Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials

<p>Abstract</p> <p>Background</p> <p>Asenapine demonstrated superiority over placebo for mania in bipolar I disorder patients experiencing acute current manic or mixed episodes in 2 randomized, placebo-and olanzapine-controlled trials. We report the results of exploratory pooled post hoc analyses from these trials evaluating asenapine's effects on depressive symptoms in patients from these trials with significant baseline depressive symptoms.</p> <p>Methods</p> <p>In the original trials (A7501004 [NCT00159744], A7501005 [NCT00159796]), 977 patients were randomized to flexible-dose sublingual asenapine (10 mg twice daily on day 1; 5 or 10 mg twice daily thereafter), placebo, or oral olanzapine 5-20 mg once daily for 3 weeks. Three populations were defined using baseline depressive symptoms: (1) Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥20 (n = 132); (2) Clinical Global Impression for Bipolar Disorder-Depression (CGI-BP-D) scale severity score ≥4 (n = 170); (3) diagnosis of mixed episodes (n = 302) by investigative site screening. For each population, asenapine and olanzapine were independently compared with placebo using least squares mean change from baseline on depressive symptom measures.</p> <p>Results</p> <p>Decreases in MADRS total score were statistically greater with asenapine versus placebo at days 7 and 21 in all populations; differences between olanzapine and placebo were not significant. Decreases in CGI-BP-D score were significantly greater with asenapine versus placebo at day 7 in all categories and day 21 in population 1; CGI-BP-D score reductions were significantly greater with olanzapine versus placebo at day 21 in population 1 and day 7 in populations 2 and 3.</p> <p>Conclusions</p> <p>These post hoc analyses show that asenapine reduced depressive symptoms in bipolar I disorder patients experiencing acute manic or mixed episodes with clinically relevant depressive symptoms at baseline; olanzapine results appeared to be less consistent. Controlled studies of asenapine in patients with acute bipolar depression are necessary to confirm the generalizability of these findings.</p

Proteomic and functional variation within black snake venoms (Elapidae: Pseudechis )

Pseudechis (black snakes) is an Australasian elapid snake genus that inhabits much of mainland Australia, with two representatives confined to Papua New Guinea. The present study is the first to analyse the venom of all 9 described Pseudechis species (plus one undescribed species) to investigate the evolution of venom composition and functional activity. Proteomic results demonstrated that the typical Pseudechis venom profile is dominated by phospholipase A2 toxins. Strong cytotoxicity was the dominant function for most species. P. porphyriacus, the most basal member of the genus, also exhibited the most divergent venom composition, being the only species with appreciable amounts of procoagulant toxins. The relatively high presence of factor Xa recovered in P. porphyriacus venom may be related to a predominantly amphibian diet. Results of this study provide important insights to guide future ecological and toxinological investigations

Trends of under-and overweight among rural and urban poor women indicate double burden of malnutrition in Bangladesh.

BACKGROUND: Although undernutrition and communicable diseases dominate the current disease burden in resource-poor countries, the prevalence of diet related chronic diseases is increasing. This paper explores current trends of under- and overweight in Bangladeshi women. METHOD: Nationally representative data on reproductive age women from rural Bangladesh (n = 242,433) and selected urban poor areas (n = 39,749) collected by the Nutritional Surveillance Project during 2000-2004 were analyzed. RESULTS: While the prevalence of chronic energy deficiency [CED, body mass index (BMI) < 18.5 kg/m(2)] continues to be major nutritional problem among Bangladeshi women (38.8% rural, 29.7% urban poor; P < 0.001), between 2000-2004, 9.1% of urban poor and 4.1% of rural women were overweight (BMI > or = 25 kg/m(2), P < 0.001). In addition, 9.8% of urban poor and 5.5% of rural women were found to be 'at risk of overweight' (BMI 23.0-<25 kg/m(2)). From 2000 to 2004, prevalence of CED decreased (urban poor: 33.8-29.3%; rural: 42.6-36.6%), while prevalence of overweight increased (urban poor: 6.8-9.1%; rural: 2.8-5.5%). The risk of being overweight was higher among women who were older and of higher socioeconomic status. Rural women with at least 14 years of education had a 8.1-fold increased risk of being overweight compared with non-educated women [95% confidence intervals (CI): 6.6-8.7]. Women living in houses of at least 1000 sq ft (93 m(2)) were 3.7 times more likely to be overweight compared with women living in <250 sq ft (23 m(2)) houses (95% CI: 3.2-4.3). CONCLUSION: The recent increase in overweight prevalence among both urban poor and rural women, along with high prevalence of CED, indicates the emergence of a double burden of malnutrition in Bangladesh

C5a receptors C5aR1 and C5aR2 mediate opposing pathologies in a mouse model of melanoma

The canonical complement component 5a (C5a) receptor (C5aR) 1 has well-described roles in tumorigenesis but the contribution of the second receptor, C5aR2, is unclear. The present study demonstrates that B16.F0 melanoma cells express mRNA for both C5aR1 and C5aR2 and signal through ERK and p38 MAPKs in response to C5a. Despite this, C5a had no impact on melanoma cell proliferation or migration in vitro. In vivo studies demonstrated that the growth of B16.F0 melanoma tumors was increased in C5aR2–/– mice but reduced in C5aR1–/– mice and wild-type mice treated with a C5aR1 antagonist. Analysis of tumor-infiltrating leukocyte populations showed no significant differences between wild-type and C5aR2–/– mice. Conversely, percentages of myeloid-derived suppressor cells, macrophages, and regulatory T lymphocytes were lower in tumors from C5aR1–/– mice, whereas total (CD3+) T lymphocytes and CD4+ subsets were higher. Analysis of cytokine and chemokine levels also showed plasma IFN-γ was higher and tumor C-C motif chemokine ligand 2 was lower in the absence of C5aR1. The results suggest that C5aR1 signaling supports melanoma growth by promoting infiltration of immunosuppressive leukocyte populations into the tumor microenvironment, whereas C5aR2 has a more restricted but beneficial role in limiting tumor growth. Overall, these data support the potential of C5aR1-inhibitory therapies for melanoma.—Nabizadeh, J. A., Manthey, H. D., Panagides, N., Steyn, F. J., Lee, J. D., Li, X. X., Akhir, F. N. M., Chen, W., Boyle, G. M., Taylor, S. M., Woodruff, T. M., Rolfe, B. E. C5a receptors C5aR1 and C5aR2 mediate opposing pathologies in a mouse model of melanoma

Very early infective endocarditis after transcatheter aortic valve replacement

International audienceBackground Scarce data exist about early infective endocarditis (IE) after trans-catheter aortic valve replacement (TAVR). Objective The objective was to evaluate the characteristics, management, and outcomes of very early (VE) IE (&lt;= 30 days) after TAVR. Methods This multicenter study included a total of 579 patients from the Infectious Endocarditis after TAVR International Registry who had the diagnosis of definite IE following TAVR. Results Ninety-one patients (15.7%) had VE-IE. Factors associated with VE-IE (vs. delayed IE (D-IE)) were female gender (p = 0.047), the use of self-expanding valves (p &lt; 0.001), stroke (p = 0.019), and sepsis (p &lt; 0.001) after TAVR. Staphylococcus aureus was the main pathogen among VE-IE patients (35.2% vs. 22.7% in the D-IE group, p = 0.012), and 31.2% of Staphylococcus aureus infections in the VE-IE group were methicillin-resistant (vs. 14.3% in the D-IE group, p = 0.001). The second-most common germ was enterococci (34.1% vs. 24.4% in D-IE cases, p = 0.05). VE-IE was associated with very high in-hospital (44%) and 1-year (54%) mortality rates. Acute renal failure following TAVR (p = 0.001) and the presence of a non-enterococci pathogen (p &lt; 0.001) were associated with an increased risk of death. Conclusion A significant proportion of IE episodes following TAVR occurs within a few weeks following the procedure and are associated with dismal outcomes. Some baseline and TAVR procedural factors were associated with VE-IE, and Staphylococcus aureus and enterococci were the main causative pathogens. These results may help to select the more appropriate antibiotic prophylaxis in TAVR procedures and guide the initial antibiotic therapy in those cases with a clinical suspicion of IE