. We recorded initial clinical parameters and batch-measured prognostic biomarkers of inflammation (pro-adrenomedullin [ProADM]), stress (copeptin) and infection (procalcitonin). Results During a 30-day follow-up, 331 of 7132 (4.6 %) participants reached the primary endpoint of death within 30 days. In logistic regression models adjusted for conventional risk factors available at ED admission, all three biomarkers strongly predicted the risk of death (AUC 0.83, 0.78 and 0.75), ICU admission (AUC 0.67, 0.69 and 0.62) and high initial triage priority (0.67, 0.66 and 0.58). For the prediction of death, ProADM significantly improved regression models including (a) clinical information available at ED admission (AUC increase from 0.79 to 0.84), (b) full clinical information at ED discharge (AUC increase from 0.85 to 0.88), and (c) triage information (AUC increase from 0.67 to 0.83) ( p <0.01 for each comparison). Similarly, ProADM also improved clinical models for prediction of ICU admission and high initial treatment urgency. Results were robust in regard to predefined patient subgroups by center, main diagnosis, presenting symptoms, age and gender. Conclusions Combination of clinical information with results of blood biomarkers measured upon ED admission allows early and more adequate risk stratification in individual unselected medical ED patients. A randomized trial is needed to answer the question whether biomarker-guided initial patient triage reduces time to initial treatment of high-risk patients in the ED and thereby improves patient flow and clinical outcomes. Trial registration ClinicalTrials.gov NCT01768494 . Registered January 9, 2013.

Research on the long-term mental health impact of the COVID-19 pandemic across mental disorders is limited, and information on the impact of public health policy measures with varying strictness is missing. This study therefore aimed at investigating psychological distress among residents of Tyrol (Austria) and South Tyrol (Italy) at the early stages of the pandemic and 5 months thereafter and examined how sociodemographic, protective, and risk factors relate to change over time. One hundred and fifteen people with severe mental illness (SMI; schizophrenia spectrum disorder, bipolar disorder, major depressive disorder with psychotic features) or major depressive disorder without psychotic features (MDD) and 481 community controls without mental disorders participated in an online survey. Next to the collection of sociodemographic and COVID-19 related variables, the Brief Symptom Checklist, the Resilience Scale, the Multidimensional Scale of Perceived Social Support, the Three-Item Loneliness Scale, and the Multidimensional State Boredom Scale-Short Form were used to assess psychological distress, resilience, perceived social support, loneliness, and boredom. Levels of psychological symptoms and the prevalence of psychological distress were significantly higher in individuals with MDD compared to the other two groups, and Italian participants were more prone to anxiety than those from Austria. Psychological distress was predicted by a lower degree of both resilience and perceived social support as well as loneliness and boredom. Notably, the prevalence of clinically relevant psychological symptoms remained unchanged among each group over time. These results underscore the relevance of tailored prevention and mitigation strategies to meet the specific needs of people both with and without mental disorders.

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.

Reducing delays in hospital discharge is important to improve transition processes and reduce health care costs. The recently proposed post-acute care discharge score focusing on the self-care abilities before hospital admission allows early identification of patients with a need for post-acute care. New limitations in self-care abilities identified during hospitalization may also indicate a risk. Our aim was to investigate whether the addition of the post-acute care discharge score and a validated self-care instrument would improve the prognostic accuracy to predict post-acute discharge needs in unselected medical inpatients. We included consecutive adult medical and neurological inpatients. Logistic regression models with area under the receiver operating characteristic curve were calculated to study associations of post-acute discharge score and self-care index with post-acute discharge risk. We calculated joint regression models and reclassification statistics including the net reclassification index and integrated discrimination improvement to investigate whether merging the self-care index and the post-acute discharge score leads to better diagnostic accuracy. Out of 1342 medical and 402 neurological patients, 150 (11.18%) and 94 (23.38%) have reached the primary endpoint of being discharged to a post-acute care facility. Multivariate analysis showed that the self-care index is an outcome predictor (OR 0.897, 95%CI 0.864-0.930). By combining the self-care index and the post-acute care discharge score discrimination for medical (from area under the curve 0.77 to 0.83) and neurological patients (from area under the curve 0.68 to 0.78) could be significantly improved. Reclassification statistics also showed significant improvements with regard to net reclassification index (14.2%, p<0.05) and integrated discrimination improvement (4.83%, p<0.05). Incorporating an early assessment of patients' actual intrahospital self-care ability to the post-acute care discharge score led to an improved prognostic accuracy for identifying adult, medical and neurological patients at risk for discharge to a post-acute care facility.

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.