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Inflammation plays a crucial role in the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). This study aimed to examine whether the dysregulation of complement components contributes to brain structural defects in patients with mood disorders.
A total of 52 BD patients, 35 MDD patients, and 53 controls were recruited. The human complement immunology assay was used to measure the levels of complement factors. Whole brain-based analysis was performed to investigate differences in gray matter volume (GMV) and cortical thickness (CT) among the BD, MDD, and control groups, and relationships were explored between neuroanatomical differences and levels of complement components.
GMV in the medial orbital frontal cortex (mOFC) and middle cingulum was lower in both patient groups than in controls, while the CT of the left precentral gyrus and left superior frontal gyrus were affected differently in the two disorders. Concentrations of C1q, C4, factor B, factor H, and properdin were higher in both patient groups than in controls, while concentrations of C3, C4 and factor H were significantly higher in BD than in MDD. Concentrations of C1q, factor H, and properdin showed a significant negative correlation with GMV in the mOFC at the voxel-wise level.
BD and MDD are associated with shared and different alterations in levels of complement factors and structural impairment in the brain. Structural defects in mOFC may be associated with elevated levels of certain complement factors, providing insight into the shared neuro-inflammatory pathogenesis of mood disorders.
Pharmacological treatment of major depressive disorder is often inefficient, and multiple strategies are used for inadequate response to antidepressants. Second-generation antipsychotics are used as augmentation measures in clinical practice; evidence of their efficacy and acceptability is insufficient, and it remains confusing as to which drug should be selected first. In this systematic review and network meta-analysis, we included randomised controlled trials of second-generation antipsychotics used as adjunctive treatment in patients with suboptimal responses. Outcome measures were efficacy (response and remission) and acceptability (dropout due to any reason and adverse events). Thirty-three trials comprising 10 602 participants were included. Regarding efficacy, response rates indicated that all antipsychotics except for ziprasidone were more efficacious than the placebo, with the odds ratios (ORs) ranging from 1.34 for olanzapine and cariprazine [95% credible interval (CrI) 1.04–1.73 and 1.07–1.67, respectively] to 2.17 for risperidone (95% CrI 1.38–3.42). When considering remission, cariprazine was not effective (OR 1.21, 95% CrI 0.96–1.54). For acceptability, quetiapine (OR 0.68, 95% CrI 0.50–0.91), brexpiprazole (OR 0.69, 95% CrI 0.55–0.86), and cariprazine (OR 0.61, 95% CrI 0.46–0.82) were worse than the placebo. With regards to tolerability, only olanzapine (OR 0.51, 95% CrI 0.25–1.07) and risperidone (OR 0.48, 95% CrI 0.10–2.21) showed no significant differences compared with placebo. The administration of adjunctive antipsychotics is associated with high effectiveness and low acceptability. Risperidone and aripiprazole are more efficacious and accepted than other atypical antipsychotics.
Grey matter (GM) reduction is a consistent observation in established late stages of schizophrenia, but patients in the untreated early stages of illness display an increase as well as a decrease in GM distribution relative to healthy controls (HC). The relative excess of GM may indicate putative compensatory responses, though to date its relevance is unclear.
343 first-episode treatment-naïve patients with schizophrenia (FES) and 342 HC were recruited. Multivariate source-based morphometry was performed to identify covarying ‘networks' of grey matter concentration (GMC). Neurocognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and symptom burden using the Positive and Negative Symptoms Scale (PANSS) were obtained. Bivariate linear relationships between GMC and cognition/symptoms were studied.
Compared to healthy subjects, FES had prominently lower GMC in two components; the first consists of the anterior insula, inferior frontal gyrus, anterior cingulate and the second component with the superior temporal gyrus, precuneus, inferior/superior parietal lobule, cuneus, and lingual gyrus. Higher GMC was seen in adjacent areas of the middle and superior temporal gyrus, middle frontal gyrus, inferior parietal cortex and putamen. Greater GMC of this component was associated with lower duration of untreated psychosis, less severe positive symptoms and better performance on cognitive tests.
In untreated stages of schizophrenia, both a distributed lower and higher GMC is observable. While the higher GMC is relatively modest, it occurs across frontoparietal, temporal and subcortical regions in association with reduced illness burden suggesting a compensatory role for higher GMC in the early stages of schizophrenia.
The influences of different plants on herbivores have recently attracted research interest; however, little is known regarding the effects of wild, local and cultivated varieties of the same plant from the same origin on herbivores. This study aimed to examine the effects of different tobacco varieties from the same origin on the oviposition preference and offspring performance of Spodoptera litura. We selected two wild (‘Bishan wild tobacco’ and ‘Badan wild tobacco’), two local (‘Liangqiao sun-cured tobacco’ and ‘Shuangguan sun-cured tobacco’) and two cultivated (‘Xiangyan No. 5’ and ‘Cunsanpi’) tobacco varieties from Hunan Province, China. We found that female S. litura varied in oviposition preferences across the tobacco varieties. They preferred to lay eggs on the cultivated varieties, followed by the local varieties, with the wild varieties being the least preferred. Furthermore, different tobacco varieties significantly influenced the life history parameters of S. litura. Survival rate, pupal weight, emergence rate and adult dry weight decreased in the following order: cultivated varieties > local varieties > wild varieties. Conversely, the pupal stage and development period decreased in the following order: wild varieties > local varieties > cultivated varieties. Therefore, we conclude that wild tobacco varieties have higher resistance to S. litura than cultivated and local varieties, reflecting the evolutionary advantages of wild tobacco varieties.
Deficits in event-related potential (ERP) including duration mismatch negativity (MMN) and P3a have been demonstrated widely in chronic schizophrenia (SZ) but inconsistent findings were reported in first-episode patients. Psychotropic medications and diagnosis might contribute to different findings on MMN/P3a ERP in first-episode patients. The present study examined MMN and P3a in first episode drug naïve SZ and bipolar disorder (BPD) patients and explored the relationships among ERPs, neurocognition and global functioning.
Twenty SZ, 24 BPD and 49 age and sex-matched healthy controls were enrolled in this study. Data of clinical symptoms [Positive and Negative Symptoms Scale (PANSS), Young Manic Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD)], neurocognition [Wechsler Adult Intelligence Scale (WAIS), Cattell's Culture Fair Intelligence Test (CCFT), Delay Matching to Sample (DMS), Rapid Visual Information Processing (RVP)], and functioning [Functioning Assessment Short Test (FAST)] were collected. P3a and MMN were elicited using a passive auditory oddball paradigm.
Significant MMN and P3a deficits and impaired neurocognition were found in both SZ and BPD patients. In SZ, MMN was significantly correlated with FAST (r = 0.48) and CCFT (r = −0.31). In BPD, MMN was significantly correlated with DMS (r = −0.54). For P3a, RVP and FAST scores were significant predictors in SZ, whereas RVP, WAIS and FAST were significant predictors in BPD.
The present study found deficits in MMN, P3a, neurocognition in drug naïve SZ and BPD patients. These deficits appeared to link with levels of higher-order cognition and functioning.
During emergency responses, public health leaders frequently serve in incident management roles that differ from their routine job functions. Leaders’ familiarity with incident management principles and functions can influence response outcomes. Therefore, training and exercises in incident management are often required for public health leaders. To describe existing methods of incident management training and exercises in the literature, we queried 6 English language databases and found 786 relevant articles. Five themes emerged: (1) experiential learning as an established approach to foster engaging and interactive learning environments and optimize training design; (2) technology-aided decision support tools are increasingly common for crisis decision-making; (3) integration of leadership training in the education continuum is needed for developing public health response leaders; (4) equal emphasis on competency and character is needed for developing capable and adaptable leaders; and (5) consistent evaluation methodologies and metrics are needed to assess the effectiveness of educational interventions.
These findings offer important strategic and practical considerations for improving the design and delivery of educational interventions to develop public health emergency response leaders. This review and ongoing real-world events could facilitate further exploration of current practices, emerging trends, and challenges for continuous improvements in developing public health emergency response leaders.
Schizophrenia is considered a polygenic disorder. People with schizophrenia and those with genetic high risk of schizophrenia (GHR) have presented with similar neurodevelopmental deficits in hemispheric asymmetry. The potential associations between neurodevelopmental abnormalities and schizophrenia-related risk genes in both schizophrenia and those with GHR remains unclear.
To investigate the shared and specific alternations to the structural network in people with schizophrenia and those with GHR. And to identify an association between vulnerable structural network alternation and schizophrenia-related risk genes.
A total of 97 participants with schizophrenia, 79 participants with GHR and 192 healthy controls, underwent diffusion tensor imaging (DTI) scans at a single site. We used graph theory to characterise hemispheric and whole-brain structural network topological metrics. For 26 people in the schizophrenia group and 48 in the GHR group with DTI scans we also calculated their schizophrenia-related polygenic risk scores (SZ-PRSs). The correlations between alterations to the structural network and SZ-PRSs were calculated. Based on the identified genetic–neural association, bioinformatics enrichment was explored.
There were significant hemispheric asymmetric deficits of nodal efficiency, global and local efficiency in the schizophrenia and GHR groups. Hemispheric asymmetric deficit of local efficiency was significantly positively correlated with SZ-PRSs in the schizophrenia and GHR groups. Bioinformatics enrichment analysis showed that these risk genes may be linked to signal transduction, neural development and neuron structure. The schizophrenia group showed a significant decrease in the whole-brain structural network.
The shared asymmetric deficits in people with schizophrenia and those with GHR, and the association between anomalous asymmetry and SZ-PRSs suggested a vulnerability imaging marker regulated by schizophrenia-related risk genes. Our findings provide new insights into asymmetry regulated by risk genes and provides a better understanding of the genetic–neural pathological underpinnings of schizophrenia.
Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design.
This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934).
Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups.
The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine.
The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.
This paper claims that palliative care (PC) is a suitable approach for offering comprehensive support to patients with life-threatening illness and unavoidable asthenia, to enhance their quality of life in aging and chronic illness. There are however some conceptual barriers to accessing that care on the Chinese Mainland: (1) Death-denying culture and society; (2) Misguidance and malpractice derived from the biomedical model; (3) Prejudice against PC and certain deviant understandings of filial piety culture. To counter these obstacles, the study introduces the philosophy of Chinese Taoist Chuang-tze to enlighten the public from ignorance and remove some illusions about death and dying; inspire people to face and accept illness and death calmly, and keep harmony and inner peace of mind to alleviate suffering, with the aim of providing wisdom and a shift of attitude toward life and death. Chuang-tze’s thoughts are consistent with the provision of palliative care, and to a certain degree, can promote its acceptability and delivery, and the conception of good death in practice.
The Arsenic (+3 oxidation state) methyltransferase (AS3MT) gene has been identified as a top risk gene for schizophrenia in several large-scale genome-wide association studies. A variable number tandem repeat (VNTR) of this gene is the most significant expression quantitative trait locus, but its role in brain activity in vivo is still unknown.
We first performed a functional magnetic resonance imaging (fMRI) scan of 101 healthy subjects during a memory span task, trained all subjects on an adaptive memory span task for 1 month, and finally performed another fMRI scan after the training. After excluding subjects with excessive head movements for one or more scanning sessions, data from 93 subjects were included in the final analyses.
The VNTR was significantly associated with both baseline brain activation and training-induced changes in multiple regions including the prefrontal cortex and the anterior and posterior cingulate cortex. Additionally, it was associated with baseline brain activation in the striatum and the parietal cortex. All these results were corrected based on the family-wise error rate method across the whole brain at the peak level.
This study sheds light on the role of AS3MT gene variants in neural plasticity related to memory span training.
Anatase phase NOx/S6+–TiO2 (x= 0, 1) film with high solar-driven activity has been successfully prepared via electro-assisted oxidation processes. The morphological and structural properties of the film were characterized by scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffraction, while the optical property was detected by UV-vis-NIR absorption spectroscopy. The results showed that the NOx/S6+–TiO2 film was composed of “flower-like” microvoids structure and displayed broad and strong optical absorption at around 544 and 1500 nm. Transient photocurrent response, photoluminescence spectroscopy, and electrochemical impedance spectroscopy indicated that the generation and separation of photogenerated charges were significantly enhanced under simulated solar irradiation. The NOx/S6+–TiO2 film exhibited excellent photoelectrocatalytic activity for the degradation of methyl orange (MO), and the decoloration rate and TOC removal respectively reached 98.97 and 59.44% at 20 min under solar irradiation. The film still had good stability after reusing ten times. Furthermore, a possible mechanism of photoelectrocatalysis was suggested in MO degradation by using NOx/S6+–TiO2 film.
Addition of carbon nanotubes (CNTs) to copper materials significantly enhances their properties. However, the performance of CNTs/Cu composites is often not as good as expected mainly because of difficulties in controlling growth and uniform dispersion of CNTs in the matrix. Our study provides an effective way to prepare CNTs/CuCr and CNTs/CuCrY composites using chemical vapor deposition. The morphology and structure of these composites were characterized by scanning electron microscope, X-ray diffraction, X-ray photoelectron spectroscopy, and Raman spectroscopy to understand how Y incorporation affects properties of these composites. Our results showed that addition of 0.1 wt% Y enhances the catalytic properties of Cr and helps to obtain purer and pristine Cu substrate. We also studied tensile strength, electric conductivity, corrosion, and wear resistance of these composites. When Y was added, composite properties improved significantly. Tensile strength and corrosion resistance increased by 35.21 and 53.28%, respectively. Electric conductivity increased to 90.9% International Annealed Copper Standard and the coefficient of friction reduced to 0.3.
Whether borderline personality disorder (BPD) and bipolar disorder are the same or different disorders lacks consistency.
To detect whether grey matter volume (GMV) and grey matter density (GMD) alterations show any similarities or differences between BPD and bipolar disorder.
Web-based publication databases were searched to conduct a meta-analysis of all voxel-based studies that compared BPD or bipolar disorder with healthy controls. We included 13 BPD studies (395 patients with BPD and 415 healthy controls) and 47 bipolar disorder studies (2111 patients with bipolar disorder and 3261 healthy controls). Peak coordinates from clusters with significant group differences were extracted. Effect-size signed differential mapping meta-analysis was performed to analyse peak coordinates of clusters and thresholds (P < 0.005, uncorrected). Conjunction analyses identified regions in which disorders showed common patterns of volumetric alteration. Correlation analyses were also performed.
Patients with BPD showed decreased GMV and GMD in the bilateral medial prefrontal cortex network (mPFC), bilateral amygdala and right parahippocampal gyrus; patients with bipolar disorder showed decreased GMV and GMD in the bilateral medial orbital frontal cortex (mOFC), right insula and right thalamus, and increased GMV and GMD in the right putamen. Multi-modal analysis indicated smaller volumes in both disorders in clusters in the right medial orbital frontal cortex. Decreased bilateral mPFC in BPD was partly mediated by patient age. Increased GMV and GMD of the right putamen was positively correlated with Young Mania Rating Scale scores in bipolar disorder.
Our results show different patterns of GMV and GMD alteration and do not support the hypothesis that bipolar disorder and BPD are on the same affective spectrum.
Previous studies have inferred a strong genetic component in schizophrenia. However, the genetic variants involved in the susceptibility to schizophrenia remain unclear.
To detect potential gene pathways and networks associated with schizophrenia, and to explore the relationship between common and rare variants in these pathways and abnormal white matter integrity in schizophrenia.
The analysis included 100 first-episode treatment-naïve patients with schizophrenia and 140 healthy controls. A network-based analysis was carried out on the data collected from the Psychiatric Genomics Consortium Phase I (PGC-I). Based on our genome-wide association study and whole-exome sequencing data-sets, we performed a gene-set analysis to detect associations between the combining effects of common and rare genetic variants and abnormal white matter integrity in schizophrenia.
Patients had significantly reduced functional anisotropy in the left and right anterior cingulate cortex, left and right precuneus and extra-nuclear (t = 4.61–5.10, PFDR < 0.01), compared with controls. Generated from co-expression network analysis of the PGC-1 summary statistics of schizophrenia, a subnetwork of 207 genes associated with schizophrenia was identified (P < 0.01), and 176 genes were co-expressed in four gene modules. Functional enrichment analysis for genes in each module revealed that the yellow module was enriched with highly co-expressed, innate immune response genes. Furthermore, rare variants of enriched genes in the yellow module were associated with reduced functional anisotropy in the left anterior cingulate cortex (P = 0.006; Padjusted = 0.024) in patients only.
The pathogenesis of schizophrenia may be substantially influenced by genes involved in the immune system, via both pathway and network.
Major depressive disorder (MDD) is a leading cause of disability worldwide and influenced by both environmental and genetic factors. Genetic studies of MDD have focused on common variants and have been constrained by the heterogeneity of clinical symptoms.
We sequenced the exome of 77 cases and 245 controls of Han Chinese ancestry and scanned their brain. Burden tests of rare variants were performed first to explore the association between genes/pathways and MDD. Secondly, parallel Independent Component Analysis was conducted to investigate genetic underpinnings of gray matter volume (GMV) changes of MDD.
Two genes (CSMD1, p = 5.32×10−6; CNTNAP5, p = 1.32×10−6) and one pathway (Neuroactive Ligand Receptor Interactive, p = 1.29×10−5) achieved significance in burden test. In addition, we identified one pair of imaging-genetic components of significant correlation (r = 0.38, p = 9.92×10−6). The imaging component reflected decreased GMV in cases and correlated with intelligence quotient (IQ). IQ mediated the effects of GMV on MDD. The genetic component enriched in two gene sets, namely Singling by G-protein coupled receptors [false discovery rate (FDR) q = 3.23×10−4) and Alzheimer Disease Up (FDR q = 6.12×10−4).
Both rare variants analysis and imaging–genetic analysis found evidence corresponding with the neuroinflammation and synaptic plasticity hypotheses of MDD. The mediation of IQ indicates that genetic component may act on MDD through GMV alteration and cognitive impairment.
In view that most Global Navigation Satellite System (GNSS) users are still using single-frequency receivers due to the low costs, single-frequency Precise Point Positioning (PPP) has been attracting increasing attention in the GNSS community. For a long period, single-frequency PPP technology has mainly relied on the Global Positioning System (GPS). With the recent revitalisation of the Russian GLONASS constellation and two newly emerging constellations, BeiDou and Galileo, it is now feasible to investigate the performance of Four-Constellation integrated Single-Frequency PPP (FCSF-PPP) with GPS, GLONASS, BeiDou and Galileo measurements. In this study, a FCSF-PPP model is presented to simultaneously process observations from all four GNSS constellations. Datasets collected at 47 globally distributed four-system Multi-GNSS Experiment (MGEX) stations on seven consecutive days and a kinematic experimental dataset are employed to fully assess the performance of FCSF-PPP. The FCSF-PPP solutions are compared to GPS-only and combined GPS/GLONASS single-frequency PPP solutions. The results indicate that the positioning performance is significantly improved by integrating multi-constellation signals.
Magnesium oxide aerogels were made by sol-gel process using magnesium methoxide as precursor, methanol and deionized water as solvent with ethanol supercritical fluid drying. The influences of the different factors on the gel time and the specific surface area of magnesium oxide aerogels were studied, and the structure and morphology were characterized by Scanning Electron Microscopy (SEM), Transmission Electron Microscope (TEM) and X-ray diffraction (XRD), and the Small Angle X-ray Scatter (SAXS) was utilized to determine the fractural structure of the magnesium oxide aerogels. The results show that MgO aerogels belong to the typical mesoporous materials with rich network and highly developed pore structure, and the specific surface area is 904.9 m2/g, the apparent density is 0.055 g/cm3, the average pore size is 19.6 nm. The results of SAXS analysis show that the fractal dimension of the MgO aerogels is 2.32 in high q area which proves the existence of rough surface and pore fractal structure.
The Palaeolithic sequence of East Asia differs from that of western Eurasia in that it is characterised by core-and-flake tools. Blade industries only appear late in the sequence, long after the first appearance of modern humans; bone tools and personal ornaments may therefore function as a better marker of modern human presence. Longquan Cave provides vital new evidence to this effect, with dated hearths indicating an initial occupation around 40 kya cal BP, followed by a second period of activity around 35–31 kya cal BP. They are associated with a polished bone awl and a structured division of settlement space, features typically associated with modern humans.
The Centers for Disease Control and Prevention (CDC) has developed an approach to ventilator-associated events (VAE) surveillance. Using these methods, this study was performed to investigate VAE incidences and to test whether VAEs are associated with poorer outcomes in China.
A 4-month, prospective multicenter surveillance study between April and July 2013.
Our study included 15 adult intensive care units (ICUs) of 15 hospitals in China.
Patients admitted to ICUs during the study period
Patients on mechanical ventilation (MV) were monitored for VAEs: ventilator-associated conditions (VACs), infection-related ventilator-associated complications (IVACs), and possible or probable ventilator-associated pneumonia (VAP). Patients with and without VACs were compared with regard to duration of MV, ICU length of stay (LOS), overall hospital LOS, and mortality rate.
During the study period, 2,356 of the 5,256 patients admitted to ICUs received MV for 8,438 ventilator days. Of these patients, 636 were on MV >2 days. VACs were identified in 94 cases (4.0%; 11.1 cases per 1,000 ventilator days), including 31 patients with IVACs and 16 with possible VAP but none with probable VAP. Compared with patients without VACs, patients with VACs had longer ICU LOS (by 6.2 days), longer duration on MV (by 7.7 days), and higher hospital mortality rate (50.0% vs 27.3%). The mortality rate attributable to VACs was 11.7%. Compared with those with VACs alone, patients with IVACs had longer duration on MV and increased ICU LOS but no higher mortality rates.
In China, surveillance of VACs and IVACs is able to identify MV patients with poorer outcomes. However, surveillance of possible and probable VAP can be problematic.
Infect. Control Hosp. Epidemiol. 2015;36(12):1388–1395