Iron is an indispensable element for the normal physiological function of the brain. In terms of neuronal metabolism, iron is involved in multiple critical biological processes such as oxygen transport, energy metabolism, DNA synthesis, neurotransmitter synthesis and myelin formation. Maintaining brain iron homeostasis is crucial for neurodevelopment and function. Iron dyshomeostasis has been associated with the onset and progression of various neuropsychiatric disorders, including Parkinson's disease, Alzheimer's disease, depression, schizophrenia, attention deficit hyperactivity disorder, and autism spectrum disorder. In neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, abnormally elevated iron levels can be detected in specific brain regions, including the basal ganglia and the prefrontal cortex. These changes are often accompanied by pathological processes such as oxidative stress, neuroinflammation, and pathological protein aggregation. Therefore, brain iron metabolism is an important entry point for understanding the pathophysiological process of neuropsychiatric disorders. Mechanistically, iron overload induces oxidative damage through the Fenton reaction, exacerbating mitochondrial dysfunction and abnormal protein aggregation. The effects of iron deficiency vary across different diseases; its impact on myelination and neurotransmitter synthesis may increase the risk of neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD), while its effects on immune activation and energy metabolism may contribute to the development of mental disorders such as depression. This article systematically reviews the current research progress of the role of cerebral iron metabolism in neuropsychiatric diseases. It focuses on the mechanisms underlying iron homeostasis imbalances in neurodegenerative and psychiatric diseases. Building on this foundation, the article analyzes the therapeutic targets and clinical significance of iron metabolism-related interventions and outlines future research directions in this field.

Schizophrenia is a severe psychiatric disorder. Catatonia is relatively common in schizophrenia; its main manifestations include catatonic stupor, mutism, negativism, and other psychomotor symptom clusters. Patients with schizophrenia are at increased risk of infections, which are also recognized triggers for Guillain-Barré syndrome (GBS). GBS typically presents with limb weakness, paresthesia, facial weakness, respiratory muscle paralysis, and autonomic symptoms, and may similarly result in severe immobility and impaired communication. Consequently, when schizophrenia (especially with catatonic features) coexists with GBS, history taking and clinical assessment can be challenging, increasing the risk of misdiagnosis or delayed diagnosis.

We report a 28-year-old man with a 3-year history of schizophrenia who was found after 2 weeks of lost contact and admitted emergently. His first episode featured hallucinations, persecutory delusions, and catatonia, which remitted with antipsychotic and other medications treatment. He subsequently relapsed twice after discontinuing medication; both relapses presented mainly with hallucinations and delusions without catatonia and remitted after re-treatment, followed by regular risperidone maintenance. In the current episode, hallucinations and delusions recurred and progressed to apathy, reduced speech and activity, and eventually complete mutism, immobility, and inability to perform self-care. Schizophrenia was initially diagnosed per DSM-5 criteria and risperidone was initiated. Further evaluation revealed pulmonary infection with limb weakness and decreased tendon reflexes, differing from the increased muscle tone typical of catatonia. Cerebrospinal fluid showed albuminocytologic dissociation (protein 0.61 g/L; leukocytes 1.2×10^6/L), and comorbid Guillain-Barré syndrome was considered. He was transferred to neurology and treated with intravenous immunoglobulin (25 g/day for 5 days) plus rehabilitation, with gradual improvement. During the 1-year follow-up, the patient continued risperidone 4 mg as maintenance to prevent psychiatric relapse; his symptoms had essentially resolved, and he returned to normal work and daily life.

In psychiatric practice, mutism and immobility are often attributed to primary psychiatric illness, particularly in patients with established diagnoses, which can lead to missed or delayed detection of medical conditions. This case underscores the importance of thorough neurologic examination and timely investigations in uncooperative patients, especially after antecedent infection, including consideration of lumbar puncture to evaluate for comorbid neurologic disorders such as Guillain-Barré syndrome.

Healthcare professionals responding to disasters, mass casualty incidents, pandemics, and sustained high-acuity clinical environments face extraordinary ethical and emotional demands. While burnout and post-traumatic stress disorder (PTSD) have historically framed clinician distress, these constructs incompletely capture the moral and existential harm experienced when clinicians are forced to act in ways that conflict with deeply held professional and ethical values. Moral injury has emerged as a distinct framework to explain this phenomenon. This review synthesizes current understanding of moral injury in disaster, mass casualty, and crisis care settings, distinguishing it from burnout and PTSD, examines prevalence and impact on clinicians and healthcare systems, identifies unique individual, organizational, and situational risk factors, and reviews mitigation and recovery strategies across the disaster continuum. Critical gaps in measurement and research are highlighted, particularly in command-driven healthcare environments. Addressing moral injury requires system-level interventions, ethical transparency, and leadership accountability to sustain the healthcare workforce beyond the immediate crisis.

Shoulder pain (SP) is prevalent, costly, and linked to low quality of life, high pain levels, disability, and mental health issues. Despite guidelines, orthopaedic surgeons vary in surgical indicators and clinical decision-making. This study investigates if clinicians adhere to guidelines in an observational study.

In a French prospective multicentre study, four clinicians assessed patients with shoulder pain, recommended surgery or conservative management, and followed up at 4, 6, and 12 months. Comparative demographic and clinical data were used at baseline. Participants receiving surgery or conservative care within diagnostic and pain severity categories were compared to guidelines. An attrition analyses compared participants at baseline and 12-month follow-up.

Of 189 participants, the majority of impingement and tendinopathy diagnoses were managed conservatively. More full-thickness tear diagnoses were recommended for surgical repair, and those recommended for surgery had more severe pain. Participants with high SMS completion (≥80%) and low SMS completion (<80%) were similar at baseline (based on age, sex, education, pain severity, duration, and disability) and at 12-month follow-up.

Clinicians recommended treatment in line with guidelines, emphasising rotator cuff tear presence and high pain intensity. Patients recommended surgery differed from those recommended conservative management, so future analyses should compare these treatment groups.

Complex traits arise from the combined effects of rare and common genetic variation, development and environment, but resolving their joint contributions has been limited by statistical power. Here, we meta-analyze effects of recurrent copy number variants (CNVs), polygenic scores, sex, age and medications on height and body mass index in 1,447,001 individuals across 6 biobanks and clinical cohorts. CNVs show largely mirror dose-dependent effects of deletions and duplications on both traits, but a subset of loci exhibit asymmetric dose-responses on adult height, consistent with buffering of one allele but not the other. Polygenic background and medications combine with CNVs in ways broadly consistent with additivity. However, detailed analyses of loci at 16p11.2 and 22q11.2 reveal context-dependent effects that vary across development, physiology and sex. At 22q11.2, the net effect of a CNV reflects opposing and reinforcing contributions of multiple genes, providing a potential mechanism for buffering of dosage effects. These results indicate that genetic effects follow additive patterns in aggregate, while context-dependent deviations are widespread for specific loci.

Identifying multiple sclerosis (MS) in children early is critical, as early therapeutic intervention can improve outcomes. The anterior visual pathway has been demonstrated to be of central importance in diagnostic considerations for MS and has recently been identified as a fifth topography in the McDonald Diagnostic Criteria for MS. Optical coherence tomography (OCT) provides high-resolution retinal imaging and reflects the structural integrity of the retinal nerve fiber and ganglion cell inner plexiform layers. Whether multimodal deep learning models can use OCT alone to diagnose pediatric onset MS (POMS) is unknown.

We analyzed 3D OCT scans collected prospectively through the Neuroinflammatory Registry of the Hospital for Sick Children (REB#1000005356). Raw macular and optic nerve head images, and 52 automatically segmented features were included. We evaluated three classification approaches: (1) deep learning models (e.g., ResNet, DenseNet) for representation learning followed by classical ML classifiers, (2) ML models trained on OCT-derived features, and (3) multimodal models combining both via early and late fusion.

Scans from individuals with POMS (onset 16.0 ± 3.1 years, 51.0% female; 211 scans) and 29 children with non-inflammatory neurological conditions (13.1 ± 4.0 years, 69.0% female, 52 scans) were included. The early fusion model achieved the highest performance (AUC: 0.90, weighted F ₁: 0.87, macro F ₁: 0.77, accuracy: 87%), outperforming both unimodal and late fusion models. The best unimodal feature-based model (SVC) yielded an AUC of 0.84, weighted F ₁ of 0.85, macro F ₁ of 0.73, and accuracy of 85%, while the best image-based model (ResNet101 with SVC) achieved an AUC of 0.79, weighted F ₁ of 0.84, macro F ₁ of 0.70, and accuracy of 87%. Late fusion underperformed, reaching 82% accuracy but failing in the minority class.

Multimodal learning with early fusion significantly enhances diagnostic performance by combining spatial retinal information with clinically relevant structural features. This approach captures complementary patterns associated with MS pathology and shows promise as an AI-driven tool to support pediatric neuroinflammatory diagnosis.

Multimodal exercise programs do not specifically target lumbar paraspinal musculature, but incorporate aspects of different exercises to have an overall benefit.

To investigate the effect of a multimodal exercise program on paraspinal muscle volume and composition, and patient outcomes in individuals with chronic low back pain (CLBP).

Thirty-four participants with CLBP either completed a 14-week high-intensity training program (n = 8) including cardiorespiratory and resistance exercises 3 sessions per week or were waitlisted (n = 26). Participants underwent magnetic resonance imaging at baseline and post-intervention to assess paraspinal muscle volume (cm3) and fatty infiltration (% FI) at L3-L4, L4-L5, and L5-S1. Pain, disability, quality of life, pain-related fear (catastrophizing and Kinesiophobia), and anxiety were assessed via validated self-reported questionnaires.

Mixed-design ANOVA revealed no significant time × group interactions for paraspinal muscle volume and %FI. An exploratory analysis revealed a significant increase in multifidus %FI in the control group at L3-L4, L4-L5, and L5-S1, with a concomitant increase in multifidus volume at L3-L4 and L5-S1. The exercise group had a significant increase in multifidus %FI and volume at L5-S1. Significant time × group interactions for pain, disability, catastrophizing and kinesiophobia, and a main effect of group in physical and mental health were found. Significant correlations were found between changes in patient-reported and functional outcomes with paraspinal muscle morphology.

Multimodal exercise programs may help prevent LBP-related paraspinal muscle atrophy and %FI, and lead to concomitant improvements in pain, disability and pain-related fear in individuals with CLBP.

Adolescent athletes have specific developmental risks for sports injury and the onset of mental health problems. Research has typically focused on mental health during specific sports injury phases, such as rehabilitation, with little consideration for factors linked to adolescence. This qualitative study retrospectively explored factors influencing adolescent athletes' mental health across the injury course, emphasising developmental, social, environmental and sport-cultural contexts. Semistructured interviews were conducted with 27 athletes aged 16-21 years who had sustained a severe time-loss injury in the past 6 months. Participants completed a visual timeline to support reflections on mental health from injury onset to rehabilitation or return to sport. Data were analysed using reflexive thematic analysis, combining inductive and deductive approaches. Five themes described factors linked to fluctuating mental health. 'Finding my inner strength' explores how injury introduced vulnerability to developing personal identities, which led to self-blame for injury-risk behaviour, training through pain and social withdrawal. 'Making sense of my emotions' describes how injury triggered overwhelming worries, amplified by unexplained pain and losing sport as a coping strategy. 'Learning to look after myself' considers how athletes' growing independence and emotional autonomy can be thwarted by parents during injury, prompting frustration and lowered self-esteem. 'Accepting peer judgement and support' explores how worries about peer evaluation led to concealing injury and social withdrawal, and social exclusion prompted lowered mood and self-esteem. 'Adapting to the system' describes how diagnostic uncertainty and rigid or unsupportive sport cultures caused frustration and lowered self-esteem, and prevented help-seeking. Cognitive flexibility and emotion regulation skills at the individual level, and social support and mental health literacy at interpersonal and organisational levels, were positive for adolescents' mental health at challenging points during injury. These factors may make suitable intervention targets to support athlete mental health while injured.

Gastroesophageal reflux (GER) is a common physiological phenomenon in infants, typically self-limited, but often a source of parental concern. When non-pharmacological measures fail to improve symptoms, thickened formulas are commonly used. Zinc-L-carnosine (Polaprezinc) is a mucosal protectant with anti-inflammatory and antioxidant properties. It is widely used in gastrointestinal disorders in adults but has not yet been extensively studied in infants. We aim to evaluate the clinical effectiveness and cost impact of a Zinc-L-carnosine-based supplement (Hepilor liquido®) compared to thickened formula in infants with persistent regurgitation.

This was a two-center, prospective, single-blind, randomized, non-inferiority study conducted in two Italian pediatric hospitals. Infants aged 4 weeks to 7 months with persistent regurgitation despite appropriate nutritional and behavioral management were randomized to receive either Hepilor liquido® or thickened formula for 8 weeks. The primary outcome was symptom improvement based on the I-GERQ-R (Infant Gastro-Esophageal Reflux Questionnaire-Revised) score. Secondary outcomes included a reduction in regurgitation frequency and treatment cost analysis.

Sixty infants aged 4 weeks to 7 months were randomized to receive either Hepilor liquido® (n = 30, 50%) or thickened formula (n = 30, 50%) for 8 weeks. Both groups showed significant improvement in I-GERQ-R scores at 8 weeks. Although no statistically significant difference was observed in overall symptomatic remission, the Hepilor liquido® group demonstrated a greater reduction in regurgitation frequency. Notably, the average treatment cost was significantly lower in the Hepilor® group compared to the thickened formula. No severe adverse events were recorded in both groups.

Zinc-L-carnosine is a safe and effective alternative to thickened formula in treating persistent infant regurgitation, after the failure of non-pharmacological measures. Its lower cost and promising clinical effect support further investigation in larger pediatric cohorts.

https://clinicaltrials.gov/study/NCT06678997, identifier: NCT06678997.

Social anxiety (SA) is highly prevalent among autistic adults, yet little is known about how autistic people respond to common therapeutic strategies, such as exposure tasks. This study examined responses to a structured speech exposure task embedded within an 8-week modified cognitive-behavioral therapy (M-CBT) program. Thirty-two autistic adults with co-occurring SA completed pre- and post-task assessments of anxiety and related cognitive appraisals, including self-focused attention, perceived performance, appearance concerns, and threat appraisals. Participants reported appropriate engagement with the task, characterized by elevated anticipatory anxiety followed by reductions in anxiety during the speech. Responses were largely consistent with CBT models of social anxiety and with reports by those in a social anxiety disorder reference group. Participants overestimated anticipatory anxiety (predicted fear) relative to experienced peak fear during the task. Higher anxiety was associated with greater self-focused attention and stronger threat appraisals, although anxiety correlated positively with self-rated performance. Importantly, the extinction of fear during the speech task was associated with post-treatment response to CBT. Among participants classified as high-extinction, 59% showed clinically significant improvement on the Liebowitz Social Anxiety Scale, Self-Report (LSAS-SR), compared with 25% of those in the low-extinction group. A parallel pattern was observed in a social anxiety disorder comparison group, indicating that the extinction-outcome relationship was similar across autistic and non-autistic adults. This study provides evidence that autistic individuals report fear and anxiety responses in a manner largely consistent with CBT models and that extinction-based processes during exposure are meaningfully associated with treatment response. Further studies employing randomized controlled trials and objective measures of fear are now needed.