Search Results (1,486)

Over 10% of US children and adolescents have attention-deficit hyperactivity disorder (ADHD), with a similar prevalence among youth athletes. While ADHD may confer certain athletic performance advantages such as heightened quickness, decision-making and periods of hyperfocus, it also poses some challenges including reduced concentration, frustration, and possible increased injury risk. Pharmacologic treatments, including stimulant-based medications, can improve attentiveness and athletic performance but could alter nutritional behaviors such as appetite suppression. This paper reviews the current literature on nutritional strategies to provide practical sports nutrition guidelines for children and adolescent athletes with ADHD. Evidence suggests that optimizing energy intake, emphasizing complex carbohydrates, improving fat quality intake, and consuming adequate amounts of micronutrients may support both athletic performance and ADHD symptom management. In contrast, excessive added sugars and saturated fats are associated with poorer outcomes and manifestation of ADHD symptoms. Although no research examining nutritional interventions in youth athletes with ADHD have been performed, applying established sports nutrition principles for youth athletes with ADHD offers a promising approach to enhance performance, reduce injury risk, and support the long-term health of the athlete. Full article

Oxidative stress and inflammation are key drivers in the pathogenesis of various chronic diseases, including cardiovascular disease, neurodegenerative disorders, chronic kidney disease, and diabetes. This study evaluated the antioxidant and anti-inflammatory activities of SHE, CME, and FCME, all cultivated in northern Thailand. Human embryonic kidney cells (HEK293) were exposed to FeSO₄ to induce oxidative stress and to LPS to stimulate inflammation. Cell viability was assessed using the MTT assay, while intracellular ROS production was measured using the DCFH-DA. Lipid peroxidation was quantified using the thiobarbituric acid reactive substances assay, and the interleukin-6 (IL-6) release was determined by ELISAs. All extracts demonstrated low cytotoxicity; however, cell death increased at 48 h compared to 24 h. At 200 µg/mL, SHE, CME, and FCME significantly reduced the H₂O₂-induced ROS generation, with the combined treatment of SHE and FCME producing a more pronounced reduction than the individual treatments. Furthermore, the combination of SHE and FCME markedly decreased malondialdehyde (MDA) and IL-6 levels compared with other groups. These findings suggest that shallot and cha-miang extracts, particularly in combination, exhibit promising antioxidant and anti-inflammatory properties in kidney cell models. This combination could therefore be explored as a nutraceutical strategy for the prevention and management of chronic kidney disease, in which oxidative stress and inflammation play pivotal roles. Overall, our finding highlight the potential of the combined use of SHE and FCME as a functional ingredients in the food and pharmaceutical industries. Full article

New wearable technology opens new possibilities for low-cost, easily accessible home-based interventions as a supplement to typical clinical rehabilitation therapy. In this pilot study, we tested a new interactive adjustable Feedback training system on 14 infants at high risk of cerebral palsy between 2 and 12 months of age to facilitate increased movements. The system consists of four wireless motion sensors placed on the infant’s limbs. Inertial sensors track the infant’s movements which control auditory and visual stimuli that act as motivational feedback. A 15 min usage of the Feedback training system four days a week for approximately six months was aimed for. None of the participants reached the recommended amount of intervention, due to time limitations. Seven of the twelve participating infants (58%) achieved at least 50% of the recommended training amount. Parents found the Feedback training system easy to use with minimal need for technical assistance. Preliminary data suggest that infants engaged more actively during training sessions where their movements actively controlled the presentation of the stimuli. The Feedback training system is promising as a user-friendly add-on to the playful and interactive stimulation of motor and cognitive development in infants with neurodevelopmental disorders. Full article

Nickel allergy remains the most prevalent cause of allergic contact dermatitis worldwide, imposing a substantial socio-epidemiological and economic burden. Beyond its classical cutaneous presentation, systemic nickel allergy syndrome highlights the systemic dimension of Nickel hypersensitivity, wherein dietary nickel intake may provoke both gastrointestinal and cutaneous symptoms through mechanisms involving gut barrier impairment and mucosal immune priming. Recent evidence highlights the contribution of angiogenesis and lymph-angiogenesis to Nickel-induced allergic contact dermatitis, through crosstalk among keratinocytes, mast cells, endothelial cells, and pro-angiogenic mediators such as vascular endothelial growth factor. Against this background, we propose to revisit palmitoylethanolamide, an endogenous ALIAmide with well-documented anti-inflammatory, anti-angiogenic, and anti-allergic properties. Already studied in pain and inflammatory disorders and employed in veterinary dermatology, palmitoylethanolamide down-modulates mast cell degranulation, suppresses VEGF expression via PPAR-α/Akt/mTOR signaling, and enhances intestinal barrier integrity, acting as a promising “gatekeeper” molecule that reduces gut hyperpermeability characterizing systemic nickel allergy as well as other gut disorders with systemic consequences. This paper is presented as a viewpoint intended to highlight the untapped therapeutic potential of palmitoylethanolamide, suitable for both oral and topical administration, as a candidate to address the multifactorial pathophysiology of Nickel allergic contact dermatitis and systemic nickel allergy. Our purpose is not to provide definitive answers, but to stimulate scientific debate on its rational use within emerging gut–skin therapeutic strategies. We thus encourage future experimental and clinical studies to explore its potential integration within emerging gut–skin therapeutic paradigms. Full article

Objective: Current data on the association between attention-deficit/hyperactivity disorder (ADHD) and essential hypertension (EH) in pediatric populations are very limited, as most research has focused on adults. This study investigated the long-term prevalence of EH in Israeli youth aged 5–18 years with ADHD, examining also trends in antihypertensive medication use. Methods: A retrospective cohort study was conducted using data from Leumit Health Services. The ADHD cohort (N = 18,558) was compared in a 1:2 ratio to controls (N = 37,116), who were strictly matched for age, gender, birth year and quarter, socioeconomic status (SES), sectors, region, and cumulative years of LHS membership up to the index date. Diagnoses of ADHD and EH were identified using ICD-9/10 codes, depending on the year of diagnosis. Logistic regression analyses were used to assess the associations between ADHD, EH and the use of antihypertensive medications over a 20-year follow-up. Results: ADHD-diagnosed children had a higher prevalence of EH, with odds ratios (ORs) of 3.17 (95% CI: 1.46–7.16, p = 0.0017) at 5 years, 2.94 (95% CI: 1.45–6.09, p = 0.0013) at 10 years, and 1.92 (95% CI: 1.26–2.93, p = 0.0015) at 20 years. ADHD patients showed a greater use of antihypertensive medications, including calcium channel blockers (OR 1.85, 95% CI: 1.02–3.35, p = 0.035), renin angiotensin system blockers (OR 2.20, 95% CI: 1.15–4.25, p = 0.013), and diuretics (OR 1.77, 95% CI: 1.21–2.60, p = 0.0028). Conclusions: These findings highlight an association between ADHD diagnosis and EH, suggesting regular cardiovascular monitoring of children with ADHD. Further studies are needed to uncover the role of stimulant medications and shared biological and behavioral factors involved in the pathogenesis. Full article

The intestinal barrier is essential for gastrointestinal and systemic homeostasis by enabling nutrient absorption while limiting the translocation of pathogens and toxins. When barrier function is impaired, bacterial components such as lipopolysaccharides (LPSs) may cross the epithelium and promote inflammatory signaling. In dogs, chronic inflammatory enteropathies are frequent disorders associated with barrier dysfunction, dysbiosis, and immune dysregulation, and may progress to protein-losing enteropathy or systemic inflammation. Humic substances, particularly humic acid (HA), are natural organic compounds with reported antioxidative, immunomodulatory, and barrier-supporting effects; however, the cellular mechanisms underlying these effects in intestinal and immune models remain insufficiently characterized. This study evaluated the effects of a commercially available HA-based supplement on epithelial barrier integrity and inflammatory responses using an in vitro system combining IPEC-J2 intestinal epithelial cells and primary canine peripheral blood mononuclear cells (PBMCs). Epithelial barrier integrity (FD4 paracellular flux), reactive oxygen species, and cytokine production (TNF-α, IL-6) were assessed under basal and LPS-stimulated conditions. HA treatment preserved epithelial barrier function and reduced LPS-induced pro-inflammatory cytokine production, supporting further investigation of HA as a nutraceutical adjunct for gut health support in dogs with chronic enteropathies. Full article

Zanthoxylum piperitum is a food and culinary plant commonly used in East Asia. In traditional medicine, its fruits, seeds, and bark have been utilized to treat digestive disorders, pain, and stomachache. Prior research has demonstrated its health benefits, particularly its significant antioxidant properties. However, limited research has investigated the specific metabolites responsible for these pharmacological effects. In this study, the antioxidant activities (EC₅₀: 9.1–1084.5 μg/mL) and metabolite profiles of different organs (fruits, pericarps, and seeds) of Z. piperitum collected from different regions were comparatively analyzed. Chemical structures of 91 metabolites from different organs were identified using UHPLC-Orbitrap-MS/MS based on untargeted metabolomics. The LC-DPPH method was employed to screen antioxidants from the extracts of the most active organ (the pericarps). The potential effects of the active compounds on oxidation-related diseases were evaluated by integrating compound–target interaction network analysis. Protein–protein interaction (PPI) networks revealed EGFR, STAT3, AKT1, TNF, BCL2, CASP3, ESR1, PPARA, CYP19A1, and CDK2 as central hub genes. The significance of compound and target interactions was further supported by molecular docking studies, which demonstrated favorable binding affinities, with most proteins exhibiting docked scores below −4.27 kcal/mol. The extracts of Z. piperitum fruits and pericarps also exhibited antioxidative activity against ROS production in LPS-stimulated RAW264.7 cells. Our findings demonstrate the application of an optimized extraction process and underscore the medicinal value of this food-plant by characterizing its bioactive constituents. The results indicate that Z. piperitum may serve not only as a health-promoting food but also has the potential for prevention or treatment of oxidative-stress-related diseases. Future research should focus on in vivo studies by exploring the therapeutic mechanisms of actions of the active extracts. Full article

Background/Objectives: Down Syndrome (DS) is frequently associated with oral-motor dysmorphologies, like oral hypotonia, tongue protrusion, short palate, and malocclusion, compromising the oral functions of sucking, chewing, swallowing, and speech production. Therapeutic interventions with stimulating palatal plates (SPP) have been proposed to prevent and improve oral-motor dysmorphologies in DS. This study proposes a new digital workflow for the manufacturing and use of a modified SPP. Methods: We report the application of the new workflow to five clinical cases, all infants with DS showing oral-motor disorders, aged between 5 and 11 months. The workflow is described step-by-step, from the mouth scanning protocol and model printing to SPP manufacturing and delivering, and assessment of oral-morphological features and language abilities via video captures and parental questionnaires. Key novel features include an SPP with an acrylic extension with a pacifier terminal and, importantly, the use of an infant-friendly intraoral scanner. Results: The new workflow had good acceptability by infants and parents, offering a safe, easy-to-implement, and feasible solution for SPP design, as it avoided the high risks associated with impression materials. It also supported the use of the SPP to promote tongue stimulation, retraction, and overall oral-muscle function in oral-motor disorders in children with DS, especially in infants. Conclusions: Within the limitations of the current study, it was shown that the proposed digital workflow constitutes a viable and infant-friendly approach to the production and use of a modified SPP, and thus promises to contribute to improving oral morphology and auditory-motor language abilities. Full article

Background: Sexualized substance use (SSU) describes the use of psychotropic substances in the context of sexual activity. Less is known about the role of sexualized substance use among individuals with substance use disorders (SUD) and its effect on the course of the disorder, e.g., regarding relapses after abstinence. Methods: A convenience sample of individuals undergoing SUD rehabilitation in Germany was surveyed. A questionnaire asked about SSU, sex as a risk factor for relapse, and the importance of sexuality in treatment. Results: N = 490 (30.1% female) participated; 55% of men and 63% of women reported SSU, and 56.5% of heterosexual and 82.9% of homosexual men reported SSU (p < 0.017; r = 0.20). Stimulant users are more likely to report SSU than alcohol (p < 0.001) and sedative users (p < 0.001; r = 0.296 and r = 0.261). Furthermore, 15% of women and 18% of men consider sexual activity a risk factor for relapse; homosexual men (65%) consider it significantly more often than heterosexual men (14%), while 41.2% of heterosexual women and 55% of homosexual women consider it a factor. Additionally, 27.4% of heterosexual and 69.4% identified sexuality as an important topic for therapy, while 19.8% of heterosexual women, 30% of homosexual women, 13.5% of heterosexual men, and 47.2% of homosexual men reported that sexuality had been addressed in their therapy. Conclusions: SSU was reported by individuals with a SUD who were undergoing rehabilitation treatment. Furthermore, patients consider sexual activity as a potential risk factor for relapse, with this being particularly the case for stimulant users. The topic of sexuality is highly important for patients and should, therefore, be given greater consideration in therapy in the future. Full article

Background/Objectives: Migraine is a complex neurological headache disorder, and transcutaneous auricular vagus nerve stimulation (taVNS) can effectively relieve headache symptoms, but its mechanism of effect is still unclear. This study aimed to explore the regulatory effects of taVNS on the locus coeruleus (LC) and the norepinephrine (NE) system in migraine mice. Methods: C57/BL6 mice were randomly assigned to four experimental groups: the control group, model group, taVNS group, and sham taVNS group. A migraine model was established by administration of nitroglycerin. Headache behaviors were assessed using the orofacial stimulation test (OST) and the mouse grimace scale (MGS). Immunofluorescence staining was conducted to evaluate the expression of NE neurons in the LC, while Western blotting was used to determine the expression levels of α-2A adrenergic receptors in the spinal trigeminal nucleus caudalis (Sp5C). Additionally, fiber-optic recording was employed to monitor the real-time dynamics of NE release in Sp5C. Results: After taVNS intervention, the drinking time of OST in the model mice was significantly prolonged(p < 0.05), and facial expression scores were reduced (p < 0.05). TaVNS increased the number of NE neurons in the LC (p < 0.05), promoted the release of NE in Sp5C (p < 0.05), and upregulated the expression of α-2A adrenergic receptors in Sp5C (p < 0.05). Conclusions: The analgesic effects of taVNS are related to the activation of the LC-NE system and the inhibition of the decrease in Sp5C in migraine mice. Full article

Background/Objectives: Citicoline, also known as CDP-choline, is a nootropic agent currently used in the treatment of glaucoma and is undergoing evaluation as a first-line therapy in a multi-center, international, phase III, randomized clinical trial involving citicoline eyedrops (ClinicalTrials.gov ID: NCT05710198). Numerous clinical and preclinical studies have linked the neuroenhancement and neuroprotective effects of citicoline to its role as a metabolic precursor for structural and functional components of cell membranes (such as phosphatidylcholine and sphingomyelin) and for neurotransmitters (e.g., acetylcholine and dopamine). However, compelling evidence suggests that the molecular mechanisms underlying its cytoprotective activity involve additional as-yet uncharacterized pharmacological actions. Methods: To further elucidate its pharmacology, we investigated the effect of two cytoprotective doses of citicoline (0.1 mM and 1 mM) on the global proteome of neuroblastoma cells using an unbiased shotgun proteomics approach. Results: With over 4000 unique proteins identified and quantified per experimental condition, the proteomics analysis revealed that citicoline, after 6 h of stimulation, induces a profound and robust remodeling of the intracellular proteome compared to untreated cells. Importantly, this effect was observed to significantly diminish by 18 h of stimulation, highlighting its transient nature (data are available via ProteomeXchange with identifier PXD061053). The clustering and rationalization of proteins upregulated by citicoline treatment identified the enrichment of key pathways for mRNA splicing, protein translation, proteostasis balance through the ubiquitin proteasome system (UPS), and mitochondrial metabolism. Conclusions: These proteomics findings introduce previously uncharacterized biological effects of citicoline and foster the working hypothesis that this drug may exert its cytoprotective activity through molecular mechanisms linked to the hormesis principle. These data further support the rationale for its clinical application in neurodegenerative processes and human disorders characterized by proteotoxicity. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread hepatic condition characterised by hepatic lipid accumulation and inflammation. Emerging research highlights the contribution of the intestinal microbiota and its metabolic byproducts to the pathogenesis of MASLD through the gut–liver axis. Apolipoprotein A-I (apoA-I), the principal structural component of high-density lipoprotein (HDL), is linked to various metabolic disorders; however, its function in MASLD has not yet been clearly elucidated. This study sought to examine whether apoA-I protects against MASLD, with a focus on the possible role of the gut microbiota and propionic acid (PPA). The contribution of the gut microbiota was evaluated using faecal microbiota transplantation (FMT) and antibiotic cocktail (ABX)-mediated depletion. Microbial composition was assessed via 16S rRNA sequencing, and concentrations of short-chain fatty acids (SCFAs) were quantified. The effects of PPA on MASLD were examined using in vivo and in vitro models. The results showed that apoA-I overexpression alleviated MASLD in a gut microbiota-dependent manner, restored microbial homeostasis, and elevated PPA levels. PPA supplementation improved MASLD phenotypes. Mechanistically, PPA treatment was associated with the activation of the GPR43–Ca²⁺–CAMKII–ATGL pathway, suggesting that PPA plays a role in stimulating hepatic lipolysis and enhancing mitochondrial β-oxidation. These findings reveal a novel pathway through which apoA-I ameliorates MASLD by modulating the gut microbiota and increasing PPA levels, which activate a hepatic lipolysis cascade. The apoA-I–microbiota–PPA axis represents a promising therapeutic target for MASLD intervention. Full article

Background and Objectives: Chronic knee pain (cKP) affects approximately 25% of adults worldwide, with prevalence increasing over recent decades. While conventional treatments have clinical limitations, several types of electrical stimulation have been suggested to improve patients’ quality of life. The electrical stimulation literature contains inadequate patient-reported outcome measures (PROMs) data. Encouraging preliminary H-Wave^® device PROMs results for chronic neck, shoulder, and low back pain have previously been published. This PROMs study’s goal is to similarly assess the efficacy of H-Wave^® device stimulation (HWDS) in patients with differing knee disorders. Materials and Methods: This is an independent, retrospective, observational cohort study analyzing H-Wave^® PROMs data, prospectively and sequentially collected over 4 years. In total, 34,192 pain management patient final surveys were screened for participants who were at least 18 years old, used H-Wave^® for any knee-related disorder, reporting chronic pain from 90 to 730 days, with device treatment duration from 22 to 365 days. PROMs included effects on function, pain, sleep quality, need for medications, ability to work, and patient satisfaction; additional data includes gender, age (when injured), chronicity of pain, prior treatments, and frequency and length of device use. Results: PROMs surveys from 34,192 HWDS patients included 1143 with “all knee”, 985 “knee injury”, and 124 “knee degeneration” diagnoses. Reported improvements in function/ADL (96.51%) and work performance (84.63%) were significant (p < 0.0001), with ≥20% pain relief in 86.76% (p < 0.0001), improving 2.96 points (average 0–10 NRS). Medication use decreased (69.85%, p = 0.0008), while sleep improved (55.33%) in knee injury patients. Patient satisfaction measures exceeded 96% (p < 0.0001). Subgroup analysis suggests that longer device use and shorter pain chronicity resulted in increased (p < 0.0001) HWDS benefits. Conclusions: HWDS PROMs data analysis demonstrated similarly encouraging outcomes for cKP patients, as previously reported for several other body regions. Knee injury and degeneration subgroups had near-equivalent benefits, as observed for all knee conditions. Despite many reported methodological limitations, which limit causal inference and preclude broader recommendations, HWDS appears to potentially offer several benefits for refractory cKP patients, requiring further studies. Full article

The stimulated assembly/disassembly of particles is a technique allowing for precise spatial and temporal control over the resulting structures to be realized. The application of a photosensitive liquid crystal (LC) allows the use of a photo-initiated order–disorder transition for the ordering and redistribution of dispersed nanoparticles. The semiconductor quantum dots (QDs) among them are useful for the imaging of such redistribution through simple luminescent microscopy with excitation by laser radiation at a wavelength of 532 nm. Doping the LC matrix with azo-chromophore molecules allowed us to localize the light-driven phase transition of the LC from the organized to the isotropic phase inside the spot, illuminated by ultraviolet (UV) light through a slit. The phase transition leads to a redistribution of the QDs within the matrix, followed by QD-rich region formation. After the termination of UV illumination, the QDs were found to form droplets in the region where UV illumination resulted in a homogeneous distribution of the QDs. The translation of the sample through the UV-illuminated spot resulted in QD accumulation inside the isotropic phase at the borders of the isotropic phase. The results obtained provide a good agreement with the model calculations of nanoparticle diffusion at the LC phase–isotropic liquid interface. Full article

Depression is a common, debilitating, and potentially life-threatening mental disorder affecting individuals across all age groups and populations. It represents one of the major challenges of contemporary medicine. It is estimated that more than 300 million people worldwide are affected, and patients with major depressive disorder (MDD) exhibit a significantly increased risk of suicide, underscoring the urgent need for effective and long-lasting therapeutic strategies. Growing evidence indicates that the pathophysiology of depression involves a complex interplay of genetic vulnerability, chronic stress, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, neuroinflammation, oxidative stress, mitochondrial dysfunction, and impaired synaptic plasticity, collectively contributing to symptom heterogeneity and treatment resistance. In this review, we synthesize data derived from PubMed, Google Scholar, and ClinicalTrials.gov databases concerning pharmacological and non-pharmacological treatment strategies, with particular emphasis on their cellular and molecular mechanisms of action. We present currently used classes of antidepressant drugs, including selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs), discussing their limitations in the context of contemporary pathophysiological models of depression. We then focus on emerging therapies targeting the glutamatergic, GABAergic, and dopaminergic systems, including ketamine, esketamine, (R)-ketamine, the dextromethorphan–bupropion combination (DMX–BUP), neurosteroids (zuranolone, brexanolone), as well as selective serotonin receptor modulators (gepirone ER) and dopaminergic modulators (cariprazine). The review is complemented by a discussion of non-pharmacological neuromodulatory approaches, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and photobiomodulation. Rather than providing another summary of clinical response indicators, this article integrates the molecular underpinnings of novel antidepressant agents and neuromodulation techniques with current concepts of depression pathophysiology, highlighting their relevance for the development of precise, mechanistically targeted, and multimodal treatment strategies. Full article