Search Results (386)

Background: Nicotine use among the youth has been on the rise, especially with the introduction of E-cigarettes. This has sparked concerns regarding E-cigarettes and traditional cigarettes in terms of patterns, dependence, and perceptions within the youth population, which are issues this study aimed to investigate. Methods: A cross-sectional survey was conducted among university students at Ajman University, which is in the Middle East and North Africa (MENA) region. Using the Cigarette Dependence Scale (CDS-12) and Penn State Electronic Cigarette Dependence Index (PS-ECDI), dependence on both cigarettes and E-cigarettes was quantified. Results: Out of 1713 respondents, 18.9% were currently using nicotine products, including E-cigarettes (12.7%) and traditional cigarettes (5.1%). Nicotine use was significantly associated more with males than females with an odds ratio of 4.14. However, there was no difference between genders in the dependence scores. In addition, dual nicotine use and an earlier onset of nicotine consumption were associated with significantly higher dependence scores than single users and a late onset of smoking. Participants overall attributed cigarettes and E-cigarettes as equally harmful. Conclusions: Both cigarette and e-cigarette use were prevalent and associated with notable dependence. Although E-cigarettes are often promoted as cessation aids, their use in our sample did not appear to facilitate quitting and may instead sustain nicotine dependence. Targeted youth-focused cessation programs and stricter marketing and sales regulations are essential to prevent further normalization. Longitudinal studies are needed to track evolving patterns and health impacts in the MENA region. Full article

(1) Background: The purpose of this study was to investigate the associations between perceived stress and anxiety in high school senior students, taking into account the possible influence from lifestyle (physical activity, nicotine dependence, and alcohol use) and social support. (2) Methods: A representative sample of high school senior students (N = 405; mean age: 18.2 ± 0.4), reflecting the overall geographic distribution of Lithuania’s student population, was investigated using anonymous questionnaires on perceived stress (Perceived Stress Scale, PSS-10), anxiety (Generalized Anxiety Disorder Scale, GAD-7), perceived social support (Multidimensional Scale of Perceived Social Support, MSPSS), lifestyle (Fagerström Test for Nicotine Dependence), alcohol use (Alcohol Use Disorders Identification Test, AUDIT), and physical activity (International Physical Activity Questionnaire, IPAQ). Hierarchical multiple regression analysis was employed, investigating mediating and moderating effects. (3) Results: The direct effect of perceived stress on anxiety was significant (B = 0.364; SE = 0.0486; 95% CI [0.268, 0.459]; p < 0.001). Furthermore, the analysis revealed a significant indirect effect via social support (B = 0.387; SE = 0.0525; 95% CI [0.284, 0.490]), indicating that a portion of the relationship between perceived stress and anxiety was mediated by social support. Physical inactivity, alcohol use, and nicotine dependence served as moderators. Our findings confirmed that all three moderators showed significant interaction effects, with standardized β = −0.124, p = 0.002, for physical inactivity, β = 0.073, p = 0.016, for alcohol dependence, and β = 0.119, p = 0.001, for nicotine dependence, in the relationship between perceived stress and anxiety among high school senior students. (4) Conclusions: These findings have practical insights for educators who implement physical activity and alcohol and nicotine usage programs for high school senior students to help reduce their stress and anxiety. Full article

The endolysosomal system plays a pivotal role in cellular function. Before reaching lysosomes for degradation, the endocytosed cargoes are sorted at various stages of endosomal trafficking for recycling and/or rerouting. The proper execution of these processes depends on tightly regulated ion fluxes across endolysosomal membranes. Recent studies have demonstrated the importance of two-pore channels (TPCs), including TPC1 and TPC2, in endolysosomal trafficking. These channels are expressed in the membranes of distinct populations of endosomes and lysosomes, where they respond to nicotinic acid adenine dinucleotide phosphate (NAADP) and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P₂] to conduct Ca²⁺ and Na⁺ release from these acidic organelles. Here, we discuss the potential implications of Ca²⁺ and Na⁺ fluxes mediated by TPCs across endolysosomal membranes in the physiological and pathophysiological functions of these organellar channels. Full article

Magnesium ions regulate synaptic and nonsynaptic neuronal excitability from intracellular (Mg²⁺_i) and extracellular (Mg²⁺_o) domains, modulating voltage- and ligand-gated ion channels. K+ inward rectifier (Kir) channel inward rectification arises from Mg²⁺_i blocking the pore and outward K⁺ current, while Mg²⁺_o targets external sites. Mg²⁺_i causes voltage-dependent Ca²⁺ voltage-gated (Ca_V) and Na⁺ voltage-gated (Na_V) channel block while phosphorylation modulates channel activity. Mg²⁺_o elicits direct voltage-dependent Ca_V channel block, and screens surface charge, and in Na_V channels reduces conduction and may cause depolarization by quantum tunneling across closed channels. Mg²⁺_i is an allosteric large conductance Ca²⁺-activated K⁺ (BK) channel activator, binding to low-affinity sites to alter Ca²⁺ and voltage sensitivity but reduces small conductance Ca²⁺-activated K⁺ (SK) channels’ outward K⁺ current and induces inward rectification. N-Methyl-D-aspartate receptor (NMDAR) channels are inhibited by Mg²⁺_i binding within the pore, while Mg²⁺_o stabilizes excitability through voltage-dependent block, Mg²⁺_o forms Mg-ATP complex modifying purinergic P2X receptor (P2XR) channel affinity and gating and directly blocks the pore. Mg²⁺_o reduces gamma-aminobutyric acid type A receptor (GABA_AR) channel Cl⁻ current amplitude and augments susceptibility to blockers. Mg²⁺_o and Mg²⁺_i block nicotinic acetylcholine receptor (nAChR) channels through voltage-dependent pore binding and surface charge screening, impeding current flow and altering gating. Full article

Parkinson’s disease (PD) involves motor and cognitive impairment that nicotinic acetylcholine receptors (nAChRs) such as the α7 subtype are responsible for regulating. The hippocampus, abundant in α7 nAChRs, was quantitatively evaluated for [¹²⁵I]α-bungarotoxin ([¹²⁵I]α-Bgtx) binding to α7 nAChRs in postmortem human PD (n = 26; 12 male, 14 female) and cognitively normal (CN) (n = 29; 14 male, 15 female) brain slices. Anti-ubiquitin and anti-α-synuclein immunostained adjacent slices were analyzed using QuPath. Autoradiographs of [¹²⁵I]α-Bgtx radioligand binding were analyzed in OptiQuant. Ubiquitin and α-synuclein distribution generally aligned with the distribution of α7 nAChRs detected by [¹²⁵I]α-Bgtx. Binding of [¹²⁵I]α-Bgtx in PD cases was significantly greater than CN with a 32% increase in gray matter binding. A weak positive correlation between age and [¹²⁵I]α-Bgtx binding was found in both PD and CN. In comparison to Alzheimer’s disease hippocampus, [¹²⁵I]α-Bgtx binding in PD gray matter was higher by 41%. Differences in nAChR expression imply unique roles depending on the neurodegenerative pathology. PD may experience an increase in α7 nAChRs as a compensatory mechanism to the loss in neurons, highlighting its neuroprotective capabilities. [¹²⁵I]α-Bgtx shows potential as a radioligand for α7 nAChRs to elucidate the complexities of PD pathology. Full article

Psychotic disorders such as schizophrenia (SCH) and bipolar affective disorder (BD) are associated with lipid metabolism abnormalities and inflammatory dysregulation. The niacin skin flush test (NSFT) has long been investigated as a non-invasive indicator of these disturbances. This study used deep learning models to assess the diagnostic utility of SKINREMS, a computerized system for automated temporal analysis of skin flush responses. The study included a total of 188 participants, comprising individuals with psychotic disorders and healthy controls. Sequential skin images were recorded after topical application of methyl nicotinate. Five convolutional neural network architectures—ResNet50, ResNet101, DenseNet121, InceptionV3, and EfficientNetB0—were evaluated for their performance in analyzing these time-dependent dermatological responses in a binary classification task. Accuracy, precision, recall, F1-score, and AUC were calculated at four time points (frames 1, 10, 20, 30). The models demonstrated distinct temporal performance profiles. ResNet50 showed consistent high performance across all time points, making it suitable for clinical environments requiring stable predictions. DenseNet121 achieved the highest AUC (up to 0.99) after 15 min, indicating its potential in extended monitoring. EfficientNetB0 offered gradual performance improvement with lower computational demands, while InceptionV3 was most effective at intermediate time points. ResNet101 showed initial high performance but declined mid-phase. AUC remained stable across all models, suggesting robust discriminative capability over time. This study highlights the importance of selecting appropriate deep learning architectures based on the temporal dynamics of biological responses. The findings demonstrate potential for future clinical application of AI in non-invasive diagnostics of psychotic spectrum disorders. Full article

Background: Chronic obstructive pulmonary disease (COPD) is a complex condition influenced by both environmental and genetic factors. Among the genetic determinants, polymorphisms in the CHRNA3/5 and EPHX1 genes have been implicated in nicotine dependence and susceptibility to COPD in several populations. However, evidence remains limited in admixed populations such as Brazilians. Methods: This cross-sectional study investigated the association between CHRNA3 (rs1051730, rs8034191) and EPHX1 (rs2234922) polymorphisms with tobacco nicotine dependence and COPD in a Brazilian cohort. Genotyping was performed using TaqMan^® SNP assays, and pulmonary function was assessed via spirometry according to ATS/ERS standards. Associations between genetic variants, tobacco intake, and COPD status were evaluated using χ² and Fisher’s exact tests, with odds ratios (ORs) and 95% confidence intervals (CIs). Post hoc power analyses were conducted to estimate detectable effect sizes. Results: A total of 123 active or former smokers were analyzed. The CHRNA3 variants (rs1051730 and rs8034191) showed a trend toward higher prevalence among individuals with heavy tobacco intake (>40 pack-years), though no significant allelic or genotypic differences were found between COPD and control groups (p > 0.05). The EPHX1 rs2234922 A allele was significantly more frequent in COPD patients, suggesting increased disease risk (p < 0.05), while the GG genotype appeared protective. Post hoc power analyses indicated moderate power (≈0.56–0.63) for the observed associations. Conclusions: In this Brazilian population, the CHRNA3/5 polymorphisms may influence nicotine dependence, while EPHX1 rs2234922 appears to be associated with COPD susceptibility. These findings support a potential genetic contribution to disease risk and tobacco nicotine dependence, warranting further large-scale studies to confirm these associations and explore their therapeutic implications. Full article

Objectives: Determining individuals’ addiction levels plays a crucial role in facilitating more effective smoking cessation. For this purpose, the Fagerstrom Test for Nicotine Dependence (FTND) is used all over the World as a traditional testing method. It can be subjective and may influence the evaluation results. This study’s key innovation is the use of physiological signals to provide an objective classification of addiction levels, addressing the limitations of the inherently subjective Fagerström Test for Nicotine Dependence (FTND). Methods: Physiological parameters were recorded from 123 voluntary participants (both male and female) aged between 18 and 60 for 120 s using the Masimo Rad-G pulse oximeter and the Hartman–Veroval blood pressure monitor. All participants were categorized into four addiction groups: healthy, lightly addicted, moderately addicted, or heavily addicted with the help of FTND. The recorded data were classified using Decision Tree, KNN, and SVM methods. SMOTE and class-weighting techniques were used to eliminate class imbalance. Also, the PCA technique was applied for dimensionality reduction, and the k-fold cross-validation method was employed to enhance the reliability of the machine learning algorithms. Results: Machine learning methods, when evaluated using the SMOTE with a (7380×7) sample of physiological signals recorded every 2 s from 123 participants, showed a high recall of 98.74%, specificity of 99.58%, precision of 98.79%, F-score of 98.74%, and accuracy of 98.75%. Also, it is extracted that there is a direct relationship between physiological parameters and smoking addiction levels. Conclusions: The study’s core novelty lies in leveraging non-invasive physiological signals to objectively classify addiction levels, addressing the subjectivity of the Fagerström Test for Nicotine Dependence (FTND). This study provides a proof-of-concept for the feasibility of using machine learning and physiological signals to assess addiction levels. The results indicate that the approach is promising. Full article

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with limited treatment options. Emerging evidence reveals bidirectional crosstalk between gut and brain through inflammatory signaling, leading us to hypothesize that anti-neuroinflammatory agents may concurrently ameliorate intestinal inflammation. The scorpion venom-derived heat-resistant synthetic peptide (SVHRSP), a bioactive peptide initially identified in scorpion venom and subsequently synthesized by our laboratory, possesses neuroprotective, anti-inflammatory, and antioxidative activities. Its properties make SVHRSP a promising candidate for investigating the therapeutic potential of anti-neuroinflammatory strategies in mitigating intestinal inflammation. Methods: Using a chronic dextran sodium sulfate (DSS)-induced colitis model in wild-type and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice, along with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, we assessed SVHRSP’s effects on inflammation, histopathology, gut permeability, oxidative stress markers, and α7nAChR-Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. Results: SVHRSP treatment significantly ameliorated colitis symptoms in wild-type mice by reducing inflammation, repairing histological damage, restoring gut barrier function, and attenuating oxidative stress, with these effects abolished in α7nAChR knockout mice. Mechanistically, SVHRSP activated JAK2/STAT3 signaling through α7nAChR engagement, suppressing proinflammatory cytokine production in macrophages. Conclusion: These results demonstrated that SVHRSP alleviated intestinal inflammation via α7nAChR-dependent JAK2/STAT3 activation. Combined with its known neuroprotective properties, our findings support the repurposing of this neuroactive peptide, SVHRSP, for treating intestinal inflammatory disorders. Full article

Neonicotinoid pesticides, including imidacloprid (IMI), are widely used in agriculture and as household insecticides. IMI displays strong affinity for insect nicotinic acetylcholine receptors (nAChRs); however, neonicotinoids still partially bind to mammalian nAChRs. Relatively little is known about how neonicotinoid exposure alters learning, memory or mood, even though nAChRs play a role in these mechanisms. We tested the hypothesis that developmental exposure to IMI impairs performance on memory tasks, and anxiety- and depressive-like behavior. We orally dosed pregnant CD-1 mice from gestation day 10 to birth with vehicle or IMI at 0.5 mg/kg/day or 5.7 mg/kg/day. When exposed animals were adults, we examined cognitive and emotional behaviors and we examined the effect of IMI on α7 and α4 nAChR subunit mRNA expression using qPCR. For both sexes, IMI exposure was associated with impaired striatal-dependent procedural learning task and hippocampal-dependent spatial learning but had no effect on hippocampal-dependent working memory. Males, but not females, displayed increased anxiety-like behavior, with low dose subjects displaying more pronounced effects, suggesting a non-linear dose response. In males, we found lower α7 subunit mRNA expression in the hippocampus and amygdala and lower α4 mRNA expression in the striatum compared to controls. Thus, exposure to IMI during a critical period is associated with disruptions to cognitive and anxiety-like behaviors. Additionally, in males, IMI exposure is associated with reduced expression of nAChR subunits in relevant brain regions. Full article

Besides its neurotoxic action and selective toxicity on insecticidal nicotinic acetylcholine receptors, recent studies have shown that imidacloprid may cause other adverse effects in mammals. In the present study, cholinesterase activity, oxidative stress response, genotoxicity in the liver and kidney, and imidacloprid levels in the urine, liver, and kidney of male Wistar rats orally administered with 0.06, 0.8, and 2.25 mg imidacloprid/kg bw/day for 28 days were evaluated. Imidacloprid urine mass concentrations in treated rats increased dose-dependently. Exposure to 0.8 mg imidacloprid/kg bw/per day significantly decreased cholinesterase activities in the liver and kidney. Reactive oxygen species levels decreased significantly in the liver at the same dose. Lipid peroxidation was significantly reduced in the liver at two higher doses. No significant changes in glutathione levels or the activities of superoxide dismutase and catalase were observed. A significant decrease in the activity of glutathione peroxidase was detected in the liver at the highest dose. DNA damage was low in both liver and kidney. Exposure to imidacloprid at studied experimental conditions did not cause a significant oxidative stress response and resulted in low genotoxic effects in the liver and kidney of rats, indicating that these organs are less susceptible to adverse imidacloprid effects at such low doses. Full article

Background/Objectives: Cerebral palsy (CP) is a leading cause of motor disability in children and is commonly associated with spasticity. Treatment with radial extracorporeal shock waves (rESWs) is an established non-invasive therapy for spasticity, although its underlying mechanisms remain poorly understood. Caenorhabditis elegans (C. elegans) represents a powerful model for neuromuscular research due to its fully mapped nervous system, conserved cholinergic pathways and suitability for high-throughput behavioral analysis. This study aimed to test whether rESWs modulate cholinergic signaling at the neuromuscular junction (NMJ) in C. elegans. Methods: Wild-type and acr-16 mutant C. elegans were exposed in liquid to varying doses of rESWs, nicotine and carbachol in different combinations. Locomotor behavior was recorded using high-resolution video tracking, and parameters including peristaltic speed, body wavelength, reversals and omega bends were quantified. Results: Exposure to rESWs transiently altered locomotion, most notably by reducing forward speed and increasing the frequency of reversals. However, rESWs did not consistently modify behavioral responses to nicotine or carbachol, and these effects were not clearly dependent on NMJ-associated nicotinic receptors. Conclusions: Exploring C. elegans as a model for rESW effects on spasticity proved informative but also revealed important limitations. Results indicate that rESWs act on the nervous system more broadly, extending beyond neuromuscular structures. This contrasts with the clinical situation, where rESWs primarily target muscles and connective tissues. While this precludes C. elegans as a direct model for CP-related spasticity, the observation that rESWs influence nervous-system function at a systemic level points to potential therapeutic avenues for neurological diseases. Full article

Objective: To synthesize the current evidence on the cardiovascular effects of electronic cigarettes (ECs) in young adults (18–30 years), distinguishing between acute and chronic exposure, and comparing their effects to conventional tobacco (CT) use. Methods: A systematic review and meta-analysis (PROSPERO: CRD420251072847) was conducted following PRISMA guidelines. A total of 21 studies (12 RCTs, 8 case–control, 1 cohort) involving 17241 participants were included. Results: Acute EC use, particularly with nicotine, significantly increased systolic blood pressure (SBP: MD = 3.14 mmHg, 95% CI: 0.76 to 5.52), diastolic blood pressure (DBP: MD = 2.05 mmHg, 95% CI: 0.85 to 3.25), and heart rate (HR: MD = 4.23 bpm, 95% CI: 2.10 to 6.37), with effects most pronounced at 0 min post-exposure and dissipating within 1 h. Chronic EC use was associated with reduced endothelium-dependent vasodilation and early atherosclerotic changes. Nicotine-free ECs induced fewer cardiovascular alterations. Comparisons with CT revealed less severe cardiovascular damage with ECs, though still significant when compared to non-smokers. Conclusion: Nicotine-containing EC use in young individuals is associated with modest, predominantly acute and dose-dependent, cardiovascular effects, including transient increases in BP and HR. While initially less harmful than CT, the evidence is largely from cross-sectional studies and acute use, so ECs cannot be considered safe and their use warrants caution in youth. Full article

Background: Mongolia is experiencing a rapid epidemiologic transition in which high burdens of micronutrient malnutrition, infection, and cardiometabolic disease are simultaneously prevalent. This cross-sectional study sought to understand how nutritional, lifestyle, and cardiometabolic risk factors are distributed among a population at high-risk for tuberculosis (TB), comprising household contacts (HHCs) and healthcare workers, (HCWs) in Ulaanbaatar, Mongolia, and how these factors are associated with TB infection. Methods: A total of 196 HHCs and 241 HCWs were assessed for latent TB infection (LTBI) using the QuantiFERON-TB Gold Plus (QFT-Plus) assay and for diabetes using fingerprick samples for fasting blood glucose. Participants also underwent assessments of their diet and physical activity, nicotine dependence, body mass index, and serum 25(OH)D concentration. We examined associations between assessed risk factors and LTBI using multivariate logistic regression. Results: The prevalence of LTBI was 47% for both HHCs and HCWs. A total of 54% percent of HHCs and 68% of HCWs had low physical activity levels; 63% of HHCs and 95% of HCWs were overweight or obese; 7% of HHCs and 4% of HCWs had impaired or diabetic fasting blood glucose [FBG]; and 49% of HHCs and 70% of HCWs were vitamin D deficient. In a multivariable analysis of HHCs, LTBI was independently associated with lower serum [25(OH)D], and the odds ratio (OR) was 3.18 (95% CI 1.38–7.79; p = 0.009). In contrast, the probability of LTBI did not differ significantly between vitamin D-deficient and non-deficient HCWs, and the OR was 0.89 (95% CI 0.59–1.37; p = 0.42). In a pooled analysis of HHCs and HCWs, the probability of LTBI did not significantly differ between vitamin D-deficient vs. non-deficient participants. The association between serum [25(OH)D] and LTBI among HHCs and HCWs was significantly modified by fasting blood glucose (FBG), such that a lower vitamin D status was significantly more common among those in the highest tertile of FBG than among those in the lowest tertile of FBG. Conclusions: Nutritional, lifestyle, and cardiometabolic risk factors are highly prevalent among HHCs and HCWs with TB in Ulaanbaatar, Mongolia. These findings underscore the importance of simultaneously controlling TB infection, malnutrition, and cardiometabolic risks among HHCs and HCWs to reduce the disease burden in Mongolia. Full article

Considering the increased risk of cognitive deficits and mood disorders programming associated with bisphenol exposure, we used a preclinical model to identify short- and long-term effects of early exposure to Bisphenol A (BPA) and its replacement, Bisphenol S (BPS), on the central cholinergic and serotonergic systems. Wistar female and male rats born to dams exposed to BPA or BPS (both at 10 μg/kg/day or 50 μg/kg/day) during pregnancy and lactation were euthanized at weaning or adulthood. Cholinergic and serotonergic biomarkers were assessed in the frontal cortex and pons + medulla oblongata. BPA and BPS disrupted these systems, with outcomes depending on the specific bisphenol, biomarker, and time point. Effects also varied across brain regions and between sexes. The nicotinic cholinergic receptor showed more pronounced alterations than the presynaptic choline transporter. Both serotonergic receptors—5-HT1AR and 5-HT2R—were affected; however, the serotonergic transporter remained unchanged. Increased binding was the predominant effect for both systems. Maternal exposure to BPA, even at low doses, induces sex-dependent short- and long-term changes in the cholinergic and serotonergic systems of the progeny. BPS affects these same neurotransmitter systems, although leading to compound-specific outcomes. These results pose both BPA and BPS as neurotoxicants that compromise neurodevelopment and program disorders later in life. Full article