Incidence and risk factors of depression in patients with metabolic syndrome.

BACKGROUND: Many studies have explored the relationship between depression and metabolic syndrome (MetS), especially in older people. China has entered an aging society. However, there are still few studies on the elderly in Chinese communities. AIM: To investigate the incidence and risk factors of depression in MetS patients in mainland China and to construct a predictive model. METHODS: Data from four waves of the China Health and Retirement Longitudinal Study were selected, and middle-aged and elderly patients with MetS (n = 2533) were included based on the first wave. According to the center for epidemiological survey-depression scale (CESD), participants with MetS were divided into depression (n = 938) and non-depression groups (n = 1595), and factors related to depression were screened out. Subsequently, the 2-, 4-, and 7-year follow-up data were analyzed, and a prediction model for depression in MetS patients was constructed. RESULTS: The prevalence of depression in middle-aged and elderly patients with MetS was 37.02%. The prevalence of depression at the 2-, 4-, and 7-year follow-up was 29.55%, 34.53%, and 38.15%, respectively. The prediction model, constructed using baseline CESD and Physical Self-Maintenance Scale scores, average sleep duration, number of chronic diseases, age, and weight had a good predictive effect on the risk of depression in MetS patients at the 2-year follow-up (area under the curve = 0.775, 95% confidence interval: 0.750-0.800, P < 0.001), with a sensitivity of 68% and a specificity of 74%. CONCLUSION: The prevalence of depression in middle-aged and elderly patients with MetS has increased over time. The early identification of and intervention for depressive symptoms requires greater attention in MetS patients.

Association between platelet distribution width and poor outcome of acute ischemic stroke after intravenous thrombolysis.

PURPOSE: The platelet distribution width (PDW) reflects the status of platelet activity and may be useful for early predictions of the clinical outcome of stroke patients. The purpose of the study was to determine the associations between PDW and clinical outcomes after intravenous thrombolysis in stroke patients. PATIENTS AND METHODS: Acute ischemic stroke patients who received intravenous treatment with recombinant tissue-type plasminogen activator were selected for inclusion in the retrospective cohort of this study. The relations between PDW at admission and clinical outcomes were analyzed, including a poor outcome as assessed using the modified Rankin Scale at 3 months, early neurological improvement, and any hemorrhage. The effect of PDW at admission on a poor outcome at 3 months was analyzed using a multivariable logistic regression model with adjustment for potential confounders. The optimal PDW cutoff for predicting poor outcome at 3 months was determined by analyzing the receiver operating characteristics curve. RESULTS: PDW was significantly higher for a good outcome than a poor outcome (p=0.005), with median (interquartile range) values of 16.2 (13.2-17.2) and 13.6 (12.5-15.9), respectively. PDW was also higher in patients with early neurological improvement than in patients without improvement (p=0.020) and did not differ between hemorrhage and nonhemorrhage patients. The association between PDW <16.05% and poor outcome remained in a multivariable logistic regression analysis, with an OR of 6.68 and a 95% CI of 1.69-26.49 (p=0.007). CONCLUSION: Results suggest a novel hypothesis that a lower PDW may be related with a poor outcome at 3 months after intravenous thrombolysis in acute ischemic stroke patients.

Impaired visual, working, and verbal memory in first-episode, drug-naive patients with major depressive disorder in a Chinese population.

Cognitive impairment has been observed in patients with major depressive disorder (MDD). However, it remains unclear whether the deficits in specific cognitive domains are present in first-episode, drug-naïve patients or medicated patients. In the present study, using the CogState battery (CSB) Chinese language version, we evaluated the visual, working, and verbal memory in first-episode drug-naive patients and medicated patients with MDD in a Chinese population. We measured the cognitive function in first-episode drug-naïve patients (n = 36), medicated MDD patients (n = 71), and age- and sex-matched healthy control subjects (n = 59) in a Chinese population. The CSB composite scores in both first-episode drug-naive patients and medicated patients were significantly poorer than those in the healthy control subjects. The CSB sub-scores, including visual, working, and verbal memory were also significantly poorer in both patient groups than those in the healthy control subjects. In contrast, processing speed, attention/vigilance, executive function, spatial working memory, and social cognition were no different from healthy controls, whereas the executive function was significantly better in the medicated patients than in the healthy control subjects and first-episode drug-naïve patients. These findings suggest an impairment in the visual, working, and verbal memory in first-episode, drug-naive MDD patients in a Chinese population.

De Ritis ratio (AST/ALT) as an independent predictor of poor outcome in patients with acute ischemic stroke.

PURPOSE: The aspartate transaminase/alanine transaminase ratio (De Ritis ratio, AAR) was reported to be associated with patients' prognosis in certain diseases recently. The objective of the current study was to determine the association between the AAR at admission and poor outcome at 3 months in acute ischemic stroke (AIS) patients. PATIENTS AND METHODS: This retrospective cohort study included patients who experienced their first-ever AIS between June 2015 and March 2016. The primary outcome measure was a poor outcome at 3 months (modified Rankin Scale score >2). Multivariate logistic regression models were used to assess the relationship between AAR quartiles and clinical outcomes among the AIS patients. Receiver operating characteristic curve analysis was applied to identify the optimal cutoff for AAR in predicting the prognosis of AIS. RESULTS: In terms of the relationship between poor outcome and AAR, the adjusted odds ratio comparing the highest and lowest AAR quartiles was 2.15 (95% confidence interval =1.14-4.05). An AAR of 1.53 was identified as the optimal cutoff. In a prespecified subgroup analysis according to the time from symptom onset to treatment (>24 vs ≤24 hours), there was no significant difference in the effect of AAR >1.53 between the two groups. CONCLUSION: An increased AAR at admission is significantly associated with a poor outcome at 3 months in AIS patients.

Effect of Hypokalemia on Functional Outcome at 3 Months Post-Stroke Among First-Ever Acute Ischemic Stroke Patients.

BACKGROUND Hypokalemia has been confirmed to be a predictor of adverse cardiovascular and renal outcomes. There is a paucity of studies focusing on the potential connection between the serum K+ level and the outcome after acute ischemic stroke (AIS). This study investigated whether hypokalemia in the acute stroke stage contributes to worse functional outcome in AIS patients. MATERIAL AND METHODS This retrospective cohort study included consecutive patients with first-ever AIS admitted between June 2015 and March 2016. Patients were divided into 2 groups: hypokalemia (K+ <3.5 mmol/L) and normokalemia (3.5 mmol/L ≤K+ ≤5.5 mmol/L). Primary outcome measure was poor outcome at 3 months (modified Rankin scale >2). Univariate and multivariate logistic regression analyses were used to assess the association between hypokalemia and poor outcome. Receiver operating curve (ROC) analysis was performed to determine the optimal cutoff point of serum K+ level for predicting poor outcome. RESULTS The percent of patients with poor outcome at 3 months was higher in the hypokalemic group (62.9%) than in the normokalemic group (45.5%). Hypokalemic patients tended to have lower fasting glucose at admission, lower Glasgow coma scale score, and longer time from symptom onset to treatment compared with normokalemic patients. Hypokalemia was associated with poor outcome at 3 months after adjusting for potential confounders (odds ratio=2.42, 95% confidence interval=1.21-4.86, P=0.013). ROC analysis showed that the optimal threshold for serum K+ level was 3.7 mmol/L. CONCLUSIONS Hypokalemia at the initial admission is associated with poor prognosis at 3 months in first-ever AIS patients.

Increased methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of patients with generalized anxiety disorder.

Previous findings on the dysfunction of hypothalamic-pituitary-adrenal (HPA) axis in generalized anxiety disorder (GAD) are controversial, and the molecular mechanisms underlying such dysfunction remain unclear. We analyzed the methylation status of the NR3C1 1F promoter and the expression of glucocorticoid receptor-α isoform (GRα) in peripheral blood mononuclear cells (PMBCs), the basal cortisol level in serum, and a functional neuroendocrine marker for GR sensitivity in the PMBCs in 64 patients with current GAD and 85 healthy controls. We found that patients with GAD had significantly elevated levels of morning basal serum cortisol (P < 0.0001) and diminished GR sensitivity in the PBMCs (P < 0.0001) compared with healthy controls. The overall methylation levels across NR3C1 1F promoter (P < 0.0001) and percent methylation at each of the 5 CpG sites including CpG12, 21, 30, 31, and 32 (P < 0.001) significantly increased. Accordingly, the mRNA levels of GRα significantly decreased (P < 0.0001) in the PBMCs in patients with GAD compared with healthy controls, with the effects specific in patients without childhood traumatic experience. Moreover, both serum basal cortisol levels and GR sensitivity in the PBMCs were negatively correlated with the overall methylation levels of the NR3C1 1F promoter (P < 0.0001) and positively correlated with GRα mRNA levels (P = 0.007) in the PBMCs. In sum, our study revealed the increased activity of the HPA axis and diminished peripheral glucocorticoid responsiveness of GR underlying episodes of GAD. Furthermore, such dysfunction of the HPA axis is associated with both increased DNA methylation of NR3C1 1F promoter and decreased GRα expression.

The effect of reintubation on ventilator-associated pneumonia and mortality among mechanically ventilated patients with intubation: A systematic review and meta-analysis.

OBJECTIVES: This meta-analysis summarized the risks that reintubation impose on ventilator-associated pneumonia (VAP) and mortality. BACKGROUND: Extubation failure increases the probability of poor clinical outcomes pertaining to mechanical ventilation. METHODS: Literature published during a 15-year period was retrieved from PubMed, Web of Knowledge databases, the Embase (Excerpa Medica database), and the Cochrane Library. Data involving reintubation, VAP, and mortality were extracted for a meta-analysis. RESULTS: Forty-one studies involving 29,923 patients were enrolled for the analysis. The summary odds ratio (OR) between VAP and reintubation was 7.57 (95% confidence interval [CI] = 3.63-15.81). The merged ORs for mortality in hospital and intensive care unit were 3.33 (95% CI = 2.02-5.49) and 7.50 (95% CI = 4.60-12.21), respectively. CONCLUSIONS: Reintubation can represent a threat to survival and increase the risk of VAP. The risk of mortality after reintubation differs between planned and unplanned extubation. Extubation failure is associated with a higher risk of VAP in the cardiac surgery population than in the general population.

Intranasal Delivery of Recombinant AAV Containing BDNF Fused with HA2TAT: a Potential Promising Therapy Strategy for Major Depressive Disorder.

Depression is a disturbing psychiatric disease with unsatisfied therapy. Not all patients are sensitive to anti-depressants currently in use, side-effects are unavoidable during therapy, and the cases with effectiveness are always accompanied with delayed onset of clinical efficacy. Delivering brain-derived neurotrophic factor (BDNF) to brain seems to be a promising therapy. However, a better approach to delivery is still rudimentary. The purpose of our present work is to look for a rapid-onset and long-lasting therapeutic strategy for major depressive disorder (MDD) by effectively delivering BDNF to brain. BDNF, fused with cell-penetrating peptides (TAT and HA2), was packaged in adenovirus associated virus (AAV) to construct the BDNF-HA2TAT/AAV for intranasally delivering BDNF to central nervous system (CNS) via nose-brain pathway. Intranasal administration of BDNF-HA2TAT/AAV to normal mice displayed anti-depression effect in forced swimming test when the delivery lasted relatively longer. The AAV applied to mice subjected to chronic mild stress (CMS) through intranasal administration for 10 days also alleviated depression-like behaviors. Western-blotting analysis revealed that BDNF-HA2TAT/AAV nasal administration enhanced hippocampal BDNF content. These results indicate intranasal administration of constructed BDNF-HA2TAT/AAV exerts anti-depression effect in CMS mice by increasing hippocampal BDNF, suggesting that this strategy holds a promising therapeutic potential for MDD.

Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect.

The present study was designed to construct a recombinant adeno-associated virus (rAAV) which can express NAP in the brain and examine whether this virus can produce antidepressant effects on C57 BL/6 mice that had been subjected to open field test and forced swimming test, via nose-to-brain pathway. When the recombinant plasmid pGEM-T Easy/NT4-NAP was digested by EcoRI, 297 bp fragments can be obtained and NT4-NAP sequence was consistent with the designed sequence confirmed by DNA sequencing. When the recombinant plasmid pSSCMV/NT4-NAP was digested by EcoRI, 297 bp fragments is visible. Immunohistochemical staining of fibroblasts revealed that expression of NAP was detected in NT4-NAP/AAV group. Intranasal delivery of NT4-NAP/AAV significantly reduced immobility time when the FST was performed after 1 day from the last administration. The effects observed in the FST could not be attributed to non-specific increases in activity since intranasal delivery of NT4-NAP/AAV did not alter the behavior of the mice during the open field test. The results indicated that a recombinant AAV vector which could express NAP in cells was successfully constructed and NAP may be a potential target for therapeutic action of antidepressant treatment.

Association Between MKP-1, BDNF, and Gonadal Hormones with Depression on Perimenopausal Women.

BACKGROUND: Studies suggest that brain-derived neurotrophic factor (BDNF) exerts effects on the neuronal function of hippocampal neurons and increases hippocampal mitogen-activated protein kinase phosphatase-1 (MKP-1) expression, which causes depressive behaviors in rat or mouse. Here we focus on the change of serum MKP-1, BDNF, testosterone (T), and estradiol (E2) levels, in order to test the hypothesis that dysregulation of MKP-1, BDNF, T, and E2 are associated with depression in perimenopausal women. METHODS: Women with depression, after meeting criteria in the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, for mental and behaviural disorders and the 17-item Hamilton Depression Rating Scale (HDRS), were included in the study. Psychosocial data and blood samples were obtained from the subjects in the study, including 38 perimenopausal and 32 young women with depression, 26 healthy control perimenopausal women, and 34 young women. RESULTS: Serum MKP-1 levels were higher and T was lower in the women with depression compared to controls (p<0.05), and depressed perimenopausal women exhibited the highest serum MKP-1 levels and lowest T levels. Logistic regression analyses showed that MKP-1 levels were positively correlated with HDRS scores in the women, and T levels were inversely correlated with HDRS scores in the perimenopausal women (p<0.05). CONCLUSIONS: This study suggests that high serum MKP-1 levels are associated with depression in women, and this association did not appear to be confounded by age. Further, the results provide evidence of association between depressive symptom severity and increasing serum MKP-1 levels in women, and decreasing T levels in perimenopausal women.

Genetic polymorphisms of CYP1A1 and risk of leukemia: a meta-analysis.

The associations between CYP1A1 polymorphisms and risk of leukemia have been studied extensively, but the results have been inconsistent. Therefore, in this study, we performed a meta-analysis to clarify associations of three CYP1A1 polymorphisms (T3801C, A2455G, and C4887A) with the risks of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Medline, EMBASE, and China National Knowledge Infrastructure databases were searched to collect relevant studies published up to April 20, 2015. The extracted data were analyzed statistically, and pooled odds ratios with 95% confidence intervals were calculated to quantify the associations. Overall, 26 publications were included. Finally, T3801C was associated with an increased risk of AML in Asians under the dominant model. For A2455G, the risk of ALL was increased among Caucasians in the recessive model and the allele-contrast model; A2455G was also associated with an increased risk of CML among Caucasians under the recessive model, dominant model, and allele-contrast model. For C4887A, few of the included studies produced data. In conclusion, the results suggest that Asians carrying the T3801C C allele might have an increased risk of AML and that Caucasians with the A2455G GG genotype might have an increased risk of ALL. Further investigations are needed to confirm these associations.

A common genetic variation in CEBPE and acute lymphoblastic leukemia: a meta-analysis of the available evidence.

Acute lymphoblastic leukemia (ALL) has been studied intensively for decades, but the details of its etiology and underlying mechanisms have yet to be fully elucidated. It is now generally acknowledged that genetic factors contribute greatly to the development of this disease. The gene encoding CCAAT/enhancer-binding protein ε (CEBPE) is involved in the development of leukemia, and in particular the rs2239633 single nucleotide polymorphism (SNP) of CEBPE. The association between rs2239633 and risk of ALL has been well studied, but remains unclear. Therefore, a meta-analysis was performed in this study to establish a more precise estimation of that relationship. A comprehensive literature search of the PubMed electronic database was conducted, and relevant studies published up to February 20, 2015 were selected for analysis. The references of the retrieved articles were also screened. The extracted data were analyzed statistically, and pooled odds ratios with 95% confidence intervals were calculated using Review Manager (version 5.2) to estimate the association strength. Finally, eleven studies were included in the meta-analysis. The pooled analyses revealed that rs2239633 was associated with an increased risk of childhood ALL in Caucasians under any contrast models (P<0.01). However, this SNP did not affect the risk of ALL in adulthood among Caucasians, or in childhood among East Asians. In conclusion, these findings confirm that the CEBPE rs2239633 SNP could be considered a good marker of pediatric ALL risk in Caucasians, but not in East Asians; it is not a good marker of adult ALL risk in Caucasians.

HINT1 is involved in the behavioral abnormalities induced by social isolation rearing.

Social isolation (SI) rearing has been demonstrated to induce behavioral abnormalities like anxiety, impulsivity, aggression, and learning and memory deficits which are relevant to core symptoms in patients with some certain neuropsychiatric disorders. But the underlying pathophysiological mechanisms remain unclear. Recent studies have revealed HINT1 has close relation with diverse neuropsychiatric diseases. In this present study, the SI rearing mice exhibited depression-like and aggressive behavior. Besides, HINT1 protein levels decreased in PFC but increased in HIP. Based on the data obtained, we concluded that HINT1 is involved in the behavioral abnormalities induced by social isolation and exerts distinct roles in different encephalic regions.

Zirconium oxide ceramic foam: a promising supporting biomaterial for massive production of glial cell line-derived neurotrophic factor.

This study investigated the potential application of a zirconium oxide (ZrO2) ceramic foam culturing system to the production of glial cell line-derived neurotrophic factor (GDNF). Three sets of ZrO2 ceramic foams with different pore densities of 10, 20, and 30 pores per linear inch (PPI) were prepared to support a 3D culturing system. After primary astrocytes were cultured in these systems, production yields of GDNF were evaluated. The biomaterial biocompatibility, cell proliferation and activation of cellular signaling pathways in GDNF synthesis and secretion in the culturing systems were also assessed and compared with a conventional culturing system. In this study, we found that the ZrO2 ceramic foam culturing system was biocompatible, using which the GDNF yields were elevated and sustained by stimulated cell proliferation and activation of signaling pathways in astrocytes cultured in the system. In conclusion, the ZrO2 ceramic foam is promising for the development of a GDNF mass production device for Parkinson's disease treatment.

Targeting of NMDA receptors in the treatment of major depression.

Major depressive disorder (MDD) is a common, recurrent mental illness that affects millions of people worldwide. Accumulating evidence suggests that the N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptors, plays an important role in the neurobiology and treatment of this disease. Currently, the non-competitive NMDA receptor antagonist ketamine is considered as one of the most attractive candidate drugs in therapy of treatment-resistant depression. A recent study demonstrated ketamine's rapid antidepressant activity in patients with treatment-resistant MDD and bipolar disorder. The response rate for ketamine ranged from 25% to 85% at 24 hours post-infusion and from 14% to 70% at 72 hours post-infusion, with generally mild adverse effects. Based on the role of the NMDA receptor in depression, a number of therapeutic drugs which interact with this receptor have been developed. In this article, we reviewed recent findings concerning the role of glutamatergic signaling in the neurobiology of MDD and potential, novel therapeutic drugs, such as ketamine, memantine, AZD6765, traxoprodil, MK-0657, GLYX-13, NRX-1047, D-cycloserine, sarcosine, all of which target this system.

Association of the GDNF gene with depression and heroin dependence, but not schizophrenia, in a Chinese population.

The association of seven GDNF tag SNPs with depression, heroin dependence (HD) and schizophrenia was evaluated in Chinese. An increased risk of HD and depression was associated with rs2910709 T/T genotype and rs884344 C allele, respectively, suggesting GDNF is a novel susceptibility gene for depression and HD.

Long-lasting antidepressant action of ketamine, but not glycogen synthase kinase-3 inhibitor SB216763, in the chronic mild stress model of mice.

BACKGROUND: Clinical studies demonstrate that the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, induces rapid antidepressant effects in patients with refractive major depressive disorder and bipolar depression. This rapid onset of action makes ketamine a highly attractive drug for patients, particularly those who do not typically respond to therapy. A recent study suggested that glycogen synthase kinase (GSK)-3 may underlie the rapid antidepressant action of ketamine, although the precise mechanisms are unclear. In this study, we examined the effects of ketamine and GSK-3 inhibitor SB216763 in the unpredictable, chronic mild stress (CMS) mouse model of mice. METHODOLOGY/PRINCIPAL FINDINGS: Adult C57/B6 male mice were divided into 2 groups, a non-stressed control group and the unpredictable CMS (35 days) group. Then, either vehicle, ketamine (10 mg/kg), or the established GSK-3 inhibitor, SB216763 (10 mg/kg), were administered into mice in the CMS group, while vehicle was administered to controls. In the open field test, there was no difference between the four groups (control+vehicle, CMS+vehicle, CMS+ketamine, CMS+SB216763). In the sucrose intake test, a 1% sucrose intake drop, seen in CMS mice, was significantly attenuated after a single dose of ketamine, but not SB216763. In the tail suspension test (TST) and forced swimming test (FST), the increased immobility time seen in CMS mice was significantly attenuated by a single dose of ketamine, but not SB216763. Interestingly, the ketamine-induced increase in the sucrose intake test persisted for 8 days after a single dose of ketamine. Furthermore, a single administration of ketamine, but not SB216763, significantly attenuated the immobility time of the TST and FST in the control (non-stressed) mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest that a single administration of ketamine, but not GSK-3 inhibitor SB216763, produces a long-lasting antidepressant action in CMS model mice.

Prevalence of PTSD and depression among junior middle school students in a rural town far from the epicenter of the Wenchuan earthquake in China.

CONTEXT: On May 12(th) 2008, a devastating earthquake measuring 8.0 on the Richter scale, struck Wenchuan county and surrounding areas in China. The prevalence of mental illness among children and adolescents in a rural town far from the earthquake epicenter is unknown. OBJECTIVE: To assess the prevalence of posttraumatic stress disorder (PTSD) and depression among junior middle school students in a rural town Ningqiang county, 327 km from the earthquake epicenter. DESIGN, SETTING, AND PARTICIPANTS: A population-based mental health survey was conducted in March, 2009. MAIN OUTCOME MEASURE: Survey Self-designed General Condition Survey Scale, Children's Revised Impact of Event Scale (CRIES-13), and the Depression Self-rating Scale for Children (DSRSC) were used to sample 1,841 junior middle school students in Ningqiang county, ten months after the Wenchuan earthquake. RESULTS: The prevalence rate of a high-risk for PTSD was 28.4%, with 32.7% among females, 23.8% among males (female vs. male, p<0.001), 38.6% in the severe exposure group and 24.3% in the mild exposure group (severe vs. mild exposure, p<0.001). For depressive symptoms, the overall prevalence was 19.5%, with 24.0% among females, 14.7% among males, 24.5% in the severe exposure group and 17.5% in the mild exposure group (female vs. male, p<0.001; severe vs. mild exposure, p<0.001, respectively). In multivariate analysis, factors such as "having felt despair", or "danger" and "having own house destroyed or damaged" were significantly associated with PTSD symptoms. Female gender and delayed evacuation in females, and earthquake related experiences in males were significantly associated with depression. CONCLUSION: Traumatic events experienced during the earthquake were significantly associated with symptoms of PTSD and depression in children and adolescents, ten months after the Wenchuan earthquake. These data highlight a need for mental health services for children and adolescents in rural areas, far from earthquake epicenters.

Screening of the Salmonella paratyphi A CMCC 50973 strain outer membrane proteins for the identification of potential vaccine targets.

Outer membrane protein antigens usually have strong immunogenicities, closely interact with the immune system and play a significant role in the development of new vaccines. The outer membrane proteins of Salmonella paratyphi A (S. paratyphi A) were screened for immunogenicity and immunoprotection for potential vaccine targets. In this study, the bactericidal effect of antiserum against the total outer membrane proteins of S. paratyphi A CMCC 50973 strain was determined, and their immunoprotection was detected with a challenge experiment on vaccinated mice. The immunogenic outer membrane proteins were identified via immunoproteomic technology, and recombinant outer membrane proteins were expressed and purified. The immunoprotection provided by the immunogenic membrane proteins was verified through active and passive immunity challenge experiments. The result revealed a number of S. paratyphi A outer membrane proteins that were proven as strong protective antigens. Twelve immunogenic outer membrane proteins were located and identified. Five recombinant proteins (LamB, pagC, TolC, nmpC and fadL) with strong immunoprotective abilities were found via the active immunity challenge experiment, with protection rates of 95, 95, 85, 80 and 70%, respectively. They were also proven to induce good immunoprotection via the passive immunity challenge experiment, with protection rates of 65, 55, 60, 55 and 50%, respectively. The immunoprotective rate of the five-antiserum combination was 85%. In conclusion, the LamB, pagC, TolC, nmpC and fadL outer membrane proteins, with strong immunogenicities and immunoprotection, are effective protein candidate targets for the development of new vaccines, whereas the recombinant outer membrane proteins are a promising tool for improving immunoprotection.

Social isolation-induced aggression potentiates anxiety and depressive-like behavior in male mice subjected to unpredictable chronic mild stress.

BACKGROUND: Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS), an animal model of depression. METHODOLOGY/PRINCIPAL FINDINGS: C57/B6 male mice were divided into 3 groups; non-stressed controls, in Group I; isolated mice subjected to the CMS protocol in Group II and aggression by physical contact in socially isolated mice subjected to the CMS protocol in Group III. In the sucrose intake test, ingestion of a 1% sucrose solution by mice in Groups II and III was significantly lower than in Group I. Furthermore, intake of this solution in Group III mice was significantly lower than in Group II mice. In the open field test, mice in Group III, showed reduced locomotor activity and reduced entry and retention time in the central zone, compared to Groups I and II mice. Moreover, the distances moved in 1 hour by Group III mice did not differ between night and morning. In the light/black box test, Groups II and III animals spent significantly less time in the light box compared to Group I animals. In the tail suspension test (TST) and forced swimming test (FST), the immobility times of Group II and Group III mice were significantly longer than in Group I mice. In addition, immobility times in the FST were significantly longer in Group III than in Group II mice. CONCLUSIONS/SIGNIFICANCE: These findings show that social isolation-induced aggression could potentiate anxiety and depressive-like behaviors in isolated male mice subjected to CMS.