Magnolia Solar (United States)

Background: Youth with attention-deficit/hyperactivity disorder (ADHD) are more likely to experience delays in obtaining their driver’s license relative to their same-aged peers. However, despite these delays, there is no evidence of improved driving outcomes for these youth. Additionally, graduated driver’s licensing laws typically terminate around the age of 18, giving some youth less structure prior to independently transitioning to the road. To date, no study has examined the cognitive and parenting factors that are related to delays in licensure for adolescents with ADHD within the context of an intervention (i.e., Supporting a Teen’s Effective Entry to the Roadway; STEER). The current study utilized logistic regression analyses to determine if teen cognitive functioning, parenting, and the intervention were related to licensure status at 12-month follow-up. Method: Baseline cognition (i.e., reaction time variability, working memory, inhibitory control), baseline parental monitoring, baseline negative parenting, and licensure status were collected on 172 adolescents with ADHD enrolled in a randomized, controlled trial. Results: There was a significant interaction between reaction time variability and the intervention on licensure status ( p = .007), and a marginal interaction between negative parenting and the intervention on licensure status ( p = .05). Those in the STEER group with more reaction time variability were more likely to be licensed at the 12-month follow-up. Although not statistically significant, those in the STEER group tended to have higher rates of licensure when negative parenting was lower. Conclusions: These findings indicate that the STEER intervention may have uniquely benefitted those adolescents who had more difficulties with reaction time prior to the intervention and, to some extent, provided additional support to parents that already had lower levels of negative parenting.

In a 4-week rat study, a nucleotide prodrug antiviral agent containing a synthetic non-natural amino acid (C-331) induced a dose-related vacuolation in the brain's white matter tracts without concurrent neuronal loss, gliosis, or neurological deficits. Routine safety pharmacology studies showed no effects. Penetration of the drug through the blood-brain barrier was negligible. Rat-specific metabolites were not evident. A follow-up 13-week rat study with a 4-week interim assessment was performed using oral doses of 0, 100, 300, or 1000mg/kg/day for 4 or 13weeks. Intermittent, transient clonic convulsions (<1min) occurred in 1 male rat at 100mg/kg/day (3 observations) and 5 animals at 1000mg/kg/day during the dosing phase but were not observed during recovery; their relationship to brain vacuolation remains uncertain. No test article-related neurobehavioral or open-field changes, or ophthalmic abnormalities were noted. In all treated groups, widespread vacuolation predominantly affecting white matter was observed in the cerebellum, thalamus, and striatum. The severity of vacuolation increased over time and persisted after the 4-week recovery period. Based on ultrastructural evaluation, the vacuolation resulted from myelin sheath splitting (intramyelinic edema) without axonal degeneration. The vacuolation was considered to be an adverse effect based on the severity and extent of the changes and the potential for causing oligodendrocyte dysfunction. An NOAEL in the rat was not identified. Because of multiple unknowns, including the lack of consistent neurobehavioral signs, species specificity, low exposure multiples, and the potential human significance, further development of C-331 was terminated. The study describes the unusual presentation of species-specific, drug-induced splitting of myelin sheaths/intramyelinic edema without clear correlative neurofunctional effects.

Introduction Systemic inflammation and mitochondrial bioenergetic failure are central drivers of multi-organ dysfunction in advanced liver disease, sepsis, and acute kidney injury (AKI). Currently available therapies remain largely supportive and fail to directly address intracellular NAD + depletion and immune-metabolic dysregulation. We investigated MP-04, a novel intravenous formulation of dihydronicotinamide riboside (NRH), for its ability to restore NAD + homeostasis, modulate immune metabolism, and confer organ protection in relevant preclinical models. Methods The NAD + -enhancement activity of nicotinamide riboside (NR) and MP-04 was evaluated in human hepatoma (HepG2), T-cell (Jurkat), kidney (HEK293) cell lines, and peripheral blood mononuclear cells (PBMCs). Cellular bioenergetics were assessed using Seahorse extracellular flux analysis. Immunomodulatory effects were examined in polyclonally activated human PBMCs and in a murine endotoxin-induced systemic inflammation model. Pharmacokinetics and pharmacodynamics were assessed following intravenous (IV) dosing in rats, and organ protection was evaluated in a cisplatin-induced AKI mouse model. Safety of MP-04 was evaluated in rat and dog Good Laboratory Practice (GLP) toxicology studies. Results MP-04 produced rapid, distinct, and dose-dependent increases in intracellular NAD + across all tested human cell types and was markedly more potent than NR. IV administration in rats resulted in sustained elevations of NAD + and NADH in blood, liver, and kidney that persisted beyond the systemic clearance of MP-04, with strong correlations between blood and tissue NAD + levels. In activated immune cells, MP-04 reduced reliance on aerobic glycolysis, and significantly attenuated pro-inflammatory cytokine production without affecting resting cells. In vivo , MP-04 reduced systemic inflammatory cytokines following endotoxin challenge and conferred significant biochemical and histological protection against cisplatin-induced AKI. MP-04 was safe and well tolerated in rat and dog following once daily IV administration for 7 days. Conclusion MP-04 is a safe and highly potent intravenous NAD + precursor that modulates cellular metabolism, reduces maladaptive immune activation, and protects against inflammation-associated organ injury in preclinical models. These findings support MP-04 as a promising metabolic-immunomodulatory therapeutic strategy for conditions characterized by systemic inflammation and organ failure, including hepatorenal syndrome–associated AKI, beyond the limits of current supportive care.

Characterize the real-world, 12-month all-cause mortality among individuals with GBS requiring hospitalization in the United States.

ABSTRACT Background Timely reperfusion is the cornerstone of ST-elevation myocardial infarction (STEMI) management. Despite major advances in primary percutaneous coronary intervention (PCI), substantial delays persist, particularly in Eastern Europe. Methods We conducted a retrospective, registry-based analysis of 151 consecutive patients with STEMI admitted to a tertiary emergency university hospital in Romania between April and October 2025. Demographic characteristics, cardiovascular risk factors, reperfusion timelines, and in-hospital outcomes were analyzed. Results Mean total ischemic time was 421 min, driven predominantly by prolonged pain-to-call (229 min) and first medical contact (FMC)-to-door (102 min) intervals. In-hospital door-to-balloon times were largely compliant with European Society of Cardiology recommendations. In-hospital mortality was 8.94%. Conclusions STEMI care in Romania is characterized by significant pre-hospital delays despite efficient in-hospital workflows. Targeted public education, optimization of emergency medical service pathways, and broader implementation of pharmaco-invasive strategies may substantially reduce ischemic time and improve outcomes.

Drug-induced QTc prolongation has emerged as a major, preventable cause of malignant ventricular arrhythmias in cancer therapy. This narrative review integrates mechanistic, clinical, and practical insights into QTc prolongation associated with antineoplastic and supportive medications. We outline direct ionic mechanisms, most notably hERG/IKr blockade and PI3K/Akt pathway modulation, as well as indirect contributors, including cytokine-mediated myocarditis, electrolyte disturbances, and structural remodeling. High-risk agents, including arsenic trioxide, vandetanib, nilotinib, sunitinib, and ribociclib, are contrasted with lower-risk alternatives and QT-sparing strategies. Polypharmacy and drug-drug interactions are emphasized as major real-world amplifiers of risk. Among supportive medications, fluoroquinolones, azole antifungals, and certain antiemetics frequently interact with QT-active anticancer agents, whereas beta-lactams, echinocandins, isavuconazole, and palonosetron may represent safer alternatives. We propose a mechanism-to-bedside framework that incorporates baseline ECG and electrolyte assessment, QT-risk stratification, and clear intervention thresholds (QTc ≥ 500 ms or an increase of ≥ 60 ms). Acute management of torsades de pointes, including intravenous magnesium and overdrive pacing, as well as structured hold-and-rechallenge algorithms, is also summarized. Finally, we highlight system-level measures, such as drug interaction stewardship, standardized discharge communication, and clinician education, to shift cardio-oncology practice from reactive arrhythmia management toward anticipatory prevention. This integrative synthesis aims to preserve oncologic efficacy while mitigating arrhythmic risk in modern cancer care.

Adverse childhood experiences (ACEs) impact later substance use; however, specific ACE patterns and their roles in substance use among emerging adults remain understudied. This study examined whether distinct ACE patterns are associated with four risk factors for substance use disorders (SUDs): hopelessness, impulsivity, and positive or negative emotional craving. Using latent class analysis (LCA), we identified ACE patterns in a sample of 221 emerging adults, primarily racial/ethnic minorities (61.5%) and female (78.7%), aged 18 to 21 (M = 19.1). Three ACE exposure profiles emerged: Low ACEs (59.6%), Emotional ACEs (20.9%), and High/Multiple ACEs (19.5%). Multinomial logistic regression was used to assess associations between these classes and SUD risk factors while adjusting for demographic variables. Findings indicated that individuals in the Emotional ACEs class had significantly higher hopelessness and impulsivity than those in the Low ACEs class. Additionally, participants in the High/Multiple ACEs class reported significantly greater negative emotional craving compared to both the Low ACEs and Emotional ACEs classes. Our findings suggest that ACE exposure patterns are associated with variation in risk factors for SUDs during the transition to adulthood. Therefore, examining qualitative ACE patterns, rather than solely counting ACEs, could be an important step in prevention and intervention efforts to reduce SUD rates among emerging adults. Tailoring prevention strategies to specific ACE patterns may also help mitigate SUD risk among this population more effectively.

A Data and Safety Monitoring Board (DSMB), also referred to as a Data Monitoring Committee (DMC), plays a critical role in safeguarding participant safety and ensuring the integrity of clinical trials. This article provides a narrative overview of best practices in DSMB structure, governance, and operations, informed by regulatory guidance from the U.S. Food and Drug Administration (FDA), National Institutes of Health (NIH), European Medicines Agency (EMA), and selected literature, as well as practical experience in clinical trial oversight. Key domains addressed include DSMB composition and independence, charter development and governance, data access and integrity, safety monitoring processes, interim analyses and adaptive decision-making, confidentiality, and sponsor responsibilities. The article also discusses common operational challenges and mitigation strategies, along with emerging trendssuch as Bayesian monitoring approaches and decentralized trial oversight. Rather than prescribing specific statistical thresholds, the manuscript emphasizes principles for maintaining scientific rigor, ethical oversight, and regulatory alignment. This overview is intended to support sponsors, Clinical Research Organizations (CROs), and DSMB members in implementing effective and compliant safety monitoring practices across a range of clinical trial settings.

Članek obravnava uporabo umetne inteligence pri pouku spoznavanja okolja v 3. razredu osnovne šole, s poudarkom na temi življenjskih okolij. Učenci so raziskovali živali, rastline in značilnosti posameznih okolij ter izbrani pojem samostojno proučili, razložili in ga umestili v ustrezno okolje. Pri delu so lahko izbirali med spletnim portalom Franček, orodjem ChatGPT in strokovno literaturo o rastlinah ter živalih. Učna ura je bila zasnovana z namenom razvijanja digitalne in informacijske pismenosti, kritičnega mišljenja ter samostojnosti pri učenju. Učenci so v skupinah predstavili ugotovitve in primerjali zanesljivost ter uporabnost posameznih virov. V analizi primera smo primerjali rabo virov in kakovost odgovorov lanskih ter letošnjih tretješolcev. Lanski učenci so pogosteje uporabljali klasične tiskane vire, letošnji pa so izrazili večji interes za uporabo umetne inteligence. Kljub temu bistvenih razlik v kakovosti znanja nismo zaznali. Rezultati kažejo, da umetna inteligenca vpliva predvsem na način dostopa do informacij, ne pa neposredno na globino razumevanja. Za razvoj trajnejšega znanja ostajajo odločilni didaktični pristopi, kot so učiteljeva razlaga, strukturiran pogovor, sprotno preverjanje razumevanja in aktivna obdelava informacij, kar je posebej pomembno v prvem vzgojno izobraževalnem obdobju. Ugotovitve poudarjajo potrebo po premišljeni integraciji tehnologije, ki podpira cilje kurikula in razvoj temeljnih učnih strategij ter odgovorno rabo digitalnih orodij.