Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

The trypomastigote small surface antigen (TSSA) is a mucin-like molecule from Trypanosoma cruzi, the etiological agent of Chagas disease, which displays amino acid polymorphisms in parasite isolates. TSSA expression is restricted to the surface of infective cell-derived trypomastigotes, where it functions as an adhesin and engages surface receptors on the host cell as a prerequisite for parasite internalization. Previous results have established TSSA-CL, the isoform encoded by the CL Brener clone, as an appealing candidate for use in serology-based diagnostics for Chagas disease. Here, we used a combination of peptide- and recombinant protein-based tools to map the antigenic structure of TSSA-CL at maximal resolution. Our results indicate the presence of different partially overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which contains most of the polymorphisms found in parasite isolates. Based on these results, we assessed the serodiagnostic performance of a 21-amino-acid-long peptide that spans TSSA-CL major antigenic determinants, which was similar to the performance of the previously validated glutathione S-transferase (GST)-TSSA-CL fusion molecule. Furthermore, the tools developed for the antigenic characterization of the TSSA antigen were also used to explore other potential diagnostic applications of the anti-TSSA humoral response in Chagasic patients. Overall, our present results provide additional insights into the antigenic structure of TSSA-CL and support this molecule as an excellent target for molecular intervention in Chagas disease.     

Can contrast-enhanced ultrasound with second-generation contrast agents replace computed tomography angiography for distinguishing between occlusion and pseudo-occlusion of the internal carotid artery?

OBJECTIVE:

The purpose of this study was to evaluate the effectiveness of contrast-enhanced ultrasound with a second-generation contrast agent in distinguishing between occlusion and pseudo-occlusion of the cervical internal carotid artery, comparing it with that of conventional Doppler ultrasound and the gold standard, computed tomography angiography.

METHOD:

Between June 2006 and June 2012, we screened 72 symptomatic vascular surgery outpatients at a public hospital. Among those patients, 78 cervical internal carotid arteries were previously classified as occluded by Doppler ultrasound (without contrast). The patients were examined again with Doppler ultrasound, as well as with contrast-enhanced ultrasound and computed tomography angiography. The diagnosis was based on the presence or absence of flow.

RESULTS:

Among the 78 cervical internal carotid arteries identified as occluded by Doppler ultrasound, occlusion was confirmed by computed tomography angiography in only 57 (73.1%), compared with 59 (77.5%) for which occlusion was confirmed by contrast-enhanced ultrasound (p>0.5 vs. computed tomography angiography). Comparing contrast-enhanced ultrasound with Doppler ultrasound, we found that the proportion of cervical internal carotid arteries classified as occluded was 24.4% higher when the latter was used (p<0.001).

CONCLUSIONS:

We conclude that, in making the differential diagnosis between occlusion and pseudo-occlusion of the cervical internal carotid artery, contrast-enhanced ultrasound with a second-generation contrast agent is significantly more effective than conventional Doppler ultrasound and is equally as effective as the gold standard (computed tomography angiography). Our findings suggest that contrast-enhanced ultrasound could replace computed tomography angiography in this regard.     

Nonsyndromic X‐linked intellectual deficiency in three brothers with a novel MED12 missense mutation [c.5922G>T (p.Glu1974His)]

X‐linked intellectual deficiency (XLID) is a large group of genetic disorders. MED12 gene causes syndromic and nonsyndromic forms of XLID. Only seven pathological mutations have been identified in this gene. Here, we report a novel mutation segregating with XLID phenotype. This mutation could be in favor of genotype–phenotype correlations.     

Socialization Patterns and Their Associations with Unprotected Anal Intercourse,HIV, and Syphilis Among High-Risk Men Who Have Sex with Men and Transgender Women in Peru

The association of socialization patterns with unprotected anal intercourse (UAI) and HIV/STI prevalence remains underexplored in men who have sex with men (MSM) and transgender women (TW) in developing country settings. We evaluated the correlation of UAI, HIV, and syphilis with MSM/TW venue attendance and social network size among high-risk MSM and TW in Peru according to self-reported sexual identity. Frequency of venue attendance and MSM/TW social network size were lowest among heterosexual MSM and highest among TW respondents. Attendance (frequent or occasional) at MSM/TW venues was associated with increased odds of insertive UAI among heterosexual participants. Frequent venue attendance was associated with increased odds of receptive UAI among gay/homosexual, bisexual, and TW participants. Further investigation of the differing socialization patterns and associations with HIV/STI transmission within subgroups of Peruvian MSM and TW will enable more effective prevention interventions for these populations.