Evaluation of antigens from various Leishmania species in a Western blot for diagnosis of American tegumentary leishmaniasis

A Western blot method that uses antigens from culture promastigote forms of Leishmania (Viannia) braziliensis, L. (Leishmania) amazonensis, L. (Leishmania) tropica, and a trypanosomatid (strain 268T) isolated from naturally infected tomatoes was evaluated for laboratory diagnosis of American tegumentary leishmaniasis (ATL). Serum samples were obtained from 108 patients with ATL (group I), 23 chagasic patients (group II), 32 patients with other diseases (group III), and 78 healthy individuals (group IV). The overall analysis showed a sensitivity of 76.90%, 90.40%, 78.50%, and 87.90%, a specificity of 100%, 93.80%, 87.80%, and 77.10%, a positive predictive value of 100%, 94.00%, 89.50%, and 72.50%, a negative predictive value of 75.70%, 90.00%, 75.40%, and 90.20%, and a concordance coefficient kappa of 0.7358, 0.8400, 0.6491, and 0.6287 for L. (V.) braziliensis, L. (L.) amazonensis, L. (L.) tropica, and strain 268T antigens, respectively. The antigenic profile recognized by serum samples from patients with ATL and with Chagas' disease permits serologic distinction between these infections.     

Prospective evaluation comparing the effects of enalapril and losartan in left ventricular remodeling after acute myocardial infarction

Background

Previous studies have compared angiotensin receptor blockers and angiotensin-converting enzyme inhibitors in patients with heart failure, but there are few data about the effect of these drugs regarding left ventricular remodeling after myocardial infarction.

Methods

Fifty-two consecutive patients with first anterior wall myocardial infarction within 24 hours of evolution were randomized to receive enalapril (as much as 20 mg; mean, 14.6 mg), or losartan (as much as 50 mg; mean, 48 mg). Left ventricular ejection fraction and ventricular volumes were analyzed in 2 serial radionuclide ventriculograpies, carried out within 4 days after the infarction (mean, 97.4 ± 114.2 hours) and after 6 months (mean, 177.7 ± 16.7 days). Ventriculographies were analyzed by a single blinded observer. Mainly because of the unexpected large SD values obtained, the power of the study to demonstrate equivalence between the groups was only 15.7%.

Results

The differences obtained between the first and the second ventriculographies, for the enalapril and losartan groups, were: for left ventricular ejection fraction, −0.4% ± 6.6% versus −1.1% ± 5.9% (P = . 67; 95% CI, 2.77-4.23); for final systolic volume, 0.07 ± 7.7 mL/m² versus −0.2 ± 6.1mL/m² (P = . 85; 95% CI, −3.57-4.26); for final diastolic volume −0.7 ± 12.1 mL/m² versus −3.6 - 9.9 mL/m² (P = . 34; 95% CI, −3.22-9.17).

Conclusion

This study, although underpowered, suggests that neither enalapril nor losartan was superior as compared with each other for left ventricular remodeling after myocardial infarction; however, powerful evidence of equivalence was not provided.     

Ca(2+)-regulated structural changes in troponin

Troponin senses Ca2+ to regulate contraction in striated muscle. Structures of skeletal muscle troponin composed of TnC (the sensor), TnI (the regulator), and TnT (the link to the muscle thin filament) have been determined. The structure of troponin in the Ca(2+)-activated state features a nearly twofold symmetrical assembly of TnI and TnT subunits penetrated asymmetrically by the dumbbell-shaped TnC subunit. Ca ions are thought to regulate contraction by controlling the presentation to and withdrawal of the TnI inhibitory segment from the thin filament. Here, we show that the rigid central helix of the sensor binds the inhibitory segment of TnI in the Ca(2+)-activated state. Comparison of crystal structures of troponin in the Ca(2+)-activated state at 3.0 angstroms resolution and in the Ca(2+)-free state at 7.0 angstroms resolution shows that the long framework helices of TnI and TnT, presumed to be a Ca(2+)-independent structural domain of troponin are unchanged. Loss of Ca ions causes the rigid central helix of the sensor to collapse and to release the inhibitory segment of TnI. The inhibitory segment of TnI changes conformation from an extended loop in the presence of Ca2+ to a short alpha-helix in its absence. We also show that Anapoe, a detergent molecule, increases the contractile force of muscle fibers and binds specifically, together with the TnI switch helix, in a hydrophobic pocket of TnC upon activation by Ca ions.     

Evaluating NRC’s Recommendations for Educating Children with Autism a Decade Later

Background

Over a decade ago, the National Research Council (NRC) published the influential book, Educating Children with Autism.

Objective

To survey parents and state-level special education administrators to evaluate how NRC’s recommendations, as published in Educating Children with Autism, have impacted educational practices for children with autism in the US.

Methods

149 parents of children with autism and 35 state-level special education administrators from 35 states were surveyed on the degree to which they agreed with NRC’s recommendations and the degree to which they believed NRC’s recommendations have been implemented.

Results

Parents and administrators agreed with most NRC recommendations; however, disagreements between parents and administrators were evident regarding labeling of students with autism, intensity of services, and training of staff. Conversely, parents and administrators concurred that the recommendations had been poorly to modestly implemented, overall. Lowest levels of implementation were found for training of qualified staff, research-based curricula, and mental health supports for families. Qualitative analysis of parents’ comments highlighted that vigorous advocacy was necessary for their children to receive appropriate services consistent with NRC’s recommendations.

Conclusions

Over a decade following publication of Educating Children with Autism, most of NRC’s recommendations have not been fully implemented. Policy makers should focus particular attention on improving professional training, disseminating research-based practices, and providing mental health supports for families.     

Ilex paraguariensis (yerba mate) improves endocrine and metabolic disorders in obese rats primed by early weaning

Purpose

We showed that early weaned rats developed obesity, hyperleptinemia, leptin and insulin resistance at adulthood. Here, we studied the potential beneficial effects of Ilex paraguariensis aqueous solution upon body composition, glycemia, lipid and hormonal profiles, leptin signaling and NPY content.

Methods

To induce early weaning, lactating rats’ teats were blocked with a bandage to interrupt lactation during the last 3 days (EW group), while control offspring had free access to milk throughout lactation (C group). In postnatal day (PN) 150, EW offspring were subdivided into: EW and EW+ mate groups treated, respectively, with water or yerba mate aqueous solution (1 g/kg BW/day, gavage) during 30 days. C offspring received water for gavage. In PN180, offspring were killed.

Results

EW+ mate group presented lower body weight (?10 %), adipose mass (retroperitoneal:?40 % and epididymal:?44 %), total body fat (?43 %), subcutaneous fat (?46 %), visceral adipocyte area (?21 %), triglyceridemia (?31 %) and hypothalamic NPY content (?37 %) compared to EW group. However, hyperglycemia and lower HDL-c levels observed in EW group were not reverted with mate treatment. Although the hyperleptinemia, lower hypothalamic JAK2 and pSTAT3 content of EW group were not corrected by mate treatment, the hyperphagia and higher hypothalamic SOCS-3 content were normalized in EW+ mate group, indicating that the central leptin resistance could be restored.

Conclusion

Thus, the therapy with yerba mate solution was capable to reverse abdominal obesity, leptin resistance and hypertriglyceridemia, suggesting an important role of this bioactive component in the management of obesity in this programming model.     

Neural correlates of reward and loss sensitivity in psychopathy

Psychopathy is a personality disorder associated with callous and impulsive behavior and criminal recidivism. It has long been theorized that psychopaths have deficits in processing reward and punishment. Here, we use structural and functional magnetic resonance imaging to examine the neural correlates of reward and loss sensitivity in a group of criminal psychopaths. Forty-one adult male prison inmates (n = 18 psychopaths and n = 23 non-psychopaths) completed a functional magnetic resonance imaging task involving the gain or loss of money. Across the entire sample of participants, monetary gains elicited robust activation within the ventral striatum (VS). Although psychopaths and non-psychopaths did not significantly differ with respect to overall levels of VS response to reward vs loss, we observed significantly different correlations between VS responses and psychopathy severity within each group. Volumetric analyses of striatal subregions revealed a similar pattern of correlations, specifically for the right accumbens area within VS. In a separate sample of inmates (n = 93 psychopaths and n = 117 non-psychopaths) who completed a self-report measure of appetitive motivation, we again found that the correlation with psychopathy severity differed between groups. These convergent results offer novel insight into the neural substrates of reward and loss processing in psychopathy.     

Plasma extracellular microRNAs are related to AIDS/cerebral toxoplasmosis co-infection

This study investigated the potential of five miRNA candidates for cerebral toxoplasmosis/HIV co-infection (CT/HIV) biomarkers. miR-155-5p, miR-146a-5p, miR-21-5p, miR-125b-5p and miR-29c-3p were tested in 79 plasma divided into groups: 32 CT/HIV patients; 27 individuals with asymptomatic toxoplasmosis (AT); and 20 individuals seronegative for toxoplasmosis (NC). From each was collected peripheral blood/EDTA for laboratory diagnosis. Blood cells for DNA extractions (molecular diagnosis), plasma for RNA extractions (gene expression) and ELISA (serological diagnosis). miRNA expression was performed by qPCR, and values were expressed in Relative Quantification (RQ). Among the five miRNAs, miR-21-5p and miR-146a-5p were up-expressed in CT/HIV group when compared with AT and NC groups. RQ means for miR-21-5p and miR-146a-5p in CT/HIV group were 3.829 and 2.500, while in AT group, were 1.815 and 1.661, respectively. Differences between 3 groups were statistically significant (Kruskal-Wallis ANOVA test), as well as CT/HIV and AT groups (Mann-Whitney test). Plasma of CT/HIV and AT groups expressed similar levels of miR-29c-3p, miR-155-5p and miR-125b-5p. As NC group was different of CT/HIV and AT groups, differences between three groups were statistically significant (Kruskal-Wallis ANOVA test). No difference was shown between CT/HIV and AT groups (Mann-Whitney test). These results suggest the host miRNAs modulation by Toxoplasma gondii.