The HEPOE Theory (High Entropy Predictive Organization Efficiency) proposes a novel conceptual framework for understanding Giftedness (HA/G), moving beyond academic performance-based models toward a biophysical and neuroscientific foundation. Through a theoretical synthesis grounded in the Free Energy Principle and Biological Thermodynamics, the gifted individual is redefined as a “Sentinel”: a high-fidelity sampling system specialized in the early detection of isomorphy and the reduction of systemic entropy. This framework reinterprets Charles Spearman’s general intelligence (g) as a macroscopic manifestation of hardware efficiency, where reasoning ability is proposed to be fundamentally constrained by working-memory capacity and the metabolic economy of ATP resynthesis. We hypothesize that the hardware operates under an “open sensory gating” regime and low latent inhibition, leading to high metabolic costs and chronic allostatic load. The paper introduces the original concept of Predictive Moral Injury to conceptualize the potential somatic damage resulting from the early perception of ethical-systemic collapses within low-resolution environments. The HEPOE Unification Matrix integrates decades of classical literature and proposes a rigorous differential diagnosis against the pathologization of ASD, ADHD, and PTSD. It hypothesizes that the Sentinel’s exhaustion is not a dysfunction, but a logistical byproduct of high predictive performance under entropy-saturated conditions.
Perceptions of mental health services among informal caregivers in Sardinia, Italy, during the post-pandemic crisis of the national health system: a comparative study between 2024 and 2025
BackgroundItaly’s community-based mental health model, grounded in Law 180, has long been regarded as a global example of rights-oriented psychiatric reform. However, recent years have witnessed a crisis in the national health system, marked by chronic and progressively accumulating underfunding, workforce shortages, and organizational strain, rather than a single acute disruption. This s/tudy compares two samples of informal caregivers of individuals receiving mental health care in Sardinia (2024 vs. 2025) to explore differences in their perceptions of service quality, organizational well-being, and respect for human rights.MethodsA cross-sectional design was used to compare independent caregiver samples (2024: n = 100; 2025: n = 74). Participants completed the Well-Being at Work and Respect for Human Rights Questionnaire (WWRR), which assesses satisfaction with care, perceptions of organizational quality, and respect for users’ and staff’s rights. Data were analyzed with ANOVA and chi-square tests.ResultsCaregivers in 2025 reported significantly higher satisfaction than those in 2024 regarding the quality of services (p = 0.007), organizational aspects (p = 0.007), and respect for the human rights of both users (p < 0.001) and staff (p = 0.037). No differences emerged in perceived user satisfaction or resource adequacy, with both cohorts expressing persistent concern about staffing and infrastructure. The perceived need for additional nurses, doctors, and support staff increased in 2025, which may indicate growing awareness of workforce fragility.ConclusionsThese differences in satisfaction should be interpreted within a context of prolonged systemic strain, which may foster adaptive or resilience-based perceptions among informal caregivers. Despite ongoing structural difficulties, informal caregivers maintain high confidence in Italy’s community mental health services and perceive them as respectful of human rights. However, their increasing concern about resource shortages highlights the urgent need for investment to preserve the ethical and organizational strengths of the Italian model.
Hyponatremia in patients with severe anorexia nervosa was associated with more severe and longer duration of disease
IntroductionSeveral mechanisms are thought to contribute to hyponatremia in patients with anorexia nervosa (AN). The aims of this descriptive, cross-sectional study among patients admitted to a specialized somatic unit for eating disorders (ED) were to determine the frequency of hyponatremia and to compare medical findings between patients with normonatremia and hyponatremia.MethodsThis retrospective, descriptive cross-sectional study included patients admitted to the unit between December 2016 and October 2021. Demographic, medical history, and clinical data were extracted from medical records. Patients were categorized according to plasma sodium concentration (<135 mmol/L vs. ≥135 mmol/L).ResultsAmong 131 patients, 17 (13%) had hyponatremia at admission. Hyponatremia was associated with lower BMI, lower nadir BMI, longer disease duration, and an adverse biochemical profile (lower albumin, higher creatinine, higher platelet counts, and higher bicarbonate levels). Thirteen patients (10%) were deceased at follow-up; hyponatremia was associated with mortality in unadjusted analysis (OR 8.03, 95% CI 2.29–28.16) but not after multivariable adjustment.DiscussionThe study found that 13% of patients admitted to a specialized somatic unit for ED had hyponatremia, which clustered with indicators of more severe and longstanding AN (lower BMI, lower nadir BMI, longer disease duration). Hyponatremia was associated with mortality in unadjusted analyses, but this association was attenuated after adjustment for age and illness severity. Despite the established potential of purging to induce hyponatremia, our findings suggest that, in this severely ill inpatient population, overall illness severity and chronic medical deterioration may be more important determinants of both hyponatremia and mortality risk than purging per se.
Metacognitive model of suicidality: a study of Iranian inpatients
BackgroundThe metacognitive model of suicidality proposes that positive metacognitions about suicide activate suicide-specific rumination, which in turn leads to the activation of negative metacognitions about suicide and an escalating aggravation of suicidal ideation/behavior. Initial studies support the model assumptions. However, investigations in highly burdened inpatient samples as well as studies in non-Western samples are missing by now.MethodsA total of 209 Iranian psychiatric inpatients (56.9% female; age M = 31.14, SD = 11.04) took part in a cross-sectional assessment. Self-report measures to assess suicidal ideation/behavior, depressive symptoms, suicide-specific rumination, and metacognitions about suicide were used.ResultsPositive metacognitions about suicide were associated with suicide-specific rumination. Suicide-specific rumination was associated with negative metacognitions about suicide. Suicidal thoughts were positively and positive metacognitions about suicide were negatively associated with lifetime suicide attempts.ConclusionThe results support assumptions of the metacognitive model of suicidality and underscore the importance of metacognitions about suicide and suicide-specific rumination in understanding the suicidal process.
Editorial: Enhancing the social skills and social competence for children and adolescents with autism spectrum disorder
Sleep-related problems among patients with rheumatoid arthritis in the World Health Organization Eastern Mediterranean region: a systematic review and meta-analysis
BackgroundSleep-related problems are common among patients with rheumatoid arthritis (RA) and contribute substantially to disease burden and reduced quality of life. Evidence from the World Health Organization Eastern Mediterranean Region (WHO EMRO) remains fragmented, with variability in reported prevalence, sleep constructs assessed, and associated risk factors. This study aimed to systematically review and meta-analyze the prevalence and correlates of sleep-related problems among adults with RA in WHO EMRO countries.MethodsA systematic search of PubMed, Scopus, Web of Science, Embase, CINAHL, and Google Scholar was conducted to identify observational studies reporting sleep-related outcomes among adults (≥18 years) with RA in WHO EMRO countries from inception to 27 July 2025. Study screening, data extraction, and quality appraisal using Joanna Briggs Institute (JBI) checklists were conducted primarily by a single author, with methodological oversight and consultation from senior collaborators. Eligible studies reported prevalence or sufficient data to calculate prevalence of specific sleep-related constructs, including subjective sleep quality, insomnia symptoms, daytime sleepiness, or obstructive sleep apnea. Random-effects meta-analysis (DerSimonian-Laird) was used to pool prevalence estimates and odds ratios (ORs) for associated risk factors. Heterogeneity was assessed using the I² statistic and Cochran’s Q test. Subgroup analyses were conducted by sleep construct, assessment method, and country. Publication bias was evaluated using funnel plots, Egger’s test, and Begg’s test, with cautious interpretation due to the small number of studies.ResultsTen studies met inclusion criteria for qualitative synthesis, and six studies (n = 2,315 participants) were included in the quantitative meta-analysis. The pooled prevalence of sleep-related problems was 60.9% (95% CI: 56.5%–65.2%), with substantial heterogeneity (I² = 88%, p < 0.001), reflecting differences in sleep constructs and assessment methods. Subgroup analyses yielded pooled prevalence estimates of 58% for insomnia symptoms, 65% for obstructive sleep apnea-related measures, and 61% for poor subjective sleep quality (PSQI above cut-off), with no statistically significant differences between subgroups. Among associated factors, depression showed the strongest association with sleep-related problems (OR = 2.65; 95% CI: 1.87–3.75), followed by pain (OR = 2.18; 95% CI: 1.68–2.84), fatigue (OR = 1.91; 95% CI: 1.45–2.52), female gender (OR = 1.67; 95% CI: 1.25–2.23), and older age (OR = 1.42; 95% CI: 1.12–1.80). Heterogeneity for risk factor analyses ranged from low to moderate. Publication bias assessments did not indicate statistically significant small-study effects but were underpowered.ConclusionSleep-related problems—assessed using heterogeneous subjective and objective measures—are highly prevalent among patients with RA in WHO EMRO countries with available data. Given substantial clinical and methodological heterogeneity and the limited number of contributing countries, findings should be interpreted as reflecting overall sleep-related burden rather than the prevalence of a single clinical disorder. Routine screening, multidisciplinary management, and culturally adapted interventions are recommended. Future large-scale, longitudinal studies using standardized diagnostic criteria across a broader range of WHO EMRO countries are needed to strengthen the evidence base.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251109906, identifier CRD420251109906.
Pathogenic germline variants identify elevated cancer risk in pediatric patients referred for genetic testing
Nature Medicine, Published online: 29 May 2026; doi:10.1038/s41591-026-04451-1
Through large-scale genomic analysis, we show that pathogenic germline variants in pediatric cancer-predisposition genes are associated with increased subsequent tumor risk, highlighting their value for counseling and surveillance.
Mapping the genetic diversity of Indigenous Americans
Nature Medicine, Published online: 29 May 2026; doi:10.1038/d41591-026-00028-0
A comprehensive analysis of Indigenous American genomes charts an evolutionary history shaped by unique geographic and cultural environments, climate shifts, and colonization, and reveals natural selection of genes involved in immunity, metabolism and reproduction.
An unexpected molecular explanation for how tau aggregation begins in Alzheimer’s disease
Nature Neuroscience, Published online: 29 May 2026; doi:10.1038/s41593-026-02298-w
Disruption of a neuronal-specific protein degradation system, the plasma membrane-bound neuroproteasome, triggers the conversion of endogenous tau into aggregates that mirror those seen in patients with Alzheimer’s disease (AD). Aging and APOE4 — the largest risk factors for AD — induce neuroproteasome loss, which provides a potential mechanistic basis for sporadic AD.
Neuroproteasomes regulate endogenous tau paired helical filament formation in an APOE genotype- and age-dependent manner
Nature Neuroscience, Published online: 29 May 2026; doi:10.1038/s41593-026-02297-x
A cellular explanation for how tau aggregates into fibrils in Alzheimer’s disease has been elusive. This paper identifies the failure of ‘neuroproteasomes’ as sufficient to convert tau into paired helical filaments, a process regulated by ApoE and aging.