Extended Analysis of HIV Infection in Cisgender Men and Transgender Women Who Have Sex with Men Receiving Injectable Cabotegravir for HIV Prevention: HPTN 083.

HPTN 083 demonstrated that injectable cabotegravir (CAB) was superior to oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We previously analyzed 58 infections in the blinded phase of HPTN 083 (16 in the CAB arm and 42 in the TDF-FTC arm). This report describes 52 additional infections that occurred up to 1 year after study unblinding (18 in the CAB arm and 34 in the TDF-FTC arm). Retrospective testing included HIV testing, viral load testing, quantification of study drug concentrations, and drug resistance testing. The new CAB arm infections included 7 with CAB administration within 6 months of the first HIV-positive visit (2 with on-time injections, 3 with ≥1 delayed injection, and 2 who restarted CAB) and 11 with no recent CAB administration. Three cases had integrase strand transfer inhibitor (INSTI) resistance (2 with on-time injections and 1 who restarted CAB). Among 34 CAB infections analyzed to date, diagnosis delays and INSTI resistance were significantly more common in infections with CAB administration within 6 months of the first HIV-positive visit. This report further characterizes HIV infections in persons receiving CAB preexposure prophylaxis and helps define the impact of CAB on the detection of infection and the emergence of INSTI resistance.

Comparison of peak expiratory Flow(PEF) and COPD assessment test (CAT) to assess COPD exacerbation requiring hospitalization: A prospective observational study.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD) resulting in hospitalization is significantly associated with the increased morbidity and mortality, but there is a lack of an effective method to assess it. This study aimed to compare the ability of peak expiratory flow (PEF) and COPD assessment test (CAT) to assess COPD exacerbations requiring hospitalization. METHODS: A cohort of 110 patients with moderate to severe COPD was studied over a period of 12 months, and their daily morning PEFs and CAT scores were recorded throughout the study. RESULTS: After 12 months of follow-up, 72 patients experienced 156 COPD exacerbations, 74 (47%) that resulted in hospitalization and 82 (53%) that did not result in hospitalization. Change in CAT score from baseline to exacerbation was significantly related to change in PEF and Spearman's rho =0.375 (95% CI, 0.227 to 0.506; p < .001). Change in PEF and CAT score from baseline to hospitalized exacerbation was significantly larger than that from baseline to non-hospitalized exacerbation (p < .05). Multivariable analysis indicated that ΔPEF (OR 1.11, 95% CI 1.06-1.16, p < .001) and ΔCAT (OR 1.64 95% CI 1.18-2.27, p = .003) were independently associated with risk of hospitalized exacerbation. ROC analysis indicated that the optimal cutoff value of ΔPEF for identifying hospitalized exacerbation was 49 L/min (27% from baseline), with a sensitivity and specificity of 82.7% and 76.7% (area under the curve [AUC] = 0.872 (95% CI 0.80-0.944, p < .05). The optimal cutoff value of ΔCAT score for identifying hospitalized exacerbation was 10.5 (63% from baseline), with a sensitivity and specificity of 67.3% and 77.4% [AUC]=0.763 (95% CI 0.67-0.857, p < .05). The AUC of ΔPEF and ΔCAT combined for the identification of hospitalized exacerbation was 0.900 (95% CI 0.841-0.959, p < .05), which was larger than that of ΔCAT or ΔPEF. CONCLUSIONS: ΔPEF and ΔCAT were independently associated with risk of hospitalized exacerbation. Compared with CAT, PEF was superior to identify hospitalized exacerbation. Identification via PEF and CAT combined is more effective than using PEF or CAT alone. These results help to assess the severity of COPD exacerbation and provide valuable information for clinical decision-making.

Characterization of Human Immunodeficiency Virus (HIV) Infection in Cisgender Men and Transgender Women Who Have Sex With Men Receiving Injectable Cabotegravir for HIV Prevention: HPTN 083.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with men. We characterized HIV infections that occurred in the blinded phase of HPTN 083. METHODS: Retrospective testing included HIV testing, viral load testing, quantification of study drugs, and HIV drug resistance testing. RESULTS: Fifty-eight infections were evaluated, including 51 incident infections (12 in CAB arm and 39 in TDF/FTC arm). In many cases (5 in CAB arm and 37 in TDF/FTC arm), infection was associated with low or unquantifiable study drug concentrations. In 4 cases, infection occurred with on-time CAB-LA injections and expected plasma CAB concentrations. CAB exposure was associated with prolonged viral suppression and delayed antibody expression. In some cases, delayed HIV diagnosis resulted in CAB provision to participants with undetected infection, delayed antiretroviral therapy, and emergence of drug resistance; most of these infections would have been detected earlier with viral load testing. CONCLUSIONS: Early detection of HIV infection and prompt antiretroviral therapy initiation could improve clinical outcomes in persons who become infected despite CAB-LA prophylaxis. Further studies are needed to elucidate the correlates of HIV protection in persons receiving CAB-LA.

Smart Insole for Robust Wearable Biomechanical Energy Harvesting in Harsh Environments.

Footfall contains the highest harvestable biomechanical energy from the human body, which can attain 67 W, showing great potential as a pervasive and sustainable power source for wearable bioelectronics in the era of the Internet of Things. Developing an effective technology for robust and efficient energy harvesting from human walking remains highly desired. Here, we present a waterproof smart insole, based on a triboelectric nanogenerator, for highly efficient and robust human biomechanical energy harvesting. This insole was rationally designed as a composite structure to fully utilize the pressure distribution of a footfall for wearable electricity generation and to deliver a power output reaching 580 µW. The insole was additionally able to withstand use in harsh environments, including pluvial conditions, without affecting the power output consistency. A total of 260 light-emitting diodes were lit up with perspiring feet and water on the floor, and a capacitor of 88 µF was charged to 2.5 V in 900 s. This work represents a practical approach to developing a highly efficient and robust smart insole that can be used as a sustainable power source for wearable bioelectronics.

LncRNA PCGEM1 accelerates non-small cell lung cancer progression via sponging miR-433-3p to upregulate WTAP.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors all over the world. In recent years, long non-coding RNAs (lncRNAs) have been proven to participate in the development of different cancers, including NSCLC. PCGEM1 prostate-specific transcript (PCGEM1) is the lncRNA which is associated with the progression of several cancers. Nevertheless, in NSCLC, the specific functions of PCGEM1 are not yet clear. METHODS: The real-time quantitative polymerase chain reaction (qPCR) was utilized to test the expression of PCGEM1 in NSCLC cells. Functional experiments, including cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry analysis and transwell assays were utilized to estimate cell proliferation, migration, invasion and apoptosis. Meanwhile, RNA pull down assay and luciferase reporter assay were utilized to evaluate the correlation of miR-433-3p with PCGEM1 or WT1 associated protein (WTAP). RESULT: PCGEM1 was highly expressed in NSCLC cells, while miR-433-3p was lowly expressed in NSCLC cells. PCGEM1 silencing or miR-433-3p overexpression inhibited cell proliferation, migration and invasion but accelerated cell apoptosis. MiR-433-3p was proven be sponged by PCGEM1. Besides, WTAP was the target of miR-433-3p and it accelerated the progression of NSCLC. In the end, rescue experiments indicated that overexpression of WTAP or knockdown of miR-433-3p reversed the inhibited roles of silencing PCGEM1 on cell behavior. CONCLUSIONS: PCGEM1 accelerates NSCLC progression via sponging miR-433-3p to upregulate WTAP.

Association of Posttraumatic Stress Disorder With Mental Stress-Induced Myocardial Ischemia in Adults After Myocardial Infarction.

Importance: Posttraumatic stress disorder (PTSD) is prevalent among patients who survived an acute coronary syndrome and is associated with adverse outcomes, but the mechanisms underlying these associations are unclear. Objective: To evaluate the association of PTSD with mental stress-induced myocardial ischemia among individuals who survived a myocardial infarction (MI). Design, Setting, and Participants: This cross-sectional study included 303 patients aged 18 to 60 years enrolled from a university-affiliated network. Participants had a verified history of MI within 8 months. Data were collected from June 2011 to March 2016, and data analysis was conducted from March to June 2019. Exposures: A clinical diagnosis of PTSD (lifetime and current) was obtained using the Structured Clinical Interview from the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), and PTSD symptom subscales were assessed with the civilian version of the PTSD Symptom Checklist. Main Outcomes and Measures: Patients received technetium 99m-labeled sestamibi myocardial perfusion imaging at rest, with mental stress (ie, a speech task) and conventional stress (ie, exercise or pharmacologic). A summed difference score (ie, the difference between stress and rest scores) was used to assess ischemia under both stress conditions. Results: Among 303 participants (148 [48.8%] women; 198 [65.3%] African American; mean [SD] age, 51 [7] years), the prevalence of PTSD was 14.5% (44 patients). Patients with PTSD had a higher rate of ischemia with mental stress than those without PTSD (12 of 44 [27.3%] vs 38 of 259 [14.7%]; P = .04) and more than twice the mean number of ischemic segments (1.2 [95% CI, 0.5-1.8] vs 0.5 [95% CI, 0.3-0.7]; P < .001), but there was no difference in conventional stress ischemia (10 of 44 [22.7%] vs 60 of 259 [23.2%]; P = .91). Increasing levels of PTSD symptoms were associated with higher odds of ischemia with mental stress (adjusted odds ratio [OR] per 5-point score increase, 1.18; 95% CI 1.04-1.35; P = .01) but not with conventional stress (adjusted OR per 5-point score increase, 1.05; 95% CI, 0.92-1.21; P = .47). Reexperiencing trauma was the symptom cluster most robustly associated with the presence of ischemia with mental stress (adjusted OR per 5-point score increase, 1.87; 95% CI 1.21-2.91; P = .005), followed by avoidance and numbing (adjusted OR per 5-point score increase, 1.51; 95% CI, 1.07-2.14; P = .02). Conclusions and Relevance: In this study of young and middle-aged individuals with MI, with a large representation of women and patients from racial/ethnic minority groups, PTSD was associated with the development of myocardial ischemia with mental stress. A higher ischemic response to mental stress represents a potential pathway associating PTSD with adverse outcomes after MI.

Determination of HIV status and identification of incident HIV infections in a large, community-randomized trial: HPTN 071 (PopART).

INTRODUCTION: The HPTN 071 (PopART) trial evaluated the impact of an HIV combination prevention package that included "universal testing and treatment" on HIV incidence in 21 communities in Zambia and South Africa during 2013-2018. The primary study endpoint was based on the results of laboratory-based HIV testing for> 48,000 participants who were followed for up to three years. This report evaluated the performance of HIV assays and algorithms used to determine HIV status and identify incident HIV infections in HPTN 071, and assessed the impact of errors on HIV incidence estimates. METHODS: HIV status was determined using a streamlined, algorithmic approach. A single HIV screening test was performed at centralized laboratories in Zambia and South Africa (all participants, all visits). Additional testing was performed at the HPTN Laboratory Center using antigen/antibody screening tests, a discriminatory test and an HIV RNA test. This testing was performed to investigate cases with discordant test results and confirm incident HIV infections. RESULTS: HIV testing identified 978 seroconverter cases. This included 28 cases where the participant had acute HIV infection at the first HIV-positive visit. Investigations of cases with discordant test results identified cases where there was a participant or sample error (mixups). Seroreverter cases (errors where status changed from HIV infected to HIV uninfected, 0.4% of all cases) were excluded from the primary endpoint analysis. Statistical analysis demonstrated that exclusion of those cases improved the accuracy of HIV incidence estimates. CONCLUSIONS: This report demonstrates that the streamlined, algorithmic approach effectively identified HIV infections in this large cluster-randomized trial. Longitudinal HIV testing (all participants, all visits) and quality control testing provided useful data on the frequency of errors and provided more accurate data for HIV incidence estimates.

Purification of recombinant human fibroblast growth factor 13 in E. coli and its molecular mechanism of mitogenesis.

Fibroblast growth factor (FGF) 13, a member of the FGF11 subfamily, is a kind of intracrine protein similar to other family members including FGF11, FGF12, and FGF14. Unlike classical FGF, FGF13 exerts its bioactivities independent of fibroblast growth factor receptors (FGFRs). However, the effect of exogenous administration of FGF13 still remains further investigated. In the present study, we established an Escherichia coli expression system for the large-scale production of FGF13 and then obtained two isoform proteins including recombinant human FGF13A (rhFGF13A) and rhFGF13B with a purity greater than 90% by column chromatography, respectively. Otherwise, soluble analysis indicated that both rhFGF13A and rhFGF13B expressed in E. coli BL21 (DE3) pLysS were soluble. Furthermore, cellular-based experiments demonstrated that rhFGF13A, rather than rhFGF13B, could promote the proliferation of NIH3T3 cells in the presence of heparin. Mechanistically, the mitogenic effect of FGF13 was mediated by activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), but not p38. Moreover, blockage of FGFRs also significantly attenuated the mitogenic effects of rhFGF13A, implying that FGFRs are still related to FGF13. Thus, our research shows that exogenous FGF13 can act as secreted FGF to participate in cell signal transmission and heparin is still required as an ancillary cofactor for the mitogenic effects of FGF13, which may help people to discover more potential functions of FGF13 in cell life activities.

Monitoring peak expiratory flow could predict COPD exacerbations: A prospective observational study.

BACKGROUND: Exacerbation of chronic obstructive pulmonary disease (ECOPD) is an important event during the course of the disease. It causes a more rapid decline in lung function, which is associated with hospitalization and the risk of death. Therefore, it is essential to discover approaches to early detection and prevention of ECOPD. Peak expiratory flow (PEF) can be safely used instead of spirometry which can assess the severity of COPD as a standard tool. We hypothesized that monitoring PEF could possibly be used to predict the ECOPD. METHOD: To verify this hypothesis, daily morning PEF was monitored for 6 months in 53 patients with moderate to severe COPD (mean FEV1 31.53%predicted) who were enrolled in Ningbo, China. RESULT: A total of 69 exacerbations of COPD (63 of gradual onset, six of sudden onset) were recorded in this study. Thirty cases (43.5%) of gradual onset exacerbations needed to be hospitalized, and the mean PEF significantly decreased (vs baseline) during the 5 days that preceded those exacerbations (from 161.9 ±â€¯39.4 L/min to 137.9 ±â€¯36.1 L/min, P < 0.05, statistical power = 0.92). However, this was not the case with non-hospitalized exacerbations (from 175.4 ±â€¯42.5 L/min to 161.5 ±â€¯39.3 L/min, P = 0.172, statistical power = 0.63). The ROC analysis demonstrated that 24 h before hospitalized exacerbation, the optimal cutoff value of ΔPEF for its prediction was 28 L/min (17% from baseline), with a sensitivity and specificity of 76.7% and 72.7%, respectively (area under the curve [AUC] = 0.84, P < 0.05, statistical power = 0.78). While 48 h before hospitalized exacerbation, the optimal cutoff value of ΔPEF for its prediction was 14 L/min (9% from baseline), with a sensitivity and specificity of 86.7% and 66.7%, respectively (AUC = 0.863, P < 0.05, statistical power = 0.87). CONCLUSIONS: As a rapid, inexpensive method, PEF could be used for the prediction and early detection of hospitalized exacerbation of COPD. This may provide opportunity for early intervention of ECOPD.

Dried blood spot microbiological assay indicates high prevalence of folate deficiency in rural adult men and women in the Haitian Central Plateau.

BACKGROUND: Although folate deficiency is linked to adverse health effects, limited data exist characterizing the problem in rural settings. This study determined the prevalence of folate deficiency and anemia in rural adults in the Haitian Central Plateau using combined laboratory methods. METHODS: Dried blood spots (DBSs) and hemoglobin measurements were collected from adult men and women selected by cluster random sampling in Haiti's Central Plateau. DBSs were analyzed for folate using a microbiological assay. Hemoglobin levels were determined using both a HemoCue photometer and the sodium lauryl sulfate microplate method. Red cell folate (RCF) levels were determined by normalizing DBS folate to hemoglobin. RESULTS: Of the 197 subjects assessed for hemoglobin, 11.4% of males and 21.0% of females were anemic (male: hemoglobin<12 g/dL; female: hemoglobin<11 g/dL). Of the 173 subjects assessed for RCF, 27.9% of men and 14.9% of women were folate deficient (RCF<340 nmol/L). Among reproductive-age women, 83.6% had RCF levels associated with a risk of neural tube defects of >14 per 10 000 live births (RCF≤699 nmol/L). CONCLUSIONS: Adults in the Haitian Central Plateau suffer from high rates of anemia and folate deficiency, putting the population at elevated risk for disease. DBSs and microbiological assay make folate evaluation feasible, even in low-resource regions.

Genome-wide association study in two populations to determine genetic variants associated with Toxoplasma gondii infection and relationship to schizophrenia risk.

T. gondii (TOXO) infects over one billion people worldwide, yet the literature lacks a Genome Wide Association Study (GWAS) focused on genetic variants controlling the persistence of TOXO infection. To identify putative T. gondii susceptibility genes, we performed a GWAS using IgG seropositivity as the outcome variable in a discovery sample (n = 790) from an Ashkenazi dataset, and a second sample of predominately African Americans (The Grady Trauma Project, n = 285). We also performed a meta-analyses of the 2 cohorts. None of the SNPs in these analyses was statistically significant after Bonferroni correction for multiple comparisons. In the Ashkenazi population, the gene region of CHIA (chitinase) showed the most nominally significant association with TOXO. Prior studies have shown that the production of chitinase by macrophages in the brain responding to TOXO infection is crucial for controlling the burden of T. gondii cysts. We found a surprising number of genes involved in neurodevelopment and psychiatric disorders among our top hits even though our outcome variable was TOXO infection. In the meta-analysis combining the Ashkenazi and Grady Trauma Project samples, there was enrichment for genes implicated in schizophrenia spectrum disorders (p < .05). Upon limiting our sample to those without mental illness, two schizophrenia related genes (CNTNAP2, GABAR2) still had significant TOXO-associated variants at the p < .05 level, but did not pass the genome wide significance threshold after correction for multiple comparisons. Using Ingenuity Systems molecular network analysis, we identified molecular nodes suggesting that while different genetic variants associated with TOXO in the two population samples, the molecular pathways for TOXO susceptibility nevertheless converged on common pathways. Molecular nodes in these common pathways included NOTCH1, CD44, and RXRA. Prior studies show that CD44 participates in TOXO-induced immunopathology and that RXRA is instrumental in regulating T-helper immune responses. These data provide new insights into the pathophysiology of this common neurotropic parasite.

Posttraumatic stress disorder is associated with enhanced interleukin-6 response to mental stress in subjects with a recent myocardial infarction.

BACKGROUND: Posttraumatic Stress Disorder (PTSD) is prevalent among patients who survived an acute coronary syndrome, and is associated with adverse outcomes, but the mechanisms underlying these associations are unclear. Individuals with PTSD have enhanced sensitivity of the noradrenergic system to stress which may lead to immune activation. We hypothesized that survivors of a myocardial infarction (MI) who have PTSD would show an enhanced inflammatory response to acute psychological stress compared to those without PTSD. METHODS: Individuals with a verified history of MI within 8 months and a clinical diagnosis of current PTSD underwent a mental stress speech task. Inflammatory biomarkers including interleukin-6 (IL-6), high-sensitivity C reactive protein (HsCRP), matrix metallopeptidase 9 (MMP-9), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and monocyte chemoattractant protein (MCP)-1 were measured at rest and 90 min after mental stress. RESULTS: Among 271 patients in the study (mean age 51 ±â€¯7 years, 50% female, 60% African-American), the prevalence of PTSD was 12%. Mental stress resulted in a significant increase in IL-6, but the increase was more marked in patients with PTSD (126% increase) than those without (63% increase) (p = 0.001). MCP-1 showed a modest increase with stress which was similar in patients with PTSD (9% increase) and without PTSD (6% increase) (p = 0.35). CRP did not increase with stress in either group. CONCLUSION: MI patients with current PTSD exhibit enhanced IL-6 response to psychosocial stress, suggesting a mechanistic link between PTSD and adverse cardiovascular outcomes as well as other diseases associated with inflammation.

Induction of immune responses by a novel recombinant fusion protein of enterovirus A71 in BALB/c mice.

Fusion protein technology is used in biotechnology and medical developments. In this study, recombinant fusion proteins from enterovirus A71 (EV-A71) subgenotype B5, Thailand were designed based two surface proteins (VP1 and VP2) and an internal protein (VP4), and named "VP0" (consisting of VP4-VP2) and "EV71" (consisting of VP4-VP2-VP1), respectively. The recombinant fusion proteins VP0 and EV71 were expressed in insect cells and successfully produced and secreted into the media. Both recombinant fusion proteins were shown to have immunogenic properties in BALB/c mice when formulated with Freund's complete/incomplete adjuvant (FA). Interestingly, EV71 formulated with FA- induced a level of IgG antibodies level similar to that induced by the recombinant protein VP1 formulated with FA (the positive control). Our results showed that VP1 alone is better at eliciting a strong cell-mediated immune response. Nontheless, EV71 formulated with FA was capable of inducing lymphocyte proliferation and increasing the cytokine-related mRNA expression levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), and IL-10 in mice after immunization. Additionally, the number of CD4+ and CD8+ T lymphocyte cells after stimulation with purified EV71 in splenic cell culture showed highly specific CD4+ and CD8+ T-cell production. We suggest that EV71, which consists of VP4-VP2-VP1, could be used as the foundation for developing a novel recombinant fusion protein-based vaccine for EV-A71.

Myocardial Ischemia and Mobilization of Circulating Progenitor Cells.

BackgroundThe response of progenitor cells (PCs) to transient myocardial ischemia in patients with coronary artery disease remains unknown. We aimed to investigate the PC response to exercise-induced myocardial ischemia (ExMI) and compare it to flow mismatch during pharmacological stress testing. Methods and ResultsA total of 356 patients with stable coronary artery disease underwent 99mTc-sestamibi myocardial perfusion imaging during exercise (69%) or pharmacological stress (31%). CD34+ and CD34+/chemokine (C-X-C motif) receptor 4 PCs were enumerated by flow cytometry. Change in PC count was compared between patients with and without myocardial ischemia using linear regression models. Vascular endothelial growth factor and stromal-derived factor-1α were quantified. Mean age was 63±9 years; 76% were men. The incidence of ExMI was 31% and 41% during exercise and pharmacological stress testing, respectively. Patients with ExMI had a significant decrease in CD34+/chemokine (C-X-C motif) receptor 4 (-18%, P=0.01) after stress that was inversely correlated with the magnitude of ischemia (r=-0.19, P=0.003). In contrast, patients without ExMI had an increase in CD34+/chemokine (C-X-C motif) receptor 4 (14.7%, P=0.02), and those undergoing pharmacological stress had no change. Plasma vascular endothelial growth factor levels increased (15%, P<0.001) in all patients undergoing exercise stress testing regardless of ischemia. However, the change in stromal-derived factor-1α level correlated inversely with the change in PC counts in those with ExMI (P=0.03), suggesting a greater decrease in PCs in those with a greater change in stromal-derived factor-1α level with exercise. ConclusionsExMI is associated with a significant decrease in circulating levels of CD34+/chemokine (C-X-C motif) receptor 4 PCs, likely attributable, at least in part, to stromal-derived factor-1α-mediated homing of PCs to the ischemic myocardium. The physiologic consequences of this uptake of PCs and their therapeutic implications need further investigation.

Inflammatory response to mental stress and mental stress induced myocardial ischemia.

BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothesized that patients with MSIMI would have a higher inflammatory response to mental stress in comparison to those without ischemia. METHODS: Patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during mental stress testing using a public speaking stressor. MSIMI was determined as impaired myocardial perfusion using a 17-segment model. Inflammatory markers including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metallopeptidase 9 (MMP-9) and high-sensitivity C reactive protein (hsCRP) were measured at rest and 90 min after mental stress. Results were validated in an independent sample of 228 post-myocardial infarction patients. RESULTS: Of 607 patients analyzed in this study, (mean age 63 ±â€¯9 years, 76% male), 99 (16.3%) developed MSIMI. Mental stress resulted in a significant increase in IL-6, MCP-1, and MMP-9 (all p <0.0001), but not hsCRP. However, the changes in these markers were similar in those with and without MSIMI. Neither resting levels of these biomarkers, nor their changes with mental stress were significantly associated with MSIMI. Results in the replication sample were similar. CONCLUSION: Mental stress is associated with acute increases in several inflammatory markers. However, neither the baseline inflammatory status nor the magnitude of the inflammatory response to mental stress over 90 min were significantly associated with MSIMI.

The Influence of Empathy and Morality of Violent Video Game Characters on Gamers' Aggression.

According to the General Aggression Model, situational factors (such as the game characters) and personal factors both affect a gamer's acquisition of aggressive behavior. Previous studies have found not only that the surface features of game characters, such as appearance and clothing, but also that their inherent characteristics, such as morality and identity, can influence a gamer's attitude and behavior. Research has also shown that empathy, as a personal factor, can protect gamers from the impact of media violence. However, past research has focused primarily on single factors affecting the player rather than more comprehensive investigations. This study investigates the influence of the game character's moral features and levels of empathy on the gamer's aggression. The participants were 120 Chinese university students (61 females and 59 males) with ages ranging from 17 to 27 years. Participants first completed a series of questionnaires: a user experience questionnaire, a video game questionnaire, the Buss-Perry Aggression Questionnaire, and a modified version of the Interpersonal Reactivity Index. All participants then had 5 min of practice playing a violent video game. They were then divided into three groups: a high empathy group, a low empathy group, and a no empathy group. After the practice, participants in the high and low empathy groups read empathy materials relating to the game characters; participants in the no empathy group began formal gameplay. All participants played the game for 20 min. Finally, participants were required to complete the Scale of Hostility Status questionnaire, the Implicit Aggression Test, and the Competitive Reaction Time Test. The results show that empathy and the morality of game characters both influence aggression, but empathy affected aggression differently in the participants playing justified roles (i.e., killing others for a moral reason in the game) compared to those playing unjustified roles (i.e., killing others for immoral reasons in the game). In the high empathy condition, the implicit aggression of justified players was significantly higher than those playing unjustified roles. However, high empathy does not always play a protective role, and its effect is restricted by the features of the game characters.

Long-Time Exposure to Violent Video Games Does Not Show Desensitization on Empathy for Pain: An fMRI Study.

As a typical form of empathy, empathy for pain refers to the perception and appraisal of others' pain, as well as the corresponding affective responses. Numerous studies investigated the factors affecting the empathy for pain, in which the exposure to violent video games (VVGs) could change players' empathic responses to painful situations. However, it remains unclear whether exposure to VVG influences the empathy for pain. In the present study, in terms of the exposure experience to VVG, two groups of participants (18 in VVG group, VG; 17 in non-VVG group, NG) were screened from nearly 200 video game experience questionnaires. And then, the functional magnetic resonance imaging data were recorded when they were viewing painful and non-painful stimuli. The results showed that the perception of others' pain were not significantly different in brain regions between groups, from which we could infer that the desensitization effect of VVGs was overrated.

Compound Wumei Powder Inhibits the Invasion and Metastasis of Gastric Cancer via Cox-2/PGE2-PI3K/AKT/GSK3ß/ß-Catenin Signaling Pathway.

To explore the role of CWP in invasion and migration of gastric cancer cells and its underlying molecular mechanism, we performed the experiment in SGC-7901 cells both in vitro and in vivo. In the cell experiment, we evaluated cell proliferation by MTT assay. The results showed that CWP can inhibit the growth of SGC-7901 cells. The influence on cell migration and invasion was detected by wound-healing and Transwell invasion assays. The results showed that the abilities of invasion and migration are restrained in CWP group. Western blot showed that CWP can decrease the expression of Cox-2 and inhibit the PI3K/AKT/GSK3ß/ß-catenin signaling pathway. In the animal experiment, we observed that CWP had an inhibitory effect on the growth of xenograft tumors of nude mice. IHC assay, ELISA, RT-PCR assay, and Western blot assay were used to test relevant cytokines of Cox-2/PGE2-PI3K/AKT/GSK3ß/ß-catenin pathway. The results showed that CWP can suppress relevant cytokines of Cox-2/PGE2-PI3K/AKT/GSK3ß/ß-catenin pathway. In conclusion, we suggest that CWP inhibits the invasion and metastasis of SGC-7901 cells via Cox-2/PGE2-PI3K/AKT/GSK3ß/ß-catenin signaling pathway.

Relationship between Toxoplasma gondii seropositivity and acoustic startle response in an inner-city population.

Toxoplasma gondii (TOXO) is a neuroinvasive protozoan parasite that induces the formation of persistent cysts in mammalian brains. It infects approximately 1.1million people in the United States annually. Latent TOXO infection is implicated in the etiology of psychiatric disorders, especially schizophrenia (SCZ), and has been correlated with modestly impaired cognition. The acoustic startle response (ASR) is a reflex seen in all mammals. It is mediated by a simple subcortical circuit, and provides an indicator of neural function. We previously reported the association of TOXO with slowed acoustic startle latency, an index of neural processing speed, in a sample of schizophrenia and healthy control subjects. The alterations in neurobiology with TOXO latent infection may not be specific to schizophrenia. Therefore we examined TOXO in relation to acoustic startle in an urban, predominately African American, population with mixed psychiatric diagnoses, and healthy controls. Physiological and diagnostic data along with blood samples were collected from 364 outpatients treated at an inner-city hospital. TOXO status was determined with an ELISA assay for TOXO-specific IgG. A discrete titer was calculated based on standard cut-points as an indicator of seropositivity, and the TOXO-specific IgG concentration served as serointensity. A series of linear regression models were used to assess the association of TOXO seropositivity and serointensity with ASR magnitude and latency in models adjusting for demographics and psychiatric diagnoses (PTSD, major depression, schizophrenia, psychosis, substance abuse). ASR magnitude was 11.5% higher in TOXO seropositive subjects compared to seronegative individuals (p=0.01). This effect was more pronounced in models with TOXO serointensity that adjusted for sociodemographic covariates (F=7.41, p=0.0068; F=10.05, p=0.0017), and remained significant when psychiatric diagnoses were stepped into the models. TOXO showed no association with startle latency (t=0.49, p=0.63) in an unadjusted model, nor was TOXO associated with latency in models that included demographic factors. After stepping in individual psychiatric disorders, we found a significant association of latency with a diagnosis of PTSD (F=5.15, p=0.024), but no other psychiatric diagnoses, such that subjects with PTSD had longer startle latency. The mechanism by which TOXO infection is associated with high startle magnitude is not known, but possible mechanisms include TOXO cyst burden in the brain, parasite recrudescence, or molecular mimicry of a host epitope by TOXO. Future studies will focus on the neurobiology underlying the effects of latent TOXO infection as a potential inroad to the development of novel treatment targets for psychiatric disease.