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Post-weaning social isolation increases reward-seeking behavior in mice.

Social isolation is a growing public health concern. Although isolation at any age is harmful, previous studies have shown that isolation during adolescence, correlating with critical periods of brain development, can impair cognitive function and increase the risk for psychiatric illness later in life. In this study, we utilized a mouse model of social isolation (SI) during adolescence (postnatal day 21-35) and compared performance of isolated and group-housed mice on a touchscreen-based continuous performance test (rCPT) and fixed ratio/progressive ratio (FR/PR) tasks in adulthood. SI improved performance in the rCPT and the improvement in performance was consistent across time bins within the 45-minute testing session. There were no effects of SI on reaction times or reward retrieval latencies. A possible confound for performance in the rCPT would be SI-induced changes in reward-seeking or motivation for the strawberry milk reward. We next compared the SI mice to their group-housed littermate controls on both PR and FR schedules of reinforcement and found that SI mice had higher breakpoints on a PR4 schedule and earned significantly more reinforcers on an FR1 schedule of reinforcement compared to their group-housed littermates, suggesting that high performance in the CPT may be due to increased motivation for food rewards. These data indicate that SI during adolescence has significant effects on reward-seeking behavior in adult mice and may provide a useful behavioral model for studying the link between SI and risk for neuropsychiatric disorders.

Animals

Does impulsivity predict treatment outcomes in PTSD with borderline personality disorder features? Results from a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). However, a substantial proportion of clients do not respond adequately or drop out of therapy prematurely. This has sparked interest in identifying individual-level predictors of treatment outcomes, including improvement in PTSD severity and dropout. Impulsivity may be a predictor because it may interfere with key therapeutic processes, such as cognitive restructuring and emotional processing. Consequently, we present a hypothesis-driven secondary analysis of a 15-month randomized clinical trial comparing Dialectical Behavior Therapy for PTSD (DBT-PTSD) and Cognitive Processing Therapy (CPT) in women with childhood abuse-related PTSD and borderline personality disorder features to test whether impulsivity, assessed at baseline, predicts PTSD improvement and dropout. We further explore whether the dimensions of impulsivity (non-planning, attentional impulsivity, and motor impulsivity) differentially affect the outcomes in DBT-PTSD vs. CPT. METHODS: A total of 193 cis women with PTSD related to childhood abuse and borderline personality disorder features were assessed using the Clinician-Administered PTSD Scale (CAPS) and the Barratt Impulsiveness Scale (BIS-10). Separate probit models and general linear models were applied to predict dropout and pre-to-post changes in PTSD severity (ΔCAPS) from total impulsivity and subscale scores, i.e. non-planning, attentional and motor impulsivity. RESULTS: Overall, dropout rates were higher for participants with higher baseline impulsivity scores (p = 0.049), particularly for those with higher non-planning impulsivity (p = 0.012). In participants randomized to CPT improvement in PTSD symptom severity (ΔCAPS) was negatively related to baseline total impulsivity (p = 0.021). In participants randomized to DBT-PTSD this relation was not significant. CONCLUSIONS: The results suggest that impulsivity may predict treatment outcomes. Specifically, patients with elevated impulsivity may be less likely to respond adequately to CPT. If replicated, these findings have implications for personalization of treatment.

Humans

Mediators of Change in Cognitive Behavioral and Mindfulness-Based Online-Interventions for Hypoactive Sexual Desire Dysfunction in Women.

Low sexual desire is a common sexual problem among women. When it is accompanied by significant personal distress, it may be diagnosed as hypoactive sexual desire dysfunction (HSDD). Both cognitive behavioral therapy (CBT) and mindfulness-based therapy (MBT) are effective treatments for HSDD when delivered in person or online. In this randomized controlled treatment study, CBT and MBT consisted of eight guided self-help modules delivered online, and participants completed measures at pretreatment and after 3, 6, and 12 months. Nine variables were examined as potential mediators of treatment outcomes (i.e., sexual desire and sexual distress), namely mindfulness, self-compassion, rumination, body connection, self-consciousness, relationship satisfaction, sexual communication, depression, and anxiety. In total, 212 women diagnosed with HSDD were randomized to either CBT or MBT (Mage = 36.3, SD = 10.2). Improvements in self-compassion, rumination, body connection, and self-consciousness partially mediated treatment outcomes in at least one of the treatment groups. Mediation effects were mostly small, explaining up to 15% of the total effects. No systematic differences in mediation pathways between CBT and MBT were found. These findings emphasize the importance of emotion regulation, metacognitive processes, and embodiment for the effective treatment of HSDD. Future research should refine treatment components to enhance efficacy and ensure that psychological interventions adequately address common concerns among women with HSDD.

Humans

List randomization for prevalence estimation of sensitive behavioral data among women with HIV of reproductive age in Lilongwe, Malawi.

Self-reported data are subject to reporting biases, including social desirability bias. List randomization is one method that can help mitigate the impact of such biases. Here, we examined the utility of list randomization among women of reproductive age living with HIV in sub-Saharan Africa. In the Family Planning and Antiretroviral Therapy study, participants were randomized to answer 5 blocks of true/false statements via either direct or list response. Each block contained 3 nonsensitive statements and 1 sensitive statement related to either condom use or HIV disclosure. For each sensitive statement, we calculated the prevalence difference (PD) comparing list response to direct response overall and stratified by socioeconomic status. The PD for 4 of the sensitive statements was negligible. However, we found that self-report of always using a condom was reported by 53.1% at list response visits vs 34.7% at direct response visits (PD, 18.5%; 95% CI, 6.2%-30.7%), a difference that was attenuated among those with higher socioeconomic status. In this setting, list randomization did not meaningfully change the estimated prevalence for most questions, except for one question, which unexpectedly produced a higher estimate for a positive behavior. Examining this method in other settings and populations is warranted.

Humans

Dissociating behavioral, neural and experiential effects of prefrontal HD-tDCS during conflict resolution.

Inconsistent evidence regarding the cognitive effects of transcranial direct current stimulation (tDCS) highlights the need for more comprehensive approaches to assess its impact. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) on conflict resolution by combining behavioral, neural, and subjective experience measures. Sixty participants were randomly assigned to anodal, cathodal, or sham HD-tDCS groups and completed a 30-min flanker task. EEG was recorded during the first and last blocks (without stimulation), while stimulation was applied during the intermediate blocks of the task. Using a multidimensional methodological approach including Drift-Diffusion Modeling (DDM), EEG spectral analysis, Lempel-Ziv complexity, and Temporal Experience Tracing (TET), we assessed the cognitive, neural, and phenomenological effects of stimulation. Behavioral results indicated no significant improvements in reaction times or accuracy across the stimulation groups. Similarly, DDM parameters showed no effect of HD-tDCS on latent cognitive processes. However, EEG data revealed a significant reduction in neural complexity in the anodal group during resting-state, suggesting a stabilization or reorganization of neural dynamics. Subjective experience analysis identified two distinct clusters of task-related feelings, though time spent in these experiential states did not differ between groups. Interestingly, sensation of stimulation was significantly higher for anodal stimulation than sham when analyzed as a single dimension. Despite null behavioral effects, this study provides important insights into the neural and subjective responses to HD-tDCS and highlights the value of integrating complementary multidimensional approaches to better characterize brain stimulation effects. These findings contribute to the ongoing debate about the efficacy of tDCS in cognitive enhancement.

Humans

Effectiveness and implementation of task-sharing cognitive-behavioral interventions for perinatal mental health: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of cognitive-behavioral interventions (CBIs) delivered by nonspecialist providers (NSPs) on perinatal depressive (PND) and anxiety symptoms, and to narratively synthesize their implementation processes and reported implementation outcomes, including acceptability, feasibility, fidelity, cost, and sustainability. METHODS: We systematically searched eight databases from inception to April 8, 2025. Eligible studies were randomised controlled trials (RCTs) assessing CBIs delivered by NSPs for PND and/or anxiety. Two reviewers independently screened, extracted, and assessed trials. Meta-analyses employed random-effects models, with subgroup, sensitivity, meta-regression, and publication bias analyses conducted in Stata 18.0. Implementation processes and outcomes were reported as frequencies or percentages across trials. RESULTS: A total of 47 trials (11, 357 participants) were included in the systematic review, of which 37 trials (8,709 participants) were included for meta-analyses. CBIs were conducted in 12 countries. Nurses and midwives delivered 45% of CBIs. CBIs were associated with reduced PND post-intervention compared with control conditions (standardized mean difference [SMD] -0.49, 95% CI -0.63 to -0.35; I² = 86.8%). Limited evidence from four trials suggested a small sustained effect at 12 months (SMD -0.14, 95% CI -0.27 to -0.02; I² = 26.4%). Reductions in anxiety symptoms were observed immediately post-intervention (SMD, -0.45, 95% CI -0.65 to -0.25; I²=81%), but evidence for longer-term effects was limited. Subgroup analyses confirmed consistent effects across diverse settings, populations, and intervention characteristics. Reporting of implementation processes (e.g., training, supervision, fidelity) was limited, with only 23.4% of trials assessing fidelity and 10.6% evaluating costs. CONCLUSIONS: NSP-delivered CBIs showed beneficial effects on PND and anxiety, with generally encouraging evidence for acceptability and feasibility. However, evidence for sustained effects beyond the immediate post-intervention period remains limited. Future studies should strengthen long-term follow-up and improve reporting of implementation processes and outcomes, particularly in rural and adolescent perinatal populations, to inform scalable and equitable task-sharing models.

Humans

Effectiveness of Embedded Social Media Content on E-cigarette Attitudes and Behaviors: Results from a Randomized Control Trial.

BACKGROUND: This longitudinal randomized controlled trial examined the effects of anti-vaping social media content on e-cigarette attitudes and intentions among U.S. young adults (ages 18-24; n=3,400). METHODS: Targeted content was embedded directly into participants' social media feeds, with varying levels of impressions. RESULTS: Results indicate that increased exposure to anti-vaping messages significantly elevated perceived risk of harm (&#x3b2;=0.11, 95% CI: 0.03-0.20, p < .01) and social unacceptability of e-cigarette use (&#x3b2;=0.10, 95% CI: 0.03-0.18, p < .01), while decreasing intentions to vape (RRR = 0.59, 95% CI: 0.36-0.97, p < .05). Notably, these attitudinal shifts occurred even with relatively low ad exposure and over an extended intervention period, while controlling for the e-cigarette use status (never, former, or current) of participants. Discussion These findings support the effectiveness of digital media campaigns in influencing health-related behaviors and attitudes among young adults. Specifically, embedding anti e-cigarette content directly in the feed of young adults is shown to be effective in shifting attitudes in a space where these young adults are already engaged. Limitations include limited ad impressions and minimal change in ad awareness recall, suggesting future research should explore longer interventions and broader nicotine product messaging.

Humans

Hippocampal teneurin-4 knockdown promotes depression-like behavioral phenotypes by disrupting oligodendrocyte differentiation in mice.

Depression is one of the most prevalent mental disorders worldwide. The limited clinical efficacy of current antidepressants highlights identifying new therapeutic targets. Emerging evidence suggests that dysfunction of oligodendrocyte lineage cells contributes to the pathophysiology of depression. Teneurin-4 (Tenm4), a transmembrane protein that promotes oligodendrocyte differentiation and myelination, has been implicated in psychiatric disorders in genome-wide association studies; however, its causal role remains unclear. To determine whether Tenm4 contributes to depressive-like behavioral phenotypes, we examined Tenm4 protein expression in mice exposed to repeated forced swimming stress and generated hippocampal Tenm4 knockdown (Tenm4KD) mice. Chronic stress reduced Tenm4 expression levels in the hippocampus. Mice with hippocampus-specific Tenm4KD exhibited depressive-like behaviors, accompanied by reduced hippocampal myelin basic protein. Importantly, administration of clemastine, a myelin formation promoter, inhibited the reduction of myelin and attenuated depression-like behavioral phenotypes. Immunohistochemical analysis showed that Tenm4KD significantly decreased the number of mature oligodendrocyte cells and increased in the number of oligodendrocyte precursor cells, without changes in the total number of oligodendrocyte lineage cells. This study provides the first evidence that hippocampal Tenm4 deficiency induces depression-like behavior phenotypes through impaired oligodendrocyte differentiation and promoting demyelination. Our results identify Tenm4 as a molecular regulator of stress-induced behavioral phenotypes and suggest that it might represent a potential therapeutic target for mood disorders associated with demyelination.

Animals

Effects of an internet-based combined exercise and cognitive-behavioral therapy intervention on endocannabinoid system biomarkers and physical fitness in adults with mild-to-moderate depression: a SONRIE randomized controlled trial.

BACKGROUND: This SONRIE randomized controlled trial (NCT05849792) examined the effects of a 12-week combined physical exercise and internet-based cognitive-behavioral therapy (iCBT) intervention on endocannabinoid system (ES) biomarkers and physical fitness in adults with mild-to-moderate depression. METHODS: Eighty adults were randomly assigned 1:1 to an intervention (IG) or control (CG) group. Outcomes included nine ES biomarkers (2-arachidonoylglycerol, 2-AG; anandamide, AEA; seven analogues) and physical fitness, including cardiorespiratory fitness (CRF; 6-minute walking test) and muscular strength. Measurements were taken at baseline, post-intervention and 8-week follow-up. Primary analysis performed 2&#x2009;&#xd7;&#x2009;3 repeated-measures ANOVA on completers; mixed-effects intention-to-treat model as sensitivity analysis. RESULTS: No significant time &#xd7; group interaction was detected for any ES biomarker, including 2-AG (F(2,88)&#x2009;=&#x2009;0.17, p&#x2009;=&#x2009;0.844) and AEA (F(2,88)&#x2009;=&#x2009;1.20, p&#x2009;=&#x2009;0.306); both groups showed comparable within-group decreases in 2-AG, 2-LG and 2-OG. The intervention significantly improved CRF [between-group difference&#x2009;+&#x2009;81.6&#xa0;m at 12 weeks (F(2,78)&#x2009;=&#x2009;7.88, p&#x2009;=&#x2009;0.001)], exceeding the established minimal clinically important difference. None of the exploratory muscular fitness outcomes reached statistical significance; the arm curl test showed a borderline non-significant interaction (F(2,78)&#x2009;=&#x2009;2.83, p&#x2009;=&#x2009;0.065). CONCLUSION: A 12-week internet-based combined exercise and iCBT intervention significantly improved CRF in adults with mild-to-moderate depression. We did not find evidence of an intervention-specific effect on plasma ES biomarkers. These findings support the inclusion of internet-delivered exercise and psychological interventions in comprehensive treatment strategies for depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT05849792 (registered 6 May 2023).

Humans

Attitudes, knowledge, and behavioral control regarding child abuse reporting in middle eastern nursing professionals: A systematic review and meta-analysis.

INTRODUCTION: Child abuse is critically underreported in the Middle East, with up to 90% of cases going unidentified. Nurses play a central role in child protection systems, yet factors influencing their reporting practices in this region have not been comprehensively synthesized. This study aims to review systematically and meta-analyze evidence on Middle Eastern nurses' knowledge, attitudes, and perceived behavioral control regarding child abuse reporting. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines. Five databases (PubMed, Scopus, Web of Science, Embase, Cochrane Library) were searched through November 2025. Studies targeting nursing professionals or students in Middle Eastern countries assessing knowledge, attitudes, intention to report, subjective norms, or perceived behavioral control were included. Random-effects meta-analyses were performed with subgroup analyses comparing students and practicing nurses. RESULTS: Fourteen studies comprising 4018 participants across six countries met the inclusion criteria. The pooled knowledge score was 61.64% (95% CI: 50.14-73.14), with nursing students scoring higher than practicing nurses (75.28% vs. 54.79%, p&#xa0;=&#xa0;0.03). The pooled attitude score was 60.69% (95% CI: 44.82-76.57). Educational interventions significantly improved knowledge (SMD&#xa0;=&#xa0;1.54, 95% CI: 0.70-2.38, p&#xa0;=&#xa0;0.0003). The pooled proportion of nurses intending to report suspected abuse was 75% (95% CI: 0.58-0.92). The pooled subjective norm score was 8.02 (95% CI: 7.75-8.29), and the pooled perceived behavioral control score was 24.34 (95% CI: 22.20-26.46). High heterogeneity (I2&#xa0;>&#xa0;95%) reflects substantial variability in educational and legal contexts across the region. CONCLUSIONS: Middle Eastern nurses show moderate knowledge and attitudes toward child abuse reporting, with notable gaps among practicing professionals. Educational interventions are effective but should be integrated with systemic reforms, including mandatory reporting legislation and clear protocols.

Humans

Efficacy of a high-frequency repetitive transcranial magnetic stimulation for craving reduction in adolescents with gaming disorder: a 4-week randomized control trial with 24-week follow-up.

BACKGROUND: With the widespread popularity of online gaming, gaming addiction has come under scrutiny. While there is ongoing research on the diagnosis and treatment of gaming disorder among adolescents, the clinical robustness and reliability of intervention strategies remain uncertain. METHODS: A 4-week, double-blind, randomized, sham-controlled clinical trial was conducted to evaluate the efficacy of noninvasive, high-frequency repetitive transcranial magnetic stimulation (rTMS) in alleviating psychological craving in adolescents diagnosed with gaming disorder. Sham rTMS was administered to the control group using the tilted-coil method. Both groups of participants were treated with SSRI medications. A total of 80 adolescents with gaming disorder participated in this study, and 73 ultimately completed the 24-week follow-up. The primary outcome was the change in craving levels before and after the rTMS intervention, as assessed by the Visual Analogue Scale (VAS). Secondary outcomes included changes in anxiety and depression levels before and after the intervention, as assessed by the HAMA and HAMD. RESULTS: We assessed levels of psychological craving, anxiety, and depression among adolescents with gaming disorder at baseline, after completing a 4-week intervention, and at a 24-week follow-up post-intervention. Our repeated-measures MANOVA results, adjusted for course variables, revealed a significant main effect of rTMS intervention on psychological craving levels in adolescents addicted to online games (F(11, 781)&#x2009;=&#x2009;11.238, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.142), as well as significant main effects on time (F(11, 781)&#x2009;=&#x2009;6.809; P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.091) and group effects (F(1, 71)&#x2009;=&#x2009;26.707, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.282). In addition, repeated-measures ANOVA results showed significant time effects for anxiety (F(2, 142)&#x2009;=&#x2009;20.747, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.234) and depression levels (F(2, 142)&#x2009;=&#x2009;22.277, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.285) among adolescents with gaming disorder, with nonsignificant between-group effects and no intergroup interaction. In the active stimulation group, changes in psychological craving levels after 4 weeks of treatment were significantly and positively correlated with changes in anxiety levels after 4 weeks of treatment in adolescents addicted to online games (r&#x2009;=&#x2009;0.335, P&#x2009;<&#x2009;0.05). CONCLUSION: Our findings indicate that high-frequency rTMS targeting the left dorsolateral prefrontal cortex may be a promising approach for reducing psychological craving in adolescents with gaming disorder. TRIAL REGISTRATION: ChiCTR2500102979 in chictr.org.cn, registered on May 22, 2025.

Humans

Identification and characterization of G protein-coupled receptors in the nocturnal halictid bee Megalopta genalis.

G protein-coupled receptors (GPCRs) are one of the largest families of membrane proteins in insects, regulating vision, neural signal transduction, and various physiological behaviors. Megalopta genalis exhibits a unique facultatively eusocial lifestyle and possesses adaptations for nocturnal activity; however, its GPCR family has not yet been systematically characterized. In this study, we performed genome-wide identification, phylogenetic analysis, and expression profiling of GPCRs in M. genalis by integrating genomic annotation and transcriptomic analysis. The results showed that a total of 99 GPCRs were identified in the genome of M. genalis, which were classified into four major families. Here, we show that M. genalis has undergone lineage-specific GPCR repertoire remodeling, marked by the expansion of novel orphan receptors and the systematic loss of multiple receptor subtypes, such as the neuropeptide receptors MIP-R and NPFR. Moreover, opsins have formed a diverse array of combinations and non-GPCR odorant receptors have undergone significant expansion via tandem duplication. Together, these features may represent part of the molecular repertoire associated with the adaptation of M. genalis to a nocturnal lifestyle. Furthermore, transcriptomic analysis revealed distinct spatiotemporal expression divergence within each of the Mth/Mthl and Fz GPCR families, suggesting functional specialization across development and adult tissues. This study provides the first systematic identification and initial functional characterization of GPCRs in M. genalis, revealing an evolutionary pattern characterized by the coexistence of contraction and expansion within the GPCR family. These findings lay a foundation for further studies aimed at elucidating the roles of these GPCRs in regulating M. genalis physiology and behavior.

Animals

Effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia: a systematic review and meta-analysis.

BACKGROUND: Despite the burden of tobacco use, access to cessation support in South Asia remains scarce. OBJECTIVE: This review evaluates the effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia. METHODS: Five relevant databases were searched from inception to February 2025. Eligibility criteria included randomized and non-randomized studies evaluating behavioral, pharmacotherapy, and multicomponent interventions delivered in clinical settings in South Asia. Data on study setting and design, participant information, intervention, comparator, and outcomes were extracted. Meta-analyses using random-effect models were conducted where possible. Certainty of evidence was assessed using GRADE. RESULTS: Thirty-seven studies were included (22 randomized and 15 non-randomized). Interventions involved pharmacotherapy (n&#x2009;=&#x2009;6; 16.2%), nicotine replacement therapy (n&#x2009;=&#x2009;7; 18.9%), behavioral counseling (n&#x2009;=&#x2009;12; 32.4%), or combined/multicomponent interventions (n&#x2009;=&#x2009;12; 32.4%). Most studies were conducted in India (n&#x2009;=&#x2009;26; 70.3%), followed by Pakistan (n&#x2009;=&#x2009;6; 16.2%), Nepal (n&#x2009;=&#x2009;3; 8.1%), and two studies (5.4%) were multi-country in India, Pakistan, and Bangladesh. Pooled analyses demonstrated higher quit rates among intervention versus control for continuous abstinence at 0-3&#x2009;months (RR: 1.21, 95%CI: 1.06 to 1.37) and >3&#x2009;months (RR: 1.68, 95%CI: 1.1.4 to 2.47), and for point abstinence at >3&#x2009;months post-intervention (RR: 2.03, 95%CI:1.35 to 3.08). Heterogeneity was high for all analyses (I2 range: 94% to 97%). Combined behavioral and pharmacotherapy interventions were most effective (RR: 1.70, 95%CI: 0.98 to 2.92), although not statistically significant (p&#x2009;=&#x2009;0.06). CONCLUSION: Tobacco cessation interventions delivered in clinical settings in South Asia are effective, particularly when combining behavioral support with pharmacotherapy. However, evidence is limited by methodological weaknesses.

Humans

Cerebellar iTBS enhances gait adaptation by modulating cortical sensorimotor network dynamics: a randomized controlled trial.

Gait adaptation enables individuals to maintain locomotor stability under persistent perturbations. Although the cerebellum is critical for sensory prediction error-based (SPE) adaptation, how cerebellar neuromodulation reshapes cortical sensorimotor networks to enhance gait adaptation remains unclear. This study investigated the behavioral effects and underlying cortical neurodynamic mechanisms of cerebellar intermittent theta-burst stimulation (iTBS) on gait adaptation. Thirty-two healthy adults received either active or sham cerebellar iTBS. Participants performed a split-belt treadmill adaptation task before and after intervention. Cortical responsiveness was evaluated using TMS-evoked EEG over primary motor cortex (M1), while resting-state EEG was analyzed to assess spectral power and directional functional connectivity. Compared to sham, cerebellar iTBS significantly enhanced gait adaptation, evidenced by a faster adaptation rate (p&#x202f;=&#x202f;0.035) and enhanced Early Adaptation SLS (p&#x202f;=&#x202f;0.011), without altering initial perturbation responses or post-adaptation outcomes. The iTBS increased TMS-evoked &#x3b1; (p&#x202f;=&#x202f;0.031) and &#x3b3; (p&#x202f;=&#x202f;0.022) power in M1, while the &#x3b1; power was correlated with faster adaptation (r&#x202f;=&#x202f;0.526, p&#x202f;=&#x202f;0.002). Furthermore, iTBS strengthened PPC-to-M1 directed connectivity in the &#x3b2; (p&#x202f;=&#x202f;0.025) and &#x3b3; (p&#x202f;=&#x202f;0.013) bands. Enhanced parieto-motor directionality were positively associated with adaptation rate (&#x3b2;: r&#x202f;=&#x202f;0.515, p&#x202f;=&#x202f;0.003; &#x3b3;: r&#x202f;=&#x202f;0.463, p&#x202f;=&#x202f;0.009). These findings suggest that cerebellar iTBS facilitates gait adaptation by modulating cortical responsiveness and directional sensorimotor network connectivity, providing multi-level neurodynamic evidence for the cerebello-cortical modulation during gait adaptation and offering a strong physiological rationale for targeted neuromodulation in gait rehabilitation strategies.

Humans

New Horizons in the Development of Treatments for Substance Use Disorders.

Substance use disorders (SUDs) are a major public health problem in the United States and cause substantial morbidity and mortality. There are meaningful gaps in the available SUD treatment options, and the development of new therapies is urgently needed. While medications with U.S. Food and Drug Administration approval are available for alcohol, nicotine, and opioid use disorders, there are no approved pharmacotherapies for cannabis, cocaine, or methamphetamine use disorders. Behavioral treatments for SUDs have significant limitations in effectiveness and accessibility, and there is a need for the development of both new behavioral treatment options and new models of treatment delivery. The next generation of treatments for SUDs will likely come from a diverse set of interventions, including new drug classes, new technologies, and new methods of delivery.

Humans

Efficacy and safety of cannabinoid-based interventions for behavioral and cognitive symptoms in dementia: systematic review and meta-analysis.

BACKGROUND: Behavioral and cognitive symptoms are frequent in Alzheimer's disease and dementia, and available pharmacological options offer limited benefit. Cannabinoid-based therapies have been proposed as alternatives, but evidence remains inconclusive. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library through November 2025 for randomized controlled trials evaluating cannabinoids in Alzheimer's disease or dementia. Primary outcomes were agitation measured by the Cohen-Mansfield Agitation Inventory (CMAI) and neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory-Nursing Home version (NPI-NH). Secondary outcomes included cognition using the Mini-Mental State Examination (MMSE) and adverse events. Standardized Mean Differences (SMDs) and Risk Ratios (RRs) were synthesized using random-effects (REML) and Bayesian random-effects models. Risk of bias was evaluated with RoB 2, and certainty of evidence with GRADE. RESULTS: Nine trials (334 participants) met inclusion criteria. Cannabinoids did not improve CMAI (SMD -0.58, 95% CI -1.71 to 0.55; I2&#x2009;=&#x2009;84%), NPI-NH total (SMD -0.02, 95% CI -1.00 to 0.96; I2&#x2009;=&#x2009;67%), NPI-NH agitation (SMD -0.44, 95% CI -1.45 to 0.57; I2&#x2009;=&#x2009;48%), or MMSE (SMD 0.86, 95% CI -16.33 to 18.06; I2&#x2009;=&#x2009;96%). Bayesian posterior estimates were close to zero, supporting the absence of effect. Leave-one-out analyses reduced heterogeneity only after excluding influential trials but did not alter results. Certainty of evidence was moderate for behavioral outcomes and low for cognition. Overall adverse events were similar to placebo, while somnolence was more frequent with cannabinoids (RR 2.03, 95% CI 1.29-3.20). CONCLUSIONS: Cannabinoid-based therapies do not improve agitation, neuropsychiatric symptoms, or cognition in Alzheimer's disease and increase somnolence.

Humans

Space to grieve and grow: A systematic review of psychosocial interventions for people newly diagnosed with multiple sclerosis.

OBJECTIVE: This systematic review synthesized evidence from intervention studies published over the past 25 years that aimed to improve coping and psychosocial well-being among individuals early in the multiple sclerosis (MS) disease course. The goal was to evaluate intervention characteristics, theoretical foundations, and psychosocial outcomes, and to identify gaps for future research. METHODS: Following PRISMA guidelines, a comprehensive search was conducted across PubMed, CINAHL, PsycINFO, and Web of Science (2000-2025). Eligible studies included quantitative or mixed-methods interventions that addressed coping or psychosocial well-being among adults newly diagnosed with MS. Data extraction and quality assessment were completed independently by multiple reviewers using the Joanna Briggs Institute Critical Appraisal Tools. RESULTS: Seven studies (n&#x202f;=&#x202f;345) met inclusion criteria, representing cognitive-behavioral therapy, mindfulness, acceptance-based, and nurse- or peer-delivered interventions. The interval between diagnosis and intervention enrollment ranged from 14 days to >4 years, suggesting different phases of adjustment. All interventions produced significant short-term improvements in at least one psychosocial domain (e.g., anxiety, depression, stress, coping, or illness acceptance). However, sustained effects beyond 6-12 months were inconsistent. Common mechanisms across interventions included enhancing self-efficacy, stress management, and adaptive coping. CONCLUSIONS: The available evidence suggests that brief psychosocial interventions for adults in the early years after MS diagnosis are feasible and may provide short-term benefits for selected psychosocial outcomes. However, the evidence base remains limited, heterogeneous, and preliminary. Future studies should more clearly define diagnosis timing, use adequately powered designs and longer follow-up, and examine mechanisms of change.

Humans

Copper-Containing Surface Engineering for Soft-Tissue Biomedical Devices: Structure-Function Relationships and Ion Release-Driven Biological Performance, A Systematic Review.

Copper and copper-based materials have gained increasing attention for the functional modification of implantable medical devices intended for prolonged soft-tissue contact, including vascular stents, catheters, and intrauterine devices. Owing to their broad-spectrum antimicrobial activity, redox reactivity, and involvement in angiogenesis and cellular signaling, copper-based systems offer significant potential for multifunctional surface engineering. However, achieving a balance between antibacterial efficacy, corrosion behavior, controlled ion release, and cytocompatibility remains a critical challenge. This PRISMA-compliant systematic review analyzes copper-containing materials and surface modification strategies for soft-tissue biomedical applications. A structured search of Scopus, Web of Science, and PubMed (2015-2025) identified 65 eligible studies. The review encompasses bulk copper-containing alloys, electrochemical and chemical surface modification techniques, physical vapor deposition approaches, and advanced hybrid systems integrating copper with polymers, hydrogels, or metal-phenolic networks. Across the reviewed literature, antibacterial performance was strongly dependent on copper concentration, microstructural distribution, and spatiotemporal ion release profiles. Moderate, well-controlled copper incorporation frequently improved antibacterial efficacy while maintaining acceptable hemocompatibility and cytocompatibility, particularly in vascular and blood-contacting devices. In contrast, excessive copper loading often accelerated corrosion and induced adverse cellular responses. Emerging multifunctional architectures demonstrated improved regulation of biological interactions, enabling simultaneous antibacterial, antithrombotic, and proendothelial effects. Overall, copper-based surface technologies represent a versatile platform for soft-tissue implant modification. Future translational progress will require precise control of copper release kinetics and comprehensive long-term in vivo validation to ensure safety and sustained therapeutic performance. From the authors' perspective, the most promising future direction involves multifunctional copper-based hybrid coatings capable of dynamically regulating ion release, host tissue integration, and antibacterial performance simultaneously. Strategies integrating hierarchical architectures, stimulus-responsive release systems, and clinically scalable fabrication methods are expected to play a key role in translating copper-containing surfaces from experimental concepts toward commercially viable soft-tissue biomedical devices.

Copper