Background: Long-term mental health support is not routinely offered to families of neonatal intensive care unit (NICU) graduates treated for non-cardiac congenital anomalies. This may reflect the paucity of evidence-based guidance for clinical practice in these diagnostic groups.Objective: This systematic review aimed to explore long-term mental health outcomes of NICU graduates and their parents, following treatment for non-cardiac congenital anomalies.Methods: A systematic review of empirical literature was conducted for the following diagnoses: congenital diaphragmatic hernia, oesophageal atresia, gastroschisis, exomphalos, Pierre Robin sequence, and Vein of Galen aneurysmal malformations. Embase, MEDLINE, and PsycINFO were comprehensively searched to identify relevant articles. Risk of bias assessments were conducted using the QualSyst quality assessment tool for articles meeting the following inclusion criteria: English- language articles published in peer-reviewed journals on or before 9 May 9 2025, that used validated quantitative mental health measures.Results: Of the 45 included articles, 38 examined child mental health and 14 investigated parental mental health (seven studies explored both child and parent mental health). Twenty-six measures were used, most commonly the Child Behavior Checklist for child mental health and the Short Form Health Survey for parental mental health. Although methodological heterogeneity yielded conflicting results, overall, the evidence summarised suggested both the child and parents were at an increased risk of long-term mental health difficulties.Conclusion: The evidence presented in this review highlights the value of incorporating routine mental health follow-up into the standard clinical care of children and families affected by congenital anomalies.

Hemp products (cannabis with ≤0.3% Δ9-tetrahydrocannabinol (Δ9-THC)) are federally legal, but few controlled experiments have explored drug test results, pharmacokinetics, or pharmacodynamics.

Healthy adults (n = 60) self-administered 1.5 mL medium-chain triglyceride (MCT) oil containing 100 mg cannabidiol (CBD) and either 0 mg, 0.5 mg, 1 mg, 2 mg, 2.8 mg or 3.7 mg Δ9-THC (n = 10 per group). The study included an 8-hour acute dose laboratory session (Phase 1), a 14-day outpatient drug exposure period with twice daily dosing (Phase 2) and a 7-day washout period (Phase 3). Measures including urine, blood, subjective drug effects, and cognitive and psychomotor performance were assessed repeatedly throughout the experiment.

At least one participant receiving Δ9-THC doses of 1.0 mg or greater had at least 1 positive urine drug test (Δ9-THC-COOH immunoassay screen ≥50ng/mL and LC-MS/MS confirmation ≥15ng/mL) during Phase 1 and the number of positive urine samples increased with Δ9-THC dose. Positive urine drug tests were observed during the Phase 2 outpatient drug exposure period from at least one participant in each dose condition that contained any amount of Δ9-THC. One urine specimen in the CBD only dose condition tested positive during Phase 2. Two positive urine samples were observed after the 1-week washout (Day 21). Blood concentrations of Δ9-THC were very low in all dose conditions, and there were no significant differences between the CBD only dose group and Δ9-THC-containing dose groups on any pharmacodynamic outcome.

Individuals subject to drug testing should recognize that hemp products contain detectable amounts of Δ9-THC. Conventional drug testing cannot reliably distinguish between illicit cannabis and legal hemp-derived product use, and a positive urine Δ9-THC test may result from low doses that do not produce intoxication or impairment.

Major depressive disorder (MDD) is a prevalent psychiatric illness, significantly contributing to disability and suicide rates. While dysfunctions in neurotransmission, notably monoaminergic transmission, are commonly attributed to MDD, involvement of the glutamatergic system in comorbid depressive disorders suggests its potential as a target for antidepressant therapy. Despite evidence of diminished glutamatergic neuron activity in the midbrain ventrolateral periaqueductal gray (vlPAG) in rodent models of depression-which projects to the ventral tegmental area (VTA), a region regulating depression-like behaviors-the precise neurocircuit mechanisms within the vlPAG remain unclear.

To investigate dysregulation of glutamatergic transmission in the vlPAG and its role in depression-like behavior, we combined behavioral testing, pharmacological manipulation, retrograde tracing, and electrophysiological recording in male C57BL/6 mice.

Mice receiving intravlPAG infusion of the mGlu2/3 receptor antagonist LY341495 exhibited reversal of depression-like behaviors. Chronic restraint stress (CRS) elicited depression-like behavior, whereas intravlPAG administration of LY341495 reversed these behaviors. VTA-projecting vlPAG neurons exhibited reduced frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) and decreased neuronal excitability. Blocking mGlu2/3 receptors, which act as autoreceptors inhibiting glutamate release, in the vlPAG rescued these effects. Moreover, intravlPAG microinjection of the L-type voltage-dependent calcium channel (VDCC) blocker verapamil, tropomyosin-related kinase B (TrkB) receptor antagonist ANA-12, mammalian target of rapamycin complex 1 inhibitor rapamycin, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione prevented LY341495-induced reversal of depression-like behaviors.

This provides the first direct evidence that blockade of mGlu2/3 receptors in the vlPAG ameliorates depression-like behavior, highlighting their role in regulating vlPAG-VTA neurocircuits implicated in MDD pathophysiology.

The new drug KarXT targets muscarinic receptors to reduce the positive and negative symptoms of schizophrenia. Haloperidol is effective in treating the positive symptoms of schizophrenia, while sulpiride has shown modest efficacy in alleviating negative symptoms. The shared and distinct molecular mechanisms of these drugs are unclear. This study aimed to determine if the mechanism for KarXT overlaps with the benefits of haloperidol for positive symptoms and sulpiride for negative symptoms.

The putative target genes for the three drugs were identified, and a protein-protein interaction network was constructed to identify core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the top 20 core targets were conducted. A drug-pathway-target-disease network was constructed.

The search yielded 179 common targets for haloperidol against positive symptoms, 96 targets for sulpiride against negative symptoms, and 99 targets for KarXT against schizophrenia. Haloperidol affects positive symptoms by targeting the IL-17 signaling pathway via TNF, IL6, IL1B, MAPK3, and CASP3, and sulpiride affects negative symptoms by targeting the PI3K-AKT signaling pathway via BDNF, INS, AKT1, IGF1, and BCL2. KarXT affects schizophrenia by targeting the MAPK signaling pathway via AKT1, FOS, CASP3, NFKB1, and IGF1. Molecular docking revealed good binding affinities between the drugs and the potential core targets.

This study provides insights into the distinct molecular mechanisms by which haloperidol and sulpiride affect distinct symptoms of schizophrenia. KarXT integrates the partial effects of both drugs, including CASP3 with haloperidol and AKT1 and IGF1 with sulpiride. Our results provide a theoretical basis for clinical applications and new directions for drug development.

CYP2D6 alleles with low frequency in Eurocentrically biased study populations are often excluded from pharmacogenetic investigation and consequently may have misassigned activity values. This health inequity may be contributing to imprecise dose predictions for CYP2D6-metabolizing drugs. The objective of this study was to determine how sub-Saharan African-specific CYP2D6*17 and *29 alleles affect risperidone metabolism. To do this, we generated the largest real-world cohort of risperidone users in an African study population for pharmacogenetic studies. Risperidone users ≤ 18 years old were recruited from the Federal Neuro-Psychiatric Hospital. Health records were obtained by parent report and paper charts. CYP2D6 genotyping was performed for > 20 variants. Plasma concentrations of risperidone and 9-hydroxyrisperidone were determined by liquid chromatography mass spectrometry. CYP2D6 activity was calculated based on the metabolic ratio 9-hydroxyrisperidone:risperidone. Multivariable linear regression modeling was performed to determine the association between our alleles of interest and log-transformed ratio-defined CYP2D6 activity relative to star alleles with established activity values. Across 208 enrolled participants, CYP2D6 activity value for *17 was found to be twice that of normal function alleles, while *29 was comparable to no function alleles. These results contrast previous values assigned to *17 and *29 from guidelines, which are not based on evidence with risperidone, suggesting the possibility of substrate specificity for these alleles. Ultimately, our findings have the potential to improve risperidone prescribing, especially for patient groups with substantial sub-Saharan African ancestry. Importantly, this work underscores the critical need to better understand the effects of ancestry-specific alleles for achieving equitable pharmacotherapeutic health outcomes.

Autism spectrum disorder involves challenges in social communication and restricted, repetitive behaviors. Historically, males have received autism diagnoses at comparatively high rates, prompting an underrepresentation of females in research and an incomplete understanding of sex-specific symptom presentations and comorbidities. This review examines sex differences in the prevalence of common comorbidities of autism to inform tailored clinical practices. These conditions include attention deficit hyperactivity disorder, anxiety disorders, conduct disorder, depression, epilepsy, intellectual disability, and tic disorders. Attention deficit hyperactivity disorder is prevalent in both sexes; however, females may more frequently exhibit the inattentive subtype. Anxiety disorders display inconsistent sex differences, while conduct disorder more frequently impacts males. Depression becomes more common with age; some studies indicate more pronounced symptoms in adolescent girls, while others suggest greater severity in males. Epilepsy is more prevalent in females, especially those with intellectual disabilities. Despite displaying a male predominance, intellectual disability may exacerbate the severity of autism to a greater degree in females. No clear sex differences have been found regarding tic disorders. Overall, contributors to sex-based differences include biases stemming from male-centric diagnostic tools, compensatory behaviors like camouflaging in females, genetic and neurobiological differences, and the developmental trajectories of comorbidities. Recognizing these factors is crucial for developing sensitive diagnostics and sex-specific interventions. Inconsistencies in the literature highlight the need for longitudinal studies with large, diverse samples to investigate autism comorbidities across the lifespan. Understanding sex differences could facilitate earlier identification, improved care, and personalized interventions, thus enhancing quality of life for individuals with autism.

Globally, viruses have impacted health, economy, and mental well-being of all humankind. Several advanced treatments and vaccines have been developed to overcome this problem. With the advancements in nanoscience and technology in the biomedical field, nanomaterials are now widely used in detection, diagnosis, and therapy. Carbon dots (CDs) have gained significant attention because of their remarkable physical, chemical, and biological properties. The bioactive features of CDs obtained from natural sources, including their antibacterial, anticancer, antiviral, and antioxidant capabilities, have been investigated. However, a broad scope exists to expand these studies and resolve the ambiguity in understanding the associated mechanisms. Hence, it is worth gathering knowledge regarding the potential natural sources of CDs that can help fight novel viral infections. In this review, we begin with a brief introduction in the first section, followed by an overview of viral structure, life cycle, modes of host entry, and current treatment strategies in the second section. The third section discusses the emergence of novel viruses. In the fourth and fifth sections, we examine the application of nanotechnology in managing viral infections, with particular emphasis on the use of CDs and their potential as protective agents against viral diseases. Section six highlights the challenges and limitations associated with the clinical application of CDs. Finally, we summarize the key findings and discuss the future prospects of CDs in antiviral therapy. This review is intended to serve as a valuable reference for the development of innovative treatment strategies against various viral infections.

In this unified series of meta-analyses, we integrate the effects of digital interventions in adults with mental disorders compared to inactive controls. We cover eight indications: depressive disorder, insomnia, specific phobias, generalized anxiety, panic, social anxiety, obsessive-compulsive, and posttraumatic stress disorder.

Digital intervention trials in patients with a diagnosed mental disorder (confirmed by clinical interviews) were extracted from the Metapsy living databases for psychological treatments. Standardized meta-analyses were conducted to pool effects for each disorder, as well as separately for guided and unguided treatments. We also examined study dropout rates, conducted meta-regression analyses stratified by disorder, and identified treatments that have since become available as prescribable digital therapeutics in routine care.

In total, 168 studies (22,144 patients) were included. Moderate effect sizes were observed for PTSD (g = 0.57), depression (g = 0.62), and obsessive-compulsive disorder (g = 0.68). Large effects emerged for generalized anxiety (g = 0.80), social anxiety (g = 0.84), insomnia (g = 0.94), panic disorder (g = 1.05), and specific phobias (g = 1.18). Pooled study dropout rates were generally moderate (≤20 %), but higher in intervention arms (RR = 1.13-2.66). Trials with low risk of bias and care-as-usual comparisons were limited across indications. We found 16 trials evaluating a prescribable digital therapeutic (g = 0.33-1.60).

Digital interventions can be effective across a wide range of diagnosed mental disorders. For some indications, more high-quality trials and comparisons against care-as-usual are needed to confirm the robustness of the effect, particularly for unguided treatments. Digital interventions are increasingly commercialized as prescribable digital therapeutics. Rising industry involvement may present both opportunities and new challenges for the field.

Biomarkers serve as a quantitative measure of brain injury and may predict cognitive outcome after cardiac arrest. This study investigates the association and predictive accuracy of acute changes in Alzheimer disease-associated biomarkers to cognitive outcome in cardiac arrest survivors.

Retrospective study of the Target Temperature Management after Out-of-Hospital cardiac arrest trial. Serum from adult cardiac arrest survivors was sampled prospectively at 24, 48, and 72 h post-arrest and analyzed for peak-levels of Alzheimer disease markers (p-tau¹⁸¹, total tau, amyloid β [Aβ40 and Aβ42]), and the neurodegenerative biomarker neurofilament light (NfL). Cognitive outcome was evaluated blinded from biomarker results using four performance-based assessments at 6 months post-arrest. Spearman correlations were calculated. Area Under the Receiver Operating Characteristics curves (AUC) were calculated for biomarkers discriminatory ability for binary results of cognitive performance.

206/342 (60 %) survivors from participating sites were included. Median was age 62 (IQR 53-69), 86 % male, 15 (7 %) had Mini-Mental State Examination (MMSE) scores < 24. Alzheimer disease biomarkers exhibited at best small correlations to cognitive outcomes (rho = -0.22 to 0.18). The correlation between outcome instruments and NfL was rho = -0.32 to -0.20 (p < 0.01). Discriminatory ability of cognitive impairment for acute changes in Alzheimer disease biomarkers was AUC 0.44-0.68 (95 % CI 0.29-0.82), and AUC 0.66-0.86 (95 % CI 0.59-0.95) for NfL.

In contrast to tau- and amyloid-related biomarkers, NfL could be more useful for predicting cognitive function in cardiac arrest survivors. Low participation by survivors with severe brain injury may have influenced results.

Evaluation of health problems in the Para athlete cohort is well-established. Nonetheless, analyses of the association between mental health and injury, illness or variability of training and competition are spare. Therefore, the purpose of this prospective observational study was to assess this potential relationship in a cohort of Para athletes.

Continuous health monitoring of German Paralympic athletes using the Oslo Sports Trauma Centre (OSTRC) questionnaire and Patient Health Questionnaire-4 (PHQ-4) on a weekly basis. Additionally, primary sporting activity, training exposure, and subjective training intensity per week were recorded. PHQ-4 scores in relation to substantial health problems were analyzed [mean (M) and 95% confidence interval (95%CI)]. A regression tree analysis was used to analyze the relationship between the independent variables age, sex, impairment type, and sport, as well as the stress level, mood, PHQ-4 sum score, subjective training intensity, training exposure, main weekly activeness, type of health problem, and if it was a substantial health problem, 4 consecutive weeks and dependent variable, the PHQ-4 sum score in the fifth week.

Over an observation period of 124 weeks, 122 Para athletes reported a total of 438 health problems and a mean PHQ-4 score of M = 1.3 (95%CI: 1.3-1.4). Highest mean score was observed during illnesses (M = 2.6; 95%CI: 2.2-3). The regression tree identified the leading PHQ-4 score and current mood or stress level as the primary predictors, while all other independent variables did not contribute to the model's prediction.

The findings suggest a potential impact of physical health concerns on mental health, though these, and variations in training or competition were not identified as predictors for the mental health status in a Para athlete cohort. In addition, mean PHQ-4 scores remained below clinical cut-off values, suggesting the need for individualized support to ensure adequate management.