Although drug shortages for outpatient chronic conditions commonly occur, population-level data on how they impact patients' ability to refill prescriptions is scarce. We sought to identify distinct patterns of refill adherence following drug shortages and patient- and prescription-level factors associated with adherence trajectories reflecting potential shortage-related treatment disruption. We retrospectively analyzed panel data assembled from 2017 to 2020 Veterans Health Administration (VHA) electronic health record data. Patients were included if they were baseline users of medications subject to a shortage within VHA. Group-based trajectory modeling was applied to users' monthly proportion of days covered (PDC) values from 6-months before to 6-months after the reported drug supply chain disruption. Patient demographics and medication characteristics were compared between identified trajectory groups using multivariable logistic regression. Among 1.5 million episodes of medication use (representing 1.3 million unique Veterans) for 29 medications in shortage in VHA, 6.3% were for female patients and the mean age was 66.4 ± 12.8 years. A 4-group trajectory model had the best fit: High Adherence (69.2% of observations), Moderate Adherence (14.1%), Potential Shortage-Related Disruption (8.5%), and Pre-Shortage Disruption (8.3%). Drug characteristics (drug class, number of manufacturers) were more strongly associated than patient characteristics with having Potential Shortage-Related Treatment Disruption vs. High Adherence. We identified 4 trajectories of refill adherence for medications subject to VHA drug shortages, with 8.5% of users of affected drugs exhibiting a trajectory consistent with shortage-related treatment disruption. Drug characteristics may modify whether drug shortages lead to treatment disruption in VHA.

Leveraging complex systems: Leading for transformative change

Altered brain activity and connectivity in adolescent obsessive-compulsive disorder and their correlations with perceived parental rearing patterns: A resting-state fMRI study.

Delirium involves neurotransmitter imbalances and disrupted neural networks. Although lacosamide may theoretically treat delirium by reducing neuronal hyperexcitability via sodium channel modulation, clinical evidence is lacking. Sodium channels in the enteric nervous system mean lacosamide can cause gastrointestinal dysmotility independent of anticholinergic pathways. Given these risks and potential disruptions to the gut-brain axis, off-label use requires extreme caution and rigorous monitoring.

In addition to its risks for morbidity and mortality, adolescent-onset depression is considered a chronic threat to youth's socioemotional development due to its potential disruption of social learning processes. Prior work has determined that youth with depression, or at-risk of developing depression due to familial history, show atypical neural responses to social feedback by peers. To better understand whether adolescents at varying levels of risk for depression show differential neural indices of social learning, the current study interrogated trial-by-trial patterns of youth's neural habituation to repeated social feedback. Seventy-six 10- to 17-year-old girls (22 diagnosed with major depressive disorder [MDD], 30 at familial risk but without MDD, 24 without MDD or familial risk) completed a chatroom task in which they repeatedly anticipated being accepted or rejected by "mean" (likely to reject) and "nice" (likely to accept) virtual peer confederates. Beta-series analyses revealed that the bilateral amygdala showed evidence of habituation to repeated social threat by the "mean" peer across groups. However, girls with MDD showed attenuated habituation in the right amygdala when anticipating feedback from the "mean" peers. Amygdala habituation was present (though attenuated) when anticipating social feedback from the "nice" peers, but did not vary by depression group. Findings identify a failure to habituate to anticipated social threat in MDD, suggesting altered social learning at the neural level. Attending to the dynamics of changing neural responses to anticipated social feedback may provide deeper insights into alterations in social and affective learning processes relevant to developing depression in adolescence.

Two systems of nanoemulsions encapsulating hexyl gallate-eugenol (GaOi) were developed for sustainable plant protection. A water-based system (GaOi-Water, F24) and a 1 % (w/v) chitosan-stabilized system (GaOi-Qs, F64) were prepared using high-energy emulsification and analyzed using DLS, AFM, and TEM. F24 displayed narrowly distributed spherical droplets (AFM: 40–150 nm; DLS mean ∼140 nm; PDI <0.3), whereas F64 formed a chitosan-encapsulated core–shell network with larger aggregates (>400 nm) embedding smaller nanodomains (20–50 nm), consistent with a polymeric shell that may confer sustained-release kinetics. Transmission electron microscopy corroborated these architectures, showing well-defined core-shell morphologies that correlated with the sustained release behavior of F64. In addition, F64 exhibited high encapsulation efficiency and pronounced colloidal stability (|ζ| > 50 mV). Functionally, microbroth (REMA) assays showed that F64 was an order of magnitude more potent than F24 (IC₉₀/MBC: 0.03125 %, 0.125 % v/v), an effect attributed to the potential disruption of the membrane by possible synergistic interaction and the prolonged availability of the antifungal on the surface. Crucially, acute ecotoxicity tests on two stingless bee species ( Melipona scutellaris and Scaptotrigona postica ) revealed no mortality or feeding impairment at active doses. Greenhouse trials on sweet orange demonstrated lesion reductions comparable to commercial copper sprays, using markedly lower active loads. Thus, the results link nano-architecture to release behavior and biological outcomes, illustrating a materials-driven pathway for high-efficacy, pollinator-safe crop protection. The GaOi-chitosan system represents a scalable and environmentally sound alternative to metal-based bactericides with strong potential for field translation. • Sustainable chitosan nanoemulsions to replace conventional agrochemicals. • Hexyl gallate-eugenol showed greater antimicrobial potency against X. citri . • Core-shell structures ensure prolonged release of the active ingredient. • No significant toxicity to native bees tested with nanoemulsions. • Effective control of citrus canker in greenhouse tests.

Stunting (low height-for-age > 2 s.d. below the WHO child growth standards median) is a key indicator of chronic malnutrition and is influenced by poor nutrition, infections, chronic inflammation and impaired gut health. In sub-Saharan Africa, stunting frequently occurs in regions where schistosomiasis is endemic. Our previous research in Zimbabwean preschool children (≤ 5 years) found that Schistosoma haematobium infection alone could account for up to one-third of stunting cases. Using epidemiological, gut microbiome and metabolomic analyses, we investigated how this parasitic infection contributes to poor growth. Infected children showed significantly altered gut microbiome profiles compared to uninfected peers, indicating potential microbiome disruption linked to disease and impaired development. Metabolomic profiling revealed that S. haematobium infection elevated energy- and purine-related metabolites, reflecting metabolic stress associated with malnutrition. Early treatment with praziquantel did not significantly alter the microbiome but did restore normal metabolic profiles, aligning with observed catch-up growth. Here, we synthesize findings from our studies and others to highlight opportunities for intervention and key research gaps, supporting the inclusion of praziquantel in early health programmes and integrated strategies combining treatment with nutrition. Further research, particularly longitudinal studies, is needed to confirm causality and optimize child health outcomes in endemic areas. This article is part of the theme issue 'Biological, biomedical and environmental drivers of stunting'.

Artificial light at night (ALAN) disrupts natural light-dark cycles, posing ecological challenges for wildlife in urban environments. This study investigated ALAN's effects on gene expression in the brain, liver, eyes, gonad and skin of green anole lizards (Anolis carolinensis), increasingly exposed to urban light pollution. We hypothesized that ALAN would alter circadian rhythms by disrupting nighttime darkness and predicted differential expression of genes involved in photoreception, circadian regulation, metabolism and photoperiodic responses. To identify affected pathways, we analysed the expression of circadian and metabolic genes under three conditions: midday in full light, midnight in full darkness and midnight under artificial light. Differential expression analysis revealed that clock-related genes were significantly altered in the brain, liver and skin following ALAN exposure. Genes involved in glucagon signalling and lipid metabolism were differentially expressed in the liver, indicating potential metabolic disruptions. The skin showed distinct responses, with genes related to cellular processes such as wound healing upregulated under natural light-dark conditions, suggesting compromised repair mechanisms under ALAN. Our findings demonstrate that ALAN disrupts core circadian genes and physiological processes, providing the first transcriptomics evidence of light pollution's impact on green anoles. We also developed an interactive online database for exploring gene expression changes under ALAN.

Numerical investigation of ultrasound-driven bubble-induced deformation of spherical solid cells.

Justicidins are naturally occurring arylnaphthalene lignans, mainly from Justicia, Phyllanthus, and Linum species. Justicidin and its derivatives have gained scientific attention for their structural adaptability and wide-ranging pharmacological activities. Their rigid arylnaphthalene core, featuring hydroxyl, methoxy, dioxymethylene groups, and a five-membered lactone ring, offers chemical stability and scope for modification, enabling targeted drug design. Preclinical studies show that justicidin has potent cytotoxicity against breast, lung, leukemia, colorectal, and bladder cancer cells through mechanisms such as apoptosis induction via mitochondrial pathways, topoisomerase inhibition, cell cycle modulation, angiogenesis suppression, and interference with metastasis-related signaling. Beyond oncology, it demonstrates anti-inflammatory, antiviral, neuroprotective, antibacterial, antiplatelet, and antiangiogenic effects. Its multi-target activity involves modulation of NF-κB, MAPK, and PI3K/Akt pathways, as well as DNA damage induction, mitochondrial membrane potential disruption, and regulation of caspases. Low toxicity in normal cells and favorable pharmacokinetics in experimental models strengthen its therapeutic promise. Advances in total synthesis and biotechnological production further enhance its research value. This review compiles current insights into the chemistry, biosynthesis, biotechnological production, pharmacology, and molecular mechanisms of justicidin, underscoring its dual potential as an anticancer lead and a versatile agent for chronic diseases. Understanding structure-activity relationships and optimizing drug-like properties may enable the development of novel, multi-target therapeutics inspired by this natural product.

Machine Learning and Regional Homogeneity Reveal Early and Subtle Brain Changes in Type 1 Diabetes.

FSH mediated endocrine disruption potential of Dibutyl phthalate in cultured ovine ovarian granulosa cells: Cytotoxicity, oxidative stress, steroidogenesis, cell senescence, and expression of related key developmental genes.

A review of Leydig cell hyperplasia in fish models: Implications for endocrine toxicity studies.

As clients increasingly use generative artificial intelligence for emotional support, psychologists now deal with unfamiliar ethical challenges that go beyond conventional risk-management strategies. While generative artificial intelligence systems like ChatGPT or therapy chatbots can be easily accessible, low cost, and oddly compassionate, using them without oversight introduces empirically documented risks such as misinformation and sycophancy, as well as emerging concerns related to cultural bias and potential therapeutic alliance disruption. Drawing from the American Psychological Association (2017) and ethical reflections offered by Chenneville et al. (2024), this conceptual and practice-oriented article applies Crowley and Gottlieb's (2012) primary risk-management model to build a forward-looking, preventive approach to these new challenges. The primary risk-management model emphasizes five iterative stages: resource accumulation, attention and detection of potential risk, initial appraisal of potential risk, preliminary risk-management efforts, and elicitation and use of feedback. Through conceptual mapping and application to a worst-case illustration, this article shows how primary risk-management model-based prevention can strengthen ethical alertness and reflexive judgment in psychologists facing generative artificial intelligence-related dilemmas. The discussion concludes with suggestions for education, professional policy, and empirical research, all aimed at reinforcing preparedness and reducing predictable harm. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Autophagy is an essential developmental and homeostatic process, defined by the endolysosomal degradation of intracellular components and pathogens. Dysfunctional autophagy is implicated in complex human disease, yet reports of congenital autophagy disorders were considered exceedingly rare until the recent report of several unrelated families with bi-allelic variants in the core autophagy effector ATG7, complementing the report of two individuals harboring ATG5 variants. We now report six affected individuals from five families with bi-allelic ATG12 variants with complex neurological phenotypes overlapping those seen in individuals with pathogenic variants in ATG5 and ATG7: developmental delay, intellectual disability, congenital ataxia, hypotonia, and seizures with cerebellar vermis hypoplasia evident on neuroradiological imaging. Structural modeling implicated a potential disruption of the ATG12-ATG5-ATG16N-ATG3 complex. Biochemical analyses of primary fibroblasts confirmed the loss of stable ATG12-ATG5 conjugate in one family and altered autophagic flux in one unrelated family. The HaloTag processing assay in HeLa cells demonstrated a decrease in ATG12-ATG5 conjugate and reduced autophagic flux in response to starvation. Complementation studies demonstrated that equivalent missense atg12 variants were unable to fully recover the biochemical defect in atg12-null yeast, with microscopy analysis demonstrating a reduced delivery of autophagy substrates to the yeast's degradative compartment. Zebrafish studies confirmed that Atg12 is required for normal growth, brain development, and neural function. Collectively, our findings underscore the pivotal role of autophagy in maintaining human neural integrity, emphasize an emerging group of congenital autophagy disorders, and expand our understanding of adaptive homeostasis in human health and disease.

Anisotropic magnetic particles with different dimensions, morphologies and surface grafting for magnetic field-assisted biofilm removal.

Nasopharyngeal carcinoma (NPC) in endemic regions remains prone to treatment failure and poor prognosis due to distant metastasis, underscoring the need for novel therapeutic strategies. Metformin exhibits anticancer activity in NPC; however, the mechanism underlying its single-agent inhibition of tumor cell viability remains incompletely defined. This study investigated the molecular basis of metformin-induced viability inhibition in NPC cells. NPC/HK1 cells were used in this study. Cell viability was quantified using the MTT assay. Apoptosis- and autophagy-associated markers were assessed by immunoblotting. Parthanatos-related events were evaluated by measuring poly(ADP-ribose) (PAR) accumulation, mitochondrial membrane potential (MMP) disruption using JC-1 staining, and the subcellular localization of poly(ADP-ribose) polymerase 1 (PARP1) and apoptosis-inducing factor (AIF) by nuclear/cytoplasmic fractionation. Functional validation was performed using the PARP inhibitors 3-aminobenzamide (3-ABA) and DPQ. Metformin reduced NPC/HK1 cell viability in a dose- and time-dependent manner (IC50=2.5 mg/ml). Metformin did not significantly induce apoptosis or autophagy, as canonical markers were not increased. In contrast, metformin increased PAR accumulation, disrupted MMP, elevated nuclear PARP1 levels, and promoted AIF translocation, consistent with parthanatos activation. Importantly, 3-ABA and DPQ partially rescued metformin-induced loss of viability in NPC/HK1 cells. Metformin suppresses NPC/HK1 cell viability predominantly via PARP1-mediated cell death rather than apoptosis or autophagy, highlighting the PARP1/PAR/AIF axis as a mechanistically informed therapeutic target and potential response biomarker in NPC.

Cortical morphometric alterations and disrupted structural covariance networks in Somatic Symptom Disorder.

Chronic exposure to Dextromethorphan disrupts intestinal integrity and brain metabolism in male mice.

Differential responses of Type I and Type II methanotrophs to nonanoic (pelargonic) acid and glyphosate.