Biomarkers of bipolar disorder based on metabolomics: A systematic review.

Bipolar disorder (BD) is a severe affective disorder characterized by recurrent episodes of depression or mania/hypomania, which significantly impair cognitive function, life skills, and social abilities of patients. There is little understanding of the neurobiological mechanisms of BD. The diagnosis of BD is primarily based on clinical assessment and psychiatric examination, highlighting the urgent need for objective markers to facilitate the diagnosis of BD. Metabolomics can be used as a diagnostic tool for disease identification and evaluation. This study summarized the altered metabolites in BD and analyzed aberrant metabolic pathways, which might contribute to the diagnosis of BD. Search of PubMed and Web of science for human BD studies related to metabolism to identify articles published up to November 19, 2022 yielded 987 articles. After screening and applying the inclusion and exclusion criteria, 16 untargeted and 11 targeted metabolomics studies were included. Pathway analysis of the potential differential biometabolic markers was performed using the Kyoto encyclopedia of genes and genomes (KEGG). There were 72 upregulated and 134 downregulated biomarkers in the untargeted metabolomics studies using blood samples. Untargeted metabolomics studies utilizing urine specimens revealed the presence of 78 upregulated and 54 downregulated metabolites. The targeted metabolomics studies revealed abnormalities in the metabolism of glutamate and tryptophan. Enrichment analysis revealed that the differential metabolic pathways were mainly involved in the metabolism of glucose, amino acid and fatty acid. These findings suggested that certain metabolic biomarkers or metabolic biomarker panels might serve as a reference for the diagnosis of BD.

Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study.

BACKGROUND: Complex immune-brain interactions that affect neural development, survival and function might have causal and therapeutic implications for psychiatric illnesses. However, previous studies examining the association between immune inflammation and schizophrenia (SCZ) have yielded inconsistent findings. METHODS: Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between immune cell signatures and SCZ in this study. Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and SCZ risk. A total of four types of immune signatures (median fluorescence intensities (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP)) were included. Comprehensive sensitivity analyses were used to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. RESULTS: After FDR correction, SCZ had no statistically significant effect on immunophenotypes. It was worth mentioning some phenotypes with unadjusted low P-values, including FSC-A on NKT (ß = 0.119, 95% CI = 0.044 ~ 0.194, P = 0.002), DN (CD4-CD8-) NKT %T cell (ß = 0.131, 95% CI = 0.054 ~ 0.208, P = 9.03 × 10- 4), and SSC-A on lymphocytes (ß = 0.136, 95% CI = 0.059 ~ 0.213, P = 5.43 × 10- 4). The causal effect of SCZ IgD on transitional was estimated to 0.127 (95% CI = 0.051 ~ 0.203, P = 1.09 × 10- 3). SCZ also had a causal effect on IgD+ %B cell (ß = 0.130, 95% CI = 0.054 ~ 0.207, P = 8.69 × 10- 4), and DP (CD4+CD8+) %T cell (ß = 0.131, 95% CI = 0.054 ~ 0.207, P = 8.05 × 10- 4). Furthermore, four immunophenotypes were identified to be significantly associated with SCZ risk: naive CD4+ %T cell (OR = 0.986, 95% CI = 0.979 ~ 0.992, P = 1.37 × 10- 5), HLA DR on CD14- CD16- (OR = 0.738 (95% CI = 0.642 ~ 0.849, P = 2.00 × 10- 5), CD33dim HLA DR+ CD11b- AC (OR = 0.631, 95% CI = 0.529 ~ 0.753, P = 3.40 × 10- 7) and activated & resting Treg % CD4 Treg (OR = 0.937, 95% CI = 0.906 ~ 0.970, P = 1.96 × 10- 4). CONCLUSIONS: Our study has demonstrated the close connection between immune cells and SCZ by genetic means, thus providing guidance for future clinical research.

A case study on the effect of light and colors in the built environment on autistic children's behavior.

Background: The importance of strategies and services by caregivers and family members substantially impact the psychological and emotional wellbeing of autistic children. The rapid research developments in clinical and non-clinical methods benefit the features of autistic children. Among various internal and external factors, the influence of the built environment also impacts the characteristics of autistic children. This study investigates primarily the psychological effect of light and colors on the mood and behavior of autistic children to identify the most favorable and preferred indoor lights and color shades. Methods: A questionnaire survey was conducted at an autism center among autistic children and their parents. This study included autistic children aged between 6 and 16 (45 males, 42 females, mean age 8.7 years, standard deviation 2.3). Eighty-seven participants were involved in the survey to determine the sensory perceptions, intolerance, preferences, and sensitivities of children with an autism spectrum disorder toward colors and lighting. The margin of error at the statistical analysis's 95% confidence level is ± 0.481. Results: As per this case report, the children have various color preferences and respond differently to different shades. Different hues have varying effects on autistic children, with many neutral tones and mellow shades proven to be autistic-friendly with their calming and soothing effect, while bright, bold, and intense colors are refreshing and stimulating. The stimulus of bright-lighting causes behavioral changes in autistic children prone to light sensitivity. Conclusion: The insights gained from this interaction with parents and caretakers of autistic children could be helpful for designers to incorporate specific autistic-friendly design elements that make productive interior spaces. A complete understanding of the effect of factors like color and lighting on the learning ability and engagement of autistic children in an indoor environment is essential for designers and clinicians. The main findings of this study could be helpful for a designer and clinicians to address designing an autism-friendly built environment with a color palette and lighting scheme conducive to their wellbeing and to maximize their cognitive functioning.

Cognitive-behavioral therapy on psychological stress and quality of life in subjects with pulmonary tuberculosis: a community-based cluster randomized controlled trial.

BACKGROUND: Anxiety and depression are two common psychological disorders in patients with pulmonary tuberculosis. We aimed to explore the effects of cognitive-behavioral therapy (CBT) on psychological stress and quality of life in patients with pulmonary tuberculosis. METHODS: From September 2018 to November 2018, 20 communities (461 participants in total) were randomly assigned in an intervention or control group following a two-level cluster random design. The intervention group underwent CBT for 2 months, whereas the control group received routine follow-up. Anxiety, depression, and quality of life were assessed using the Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder questionnaire (GAD-7), and 36-Item Short-Form Health Survey (SF-36) scales, respectively. Comparisons between the two groups were conducted using independent samples t-tests, and differences between the two groups before and after treatment were analyzed using paired samples t-tests. RESULTS: There were a total of 454 participants in the final analysis. After 2 months of CBT intervention, the CBT group had a GAD-7 score that was 1.72 lower than the control group (1.47-1.99, p < 0.001), a PHQ-9 score of the CBT group that was 2.05 lower than that of the control group (1.74-2.37, p < 0.001). The CBT group had a total SF-36 score that was 10.7 lower than that of the control group (95% CI: 7.9-13.5, p < 0.001). In patients with different degrees of anxiety and depression, only those in the intervention group who had mild and moderate anxiety and depression symptoms showed a significant reduction in anxiety and depression scores following the intervention. CONCLUSIONS: CBT can relieve anxiety, and depression symptoms and increase the quality of life in subjects with pulmonary tuberculosis. TRIALS REGISTRATION: ChiCTR-TRC-12001958 Date of Registration: 22/02/2012.

Effects of expressive art therapy on health status of patients with chronic obstructive pulmonary disease: a community-based cluster randomized controlled trial.

BACKGROUND AND OBJECTIVE: This study was performed to investigate the effect of expressive art therapy (EAT) on the health status of patients with chronic obstructive pulmonary disease (COPD). METHODS: This community-based cluster randomized controlled trial involved patients with COPD from 16 communities in China. Participants received either EAT plus usual care (UC) or UC only. General practitioners were trained in EAT before the intervention. The primary outcomes were depression and anxiety symptoms, measured with the Hospital Anxiety and Depression Scale (HADS) and expressed as the HADS score for depression or anxiety (HADS-D or HADS-A, respectively). The secondary outcomes were the quality of life and dyspnoea, measured with the COPD assessment test (CAT). Dyspnoea was assessed using the modified Medical Research Council (mMRC) dyspnoea scale. Lung function was expressed as the forced expiratory volume in 1 s as a percentage of the predicted value [FEV1 (% pred)]. Outcome data were collected from all participants at baseline, 2 and 6 months. RESULTS: In total, 360 participants with COPD and comorbid depression were included in the analysis with the control group of 181 receiving UC only and the intervention group of 179 receiving EAT plus UC. The EAT group showed significantly greater improvement in the HADS-D and HADS-A scores than the UC group at 2 months (p < 0.0001 and p < 0.001, respectively) and 6 months (p < 0.001 for both). The CAT and mMRC scores were significantly lower in the EAT group than in the UC group at 2 and 6 months (p < 0.001 for all). The FEV1 (% pred) was significantly higher in the EAT group than in the UC group at 6 months (p < 0.01). CONCLUSION: General practitioners can deliver EAT interventions. EAT can effectively reduce anxiety and depression symptoms and dyspnoea, improve quality of life and improve the pulmonary function of patients with COPD.

Deep Learning Model for Prediction of Progressive Mild Cognitive Impairment to Alzheimer's Disease Using Structural MRI.

Alzheimer's disease (AD) is an irreversible neurological disorder that affects the vast majority of dementia cases, leading patients to experience gradual memory loss and cognitive function decline. Despite the lack of a cure, early detection of Alzheimer's disease permits the provision of preventive medication to slow the disease's progression. The objective of this project is to develop a computer-aided method based on a deep learning model to distinguish Alzheimer's disease (AD) from cognitively normal and its early stage, mild cognitive impairment (MCI), by just using structural MRI (sMRI). To attain this purpose, we proposed a multiclass classification method based on 3D T1-weight brain sMRI images from the ADNI database. Axial brain images were extracted from 3D MRI and fed into the convolutional neural network (CNN) for multiclass classification. Three separate models were tested: a CNN built from scratch, VGG-16, and ResNet-50. As a feature extractor, the VGG-16 and ResNet-50 convolutional bases trained on the ImageNet dataset were employed. To achieve classification, a new densely connected classifier was implemented on top of the convolutional bases.

Effects of cognitive behavioral therapy on sleep disturbances and quality of life among adults with type 2 diabetes mellitus: A randomized controlled trial.

BACKGROUND AND AIMS: Cognitive behavioral therapy (CBT) is recommended as the first-line nonpharmacotherapy for sleep complaints. However, there are no studies that tested CBT for improving sleep quality and increasing quality of life (QOL) in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aims to test the effect of CBT on sleep disturbances and QOL in patients with T2DM. METHODS AND RESULTS: In total, 187 participants with T2DM and comorbid poor sleep quality were included in the analysis with the control group of 93 receiving usual care (UC) only and the intervention group of 94 receiving CBT with aerobic exercise plus UC, The Pittsburgh Sleep Quality Index (PSQI), the Diabetes-Specific Quality of Life Scale (DSQLS) and the glycated hemoglobin (HbA1C) values were collected at baseline, after the 2-month intervention, and 6 months of follow-up. The CBT group had 3.03 points lower PSQI scores (95% confidence interval [CI]: 2.07-4.00, P < 0.001) and 7.92 points lower total DSQLS scores (95% CI: 4.98-10.87, P < 0.001) than the control group after 6-month follow-up. No difference was found in HbAlc between the two groups (t = -0.47, P = 0.64) after 2-month intervention, while the CBT group had 0.89 units lower HbAlc (95% CI: 0.49-1.28, P < 0.001) than the control group after 6-month follow-up. CONCLUSION: CBT is effective for sleep disturbances and can also improve sleep quality, increase QOL, and decrease glycemic levels in participants with T2DM. TRIAL REGISTRATION: Chinese Clinical Trials Registration (Practical study of the appropriate technique for improvement of quality of life of the patients with type 2 diabetes in communities: ChiCTR-IOP-16008045).

Co-Precipitation, Strength and Electrical Resistivity of Cu-26 wt % Ag-0.1 wt % Fe Alloy.

Both a Cu-26 wt % Ag (Fe-free) alloy and Cu-26 wt % Ag-0.1 wt % Fe (Fe-doping) alloy were subjected to different heat treatments. We studied the precipitation kinetics of Ag and Cu, microstructure evolution, magnetization, hardness, strength, and electrical resistivity of the two alloys. Fe addition was incapable of changing the precipitation kinetics of Ag and Cu; however, it decreased the size and spacing of rod-shaped Ag precipitates within a Cu matrix, because Fe might affect the elastic strain field and diffusion field, suppressing the nucleation of Ag precipitates. Magnetization curves showed that γ-Fe precipitates were precipitated out of the Cu matrix, along with Ag precipitates in Fe-doping alloy after heat treatments. The yield strength of the Fe-doping alloy was higher than that of the Fe-free alloy, and the maximum increment was about 41.3%. The electrical conductivity in the aged Fe-doping alloy was up to about 67% IACS (International Annealed Copper Standard). Hardness, strength, and electrical resistivity were intensively discussed, based on the microstructural characterization and solute contributions of both alloys. Our results demonstrated that an increasing fraction of nanoscale γ-Fe precipitates and decreasing spacing between Ag precipitates resulted in the increasing strength of the Fe-doping alloy.

Numerical Simulation of Droplets Behavior of Cu-Pb Immiscible Alloys Solidifying under Magnetic Field.

A model has been presented for the coarsening of the dispersed phase of liquid-liquid two-phase mixtures in Cu-Pb alloys under the effect of a high magnetic field (HMF). The numerical results show that the evolution of size distribution is the result of several factors and the diffusional growth, the collision-coagulation of the Cu-rich droplets (gravity sedimentation and Marangoni migration), and melt flow also have obvious effects on the movement of droplets and coarsening process. The effect of the HMF in the coarsening process of Cu-Pb alloy is studied in this work both by simulation and experiment. The analysis shows that the HMF leads to a decrease in the melt flow velocity, and can also lead to a decrease in the moving velocity of Cu-rich droplets. The HMF significantly reduces the coarsening rate of droplets as compared by the distribution evolutions. Finally, it is shown that droplet collision and coagulation can be dramatically retarded by the HMF. The results of the simulation are compared with the experiments performed with immiscible Cu-Pb alloys, and the discrepancy between theory and experiment is discussed.

Influence of grain boundary characteristics on thermal stability in nanotwinned copper.

High density grain boundaries provide high strength, but may introduce undesirable features, such as high Fermi levels and instability. We investigated the kinetics of recovery and recrystallization of Cu that was manufactured to include both nanotwins (NT) and high-angle columnar boundaries. We used the isothermal Johnson-Mehl-Avrami-Kolmogorov (JMAK) model to estimate activation energy values for recovery and recrystallization and compared those to values derived using the non-isothermal Kissinger equation. The JMAK model hinges on an exponent that expresses the growth mechanism of a material. The exponent for this Cu was close to 0.5, indicating low-dimensional microstructure evolution, which is associated with anisotropic twin coarsening, heterogeneous recrystallization, and high stability. Since this Cu was of high purity, there was a negligible impurity-drag-effect on boundaries. The twin coarsening and heterogeneous recrystallization resulted from migration of high-angle columnar boundaries with their triple junctions in one direction, assisted by the presence of high concentration vacancies at boundaries. Analyses performed by electron energy loss spectroscopy of atomic columns at twin boundaries (TBs) and in the interior showed similar plasma peak shapes and L3 edge positions. This implies that values for conductivity and Fermi level are equal for atoms at TBs and in the interior.

Influence of Growth Rate and Magnetic Field on Microstructure and Properties of Directionally Solidified Ag-Cu Eutectic Alloy.

We report the influence of growth rate and external magnetic field on the eutectic lamellar spacing and properties of directionally-solidified Ag-Cu eutectic alloys. The results indicated that the relationship between the lamellar spacing of directionally-solidified Ag-Cu alloys and the growth rate matched the prediction of the Jackson-Hunt model, and the constant was 5.8 µm³/s. The increasing external magnetic field during solidification tilted the growth direction of the lamellar eutectics, and coarsened the eutectic lamellar spacing. These decreased the microhardness and strength of Ag-Cu alloys, but increased their electrical conductivity. The competitive strengthening contributions between the refinement of the eutectic lamellar spacing and the change in growth direction of the eutectics resulted in higher strength in the as-rolled sample with a 0.8 T magnetic field than with other samples, which was confirmed from higher relieved deformation energy using differential scanning calorimetry.