RESUMO
The outer membrane structure is common in Gram-negative bacteria, mitochondria and chloroplasts, and contains outer membrane ß-barrel proteins (OMPs) that are essential interchange portals of materials1-3. All known OMPs share the antiparallel ß-strand topology4, implicating a common evolutionary origin and conserved folding mechanism. Models have been proposed for bacterial ß-barrel assembly machinery (BAM) to initiate OMP folding5,6; however, mechanisms by which BAM proceeds to complete OMP assembly remain unclear. Here we report intermediate structures of BAM assembling an OMP substrate, EspP, demonstrating sequential conformational dynamics of BAM during the late stages of OMP assembly, which is further supported by molecular dynamics simulations. Mutagenic in vitro and in vivo assembly assays reveal functional residues of BamA and EspP for barrel hybridization, closure and release. Our work provides novel insights into the common mechanism of OMP assembly.
Assuntos
Proteínas da Membrana Bacteriana Externa , Proteínas de Escherichia coli , Escherichia coli , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/metabolismo , Escherichia coli/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Simulação de Dinâmica Molecular , Dobramento de Proteína , Especificidade por SubstratoRESUMO
The peptidoglycan (PG) layer is a critical component of the bacterial cell wall and serves as an important target for antibiotics in both gram-negative and gram-positive bacteria. The hydrolysis of septal PG (sPG) is a crucial step of bacterial cell division, facilitated by FtsEX through an amidase activation system. In this study, we present the cryo-EM structures of Escherichia coli FtsEX and FtsEX-EnvC in the ATP-bound state at resolutions of 3.05 Å and 3.11 Å, respectively. Our PG degradation assays in E. coli reveal that the ATP-bound conformation of FtsEX activates sPG hydrolysis of EnvC-AmiB, whereas EnvC-AmiB alone exhibits autoinhibition. Structural analyses indicate that ATP binding induces conformational changes in FtsEX-EnvC, leading to significant differences from the apo state. Furthermore, PG degradation assays of AmiB mutants confirm that the regulation of AmiB by FtsEX-EnvC is achieved through the interaction between EnvC-AmiB. These findings not only provide structural insight into the mechanism of sPG hydrolysis and bacterial cell division, but also have implications for the development of novel therapeutics targeting drug-resistant bacteria.
Assuntos
Trifosfato de Adenosina , Divisão Celular , Proteínas de Escherichia coli , Escherichia coli , Peptidoglicano , Peptidoglicano/metabolismo , Hidrólise , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/química , Escherichia coli/metabolismo , Escherichia coli/genética , Trifosfato de Adenosina/metabolismo , Microscopia Crioeletrônica , Parede Celular/metabolismo , Conformação Proteica , Modelos Moleculares , N-Acetil-Muramil-L-Alanina Amidase/metabolismo , N-Acetil-Muramil-L-Alanina Amidase/genética , Proteínas da Membrana Bacteriana Externa , Transportadores de Cassetes de Ligação de ATP , Regulador de Condutância Transmembrana em Fibrose Cística , Lipoproteínas , Proteínas de Ciclo CelularRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) are autoimmune diseases that often coexist clinically. This phenomenon might be due to shared genetic components. METHODS: Genome-wide association study (GWAS) data for IBD and SLE were analyzed to determine both global and local genetic correlations using three methodologies: linkage disequilibrium score regression (LDSC), genetic covariance analyzer (GNOVA), and SUPERGNOVA. The genetic overlap and risk loci were subsequently examined using the conditional/conjunctional false discovery rate (cond/conjFDR) statistical framework. Furthermore, a multi-trait analysis of MTAG was employed to validate the loci, followed by an LDSC analysis focusing on tissue-specific gene expression. RESULTS: GWAS findings demonstrated a marked global genetic correlation between IBD (including Crohn's disease and ulcerative colitis) and SLE. Locally, SLE showed a strong association with IBD and Crohn's disease on chromosomes 10, 19, and 22. ConjFDR analysis confirmed the genetic overlap and identified relevant genetic risk loci. MTAG further validated several shared susceptibility genes. Additionally, the LDSC-SEG analysis results indicate that IBD (including CD and UC) and SLE are jointly enriched in the tissues of Spleen and Whole Blood. CONCLUSION: This study confirms a genetic overlap between IBD and SLE, identifying marked comorbid genes and offering new insights for treating these diseases.
Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Doenças Inflamatórias Intestinais , Desequilíbrio de Ligação , Lúpus Eritematoso Sistêmico , Lúpus Eritematoso Sistêmico/genética , Humanos , Doenças Inflamatórias Intestinais/genética , Polimorfismo de Nucleotídeo Único , Locos de Características QuantitativasRESUMO
In Alzheimer's disease (AD) brain, inflammatory activation regulates protein levels of amyloid-ß-peptide (Aß) and phosphorylated tau (p-tau), as well as neurodegeneration; however, the regulatory mechanisms remain unclear. We constructed APP- and tau-transgenic AD mice with deletion of IKKß specifically in neurons, and observed that IKKß deficiency reduced cerebral Aß and p-tau, and modified inflammatory activation in both AD mice. However, neuronal deficiency of IKKß decreased apoptosis and maintained synaptic proteins (e.g., PSD-95 and Munc18-1) in the brain and improved cognitive function only in APP-transgenic mice, but not in tau-transgenic mice. Additionally, IKKß deficiency decreased BACE1 protein and activity in APP-transgenic mouse brain and cultured SH-SY5Y cells. IKKß deficiency increased expression of PP2A catalytic subunit isoform A, an enzyme dephosphorylating cerebral p-tau, in the brain of tau-transgenic mice. Interestingly, deficiency of IKKß in neurons enhanced autophagy as indicated by the increased ratio of LC3B-II/I in brains of both APP- and tau-transgenic mice. Thus, IKKß deficiency in neurons ameliorates AD-associated pathology in APP- and tau-transgenic mice, perhaps by decreasing Aß production, increasing p-tau dephosphorylation, and promoting autophagy-mediated degradation of BACE1 and p-tau aggregates in the brain. However, IKKß deficiency differently protects neurons in APP- and tau-transgenic mice. Further studies are needed, particularly in the context of interaction between Aß and p-tau, before IKKß/NF-κB can be targeted for AD therapies.
Assuntos
Doença de Alzheimer , Neuroblastoma , Humanos , Camundongos , Animais , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Quinase I-kappa B , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/metabolismo , Neurônios/metabolismo , Modelos Animais de DoençasRESUMO
BACKGROUND: Inflammatory bowel disease (IBD), a chronic inflammatory condition, is caused by several factors involving aberrant immune responses. Genetic factors are crucial in IBD occurrence. Mendelian randomization (MR) can offer a new perspective in understanding IBD's genetic background. METHODS: Single nucleotide polymorphisms (SNPs) were considered instrumental variables (IVs). We analyzed the relationship between 731 immunophenotypes, 1,400 metabolite phenotypes, and IBD. The total effect was decomposed into indirect and direct effects, and the ratio of the indirect effect to the total effect was calculated. RESULTS: We identified the causal effects of HLA-DR-expressing CD14 + monocytes on IBD through MR analysis. The phenotype "HLA-DR expression on CD14 + monocytes" showed the strongest association among the selected 48 immune phenotypes. Chiro-inositol metabolites mediated the effect of CD14 + monocytes expressing HLA-DR on IBD. An increase in Chiro-inositol metabolites was associated with a reduced risk of IBD occurrence, accounting for 4.97%. CONCLUSION: Our findings revealed a new pathway by which HLA-DR-expressing CD14 + monocytes indirectly reduced the risk of IBD occurrence by increasing the levels of Chiro-inositol metabolites. The results provided a new perspective on the immunoregulatory mechanisms underlying IBD, laying a theoretical foundation for developing new therapeutic targets in the future.
Assuntos
Antígenos HLA-DR , Doenças Inflamatórias Intestinais , Inositol , Receptores de Lipopolissacarídeos , Monócitos , Polimorfismo de Nucleotídeo Único , Humanos , Monócitos/metabolismo , Monócitos/imunologia , Receptores de Lipopolissacarídeos/metabolismo , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Antígenos HLA-DR/genética , Antígenos HLA-DR/metabolismo , Inositol/metabolismo , Análise da Randomização Mendeliana , Fenótipo , Imunofenotipagem , Feminino , MasculinoRESUMO
BACKGROUND: Prior studies have identified a correlation between breakfast skipping and a heightened risk of mental health issues. This investigation aimed to employ a Two-Sample Mendelian Randomization (MR) approach to explore the potential causal links between breakfast skipping and various psychiatric, neurological disorders, cognitive performance, and frailty. METHODS: Utilizing data from genome-wide association studies within European demographics, this research scrutinized the association between breakfast habits and several neuropsychiatric conditions and physical health outcomes, including Alzheimer's disease (AD), Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BD), Major Depressive Disorder (MDD), Narcolepsy, Insomnia, cognitive performance, and frailty. In this MR analysis, the Inverse Variance Weighted (IVW) method was primarily utilized for evaluation. Outcomes were reported as Odds Ratios (OR) and regression coefficients (ß), and underwent validation through False Discovery Rate (FDR) corrections, thereby offering a rigorous evaluation of the effects of breakfast habits on both mental and physical health dimensions. RESULTS: Findings demonstrate a significant causal link between skipping breakfast and an increased risk of ADHD (OR = 2.74, 95%CI: 1.54-4.88, PFDR = 0.003) and MDD (OR = 1.7, 95%CI: 1.22-2.37, PFDR = 0.005). Conversely, no substantial causal associations were identified between breakfast skipping and AD, BD, narcolepsy, or insomnia (PFDR > 0.05). Moreover, a notable causal relationship was established between skipping breakfast and a reduction in cognitive performance (ß = -0.16, 95%CI: -0.29-0.04, PFDR = 0.024) and an increase in frailty (ß = 0.29, 95%CI: 0.12-0.45, PFDR = 0.003). CONCLUSION: The MR analysis reveals that skipping breakfast is associated with an increased risk of ADHD, MDD, decreased cognitive performance, and greater frailty, while showing no associations were found with AD, BD, narcolepsy, or insomnia. These findings warrant further investigation into the underlying mechanisms and emphasize the importance of regular breakfast consumption for mental and physical well-being.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Transtorno Depressivo Maior , Fragilidade , Narcolepsia , Distúrbios do Início e da Manutenção do Sono , Humanos , Desjejum , Estudo de Associação Genômica Ampla , Jejum Intermitente , Análise da Randomização MendelianaRESUMO
BACKGROUND: Observational studies and diagnostic criteria have indicated that Attention Deficit Hyperactivity Disorder (ADHD) frequently comorbid with various psychiatric disorders. Therefore, we conducted a Mendelian randomization (MR) study to explore this potential genetic association between ADHD and six psychiatric disorders. METHODS: Using a two-sample Mendelian randomization (MR) design, this study systematically screened genetic instrumental variables (IVs) based on the genome-wide association studies (GWAS) of ADHD and six psychiatric disorders, with the inverse variance weighted (IVW) method as the primary approach. RESULTS: The study revealed a positive and causal association between ADHD and the risk of ASD, with an odds ratio (OR) of 2.328 (95%CI: 1.241-4.368) in the IVW MR analysis. Additionally, ADHD showed a positive causal effect on an increased risk of schizophrenia, with an OR of 1.867 (95%CI: 1.260-2.767) in the IVW MR analysis. However, no causal effect of Tic disorder, Mental retardation, Mood disorders and Anxiety disorder with ADHD was found in the analysis mentioned above. CONCLUSION: Our MR analysis provides robust evidence of the causal role of ADHD in increasing the risk of ASD and schizophrenia. However, ADHD is not associated with the risk of Tic Disorder, Mental Retardation, Mood Disorders and Anxiety Disorder. This suggests the need for increased attention to the co-occurrence of ADHD-ASD or ADHD-schizophrenia and the implementation of timely intervention and treatment.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Deficiência Intelectual , Transtornos de Tique , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Estudo de Associação Genômica Ampla , Análise da Randomização MendelianaRESUMO
BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children, and adalimumab is one of the primary treatment options. Although it is widely used for inflammatory diseases, there is limited research on its safety and efficacy in patients with psychiatric disorders or in those with inflammatory diseases who also have comorbid psychiatric conditions. CASE REPORT: We report a 12-year-old adolescent boy who presented with emotional instability for 1 year, exacerbated leading to hospital admission in the past month. Upon detailed evaluation after admission, it was found that the patient's emotional fluctuations may be related to the use of Adalimumab. Follow-up after psychiatric inpatient treatment revealed that the patient did not experience emotional excitement again after discontinuing Adalimumab. CONCLUSIONS: Although tumor necrosis factor-α inhibitors have positive effects on the emotional, cognitive, and physical functions of patients with inflammatory diseases, their use may induce mood swings in patients with comorbid mood disorders. This is particularly important for adolescents with rapid mood changes, where greater caution is required. Further research is necessary to clarify the correlation between the adverse effects of these drugs and their impact on patients with bipolar disorder.
Assuntos
Adalimumab , Antirreumáticos , Artrite Juvenil , Transtorno Bipolar , Humanos , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/complicações , Masculino , Adalimumab/efeitos adversos , Adalimumab/uso terapêutico , Criança , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Mania/induzido quimicamente , AdolescenteRESUMO
BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for depressive disorder. However, the use of ECT is limited by its cognitive side effects (CSEs), and no specific intervention has been developed to address this problem. As transcranial direct current stimulation (tDCS) is a safe and useful tool for improving cognitive function, the main objective of this study was to explore the ability to use tDCS after ECT to ameliorate the cognitive side effects. METHODS: 60 eligible participants will be recruited within two days after completing ECT course and randomly assigned to receive either active or sham stimulation in a blinded, parallel-design trial and continue their usual pharmacotherapy. The tDCS protocol consists of 30-min sessions at 2 mA, 5 times per week for 2 consecutive weeks, applied through 15-cm2 electrodes. An anode will be placed over the left dorsolateral prefrontal cortex (DLPFC), and a cathode will be placed over the right supraorbital cortex. Cognitive function and depressive symptoms will be assessed before the first stimulation (T0), after the final stimulation (T1), 2 weeks after the final stimulation (T2), and 4 weeks after the final stimulation (T3) using the Cambridge Neuropsychological Test Automated Battery (CANTAB). DISCUSSION: We describe a novel clinical trial to explore whether the administration of tDCS after completing ECT course can accelerates recovery from the CSEs. We hypothesized that the active group would recover faster from the CSEs and be superior to the sham group. If our hypothesis is supported, the use of tDCS could benefit eligible patients who are reluctant to receive ECT and reduce the risk of self-inflicted or suicide due to delays in treatment. TRIAL REGISTRATION DETAILS: The trial protocol is registered with https://www.chictr.org.cn/ under protocol registration number ChiCTR2300071147 (date of registration: 05.06.2023). Recruitment will start in November 2023.
Assuntos
Eletroconvulsoterapia , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Eletroconvulsoterapia/efeitos adversos , Depressão/terapia , Córtex Pré-Frontal/fisiologia , Cognição , Método Duplo-Cego , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) and psoriasis (Ps) are common immune-mediated diseases that exhibit clinical comorbidity, possibly due to a common genetic structure. However, the exact mechanism remains unknown. METHODS: The study population consisted of IBD and Ps genome-wide association study (GWAS) data. Genetic correlations were first evaluated. Then, the overall evaluation employed LD score regression (LDSC), while the local assessment utilized heritability estimation from summary statistics (HESS). Causality assessment was conducted through two-sample Mendelian randomization (2SMR), and genetic overlap analysis utilized the conditional false discovery rate/conjunctional FDR (cond/conjFDR) method. Finally, LDSC applied to specifically expressed genes (LDSC-SEG) was performed at the tissue level. For IBD and Ps-specific expressed genes, genetic correlation, causality, shared genetics, and trait-specific associated tissues were methodically examined. RESULTS: At the genomic level, both overall and local genetic correlations were found between IBD and Ps. MR analysis indicated a positive causal relationship between Ps and IBD. The conjFDR analysis with a threshold of < 0.01 identified 43 loci shared between IBD and Ps. Subsequent investigations into disease-associated tissues indicated a close association of IBD and Ps with whole blood, lung, spleen, and EBV-transformed lymphocytes. CONCLUSION: The current research offers a novel perspective on the association between IBD and Ps. It contributes to an enhanced comprehension of the genetic structure and mechanisms of comorbidities in both diseases.
Assuntos
Doenças Inflamatórias Intestinais , Psoríase , Humanos , Estudo de Associação Genômica Ampla , Psoríase/genética , Pele , Doenças Inflamatórias Intestinais/genética , Expressão GênicaRESUMO
Geomagnetic matching navigation is extensively utilized for localization and navigation of autonomous robots and vehicles owing to its advantages such as low cost, wide-area coverage, and no cumulative errors. However, due to the influence of magnetometer measurement noise, geomagnetic localization algorithms based on single-point particle filters may encounter mismatches during continuous operation, consequently limiting their long-range localization performance. To address this issue, this paper proposes a real-time sequential particle filter-based geomagnetic localization method. Firstly, this method mitigates the impact of noise during continuous operation while ensuring real-time performance by performing real-time sequential particle filtering. Then, it enhances the long-range positioning accuracy of the method by rectifying the trajectory shape of the odometry through odometry calibration parameters. Finally, by performing secondary matching on the preliminary matching results via the MAGCOM algorithm, the positioning error of the method is further minimized. Experimental results show that the proposed method has higher positioning accuracy compared to related algorithms, resulting in reductions of over 28.58%, 37.11%, and 0.77% in RMSE, max error, and error at the end, respectively.
RESUMO
BACKGROUND: Subacute combined degeneration of the spinal cord (SCD) is mainly caused by deficiency of Vitamin B12 and characterized by deep hypoesthesia, sensory ataxia and spasmodic paralysis of lower limbs. SCD often accompanies with megaloblastic anemia. Psychiatric symptoms could be the initial manifestations of SCD by lack of Vitamin B12, but are rarely considered secondary to physical discomfort and psychological factors in SCD. Additionally, treatment experience for psychiatric symptoms in SCD remains little reported. CASE REPORT: We presented a case of a 37-year-old female who complained of being persecuted and controlled for one week and thus was admitted to the psychiatry department. Before that, she had went through persistent paresthesia and numbness of her lower extremities for two-month. Low Vitamin B12 level and hemoglobin concentration, neurologic symptoms and bone marrow smear results supported the clinical diagnosis of SCD and megaloblastic anemia. With supplementation of Vitamin B12 and blood transfusion and short-term prescription of antipsychotics and antidepressants, physical symptoms were improved and psychological symptoms disappeared within 2 weeks. CONCLUSIONS: Psychiatric symptoms of SCD could be generated from lack of Vitamin B12, anemia and neurologic symptoms, where short-term use of antipsychotics and antidepressants may be effective.
Assuntos
Anemia Megaloblástica , Antipsicóticos , Degeneração Combinada Subaguda , Feminino , Humanos , Adulto , HospitalizaçãoRESUMO
BACKGROUND: Prior observational studies have identified a relationship between the composition of gut microbiota and the onset of acne. To ascertain the causal relationship underlying this association, we adopted the Mendelian randomization (MR) method, which offers a powerful approach to causal inference. METHODS: Summary statistics on gut microbiota and acne were obtained from the MiBioGen and FinnGen consortium, respectively. The causal relationship was assessed using multiple methods in a two-sample framework, including MR Egger, weighted median, inverse variance weighted (IVW), and weighted mode. Furthermore, the heterogeneity and horizontal pleiotropy analyses were conducted, along with the leave-one-out method. RESULTS: The IVW estimation indicated that Allisonella (odds ratio [OR] = 1.42, 95% confidence interval [CI] = 1.18-1.70, p = 0.0002) and Bacteroides (OR = 2.25, 95% CI = 1.48-3.42, p = 0.0001) have adverse effects on acne. By contrast, Ruminococcus torques group (OR = 0.41, 95% CI = 0.25-0.65, p = 0.0002) showed a beneficial effect on acne. In addition, Candidatus soleaferrea (OR = 0.75, 95% CI = 0.60-0.95, p = 0.0149), Eubacterium coprostanoligenes group (OR = 0.67, 95% CI = 0.47-0.95, p = 0.0230), Fusicatenibacter (OR = 0.71, 95% CI = 0.52-0.97, p = 0.02897), and Lactobacillus (OR = 0.72, 95% CI = 0.58-0.90, p = 0.0046) showed suggestive associations with acne. CONCLUSION: The present investigation suggests a causal effect of gut microbiota on acne.
Assuntos
Acne Vulgar , Microbioma Gastrointestinal , Humanos , Análise da Randomização Mendeliana , Acne Vulgar/genéticaRESUMO
In industrial production, it is very difficult to make a robot plan a safe, collision-free, smooth path with few inflection points. Therefore, this paper presents a safe heuristic path-planning method based on a search strategy. This method first expands the scope of the search node, then calculates the node state based on the search strategy, including whether it is a normal or dangerous state, and calculates the danger coefficient of the corresponding point to select the path with a lower danger coefficient. At the same time, the optimal boundary is obtained by incorporating the environmental facilities, and the optimal path between the starting point, the optimal boundary point and the end point is obtained. Compared to the traditional A-star algorithm, this method achieved significant improvements in various aspects such as path length, execution time, and path smoothness. Specifically, it reduced path length by 2.89%, decreased execution time by 13.98%, and enhanced path smoothness by 93.17%. The resulting paths are more secure and reliable, enabling robots to complete their respective tasks with reduced power consumption, thereby mitigating the drain on robot batteries.
RESUMO
Surgical site wound infection is one of the most common postoperative complications in orthopaedic clinical practice. This study employed a meta-analysis approach to comprehensively evaluate the effect of operating room nursing interventions on the prevention of surgical site wound infections in orthopaedic surgical patients. A computer search was conducted using PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP, and Wanfang databases from the inception of each database until May 2023 for randomised controlled trials (RCTs) that investigated the application of operating room nursing interventions in orthopaedic surgery. Two reviewers independently screened the literature, extracted data, and assessed study quality. The meta-analysis was conducted using Stata 17.0. A total of 29 studies involving 3567 patients were included, with 1784 patients in the intervention group, and 1783 patients in the control group. The results of the meta-analysis showed that compared with the control group, the use of operating room nursing interventions significantly reduced the incidence of surgical site wound infection after orthopaedic surgery (2.85% vs. 13.24%; odds ratio: 0.18, 95% confidence interval: 0.14-0.25; p < 0.001). Current evidence suggests that operating room nursing interventions reduce the incidence of surgical site wound infections. However, owing to the limited number and low quality of the studies, more high-quality, large-sample RCTs are needed to further verify these findings.
Assuntos
Procedimentos Ortopédicos , Ortopedia , Humanos , Salas Cirúrgicas , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Procedimentos Ortopédicos/efeitos adversos , ChinaRESUMO
Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.
Assuntos
Transtorno Depressivo Maior , Encéfalo , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética/métodos , Vias Neurais , Tamanho da AmostraRESUMO
BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.
Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.
Assuntos
Encéfalo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Mapeamento Encefálico/métodos , China , Conectoma/métodos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Vias Neurais/fisiopatologia , Descanso/fisiologiaRESUMO
As a classic positioning algorithm with a simple principle and low computational complexity, the trilateration positioning algorithm utilizes the coordinates of three anchor nodes to determine the position of an unknown node, which is widely applied in various positioning scenes. However, due to the environmental noise, environmental interference, the distance estimation error, the uncertainty of anchor nodes' coordinates, and other negative factors, the positioning error increases significantly. For this problem, we propose a new trilateration algorithm based on the combination and K-Means clustering to effectively remove the positioning results with significant errors in this paper, which makes full use of the position and distance information of the anchor nodes in the area. In this method, after analyzing the factors affecting the optimization of the trilateration and selecting optimal parameters, we carry out experiments to verify the effectiveness and feasibility of the proposed algorithm. We also compare the positioning accuracy and positioning efficiency of the proposed algorithm with those of other algorithms in different environments. According to the comparison of the least-squares method, the maximum likelihood method, the classical trilateration and the proposed trilateration, the results of the experiments show that the proposed trilateration algorithm performs well in the positioning accuracy and efficiency in both light-of-sight (LOS) and non-light-of-sight (NLOS) environments. Then, we test our approach in three realistic environments, i.e., indoor, outdoor and hall. The experimental results show that when there are few available anchor nodes, the proposed localization method reduces the mean distance error compared with the classical trilateration, the least-squares method, and the maximum likelihood.
RESUMO
In wireless sensor networks, due to the significance of the location information of mobile nodes for many applications, location services are the basis of many application scenarios. However, node state and communication uncertainty affect the distance estimation and position calculation of the range-based localization method, which makes it difficult to guarantee the localization accuracy and the system robustness of the distributed localization system. In this paper, we propose a distributed localization method based on anchor nodes selection and particle filter optimization. In this method, we first analyze the uncertainty of error propagation to the least-squares localization method. According to the proportional relation between localization error and uncertainty propagation, anchor nodes are selected optimally in real-time during the movement of mobile nodes. Then we use the ranging and position of the optimally selected anchor nodes to obtain the location information of the mobile nodes. Finally, the particle filter (PF) algorithm is utilized to gain the optimal estimation of the localization results. The experimental evaluation results verified that the proposed method effectively improves the localization accuracy and the robustness of the distributed system.