Mental health resources and awareness of anxiety and depressive disorders in general hospitals in China

Background: Mental health disorders are common in China. There is a lack of knowledge and resources of mental health in China. Objectives: To assess the levels of psychiatric resources and services in general hospitals in China. Methods: Data regarding psychiatric departments, wards and staff were collected from 57 general hospitals in four provinces of China (Hubei, Zhejiang, Heilongjiang and Yunnan) between April 2014 and June 2014. Questionnaires were distributed to 1,200 non-psychiatric clinicians. Results: Among the 57 hospitals, 50 provided mental health services, 36 had mental health wards, and seven had neither mental health clinics nor wards. The median number of mental health clinicians was six per hospital. The median number of specialized nurses was 42 per hospital. A total of 1,152 non-psychiatric clinicians with a career duration of 9.4 ± 8.9 years returned completed questionnaires. Only 6.9% reported a good understanding of the manifestation of anxiety and depressive disorders, 4.5% reported a good understanding of the diagnostic criteria, and 3.8% reported a good understanding of the treatment protocols. Discussion: There is inadequate awareness of anxiety and depressive disorders among non-psychiatric clinicians in general hospitals in China. This awareness/understanding increased with increasing hospital level

Single-cell transcriptome sequencing reveals heterogeneity of gastric cancer: progress and prospects

Gastric cancer is one of the most serious malignant tumor and threatens the health of people worldwide. Its heterogeneity leaves many clinical problems unsolved. To treat it effectively, we need to explore its heterogeneity. Single-cell transcriptome sequencing, or single-cell RNA sequencing (scRNA-seq), reveals the complex biological composition and molecular characteristics of gastric cancer at the level of individual cells, which provides a new perspective for understanding the heterogeneity of gastric cancer. In this review, we first introduce the current procedure of scRNA-seq, and discuss the advantages and limitations of scRNA-seq. We then elaborate on the research carried out with scRNA-seq in gastric cancer in recent years, and describe how it reveals cell heterogeneity, the tumor microenvironment, oncogenesis and metastasis, as well as drug response in to gastric cancer, to facilitate early diagnosis, individualized therapy, and prognosis evaluation

Nicotinamide reverses deficits in puberty-born neurons and cognitive function after maternal separation.

Background Early life stress (ELS) is associated with the development of schizophrenia later in life. The hippocampus develops significantly during childhood and is extremely reactive to stress. In rodent models, ELS can induce neuroinflammation, hippocampal neuronal loss, and schizophrenia-like behavior. While nicotinamide (NAM) can inhibit microglial inflammation, it is unknown whether NAM treatment during adolescence reduces hippocampal neuronal loss and abnormal behaviors induced by ELS. Methods Twenty-four hours of maternal separation (MS) of Wistar rat pups on post-natal day (PND)9 was used as an ELS. On PND35, animals received a single intraperitoneal injection of BrdU to label dividing neurons and were given NAM from PND35 to PND65. Behavioral testing was performed. Western blotting and immunofluorescence staining were used to detect nicotinamide adenine dinucleotide (NAD+)/Sirtuin3 (Sirt3)/superoxide dismutase 2 (SOD2) pathway-related proteins. Results Compared with controls, only MS animals in the adult stage (PND56–65) but not the adolescent stage (PND31–40) exhibited pre-pulse inhibition deficits and cognitive impairments mimicking schizophrenia symptoms. MS decreased the survival and activity of puberty-born neurons and hippocampal NAD+ and Sirt3 expression in adulthood. These observations were related to an increase in acetylated SOD2, microglial activation, and significant increases in pro-inflammatory IL-1β, TNF-α, and IL-6 expression. All the effects of MS at PND9 were reversed by administering NAM in adolescence (PND35–65). Conclusions MS may lead to schizophrenia-like phenotypes and persistent hippocampal abnormalities. NAM may be a safe and effective treatment in adolescence to restore normal hippocampal function and prevent or ameliorate schizophrenia-like behavior

Interaction between CRHR1 and BDNF Genes Increases the Risk of Recurrent Major Depressive Disorder in Chinese Population

BACKGROUND: An important etiological hypothesis about depression is stress has neurotoxic effects that damage the hippocampal cells. Corticotropin-releasing hormone (CRH) regulates brain-derived neurotrophic factor (BDNF) expression through influencing cAMP and Ca2+ signaling pathways during the course. The aim of this study is to examine the single and combined effects of CRH receptor 1 (CRHR1) and BDNF genes in recurrent major depressive disorder (MDD). METHODOLOGY/PRINCIPAL FINDING: The sample consists of 181 patients with recurrent MDD and 186 healthy controls. Whether genetic variations interaction between CRHR1 and BDNF genes might be associated with increased susceptibility to recurrent MDD was studied by using a gene-based association analysis of single-nucleotide polymorphisms (SNPs). CRHR1 gene (rs1876828, rs242939 and rs242941) and BDNF gene (rs6265) were identified in the samples of patients diagnosed with recurrent MDD and matched controls. Allelic association between CRHR1 rs242939 and recurrent MDD was found in our sample (allelic: p = 0.018, genotypic: p = 0.022) with an Odds Ratio 0.454 (95% CI 0.266-0.775). A global test of these four haplotypes showed a significant difference between recurrent MDD group and control group (chi-2 = 13.117, df = 3, P = 0.016. Furthermore, BDNF and CRHR1 interactions were found in the significant 2-locus, gene-gene interaction models (p = 0.05) using a generalized multifactor dimensionality reduction (GMDR) method. CONCLUSION: Our results suggest that an interaction between CRHR1 and BDNF genes constitutes susceptibility to recurrent MDD

A De Novo Protein Binding Pair By Computational Design and Directed Evolution

The de novo design of protein-protein interfaces is a stringent test of our understanding of the principles underlying protein-protein interactions and would enable unique approaches to biological and medical challenges. Here we describe a motif-based method to computationally design protein-protein complexes with native-like interface composition and interaction density. Using this method we designed a pair of proteins, Prb and Pdar, that heterodimerize with a Kd of 130 nM, 1000-fold tighter than any previously designed de novo protein-protein complex. Directed evolution identified two point mutations that improve affinity to 180 pM. Crystal structures of an affinity- matured complex reveal binding is entirely through the designed interface residues. Surprisingly, in the in vitro evolved complex one of the partners is rotated 180 relative to the original design model, yet still maintains the central computationally designed hotspot interaction and preserves the character of many peripheral interactions. This work demon- strates that high-affinity protein interfaces can be created by designing complementary interaction surfaces on two noninteracting partners and under- scores remaining challenges.Chemistry and Chemical Biolog

Drug dosing during pregnancy—opportunities for physiologically based pharmacokinetic models

Drugs can have harmful effects on the embryo or the fetus at any point during pregnancy. Not all the damaging effects of intrauterine exposure to drugs are obvious at birth, some may only manifest later in life. Thus, drugs should be prescribed in pregnancy only if the expected benefit to the mother is thought to be greater than the risk to the fetus. Dosing of drugs during pregnancy is often empirically determined and based upon evidence from studies of non-pregnant subjects, which may lead to suboptimal dosing, particularly during the third trimester. This review collates examples of drugs with known recommendations for dose adjustment during pregnancy, in addition to providing an example of the potential use of PBPK models in dose adjustment recommendation during pregnancy within the context of drug-drug interactions. For many drugs, such as antidepressants and antiretroviral drugs, dose adjustment has been recommended based on pharmacokinetic studies demonstrating a reduction in drug concentrations. However, there is relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Examples of using pregnancy PBPK models to predict feto-maternal drug exposures and their applications to facilitate and guide dose assessment throughout gestation are discussed

Structural Insight into the Mechanisms of Targeting and Signaling of Focal Adhesion Kinase

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase whose focal adhesion targeting (FAT) domain interacts with other focal adhesion molecules in integrin-mediated signaling. Localization of activated FAK to focal adhesions is indispensable for its function. Here we describe a solution structure of the FAT domain bound to a peptide derived from paxillin, a FAK-binding partner. The FAT domain is composed of four helices that form a “right-turn” elongated bundle; the globular fold is mainly maintained by hydrophobic interactions. The bound peptide further stabilizes the structure. Certain signaling events such as phosphorylation and molecule interplay may induce opening of the helix bundle. Such conformational change is proposed to precede departure of FAK from focal adhesions, which starts focal adhesion turnover

A Novel Electromagnetic Centric Multiphysics Parametric Modeling Approach Using Neuro-Space Mapping for Microwave Passive Components

An advanced Neuro-space mapping (Neuro-SM) multiphysics parametric modeling approach for microwave passive components is proposed in this paper. The electromagnetic (EM) domain model, which represents the EM responses with respect to geometrical parameters, is regarded as a coarse model. The multiphysics domain model, which represents the multiphysics responses with respect to both geometrical parameters and multiphysics parameters, is regarded as a fine model. The proposed model is constructed by the input mapping, the output mapping and the coarse model. The input mapping is used to map multiphysics parameters to EM parameters. The output mapping is introduced to further narrow the gap between the output of the coarse model and the multiphysics data. In addition, a three-stage training method is proposed for efficiently developing the proposed multiphysics model. The proposed technique, which combines the efficiency of EM analysis and the accuracy of multiphysics analysis, can achieve better accuracy with less multiphysics data than existing modeling methods. The developed Neuro-SM multiphysics model provides accurate and fast predictions of multiphysics responses. Therefore, the design cycle of microwave passive components is shortened while the modeling cost is significantly reduced. Two microwave filter examples are utilized to demonstrate the accuracy of the proposed parametric modeling technique

Reduced Prefrontal Activation During the Tower of London and Verbal Fluency Task in Patients With Bipolar Depression: A Multi-Channel NIRS Study

Background: The Tower of London (TOL) task is one of the most commonly used tests for evaluating executive functions, and can indicate planning and problem-solving abilities. The aim of this study was to evaluate hemodynamic changes between the task period and rest period in patients with bipolar depression during the TOL task and the verbal fluency task (VFT) using near-infrared spectroscopy (NIRS).Methods: Forty-three patients with bipolar depression and 32 healthy controls (HCs) matched for sex, age, handedness, and years of education were enrolled in this study. All participants were aged between 16 and 50. All patients in our study were taking medications such as antidepressants, antipsychotics and mood stabilizers at the time of measurement. Changes in oxygenated hemoglobin (oxy-Hb) levels in frontal areas during the TOL task and VFT were evaluated using a 41-channel NIRS system.Results: During the TOL task, the patients with bipolar depression exhibited significantly smaller changes in the bilateral dorsal-lateral prefrontal cortex (DLPFC) than the HCs. During the VFT task, the patients with bipolar depression exhibited significantly smaller changes in the right ventrolateral prefrontal cortex (VLPFC), the right DLPFC and both the right and left prefrontal cortex (PFC) than the HCs.Limitations: Our sample size was small, and the effects of medication cannot be excluded.Conclusions: These results indicate that planning and problem solving dysfunction is related to the impairment of the prefrontal cortex in patients with bipolar depression, and NIRS can be used to assess planning and problem solving abilities, which are essential to daily life in patients with bipolar disorder