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Altered immunity and metabolic profiles have been compared between bipolar depression (BD) and major depressive disorder (MDD). This study aimed at developing a composite predictor of appetite hormones and proinflammatory cytokines to differentiate BD from MDD.
This cross-sectional study enrolled patients with BD and those with MDD aged 20 to 59 years and displaying depressive episodes. Clinical characteristics (age, sex, body mass index, and depression severity), cytokines (C-reactive protein, interleukin [IL]-2, IL-6, tumor necrosis factor [TNF]-α, P-selectin, and monocyte chemoattractant protein), and appetite hormones (leptin, adiponectin, ghrelin, and insulin) were assessed as potential predictors using a classification and regression tree (CRT) model for differentiating BD from MDD.
The predicted probability of a composite predictor of ghrelin and TNF-α was significantly greater (for BD: area under curve = 0.877; for MDD: area under curve = 0.914) than that of any one marker (all P > .05) to distinguish BD from MDD. The most powerful predictors for diagnosing BD were high ghrelin and TNF-α levels, whereas those for MDD were low ghrelin and TNF-α levels.
A composite predictor of ghrelin and TNF-α driven by CRT could assist in the differential diagnosis of BD from MDD with high specificity. Further clinical studies are warranted to validate our results and to explore underlying mechanisms.
Recent imaging studies of large datasets suggested that psychiatric disorders have common biological substrates. This study aimed to identify all the common neural substrates with connectomic abnormalities across four major psychiatric disorders by using the data-driven connectome-wide association method of multivariate distance matrix regression (MDMR).
This study analyzed a resting functional magnetic resonance imaging dataset of 100 patients with schizophrenia, 100 patients with bipolar I disorder, 100 patients with bipolar II disorder, 100 patients with major depressive disorder, and 100 healthy controls (HCs). We calculated a voxel-wise 4,330 × 4,330 matrix of whole-brain functional connectivity (FC) with 8-mm isotropic resolution for each participant and then performed MDMR to identify structures where the overall multivariate pattern of FC was significantly different between each patient group and the HC group. A conjunction analysis was performed to identify common neural regions with FC abnormalities across these four psychiatric disorders.
The conjunction of the MDMR maps revealed that the four groups of patients shared connectomic abnormalities in distributed cortical and subcortical structures, which included bilateral thalamus, cerebellum, frontal pole, supramarginal gyrus, postcentral gyrus, lingual gyrus, lateral occipital cortex, and parahippocampus. The follow-up analysis based on pair-wise FC of these regions demonstrated that these psychiatric disorders also shared similar patterns of FC abnormalities characterized by sensory/subcortical hyperconnectivity, association/subcortical hypoconnectivity, and sensory/association hyperconnectivity.
These findings suggest that major psychiatric disorders share common connectomic abnormalities in distributed cortical and subcortical regions and provide crucial support for the common network hypothesis of major psychiatric disorders.
Mach reflection subjected to the influence of an upstream shock wave from the same side is studied here. This situation occurs when two incident shock waves induced by a double wedge reflect at the same point of the reflecting surface and when the downstream incident shock wave is stronger than the upstream one. A shock polar analysis is used to show that this configuration produces an inverted Mach stem and a type IV shock interference between the Mach stem and the upstream shock wave. This shock interference produces a jet that divides the flow stream downstream of the Mach stem into two ducts with different sonic throats, thus complicating the mechanism by which the Mach stem size is determined. A transition analysis shows that the Mach reflection of the downstream shock wave is promoted by the upstream one. Computational fluid dynamics is used to assess the flow pattern anticipated by shock polar analysis and demonstrates how the heights of Mach stem and jet depend on the inflow Mach number and wedge turning angle.
Studies have suggested an association between metabolic and cerebrocardiovascular diseases and major depressive disorder (MDD). However, the risk of metabolic and cerebrocardiovascular diseases in the unaffected siblings of patients with MDD remains uncertain. Using the Taiwan National Health Insurance Research Database, 22,438 unaffected siblings of patients with MDD and 89,752 age-/sex-matched controls were selected and followed up from 1996 to the end of 2011. Individuals who developed metabolic and cerebrocardiovascular diseases during the follow-up period were identified. Compared with the controls, the unaffected siblings of patients with MDD had a higher prevalence of metabolic diseases, such as hypertension (5.0% vs. 4.5%, p = 0.007), dyslipidemia (5.6% vs. 4.8%, p < 0.001), and obesity (1.7% vs. 1.5%, p = 0.028), and cerebrocardiovascular diseases, such as ischemic stroke (0.6% vs. 0.4%, p < 0.005) and ischemic heart disease (2.1% vs. 1.7%, p < 0.001). Logistic regression analyses revealed that the unaffected siblings of patients with MDD were more likely to develop hypertension, dyslipidemia, ischemic stroke, and ischemic heart diseases during the follow-up period than the controls. Our study revealed a familial coaggregation between MDD and metabolic and cerebrocardiovascular diseases. Additional studies are required to investigate the shared pathophysiology of MDD and metabolic and cerebrocardiovascular diseases.
Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive.
This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID).
FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50–19.67), ADHD 3.94 (CI 3.72–4.17), schizophrenia 3.05 (CI 2.74–3.40), BD 2.22 (CI 1.98–2.48) and MDD 1.88 (CI 1.76–2.00). Higher RRs of schizophrenia (4.47, CI 3.95–5.06) and ASD (18.54, CI 16.18–21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only.
The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.
In order to clarify fine structures of the hypothetical meridian conduits of Chinese traditional medicine (CTM) in the skin, the present study used light and transmission electron microscopy to examine fasciae in different vertebrate species. Collagen fiber bundles and layers were arranged in a crisscross pattern, which developed into a special tissue micro-channel (TMC) network, in a manner that was analogs to the proposed skin meridian conduits. It was further revealed that tissue fluid in lateral TMC branches drained into wide longitudinal channels, which were distinctly different from lymphatic capillary. Mast cells, macrophages, and extracellular vesicles such as ectosomes and exosomes were distributed around telocytes (TCs) and their long processes (Telopodes, Tps) within the TMC. Cell junctions between TCs developed, which could enable the communication between contiguous but distant Tps. On the other hand, winding free Tps without cell junctions were also uncovered inside the TMC. Tissue fluid, cell junctions of TCs, mast cells, macrophages, and extracellular vesicles within the TMC corresponded to the circulating “气血” (“Qi-Xue”, i.e., information, message, and energy) of meridian conduits at the cytological level. These results could provide morphological evidence for the hypothesis that “meridians are the conduit for Qi-Xue circulation” in CTM.
Studies have suggested the detrimental effects of obesity and systemic inflammation on the cognitive function of patients with bipolar or major depressive disorder. However, the complex associations between affective disorder, obesity, systemic inflammation, and cognitive dysfunction remain unclear.
Overall, 110 patients with affective disorder (59 with bipolar I disorder and 51 with major depressive disorder) who scored ≥61 on the Global Assessment of Functioning and 51 age- and sex-matched controls were enrolled. Body mass index ≥25 kg/m2 was defined as obesity or overweight. Levels of proinflammatory cytokines—including interleukin-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP)—were measured, and cognitive function was assessed using various methods, including the Wisconsin Card Sorting Test (WCST) and go/no-go task.
Patients with bipolar I disorder or major depressive disorder were more likely to be obese or overweight, had higher CRP and TNF-α levels, and had greater executive dysfunction in the WCST than the controls. TNF-α level (P < .05) but not affective disorder diagnosis or obesity/overweight was significantly associated with cognitive function deficits, although obesity/overweight and diagnosis were significantly associated with increased TNF-α level.
Our findings may indicate that proinflammatory cytokines, but not obesity or overweight, have crucial effects on cognitive function in patients with bipolar I disorder or major depressive disorder, although proinflammatory cytokines and obesity or overweight were found to be strongly associated. The complex relationships between affective disorder diagnosis, proinflammatory cytokine levels, obesity or overweight, and cognitive function require further investigation.
The antidepressant effect of low-dose ketamine infusion on Taiwanese patients with anxious vs nonanxious treatment-resistant depression (ANX-TRD vs NANX-TRD) has remained unknown.
In total, 71 patients with TRD were randomized to three groups. Each group had participants who received saline infusions mixed with 0 (a normal saline infusion), 0.2, and 0.5 mg/kg of ketamine. Participants were followed up for 2 weeks. Anxious depression was defined as major depressive disorder with a total score of 7 or more on the 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor. Generalized estimating equation models were used to investigate the effects of treatment (ketamine vs placebo) and depression type (ANX-TRD vs NANX-TRD) in the reduction of depressive symptoms during the follow-up period.
Patients with ANX-TRD were less likely to respond to a single low-dose ketamine infusion than those with NANX-TRD. Among patients with NANX-TRD, low-dose ketamine infusion was significantly superior to placebo for reducing depressive symptoms. However, among patients with ANX-TRD, ketamine was not superior to placebo; nonetheless, approximately 30% of the patients responded to ketamine infusion compared to 13% who responded to the placebo.
Low-dose ketamine infusion was effective for Taiwanese patients with NANX-TRD but not so effective for those with ANX-TRD. A higher level of anxiety severity accompanying depression was related to greater depression severity. This may confound and reduce the antidepressant effect of ketamine infusion.
Telocytes (TCs) are very long, non-neuronal, somatic cells whose function is widely believed to be involved in providing connections between different cells within the body. The cellular characteristics of TCs in various organs have been studied by immunohistochemistry, double immunofluorescence and electron microscopy in different vertebrate species, and here we investigate the proposed properties of these cells in the context of the “meridian” in Chinese Traditional Medicine (CTM). The results show that TCs and their long extensions, telopodes (Tps) develop a complicated network by homo- and heterocellular junctions in the connective tissue throughout the body, which can connect the skin with distant organs. In concept, this is the analogue of ancient meridian maps connecting skin acupoints with the viscera. Various active cells and extracellular vesicles including exosomes move along Tps, which, along with developed mitochondria within the podoms of Tps, may account for the structural evidence for “Qi” (vital energy and signal communication) in CTM. Morphological associations of TCs with the nerve, vascular, endocrine, and immune systems are also compatible with previously proposed meridian theories in CTM. Close relationships exist between TCs and collagen fiber bundles and some structures in skin fascia provide the microanatomical support for acupuncture treatment based on the meridian principle. The dynamicity in the distribution and structure of TCs reflects the plasticity of the meridian at the cellular level. As the same attribute, both the meridian and the TC have been associated with various diseases. Here, we summarize structural analogues between the TC and the meridian, suggesting that TCs have the cytological characteristics of the CTM meridian. We, therefore, hypothesize that TCs are the “essence cells” of the CTM meridian, which can connect and integrate different cells and structures in the connective tissue.
The core toroidal plasma intrinsic rotation has been studied by experiments and simulations in the Joint Texas Experimental Tokamak (J-TEXT). The direction of core intrinsic rotation in the J-TEXT plasma is counter-current. As the plasma density ramps up, the rotation velocity increases in the counter-current direction. By comparing four different electron densities, linear local gyrokinetic simulations have been performed by the Gyrokinetic Electromagnetic Numerical Experiment code for the first time on J-TEXT. It is found that the most dominant turbulence is the ion temperature gradient at
is the minor radius of the plasma and this is unchanged during the plasma density ramp up. By scanning the radial wave vectors, it is found that the residual stress term reverses from negative to positive when the plasma density exceeds a certain threshold. The pinch term is larger than the residual stress term at all four electron densities, which means that the pinch term is always dominant in the core of a J-TEXT plasma.
Post-testicular maturation of spermatozoa is crucial for attaining the morphological and functional capabilities needed for successful fertilization. Epididymal epithelia offer a favorable environment for spermatozoa that are stored long term in the turtle epididymis; however, sperm–epithelial interactions during storage, which are enormously important for sperm functional and morphological maturation, are still largely unknown in turtles. The present study examined the epididymis during the sperm-storage period (November–April) in the Chinese soft-shelled turtle (Pelodiscus sinensis). Light and transmission electron microscopy were used to determine the cellular features of each epididymal segment (caput, corpus, and cauda) and their epithelial interactions with the spermatozoa. Spermatozoa were mainly located in the lumena of caput, corpus, and cauda epididymides. Numerous spermatozoa were bound to apical surfaces of the epithelia, and several were even embedded in the epithelial cytoplasm of the caput and corpus epididymides. No embedded spermatozoa were found in the cauda epididymis. In all epididymal segments, principal and clear cells showed the synthetic activity, evidenced by a well-developed endoplasmic reticulum network and high and low electron-dense secretory materials, respectively. Principal and clear cells in the caput and corpus segments showed embedded spermatozoa in electron-dense secretions and in the lipid droplets within the cytoplasm. No lysosomes were observed around the embedded spermatozoa. The lumena of the caput and corpus segments showed few apocrine and low electron density secretions. In the lumen of the cauda epididymidis, different secretions, such as holocrine with low and high electron density and their fragmentation, apocrine, and dictyosome, were found and are summarized. Altogether, sperm physical interactions with secretions either in the cytoplasm of epithelium or in the lumen may support the viability, morphological maintenance, and transfer of various proteins involved in long-term sperm storage in the turtle. This interaction could help us to understand the mechanisms of long-term sperm storage and provide more insights into the reproductive strategies of turtle sperm preservation.
In recent years, there have been a significant influenza activity and emerging influenza strains in China, resulting in an increasing number of influenza virus infections and leading to public health concerns. The aims of this study were to identify the epidemiological and aetiological characteristics of influenza and establish seasonal autoregressive integrated moving average (SARIMA) models for forecasting the percentage of visits for influenza-like illness (ILI%) in urban and rural areas of Shenyang. Influenza surveillance data were obtained for ILI cases and influenza virus positivity from 18 sentinel hospitals. The SARIMA models were constructed to predict ILI% for January–December 2019. During 2010–2018, the influenza activity was higher in urban than in rural areas. The age distribution of ILI cases showed the highest rate in young children aged 0–4 years. Seasonal A/H3N2, influenza B virus and pandemic A/H1N1 continuously co-circulated in winter and spring seasons. In addition, the SARIMA (0, 1, 0) (0, 1, 2)12 model for the urban area and the SARIMA (1, 1, 1) (1, 1, 0)12 model for the rural area were appropriate for predicting influenza incidence. Our findings suggested that there were regional and seasonal distinctions of ILI activity in Shenyang. A co-epidemic pattern of influenza strains was evident in terms of seasonal influenza activity. Young children were more susceptible to influenza virus infection than adults. These results provide a reference for future influenza prevention and control strategies in the study area.
Mach reflection in steady supersonic flow with two incident shock waves that reflect at the same point on the reflecting surface has been studied recently. Under some conditions we have pre-Mach reflection, where the first incident shock wave produces Mach reflection, the reflected shock wave of which intersects the second incident shock wave, leading to a type I shock interference structure. In this study, we find that a critical condition exists to have a double solution of this shock interference, i.e. we may either have type I interference or type II interference. However, numerical simulation shows that, for inverted Mach reflection, the double solution domain is below the theoretical one and for usual Mach reflection, the double solution domain is above the theoretical one. This discrepancy is found to be due to secondary Mach waves on the initial segment of the slipline of the Mach reflection, thus demonstrating for the first time a case where the transition criterion is modified by secondary Mach waves developed over the primary flow structure.
Stem cells are an immortal cell population capable of self-renewal; they are essential for human development and ageing and are a major focus of research in regenerative medicine. Despite considerable progress in differentiation of stem cells in vitro, culture conditions require further optimization to maximize the potential for multicellular differentiation during expansion. The aim of this study was to develop a feeder-free, serum-free culture method for human embryonic stem cells (hESCs), to establish optimal conditions for hESC proliferation, and to determine the biological characteristics of the resulting hESCs. The H9 hESC line was cultured using a homemade serum-free, feeder-free culture system, and growth was observed. The expression of pluripotency proteins (OCT4, NANOG, SOX2, LIN28, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81) in hESCs was determined by immunofluorescence and western blotting. The mRNA expression levels of genes encoding nestin, brachyury and α-fetoprotein in differentiated H9 cells were determined by RT-PCR. The newly developed culture system resulted in classical hESC colonies that were round or elliptical in shape, with clear and neat boundaries. The expression of pluripotency proteins was increased, and the genes encoding nestin, brachyury, and α-fetoprotein were expressed in H9 cells, suggesting that the cells maintained in vitro differentiation capacity. Our culture system containing a unique set of components, with animal-derived substances, maintained the self-renewal potential and pluripotency of H9 cells for eight passages. Further optimization of this system may expand the clinical application of hESCs.
This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment.
This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization.
A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects.
After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.
Whether the first-degree relatives (FDRs) of patients with obsessive-compulsive disorder (OCD) have an increased risk of the major psychiatric disorders, namely schizophrenia, bipolar disorder, OCD, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD), remains unclear.
Using the Taiwan National Health Insurance Research Database with the whole population sample size (n = 23 258 175), 89 500 FDRs, including parents, offspring, siblings, and twins, of patients with OCD were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with OCD.
FDRs of patients with OCD had higher RRs of major psychiatric disorders, namely OCD (RR 8.11, 95% confidence interval (CI) 7.68–8.57), bipolar disorder (RR 2.85, 95% CI 2.68–3.04), MDD (RR 2.67, 95% CI 2.58–2.76), ASD (RR 2.38, 95% CI 2.10–2.71), ADHD (RR 2.19, 95% CI 2.07–2.32), and schizophrenia (RR 1.97, 95% CI 1.86–2.09), compared with the total population. Different familial kinships of FDRs, such as parents, offspring, siblings, and twins consistently had increased risks for these disorders. In addition, a dose-dependent relationship was found between the numbers of OCD probands and the risk of each major psychiatric disorder.
The FDRs, including parents, offspring, siblings, and twins, of patients with OCD have a higher risk of OCD, schizophrenia, bipolar disorder, MDD, ADHD, and ASD. The familial co-aggregation of OCD with OCD and other major psychiatric disorders was existent in a dose-dependent manner. Given the increased risks of psychiatric disorders, medical practitioners should closely monitor the mental health of the FDRs of patients with OCD.
Terrorist attacks can occur anywhere. As the threat of terrorism develops, the China-Eurasia Expo held in Ürümqi, China is attracting fewer potential visitors. A nationwide survey of 2034 residents from 31 provinces and municipalities in China was conducted to examine the relation between the distance to respondents’ city of residence from Ürümqi and their levels of concern for safety and security concerning the Expo. The two were found to be positively related: the closer the respondents lived to Ürümqi, the less concerned they were with the safety and security of the Expo. This is consistent with the “psychological typhoon eye” effect, which states that people living closer to the center of an unfortunate event (whether natural or man-made hazards) are less concerned with the event’s negative consequences. This effect appears to hold for terrorism. There are implications of this finding for international counter-terrorism practice, tourism, and research.
Blockchain technology has rapidly emerged as a decentralized trusted network to replace the traditional centralized intermediator. Especially, the smart contracts that are based on blockchain allow users to define the agreed behaviour among them, the execution of which will be enforced by the smart contracts. Based on this, we propose a decentralized booking system that uses the blockchain as the intermediator between hoteliers and travellers. The system enjoys the trustworthiness of blockchain, improves efficiency and reduces the cost of the traditional booking agencies. The design of the system has been formally modelled using the CSP# language and verified using the model checker Process Analysis Toolkit. We have implemented a prototype decentralized booking system based on the Ethereum ecosystem.
The self-assembly of optically active building blocks into functional nanocrystals as high-activity photocatalysts is a key in the field of photocatalysis. Cobalt porphyrin with abundant catalytic properties is extensively studied in photocatalytic water oxidation and CO2 reduction. Here, we present the fabrication of cobalt porphyrin nanocrystals through a surfactant-assisted interfacial self-assembly process using Co-tetra(4-pyridyl) porphyrin as building block. The self-assembly process relies on the combined noncovalent interactions such as π-π stacking and axial Co-N coordination between individual porphyrin molecules within surfactant micelles. Tuning different reaction conditions (temperature, the ratio of co-solvent DMF) and types of surfactant, various nanocrystals with well-defined 1D to 3D morphologies such as nanowires, nanorods and nano hexagonal prism were obtained. Due to the ordered accumulation of molecules, the nanocrystals exhibit the properties of the enhanced capability of visible light capture and can conduce to improve the transport and separation efficiency of the photogenerated carriers, which is important for photocatalysis. Further studies of photocatalytic CO2 reduction are being performed to address the relationship between the size and shape of the nanocrystals with the photocatalytic activity.
Several studies suggested a potential role of viral infection in the pathophysiology of Parkinson’s disease (PD). However, the association between herpes zoster and PD was not investigated well till now.
Using the Taiwan National Health Insurance Research Database, 13 083 patients aged ≥45 years with herpes zoster and 52 332 (1:4) age-/sex-matched controls were enrolled between 1998 and 2008 and followed to the end of 2011. Those who developed PD during the follow-up period were identified.
The Cox regression analysis with adjustment of demographic characteristics, health system utilization, and comorbidities demonstrated that patients with herpes zoster had an increased risk (hazard ratio [HR]: 1.80, 95% confidence interval [CI]: 1.43-2.28) of developing PD in later life compared to the control group. Sensitivity tests after excluding the first year (HR: 1.50, 95% CI: 1.16-1.93) and first 2-year (HR: 1.44, 95% CI: 1.10-1.88) observation periods showed consistent results.
Patients with herpes zoster were more likely to develop PD in later life compared to the controls. Additional studies are necessary for validating our results and to clarify the underlying pathophysiology between herpes zoster and PD.