Determining the optimal duration of antibiotic therapy for infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a critical challenge in clinical medicine, balancing therapeutic efficacy against the risks of adverse effects and antimicrobial resistance. This narrative review synthesises current evidence and guidelines regarding antibiotic duration for MDR-GNB infections, emphasising bloodstream infections (BSI), hospital-acquired and ventilator-associated pneumonia (HAP/VAP), complicated urinary tract infections (cUTIs), and intra-abdominal infections (IAIs). Despite robust evidence supporting shorter courses (3–7 days) in uncomplicated infections caused by more susceptible pathogens, data guiding optimal therapy duration for MDR-GNB remain limited, particularly concerning carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), and carbapenem-resistant Acinetobacter baumannii (CRAB). Current guidelines from major societies, including IDSA and ESCMID, provide explicit antimicrobial selection advice but notably lack detailed recommendations on the duration of therapy. Existing studies demonstrate non-inferiority of shorter versus longer antibiotic courses in specific clinical contexts but frequently exclude critically ill patients or those infected with non-fermenting MDR pathogens. Individualised duration decisions must integrate clinical response, patient immunologic status, infection severity, source control adequacy, and pharmacologic considerations. Significant knowledge gaps persist, underscoring the urgent need for targeted research, particularly randomised controlled trials assessing optimal antibiotic duration for the most challenging MDR-GNB infections. Clinicians must navigate considerable uncertainty, relying on nuanced judgement and close monitoring to achieve successful outcomes while advancing antimicrobial stewardship goals.

Individuals suffering from diverse neuropsychiatric and neurodegenerative disorders often have comparable symptoms, which may underline the implication of shared hereditary influences and the same biological processes. Lysophosphatidic acid (LPA) is a bioactive phospholipid and a crucial regulator of the development of adult neuronal systems; hence, it may play an important role in the onset of certain diseases such as Alzheimer’s, Parkinson’s disease, and schizophrenia. During development, LPA signaling regulates many cellular processes such as proliferation, survival, migration, differentiation, cytoskeleton reorganization, and DNA synthesis. So far, six lysophosphatidic acid receptors that respond to LPA have been discovered and categorized based on their homology. Despite the abundance of evidence relating LPA cellular activities to different pathological conditions, little is known about the involvement of LPA in the field of neuropsychiatric and neurodegenerative diseases. The purpose of this review is to define LPA activities related to the illnesses stated above in order to better understand these pathologies and provide future novel treatment strategies based on the latest data.

Oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) are endogenous lipids that act as agonists of the peroxisome proliferator-activated receptor α (PPARα). Recently, an interest in the role of these lipids in malignant tumors has emerged. Nevertheless, the effects of OEA and PEA on human neuroblastoma cells are still not documented. Type I interferons (IFNs) are immunomodulatory cytokines endowed with antiviral and anti-proliferative actions and are used in the treatment of various pathologies such as different cancer forms (i.e., non-Hodgkin’s lymphoma, melanoma, leukemia), hepatitis B, hepatitis C, multiple sclerosis, and many others. In this study, we investigated the effect of OEA and PEA on human neuroblastoma SH-SY5Y cells treated with IFNβ. We focused on evaluating cell viability, cell proliferation, and cell signaling. Co-exposure to either OEA or PEA along with IFNβ leads to increased apoptotic cell death marked by the cleavage of caspase 3 and poly-(ADP ribose) polymerase (PARP) alongside a decrease in survivin and IKBα levels. Moreover, we found that OEA and PEA did not affect IFNβ signaling through the JAK-STAT pathway and the STAT1-inducible protein kinase R (PKR). OEA and PEA also increased the phosphorylation of p38 MAP kinase and programmed death-ligand 1 (PD-L1) expression both in full cell lysate and surface membranes. Furthermore, GW6471, a PPARα inhibitor, and the genetic silencing of the receptor were shown to lower PD-L1 and cleaved PARP levels. These results reveal the presence of a novel mechanism, independent of the IFNβ-prompted pathway, by which OEA and PEA can directly impair cell survival, proliferation, and clonogenicity through modulating and potentiating the intrinsic apoptotic pathway in human SH-SY5Y cells.

Neuroblastoma (NB) represents a paradigmatic developmental malignancy in which lineage specification, oncogenic signalling, and epigenetic regulation converge to define tumour behaviour. Among the molecular axes shaping NB heterogeneity, neurotrophin receptors of the tropomyosin receptor kinase (Trk) family (TrkA, TrkB, and TrkC) and the p75NTR occupy a central position at the intersection between neuronal differentiation programs and malignant plasticity. While high TrkA and TrkC expression is associated with adrenergic identity, differentiation competence, and favourable clinical outcome, TrkB, frequently sustained by BDNF-driven autocrine loops, characterises mesenchymal-like, therapy-resistant states enriched in metabolic and inflammatory adaptations. Importantly, in NB, the dysregulation of neurotrophin signalling rarely arises from recurrent genetic alterations of neurotrophic tyrosine receptor kinase (NTRK) loci. Instead, Trk receptor expression is dynamically shaped by promoter methylation, polycomb repressive complex 2/Enhancer of Zeste homolog 2 (PRC2/EZH2)-dependent chromatin repression, MYCN-driven transcriptional silencing, enhancer rewiring, and microRNA-mediated control. These epigenetic mechanisms govern reversible transitions along the adrenergic–mesenchymal (ADRN–MES) continuum, enabling tumour cells to adapt to microenvironmental and therapeutic stress. Single-cell and spatial multi-omics approaches have further revealed that Trk-associated phenotypes are embedded within complex regulatory circuits integrating receptor tyrosine kinase (RTK) networks, cytokine signalling, metabolic remodelling, and stromal reinforcement. Here, we provide a comprehensive synthesis of the epigenetic and microenvironmental mechanisms regulating neurotrophin receptors in NB, with particular emphasis on how chromatin plasticity and cell-state transitions reshape Trk-dependent signalling outputs. We discuss advanced three-dimensional and organoid-based models that recapitulate niche-specific regulation of the Trk axis and evaluate emerging therapeutic strategies combining epigenetic modulators, differentiation-inducing agents, and RTK-targeted compounds. Understanding the temporal and spatial dynamics of Trk signalling may open new opportunities to therapeutically stabilise differentiation states and disrupt adaptive resistance programs in high-risk NB.

HIV-associated neurocognitive disorders (HANDs) refer to a range of cognitive deficits that afflict people living with the Human Immunodeficiency Virus (HIV). The fundamental processes of HAND include persistent inflammation, immunological activation, and direct viral impact on the central nervous system. Emerging research shows that nutritional status, especially food consumption and body weight, is critical in determining the course and severity of HAND. Malnutrition exacerbates neurocognitive impairment by increasing inflammation and oxidative stress, while obesity may contribute to HAND through the promotion of metabolic disruption, gut microbiota alterations, and systemic inflammation. Additionally, the introduction of antiretroviral treatment (ART) has substantially enhanced the prognosis of people living with HIV by lowering viral load and improving immune function. However, depending on the regimen, ART can cause changes in body weight, which may influence the progression of HAND. This emphasizes the intricate interplay between HIV, nutrition, body weight, and neurocognitive health. As a result, various dietary approaches are currently being investigated to improve the quality of life of individuals with HIV and possibly help prevent neurocognitive decline in this population. This review aims to elucidate the relationship between nutrition and neurocognitive function in individuals living with HIV, shedding light on aspects of HANDs related to diet, body weight fluctuations, and metabolic syndrome. It explores the shift from current pharmacological treatments to innovative non-pharmacological interventions, including specific dietary strategies, to support overall health and cognitive well being in HIV-positive people.