Search Results (38,310)

Background: Post-psychotic depression (PPD) is an underestimated but clinically significant affective syndrome that occurs during remission from psychosis, particularly in schizophrenia. Material and Methods: This comprehensive review traces the evolution of this concept over five decades of research, starting from its initial differentiation from primary depression and schizoaffective disorders in the 1970s. Relying on more than thirty studies, we analyze historical definitions, biological and psychosocial mechanisms, diagnostic controversies, and therapeutic implications. Results: Research indicates that PPD develops from multiple contributing factors, including psychological insight, autobiographical disturbances, pharmacological influences, and social losses, rather than simply as a byproduct of psychosis or pharmacological treatment. We discuss the persistence of depressive symptoms after acute remission, their role in suicidal tendencies, and the diagnostic challenges arising from the overlap of negative symptoms and demoralization. Despite its exclusion from current diagnostic standards, PPD continues to affect a significant fraction of patients, particularly those with high insight and early onset. Conclusions: Effective treatment requires a multidimensional, phase-specific approach combining antidepressants, atypical antipsychotics such as lurasidone, and psychological interventions targeting identity, self-esteem, and narrative processing. We argue that PPD should be reintroduced as a distinct clinical unit and incorporated into psychiatric guidelines to reduce diagnostic oversights and improve patient outcomes. Full article

Advanced Glycation End Products (AGEs) are reactive compounds formed through the non-enzymatic glycation of proteins, lipids, or nucleic acids due to exposure to reducing sugars. They accumulate through endogenous metabolic dysregulation and exogenous dietary intake, particularly high-fat and high-sugar foods prepared at high temperatures. The interaction between AGEs and their receptor, RAGE (receptor for Advanced Glycation End Products), has been implicated in a range of pathological conditions, including diabetes and metabolic syndrome. However, the impact of AGEs accumulation on neurodevelopment remains poorly understood. In this study, we investigated the effects of AGEs on human-induced pluripotent stem cell (iPSC)-derived cerebral organoids comprising neurons, astrocytes, and microglia. Our findings reveal that AGEs induce RAGE expression, leading to microglial activation, increased deposition of amyloid-beta (Aβ) aggregates, and impaired neurodevelopment. Additionally, elevated levels of AGE-modified proteins, along with altered microglial polarization, were observed in cerebral organoids modeling Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism–Dementia Complex (ALS-PDC). These findings demonstrate AGEs as active drivers of neurodevelopmental disruption and establish a mechanistic link between metabolic stress and increased susceptibility to neurodegenerative disease. Full article

Zinner syndrome is a rare congenital anomaly of the male genitourinary tract, characterized by the triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst, and ejaculatory duct obstruction. Owing to its low prevalence and nonspecific clinical presentation, diagnosis is often delayed or incidental, with imaging playing a central role in detection and characterization. This study presents a narrative review with an illustrative case report, aiming to summarize the imaging features of Zinner syndrome, outline the main radiologic differential diagnoses of seminal vesicle cysts, and highlight common diagnostic pitfalls, with emphasis on cross-sectional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI). The narrative review of the literature highlights that CT and MRI are essential for accurate anatomical localization, characterization of cystic content, and identification of associated genitourinary anomalies. MRI, in particular, provides superior soft-tissue contrast and is considered the reference modality for diagnosis and differential evaluation of male pelvic cystic lesions. Key differential diagnoses include Müllerian duct cysts, prostatic utricle cysts, and ejaculatory duct cysts. As an illustrative example, we report the case of a young adult male presenting with pelvic discomfort, infertility, and mild lower urinary tract symptoms. Imaging findings, including ultrasound and cross-sectional studies, demonstrated a seminal vesicle cyst associated with ipsilateral renal agenesis, consistent with Zinner syndrome. Zinner syndrome should be considered in the evaluation of male pelvic cystic lesions, particularly in the presence of unilateral renal agenesis. Awareness of its characteristic imaging features is essential for accurate diagnosis and appropriate management, with MRI playing a pivotal role in confirming the diagnosis and distinguishing it from other pelvic cystic entities. Full article

Background: Congenital heart disease (CHD) represents a major cause of perinatal morbidity and mortality, and fetal echocardiography is essential for its early diagnosis and management. Maternal smoking has been suggested as a potential teratogenic factor affecting fetal cardiovascular development; however, findings regarding its association with CHD remain inconsistent. This study aimed to evaluate the relationship between maternal smoking during pregnancy and the risk of CHD. Methods: A total of 2715 pregnant women and 2784 fetuses who underwent fetal echocardiography at ≥20 weeks’ gestation between 1 January 2024 and 1 November 2025 were analyzed. Pregnancies complicated by known chromosomal or syndromic abnormalities, significant teratogenic exposure, duplicate assessments, or nonstandard examinations were excluded. Maternal smoking status during pregnancy was recorded and categorized according to daily cigarette consumption. The prevalence of CHD and the distribution of CHD subtypes were evaluated and compared according to smoking status. Fetal cardiac diagnoses were classified based on the classical morphological classification system. Results: A total of 2715 pregnancies (2784 fetuses) were analyzed, including 2530 fetuses in the non-smoking group and 254 in the smoking group. Congenital heart disease was detected in 12.5% of fetuses in the non-smoking group and 14.2% in the smoking group, with no statistically significant difference (p = 0.442). According to the classical morphological classification, the distribution of fetal echocardiographic pathologies did not differ significantly between groups (p = 0.607). Septal defects were the most common subtype in both groups. Although conotruncal defects were proportionally more frequent in the smoking group, this difference did not reach statistical significance. After reclassifying daily cigarette consumption into four exposure categories, no association was detected between maternal smoking and CHD risk (OR = 1.04; 95% CI: 0.86–1.26; p = 0.691). Conclusion: In this cohort referred for fetal echocardiographic evaluation, no association was detected between maternal smoking during pregnancy and the risk of congenital heart disease or alterations in CHD subtype distribution. No consistent dose–response relationship was observed. These findings suggest that no association was detected between maternal smoking exposure and CHD. Further large-scale prospective studies are needed to clarify phenotype-specific associations. Full article

Obesity is associated with menstrual dysfunction, anovulation, and infertility, particularly in women with polycystic ovary syndrome (PCOS). This narrative review summarizes evidence on the effects of bariatric surgery [focusing on sleeve gastrectomy (SG) Roux-en-Y gastric bypass (RYGB)] on female reproductive function and fertility outcomes. Developed according to SANRA (Scale for the Assessment of Narrative Review Articles) principles, a structured search of PubMed, Scopus, and Web of Science (English language; inception–30 September 2025) was conducted, using fertility-related terms (e.g., fertility, ovulation, IVF/ART, AMH, PCOS, pregnancy, live birth, time to conception) combined with bariatric surgery terms (SG/VSG, RYGB, metabolic/bariatric surgery, and weight loss surgery). Guidelines from IFSO, BOMSS, and ASMBS were also reviewed. Findings were synthesized narratively. Across mainly observational studies, bariatric surgery is associated with improved menstrual regularity, increased ovulation, reduced hyperandrogenism, and improved insulin sensitivity, with higher conception rates reported after substantial weight loss. AMH responses are inconsistent across studies and their clinical significance remains uncertain. SG and RYGB appear to improve fertility-related outcomes in women with obesity. Programming of pregnancy and nutritional monitoring are critical. In conclusion, long-term, standardized reproductive endpoints are needed to clarify bariatric surgery-associated effects during pregnancy. Full article

Background: Wolfram syndrome (WFS) is a rare neurodegenerative disease that is genetically determined and inherited in an autosomal recessive manner. Although the first clinical symptom appearing in early childhood is diabetes mellitus, subsequent symptoms are associated with optic nerve atrophy, followed by central nervous system atrophy. Methods: The aim of the study was to analyse magnetic resonance images (MRI) of the brain in combination with single-voxel magnetic resonance spectroscopy (MRS) and to assess the copy number of mitochondrial DNA (mtDNA-CN) in 10 patients with WFS compared with a control group of 17 healthy individuals. Results: A significant decrease in the amount of selected metabolites was observed in WFS patients compared to controls in all assessed brain regions (pons, cerebellum, white matter, thalamus, and hippocampus). For three metabolites, Glutamate (Glu), Glutamate + Glutamine (Glx) and total N-acetylaspartate (TNAA), significant differences in concentrations were found between the study groups in almost all matrices evaluating specific areas of the brain (p < 0.011), with the exception of a trend toward reduced TNAA in the hippocampus (p = 0.065). In addition, patients with WFS had a significant decrease in the mitochondrial-to-nuclear DNA ratio compared to controls (p < 0.0003). Some metabolites, such as N-acetylaspartate and total N-acetylaspartate, showed strong correlations with specific regions of the visual pathway on MRI scans in patients with WFS. Conclusions: Selected brain metabolites and mtDNA-CN may become potential markers of WFS, and the results of this study may be used to define indicators for future therapeutic strategies. Full article

Background: Rome IV criteria promote a symptom-based (“positive”) diagnosis of pediatric disorders of gut–brain interaction (DGBIs). In clinical practice, however, organic gastrointestinal diseases may mimic DGBIs and lead to diagnostic revision after further evaluation. We aimed to quantify the diagnostic stability of an initial Rome IV-oriented functional diagnosis in a tertiary pediatric outpatient setting and to identify symptom phenotypes associated with a higher likelihood of later organic reclassification. Methods: We performed a single-center retrospective cohort study (2014–14 May 2021) based on outpatient chart review. Eligible patients were children and adolescents aged 0–18 years with an initial Rome IV-oriented functional diagnosis. Diagnostic reassessment was based on follow-up data, available laboratory and instrumental investigations, and/or response to exclusion therapies. Final diagnoses after reassessment were categorized as functional only, organic, or mixed. Groups were compared using Pearson’s chi-square test. Results: The cohort included 220 males (50.0%) and 220 females (50.0%), with a mean age of 8.86 ± 4.65 years. After reassessment, 343/440 (77.95%) remained functional, 73/440 (16.59%) were reclassified as organic, and 24/440 (5.45%) were classified as mixed. Final diagnosis differed by GI tract involvement (p = 0.001) and by symptom cluster (p = 0.001). Upper GI/dyspepsia-spectrum presentations showed the highest organic yield (27.03%), followed by lower abdominal pain/IBS-spectrum presentations (19.61%). Diarrhea and vomiting/cyclic vomiting each showed 16.67% organic diagnoses (mixed: 10.0% and 7.14%, respectively), whereas constipation showed the greatest diagnostic stability (98.89% functional; 1.11% organic). Functional confirmation rates were similar before and during the pandemic (77.71% vs. 78.70%; p = 0.756). Monthly case volume was higher in 2020–2021 (6.29 vs. 4.61 cases/month). Conclusions: In this tertiary cohort, about one in six children initially diagnosed with a functional disorder were later found to have an organic disease, and an additional 5% had mixed organic–functional presentations. Diagnostic revision was associated with presenting phenotype, with the highest organic yield observed in dyspepsia/upper GI presentations and the lowest in constipation. These findings support symptom-stratified evaluation and follow-up alongside Rome IV criteria. Full article

Liver transplantation is the definitive therapy for end-stage liver disease, yet persistent organ shortages result in approximately 10% of recovered livers being discarded, with markedly higher discard rates among marginal grafts from elderly donors, donation after circulatory death (DCD), and those with macrovesicular steatosis. Machine perfusion (MP) has emerged as a paradigm-shifting preservation strategy with the potential to safely expand the usable donor pool. This narrative review examines the current evidence for three MP modalities—hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), and normothermic regional perfusion (NRP)—across various marginal donor populations, including elderly donors, steatotic grafts, donors with infectious diseases, and split liver transplantation. Current evidence demonstrates that MP significantly increases utilization of steatotic grafts with up to an eightfold rise in usage of severely steatotic organs. HMP consistently reduces non-anastomotic biliary strictures and early allograft dysfunction across donor types, while NMP enables real-time viability assessment and reduces post-reperfusion syndrome in steatotic grafts. NRP shows particular benefit in DCD organs, reducing biliary complications and improving one-year survival. Additionally, MP extends preservation times enabling next-day split liver transplantation and shows promise as a platform for ex situ antiviral therapy. Despite compelling evidence supporting MP in marginal grafts, widespread adoption remains constrained by high costs, logistical complexity, and the absence of standardized protocols. Future progress will require multicenter studies evaluating long-term outcomes alongside consensus-driven implementation frameworks. Full article

This study examined the association between sensory-rich messy play and language development in children with Down syndrome (DS) and children with intellectual disabilities of unknown etiology (IDUE). Drawing on Vygotsky’s sociocultural theory and the framework of embodied cognition, the study investigated whether different play contexts are differentially associated with expressive and receptive language outcomes across developmental populations. A 2 × 2 quasi-experimental pretest–posttest design was employed. Forty children aged 4 to 6 years were assigned to one of four conditions based on diagnostic group (DS vs. IDUE) and intervention type (sensory-rich messy play vs. structured non-sensory play). Language development was assessed before and after a 12-week intervention using the LaTo standardized test. Mixed-design analyses of variance revealed significant improvements in language performance over time, as well as significant effects of intervention type and diagnostic group. Children who participated in sensory-rich messy play demonstrated greater gains in expressive and receptive language compared to those engaged in structured play. A significant interaction between diagnostic group and intervention type was also observed, indicating that the association between play context and language development differed across groups. In particular, children with DS in the messy play condition showed the most pronounced improvements, especially in expressive language. These findings suggest that sensory-rich play contexts are associated with enhanced language outcomes, particularly for children with DS. However, due to the quasi-experimental design, causal interpretations should be made with caution. These findings suggest that sensory-rich play contexts are associated with enhanced short-term language outcomes, particularly for children with DS. However, due to the quasi-experimental design and the absence of follow-up assessment, conclusions regarding long-term or causal effects should be made with caution. Full article

Background and aims: Abdominal aortic aneurysm (AAA) is a vascular disease characterized by the progressive dilation of the aorta, culminating in rupture. At present, there are no pharmacological treatments to prevent AAA development or reduce rupture rate. A recent study showed that patients prescribed Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have significantly lower risks of mortality, AAA repair, and acute abdominal aortic syndrome. Semaglutide is a GLP-1RA with increased agonist capacity and longer half-life, compared to earlier generations of GLP-1RAs. In this study, we aimed to investigate the role and mechanisms of semaglutide in the prevention of AAA development and rupture in a murine model. Methods: AAA was induced in apolipoprotein-E-deficient mice, by continuous subcutaneous infusion of angiotensin II. Treatment with semaglutide (12 µg/kg) began seven days after disease induction (rescue trial) or simultaneously with disease induction (prophylactic trial). At experimental endpoint, aortic diameter was measured by high-frequency ultrasound and the aortic tissue was collected for histological analysis. Results: Prophylactic treatment with semaglutide drastically reduced mortality by dissection and rupture during the first seven days of disease development, but did not affect AAA formation at 28 days. Histological evaluation of the aorta at day seven showed a normal vessel wall thickness with a trend for a higher content of collagen in the aortic wall in mice treated with semaglutide, compared to controls. Conclusions: Semaglutide prevents aortic rupture and dissection in the early phases of AAA development in the angiotensin II mouse model, likely by promoting the maintenance of an adequate proportion of collagen in the vessel wall. Full article

Background/Objectives: Surfactant has been delivered via less-invasive surfactant administration (LISA) in our neonatal intensive care unit (NICU) since 2020. Data have been monitored and the literature regularly reviewed to improve our LISA practice. The purpose of this project is to share the clinical practice changes made to help other NICU providers fine-tune their LISA practice. Methods: The original LISA criteria included babies with GA 27–36 6/7 w, on > 21% O₂, on continuous positive airway pressure (CPAP), pCO₂ < 70 if a blood gas was obtained, and radiographic and/or clinical evidence of respiratory distress syndrome (RDS). Current criteria include GA 25–35 6/7 w and minimum CPAP + 6. This manuscript highlights the changes made since 2023. To monitor these changes, targeted data from the entire cohort were examined before and after each change. Results: LISA was attempted on 399 babies (average (SD) GA 31.7 (2.7), birth weight 1752 (590), with a procedural success rate of 97%. Overall, 18% required intubation within 7 days after LISA. The median (IQR) for FiO₂ was 32 (28, 40) prior to LISA and 23 (21, 30) post-LISA and the hour of age of LISA was 4 (2.5, 9.9). LISA procedure success rate was increased by the use of video laryngoscopy as well as reinforcement of the use of sucrose sedation and swaddling; our first attempt success increased overall from 39% to 52%. After the introduction of a clinical RDS score (Downes), there was an expected and logical increase in the number of infants requiring intubation within 7 days of LISA indicating likely over-treatment prior to this change. After implementation of a clearly described plan for babies <28 w gestation there was a decrease in the hour of age of LISA from 3 (2.5, 4.5) to 2 (0.8, 3) h. Conclusions: It is critical to continually evaluate a new practice and identify strategic changes. We offer our changes to assist others starting or using LISA. Full article

Resveratrol (RSV), a bioactive polyphenol, has emerged as a pleiotropic modulator within the integrated pathophysiology of cardiovascular disease (CVD) across the life course. Effective CVD management requires a transition from organ-centric frameworks to systems-level models that acknowledge dynamic crosstalk among metabolic, renal, and cardiovascular networks. Oxidative stress constitutes a central unifying axis in this interconnected biology, propagating cross-organ injury from early developmental stages onward. Mechanistically, RSV acts as a redox-responsive gene regulator by activating the Nrf2–ARE pathway, restoring nitric oxide bioavailability, and orchestrating SIRT1, AMPK, and NF-κB signaling to recalibrate mitochondrial function, inflammatory tone, and endothelial integrity. Within the Developmental Origins of Health and Disease (DOHaD) paradigm, RSV exhibits reprogramming potential that attenuates the intergenerational transmission of hypertension, kidney disease, and metabolic dysfunction. Although clinical translation is constrained by limited bioavailability and rapid metabolism, advanced delivery systems and artificial intelligence-enabled optimization strategies provide promising avenues to enhance therapeutic precision and scalability. This narrative review integrates mechanistic and translational insights to position RSV as a systems-oriented life-course intervention with sustained and intergenerational relevance in CVD. Full article

Background/Objectives: Survival after pediatric intensive care unit (PICU) admission has improved, yet many children experience post-intensive care syndrome in pediatrics (PICS-p), including persistent feeding difficulties that impair growth and quality of life. An intensive feeding program (IFP), also known as intensive interdisciplinary behavioral treatment (IIBT), reduces tube dependence and improves oral intake; however, outcomes in PICU survivors remain understudied. This study aimed to evaluate feeding outcomes in children with prior PICU admission who completed IIBT. Methods: This study was a retrospective case series of children (0–18 years) admitted to the HDVCH, Corewell Health, Grand Rapids, Michigan, who subsequently completed IIBT (from 2007 to 2024). Variables included demographics, PICU course (admission indication, complications, length of stay, ventilation, and nutrition status) and IIBT outcomes (feeding modality, oral skills, and malnutrition status). Feeding outcomes were compared pre- and post-IIBT. Results: Sixteen patients were included (62.5% female; mean age 1.44 ± 1.21 years). Primary PICU admission causes were post-operative recovery (68.8%) and acute respiratory failure (25%). PICU complications included acute respiratory failure (43.8%) and the need for respiratory support beyond baseline (62.5%). At PICU discharge, 75% remained tube-fed and 18.8% were malnourished. The mean time from PICU discharge to IIBT initiation was 641 ± 385 days. At IIBT baseline, 75% were tube-fed and all were non-self-feeders. Following IIBT completion (mean length of stay 4.8 ± 0.9 weeks), 58% of tube-fed patients achieved tube removal eligibility; 44% transitioned to partial or full self-feeding; problematic mealtime behaviors decreased (45.7% → 9.9%); oral acceptance improved (62% → 95%); and mouth clearance improved (59% → 96%). Malnutrition prevalence decreased (20% → 12%). Conclusions: Children with prior PICU admission demonstrated substantial feeding and behavioral improvement during IIBT participation, with over half achieving tube-weaning eligibility. The time from referral to program start reflects barriers that delay intervention. Full article

Background/Objectives: Sleep disturbances have an impact on children’s physical and psychological development, yet little is known about the changes and factors influencing sleep after PICU discharge. To explore the trajectory of changes in sleep quality of critically ill children and to identify factors affecting sleep quality three months after Pediatric Intensive Care Unit (PICU) discharge. Methods: A longitudinal observation study was conducted between November 2022 and November 2023 at a tertiary children’s hospital. The Children’s Sleep Habits Questionnaire (CSHQ) was used at six time points: PICU-admission (T0), 1 week (T1), 2 weeks (T2), 1 month (T3), 2 months (T4), and 3 months (T5) after PICU discharge. The CSHQ is a 33-item parent-report outcome measure evaluating sleep problems. Total scores range between 33 and 99 points. A score of ≤41 indicates normal sleep; a score of >41 indicates sleep disturbance. Data were analyzed using the latent category growth model, univariate analysis, and multifactorial logistic regression. Results: Parents of 237 children completed all follow-up surveys. Prevalence of sleep disorders at T0-T5 of children with a score >41 were 46.5%, 83.5%, 69.7%, 54.3%, 50.2%, and 51.7%, respectively. General linear modeling revealed significant changes in CSHQ scores over time (F = 63.77, p < 0.05). The trajectories of identifying sleep changes were divided into three latent categories: High Sleep Disorder Group (n = 15, 6.33%), Moderate Sleep Disorder Group (n = 110, 45.2%), and No Sleep Disorder Group (n = 115, 48.52%). The trajectories were significantly different among preschool age, baseline sleep habit scores, surgery, and length-of-stay in pediatric wards (p < 0.05). The child’s age and surgical history were independent factors of sleep disturbance. Conclusions: The observed peak in sleep disturbances at 1-month post-PICU suggests that this period may be a critical window to develop and implement targeted interventions to improve sleep. The persistent sleep disorders highlight the need for long-term monitoring. Full article