FACTORS ASSOCIATED TO ADHERENCE TO DIFFERENT TREATMENT SCHEMES WITH MEGLUMINE ANTIMONIATE IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS

The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule); we observed 82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods.     

Baroreflex Sensitivity and its Association with Arrhythmic Events in Chagas Disease

Background

Sudden death is the leading cause of death in Chagas disease (CD), even in patients with preserved ejection fraction (EF), suggesting that destabilizing factors of the arrhythmogenic substrate (autonomic modulation) contribute to its occurrence.

Objective

To determine baroreflex sensitivity (BRS) in patients with undetermined CD (GI), arrhythmogenic CD with nonsustained ventricular tachycardia (NSVT) (GII) and CD with spontaneous sustained ventricular tachycardia (STV) (GIII), to evaluate its association with the occurrence and complexity of arrhythmias.

Method

Forty-two patients with CD underwent ECG and continuous and noninvasive BP monitoring (TASK force monitor). The following were determined: BRS (phenylephrine method); heart rate variability (HRV) on 24-h Holter; and EF (echocardiogram).

Results

GIII had lower BRS (6.09 ms/mm Hg) as compared to GII (11.84) and GI (15.23). The difference was significant between GI and GIII (p = 0.01). Correlating BRS with the density of ventricular extrasystoles (VE), low VE density (<10/h) was associated with preserved BRS. Only 59% of the patients with high VE density (> 10/h) had preserved BRS (p = 0.003). Patients with depressed BRS had higher VE density (p = 0.01), regardless of the EF. The BRS was the only variable related to the occurrence of SVT (p = 0.028).

Conclusion

The BRS is preserved in undetermined CD. The BRS impairment increases as disease progresses, being more severe in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with EF, but with the density and complexity of ventricular arrhythmias.     

Long-term results of slow pathway ablation in patients with atrioventricular nodal reentrant tachycardia: simple approach

AimsThe aim of this study was to report the short- and long-term results of slow pathway radiofrequency (RF) ablation in patients with atrioventricular (AV) nodal reentrant tachycardia (AVNRT) using a simplified approach (2 catheters and short applications of RF).Materials and MethodsThis was a retrospective study that included consecutive patients with AVNRT. We used an anatomical approach with only 2 catheters. Decremental AV nodal conduction and atrial-His conduction interval jump were measured. To detect the onset of the QRS, we used surface lead II. During the stimulation protocol, we performed S2-QRS and S3-QRS measurements. An increase in the S3-QRS3 interval of 50 milliseconds or greater in response to a decrease in the S2-QRS2 coupling interval of 10 milliseconds was defined as a discontinuous AV nodal function curve and taken as evidence of dual antegrade AV pathways. Atrioventricular nodal reentrant tachycardia was demonstrated by the presence of dual AV nodal physiology, atrial echoes, and tachycardia induction with a 1:1 AV relationship and a VA interval of less than 70 milliseconds. Short RF applications (10-15 seconds) were delivered at an intermediate point between the posteroseptal and medioseptal regions of the Koch triangle. The applications were considered effective when junctional rhythm appeared. The end point was the demonstration of slow pathway modification without AVNRT induction.ResultsThree hundred forty-four patients (age, 49.22 ± 17.47 years; 254 were female) were included. Discontinuous AV nodal function curves were found in 271 patients (78.77%), and short-term success was achieved in all patients. The anterograde jump in AV nodal conduction was abolished after RF in 222 patients (81.91%), and discontinuous AV nodal conduction and single AV nodal echo beats persisted in 49 cases (18%). The mean number of RF application was 7.79 ± 2.23, the mean number of effective applications was 4.63 ± 0.62, and the mean RF application time was 54.92 ± 8.03 seconds. The total procedure and fluoroscopy time was 29.45 ± 9.6 and 10.87 ± 2.36 minutes, respectively. After the procedure, all patients were followed up for a mean of 46.44 ± 18.89 months, and 7 patients (2%) presented AVNRT recurrences. Complications were observed in 4 patients (1.16%); no permanent AV block was observed.ConclusionIn this study, slow pathway RF ablation using a simplified approach technique is an effective and safe approach for the treatment of AVNRT.     

Mechanical elasticity as a physical signature of conformational dynamics in a virus particle

In this study we test the hypothesis that mechanically elastic regions in a virus particle (or large biomolecular complex) must coincide with conformationally dynamic regions, because both properties are intrinsically correlated. Hypothesis-derived predictions were subjected to verification by using 19 variants of the minute virus of mice capsid. The structural modifications in these variants reduced, preserved, or restored the conformational dynamism of regions surrounding capsid pores that are involved in molecular translocation events required for virus infectivity. The mechanical elasticity of the modified capsids was analyzed by atomic force microscopy, and the results corroborated every prediction tested: Any mutation (or chemical cross-linking) that impaired a conformational rearrangement of the pore regions increased their mechanical stiffness. On the contrary, any mutation that preserved the dynamics of the pore regions also preserved their elasticity. Moreover, any pseudo-reversion that restored the dynamics of the pore regions (lost through previous mutation) also restored their elasticity. Finally, no correlation was observed between dynamics of the pore regions and mechanical elasticity of other capsid regions. This study (i) corroborates the hypothesis that local mechanical elasticity and conformational dynamics in a viral particle are intrinsically correlated; (ii) proposes that determination by atomic force microscopy of local mechanical elasticity, combined with mutational analysis, may be used to identify and study conformationally dynamic regions in virus particles and large biomolecular complexes; (iii) supports a connection between mechanical properties and biological function in a virus; (iv) shows that viral capsids can be greatly stiffened by protein engineering for nanotechnological applications.     

Fracture strength of incisor crowns after intracoronal bleaching with sodium percarbonate

Abstract – Objectives: To compare the fracture resistance of bovine teeth after intracoronal bleaching with sodium percarbonate (SPC) or sodium perborate (SP) mixed with water or 20% hydrogen peroxide (HP). Materials and methods: Fifty extracted bovine teeth were divided into four experimental groups (G1–G4) and one control (n = 10) after endodontic treatment. Following root canal obturation, a glass ionomer barrier was placed at the cemento–enamel junction. After that, the pulp chambers were filled with: G1 – SP with water; G2 – SP with 20% HP; G3 – SPC with water; and G4 – SPC with 20% HP. No bleaching agent was used in the control group. Coronal access cavities were sealed with glass ionomer and specimens were immersed in artificial saliva. The bleaching agents were replaced after 7 days, and teeth were kept in artificial saliva for an additional 7 days, after which the pastes were removed and the coronal access cavities were restored with glass ionomer. Crowns were subjected to compressive load at a cross head speed of 0.5 mm min^?1 applied at 135° to the long axis of the root by an EMIC DL2000 testing machine, until coronal fracture. Data were statistically analysed by anova and Tukey test. Results: No differences in fracture resistance were observed between the experimental groups (P > 0.05). However, all experimental groups presented lower fracture resistance than the control group (P < 0.05). Conclusion: SPC and SP led to equal reduction on fracture resistance of dental crowns, regardless of being mixed with water or 20% HP.     

Development of polymorphic microsatellite markers for the microendemic pupfishes Cyprinodon julimes and C. pachycephalus

We developed microsatellite loci for the Julimes pupfish, Cyprinodon julimes. Twenty-five loci were screened across 19 individuals from Julimes Spring, Chihuahua, Mexico. The number of alleles per locus ranged from 2 to 14, observed heterozygosity ranged from 0.105 to 0.947, and the probability of identity values ranged from 0.022 to 0.588. We then tested for cross-amplification in the bighead pupfish, C. pachycephalus; twenty-three individuals from San Diego de Alcalá, Chihuahua, Mexico, were screened across the 20 loci that amplified cleanly. These new loci will be used for long-term genetic monitoring of these critically endangered species.     

Immunogenicity of Recombinant Proteins Consisting of Plasmodium vivax Circumsporozoite Protein Allelic Variant-Derived Epitopes Fused with Salmonella enterica Serovar Typhimurium Flagellin

A Plasmodium falciparum circumsporozoite protein (CSP)-based recombinant fusion vaccine is the first malaria vaccine to reach phase III clinical trials. Resistance to infection correlated with the production of antibodies to the immunodominant central repeat region of the CSP. In contrast to P. falciparum, vaccine development against the CSP of Plasmodium vivax malaria is far behind. Based on this gap in our knowledge, we generated a recombinant chimeric protein containing the immunodominant central repeat regions of the P. vivax CSP fused to Salmonella enterica serovar Typhimurium-derived flagellin (FliC) to activate the innate immune system. The recombinant proteins that were generated contained repeat regions derived from each of the 3 different allelic variants of the P. vivax CSP or a fusion of regions derived from each of the 3 allelic forms. Mice were subcutaneously immunized with the fusion proteins alone or in combination with the Toll-like receptor 3 (TLR-3) agonist poly(I·C), and the anti-CSP serum IgG response was measured. Immunization with a mixture of the 3 recombinant proteins, each containing immunodominant epitopes derived from a single allelic variant, rather than a single recombinant protein carrying a fusion of regions derived from each of 3 allelic forms elicited a stronger immune response. This response was independent of TLR-4 but required TLR-5/MyD88 activation. Antibody titers significantly increased when poly(I·C) was used as an adjuvant with a mixture of the 3 recombinant proteins. These recombinant fusion proteins are novel candidates for the development of an effective malaria vaccine against P. vivax.