The orexin (hypocretin) system plays a central role in regulating the sleep–wake cycle through two neuropeptides, orexin-A and orexin-B, which act on OX1R and OX2R receptors. Emerging evidence links heightened orexin signaling with the pathophysiology of chronic insomnia. This review outlines the neurobiology of the orexinergic system, compares the pharmacological profile of dual orexin receptor antagonists (DORAs) to traditional GABAergic hypnotics, and evaluates the clinical efficacy and safety of Suvorexant, Lemborexant, and Daridorexant. DORAs function by selectively dampening orexin-driven arousal, thereby facilitating sleep onset and maintenance without disrupting natural sleep architecture. Clinical trials have shown that these agents significantly reduce sleep latency and enhance sleep continuity, with a favorable side effect profile. Overall, DORAs represent a distinct and clinically advantageous option for insomnia treatment, with growing interest in their potential utility across mood, anxiety, and neurodegenerative disorders.

Background: Driving is a coordinated psychomotor activity that involves reaction time, attention, and decision-making. Psychoactive substances such as 2-phenylethylamine (PEA) derivatives and opioids may affect these functions and contribute to traffic safety. This systematic review revealed the effects of the selected PEA derivatives and opioids on psychomotor performance among drivers and potential road safety outcomes. Methods: The review followed PRISMA 2020 standards. Using the PICO method, we conducted a systematic search in Embase, PubMed, and Web of Science (2000–2025). Included studies involved adult participants and quantified the effect of PEA derivatives or opioids on driving-related psychomotor function. Thirty-one articles, such as randomized controlled trials, crossover studies, observational studies, and simulator-based studies, were examined. Risk of bias was evaluated using the RoB2 tool. Results: Evidence indicates therapeutic amphetamine and methylphenidate doses can enhance psychomotor function and safety in patients with ADHD. Recreational or high-dose use of methamphetamine and MDMA is associated with impaired coordination, variable speed, and increased impulsivity. Opioid effects are tolerance- and dose-dependent. Small therapeutic doses of fentanyl in chronically treated patients do not notably impair driving. On the other hand, methadone and tramadol commonly cause somnolence, retardation of reaction, and increased accident risk. Conclusions: The impact of opioids and PEA derivatives on psychomotor function is multifactorial, depending on dose, time, route of administration, and patient status. These substances can either improve or impair driving safety. The findings confirm the need for individual-specific pharmacotherapy treatment. They also highlight the importance of further studies to formulate evidence-based clinical and legislative guidelines.

This paper provides a comprehensive review of the current state of knowledge on irritable bowel syndrome (IBS), one of the most common gastrointestinal disorders, currently classified as a disorder of gut–brain interaction (DGBI). The review discusses the epidemiology, pathophysiology, clinical presentation, diagnostic approach, therapeutic management, and emerging research directions in IBS. The prevalence of IBS ranges from 3.8% to as high as 14% of the global population, with significant regional and sex-related differences. IBS is a multifactorial disorder involving disturbances of the gut–brain axis, visceral hypersensitivity, alterations in the gut microbiota (dysbiosis), immune dysfunction, as well as genetic, hormonal, and psychological factors. The clinical manifestations include recurrent abdominal pain, altered bowel habits (constipation-predominant, diarrhea-predominant, and mixed subtypes), abdominal bloating, and extraintestinal symptoms such as fatigue, sleep disturbances, anxiety, and depression. The diagnosis is based on the Rome IV criteria and the exclusion of organic diseases, particularly in the presence of alarm features ("red flags"). A multidisciplinary therapeutic approach includes patient education, dietary interventions (including the low-FODMAP and Mediterranean diets), probiotics, pharmacological treatment tailored to the IBS subtype, and psychological therapies such as cognitive behavioral therapy (CBT) and gut-directed hypnotherapy. Emerging therapeutic strategies include modulation of the gut microbiota through fecal microbiota transplantation (FMT) and next-generation probiotics, as well as mechanism-based pharmacological agents, including elobixibat and olorinab.

Tattooing involves intradermal deposition of pigment that elicits a long‑lasting immune response. Dermal macrophages play a key role in maintaining pigment by capturing pigment particles and retaining them inside their phagolysosomes. The aim of this paper is to analyze the mechanisms of phagocytosis of tattoo pigment by dermal macrophages, their impact on tattoo persistence, and to assess the significance of phenotypic differentiation (M1/M2) in the context of inflammation, laser therapy, and potential biomedical applications. We reviewed data from recent experimental studies, including 3D skin models, electron microscopy, flow cytometry, and TPE‑FLIM imaging. We also considered the effect of pigment chemical composition on activation of immune cells. Dermal macrophages demonstrate high efficiency in phagocytosis and long‑term storage of pigment. The observed “capture–release–recapture” mechanism ensures pigment stability despite natural cellular turnover. Pigment composition influences macrophage polarization (M1 or M2), which may determine chronic inflammation versus regeneration. Understanding macrophage–pigment dynamics provides new insights into tattoo durability and opens opportunities to improve the effectiveness of laser removal. Advances in imaging and the use of biosensor cells point to potential future applications of tattoos in diagnostic and regenerative medicine.

Migraine is one of the most common and burdensome neurological disorders, affecting approximately 15% of the global population. This paper provides a review of the current knowledge on the epidemiology, pathophysiology, and treatment of chronic migraine, with particular emphasis on the role of botulinum toxin type A. It presents the key biological mechanisms underlying migraine, including activation of the trigeminovascular system, the significance of neuropeptides such as CGRP, and the involvement of cortical spreading depression (CSD) in migraine with aura. Modern pathophysiological concepts related to autonomic and metabolic system dysfunction are also discussed. Based on an analysis of clinical trials and meta-analyses, the efficacy and safety of onabotulinumtoxinA therapy according to the PREEMPT protocol are evaluated, as well as its place in current therapeutic guidelines. The paper concludes with a discussion of future research perspectives, including the potential for synergy with biological therapies (anti-CGRP), optimization of treatment regimens, and the use of biomarkers.