Effects Of Depression Research Articles

A refined formula derived from Jiawei-Xiaoyao pill exerts rapid antidepressant-like effects in LPS-induced depression by reducing neuroinflammation and restoring neuroplasticity signaling

Ethnopharmacological relevanceJiawei-Xiaoyao Pill (JWX), a classic formula in traditional Chinese medicine, is derived from Xiaoyao Pill by adding significant amounts of Gardeniae Fructus (GF) and Moutan Cortex (MC). It is frequently used for the treatment of depression. JWX has been demonstrated to uniquely elicit rapid antidepressant-like effects within the prescribed dosage range. To date, GF has been shown to have rapid antidepressant-like effects, but a much higher dose is required than its proportion in JWX. It is assumed that the synergism of GF with a minimum number of other herbs in JWX serves as a refined formula that exerts these rapid antidepressant-like effects. Identification of a refined formula is important for prioritizing the herbs and ingredients to optimize the quality control of JWX. However, such a refined formula for JWX has not been identified yet. Aim of the studyHere we aimed to identify a refined formula derived from JWX for optimized rapid antidepressant-like effects. Since the neuroinflammation mechanism involving in depression treatment has not been previously investigated for JWX, we tested the mechanism for both JWX and the refined formula. Materials and methodsIndividual herbs (MC; ASR, Angelica Sinensis Radix; Bupleuri Radix; Paeonia Radix Alba) that show antidepressant-like responses were mixed with GF at the proportional dosage in JWX to identify the refined formula. Rapid antidepressant-like effects were assessed by using NSF (Novelty Suppressed Feeding Test) and other behavioral tests following a single administration. The identified formula was further tested in a lipopolysaccharide (LPS)-induced depressive model, and the molecular signaling mechanisms were investigated using Western blot analysis, immunofluorescence, and pharmacological inhibition of mTOR signaling. Scopolamine (Scop) was used as a positive control for induction of rapid antidepressant effects. ResultsA combination of GF, MC and ASR (GMA) at their dosages proportional to JWX induced behavioral signs of rapid antidepressant-like responses in both normal and LPS-treated mice, with the antidepressant-like effects sustained for 5 d. Similar to JWX or Scop, GMA rapidly reduced the neuroinflammation signaling of Iba-1-NF-кB, enhanced neuroplasticity signaling of CaMKII-mTOR-BDNF, and attenuated the upregulated expressions of the NMDAR sub-units GluN1 and GluN2B in the hippocampus of LPS-treated mice. GMA, JWX and Scop rapidly restored the number of BDNF-positive cells reduced by LPS treatment in the CA3 region of the hippocampus. Furthermore, rapamycin, a selective inhibitor of mTOR, blunted the rapid antidepressant-like effects and hippocampal BDNF signaling upregulation by GMA. ConclusionGMA may serve as a refined formula from JWX, capable of inducing rapid antidepressant-like effects. In the LPS-induced depression model, the effects of GMA were mediated via rapidly alleviating neuroinflammation and enhancing neuroplasticity.

Living well with chronic pain: a 12-month randomized controlled trial revealing impact from the digital pain self-management program EPIO.

Chronic pain affects a wide range of physical and psychological aspects of life for those impacted. Psychosocial treatment approaches may be of support, but outreach is still limited. To evaluate the efficacy of EPIO, an evidence-informed, user-centered digital self-management intervention for people with chronic pain, in a 12-month randomized controlled trial. People living with chronic pain (N = 266) were randomized to the EPIO intervention (n = 132) or a usual-care control group (n = 134). The intervention was delivered in a simple blended care model, and outcome measures collected at baseline, 6 months, and 12 months. Generalized linear models for repeated measures were fitted to compare groups over time. Participants were primarily female (81%), median age 49 years (range 22-78), with heterogeneous pain conditions, and had lived with pain >5 years (77.6%). A mixed linear model with all timepoints included revealed no statistically significant group differences for the primary outcome of pain interference. Significant psychological benefits in favor of the intervention group were however detected for depression (P = 0.022), self-regulatory fatigue (P = 0.024), vitality (P = 0.016), and mental health (P = 0.047). Baseline to 12-month changes showed additional favorable effects for anxiety (between-group mean differences [MDs] = 0.79, P = 0.047), depression (MD = 1.08, P = 0.004), self-regulatory fatigue (MD = 2.42, P = 0.021), pain catastrophizing (MD = 2.62, P = 0.009), and health-related quality of life. The EPIO program aims to improve outreach of evidence-based pain self-management interventions. Findings demonstrate how using EPIO can lead to sustainable psychological change, enhancing mental health and health-related quality of life for people suffering from pain, providing a chance to live well with the pain.

Effects of a dual intervention (motor and virtual reality-based cognitive) on cognition in patients with mild cognitive impairment: a single-blind, randomized controlled trial

BackgroundThe increase in cases of mild cognitive impairment (MCI) underlines the urgency of finding effective methods to slow its progression. Given the limited effectiveness of current pharmacological options to prevent or treat the early stages of this deterioration, non-pharmacological alternatives are especially relevant.ObjectiveTo assess the effectiveness of a cognitive-motor intervention based on immersive virtual reality (VR) that simulates an activity of daily living (ADL) on cognitive functions and its impact on depression and the ability to perform such activities in patients with MCI.MethodsThirty-four older adults (men, women) with MCI were randomized to the experimental group (n = 17; 75.41 ± 5.76) or control (n = 17; 77.35 ± 6.75) group. Both groups received motor training, through aerobic, balance and resistance activities in group. Subsequently, the experimental group received cognitive training based on VR, while the control group received traditional cognitive training. Cognitive functions, depression, and the ability to perform activities of daily living (ADLs) were assessed using the Spanish versions of the Montreal Cognitive Assessment (MoCA-S), the Short Geriatric Depression Scale (SGDS-S), and the of Instrumental Activities of Daily Living (IADL-S) before and after 6-week intervention (a total of twelve 40-minutes sessions).ResultsBetween groups comparison did not reveal significant differences in either cognitive function or geriatric depression. The intragroup effect of cognitive function and geriatric depression was significant in both groups (p < 0.001), with large effect sizes. There was no statistically significant improvement in any of the groups when evaluating their performance in ADLs (control, p = 0.28; experimental, p = 0.46) as expected. The completion rate in the experimental group was higher (82.35%) compared to the control group (70.59%). Likewise, participants in the experimental group reached a higher level of difficulty in the application and needed less time to complete the task at each level.ConclusionsThe application of a dual intervention, through motor training prior to a cognitive task based on Immersive VR was shown to be a beneficial non-pharmacological strategy to improve cognitive functions and reduce depression in patients with MCI. Similarly, the control group benefited from such dual intervention with statistically significant improvements.Trial registrationClinicalTrials.gov NCT06313931; https://clinicaltrials.gov/study/NCT06313931.

Comparison between hemodynamic effects of remimazolam and propofol during general anesthesia: a systematic review and meta-analysis.

The need for safe anesthetic agents with minimal side effects has led to the development of remimazolam, a new benzodiazepine designed to be an alternative to the commonly used drug propofol, which has significant hemodynamic effects. This study aims to compare the hemodynamic effects of remimazolam with propofol during general anesthesia. A systematic search was conducted in Embase, Web of Science, Cochrane Library, Scopus, and PubMed databases on 13/02/2023, following the recommendations of Cochrane Handbook and the PRISMA statement. The measure of association used was Risk Ratio (RR) or standardized mean difference, with 95% confidence intervals (CI) and 95% Prediction intervals (PI). An additional search was conducted on 04/09/2023. A Trial Sequential Analysis and a GRADE (Grading of Recommendations Assessment, Development and Evaluation) evidence table were conducted based on the editor's recommendation. After applying eligibility criteria and removing duplicates, 16 randomized clinical trials comprising 1951 patients were included in the meta-analysis. Significant associations favoring remimazolam over propofol were observed in the following aspects: intraoperative hypotension events (RR=0.47; 95% CI=0.41 to 0.54; 95% PI=0.40 to 0.55); frequency of vasoactive drug administration (RR=0.54; 95% CI=0.46 to 0.64; 95% PI=0.41 to 0.74); intraoperative bradycardia (RR=0.39; 95% CI=0.27 to 0.57; 95% PI=0.26 to 0.66); mean arterial pressure at induction (MD=7.77; 95% CI=6.00 to 9.55; 95% PI=4.39 to 11.15); heart rate at induction (MD=6.40; 95% CI=4.07 to 8.73; 95% PI=0.33 to 12.48); and heart rate at intubation (MD=6.06; 95% CI=2.33 to 9.78; 95% PI=-5.59 to 17.71). This study provides evidence that remimazolam induces fewer cardiorespiratory depressant effects and has a more favorable side effect profile compared to propofol during general anaesthesia.

Self-rated health and health-related quality of life among cancer patients: the serial multiple mediation of anxiety and depression

BackgroundHealth-related quality of life (HRQOL) in cancer patients has attracted increasing attention, which may be associated with self-rated health (SRH), anxiety, and depression. However, limited studies have focused on the mediating role of anxiety and depression in the relationship between SRH and HRQOL among cancer patients. Therefore, this study aims to explore the serial multiple mediating effects of anxiety and depression between SRH and HRQOL in cancer patients.MethodsThis cross-sectional study investigated a total of 565 hospitalized cancer patients in Anhui province in China from November 2020 to October 2021. SRH was assessed using a single-item measure, anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS) and HRQOL was assessed using the EuroQol-5 Dimension (EQ-5D, three-level version). Socio-demographic and clinical characteristics were analyzed using descriptive statistics. The relationships between SRH, anxiety, depression, and HRQOL were evaluated by Pearson correlation analysis. The serial multiple mediation of anxiety and depression was assessed by SPSS PROCESS macro.ResultsSRH, anxiety, depression and HRQOL were significantly correlated(P < 0.001). In comparison to the fair SRH, the good SRH exhibited a significantly positive direct effect (Effect = 0.2366, Bootstrap 95%CI: 0.0642 ~ 0.4090) and total effect on HRQOL (Effect = 0.4761, Bootstrap 95%CI: 0.2975 ~ 0.6546). Conversely, the poor SRH demonstrated a significantly negative total effect on HRQOL (Effect= -0.4321, Bootstrap 95%CI: -0.7544~ -0.1099). When considering the fair SRH as the reference group, the poor SRH displayed a negative indirect effect on HRQOL through the single mediation of anxiety (Effect= -0.1058, Bootstrap 95%CI: -0.2217~ -0.0107) and the serial mediation of anxiety and depression (Effect= -0.0528, Bootstrap 95%CI: -0.1233~ -0.0035). Conversely, the good SRH had a positive indirect impact on HRQOL through the single mediation of anxiety (Effect = 0.1153, Bootstrap 95%CI: 0.0583 ~ 0.1900) and depression (Effect = 0.0667, Bootstrap 95%CI: 0.0206 ~ 0.1234), as well as the serial mediation of anxiety and depression (Effect = 0.0575, Bootstrap 95%CI: 0.0192 ~ 0.1030).ConclusionSRH can improve HRQOL through the decrease of anxiety and depression in cancer patients. Focusing on SRH would be beneficial for their mental health and HRQOL in cancer patients.

LSD-assisted therapy in patients with anxiety: open-label prospective 12-month follow-up.

Anxiety disorders are a major public health burden with limited treatment options. We investigated the long-term safety and efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with anxiety with or without life-threatening illness. This study was an a priori-planned long-term follow-up of an investigator-initiated, two-centre trial that used a double-blind, placebo-controlled, two-period, random-order, crossover design with two sessions with either oral LSD (200 μg) or placebo per period. Participants (n = 39) were followed up 1 year after the end-of-study visit to assess symptoms of anxiety, depression and long-term effects of psychedelics using Spielberger's State-Trait Anxiety Inventory-Global (STAI-G), the Beck Depression Inventory (BDI), the Persisting Effects Questionnaire and measures of personality traits using the NEO-Five-Factor Inventory. Participants reported a sustained reduction of STAI-G scores compared with baseline (least square means (95% CI) = -21.6 (-32.7, -10.4), d = 1.04, P < 0.001, for those who received LSD in the first period (94 weeks after the last LSD treatment) and -16.5 (-26.2, -6.8), d = 1.02, P < 0.05, for those who received LSD in the second period (68 weeks after the last LSD treatment)). Similar effects were observed for comorbid depression with change from baseline BDI scores of -8.1 (-13.2, -3.1), d = 0.71, P < 0.01, and -8.9 (-12.9, -4.9), d = 1.21, P < 0.01, for the LSD-first and placebo-first groups, respectively. Personality trait neuroticism decreased (P < 0.0001) and trait extraversion increased (P < 0.01) compared with study inclusion. Individuals attributed positive long-term effects to the psychedelic experience. Patients reported sustained long-term effects of LSD-assisted therapy for anxiety.

Gut microbiome, and immune cells mediated effect on depression: A two-step, two-sample Mendelian randomization analysis

BackgroundThe gut microbiota (GM) plays an important role in the development of immune-related diseases, and the immune response is one of the pathomechanisms of depression (Dep); whether the effect of GM on Dep is mediated by immune cells (ImC) is unclear. ObjectiveImC may mediate the effect of GM on Dep. Our aim is to identify and quantify the role of immune characteristics as potential mediators. MethodsPooled statistics for GM (n = 7738) and ImC (n = 3757) were obtained from publicly available genome-wide association studies (GWAS), and for Dep (n = 47,696) from the Finnish database R10. We used a mediated Mendelian randomization (MR) study to investigate the causal relationship between GM and Dep and the mediating role of ImC between GM and Dep associations. ResultsThe results showed that the genetically predicted GM was significantly correlated with both ImC as well as Dep. MR analysis identified five microbiomes that had significant causal effects on Dep (Methionine biosynthesis III, PWY-6737-Starch degradation V, Parasutterella excrementihominis, Parasutterella, and Lysine biosynthesis I). In addition, five of the 26 ImC trait significantly associated with GM were most closely associated with Dep (T cell %lymphocyte、CD28-CD127-CD25++CD8br AC、CD28-CD8br AC、CD27 receptor on peripheral blood plasma cells (CD27 on PB/PC) and CD11b receptor on mononuclear myeloid-derived suppressor cells (CD11b on Mo MDSC)). This mediated MR illustrates the causal role of methionine biosynthesis III on Dep (IVW: OR = 1.08, 95%CI [1.04,1.14], P = 0.001). And there was no strong evidence for a causal effect of depression on methionine biosynthesis III. In the B cell group, the proportion of CD27 on PB/PC mediated was 7.88 %(95%CI [−0.04,0.03]) of the total effect. This study further suggests that Dep patients should actively seek immunologic intervention therapy. ConclusionThis MR study found that GM may play a causal role in Dep by mediating ImC. Our findings will help to understand the pathogenic mechanism of GM in Dep and the risk of immune mediation.

How does the issuance of green bonds impact stock price crash risk: An analysis utilizing the NCSKEW and DUVOL

China's rapid development in the context of carbon neutrality has positioned it as the global leader in green bond issuance. As the Chinese A-share market continues to slump, adverse shocks are accumulating. Thus, the question arises: How will the issuance of green bonds (GB) impact stock price crash risk (SPCR)? The present study utilizes datasets of Chinese A-share listed firms from 2012 to 2022 and conducts a differences-in-difference analysis to address this inquiry. The findings indicate that issuing GB can significantly reduce SPCR, suggesting that GB plays a stabilizing role in the capital market. This effect remains robust after consideration of parallel trend testing, placebo tests, propensity score matching, replacement of explained variables, and controlling for geographic and industrial factors. The mechanism studies demonstrate that the issuance of GB can effectively alleviate financing constraints faced by companies and reduce SPCR through the financing constraints mechanism. The issuance can also enhance firm exposure and attract investor attention, thereby mitigating SPCR through the investor attention mechanism. The issuance contributes to the formation of a positive reputation image among investors and can diminish SPCR through the investor sentiment mechanism. The heterogeneity analyses show that the depressive effect of issuing GB on SPCR is more pronounced in state-owned enterprises, heavily polluting industries, and regions with a higher degree of marketization. Further discussion suggests that given the influence of externalities, the green signals released when a firm issues GB can spread within the capital market, generating a positive spillover effect on the decrease in SPCR of other firms in the same region and a negative spillover effect on the increase in SPCR of other firms in the same industry. This study not only confirms GB's stabilization role in the capital market, but also offers theoretical insights for improving the institutional design of the green bond market and promoting sustainable green development.

Antihyperalgesic effect of γ-terpinene complexed in β-cyclodextrin on neuropathic pain model induced by tumor cells

Neuropathic pain is a high-intensity pain that can be caused by compression, transection, injury, nerve infiltration and drug treatment of cancer. Furthermore, drug therapy has low clinical efficacy, many adverse effects and remission of painful symptoms. In this way, natural products derived from plants constitute a promising therapeutic alternative. Therefore, the aim of this study was to evaluate the antihyperalgesic effect of γ-terpinene (γ-TPN) e γ-terpinene in β-cyclodextrin inclusion complexes (TPN/CD) on neuropathic pain induced by tumor cells. Complexation extended the effect time for another 5 h and daily treatment for six days with γ-TPN (50 mg/kg, p.o.) and γ-TPN/β-CD (50 mg/kg, p.o.) significantly reduced (p < 0.001) the mechanical hyperalgesia induced by the administration of 2x106 sarcoma cells 180 in the around the sciatic nerve. In addition, the Grip and Rota-rod techniques demonstrated that there was no interference on the muscle strength and motor coordination of the animals, suggesting that the compound under study does not have central nervous system depressant effects at the doses used. Molecular docking studies demonstrate favorable binding energies between γ-TPN and β-CD, and alpha-2 adrenergic, glutamatergic, opioid and cholinergic receptors. Thus, this study demonstrates the potential of terpinene complexation in controlling neuropathic pain induced by tumor cells.

Examining the Longitudinal Effects of Insomnia on Depression and Medication Adherence in People Living with HIV

ABSTRACT Objective The management of HIV has shifted from a focus solely on the disease to a broader perspective encompassing co-occurring medical conditions and quality of life. Mental health concerns such as depression and sleep disturbances, particularly insomnia, are often overlooked in HIV care. The aim of the study was to investigate the longitudinal impact of insomnia on depression and medication adherence among (PLWH). Methods This study, conducted in an urban HIV clinic, involved active patients and assessed depression, insomnia, and medication adherence at baseline, 3-month, and 6-month intervals. Hierarchical linear models were employed to analyze the fixed and random effects of time, within-person and between-person insomnia on depression, as well as the effects of time, within-person and between-person depression on ART adherence. Results Within-person effects revealed that each one unit increase in the Insomnia Severity Index (ISI) was associated with a b = 0.267-point rise in Patient Health Questionnaire-9 (PHQ-9) scores (p < .001). Between-person effects revealed that each one-point increase in an individual’s average ISI score was associated with a 0.476-point elevation in their PHQ-9 scores (p < .001). The between-person effects of depression on medication adherence indicated significance, with each point increase in an individual’s average PHQ-9 score being linked to a 0.36% decrease in adherence (p = .012). Conclusion The study underscores the potential impact of insomnia on mental health and treatment adherence in people living with HIV (PLWH). This study emphasizes the necessity of comprehensive care models considering the interplay between sleep quality, mental health, and medication adherence for PLWH.

Depressive Disorder and Trimalleolar Fractures: An Analysis of Outcomes and Costs.

Studies have suggested a strong association between depression and poor outcomes following various orthopaedic surgeries. However, depression's impact on complications following open reduction/internal fixation (ORIF) of trimalleolar fractures has not been elucidated. Therefore, this study aimed to determine whether depression is associated with higher rates of readmissions and medical complications following ORIF of trimalleolar fractures. A database query from January, 2020, through March, 2021, identifying adults who underwent trimalleolar ORIF generated 50 154 patients. Those with depression were matched 1:1 to controls without depression by age, sex, chronic obstructive pulmonary disease, anxiety, and other prominent comorbidities. Primary endpoints compared 90-day all-cause readmissions and medical complications. Odds ratios (ORs) of the effect of depression on readmissions and medical complications were calculated. Patients with depression who underwent ORIF of trimalleolar fractures had significantly higher odds of being readmitted within 90 days of the initial procedure (OR: 1.37; P < .0001). Ninety-day odds of developing medical complications were significantly higher (OR: 4.61; P < .0001) in patients with depression compared with patients within the control group. Patients with depression undergoing trimalleolar ORIF face an increased risk of readmission and multiple postoperative complications. Orthopaedic surgeons should factor depression into their preoperative evaluation, given the already high burden of complications following ORIF of trimalleolar fractures. Level III: Retrospective cohort study.

Association between Menopausal Women’s Quality of Life and Aging Anxiety: The Role of Life Satisfaction and Depression

Background and Objectives: This study investigated the links among quality of life, life satisfaction, depression, and aging anxiety in menopausal middle-aged women. The objective was to establish an understanding of how these factors are associated, which would be the foundation for developing programs aimed at enhancing the health and well-being of menopausal women. Materials and Methods: An online survey was administered to 993 middle-aged women, aged 45 to 65, residing in Seoul, Korea. The survey evaluated menopausal quality of life, life satisfaction, depression, and aging anxiety. Additionally, a Process Macro Model 4 was used to assess the links between life satisfaction, depression, menopausal quality of life, and aging anxiety. Results: Aging anxiety in middle-aged women was associated with a lower score on the menopausal quality of life scale (r = 0.37, p &lt; 0.001), lower life satisfaction (r = −0.46, p &lt; 0.001), and higher depression (r = 0.42, p &lt; 0.001). In addition, there was an indirect effect—mediated by depression (95% CI = 0.025, 0.058) and life satisfaction (95% CI = 0.038, 0.064)—between menopausal quality of life and aging anxiety. Conclusions: The present study demonstrated a direct effect of low menopausal quality of life on aging anxiety and a mediating effect of low depression and higher life satisfaction on aging anxiety. These results suggest the need for programs to increase menopausal quality of life, decrease depression and improve life satisfaction to reduce aging anxiety.

Identification of differentially expressed genes in the medial prefrontal cortex of rats subjected to chronic unpredictable mild stress and treated with electroacupuncture

Major depressive disorder is a chronic mental health condition that seriously impacts afflicted individuals. Although electroacupuncture has proven to be an effective therapy for depression, its underlying biological mechanism remains largely unknown. In this study, we aimed to investigate the effects of electroacupuncture on depression-like behavior and to identify potential target genes related to those effects. To achieve this, we subjected rats to chronic unpredictable mild stress (CUMS) and used sucrose preference, forced swimming, and open-field tests to determine their depression-like behavior in the absence or after receipt of electroacupuncture treatment. RNA sequencing technology was then used to reveal the differentially expressed genes associated with depression and electroacupuncture treatment effects in the medial prefrontal cortex (mPFC). Repeated electroacupuncture treatments at the Baihui (GV20) and Taichong (LR3) acupoints significantly alleviated depression-like behavioral defects in the animals. Genomic RNA sequencing revealed several significant changes in the mPFC transcriptome of rats that received treatment. Through differential gene expression analysis, we found that electroacupuncture reversed the CUMS-induced downregulation of 46 genes and upregulation of 13 genes. Among the differentially expressed genes, Casr, Bdkrb2, Gnb3, and Ccl1 were found to be associated with depression and electroacupuncture treatment effects. In conclusion, we verified that electroacupuncture treatment has an effective antidepressant effect, and the underlying mechanism involves multiple systems and targets.

Effects of depression and stress on oral self-care among perinatal women in Appalachia: A longitudinal study.

Oral health during the perinatal period and beyond affects the health and well-being of women and their offspring. Oral self-care behaviours can maintain or improve oral health; depression or stress during the perinatal period may compromise these behaviours. The aim of the study was to investigate the independent and combined effects of depression and stress on oral self-care behaviours of perinatal women in Appalachia, given the high burden of oral disease in this region. A total of 1172 women in the first or second trimester of pregnancy were enrolled in the Center for Oral Health Research in Appalachia, cohort 2 (COHRA2) in West Virginia or Pittsburgh, Pennsylvania. Participants completed the Center for Epidemiological Studies Depression Scale, Perceived Stress Scale-10, and self-report items about oral self-care behaviours (i.e. toothbrushing and flossing) during pregnancy and five times in the 2+ years following birth. A Generalized Estimating Equation approach was used to analyse the longitudinal data. Maternal depression and stress were independently negatively related to toothbrushing and flossing frequency. These findings for toothbrushing were more pronounced in those with high levels of depression and high levels of stress, so there were both independent and combined effects. Frequency of toothbrushing and flossing stayed constant over time, so time was not associated with outcomes. About three-fourths of the sample reported toothbrushing levels that are consistent with established guidelines (i.e. two times daily), but almost half of the participants had very low levels of flossing (i.e. once or less a week). Interventions targeting stress and depression throughout the perinatal period might be helpful in improving oral self-care behaviours and oral health among women in Appalachia, in addition to the benefit of decreasing emotional distress.

Maternal AMPK pathway activation with uterine artery blood flow and fetal growth maintenance during hypoxia.

High altitude (HA) hypoxia lowers uterine artery (UtA) blood flow during pregnancy and birth weight. Adenosine monophosphate kinase (AMPK) activation has selective, uteroplacental vasodilator effects which lessen hypoxia-associated birth weight reductions. In this study, we determined the relationship between AMPK-pathway gene expression and metabolites in the maternal circulation during HA pregnancy as well as with the maintenance of UtA blood flow and birth weight at HA. HA (2793 m) vs low altitude (LA; 1640 m) residents had smaller UtA diameters at weeks 20 and 34, lower UtA blood flow at week 20, and lower birth weight babies. At week 34, HA vs LA women had decreased expression of up- and down-stream AMPK-pathway genes. Expression of the a-1 AMPK catalytic subunit, PRKAA1, correlated positively with UtA diameter and blood flow at week 20 (HA) and 34 (LA). Downstream AMPK-pathway gene expression positively correlated with week 20 fetal biometry at both altitudes and with UtA diameter and birth weight at LA. Reduced gene expression of AMPK activators and downstream targets in HA versus LA women, together with positive correlations between PRKAA1 gene expression, UtA diameter, and blood flow suggest that greater sensitivity to AMPK activation at mid-gestation at HA may help offset later depressant effects of hypoxia on fetal growth.

Associations between maternal early pregnancy depression and longitudinal fetal growth

BackgroundThe impacts of maternal depression during mid-to-late pregnancy on fetal growth have been extensively investigated. However, the association between maternal depression during early pregnancy and fetal intrauterine growth are less clear. MethodsA prospective study comprised 23,465 eligible pregnant women and their offspring was conducted at a hospital-based center in Shanghai. Prenatal depression was assessed used using Patient Health Questionnaire (PHQ-9) before 14 gestational weeks. Differences in fetal growth trajectory of different maternal depressive statuses during three periods (16–23, 24–31, and 32–41 gestational weeks) were compared using a multilevel model with fractional polynomials. ResultsWomen with depressive symptoms during early pregnancy had higher longitudinal fetal trajectories, with an estimated increase in fetal weight (β = 0.33; 95 % CI, 0.06–0.61), compared to those without depressive symptoms. Increases in fetal abdominal circumference among women with depressive symptoms were observed before 23 gestational weeks. Offspring born to mothers with early pregnancy depression had a significantly higher birth weight of 14.13 g (95 % CI, 1.33–27.81 g) and an increased risk of severe large size for gestational age (adjusted odds ratio [aOR], 1.64; 95 % CI, 1.32–2.04) and macrosomia (aOR, 1.21; 95 % CI, 1.02–1.43). LimitationsSelf-rated scale was used to assess depressive symptoms rather than clinical diagnosis. And Long-term effects of early pregnancy depression on offspring were not explored. ConclusionsThe study revealed an association between maternal depression during early pregnancy and increased fetal biometrics, higher birth weight, and an elevated risk of severe large size for gestational age and macrosomia.

Depression increases the risk of gallstone: A cross-sectional study and Mendelian randomization analysis

BackgroundGallstone, a common digestive disorder, poses a significant public health burden. Concurrently, depression is acknowledged as a health risk. However, limited information exists on depression's impact on gallstone formation. This study investigates depression's causal effect on gallstone risk. MethodsUsing National Health and Nutrition Examination Survey (NHANES) data, we conducted an observational study. The severity of depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression and subgroup analyses explored the correlation between depression and gallstone risk. Mendelian Randomization (MR) analysis, leveraging Genome-Wide Association Studies (GWAS) data, reduced observational bias and elucidated causality. Inverse Variance Weighting (IVW) was the primary method, with sensitivity analyses validating results. ResultsIn the observational study (7707 participants), gallstone risk was elevated in mild (OR: 1.58, 95 % CI 1.31–1.90, P < 0.001), moderate (OR: 2.07, 95 % CI 1.59–2.67, P < 0.001), and severe (OR: 2.41, 95 % CI 1.70–3.34, P < 0.001) depression groups (P for trend <0.001). Subgroup analyses revealed a stronger association in those under 65, females, non-Hispanic Black, individuals with obesity, smokers, and those with college education or higher. Mendelian Randomization indicated a causal link between genetically predicted depression and higher cholelithiasis risk (OR: 2.06, 95 % CI 1.34–3.17, P = 0.001), validated through sensitivity analyses and multi-cohort verification. ConclusionDepression independently increases gallstone risk, particularly in those under 65, females, non-Hispanic Black, individuals with obesity, smokers, and those with college education or higher. Further validation is needed through multi-center, prospective cohort studies.

Dexmedetomidine as a total intravenous anesthetic in pediatric patients undergoing cleft lip and palate surgery: a case series

BackgroundSurgery for pediatric cleft lip and palate repair often utilizes high-dose opioids and inhaled anesthesia, thereby causing postoperative complications such as desaturation and/or severe agitation after anesthesia. These complications are detrimental to the child and medical personnel and cause tremendous psychologic stress to parents. Our aim is to decrease these complications through dexmedetomidine, an alpha-2 receptor agonist with anxiolytic, sympatholytic, and analgetic properties. Devoid of respiratory depressant effect, it allows patients to maintain effective ventilation and reduce agitation, postoperatively. Its unique anesthetic property may shed light on providing safe anesthesia and gentle emergence to this young, vulnerable population.Case presentationA total of 21 patients of Sundanese ethnicity, aged 3 months to 8 years (9 males and 12 females), underwent cleft lip or cleft palate surgery using total intravenous dexmedetomidine. Anesthesia was induced using sevoflurane, fentanyl, and propofol, and airway was secured. Intravenous dexmedetomidine 1.5 μg/kg was administered within 10 minutes, and a maintenance dose of 1.5 μg/kg/hour was continued as the sole anesthetic maintenance agent thereafter. Hemodynamics and anesthetic depth using Patient State Index (SEDLine™ monitor, Masimo Corporation, Irvine, CA, USA) were monitored carefully throughout the surgical procedure. Dexmedetomidine did not cause any hemodynamic derangements or postoperative complications in any of our patients. We found agitation in 9.5% (2/21) of patients.ConclusionDexmedetomidine can be used as a total intravenous anesthetic agent to maintain anesthesia and provide gentle emergence to infants and young children undergoing cleft lip and palate repair.

Diabetes Mellitus Inequality in South Korean Adults by Region: The Influence of Obesity and Depression.

Diabetes mellitus (DM) has different prevalence by region. This study aimed to identify the differences in the effects of obesity and depression on DM in South Korean adults by region. The participants were 14,343 adults (≥30 yr) from Ulsan (regions with the lowest prevalence of DM) and Jeonbuk (regions with the highest prevalence of DM), and data were extracted from the Community Health Survey 2019. We applied a complex sampling design analysis to reflect the stratified, clustering and weights. The data were analyzed using the unweighted frequencies, weighted percentage, mean, standard error, Chi-Square test and multiple logistic regression analysis (SPSS 25.0). Regarding the main result for Ulsan, the odds ratio of DM increased by 1.94, 2.52,1.57, and 4.87 times for obesity(25-29.9kg/m2), high obesity(≥30kg/m2), depression, and receipt of psychological counseling for depression, respectively. In Jeonbuk, the odds ratio of DM increased by 1.79, 2.84, and 3.59 times for obesity, high obesity, and unmet medical experience, respectively. On the other hand, depression-related variables were found to not influence DM. We provided the rationale for conducting a health project that interventions for obesity and depression should be included in DM management programs differently in Ulsan and Jeonbuk regions.

Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma

Background & aimsPatients with intrahepatic cholangiocarcinoma (iCCA) respond poorly to immune checkpoint blockades (ICBs). In this study, we aimed to dissect the potential mechanisms underlying poor response to ICBs and explore a rational ICB-based combination therapy in iCCA.MethodsscRNA-seq dataset GSE151530 was analyzed to investigate the differentially expressed genes in malignant cells following ICBs therapy. RNA-seq analysis and western blot assays were performed to examine the upstream and downstream signaling pathways of CD73. Subcutaneous tumor xenograft models were utilized to investigate the impact of CD73 on iCCA growth. Plasmid AKT/NICD-induced spontaneous murine iCCAs were used to explore the therapeutic efficacy of CD73 enzymatic inhibitor AB680 combined with PD-1 blockade. Time-of-flight mass cytometry (CyTOF) was conducted to identify the tumor-infiltrating immune cell populations and their functional changes in murine iCCAs treated with AB680 in combination with PD-1 antibody.ResultsscRNA-seq analysis identified elevated CD73 expression in malignant cells in response to ICBs therapy. Mechanistically, ICBs therapy upregulated CD73 expression in malignant cells via TNF-α/NF-κB signaling pathway. In vivo studies revealed that CD73 inhibition suppressed the growth of subcutaneous tumors, and achieved synergistic depression effects with gemcitabine and cisplatin (GC). Adenosine produced by CD73 activates AKT/GSK3β/β-catenin signaling axis in iCCA cells. CD73 inhibitor AB680 potentiates anti-tumor efficacy of PD-1 antibody in murine iCCAs. CyTOF analysis showed that AB680 combined with anti-PD-1 therapy promoted the infiltration of CD8+ T, CD4+ T cells, and NK cells in murine iCCAs, while simultaneously decreased the proportions of macrophages and neutrophils. Moreover, AB680 combined with anti-PD-1 significantly upregulated the expression of Granzyme B, Tbet and co-stimulatory molecule ICOS in infiltrating CD8+ T cells.ConclusionsCD73 inhibitor AB680 limits tumor progression and potentiates therapeutic efficacy of GC chemotherapy or anti-PD-1 treatment in iCCA. AB680 combined with anti-PD-1 therapy effectively elicits anti-tumor immune response.