Menstrual Dysfunction in Women With Schizophrenia During Risperidone Maintenance Treatment.

BACKGROUND: A percentage of women patients with schizophrenia may suffer from menstrual dysfunction associated with antipsychotic medication. This study evaluated menstrual dysfunction in women with schizophrenia given maintenance risperidone, and investigated the association between menstrual dysfunction and the duration and dose of risperidone and clinical symptoms. METHODS: The data of 161 women were obtained from the Risperidone Maintenance Treatment in Schizophrenia study, including patients' characteristics, menstrual conditions, and duration and dosage of risperidone. Qualitative data regarding menstrual health were evaluated at baseline (clinical stabilization after 4-8 weeks maintenance treatment with a standard risperidone dose 4-8 mg/d) and follow-up interviews up to 52 weeks. RESULTS: At baseline, 73.2% (119/161) of the patients were eumenorrheic; specific rates of menstrual dysfunction were 14.3% (23/161) irregular menstruation, 6.8% (11/161) oligomenorrhea, and 5.0% (8/161) amenorrhea. At the end of follow-up, 16.0% (19/119) of those with eumenorrhea at baseline reported menstrual dysfunction. During the entire risperidone maintenance treatment, 37.9% (61/161) experienced menstrual dysfunction. The range of onset time from the beginning of risperidone treatment to menstrual dysfunction was 64 to 243 days. Risperidone dose was positively associated with menstrual dysfunction (r = 0.187, P = 0.046). The total Positive and Negative Syndrome Scale score was significantly associated with menstrual dysfunction (r = 0.274, P = 0.001). CONCLUSIONS: Attention should be given to menstrual dysfunction of women with schizophrenia that is an adverse effect of risperidone maintenance treatment. Menstrual dysfunction may occur early or late during maintenance treatment, partly depending on the dose.ClinicalTrials.govidentifier: NCT00848432.

Cognitive Behavioural Therapy for Insomnia Monotherapy in Patients with Medical or Psychiatric Comorbidities: a Meta-Analysis of Randomized Controlled Trials.

This is a meta-analysis of randomized controlled trials (RCTs) comparing cognitive behaviour therapy for insomnia (CBT-I) monotherapy with active control treatment for insomnia in patients with medical or psychiatric comorbidities. Both international (PubMed, EMBASE, PsycINFO, Cochrane Library) and Chinese (WanFang, and CNKI) databases were systematically searched. The random effects model was used. Thirteen RCTs comparing CBT-I (n = 441) and active controls (n = 412) groups were included. CBT-I group showed significant advantage over active controls at post-treatment assessment in terms of Insomnia Severity Index (ISI; SMD = -0.74), sleep onset latency (SMD = -0.36), wake after sleep onset (SMD = -0.21), sleep quality (SMD = 0.56), Pittsburgh sleep quality index total scores (PSQI; SMD = -0.76) and the total score of dysfunctional beliefs and attitudes about sleep scale (DBAS; SMD = -1.09). Subgroup analyses revealed significant improvement in sleep onset latency in patients with psychiatric disorders (SMD = -0.45), while significant reduction of number of wakeup after sleep onset was found in patients with medical conditions (SMD = -0.31). This meta-analysis found that CBT-I monotherapy had greater efficacy than other active control treatment for insomnia in patients with medical or psychiatric comorbidities.

Two cases of high serum clozapine concentrations occurring during inflammation in Chinese patients.

Objective Serious infections or inflammations have been associated with serum clozapine concentration increases and sometimes with clozapine toxicity. Method These two cases describe Chinese patients (Case 1: a 57-year-old female nonsmoker with severe dermatitis and Case 2: a 47-year-old male nonsmoker with influenza and secondary infection). Results In both cases, the Drug Interaction Probability Scale established the presence of a probable drug-drug interaction. In both cases, the clozapine and the total clozapine concentration-to-dose ratios followed a temporal pattern (normal-high-normal), consistent with an inhibition of clozapine metabolism during peak inflammation. In the first case, the total clozapine concentration-to-dose ratio (8 with no/low inflammation: median of 3.10 and 2 at peak inflammation: median of 3.90) provided a significant difference (P = 0.044). In the second patient, because of the smaller sample size and reduced statistical power (4 with no infection: a median of 1.59 and 2 at peak infection: 3.46), the increase did not reach significance (P = 0.13). In the first case, the median baseline clozapine concentration-to-dose ratio increased by a factor of 1.45 from 2.00 to a peak of 2.89. To compensate for the inhibition of clozapine metabolism, the dose correction factor was 0.69 (1/1.45) or a decrease in dose of approximately one-third. In the second case, the median baseline clozapine concentration-to-dose ratio increased by a factor of 2.56 from 1.15 to a peak of 2.94. Conclusion This provided a dose correction factor of 0.40 (1/2.56) or approximately half the dose, similar to published cases in Caucasians with serious respiratory infections.

Knowledge and attitudes of older psychiatric patients and their caregivers towards electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for older patients with severe psychiatric disorders, but their knowledge and attitudes regarding ECT have not been well studied. This study examined the knowledge and attitudes of older Chinese patients and their caregivers towards ECT. METHOD: A total of 216 participants comprising older patients treated with ECT (n = 108) and their caregivers (n = 108) were recruited. Their knowledge and attitudes regarding ECT were assessed using self-reported questionnaires. RESULTS: Most caregivers received sufficient information on the therapeutic effects of ECT, but inadequate information about the ECT process, its adverse effects, and risks was provided to caregivers and patients before treatment. Although ECT was generally viewed as beneficial, effective, and safe, around two-thirds of patients and caregivers believed that ECT should be used only for critically ill patients. Over half of the patients reported adverse effects caused by ECT, with memory impairment being the most commonly reported. CONCLUSIONS: Clinicians in Chinese psychiatric hospitals need to provide sufficient information on ECT to older patients and their caregivers before treatment, particularly regarding the treatment process and adverse effects.

Activation of Kaposi's sarcoma-associated herpesvirus (KSHV) by inhibitors of class III histone deacetylases: identification of sirtuin 1 as a regulator of the KSHV life cycle.

UNLABELLED: Kaposi's sarcoma-associated herpesvirus (KSHV) establishes persistent latent infection in immunocompetent hosts. Disruption of KSHV latency results in viral lytic replication, which promotes the development of KSHV-related malignancies in immunocompromised individuals. While inhibitors of classes I and II histone deacetylases (HDACs) potently reactivate KSHV from latency, the role of class III HDAC sirtuins (SIRTs) in KSHV latency remains unclear. Here, we examined the effects of inhibitors of SIRTs, nicotinamide (NAM) and sirtinol, on KSHV reactivation from latency. Treatment of latently KSHV-infected cells with NAM or sirtinol induced transcripts and proteins of the master lytic transactivator RTA (ORF50), early lytic genes ORF57 and ORF59, and late lytic gene ORF65 and increased the production of infectious virions. NAM increased the acetylation of histones H3 and H4 as well as the level of the active histone H3 trimethyl Lys4 (H3K4me3) mark but decreased the level of the repressive histone H3 trimethyl Lys27 (H3K27me3) mark in the RTA promoter. Consistent with these results, we detected SIRT1 binding to the RTA promoter. Importantly, knockdown of SIRT1 was sufficient to increase the expression of KSHV lytic genes. Accordingly, the level of the H3K4me3 mark in the RTA promoter was increased following SIRT1 knockdown, while that of the H3K27me3 mark was decreased. Furthermore, SIRT1 interacted with RTA and inhibited RTA transactivation of its own promoter and that of its downstream target, the viral interleukin-6 gene. These results indicate that SIRT1 regulates KSHV latency by inhibiting different stages of viral lytic replication and link the cellular metabolic state with the KSHV life cycle. IMPORTANCE: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causal agent of several malignancies, including Kaposi's sarcoma, commonly found in immunocompromised patients. While latent infection is required for the development of KSHV-induced malignancies, viral lytic replication also promotes disease progression. However, the mechanism controlling KSHV latent versus lytic replication remains unclear. In this study, we found that class III histone deacetylases (HDACs), also known as SIRTs, whose activities are linked to the cellular metabolic state, mediate KSHV replication. Inhibitors of SIRTs can reactivate KSHV from latency. SIRTs mediate KSHV latency by epigenetically silencing a key KSHV lytic replication activator, RTA. We found that one of the SIRTs, SIRT1, binds to the RTA promoter to mediate KSHV latency. Knockdown of SIRT1 is sufficient to induce epigenetic remodeling and KSHV lytic replication. SIRT1 also interacts with RTA and inhibits RTA's transactivation function, preventing the expression of its downstream genes. Our results indicate that SIRTs regulate KSHV latency by inhibiting different stages of viral lytic replication and link the cellular metabolic state with the KSHV life cycle.

Kaposi's sarcoma-associated herpesvirus induces rapid release of angiopoietin-2 from endothelial cells.

Kaposi sarcoma-associated herpesvirus (KSHV) stimulates proliferation, angiogenesis, and inflammation to promote Kaposi sarcoma (KS) tumor growth, which involves various growth factors and cytokines. Previously, we found that KSHV infection of human umbilical vein endothelial cells (HUVECs) induces a transcriptional induction of the proangiogenic and proinflammatory cytokine angiopoietin-2 (Ang-2). Here, we report that KSHV induces rapid release of Ang-2 that is presynthesized and stored in the Weibel-Palade bodies (WPB) of endothelial cells upon binding to its integrin receptors. Blocking viral binding to integrins inhibits Ang-2 release. KSHV binding activates the integrin tyrosine kinase receptor signaling pathways, leading to tyrosine phosphorylation of focal adhesion kinase (FAK), the tyrosine kinase Src, and the Calα2 subunit of the l-type calcium channel to trigger rapid calcium (Ca(2+)) influx. Pretreatment of endothelial cells with specific inhibitors of protein tyrosine kinases inhibits KSHV-induced Ca(2+) influx and Ang-2 release. Inhibition of Ca(2+) mobilization with calcium channel blockers also inhibits Ang-2 release. Thus, the interaction between KSHV and its integrin receptors plays a key role in regulating rapid Ang-2 release from endothelial cells. This finding highlights a novel mechanism of viral induction of angiogenesis and inflammation, which might play important roles in the early event of KS tumor development.

Longitudinal changes in cognitive function in early psychosis: a meta-analysis with the MATRICS consensus cognitive battery (MCCB).

INTRODUCTION: A previous meta-analysis indicated stable progress in cognitive functions in early psychosis, assessed through various tools. To avoid assessment-related heterogeneity, this study aims to examine the longitudinal cognitive function changes in early psychosis utilizing the MATRICS Consensus Cognitive Battery (MCCB). METHODS: Embase, PubMed, and Scopus were systematically searched from their inception to September 26th 2023. The inclusion criteria were longitudinal studies that presented follow-up MCCB data for individuals experiencing first-episode psychosis (FEP) and those with ultra-high risk for psychosis (UHR). RESULTS: Twelve studies with 791 participants (566 FEP patients and 225 healthy controls) were subjected to analysis. Suitable UHR studies were absent. Over time, both FEP patients and healthy controls showed significant improvements in MCCB total scores. Furthermore, FEP patients demonstrated improvements across all MCCB domains, while healthy controls only showed augmentations in specific domains such as speed of processing, attention, working memory, and reasoning and problem-solving. Visuospatial learning improvements were significantly greater in FEP patients compared to healthy controls. Subgroup analyses suggested that neither diagnostic type nor follow-up duration influenced the magnitude of cognitive improvement in FEP patients. CONCLUSION: The magnitude of cognitive improvement for MCCB domains was not significantly different between FEP and healthy controls other than visuospatial learning. This underscores visuospatial learning as a potentially sensitive cognitive marker for early pathologic state changes in psychotic disorders.

Interaction between BDNF Val66Met polymorphism and mismatch negativity for working memory capacity in schizophrenia.

Both the brain-derived neurotrophic factor (BDNF) valine (Val)/methionine (Met) polymorphism and mismatch negativity (MMN) amplitude are reportedly linked to working memory impairments in schizophrenia. However, there is evident scarcity of research aimed at exploring the relationships among the three factors. In this secondary analysis of a randomized, controlled, double-blind trial, we investigated these relationships. The trial assessed the efficacy of transcranial direct current stimulation for enhancing working memory in clinically stable schizophrenia patients, who were randomly divided into three groups: dorsolateral prefrontal cortex stimulation, posterior parietal cortex stimulation, and sham stimulation groups. Transcranial direct current stimulation was administered concurrently with a working memory task over five days. We assessed the BDNF genotype, MMN amplitude, working memory capacity, and interference control subdomains. These assessments were conducted at baseline with 54 patients and followed up post-intervention with 48 patients. Compared to BDNF Met-carriers, Val homozygotes exhibited fewer positive and general symptoms and increased working memory capacity at baseline. A correlation between MMN amplitude and working memory capacity was noted only in BDNF Val homozygotes. The correlations were significantly different in the two BDNF genotype groups. Furthermore, in the intervention group that showed significant improvement in MMN amplitude, BDNF Val homozygotes exhibited greater enhancement in working memory capacity than Met-carriers. This study provides in vivo evidence for the interaction between MMN and BDNF Val/Met polymorphism for working memory capacity. As MMN has been considered a biomarker of N-methyl-D-aspartate receptor (NMDAR) function, these data shed light on the complex interactions between BDNF and NMDAR in terms of working memory in schizophrenia.

Independent effects of early life adversity on social cognitive function in patients with schizophrenia.

Objective: The aim of this study was to investigate the impact of early life adversity on cognitive function in patients with schizophrenia, with a focus on social cognition (SC). Methods: Two groups of patients with schizophrenia were recruited and matched on sociodemographic and clinical characteristics. One group consisted of 32 patients with a history of childhood trauma (SCZ-ct), and the other group consisted of 30 patients without a history of childhood trauma (SCZ-nct). In addition, 39 healthy controls without a history of childhood trauma (HC-nct) were also recruited. The intelligence of the three groups was assessed using the Wechsler Abbreviated Scale of Intelligence (WAIS-RC) short version. The cognitive function evaluation was conducted using the MATRICS Consensus Cognitive Battery (MCCB), and early life adversity was measured using the Childhood Trauma Questionnaire-Short Form (CTQ) and Bullying Scale for Adults (BSA). Results: Patients with schizophrenia endosed significantly higher scores on the CTQ (F=67.61, p<0.001) and BSA (F=9.84, p<0.001) compared to the HC-nct. Analysis of covariance (ANCOVA) and post-hoc analyses revealed that SCZ-ct (F=11.20, p<0.001) exhibited the most pronounced cognitive impairment among the three groups, as indicated in MCCB total scores and in the domain score of SC. CTQ exhibited a negative correlation with MCCB (r=-0.405, p< 0.001); SC was negatively correlated with physical abuse (PA) of CTQ (r=-0.271, p=0.030) and emotional abuse (EA) of BSA (r=-0.265, p=0.034) in the whole patient sample. Higher SC performance was significantly predicted by CT_total (Beta =-0.582, p<0.001, 95% CI -0.96-0.46), and years of education (Beta=0.260, p =0.014, 95% CI 0.20-1.75) in schizophrenia. Conclusions: Besides familial trauma, schizophrenia patients appear to have a higher likelihood of experiencing bullying in their early life. These experiences seem to contribute significantly to their severe impairments in SC.

Further clarification of cognitive processes of prospective memory in schizophrenia by comparing eye-tracking and ecologically-valid measurements.

The aim of this study is to compare ecologically-valid measure (the Cambridge Prospective Memory Test, CAMPROMPT) and laboratory measure (eye-tracking paradigm) in assessing prospective memory (PM) in individuals with schizophrenia spectrum disorders (SSDs). In addition, eye-tracking indices are used to examine the relationship between PM and other cognitive domains in SSDs patients. Initially, the study sample was formed by 32 SSDs patients and 32 healthy control subjects (HCs) who were matched in sociodemographic profile and the performance on CAMPROMPT. An eye-tracking paradigm was employed to examine the differences in PM accuracy and key cognitive processes (e.g., cue monitoring) between the two groups. Additional 31 patients were then recruited to investigate the relationship between PM cue monitoring, other cognitive functions, and the severity of clinical symptoms within the SSDs group. The monitoring of PM cue was reflected in total fixation time and total fixation counts for distractor words. Cognitive functions were assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). The Positive and Negative Syndrome Scale (PANSS) was applied to assess psychopathology. SSDs patients exhibited fewer total fixation counts for distractor words and lower PM accuracy compared to HCs, even though they were priori matched on CAMPROMPT. Correlation analysis within the SSDs group (63 cases) indicated a negative correlation between PM accuracy and PANSS total score, and a positive correlation with working memory and attention/vigilance. Regression analysis within the SSDs group revealed that higher visual learning and lower PANSS total scores independently predicted more total fixation counts on distractor words. Impairment in cue monitoring is a critical factor in the PM deficits in SSDs. The eye-tracking laboratory paradigm has advantages over the ecologically-valid measurement in identifying the failure of cue detection, making it a more sensitive tool for PM deficits in patients with SSDs.

Effect of transcranial direct current stimulation with concurrent cognitive performance targeting posterior parietal cortex vs prefrontal cortex on working memory in schizophrenia: a randomized clinical trial.

Working memory deficits are linked to irregularities in the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in schizophrenia, effective intervention strategies are lacking. We evaluated the differential efficacy and underlying neuromechanisms of targeting transcranial direct current stimulation (tDCS) at the DLPFC and the PPC with concurrent cognitive performance for working memory in schizophrenia. In a randomized and double-blind clinical trial, sixty clinically stable schizophrenic patients with below-average working memory were randomly assigned to active DLPFC, active PPC, and sham tDCS groups. Two sessions of tDCS during N-back task were delivered daily for five days. The primary outcome was changes in spatial span test scores from baseline to week 1. The secondary outcomes included changes in scores of color delay-estimation task, other cognitive tasks, and mismatch negativity (biomarker of N-methyl-d-aspartate receptor functioning). Compared with the active DLPFC group, the active PPC group demonstrated significantly greater improvement in spatial span test scores (p = 0.008, d = 0.94) and an augmentation in color delay-estimation task capacity at week 1; the latter sustained to week 2. Compared with the sham tDCS group, the active PPC group did not show a significant improvement in spatial span test scores at week 1 and 2; however, significant enhancement was observed in their color delay-estimation task capacity at week 2. Additionally, mismatch negativity amplitude was enhanced, and changes in theta band measures were positively correlated with working memory improvement in the active PPC group, while no such correlations were observed in the active DLPFC group or the sham tDCS group. Our results suggest that tDCS targeting the PPC relative to the DLPFC during concurrent cognitive performance may improve working memory in schizophrenia, meriting further investigation. The improvement in working memory appears to be linked to enhanced N-methyl-d-aspartate receptor functioning.

Interaction between catechol-O-methyltransferase Val/Met polymorphism and cognitive reserve for negative symptoms in schizophrenia.

BACKGROUND: Cognitive reserve (CR) and the catechol-O-methyltransferase (COMT) Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia. However, the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined. AIM: To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism. METHODS: In a cross-sectional study, 54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype, CR, and negative symptoms. CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale. RESULTS: COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes. In the total sample, significant negative correlations were found between negative symptoms and information, similarities. Associations between information, similarities and negative symptoms were observed in Val homozygotes only, with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms (information, ß = -0.282, 95%CI: -0.552 to -0.011, P = 0.042; similarities, ß = -0.250, 95%CI: -0.495 to -0.004, P = 0.046). CONCLUSION: This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.

Antibodies targeting the glycan cap of Ebola virus glycoprotein are potent inducers of the complement system

Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. Both neutralization and some of the Fc-mediated effects are known to contribute the protection conferred by antibodies of various epitope specificities. At the same time, the role of the complement system remains unclear. Here, we compare complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of GP. Binding of GC-specific mAbs to GP induces complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs. In the mouse model of EBOV infection, depletion of the complement system leads to an impairment of protection exerted by one of the GC-specific, but not MPER-specific mAbs. Our data suggest that activation of the complement system represents an important mechanism of antiviral protection by GC antibodies.

p53 binding prevents phosphatase-mediated inactivation of diphosphorylated c-Jun N-terminal kinase.

c-Jun N-terminal kinase (JNK) is a serine/threonine phosphotransferase whose sustained activation in response to genotoxic stress promotes apoptosis. In Drosophila, the normally rapid JNK-dependent apoptotic response to genotoxic stress is significantly delayed in Dmp53 (Drosophila p53) mutants. Likewise, the extent of JNK activity after UV irradiation is dependent on p53 in murine embryonic fibroblasts with loss of p53 resulting in diminished JNK activity. Together, these results suggest that p53 potentiates the JNK-dependent response to genotoxic stress; however, the mechanism whereby p53 stimulates JNK activity remains undefined. Here, we demonstrate that both Drosophila and human p53 can directly stimulate JNK activity independently of p53-dependent gene transcription. Furthermore, we demonstrate that both the Drosophila and human p53 orthologs form a physical complex with diphosphorylated JNK ((DP)JNK) both in vivo and in vitro, suggesting that the interaction is evolutionarily conserved. Focusing on human p53, we demonstrate that the interaction maps to the DNA binding domain (hp53(DBD)). Intriguingly, binding of p53(DBD) alone to (DP)JNK prevented its inactivation by MAPK phosphatase (MKP)-5; however, JNK was still able to phosphorylate c-Jun while in a complex with the p53(DBD). Apparent dissociation constants for the p53(DBD)·(DP)JNK (274 ± 14 nm) and MKP-5·(DP)JNK (55 ± 8 nm) complexes were established; however, binding of MKP-5 and p53 to JNK was not mutually exclusive. Together, these results suggest that stress-dependent increases in p53 levels potentiate JNK activation by preventing its rapid dephosphorylation by MKPs and that the simultaneous activation of p53 and JNK may constitute a "fail-safe" switch for the JNK-dependent apoptotic response.

Reactive oxygen species hydrogen peroxide mediates Kaposi's sarcoma-associated herpesvirus reactivation from latency.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent infection in the host following an acute infection. Reactivation from latency contributes to the development of KSHV-induced malignancies, which include Kaposi's sarcoma (KS), the most common cancer in untreated AIDS patients, primary effusion lymphoma and multicentric Castleman's disease. However, the physiological cues that trigger KSHV reactivation remain unclear. Here, we show that the reactive oxygen species (ROS) hydrogen peroxide (H2O2) induces KSHV reactivation from latency through both autocrine and paracrine signaling. Furthermore, KSHV spontaneous lytic replication, and KSHV reactivation from latency induced by oxidative stress, hypoxia, and proinflammatory and proangiogenic cytokines are mediated by H2O2. Mechanistically, H2O2 induction of KSHV reactivation depends on the activation of mitogen-activated protein kinase ERK1/2, JNK, and p38 pathways. Significantly, H2O2 scavengers N-acetyl-L-cysteine (NAC), catalase and glutathione inhibit KSHV lytic replication in culture. In a mouse model of KSHV-induced lymphoma, NAC effectively inhibits KSHV lytic replication and significantly prolongs the lifespan of the mice. These results directly relate KSHV reactivation to oxidative stress and inflammation, which are physiological hallmarks of KS patients. The discovery of this novel mechanism of KSHV reactivation indicates that antioxidants and anti-inflammation drugs could be promising preventive and therapeutic agents for effectively targeting KSHV replication and KSHV-related malignancies.

Factors associated with suicidal attempts in female patients with mood disorder.

Aim: This study aims to establish a nomogram model to predict the relevance of SA in Chinese female patients with mood disorder (MD). Method: The study included 396 female participants who were diagnosed with MD Diagnostic Group (F30-F39) according to the 10th Edition of Disease and Related Health Problems (ICD-10). Assessing the differences of demographic information and clinical characteristics between the two groups. LASSO Logistic Regression Analyses was used to identify the risk factors of SA. A nomogram was further used to construct a prediction model. Bootstrap re-sampling was used to internally validate the final model. The Receiver Operating Characteristic (ROC) curve and C-index was also used to evaluate the accuracy of the prediction model. Result: LASSO regression analysis showed that five factors led to the occurrence of suicidality, including BMI (ß = -0.02, SE = 0.02), social dysfunction (ß = 1.72, SE = 0.24), time interval between first onset and first dose (ß = 0.03, SE = 0.01), polarity at onset (ß = -1.13, SE = 0.25), and times of hospitalization (ß = -0.11, SE = 0.06). We assessed the ability of the nomogram model to recognize suicidality, with good results (AUC = 0.76, 95% CI: 0.71-0.80). Indicating that the nomogram had a good consistency (C-index: 0.756, 95% CI: 0.750-0.758). The C-index of bootstrap resampling with 100 replicates for internal validation was 0.740, which further demonstrated the excellent calibration of predicted and observed risks. Conclusion: Five factors, namely BMI, social dysfunction, time interval between first onset and first dose, polarity at onset, and times of hospitalization, were found to be significantly associated with the development of suicidality in patients with MD. By incorporating these factors into a nomogram model, we can accurately predict the risk of suicide in MD patients. It is crucial to closely monitor clinical factors from the beginning and throughout the course of MD in order to prevent suicide attempts.

Blocking of ebolavirus spread through intercellular connections by an MPER-specific antibody depends on BST2/tetherin.

Ebola virus (EBOV) and Bundibugyo virus (BDBV) belong to the family Filoviridae and cause a severe disease in humans. We previously isolated a large panel of monoclonal antibodies from B cells of human survivors from the 2007 Uganda BDBV outbreak, 16 survivors from the 2014 EBOV outbreak in the Democratic Republic of the Congo, and one survivor from the West African 2013-2016 EBOV epidemic. Here, we demonstrate that EBOV and BDBV are capable of spreading to neighboring cells through intercellular connections in a process that depends upon actin and T cell immunoglobulin and mucin 1 protein. We quantify spread through intercellular connections by immunofluorescence microscopy and flow cytometry. One of the antibodies, BDBV223, specific to the membrane-proximal external region, induces virus accumulation at the plasma membrane. The inhibiting activity of BDBV223 depends on BST2/tetherin.

EMDR versus waiting list in individuals at clinical high risk for psychosis with post-traumatic stress symptoms: A randomized controlled trial.

BACKGROUND: Post-traumatic stress disorder (PTSD) is highly prevalent in the individuals at clinical-high risk for psychosis (CHR). The aim of this study was to examine the efficacy and safety of Eye Movement Desensitization and Reprocessing (EMDR) in individuals at CHR with comorbid PTSD or subthreshold PTSD in a randomized controlled trial. METHODS: Fifty-seven individuals at CHR with PTSD or subthreshold PTSD formed the study sample. The eligible participants were randomly assigned to a 12 weeks EMDR treatment (N = 28) or a waiting list condition (WL, N = 29). The structured interview for psychosis risk syndrome (SIPS), the clinician administered post-traumatic stress disorder scale (CAPS) and a battery of self-rating inventories covering depressive, anxiety and suicidal symptoms were administered. RESULTS: Twenty-six participants in the EMDR group and all the participants in the WL group completed the study. The analyses of covariance revealed greater reduction of the mean scores on CAPS (F = 23.2, Partial η2 = 0.3, P < 0.001), SIPS positive scales (F = 17.8, Partial η2 = 0.25, P < 0.001) and all the self-rating inventories in the EMDR group than in the WL group. Participants in the EMDR group were more likely to achieve remission of CHR compared to those in the WL group at endpoint (60.7 % vs. 31 %, P = 0.025). CONCLUSIONS: EMDR treatment not only effectively improved traumatic symptoms, but also significantly reduced the attenuated psychotic symptoms and resulted in a higher remission rate of CHR. This study highlighted the necessity of adding a trauma-focused component to the present approach of early intervention in psychosis.

Nitric oxide suppression by secreted frizzled-related protein 2 drives retinoblastoma.

Retinoblastoma is a cancer of the infant retina primarily driven by loss of the Rb tumor suppressor gene, which is undruggable. Here, we report an autocrine signaling, mediated by secreted frizzled-related protein 2 (SFRP2), which suppresses nitric oxide and enables retinoblastoma growth. We show that coxsackievirus and adenovirus receptor (CXADR) is the cell-surface receptor for SFRP2 in retinoblastoma cells; that CXADR functions as a "dependence receptor," transmitting a growth-inhibitory signal in the absence of SFRP2; and that the balance between SFRP2 and CXADR determines nitric oxide production. Accordingly, high SFRP2 RNA expression correlates with high-risk histopathologic features in retinoblastoma. Targeting SFRP2 signaling by SFRP2-binding peptides or by a pharmacological inhibitor rapidly induces nitric oxide and profoundly inhibits retinoblastoma growth in orthotopic xenograft models. These results reveal a cytokine signaling pathway that regulates nitric oxide production and retinoblastoma cell proliferation and is amenable to therapeutic intervention.