Geographic variation of Trypanosoma cruzi discrete typing units from Triatoma infestans at different spatial scales

We assessed the diversity and distribution of Trypanosoma cruzi discrete typing units (DTU) in Triatoma infestans populations and its association with local vector-borne transmission levels at various geographic scales. At a local scale, we found high predominance (92.4%) of TcVI over TcV in 68 microscope-positive T. infestans collected in rural communities in Santiago del Estero province in northern Argentina. TcV was more often found in communities with higher house infestation prevalence compatible with active vector-borne transmission. Humans and dogs were the main bloodmeal sources of the TcV- and TcVI-infected bugs. At a broader scale, the greatest variation in DTU diversity was found within the Argentine Chaco (227 microscope-positive bugs), mainly related to differences in equitability between TcVI and TcV among study areas. At a country-wide level, a meta-analysis of published data revealed clear geographic variations in the distribution of DTUs across countries. A correspondence analysis showed that DTU distributions in domestic T. infestans were more similar within Argentina (dominated by TcVI) and within Bolivia (where TcI and TcV had similar relative frequencies), whereas large heterogeneity was found within Chile. DTU diversity was lower in the western Argentine Chaco region and Paraguay (D = 0.14–0.22) than in the eastern Argentine Chaco, Bolivia and Chile (D = 0.20–0.68). Simultaneous DTU identifications of T. cruzi-infected hosts and triatomines across areas differing in epidemiological status are needed to shed new light on the structure and dynamics of parasite transmission cycles.     

Predictive imaging of chemotherapeutic response in a transgenic mouse model of pancreatic cancer

The underglycosylated mucin 1 tumor antigen (uMUC1) is a biomarker that forecasts the progression of adenocarcinomas. In this study, we evaluated the utility of a dual‐modality molecular imaging approach based on targeting uMUC1 for monitoring chemotherapeutic response in a transgenic murine model of pancreatic cancer (KCM triple transgenic mice). An uMUC1‐specific contrast agent (MN‐EPPT) was synthesized for use with magnetic resonance imaging (MRI) and fluorescence optical imaging. It consisted of dextran‐coated iron oxide nanoparticles conjugated to the near infrared fluorescent dye Cy5.5 and to a uMUC1‐specific peptide (EPPT). KCM triple transgenic mice were given gemcitabine as chemotherapy while control animals received saline injections following the same schedule. Changes in uMUC1 levels following chemotherapy were monitored using T2‐weighted MRI and optical imaging before and 24 hr after injection of the MN‐EPPT. uMUC1 expression in tumors from both groups was evaluated by histology and qRT‐PCR. We observed that the average delta‐T2 in the gemcitabine‐treated group was significantly reduced compared to the control group indicating lower accumulation of MN‐EPPT, and correspondingly, a lower level of uMUC1 expression. In vivo optical imaging confirmed the MRI findings. Fluorescence microscopy of pancreatic tumor sections showed a lower level of uMUC1 expression in the gemcitabine‐treated group compared to the control, which was confirmed by qRT‐PCR. Our data proved that changes in uMUC1 expression after gemcitabine chemotherapy could be evaluated using MN‐EPPT‐enhanced in vivo MR and optical imaging. These results suggest that the uMUC1‐targeted imaging approach could provide a useful tool for the predictive assessment of therapeutic response.     

High-Throughput Generation of P. falciparum Functional Molecules by Recombinational Cloning

Large-scale functional genomics studies for malaria vaccine and drug development will depend on the generation of molecular tools to study protein expression. We examined the feasibility of a high-throughput cloning approach using the Gateway system to create a large set of expression clones encoding Plasmodium falciparum single-exon genes. Master clones and their ORFs were transferred en masse to multiple expression vectors. Target genes (n = 303) were selected using specific sets of criteria, including stage expression and secondary structure. Upon screening four colonies per capture reaction, we achieved 84% cloning efficiency. The genes were subcloned in parallel into three expression vectors: a DNA vaccine vector and two protein expression vectors. These transfers yielded a 100% success rate without any observed recombination based on single colony screening. The functional expression of 95 genes was evaluated in mice with DNA vaccine constructs to generate antibody against various stages of the parasite. From these, 19 induced antibody titers against the erythrocytic stages and three against sporozoite stages. We have overcome the potential limitation of producing large P. falciparum clone sets in multiple expression vectors. This approach represents a powerful technique for the production of molecular reagents for genome-wide functional analysis of the P. falciparum genome and will provide for a resource for the malaria resource community distributed through public repositories.     

Bilateral hydrosalpinx in patients with Hirschsprung’s disease

Purpose

Hirschsprung's disease (HD) is uncommon in females. There are very few reports on the patients' obstetric and gynecological outcome. Hydrosalpinx causes pain and infertility. It is rare in nonsexually active teenagers. It may be because of an intrinsic disease of the fallopian tubes or secondary to surgery. Aim: to describe the relationship between hydrosalpinx and HD or its surgical approach; to report the impact of bilateral hydrosalpinx on fertility in HD.

Floating right heart thrombi: A pooled analysis of cases reported over the past 10 years

Introduction

Floating right heart thrombi (FRHTS) are a rare phenomenon associated with high mortality. Immediate treatment is mandatory, but optimal therapy is controversial.