Withdrawal from 3-Fluoroethamphetamine induces hyperactivity and depression-like behaviors in male mice.

3-Fluoroethamphetamine (3-FEA) belongs to the amphetamine class of stimulant drugs and functions as a releasing agent for the monoamine neurotransmitters norepinephrine, dopamine, and serotonin. 3-FEA acts on the central nervous system and elicits physical and mental side effects, such as euphoria, increased heart rate, and excitement. However, little is known about the withdrawal symptoms and behavioral changes induced by 3-FEA administration. This study aimed to evaluate the short-term consequences of 3-FEA administration (twice a day, 7 days, i.p.; 1 and 10 mg/kg) in C57BL/6J mice (male, 7 weeks old) at three behavioral levels following 1-4 days of withdrawal. The evaluation included (1) withdrawal score, (2) hyperactivity (open field [OF], elevated plus maze [EPM], and cliff avoidance [CA] test), and (3) depression-like behavior (forced-swim test). In the withdrawal score test, withdrawal behavior increased in all 3-FEA groups at 16 and 40 h after withdrawal. In the OF, EPM, and CA tests, the 3-FEA administration group showed significant changes in terms of hyperactivity. In addition, in the forced-swim test, both the 1 mg/kg and 10 mg/kg 3-FEA groups showed increased immobility time. These findings indicate that 3-FEA administration may lead to physical dependence, demonstrated by the withdrawal score increase and significant changes in hyperactivity and depression-like behavior following repeated administration and drug cessation. In conclusion, this study reveals the adverse consequences of 3-FEA administration and highlights the need for awareness raising and regulatory action to control the use of this new psychoactive substance.

Lyso-H2S: A Mycophenolic Acid-Derived Probe for Ultra-Low Toxicity, Intracellular H2S Detection, and Zebrafish Model Validation.

In several biological processes, H2S is known to function as an endogenous gaseous agent. It is very necessary to monitor H2S and relevant physiological processes in vivo. Herein, a new type of fluorophore with a reliable leaving group allows for excited-state intramolecular transfer characteristics (ESIPT), inspired by mycophenolic acid. A morpholine ring was connected at the maleimide position to target the lysosome. Subsequently, the dinitrophenyl group known for a photoinduced electron transfer (PET) effect, was connected to allow for an effective "turn-on" probe Lyso-H2S. Lyso-H2S demonstrated strong selectivity towards H2S, large Stokes shift (111 nm), and an incredibly low detection limit (41.8 nM). The imaging of endogenous and exogenous H2S in living cells (A549 cell line) was successfully achieved because of the specificity and ultra-low toxicity (100 % cell viability at 50 µM concentration of Lyso-H2S.) Additionally, Lyso-H2S was also employed to visualize the activity of H2S in the gallbladder and intestine in a living zebrafish model. This is the first report of a fluorescent probe to track H2S sensing in specific organ systems to our knowledge.

COUP-TFII plays a role in cAMP-induced Schwann cell differentiation and in vitro myelination by up-regulating Krox20.

Schwann cells (SCs) are known to produce myelin for saltatory nerve conduction in the peripheral nervous system (PNS). Schwann cell differentiation and myelination processes are controlled by several transcription factors including Sox10, Oct6/Pou3f1, and Krox20/Egr2. Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII/NR2F2) is an orphan receptor that plays a role in the development and differentiation. However, the role of COUP-TFII in the transcriptional regulatory network of SC differentiation has not been fully identified yet. Thus, the objective of this study was to investigate the role and molecular hierarchy of COUP-TFII during cAMP-induced SC differentiation. Our results showed that dibutyryl-cAMP (db-cAMP) increased expression levels of COUP-TFII along with the expressions of Oct6, Krox20, and myelin-related genes known to be related to SC differentiation. Our mechanistic studies showed that COUP-TFII acted downstream of Hsp90/ErbB2/Gab1/ERK-AKT pathway during db-cAMP-induced SC differentiation. In addition, we found that COUP-TFII induced Krox20 expression by directly binding to Krox20-MSE8 as revealed by chromatin immunoprecipitation assay and promoter activity assay. In line with this, the expression of COUP-TFII was increased before up-regulation of Oct6, Krox20, and myelin-related genes in the sciatic nerves during early postnatal myelination period. Finally, COUP-TFII knockdown by COUP-TFII siRNA or via AAV-COUP-TFII shRNA in SCs inhibited db-cAMP-induced SC differentiation and in vitro myelination of sensory axons, respectively. Taken together, these findings indicate that COUP-TFII might be involved in postnatal myelination through induction of Krox20 in SCs. Our results present a new insight into the transcriptional regulatory mechanism in SC differentiation and myelination.

The Psychological Costs of the COVID-19 Pandemic and Heterogeneous Effects in South Korea: Evidence from a Difference-in-Differences Analysis.

This study estimates the effects of the COVID-19 pandemic on life satisfaction and stress and examines whether these effects vary across different sociodemographic groups using a nationally representative sample in South Korea. We estimate the causal effects of COVID-19 on psychological well-being by exploiting regional variation in the spread of the pandemic in South Korea. While the number of confirmed cases was very small in other provinces in the first half of 2020, the coronavirus spread rapidly in Daegu after an outbreak in one church. We employ a difference-in-differences approach that compares changes in people's life satisfaction and stress before-and-after the initial surge of COVID-19 cases in Daegu and other provinces. Our results show that the proportion of people who are dissatisfied with life increased by 2.8-6.5 percentage points more in Daegu than in other provinces after the COVID-19 outbreak. During the same period, the proportion of people who reported feeling stressed increased more in Daegu than in other provinces by 5.8-8.9 percentage points. Our results also suggest that the negative impact of the COVID-19 outbreak on psychological well-being is significantly greater for men, young adults, middle-aged adults, self-employed workers, and middle-income individuals. On the other hand, the proportion of people who report feeling stressed among the highest-educated (a master's degree or higher) and high-income individuals decreased after the onset of the COVID-19 outbreak.

The impact of panel composition and topic on stakeholder perspectives: Generating hypotheses from online maternal and child health modified-Delphi panels.

INTRODUCTION: Multistakeholder engagement is crucial for conducting health services research. Delphi-based methodologies combining iterative rounds of questions with feedback on and discussion of group results are a well-documented approach to multistakeholder engagement. This study develops hypotheses about the impact of panel composition and topic on the propensity and meaningfulness of response changes in multistakeholder modified-Delphi panels. METHODS: We conducted three online modified-Delphi (OMD) multistakeholder panels using the same protocol. We assigned 60 maternal and child health professionals to a homogeneous (professionals only) panel, 60 pregnant or postpartum women (patients) to a homogeneous panel, and 30 professionals and 30 patients to a mixed panel. In Round 1, participants rated the seriousness of 11 maternal and child health outcomes using a 0-100 scale and explained their ratings. In Round 2, participants saw their own and their panel's Round 1 results and discussed them using asynchronous, anonymous discussion boards moderated by the study investigators. In Round 3, participants revised their original ratings. Our outcome measures included binary indicators of response changes to ratings of the low, medium and high severity maternal and child health outcomes and their meaningfulness, measured by a change of 10 or more points. RESULTS: Participants changed 818 of 1491 (55%) of responses; the majority of response changes were meaningful. Patterns of response changes were different for patients and professionals and for different levels of outcome seriousness. Using study results and the literature, we developed three hypotheses. First, OMD participants, regardless of their stakeholder group, are more likely to change their responses on preference-sensitive topics where there is a range of viable alternatives or perspectives. Second, patients are more likely to change their responses and to do so meaningfully in mixed panels, whereas professionals are more likely to do so in homogeneous panels. Third, the association between panel composition and response change varies according to the topic (e.g., the level of outcome seriousness). CONCLUSIONS: Results of our work not only helped generate empirically derived hypotheses to be tested in future research but also offer practical recommendations for designing multistakeholder OMD panels. PATIENT OR PUBLIC CONTRIBUTION: Pregnant or postpartum women were involved in this study.

Loss of splicing factor IK impairs normal skeletal muscle development.

BACKGROUND: IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an ik knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo. RESULTS: The ik KO embryos display severe pleiotropic phenotypes, implying an essential role of IK in embryonic development in vertebrates. RNA-seq analysis reveals downregulation of genes involved in skeletal muscle differentiation in ik KO embryos, and there exist genes having improper pre-mRNA splicing among downregulated genes. The ik KO embryos display impaired neuromuscular junction (NMJ) and fast-twitch muscle development. Depletion of ik reduces myod1 expression and upregulates pax7a, preventing normal fast muscle development in a non-cell-autonomous manner. Moreover, when differentiation is induced in IK-depleted C2C12 myoblasts, myoblasts show a reduced ability to form myotubes. However, inhibition of IK does not influence either muscle cell proliferation or apoptosis in zebrafish and C2C12 cells. CONCLUSION: This study provides that the splicing factor IK contributes to normal skeletal muscle development in vivo and myogenic differentiation in vitro.

MicroRNA expression profiling of adult hippocampal neural stem cells upon cell death reveals an autophagic cell death-like pattern.

Adult hippocampal neural (HCN) stem cells promptly undergo irreversible autophagic cell death (ACD) if deprived of insulin in culture. Small, non-coding microRNAs (miRNA) play an important role in regulating biological processes, including proliferation and cell death. However, there have been no reports thus far regarding miRNA involvement in the induction of adult HCN stem cell death under insulin-deprived conditions, for which we performed a microarray-based analysis to examine the expression signature of miRNAs in adult rat HCN stem cells. Three independent specimens per culture condition either with or without insulin were prepared and a miRNA microarray analysis carried out. A total of 12 exhibited significantly altered expression levels upon cell death due to the absence of insulin when compared to HCN stem cells cultured with insulin present (cut-off limit; p < 0.05 and fold-change >1.3) The resulting volcano plot showed that, among these miRNAs, seven were upregulated and five were downregulated. The upregulated miRNAs were capable of modulating HCN stem cell death. Caspase-3 activity analysis, LC3 conversion, and TEM of autophagosome formation consistently suggested that ACD, not apoptosis, was most likely the mechanism affecting HCN cell death. As such, we have come to term these miRNAs, "HCN stem cell-specific autophagic cell death regulators." Taken together, our data suggest that the miRNA expression profile of HCN stem cells is altered during ACD occurring due to insulin deprivation and that differentially expressed miRNAs are involved in HCN stem cell viability. Detailed explorations of the underlying mechanisms regarding HCN stem cell viability modulation by these miRNAs would be beneficial in further understanding the physiological features of adult HCN stem cells and are currently being investigated.

The mediating role of perceived crime in gender and built environment associations with park use and park-based physical activity among park users in high poverty neighborhoods.

Women use parks less for physical activity than men, and explanations include gendered concerns regarding personal safety and access to walking paths. This study conducted mediation analyses to examine the effects of gender and presence of park walking path on park use, participation in park programs, and park-based physical activity through the hypothesized mediator (perception of crime). The sample included 3213 park users from 48 parks in high poverty neighborhoods in Los Angeles surveyed between 2013 and 2015; park-level factors were assessed through systematic observations of study parks. Women reported fewer park visits than men in the last 7 days (ß = -0.17, p = 0.02) and had significantly higher perceived crime (ß = 0.12, p < 0.0001) and perceived crime partially mediated the gender association with park visits (ßgender, direct = -0.09, p = 0.19; ßgender, indirect = -0.07, p < 0.0001). Similarly, the existence of a walking path in the park was significantly related to increased park use (ß = 0.27, p = 0.006) and a lower level of perceived crime (ß = -0.25, p = 0.0034) and perceived crime partially mediated the association of walking path with park visits (ßwalking path, direct = 0.18, p = 0.10; ßwalking path, indirect = 0.15, p = 0.005). The associations between gender, walking path, and park-based exercise and program participation were not meaningfully mediated by perceived crime. Among park users in majority Latino, high poverty neighborhoods, addressing crime concerns are likely necessary to increase park use among women and adults whose parks do not have a walking path. For park-based exercise and participation in park programs, gendered preferences regarding park-based physical activity should be explored.

Park Use and Park-Based Physical Activity in Low-Income Neighborhoods.

Routine physical activity is important for everyone, and most urban areas have an infrastructure of neighborhood parks that are intended to serve as a setting for recreation and leisure. However, parks are not used proportionally by all age groups, genders, and socioeconomic groups. This paper explores factors associated with park use by different age and gender groups in low-income neighborhoods in Los Angeles, CA. We found that women's visits to parks generally centered around children, whereas men's visits were more likely to be associated with their own physical activity. Barriers for seniors are associated with limited facilities and programming that meet their needs. Park managers should consider park renovations that include social meeting places, comfortable sitting areas, and walking paths to better serve women and seniors.

Contributions of Neighborhood Parks to Physical Activity in High-Poverty Urban Neighborhoods.

Neighborhood parks are important venues for the urban population to do moderate-to-vigorous physical activity in leisure time. Parks can be particularly important for low-income neighborhoods, whose residents suffer from high rates of chronic diseases and may have less access to fee-based fitness exercise facilities. This study assessed the contribution of parks to local populations' physical activity in 48 high-poverty neighborhoods in the city of Los Angeles, using systematic observation of park use and surveys of park users and residents conducted between 2013 and 2015. We found that parks accounted for approximately 2.1% (between-park SD = 1.4%) of moderate physical activity time and 3.1% (between-park SD = 2.1%) of vigorous physical activity time of the local population, both of which were notably lower than the city-level average previously reported. Parks' contribution to physical activity was positively associated with park size (ß = 0.13, p < 0.0001) and negatively associated with poverty (ß = - 0.10, p < 0.0001) and local population density (ß = - 0.25, p = 0.005). Parks in high-poverty neighborhoods in Los Angeles are underutilized, and more efforts are needed to fully realize their potential for population health.

Suppression of ABCD2 dysregulates lipid metabolism via dysregulation of miR-141:ACSL4 in human osteoarthritis.

Even though increasing evidence indicates the importance of peroxisomal lipid metabolism in regulating biological and pathological events, its involvement in cartilage development has not been well studied. Here, we identified the importance of peroxisomal function, particularly the functional integrity of ABCD2, in the pathogenesis of osteoarthritis (OA). Knockdown of ABCD2 in OA chondrocytes induced the accumulation of very long chain fatty acids (VLCFAs) and apoptotic cell death. Moreover, knockdown of ABCD2 altered profiles of miRNAs that affect the expression level of ACSL4, a known direct regulator of lipid metabolism. Suppression of ACSL4 in human chondrocytes-induced VLCFA accumulation, MMP-13 expression, and apoptotic cell death. In vivo morph-down of the ACSL4 homologue in zebrafish resulted in significant defects in cartilage development and in vivo knockdown of ACSL4 in cartilage tissue of an OA model mice promoted severe cartilage degradation. In summary, to the best of our knowledge, this is the first report suggesting that the regulatory network among peroxisomal ABCD2:ACSL4:VLCFA serves as a novel regulator of cartilage homeostasis, and these data may provide novel insights into the role of peroxisomal fatty acid metabolism in pathogenesis of human OA. SIGNIFICANCE OF THE STUDY: Our study indicates that peroxisomal dysfunction is closely related to OA pathogenesis. Particularly, the functional integrity of ABCD2 may play an important role in OA pathogenesis via the accumulation of VLCFAs and stimulation of apoptotic death through altering profiles of miRNAs that target ACSL4. Our findings suggest that targeting the regulatory network among the peroxisomal ABCD2:ACSL4:VLCFA axis may provide a new potential therapeutic strategy for OA pathogenesis.

The death of an adult child and trajectories of parental depressive symptoms: A gender-based longitudinal analysis.

RATIONALE: Despite the existing body of research on the impact of child bereavement, little is known about whether time to the death of an adult child is longitudinally associated with changes in depressive symptoms among older parents. OBJECTIVE: This study examines (a) trajectories of depressive symptoms before and after the loss of an adult child and (b) whether these trajectories differ across parent-child gender dyads (father-son, father-daughter, mother-son, and mother-daughter). METHODS: Using eight waves of the Korean Longitudinal Study of Ageing (KLoSA), this study employs fixed effects models to mitigate potential bias due to unobserved individual-level heterogeneity. Gender-stratified fixed effects models were estimated to investigate potential heterogeneity in the trajectories of depressive symptoms by parent-child gender dyads. RESULTS: The result of this study revealed that depressive symptoms increased within the first year following the loss of an adult child among bereaved parents. Within a year of the loss of a child, both mothers and fathers experienced an increase in depressive symptoms. However, only fathers experienced lasting effects for up to two years. Different patterns in psychological adjustment to bereavement were observed across different parent-child gender dyads. Among daughter-bereaved fathers, depressive symptoms surged within the first year and persisted even beyond the fourth year of loss. In contrast, for other dyads, only an immediate rise in depressive symptoms within the first year of loss was observed. CONCLUSIONS: The loss of an adult child increases the depressive symptoms of parents. This study highlights the importance of considering the different trajectories of psychological adjustment to bereavement, particularly based on parent-child gender dyads, when formulating policies for providing psychological support to older parents who have experienced the loss of their child.

Disability acceptance and depressive symptoms: the moderating role of social support.

Purpose: This study aims to estimate (a) the relationship between disability acceptance and depressive symptoms, and (b) how the quality and quantity of social support might moderate the link between disability acceptance and depressive symptoms.Materials and methods: The data for this study included information from 5165 individuals with disability who participated in 3 waves of the Disability and Life Dynamic Panel spanning years 2018 to 2020. This study employed fixed effects models to estimate the association between disability acceptance and depressive symptoms. Interaction models were used to assess the moderating effects of both the quantity and quality of social support.Results: A lower acceptance of disability was positively associated with depressive symptoms. Moreover, both the quantity and quality of social support were associated with a decrease in depressive symptoms. Only the quality of social support played a significant role in moderating the relationship between disability acceptance and depressive symptoms.Conclusion: A lower acceptance of disability increases depressive symptoms in individuals with disabilities. This study underscores the need for interventions to focus on enhancing the quality of social support to mitigate the link between disability acceptance and depressive symptoms.

A lower acceptance of disability is positively associated with depressive symptoms among persons with disability.The association between lower disability acceptance and depressive symptoms attenuates as emotional support from family and friends increases.The number of family and friends does not significantly change the relationship between lower disability acceptance and depressive symptoms.The findings highlight the importance of interventions enhancing quality of social support in order to mitigate the association between disability acceptance and psychological health.

Follistatin-like 1 is a myokine regulating lipid mobilization during endurance exercise and recovery.

OBJECTIVE: The aim of this study was to investigate the role of the follistatin-like 1 (Fstl1) and disco-interacting protein 2 homolog A (DIP2a) axis in relation to lipid metabolism during and after endurance exercise and to elucidate the mechanisms underlying the metabolic effects of Fstl1 on adipocytes, considering its regulation by exercise and muscle mass and its link to obesity. METHODS: Twenty-nine sedentary males participated in endurance exercise, and blood samples were collected during and after the exercise. Body composition, Fstl1, glycerol, epinephrine, growth hormone, and atrial natriuretic peptide were measured. 3T3-L1 adipocytes, with or without DIP2a knockdown, were treated with Fstl1 to assess glycerol release, cyclic AMP/cyclic GMP production, and hormone sensitive lipase phosphorylation. The association between DIP2a gene expression levels in human adipose tissues and exercise-induced lipolysis was examined. RESULTS: Fstl1 levels significantly increased during endurance exercise and following recovery, correlating with lean body mass and lipolysis. In 3T3-L1 adipocytes, Fstl1 increased glycerol release, cyclic GMP production, and hormone sensitive lipase activation, but these effects were attenuated by DIP2a knockdown. DIP2a gene expression in human adipose tissues correlated with serum glycerol concentrations during endurance exercise. CONCLUSIONS: Fstl1 is a myokine facilitating lipid mobilization during and after endurance exercise through DIP2a-mediated lipolytic effects in adipocytes.

Bioconversion of citrus waste into mucic acid by xylose-fermenting Saccharomyces cerevisiae.

Mucic acid holds promise as a platform chemical for bio-based nylon synthesis; however, its biological production encounters challenges including low yield and productivity. In this study, an efficient and high-yield method for mucic acid production was developed by employing genetically engineered Saccharomyces cerevisiae expressing the NAD+-dependent uronate dehydrogenase (udh) gene. To overcome the NAD+ dependency for the conversion of pectin to mucic acid, xylose was utilized as a co-substrate. Through optimization of the udh expression system, the engineered strain achieved a notable output, producing 20 g/L mucic acid with a highest reported productivity of 0.83 g/L-h and a theoretical yield of 0.18 g/g when processing pectin-containing citrus peel waste. These results suggest promising industrial applications for the biological production of mucic acid. Additionally, there is potential to establish a viable bioprocess by harnessing pectin-rich fruit waste alongside xylose-rich cellulosic biomass as raw materials.

Advanced Multiparallel-Connected Piezoresistive Physical Sensors: Elevating Performance Reliability of Flexible Strain and Pressure Sensors.

A physical sensor with a sensing medium comprising multiparallel-connected (MPC) piezoresistive pathways in both the vertical and horizontal directions was developed to achieve improved sensing performance. The MPC sensing medium reduces the total resistance and offsets noise, offering enhanced signal stability and device reliability and providing a high-performance sensing platform. The signal change and gauge factor (GF) of the 3PW-5L strain sensor (comprising three lines and five layers of piezoresistive pathways horizontally and vertically, respectively) were, respectively, 5.9 and 4.7 times higher than those of the 1PW-1L sensor composed of a monosensing pathway; the hysteresis of the detected signal was also significantly reduced. The linearity of the detected signal increased from 0.912 for 1PW-1L to 0.995 for 3PW-5L, indicating a greater sensing reliability. The direction of the applied tensile strain was successfully detected using the MPC sensing medium with an orthogonal configuration. The MPC piezoresistive sensor composing vertically stacked piezoresistive pathways demonstrated excellent performance as a pressure sensor; the 3PW-5L pressure sensor afforded a GF of 0.121 ± 0.002 kPa-1 with a linearity of 0.998 under an applied pressure ≥16.4 kPa. The MPC piezoresistive physical sensor offers a superior sensing performance and should contribute to the future development of wearable sensors and electronic devices.

The mechanism underlying correlation of particulate matter-induced ferroptosis with inflammasome activation and iron accumulation in macrophages.

Particulate matter (PM) is a global environmental hazard, which affects human health through free radical production, cell death induction, and immune responses. PM activates inflammasomes leading to excessive inflammatory responses and induces ferroptosis, a type of cell death. Despite ongoing research on the correlation among PM-induced ferroptosis, immune response, and inflammasomes, the underlying mechanism of this relationship has not been elucidated. In this study, we demonstrated the levels of PM-induced cell death and immune responses in murine macrophages, J774A.1 and RAW264.7, depending on the size and composition of particulate matter. PM2.5, with extraction ions, induced significant levels of cell death and immune responses; it induces lipid peroxidation, iron accumulation, and reactive oxygen species (ROS) production, which characterize ferroptosis. In addition, inflammasome-mediated cell death occurred owing to the excessive activation of inflammatory responses. PM-induced iron accumulation activates ferroptosis and inflammasome formation through ROS production; similar results were observed in vivo. These results suggest that the link between ferroptosis and inflammasome formation induced by PM, especially PM2.5 with extraction ions, is established through the iron-ROS axis. Moreover, this study can effectively facilitate the development of a new therapeutic strategy for PM-induced immune and respiratory diseases.

Timing of treatment for opioid use disorder among birthing people.

BACKGROUND: The number of pregnant women with opioid use disorder (OUD) has increased over time. Although effective treatment options exist, little is known about the extent to which women receive treatment during pregnancy and at what stage of pregnancy care is initiated. METHODS: Using a national private health insurance claims database, we identified women aged 13-49 who gave birth in 2006-2019 and had an OUD or nonfatal opioid overdose (NFOO) diagnosis during the year prior to or at delivery. We then identified women who received their first OUD treatment prior to or during pregnancy. In this cross-sectional study, we investigated how rates and timing of the initial OUD treatment changed over time. Furthermore, we examined factors associated with early initiation of OUD treatment among birthing people. RESULTS: Of the 7057 deliveries from 6747 women with OUD or NFOO, 63.3 % received any OUD treatment. Rates of OUD treatment increased from 42.9 % in 2006 to 69 % in 2019. Of those treated, in 2006, 54.5 % received their first treatment prior to conception and 24.2 % initiated care during the 1st trimester. In 2019, 68.9 % received their first treatment prior to conception, and 15.1 % initiated care during the 1st trimester. The percentage of women who were first treated in the 2nd trimester or later decreased from 21.2 % in 2006 to 16.1 % in 2019. Factors associated with early treatment initiation include being 25 years or older (age 25-34: aOR, 1.51, 95 % CI, 1.28-1.78; age 35-49: aOR, 1.82, 95 % CI, 1.39-2.37), living in urban areas (aOR, 1.28; 95 % CI, 1.05-1.56), having pre-existing behavioral health comorbidities such as anxiety disorders (aOR, 1.8; 95 % CI, 1.40-2.32), mood disorders (aOR, 1.63; 95 % CI, 1.02-2.61), and substance use disorder other than OUD (aOR, 2.56; 95 % CI, 2.03-3.32). CONCLUSION: Overall, rates of OUD treatment increased over time, and more women initiated OUD treatment prior to conception. Despite these improvements, over one-third of pregnant women with OUD/NFOO either received no treatment or did not initiate care until the 3rd trimester in 2019. Future research should examine barriers to OUD treatment initiation among pregnant women.

Anti-Inflammatory Effects of Idebenone Attenuate LPS-Induced Systemic Inflammatory Diseases by Suppressing NF-κB Activation.

Inflammation is a natural protective process through which the immune system responds to injury, infection, or irritation. However, hyperinflammation or long-term inflammatory responses can cause various inflammatory diseases. Although idebenone was initially developed for the treatment of cognitive impairment and dementia, it is currently used to treat various diseases. However, its anti-inflammatory effects and regulatory functions in inflammatory diseases are yet to be elucidated. Therefore, this study aimed to investigate the anti-inflammatory effects of idebenone in cecal ligation puncture-induced sepsis and lipopolysaccharide-induced systemic inflammation. Murine models of cecal ligation puncture-induced sepsis and lipopolysaccharide-induced systemic inflammation were generated, followed by treatment with various concentrations of idebenone. Additionally, lipopolysaccharide-stimulated macrophages were treated with idebenone to elucidate its anti-inflammatory effects at the cellular level. Idebenone treatment significantly improved survival rate, protected against tissue damage, and decreased the expression of inflammatory enzymes and cytokines in mice models of sepsis and systemic inflammation. Additionally, idebenone treatment suppressed inflammatory responses in macrophages, inhibited the NF-κB signaling pathway, reduced reactive oxygen species and lipid peroxidation, and normalized the activities of antioxidant enzyme. Idebenone possesses potential therapeutic application as a novel anti-inflammatory agent in systemic inflammatory diseases and sepsis.