UNASSIGNED: Determining how individuals engage with digital health interventions over time is crucial to understand and optimize intervention outcomes.
UNASSIGNED: To identify the engagement trajectories with a mobile chat-based smoking cessation intervention and examine its association with biochemically validated abstinence.
UNASSIGNED: A secondary analysis of a pragmatic, cluster randomized clinical trial conducted in Hong Kong with 6-month follow-up. From June 18 to September 30, 2017, 624 adult daily smokers were recruited from 34 community sites randomized to the intervention group. Data were analyzed from March 6 to October 30, 2023.
UNASSIGNED: Chat-based cessation support delivered by a live counselor via a mobile instant messaging app for 3 months from baseline.
UNASSIGNED: Group-based trajectory modeling was used to identify engagement trajectories using the participants\' weekly responses to the messages from the counselor over the 3-month intervention period. The outcome measures were biochemically validated tobacco abstinence at 3-month (end of treatment) and 6-month follow-ups. Covariates included sex, age, educational level, nicotine dependence, past quit attempt, and intention to quit at baseline.
UNASSIGNED: Of 624 participants included in the analysis, 479 were male (76.8%), and the mean (SD) age was 42.1 (16.2) years. Four distinct engagement trajectories were identified: low engagement group (447 [71.6%]), where participants maintained very low engagement throughout; rapid-declining group (86 [13.8%]), where participants began with moderate engagement and rapidly decreased to a low level; gradual-declining group (58 [9.3%]), where participants had high initial engagement and gradually decreased to a moderate level; and high engagement group (58 [5.3%]), where participants maintained high engagement throughout. Compared with the low engagement group, the 6-month validated abstinence rates were significantly higher in the rapid-declining group (adjusted relative risk [ARR], 3.30; 95% CI, 1.39-7.81), gradual-declining group (ARR, 5.17; 95% CI, 2.21-12.11), and high engagement group (ARR, 4.98; 95% CI, 1.82-13.60). The corresponding ARRs (95% CI) of 3-month validated abstinence were 4.03 (95% CI, 1.53-10.59), 5.25 (95% CI, 1.98-13.88), and 9.23 (95% CI, 3.29-25.86).
UNASSIGNED: The findings of this study suggest that higher levels of engagement with the chat-based smoking cessation intervention were associated with greater biochemically validated tobacco abstinence. Improving engagement with digital interventions may increase intervention benefits.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT03182790.

Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut microbiota (GM) influences addictive behaviors, but the pattern of GM changes during addiction in animals of different species remains unclear. The aim of this study was to explore the association between dynamic changes in GM and MA self-administration acquisition among two classical mammals, rhesus monkeys (Macaca mulatta) and rats, MA self-administration models. Male Sprague-Dawley rats and male rhesus monkeys were subjected to classical MA self-administration training, and fecal samples were collected before and after MA self-administration training, respectively. 16S rRNA sequencing was used for GM analyses. We found that GM changes were more pronounced in rats than in rhesus monkeys, as evidenced by more GM taxa producing significant differences before and after MA self-administration training in rats than in monkeys. We also found that the expression of the genus Clostridia_vadinBB60_group significantly decreased after MA self-administration training in both rats and rhesus monkeys. Lactobacillus changes were significantly negatively correlated with total MA uptake in rats (Pearson R =  - 0.666, p = 0.035; Spearman R =  - 0.721, p = 0.023), whereas its change was also highly negatively correlated with total MA uptake in rhesus monkeys (Pearson R =  - 0.882, p = 0.118; Spearman R =  - 1.000, p = 0.083), although this was not significant. These findings suggest that MA causes significant alterations in GM in both rhesus monkeys and rats and that the genus Lactobacillus might be a common therapeutic target for MA uptake prevention across the species.

Methamphetamine (METH), an amphetamine-type stimulant, has been extensively abused globally in the past decades. METH use causes great harm to the major systems of the human body. Specifically, METH has a negative impact on the hypothalamic- pituitary-testicular axis, testicular structure, sperm function, ovarian folliculogenesis, oocyte quality, embryo development, and newborns. However, the mechanisms underlying these toxic effects have not yet been fully described. This study reviews the evidence concerning the impact of METH on male and female reproduction in the context of the testis, sperm, ovaries, oocytes, reproductive hormones, embryo development, and newborns, discussing the potential pathophysiological mechanisms in the reproductive toxicity induced by METH.

Sleep problems and impulsivity frequently occur in methamphetamine (MA) abstainers and are linked to aberrant brain function. However, the interplay between these factors remains poorly understood. This study aimed to investigate the relationship between sleep, impulsivity, and regional homogeneity (ReHo) through mediation analysis in MA abstainers. 46 MA abstainers and 44 healthy controls were included. Impulsivity and sleep problems were evaluated using the Barratt Impulsivity Scale and the Pittsburgh Sleep Quality Scale, respectively. ReHo, indicative of local brain spontaneous neural activity, was assessed using resting-state functional magnetic resonance imaging. Results unveiled correlations between different dimensions of impulsivity and ReHo values in specific brain regions. Motor impulsivity correlated with ReHo values in the left postcentral gyrus and left precentral gyrus, while non-planning impulsivity was only associated with ReHo values in the left precentral gyrus. Additionally, the need for sleep medications correlated with ReHo values in the left precentral gyrus and bilateral postcentral gyrus. Also, the need for sleep medications was positively correlated with cognitive impulsivity and motor impulsivity. Mediation analysis indicated that reduced ReHo values in the left precentral gyrus mediated the association between impulsivity and the need for sleep medications. These findings imply that addressing sleep problems, especially the need for sleep medications, might augment spontaneous neural activity in specific brain regions linked to impulsivity among MA abstainers. This underscores the importance of integrating sleep interventions into comprehensive treatment strategies for MA abstainers.

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 μg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.

OBJECTIVE: To investigate the effects of electroacupuncture combined with paliperidone palmitate long-acting injection (PP-LAI) on withdrawal symptoms and neurotransmitters in methamphetamine (MA) addicts.
METHODS: A total of 109 methamphetamine addicts, who were treated in the hospital from October 2021 to October 2022, were selected. According to the random number table, the patients were divided into the study group (n=54) and the control group (n=55), in which the control group was treated with PP-LAI and the study group was treated with electroacupuncture on the basis of the control group; the methamphetamine withdrawal symptom score scale was used to assess the therapeutic effect before treatment and within 12 months after treatment; the changes of brain neurotransmitters dopamine, γ-aminobutyric acid, serotonin, acetylcholine values were compared between the two groups.
RESULTS: 1) There was no statistical difference in MA withdrawal symptom scores between the two groups before treatment (p>0.05); 2) MA withdrawal symptom scores have a statistically significant difference between the study group and the control group after 3 and 6 months of treatment; 3) dopamine levels in the study group were significantly higher than those in the control group after 6 months of completion of treatment, and γ-aminobutyric acid values and 5- serotonin values in the study group were significantly lower than those in the control group (p<0.05).
CONCLUSIONS: Electroacupuncture combined with PP-LAI can partially improve the withdrawal symptoms and anxiety of methamphetamine addicts. This is a potential treatment for preventing relapse of withdrawal symptoms.

Disulfiram (DSF) metabolites exhibit antitumor properties when bound to Cu2+. This combination also promotes the generation of reactive oxygen species (ROS), ultimately leading to tumor cell death. In this study, CuO2 served as a carrier for DSF, forming a dual-drug delivery system with Cu2+ and DSF encapsulated in polydopamine (PDA). In the final delivery system, CuO2 (DSF-CuO2@PDA) was hydrolyzed at the tumor site, releasing both Cu2+ and H2O2. Cu2+ reacts with DSF metabolites to form Bis(diethyldithiocarbamate)-Cu (CuET), which triggers a Fenton-like reaction that generates ROS. Chemotherapy and chemodynamic therapy exhibited significant tumor-suppressive capabilities, with an inhibition rate of 61 %. In addition, the DSF-CuO2@PDA complex demonstrated superlative tumor-targeting ability and biocompatibility.

Methamphetamine (METH) is a widely abused amphetamine-type psychoactive drug that causes serious health problems. Previous studies have demonstrated that METH can induce neuron autophagy and apoptosis in vivo and in vitro. However, the molecular mechanisms underlying METH-induced neuron autophagy and apoptosis remain poorly understood. Stromal interacting molecule 1 (STIM1) was hypothesized to be involved in METH-induced neuron autophagy and apoptosis. Therefore, the expression of STIM1 protein was measured and the effect of blocking STIM1 expression with siRNA was investigated in cultured neuronal cells, and the hippocampus and striatum of mice exposed to METH. Furthermore, intracellular calcium concentration and endoplasmic reticulum (ER) stress-related proteins were determined in vitro and in vivo in cells treated with METH. The results suggested that STIM1 mediates METH-induced neuron autophagy by activating the p-Akt/p-mTOR pathway. METH exposure also resulted in increased expression of Orai1, which was reversed after STIM1 silencing. Moreover, the disruption of intracellular calcium homeostasis induced ER stress and up-regulated the expression of pro-apoptotic protein CCAAT/enhancer-binding protein homologous protein (CHOP), resulting in classic mitochondria apoptosis. METH exposure can cause neuronal autophagy and apoptosis by increasing the expression of STIM1 protein; thus, STIM1 may be a potential gene target for therapeutics in METH-caused neurotoxicity.

Maintenance therapy with buprenorphine and methadone is the gold standard pharmacological treatment for opioid use disorder (OUD). Despite these compounds demonstrating substantial efficacy, a significant number of patients do not show optimal therapeutic responses. The abuse liability of these medications is also a concern. Here we used rats to explore the therapeutic potential of the new long-acting pan-opioid agonist Cebranopadol in OUD. We tested the effect of cebranopadol on heroin self-administration and yohimbine-induced reinstatement of heroin seeking. In addition, we evaluated the abuse liability potential of cebranopadol in comparison to that of heroin under fixed ratio 1 (FR1) and progressive ratio (PR) operant self-administration contingencies. Oral administration of cebranopadol (0, 25, 50μg/kg) significantly attenuated drug self-administration independent of heroin dose (1, 7, 20, 60μg/inf). Cebranopadol also reduced the break point for heroin (20 μg/inf). Finally, pretreatment with cebranopadol significantly attenuated yohimbine-induced reinstatement of drug seeking. In abuse liability experiments under FR1 contingency, rats maintained responding for heroin (1, 7, 20, 60μg/inf) to a larger extent than cebranopadol (0.03, 0.1, 0.3, 1.0, 6.0μg/inf). Under PR contingency, heroin maintained responding at high levels at all except the lowest dose, while the break point (BP) for cebranopadol did not differ from that of saline. Together, these data indicate that cebranopadol is highly efficacious in attenuating opioid self-administration and stress-induced reinstatement, while having limited abuse liability properties. Overall, the data suggest clinical potential of this compound for OUD treatment.

The escalating issue of drug abuse poses a significant threat to public health and societal stability worldwide. An on-site drug detection platform is vital for combating drug abuse and trafficking, as it eliminates the need for additional tools, extensive processes, or specialized training. Therefore, it is imperative to develop a fast, sensitive, non-invasive, and reliable multiplex drug testing platform. In this study, we have presented a silica core@dual quantum dot-shell nanocomposite (SI/DQD)-based fluorescent lateral flow immunoassay (LFIA) platform for the highly sensitive and simultaneous point-of-care (POC) detection of methamphetamine (MET) and tramadol (TR). A 3D-printed attachment was designed to integrate optical and electrical components, facilitating the miniaturization of the instrument and reducing both cost and complexity. The device\'s advanced hardware and effective fluorescence extraction algorithm with waveform reconstruction enable swift, automatic noise reduction and data analysis. SI/DQD nanocomposites were utilized as fluorescent nanotags in the LFIA strips due to their outstanding luminous efficiency and robustness. This LFIA platform achieves impressive detection limits (LODs) of 0.11 ng mL-1 for MET and 0.017 ng mL-1 for TR. The method has also successfully detected MET and TR in complex biological samples, demonstrating its practical application capabilities. The proposed fluorescent LFIA platform, based on SI/DQD technology, holds significant promise for the swift and accurate POC detection of these substances. Its affordability, compact size, and excellent analytical performance make it suitable for on-site drug testing, including at borders and roadside checks, and open up new possibilities for the design and implementation of drug testing methods.