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International Journal of Environmental... Jun 2024Despite the lack of evidence, opioids are still routinely used as a solution to long-term management for chronic noncancer pain (CNCP). Given the significant risks... (Review)
Review
Despite the lack of evidence, opioids are still routinely used as a solution to long-term management for chronic noncancer pain (CNCP). Given the significant risks associated with long-term opioid use, including the increased number of unregulated opioid pills at large in the opioid ecosystem, opioid cessation or reduction may be the desired goal of the patient and clinician. Viable nonpharmacological interventions (NPIs) to complement and/or replace opioids for CNCP are needed. Comprehensive reviews that address the impact of NPIs to help adults with CNCP reduce opioid use safely are lacking. We conducted a literature search in PubMed, CINAHL, Embase, PsycINFO, and Scopus for studies published in English. The initial search was conducted in April 2021, and updated in January 2024. The literature search yielded 19,190 relevant articles. Thirty-nine studies met the eligibility criteria and underwent data extraction. Of these, nineteen (49%) were randomized controlled trials, eighteen (46%) were observational studies, and two (5%) were secondary analyses. Among adults with CNCP who use opioids for pain management, studies on mindfulness, yoga, educational programs, certain devices or digital technology, chiropractic, and combination NPIs suggest that they might be an effective approach for reducing both pain intensity and opioid use, but other NPIs did not show a significant effect (e.g., hypnosis, virtual reality). This review revealed there is a small to moderate body of literature demonstrating that some NPIs might be an effective and safe approach for reducing pain and opioid use, concurrently.
Topics: Humans; Chronic Pain; Analgesics, Opioid; Opioid-Related Disorders; Pain Management
PubMed: 38929040
DOI: 10.3390/ijerph21060794 -
International Journal of Environmental... Jun 2024We evaluated the impact of Medicaid policies in Virginia (VA), namely the Addiction and Recovery Treatment Services (ARTS) program and Medicaid expansion, on the number...
The Cumulative Effect of Expanding the Breadth and Scope of Coverage for Substance Use Disorder Treatment on Behavioral Health Acute Inpatient Admissions: Evidence from Virginia Medicaid.
We evaluated the impact of Medicaid policies in Virginia (VA), namely the Addiction and Recovery Treatment Services (ARTS) program and Medicaid expansion, on the number of behavioral health acute inpatient admissions from 2016 to 2019. We used Poisson fixed-effect event study regression and compared average proportional differences in admissions over three time periods: (1) prior to ARTS; (2) following ARTS but before Medicaid expansion; (3) post-Medicaid expansion. The number of behavioral health acute inpatient admissions decreased by 2.6% (95% CI [-5.1, -0.2]) in the first quarter of 2018 and this decrease gradually intensified by 4.9% (95% CI [-7.5, -2.4]) in the fourth quarter of 2018 compared to the second quarter of 2017 (beginning of ARTS) in VA relative to North Carolina (NC). Following the first quarter of 2019 (beginning of Medicaid expansion), decreases in VA admissions became larger relative to NC. The average proportional difference in admissions estimated a decrease of 2.7% (95% CI, [-4.1, -0.8]) after ARTS but before Medicaid expansion and a decrease of 2.9% (95% CI, [-6.1, 0.4]) post-Medicaid expansion compared to pre-ARTS in VA compared to NC. Behavioral health acute inpatient admissions in VA decreased following ARTS implementation, and the decrease became larger after Medicaid expansion.
Topics: Medicaid; Virginia; Humans; Substance-Related Disorders; United States; Hospitalization; Male; Adult; Female; Inpatients; Middle Aged
PubMed: 38929023
DOI: 10.3390/ijerph21060777 -
International Journal of Environmental... May 2024Drugged driving, the act of driving a vehicle under the influence of illicit drugs, by adolescents is a serious public health concern. Many factors contribute to this...
Drugged driving, the act of driving a vehicle under the influence of illicit drugs, by adolescents is a serious public health concern. Many factors contribute to this risk behavior, but much less is known regarding the role of parenting behaviors in this phenomenon. The purpose of this study was to examine specific parenting behaviors and their influence among a nationally representative sample of adolescents. Pooled data from the 2016-2019 National Survey on Drug Use and Health (NSDUH) among 17,520 adolescents ages 16-17 years old were analyzed. Differences were found in specific parenting behaviors and adolescent drugged/drunk driving, with parents not checking homework and not telling their children they are proud of them being the most influential. Findings from the present study may inform drugged driving prevention programs for parents and adolescents and enhance road safety interventions.
Topics: Humans; Adolescent; Parenting; United States; Female; Male; Driving Under the Influence; Adolescent Behavior; Automobile Driving; Risk-Taking; Substance-Related Disorders
PubMed: 38928941
DOI: 10.3390/ijerph21060695 -
Brain Sciences Jun 2024The study aimed to examine the bidirectional relationship between sarcopenia and depressive symptoms in a national, community-based cohort study, despite the unclear...
BACKGROUND
The study aimed to examine the bidirectional relationship between sarcopenia and depressive symptoms in a national, community-based cohort study, despite the unclear temporal sequence demonstrated previously.
METHODS
Data were derived from four waves (2011 baseline and 2013, 2015, and 2018 follow-ups) of the China Health and Retirement Longitudinal Study (CHARLS). A total of 17,708 participants aged 45 years or older who had baseline data on both sarcopenia status and depressive symptoms in 2011 were included in the study. For the two cohort analyses, a total of 8092 adults without depressive symptoms and 11,292 participants without sarcopenia in 2011 were included. Sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria. Depressive symptoms were defined as a score of 20 or higher on the 10-item Center for Epidemiologic Studies Depressive Scale (CES-D-10). Cox proportional hazard regression models were conducted to examine the risk of depressive symptoms and sarcopenia risk, while cross-lagged panel models were used to examine the temporal sequence between depressive symptoms and sarcopenia over time.
RESULTS
During a total of 48,305.1 person-years follow-up, 1262 cases of incident depressive symptoms were identified. Sarcopenia exhibited a dose-response relationship with a higher risk of depressive symptoms (HR = 1.7, 95%CI: 1.2-2.3 for sarcopenia, and HR = 1.5, 95%CI: 1.2-1.8 for possible sarcopenia, trend < 0.001). In the second cohort analysis, 240 incident sarcopenia cases were identified over 39,621.1 person-years. Depressive symptoms (HR = 1.5, 95%CI: 1.2-2.0) are significantly associated with a higher risk of developing sarcopenia after multivariable adjustment ( < 0.001, Cross-lagged panel analyses demonstrated that depressive symptoms were associated with subsequent sarcopenia (β = 0.003, < 0.001). Simultaneously, baseline sarcopenia was also associated with subsequent depressive symptoms (β = 0.428, < 0.001).
CONCLUSION
This study identified a bidirectional relationship between depressive symptoms and sarcopenia. It seems more probable that baseline sarcopenia is associated with subsequent depressive symptoms in a stronger pattern than the reverse pathway. The interlinkage indicated that maintaining normal muscle mass and strength may serve as a crucial intervention strategy for alleviating mood disorders.
PubMed: 38928593
DOI: 10.3390/brainsci14060593 -
International Journal of Molecular... Jun 2024Alcohol use disorder is considered a chronic and relapsing disorder affecting the central nervous system. The serotonergic system, mainly through its influence on the...
Alcohol use disorder is considered a chronic and relapsing disorder affecting the central nervous system. The serotonergic system, mainly through its influence on the mesolimbic dopaminergic reward system, has been postulated to play a pivotal role in the underlying mechanism of alcohol dependence. The study aims to analyse the association of the rs6295 polymorphism of the gene in women with alcohol use disorder and the association of personality traits with the development of alcohol dependence, as well as the interaction of the rs6295, personality traits, and anxiety with alcohol dependence in women. The study group consisted of 213 female volunteers: 101 with alcohol use disorder and 112 controls. NEO Five-Factor and State-Trait Anxiety Inventories were applied for psychometric testing. Genotyping of rs6295 was performed by real-time PCR. We did not observe significant differences in rs6295 genotypes ( = 0.2709) or allele distribution ( = 0.4513). The AUD subjects scored higher on the anxiety trait ( < 0.0001) and anxiety state ( < 0.0001) scales, as well as on the neuroticism ( < 0.0001) and openness ( = 0134) scales. Significantly lower scores were obtained by the AUD subjects on the extraversion ( < 0.0001), agreeability ( < 0.0001), and conscientiousness ( < 0.0001) scales. Additionally, we observed a significant effect of rs6295 genotype interaction and alcohol dependency, or lack thereof, on the openness scale ( = 0.0016). In summary, this study offers a comprehensive overview of alcohol dependence among women. It offers valuable insights into this complex topic, contributing to a more nuanced understanding of substance use among this specific demographic. Additionally, these findings may have implications for developing prevention and intervention strategies tailored to individual genetic and, most importantly, personality and anxiety differences.
Topics: Humans; Female; Receptor, Serotonin, 5-HT1A; Alcoholism; Personality; Adult; Anxiety; Middle Aged; Polymorphism, Single Nucleotide; Genotype; Genetic Predisposition to Disease; Alleles; Genetic Association Studies; Case-Control Studies
PubMed: 38928270
DOI: 10.3390/ijms25126563 -
International Journal of Molecular... Jun 2024Glutamate is the main excitatory neurotransmitter in the brain wherein it controls cognitive functional domains and mood. Indeed, brain areas involved in memory... (Review)
Review
Glutamate is the main excitatory neurotransmitter in the brain wherein it controls cognitive functional domains and mood. Indeed, brain areas involved in memory formation and consolidation as well as in fear and emotional processing, such as the hippocampus, prefrontal cortex, and amygdala, are predominantly glutamatergic. To ensure the physiological activity of the brain, glutamatergic transmission is finely tuned at synaptic sites. Disruption of the mechanisms responsible for glutamate homeostasis may result in the accumulation of excessive glutamate levels, which in turn leads to increased calcium levels, mitochondrial abnormalities, oxidative stress, and eventually cell atrophy and death. This condition is known as glutamate-induced excitotoxicity and is considered as a pathogenic mechanism in several diseases of the central nervous system, including neurodevelopmental, substance abuse, and psychiatric disorders. On the other hand, these disorders share neuroplasticity impairments in glutamatergic brain areas, which are accompanied by structural remodeling of glutamatergic neurons. In the current narrative review, we will summarize the role of glutamate-induced excitotoxicity in both the pathophysiology and therapeutic interventions of neurodevelopmental and adult mental diseases with a focus on autism spectrum disorders, substance abuse, and psychiatric disorders. Indeed, glutamatergic drugs are under preclinical and clinical development for the treatment of different mental diseases that share glutamatergic neuroplasticity dysfunctions. Although clinical evidence is still limited and more studies are required, the regulation of glutamate homeostasis is attracting attention as a potential crucial target for the control of brain diseases.
Topics: Humans; Glutamic Acid; Mental Disorders; Animals; Neurodevelopmental Disorders; Neuronal Plasticity; Brain; Adult; Substance-Related Disorders; Autism Spectrum Disorder
PubMed: 38928227
DOI: 10.3390/ijms25126521 -
International Journal of Molecular... Jun 2024It seems that BDNF has a direct influence on the brain pathways and is typically engaged during the processing of rewards. A surge in BDNF levels in the ventral...
It seems that BDNF has a direct influence on the brain pathways and is typically engaged during the processing of rewards. A surge in BDNF levels in the ventral tegmental area (the region from which the dopaminergic neurons of the mesocorticolimbic dopamine system originate and extend to the dorsolateral and ventromedial striatum) triggers a state of reward similar to that produced by opiates in animal studies. The aims of the study were (1) to analyze the association of the gene rs6265 polymorphism with AUD (alcohol use disorder) in women, (2) analyze personality and anxiety in alcohol-dependent and control woman, and (3) conduct an interaction analysis of rs6265 on personality, anxiety, and alcohol dependence. Our study found a notable interaction between the anxiety (trait and state), neuroticism, rs6265, and AUD. The alcohol AUD G/A genotype carriers revealed higher level of the anxiety trait ( < 0.0001) and neuroticism ( < 0.0001) compared to the control group with G/A and G/G genotypes. The alcohol use disorder subjects with the G/A genotype displayed higher levels of an anxiety state than the control group with G/A ( < 0.0001) and G/G ( = 0.0014) genotypes. Additionally, the alcohol use disorder subjects with the G/G genotype obtained lower levels of agreeability compared to the controls with G/A ( < 0.0001) and G/G ( < 0.0001) genotypes. Our study indicates that anxiety (trait and state) and neuroticism are interacting with the gene rs6265 polymorphism in alcohol-dependent women. Characteristics like anxiety (both as a trait and a state) and neuroticism could have a significant impact on the mechanism of substance dependency, particularly in females who are genetically susceptible. This is regardless of the reward system that is implicated in the emotional disruptions accompanying anxiety and depression.
Topics: Humans; Brain-Derived Neurotrophic Factor; Female; Alcoholism; Adult; Polymorphism, Single Nucleotide; Personality; Middle Aged; Anxiety; Genetic Predisposition to Disease; Genotype; Neuroticism; Case-Control Studies
PubMed: 38928154
DOI: 10.3390/ijms25126448 -
International Journal of Molecular... Jun 2024Alcohol use disorder (AUD) is a chronic neurobehavioral condition characterized by a cycle of tolerance development, increased consumption, and reinstated craving and...
Alcohol use disorder (AUD) is a chronic neurobehavioral condition characterized by a cycle of tolerance development, increased consumption, and reinstated craving and seeking behaviors during withdrawal. Understanding the intricate mechanisms of AUD necessitates reliable animal models reflecting its key features. (), with its conserved nervous system and genetic tractability, has emerged as a valuable model organism to study AUD. Here, we employ an ethanol vapor exposure model in , recapitulating AUD features while maintaining high-throughput scalability. We demonstrate that ethanol vapor exposure induces intoxication-like behaviors, acute tolerance, and ethanol preference, akin to mammalian AUD traits. Leveraging this model, we elucidate the conserved role of c-jun N-terminal kinase (JNK) signaling in mediating acute ethanol tolerance. Mutants lacking JNK signaling components exhibit impaired tolerance development, highlighting JNK's positive regulation. Furthermore, we detect ethanol-induced JNK activation in . Our findings underscore the utility of with ethanol vapor exposure for studying AUD and offer novel insights into the molecular mechanisms underlying acute ethanol tolerance through JNK signaling.
Topics: Animals; Caenorhabditis elegans; Ethanol; Drug Tolerance; Caenorhabditis elegans Proteins; MAP Kinase Signaling System; JNK Mitogen-Activated Protein Kinases; Alcoholism; Disease Models, Animal
PubMed: 38928105
DOI: 10.3390/ijms25126398 -
Biomedicines May 2024A sodium current (I) reduction occurs in the setting of many acquired and inherited conditions and is associated with cardiac conduction slowing and increased arrhythmia...
A sodium current (I) reduction occurs in the setting of many acquired and inherited conditions and is associated with cardiac conduction slowing and increased arrhythmia risks. The sodium channel blocker mexiletine has been shown to restore the trafficking of mutant sodium channels to the membrane. However, these studies were mostly performed in heterologous expression systems using high mexiletine concentrations. Moreover, the chronic effects on I in a non-diseased cardiomyocyte environment remain unknown. In this paper, we investigated the chronic and acute effects of a therapeutic dose of mexiletine on I and the action potential (AP) characteristics in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) of a healthy individual. Control hiPSC-CMs were incubated for 48 h with 10 µM mexiletine or vehicle. Following the wash-out of mexiletine, patch clamp analysis and immunocytochemistry experiments were performed. The incubation of hiPSC-CMs for 48 h with mexiletine (followed by wash-out) induced a significant increase in peak I of ~75%, without any significant change in the voltage dependence of (in)activation. This was accompanied by a significant increase in AP upstroke velocity, without changes in other AP parameters. The immunocytochemistry experiments showed a significant increase in membrane Na1.5 fluorescence following a 48 h incubation with mexiletine. The acute re-exposure of hiPSC-CMs to 10 µM mexiletine resulted in a small but significant increase in AP duration, without changes in AP upstroke velocity, peak I density, or the I voltage dependence of (in)activation. Importantly, the increase in the peak I density and resulting AP upstroke velocity induced by chronic mexiletine incubation was not counteracted by the acute re-administration of the drug. In conclusion, the chronic administration of a clinically relevant concentration of mexiletine increases I density in non-diseased hiPSC-CMs, likely by enhancing the membrane trafficking of sodium channels. Our findings identify mexiletine as a potential therapeutic strategy to enhance and/or restore I and cardiac conduction.
PubMed: 38927420
DOI: 10.3390/biomedicines12061212 -
Biomedicines May 2024The escalating rates of morbidity and mortality associated with opioid use disorder (OUD) have spurred a critical need for improved treatment outcomes. This study aimed...
The escalating rates of morbidity and mortality associated with opioid use disorder (OUD) have spurred a critical need for improved treatment outcomes. This study aimed to investigate the impact of prolonged exposure to Fentanyl, a potent opioid, on behavior, biochemical markers, oxidative stress, and the composition of the gut microbiome. Additionally, we sought to explore the therapeutic potential of in mitigating the adverse effects of Fentanyl withdrawal. The study unveiled that chronic Fentanyl administration induced a withdrawal syndrome characterized by elevated cortisol levels (12.09 mg/mL, compared to 6.3 mg/mL for the control group). This was accompanied by heightened anxiety, indicated by a reduction in time spent and entries made into the open arm in the Elevated Plus Maze Test, as well as depressive-like behaviors, manifested through increased immobility time in the Forced Swim Test. Additionally, Fentanyl exposure correlated with decreased gut microbiome density and diversity, coupled with heightened oxidative stress levels, evidenced by elevated malondialdehyde (MDA) and reduced levels of catalase (CAT) and superoxide dismutase (SOD). However, both post- and co-administration of exhibited substantial improvements in these adverse effects, effectively alleviating symptoms associated with OUD withdrawal syndrome and eliciting positive influences on gut microbiota. In conclusion, this research underscores the therapeutic potential of in managing Fentanyl withdrawal symptoms. The findings indicate promising effects in alleviating behavioral impairments, reducing stress, restoring gut microbiota, and mitigating oxidative stress, offering valuable insights for addressing the challenges of OUD treatment.
PubMed: 38927359
DOI: 10.3390/biomedicines12061152