Distinct variation in vector competence among nine field populations of Aedes aegypti from a Brazilian dengue-endemic risk city

Background: In Brazil, dengue epidemics erupt sporadically throughout the country and it is unclear if outbreaks may initiate a sustainable transmission cycle. There are few studies evaluating the ability of Brazilian Aedes aegypti populations to transmit dengue virus (DENV). The aim of this study was to compare DENV susceptibility of field-captured Ae. aegypti populations from nine distinct geographic areas of the city of Belo Horizonte in 2009 and 2011. Infection Rate (IR), Vector Competence (VC) and Disseminated Infection Rate (DIR) were determined. Methods: Aedes aegypti eggs from each region were collected and reared separately in an insectary. Adult females were experimentally infected with DENV-2 and the virus was detected by qPCR in body and head samples. Data were analyzed with the Statistical Package for the Social Sciences version 17. Results: IR varied from 40.0% to 82.5% in 2009 and 60.0% to 100.0% in 2011. VC ranged from 25.0% to 77.5% in 2009 and 25.0% to 80.0% in 2011. DIR oscillated from 68.7% to 100.0% in 2009 and 38.4% to 86.8 in 2011. When the results were evaluated by a logistic model using IR as covariate, North, Barreiro, South-Central and Venda Nova showed the strongest association in 2009. In 2011, a similar association was observed for South-Central, Venda Nova, West and Northeast regions. Using VC as covariate, South-Central and Venda Nova showed the most relevant association in 2009. In 2011, South-Central, Venda Nova and Barreiro presented the greatest revelation associations. When DIR data were analyzed by logistic regression models, Pampulha, South-Central, Venda Nova, West, Northeast and East (2009) as well as South-Central, Venda Nova and West (2011) were the districts showing the strongest associations. Conclusions: We conclude that Ae. aegypti populations from Belo Horizonte exhibit wide variation in vector competence to transmit dengue. Therefore, vector control strategies should be adapted to the available data for each region. Further analysis should be conducted to better understand the reasons for this large variability in vector competence and how these parameters correlate with epidemiological findings in subsequent years

Gravity waves and the LHC: Towards high-scale inflation with low-energy SUSY

It has been argued that rather generic features of string-inspired inflationary theories with low-energy supersymmetry (SUSY) make it difficult to achieve inflation with a Hubble scale H > m_{3/2}, where m_{3/2} is the gravitino mass in the SUSY-breaking vacuum state. We present a class of string-inspired supergravity realizations of chaotic inflation where a simple, dynamical mechanism yields hierarchically small scales of post-inflationary supersymmetry breaking. Within these toy models we can easily achieve small ratios between m_{3/2} and the Hubble scale of inflation. This is possible because the expectation value of the superpotential relaxes from large to small values during the course of inflation. However, our toy models do not provide a reasonable fit to cosmological data if one sets the SUSY-breaking scale to m_{3/2} < TeV. Our work is a small step towards relieving the apparent tension between high-scale inflation and low-scale supersymmetry breaking in string compactifications.Comment: 21+1 pages, 5 figures, LaTeX, v2: added references, v3: very minor changes, version to appear in JHE

Effect of voriconazole on Candida tropicalis biofilms: Relation with ERG genes expression

Candida tropicalis has emerged as the third most prevalent fungal pathogens and its ability to form biofilms has been considered one of the most important virulence factors, since biofilms represent high tolerance to antifungal agents. However, the mechanisms of C. tropicalis biofilm resistance to antifungals remain poorly understood. Thus, the main aim of this work was to infer about the effect of voriconazole on the formation and control of C. tropicalis biofilms and disclose its relationship with ERG genes' expression. Planktonic cells tolerance of several C. tropicalis clinical isolates to voriconazole was determined through of antifungal susceptibility test, and the effect of this azole against C. tropicalis biofilm formation and pre-formed biofilms was evaluated by cultivable cells determination and total biomass quantification. ERG genes expression was analyzed by quantitative real-time polymerase chain reaction. This work showed that C. tropicalis resistance to voriconazole is strain dependent and that voriconazole was able to partially control biofilm formation, but was unable to eradicate C. tropicalis pre-formed biofilms. Moreover, C. tropicalis biofilms resistance to voriconazole seems to be associated with alterations of sterol content in the cell membrane, resulting in ERG genes overexpression. Voriconazole is unable to control C. tropicalis biofilms, and the overexpression of ERG genes is a possible mechanism of biofilm resistance.TheauthorsthanktheFCTfortheStrategic Project of the UID/BIO/04469/2013 unit, FCT and European Union funds (FEDER/COMPETE) for the project RECI/BBBEBI/0179/2012 (FCOMP-01-0124-FEDER-027462). We also would like to acknowledge Pfizer , S.A. for the kindly donation of voriconazole

Tnni3k Modifies Disease Progression in Murine Models of Cardiomyopathy

The Calsequestrin (Csq) transgenic mouse model of cardiomyopathy exhibits wide variation in phenotypic progression dependent on genetic background. Seven heart failure modifier (Hrtfm) loci modify disease progression and outcome. Here we report Tnni3k (cardiac Troponin I-interacting kinase) as the gene underlying Hrtfm2. Strains with the more susceptible phenotype exhibit high transcript levels while less susceptible strains show dramatically reduced transcript levels. This decrease is caused by an intronic SNP in low-transcript strains that activates a cryptic splice site leading to a frameshifted transcript, followed by nonsense-mediated decay of message and an absence of detectable protein. A transgenic animal overexpressing human TNNI3K alone exhibits no cardiac phenotype. However, TNNI3K/Csq double transgenics display severely impaired systolic function and reduced survival, indicating that TNNI3K expression modifies disease progression. TNNI3K expression also accelerates disease progression in a pressure-overload model of heart failure. These combined data demonstrate that Tnni3k plays a critical role in the modulation of different forms of heart disease, and this protein may provide a novel target for therapeutic intervention

Rheumatoid arthritis patients receive less frequent acute reperfusion and secondary prevention therapy after myocardial infarction compared with the general population

INTRODUCTION: The 30-day case-fatality rate after acute myocardial infarction (MI) for rheumatoid arthritis (RA) patients is twice that of the general population. This study compared the frequency and timeliness of early reperfusion therapy and treatment with secondary prevention medications after acute MI in RA patients and controls. METHODS: We performed a structured medical chart review of RA patients and matched controls who had been admitted with acute MI to one of three hospitals in Victoria, Australia, between 1995 and 2005. The administration and timing of acute reperfusion therapy and in-hospital treatment with secondary prevention medications were compared between the two groups. Acute reperfusion was defined as thrombolysis or percutaneous coronary intervention (PCI) within 12 hours of the first symptom of MI. RESULTS: The medical charts of 90 RA patients and 90 matched controls were reviewed. The RA patients were significantly less likely to receive acute reperfusion compared with the controls (16% versus 37%: odds ratio (OR), 0.27; 95% confidence interval (CI), 0.10 to 0.64)), and this difference persisted after adjusting for type of MI, clinical setting of MI, and prior MI (OR, 0.2; 95% CI, 0.05 to 0.6). The RA patients also received less-frequent in-hospital treatment with beta blockers (71% versus 83%; OR, 0.42; 95% CI, 0.18 to 0.96) and lipid-lowering agents (40% versus 70%; OR, 0.21; 95% CI, 0.09 to 0.46). CONCLUSIONS: RA patients who experience acute MI receive acute reperfusion and secondary prevention medications less frequently than do controls. This may contribute to higher case-fatality rates after MI in RA patients

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Assessing Syndromic Surveillance of Cardiovascular Outcomes from Emergency Department Chief Complaint Data in New York City

Prospective syndromic surveillance of emergency department visits has been used for near-real time tracking of communicable diseases to detect outbreaks or other unexpected disease clusters. The utility of syndromic surveillance for tracking cardiovascular events, which may be influenced by environmental factors and influenza, has not been evaluated. We developed and evaluated a method for tracking cardiovascular events using emergency department free-text chief complaints.There were three phases to our analysis. First we applied text processing algorithms based on sensitivity, specificity, and positive predictive value to chief complaint data reported by 11 New York City emergency departments for which ICD-9 discharge diagnosis codes were available. Second, the same algorithms were applied to data reported by a larger sample of 50 New York City emergency departments for which discharge diagnosis was unavailable. From this more complete data, we evaluated the consistency of temporal variation of cardiovascular syndromic events and hospitalizations from 76 New York City hospitals. Finally, we examined associations between particulate matter ≤2.5 µm (PM(2.5)), syndromic events, and hospitalizations. Sensitivity and positive predictive value were low for syndromic events, while specificity was high. Utilizing the larger sample of emergency departments, a strong day of week pattern and weak seasonal trend were observed for syndromic events and hospitalizations. These time-series were highly correlated after removing the day-of-week, holiday, and seasonal trends. The estimated percent excess risks in the cold season (October to March) were 1.9% (95% confidence interval (CI): 0.6, 3.2), 2.1% (95% CI: 0.9, 3.3), and 1.8% (95%CI: 0.5, 3.0) per same-day 10 µg/m(3) increase in PM(2.5) for cardiac-only syndromic data, cardiovascular syndromic data, and hospitalizations, respectively.Near real-time emergency department chief complaint data may be useful for timely surveillance of cardiovascular morbidity related to ambient air pollution and other environmental events

A Large Change in Temperature between Neighbouring Days Increases the Risk of Mortality

Background: Previous studies have found high temperatures increase the risk of mortality in summer. However, little is known about whether a sharp decrease or increase in temperature between neighbouring days has any effect on mortality. Method: Poisson regression models were used to estimate the association between temperature change and mortality in summer in Brisbane, Australia during 1996–2004 and Los Angeles, United States during 1987–2000. The temperature change was calculated as the current day’s mean temperature minus the previous day’s mean. Results: In Brisbane, a drop of more than 3 °C in temperature between days was associated with relative risks (RRs) of 1.157 (95% confidence interval (CI): 1.024, 1.307) for total non external mortality (NEM), 1.186 (95%CI: 1.002, 1.405) for NEM in females, and 1.442 (95%CI: 1.099, 1.892) for people aged 65–74 years. An increase of more than 3 °C was associated with RRs of 1.353 (95%CI: 1.033, 1.772) for cardiovascular mortality and 1.667 (95%CI: 1.146, 2.425) for people aged < 65 years. In Los Angeles, only a drop of more than 3 °C was significantly associated with RRs of 1.133 (95%CI: 1.053, 1.219) for total NEM, 1.252 (95%CI: 1.131, 1.386) for cardiovascular mortality, and 1.254 (95%CI: 1.135, 1.385) for people aged ≥75 years. In both cities, there were joint effects of temperature change and mean temperature on NEM. Conclusion : A significant change in temperature of more than 3 °C, whether positive or negative, has an adverse impact on mortality even after controlling for the current temperature

Response to 2009 Pandemic Influenza A (H1N1) Vaccine in HIV-Infected Patients and the Influence of Prior Seasonal Influenza Vaccination

Background: The immunogenicity of 2009 pandemic influenza A(H1N1) (pH1N1) vaccines and the effect of previous influenza vaccination is a matter of current interest and debate. We measured the immune response to pH1N1 vaccine in HIV-infected patients and in healthy controls. In addition we tested whether recent vaccination with seasonal trivalent inactivated vaccine (TIV) induced cross-reactive antibodies to pH1N1. (clinicaltrials.gov Identifier:NCT01066169) Methods and Findings: In this single-center prospective cohort study MF59-adjuvanted pH1N1 vaccine (Focetria®, Novartis) was administered twice to 58 adult HIV-infected patients and 44 healthy controls in November 2009 (day 0 and day 21). Antibody responses were measured at baseline, day 21 and day 56 with hemagglutination-inhibition (HI) assay. The seroprotection rate (defined as HI titers ≥1:40) for HIV-infected patients was 88% after the first and 91% after the second vaccination. These rates were comparable to those in healthy controls. Post-vaccination GMT, a sensitive marker of the immune competence of a group, was lower in HIV-infected patients. We fou

Examination of potential virulence factors of Candida tropicalis clinical isolates from hospitalized patients

Candida tropicalis has been reported to be one of the Candida species which is most likely to cause bloodstream and urinary tract infections in hospitalized patients. Accordingly, the aim of this study was to characterize the virulence of C. tropicalis by assessing antifungal susceptibility and comparing the expression of several virulence factors. This study was conducted with seven isolates of C. tropicalis from urine and blood cultures and from central venous catheter. C. tropicalis ATCC 750 was used as reference strain. Yeasts adhered (2 h) to epithelial cells and silicone and 24 h biofilm biomass were determined by crystal violet staining. Pseudohyphae formation ability was determined after growth in fetal bovine serum. Enzymes production (hemolysins, proteases, phospholipases) was assessed by halo formation on agar plates. Susceptibility to antifungal agents was determined by E-test. Regarding adhesion, it can be highlighted that C. tropicalis strains adhered significantly more to epithelium than to silicone. Furthermore, all C. tropicalis strains were able to form biofilms and to express total hemolytic activity. However, protease was only produced by two isolates from urine and by the isolates from catheter and blood. Moreover, only one C. tropicalis (from catheter) was phospholipase positive. All isolates were susceptible to voriconazole, fluconazole and amphotericin B. Four strains were susceptible-dose dependent to itraconazole and one clinical isolate was found to be resistant