Association between serum and urinary environmental metal levels and major depressive disorder: a study based on logistic regression and quantile regression.

Background: Major depressive disorder (MDD) is a prevalent mental disorder globally. Increasing evidence suggests that Environmental Metal (EM) play a crucial role in MDD. Therefore, this study investigated the roles of barium (Ba), cesium (Cs), nickel (Ni), manganese (Mn), lead (Pb), mercury (Hg), cadmium (Cd), and tin (Sn) in the etiology of MDD. Methods: The study included 72 MDD patients and 75 healthy controls (HCs) from the Second People's Hospital of Zhumadian, China. Inductively coupled plasma mass spectrometer (ICP-MS) measured the metal levels in serum and urine samples from both groups. Results: Significant differences in serum and urine levels of EMs were observed between MDD patients and HCs. After adjusting for age, gender, and BMI, logistic regression and quantile regression models revealed significant associations between EMs and MDD. In serum samples, higher Sn levels (OR = 1.22, p = 0.044) increased MDD risk, whereas higher Cs levels (OR = 0.02, p < 0.001), Cd (OR = 0.06, p = 0.047), and Mn (OR = 0.54, p = 0.016) decreased MDD risk. In urine samples, higher Ba levels (OR = 0.94, p = 0.015), Ni (OR = 0.87, p = 0.0024), Sn (OR = 1.62, p < 0.001), and Mn (OR = 0.77, p = 0.037) were significantly associated with MDD. Sn significantly positively predicted HAMD-24 scores at the 0.50 and 0.75 quantiles (ß = 0.96, p = 0.018; ß = 1.25, p = 0.008) as did Pb (ß = 5.15, p = 0.001; ß = 4.19, p = 0.004). Ba positively predicted depressive symptoms across all quantiles (all p < 0.05). Hg positively predicted HAMD-24 scores at the 0.50 quantile (ß = 9.20, p = 0.050). Conclusion: These findings underscore EMs' importance in depression, aiding in targeted interventions for varying degrees of depression and necessitating future studies to clarify causality and mechanisms.

Emphasizing autonomic dysregulation evaluation contributes to the diagnosis of ROHHAD syndrome.

OBJECTIVE: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is rare, and manifestations of autonomic dysregulation are diverse and may be overlooked. We aimed to evaluate the incidence of these manifestations. METHODS: Patients with ROHHAD syndrome reported before and after 2019 were divided into Groups 1 and 2. Patients who were diagnosed at three regional hospitals in China were included in Group 3. We collected the age of each specific term of the ROHHAD (neurogenic tumor, NET) acronym and the detailed manifestations of each term, and compared them among the three groups. RESULTS: A total of 16 patients were diagnosed within the 2-year period. Two had neurogenic tumors and cognitive and behavioral abnormalities before developing rapid obesity. At least 93.8% of the patients had ≥ 4 symptoms of autonomic dysregulation. When comparing autonomic dysregulation among Groups 1-3, the rates of cardiovascular manifestations were NA vs. 12.8% vs. 81.2%; gastrointestinal disturbances were 11.4% vs. 8.5% vs. 62.5%; strabismus was 25.7% vs. 12.8% vs. 62.5%; sleep disturbance was NA vs. 6.4% vs. 50.0%; and abnormal pain threshold was NA vs. 10.6% vs. 25.0% (all p<0.05). The rates of cognitive and behavioral abnormalities were NA vs 29.8% and 87.5% (p<0.01). CONCLUSIONS: Rapid-onset obesity is not always the first sign of ROHHAD syndrome. Higher rates of autonomic dysregulation and cognitive and behavioral abnormalities with multiple manifestations of autonomic dysregulation coexisted in our cohort, indicating that evaluations of autonomic function and the limbic system should be strengthened when assessing this condition.

Association between cognitive functioning, suicidal ideation and suicide attempts in major depressive disorder, bipolar disorder, schizophrenia and related disorders: A systematic review and meta-analysis.

INTRODUCTION: Treatable mental disorders, such as psychotic, major depressive disorder (MDD), and bipolar disorder (BD), contribute to a substantial portion of suicide risk, often accompanied by neurocognitive deficits. We report the association between cognitive function and suicidal ideation/suicide attempts (SI/SA) in individuals with schizoaffective disorder, BD, and MDD. METHODS: A systematic search was conducted on PubMed, Ovid and Scopus databases for primary studies published from inception to April 2024. Eligible articles that reported on the effect size of association between cognition and SI/SA were pooled using a random effects model. RESULTS: A total of 41 studies were included for analysis. There was a negative association between executive functioning and SI/SA in schizoaffective disorder (SA: Corr = -0·78, 95 % CI [-1·00, 0·98]; SI: Corr = -0·06, 95 % CI [-0·85, 0·82]) and MDD (SA: Corr = -0·227, 95 % CI [-0·419, -0·017]; SI: Corr = -0·14, 95 % CI [-0·33, 0·06]). Results were mixed for BD, with a significant positive association between SA and global executive functioning (Corr = 0·08, 95 % CI [0·01, 0·15]) and negative association with emotion inhibition. Mixed results were observed for processing speed, attention, and learning and memory, transdiagnostically. LIMITATIONS: There is heterogeneity across sample compositions and cognitive measures. We did not have detailed information on individuals with respect to demographics and comorbidities. CONCLUSIONS: We observed a transdiagnostic association between measures of cognitive functions and aspects of suicidality. The interplay of cognitive disturbances, particularly in reward-based functioning, may underlie suicidality in individuals with mental disorders. Disturbances in impulse control, planning, and working memory may contribute to self-injurious behavior and suicide.

Review of Baduanjin and resistance exercise for the mental health of patients with hematologic malignancies.

Patients with hematological tumors experience physical and psychological stress, and negative psychological states. Baduanjin, an emerging psychological rehabilitation method combined with resistance exercise, has received widespread attention. This study reviews the current status of the application of Baduanjin combined with resistance exercise in improving the negative psychological state of patients with hematological tumors and discusses its problems and prospects. Through a literature review and comprehensive analysis, the application of Baduanjin and resistance exercise in the psychological rehabilitation of patients with hematological tumors was identified and evaluated. The results showed that Baduanjin with resistance exercise had a positive effect on improving negative psychological states of patients with hematological tumors, which can alleviate anxiety, depression, and other adverse emotions, and improve quality of life. However, there is a lack of unified and standardized exercise intervention programs for practical application, and patient participation and compliance must be improved. Baduanjin combined with resistance exercise can potentially improve the negative psychological status of patients with hematological tumors; however, it is still necessary to further standardize and improve the exercise program improving patient participation and compliance. Future studies should strengthen theoretical exploration and empirical research, providing more effective psychological rehabilitation strategies for patients with hematological tumors.

Characterization and application of LysSGF2 and HolSGF2 as potential biocontrol agents against planktonic and biofilm cells of common pathogenic bacteria.

Antimicrobial resistance represents a global health emergency, necessitating the introduction of novel antimicrobial agents. In the present study, lysozyme and holin from Shigella flexneri 1.1868 phage SGF2, named LysSGF2 and HolSGF2, respectively, were cloned, expressed, and characterized. LysSGF2 and HolSGF2 showed lytic activities against S. flexneri 1.1868 cells at 4-55 °C and pH 3.1-10.3. LysSGF2 exhibited antimicrobial activity against five gram-negative and two gram-positive bacteria. HolSGF2 showed antimicrobial activity against four gram-negative and one gram-positive species. The antibacterial activities of LysSGF2 and HolSGF2 were determined in liquid beverages, including bottled water and milk. The relative lytic activity of LysSGF2 combined with HolSGF2 against the tested bacteria was approximately 46-77 % in water. Furthermore, the combination markedly decreased the viable counts of tested bacteria by approximately 3-5 log CFU/mL. LysSGF2 and HolSGF2 could efficiently remove biofilms on polystyrene, glass, and stainless-steel. The efficacy of the LysSGF2 and HolSGF2 combination against the tested bacteria on polystyrene was 58-71 %. Combination treatment effectively killed biofilm cells formed on stainless-steel and glass by 1-4 log CFU/mL. ese results indicate that LysSGF2 and HolSGF2 can successfully control both the planktonic and biofilm cells of common pathogenic bacteria, suggesting that the combined or single use of LysSGF2 and HolSGF2 may be of great value in food processing.

Associations of methylmalonic acid and depressive symptoms with mortality: a population-based study.

Methylmalonic acid (MMA), a biomarker of mitochondrial dysfunction, has been reported to be associated with depression in specific populations (i.e., older adults and postpartum women). Our study aimed to investigate to what extent MMA was associated with depressive symptoms and mortality in the general population, and assess whether depressive symptoms mediate the relationship between MMA and mortality. We analyzed cross-sectional data from 8343 participants from the US National Health and Nutrition Examination Survey. MMA was measured by liquid chromatography-tandem mass spectrometry, while depressive symptoms were measured by the Patient Health Questionnaire-9. Mortality data were obtained through linkage with National Death Index records. Linear regression models were performed to assess the association between MMA and depressive symptoms. The Cox proportional hazard regression model was utilized to assess the association of MMA and depressive symptoms with mortality. Mediation analysis was conducted within the counterfactual framework. In this general population, each SD (around 0.49 µmol/L) increase in MMA was associated with a 0.03 SD (approximately 0.15 score) increase in depressive symptoms (ß = 0.033, 95% CI: 0.010, 0.055, p = 0.005). Notably, this association was more pronounced in men and participants over 60 years old. Higher levels of MMA and having more depressive symptoms were associated with a higher risk of mortality. However, depressive symptoms do not mediate the relationship between MMA and mortality. Elevated MMA levels were associated with depressive symptoms and an increased risk of mortality. These findings suggest that mitochondrial dysfunction may contribute to the multifactorial etiology of depression.

What influences the close contact between health care workers and patients? An observational study in a hospital dental outpatient department.

BACKGROUND: Dental outpatient departments, characterized by close proximity and unmasked patients, present a considerable risk of respiratory infections for health care workers (HCWs). However, the lack of comprehensive data on close contact (<1.5m) between HCWs and patients poses a significant obstacle to the development of targeted control strategies. METHODS: An observation study was conducted at a hospital in Shenzhen, China, utilizing depth cameras with machine learning to capture close-contact behaviors of patients with HCWs. Additionally, questionnaires were administered to collect patient demographics. RESULTS: The study included 200 patients, 10 dental practitioners, and 10 nurses. Patients had significantly higher close-contact rates with dental practitioners (97.5%) compared with nurses (72.8%, P < .001). The reason for the visit significantly influenced patient-practitioner (P = .018) and patient-nurse (P = .007) close-contact time, with the highest values observed in prosthodontics and orthodontics patients. Furthermore, patient age also significantly impacted the close-contact rate with nurses (P = .024), with the highest rate observed in patients below 14 years old at 85% [interquartile range: 70-93]. CONCLUSIONS: Dental outpatient departments exhibit high HCW-patient close-contact rates, influenced by visit purpose and patient age. Enhanced infection control measures are warranted, particularly for prosthodontics and orthodontics patients or those below 14 years old.

A new integrated rough multi-criteria decision-making model for enterprise resource planning software selection.

Enterprise resource planning (ERP) is widely used to boost the total market power of businesses. The wrong selection is one of the key reasons why ERP installations fail. Due to the complexity of the business environment and the range of ERP systems, choosing an ERP system is a complex and time-consuming procedure. ERP alternatives may be assessed using several criteria, so the ERP selection process may be considered a multi-criteria decision-making (MCDM) problem. In this study, the rough best worst method (BWM) was used to determine criteria weights, while the newly developed rough integrated simple weighted sum product (WISP) was used to rank ERP alternatives. Results suggest that the SFT-4 coded software is regarded as the best option, followed by SFT-5, SFT-6, SFT-2, SFT-3, and SFT-1. Results of the newly developed rough WISP method are compared to those of existing rough techniques in the sensitivity analysis. The differences between them have been found to be negligible. The outcomes show how effectively developed rough BWM and WISP integrated method performs in terms of ERP selection with usability, accuracy, ease of use, and consistency. This study will help decision-makers in a context where ERP is implemented choose the best ERP software for different sectors.

Relationship between anhedonia and psychosocial functioning in post-COVID-19 condition: a post-hoc analysis.

BACKGROUND: Post-COVID-19 condition (PCC), also known as "long COVID," is characterized by persistent symptoms, negatively affecting the well-being of individuals with PCC. Anhedonia (i.e. reduced capacity for pleasure) and compromised psychosocial functioning are notable symptoms in those with PCC. We aimed to provide insights to understand the effects of anhedonia and impaired psychosocial functioning of individuals with PCC. METHODS: This post-hoc analysis used data from an 8-week, double-blind, randomized, placebo-controlled trial which evaluated vortioxetine for cognitive deficits in individuals with PCC (Clinicaltrials.gov Identifier: NCT05047952). A total of 147 eligible participants were randomly assigned to receive vortioxetine or matching placebo over eight weeks of double-blind treatment. Our study investigated the relationship between anhedonia, assessed by the Snaith-Hamilton Pleasure Scale (SHAPS), and psychosocial functioning, measured with the Post-COVID Functional Status (PCFS) scale. The analysis was conducted using a generalized linear model, with adjustments for relevant covariates such as age, sex, education, suspected versus confirmed COVID diagnosis, MDD diagnosis, and alcohol consumption. RESULTS: Of the 147 participants, 143 participants had available baseline data for analysis. We observed that baseline PCFS score was statistically significantly positively correlated to baseline SHAPS score (ß = 0.070, p = 0.045, 95% CI). DISCUSSIONS: Our analysis revealed a significant relationship between measures of anhedonia and psychosocial functioning in adults with PCC. Strategies that aim to improve patient-reported outcomes with PCC need to prioritize the prevention and treatment of hedonic disturbances in patients experiencing PCC.

A replication study using the World Health Organization pharmacovigilance database (VigiBase®) to evaluate whether an association between ketamine and esketamine and alcohol and substance misuse exists.

BACKGROUND AND OBJECTIVES: Ketamine and esketamine are increasingly prescribed in the treatment of resistant mood disorders and persons at risk of suicide. Ketamine is a drug of misuse with increasing non-therapeutic use in the general population. Herein, our aim was to determine whether ketamine and/or esketamine are disproportionately associated with reports of substance and/or alcohol misuse. METHODS: Replicating a similar analysis recently conducted using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, we identified cases of "alcohol problem, alcoholism, alcohol abuse, substance dependence, substance use disorder (SUD), substance abuse, drug dependence, drug use disorder and drug abuse" in association with ketamine and esketamine reported to the World Health Organization Pharmacovigilance Database (WHO VigiBase). We searched the database from inception to January 2024. The reporting odds ratio (ROR) of each of the aforementioned parameters was calculated; acetaminophen was used as the control. The numerator of the equation represents the number of cases (n) and the denominator represents the total cases of psychiatric disorders (N). Significance was obtained when the lower limit of the 95 % confidence (CI) > 1.0. RESULTS: The RORs for ketamine was increased for most parameters (i.e., alcohol abuse (3.24), substance dependence (12.48), substance use disorder (170.44), substance abuse (2.94), drug dependence (2.88), drug use disorder (11.54) and drug abuse (2.85), respectively). With respect to esketamine, the RORs were observed to be different from ketamine insofar as we observed a reduction in the RORs for three parameters (i.e., substance abuse (0.41), drug dependence (0.083) and drug abuse (0.052), respectively). The IC025 values were significant for ketamine in cases of alcohol abuse (0.35), substance dependence (0.50), substance use disorder (2.77), substance abuse (0.83), drug dependence (0.97), drug use disorder (1.95) and drug abuse (0.94). Additionally, oxycontin showed significant IC025 values for substance use disorder (0.0014), substance abuse (0.042), and drug dependence (0.17). CONCLUSION: Esketamine was not associated with an increased ROR for any parameter of alcohol and/or substance use disorder. Mixed results were observed with ketamine with some RORs increased and others decreased. Estimating RORs using a pharmacovigilance database does not establish causation in the case of elevated RORs and cannot be assumed to be a therapeutic effect when lower RORs were observed.

Impact of vortioxetine on depressive symptoms moderated by symptoms of anxiety in persons with post-COVID-19 condition: A secondary analysis.

OBJECTIVE: Recovery from a COVID-19 infection can lead to post-COVID-19 condition (PCC), which causes a multitude of debilitating symptoms that negatively affect an individual's health-related quality of life, including depressive and anxiety symptoms. We aim to examine the mediatory effects of anxiety on depressive symptoms in persons with PCC receiving vortioxetine. METHODS: We performed a post-hoc analysis of a randomized, double-blinded, placebo-controlled clinical trial investigating vortioxetine treatment on cognitive functioning in persons with PCC. Anxiety and depressive symptoms were measured by the 7-Item Generalized Anxiety Disorder (GAD-7) Scale and the 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR-16), respectively. RESULTS: Based on data of 147 participants, GAD-7 scores were significantly positively associated with QIDS-SR-16 scores (ß=0.038, 95 % CI [0.029,0.047], p < 0.001). After adjusting for covariates, a significant group (χ2=176.786, p < 0.001), time (χ2=8.914, p = 0.003), and treatment x time x GAD-7 score interaction (χ2=236.483, p < 0.001) effect was observed. Vortioxetine-treated participants had a significant difference in overall change in depressive symptoms (mean difference=-3.15, SEM=0.642, 95 % CI [-4.40,-1.89], p < 0.001). CONCLUSION: Anxiety symptoms were significantly associated with depressive symptoms in persons with PCC. Antidepressant efficacy on ameliorating depressive symptoms is dependent on improving anxiety symptoms, underscoring significant implications in improving treatment efficacy and patient quality of life.

Preclinical and clinical efficacy of kappa opioid receptor antagonists for depression: A systematic review.

BACKGROUND: Approximately 30 % of persons with Major Depressive Disorder (MDD) inadequately respond to conventional antidepressants. Kappa opioid receptor (KOR) antagonists, aticaprant and navacaprant, are in development as treatments for MDD. Herein, we aim to comprehensively evaluate the safety, efficacy and pharmacology of aticaprant and navacaprant for MDD. METHODS: We performed a systematic review of primary research investigating aticaprant and navacaprant on PubMed, OVID, and Scopus databases from inception to April 2024. Studies that reported on the pharmacological profile and/or safety and efficacy of aticaprant and navacaprant were included. RESULTS: Navacaprant monotherapy and aticaprant adjunctive therapy are in development for MDD. Navacaprant exhibits 300-fold selectivity for the KOR compared to the mu-opioid receptor, while aticaprant exhibits 30-fold selectivity. At clinically-relevant doses, navacaprant and aticaprant occupy 87-95 % and 73-94 % of KORs, respectively. Clinical trials of the foregoing agents (navacaprant as monotherapy and actiprant as adjunctive therapy) reported significant improvement in depressive symptoms and may clinically benefit measures of anhedonia. Both agents appear well-tolerated, with most adverse events mild and no known safety concerns. LIMITATIONS: Aticaprant and navacaprant treatment for MDD are in early stages of clinical trials and results from Phase 3 pivotal trials are not yet available. CONCLUSIONS: Kappa opioid receptor antagonists may serve as mechanistically-novel treatments for MDD and persons who inadequately respond to index conventional antidepressants. Anhedonia is debilitating and insufficiently treated with conventional antidepressants. Future research vistas should establish the efficacy and safety of KORAs in phase 3 studies in both acute and maintenance paradigms.

Comparative Efficacy of Omega-3 Fatty Acid with Other Interventions for Depression in Children and Adolescents: A Systematic Review and Network Meta-Analysis.

Background: The administration of omega-3 polyunsaturated fatty acid supplements is recommended as an adjuvant therapy for adults diagnosed with major depressive disorder. The evaluation of replicated data in combination treatment with omega-3 has been extensively conducted in adults over the past decade. However, the generalizability of these findings to pediatric groups is still uncertain. The objectives of this evaluation were twofold: (1) to evaluate the effectiveness of omega-3 and associated combination therapies in reducing the severity of depressive symptoms, and (2) to include remission rates (i.e., reduction of more than 50% in depression symptoms) as a measure of therapeutic efficacy. Methods: We conducted a literature search on PubMed/EMBASE from inception to October 2023. Data analyses were conducted using Stata (version 17.0). Results: We identified a total of 3168 articles. After eligibility screening of identified studies, nine studies (n = 561 participants) were included in our analysis herein. Pairwise comparisons revealed no significant improvement in depression symptoms for any intervention versus placebo. However, a clustered ranking plot identified omega-3 plus inositol as the most effective treatment for pediatric depression (77.3% efficacy). Omega-3 paired with psychoeducational psychotherapy significantly lowered the remission rate compared to placebo (standardized mean difference = 0.44, 95% confidence interval: 0.00-0.87, p = 0.048), resulting in a 91.5% remission rate, making it the most effective treatment in the study. Conclusions: Taken together, this network meta-analysis presents compelling evidence supporting the antidepressant effects of omega-3 in pediatric groups with depression. Future research should aim to investigate omega-3 as monotherapy for young individuals with depression, as well as investigate the efficacy of omega-3 in comparison to psychosocial interventions for affected individuals.

Association between fatigue and depressive symptoms in persons with post-COVID-19 condition: a post hoc analysis.

OBJECTIVE: Post-COVID-19 Condition (PCC) is a prevalent, persistent and debilitating phenomenon occurring three or more months after resolution of acute COVID-19 infection. Fatigue and depressive symptoms are commonly reported in PCC. We aimed to further characterize PCC by assessing the relationship between fatigue and depressive symptom severity in adults with PCC. METHODS: A post hoc analysis was conducted on data retrieved from a randomized, double-blinded, placebo-controlled study evaluating vortioxetine for cognitive deficits in persons with PCC. We sought to determine the relationship between baseline fatigue [i.e. Fatigue Severity Scale (FSS) total score] and baseline depressive symptom severity [i.e. 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR-16) total score] in adults with PCC. RESULTS: The statistical analysis included baseline data from 142 participants. After adjusting for age, sex, education, employment status, history of major depressive disorder (MDD) diagnosis, self-reported physical activity, history of documented acute SARS-CoV-2 infection and body mass index (BMI), baseline FSS was significantly correlated with baseline QIDS-SR-16 (ß = 0.825, p = .001). CONCLUSION: In our sample, baseline measures of fatigue and depressive symptoms are correlated in persons living with PCC. Individuals presenting with PCC and fatigue should be screened for the presence and severity of depressive symptoms. Guideline-concordant care should be prescribed for individuals experiencing clinically significant depressive symptoms. Fatigue and depressive symptom severity scores were not pre-specified as primary objectives of the study. Multiple confounding factors (i.e. disturbance in sleep, anthropometrics and cognitive impairment) were not collected nor adjusted for in the analysis herein. TRIAL REGISTRATION: Unrestricted Research Grant from H. Lundbeck A/S, Copenhagen, Denmark. ClinicalTrials.gov Identifier: NCT05047952.

Association of four metalloids in the serum and urine of individuals with major depressive disorders: a case-control study.

Background: Major depressive disorder (MDD) pathogenesis may involve metalloids in a significant way. The aim of our study was to identify potential links between MDD and metalloid elements [boron (B), germanium (Ge), arsenic (As), antimony (Sb)]. Methods: A total of 72 MDD cases and 75 healthy controls (HCs) were recruited from Zhumadian Second People's Hospital in Henan Province, China. The levels of four metallic elements (B, Ge, As, and Sb) in the serum and urine were measured using inductively coupled plasma mass spectrometry (ICP-MS). Results: In comparison to the HCs, the B, As, and Sb levels were considerably lower in the MDD group (p < 0.05) in the serum; the MDD group had significantly higher (p < 0.05) and significantly lower (p < 0.001) B and Sb levels in the urine. After adjusting for potential confounders, serum B (OR = 0.120; 95% CI, 0.048, 0.300; p < 0.001) and Sb (OR = 0.133; 95% CI, 0.055, 0.322; p < 0.001) showed a negative correlation with MDD. Urine B had a negative correlation (OR = 0.393; 95% CI, 0.193, 0.801; p = 0.01) with MDD, while urine Sb had a positive correlation (OR = 3.335; 95% CI, 1.654, 6.726; p = 0.001) with MDD. Conclusion: Our current research offers insightful hints for future investigation into the function of metalloids in connection to MDD processes.

Comparing suicide completion rates in bipolar I versus bipolar II disorder: A systematic review and meta-analysis.

BACKGROUND: Bipolar disorder (BD) has a high disease burden and the highest mortality risk in BD comes from suicide. Bipolar disorder type II (BD-II) has been described as a milder form of bipolar disorder; however, extant literature is inconsistent with this description and instead describe illness burden and notably suicidality comparable to persons with bipolar I disorder (BD-I). Towards quantifying the hazard of BD-II, herein we aim via systematic review and meta-analysis to evaluate the rates of completed suicide in BD-I and BD-II. METHOD: We conducted a literature search on PubMed, OVID (Embase, Medline) and PsychINFO databases from inception to June 30th, 2023, according to PRISMA guidelines. Articles were selected based on the predetermined eligibility criteria. A meta-analysis was performed, comparing the risk of completed suicide between individuals diagnosed with BD-I to BD-II. RESULTS: Four out of eight studies reported higher suicide completion rates in persons living with BD-II when compared to persons living with BD-I; however, two of the studies reported non-significance. Two studies reported significantly higher suicide completion rates for BD-I than BD-II. The pooled odds ratio of BD-II suicide rates to BD-I was 1.00 [95 % CI = 0.75, 1.34]. LIMITATIONS: The overarching limitation is the small number of studies and heterogeneity of studies that report on suicide completion in BD-I and BD-II. CONCLUSION: Our study underscores the severity of BD-II, with a risk for suicide not dissimilar from BD-I. The greater propensity to depression, comorbidity and rapid-cycling course reported in BD-II are contributing factors to the significant mortality hazard in BD-II.

Association between dual orexin receptor antagonists (DORAs) and suicidality: reports to the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

BACKGROUND: Package inserts for the FDA-approved dual orexin receptor antagonists (DORAs) suvorexant, lemborexant and daridorexant state that suicide risk should be monitored. It remains unknown whether suicidality is attributed to DORAs. We aim to evaluate suicidality associated with DORAs reported to the FDA Adverse Event Reporting System (FAERS). METHODS: The reporting odds ratio (ROR) was determined with trazodone as the control. Significant disproportionate reporting was determined when 95% confidence intervals (CIs) did not encompass 1.0. We used information components (ICs) to calculate the lower limit of the 95% CI (IC025). IC was significantly increased when the IC025 ≥0. RESULTS: Suvorexant (0.025 ROR), lemborexant (0.019 ROR) and daridorexant (0.002 ROR) were significantly associated with lower odds of reported completed suicides compared to trazodone (p < 0.05). There was no significantly increased RORs for the DORAs regarding suicidal ideation, depression suicidal, suicidal behavior and suicide attempts. Nonsignificant associations between all parameters of suicidality were observed for each DORA using IC025. CONCLUSION: We did not find a significant association between any parameter of suicidality captured in the FAERS for each DORA. All persons treated for insomnia pharmacologically/non-pharmacologically should be evaluated for emergence/worsening of any suicidality aspect.

Effects of polyurethane microplastics combined with cadmium on maize growth and cadmium accumulation under different long-term fertilisation histories.

Agricultural production uses different types of fertilisation treatments, typically employing the combined application of organic fertiliser (OF) or organic-inorganic fertiliser (OIF) to improve soil quality. When coupled with cadmium (Cd), microplastics (MPs) affect plant growth and Cd accumulation in soils treated with different fertilisers. This study systematically examined the effects of polyurethane (PU) MPs coupled with Cd on the growth characteristics, root metabolite characteristics, rhizosphere bacterial community structure, and Cd bioavailability of maize under different long-term fertilisation treatments and soil types (red/cinnamon soil). The combined effects of PU MPs and Cd on maize growth differed across fertilisation treatments. Under OF, maize plants accumulated more Cd than under OIF. The accumulation of Cd in maize plants in red soil was twice that in cinnamon soil. Under OF, PU MPs promoted Cd activation by decreasing the soil pH, while root metabolites promoted Cd adsorption sites by synthesising specific amino acids, degrading aromatic compounds, and synthesising pantothenic acid and coenzyme A. Under OF, PU MPs can lower the soil pH to promote the activation of cadmium, while root metabolites promote root growth and increase cadmium adsorption sites by synthesizing specific amino acids, degrading aromatic compounds, and synthesizing pantothenic acid and coenzyme A, hereby promoting root Cd absorption. Under OIF, PU MPs act by influencing the biosynthesis of amino acids in root metabolites, enriching energy metabolism pathways, promoting the transport and translocation of mineral nutrients, thereby amplifying the "toxic effects" of Cd. This study provides new insights into the risk assessment of PU MPs and Cd coupling under different fertilisation treatments, and suggests that the prevention and control of combined PU MPs and Cd pollution in red soil under OF treatment should receive more attention in the future.

Cornus officinalis Sieb. Et Zucc. attenuates Aß25-35-induced mitochondrial damage and neuroinflammation in mice by modulating the ERK pathway.

BACKGROUND: Cornus officinalis Sieb. Et Zucc. has the efficacy of tonifying the marrow and filling up the essence, breaking up the accumulation and opening up the orifices. Our research team found that CoS extracts were protective against Aß25-35-induced memory impairment in mice. However, the pharmacodynamic components and mechanisms by which CoS improves AD have yet to be thoroughly explored and investigated. PURPOSE: This study focused on exploring the bioactive components and pharmacodynamic mechanisms of CoS aqueous extract underlying mitochondrial damage and neuroinflammation to improve Aß25-35-induced AD. METHODS: AD mouse models were generated using Aß25-35 brain injections. Different doses of CoS aqueous extract were orally administered to mice for 28 days. The cognitive function, neuronal and synaptic damage, mitochondrial damage (mitochondrial length, mitochondrial fusion fission-related protein expression), neuroglial activation, and immune inflammatory factor and ERK pathway-related protein levels of mice were assessed. The CoS aqueous extracts components were identified using UPLC-TQ/MS and screened for cellular activity. Midivi-1 (Drp1 inhibitor) or PD98059 (ERK inhibitor) was added to Aß25-35-exposed PC12 cells to assess whether CoS and its active compounds mMorB and CorE regulate mitochondrial fission through ERK/Drp1. PC12-N9 cells were cocultured to investigate whether mMorB and CorE could regulate mitochondrial division through the ERK pathway to modulate neuroinflammation. RESULTS: CoS improved exploration and memory in AD mice, reduced synaptic and mitochondrial damage in their hippocampus, and modulated disturbed mitochondrial dynamics. Moreover, CoS inhibited ERK pathway signaling and attenuated abnormal activation of glial cells and secondary immune inflammatory responses. Additionally, in vitro experiments revealed that CoS and its compounds 7ß-O-methylmorroniside (mMorB) and Cornusdiridoid E (CorE) ameliorated mitochondrial injury caused by Aß25-35 in PC12 cells through inhibition of the ERK/Drp1 pathway. Meanwhile, mMorB and CorE ameliorated cellular inflammation by inhibiting the Ras/ERK/CREB signaling pathway. CONCLUSION: CoS aqueous extract ameliorates behavioral deficits and brain damage in Aß25-35-induced AD mice by modulating the ERK pathway to attenuate mitochondrial damage and neuroinflammation, and the compounds mMorB and CorE are the therapeutically active ingredients.

Oxygen self-sufficient nanodroplet composed of fluorinated polymer for high-efficiently PDT eradicating oral biofilm.

Oral biofilm is the leading cause of dental caries, which is difficult to completely eradicate because of the complicated biofilm structure. What's more, the hypoxia environment of biofilm and low water-solubility of conventional photosensitizers severely restrict the therapeutic effect of photodynamic therapy (PDT) for biofilm. Although conventional photosensitizers could be loaded in nanocarriers, it has reduced PDT effect because of aggregation-caused quenching (ACQ) phenomenon. In this study, we fabricated an oxygen self-sufficient nanodroplet (PFC/TPA@FNDs), which was composed of fluorinated-polymer (FP), perfluorocarbons (PFC) and an aggregation-induced emission (AIE) photosensitizer (Triphenylamine, TPA), to eradicate oral bacterial biofilm and whiten tooth. Fluorinated-polymer was synthesized by polymerizing (Dimethylamino)ethyl methacrylate, fluorinated monomer and 1-nonanol monomer. The nanodroplets could be protonated and behave strong positive charge under bacterial biofilm acid environment promoting nanodroplets deeply penetrating biofilm. More importantly, the nanodroplets had extremely high PFC and oxygen loading efficacy because of the hydrophobic affinity between fluorinated-polymer and PFC to relieve the hypoxia environment and enhance PDT effect. Additionally, compared with conventional ACQ photosensitizers loaded system, PFC/TPA@FNDs could behave superior PDT effect to ablate oral bacterial biofilm under light irradiation due to the unique AIE effect. In vivo caries animal model proved the nanodroplets could reduce dental caries area without damaging tooth structure. Ex vivo tooth whitening assay also confirmed the nanodroplets had similar tooth whitening ability compared with commercial tooth whitener H2O2, while did not disrupt the surface microstructure of tooth. This oxygen self-sufficient nanodroplet provides an alternative visual angle for oral biofilm eradication in biomedicine.