Multiple mitochondrial introgression events and heteroplasmy in trypanosoma cruzi revealed by Maxicircle MLST and next generation sequencing

Background Mitochondrial DNA is a valuable taxonomic marker due to its relatively fast rate of evolution. In Trypanosoma cruzi, the causative agent of Chagas disease, the mitochondrial genome has a unique structural organization consisting of 20–50 maxicircles (∼20 kb) and thousands of minicircles (0.5–10 kb). T. cruzi is an early diverging protist displaying remarkable genetic heterogeneity and is recognized as a complex of six discrete typing units (DTUs). The majority of infected humans are asymptomatic for life while 30–35% develop potentially fatal cardiac and/or digestive syndromes. However, the relationship between specific clinical outcomes and T. cruzi genotype remains elusive. The availability of whole genome sequences has driven advances in high resolution genotyping techniques and re-invigorated interest in exploring the diversity present within the various DTUs. Methodology/Principal Findings To describe intra-DTU diversity, we developed a highly resolutive maxicircle multilocus sequence typing (mtMLST) scheme based on ten gene fragments. A panel of 32 TcI isolates was genotyped using the mtMLST scheme, GPI, mini-exon and 25 microsatellite loci. Comparison of nuclear and mitochondrial data revealed clearly incongruent phylogenetic histories among different geographical populations as well as major DTUs. In parallel, we exploited read depth data, generated by Illumina sequencing of the maxicircle genome from the TcI reference strain Sylvio X10/1, to provide the first evidence of mitochondrial heteroplasmy (heterogeneous mitochondrial genomes in an individual cell) in T. cruzi. Conclusions/Significance mtMLST provides a powerful approach to genotyping at the sub-DTU level. This strategy will facilitate attempts to resolve phenotypic variation in T. cruzi and to address epidemiologically important hypotheses in conjunction with intensive spatio-temporal sampling. The observations of both general and specific incidences of nuclear-mitochondrial phylogenetic incongruence indicate that genetic recombination is geographically widespread and continues to influence the natural population structure of TcI, a conclusion which challenges the traditional paradigm of clonality in T. cruzi

Outcomes of total hip arthroplasty, as a salvage procedure, following failed internal fixation of intracapsular fractures of the femoral neck: a systematic review and meta-analysis.

AIMS: The optimal management of intracapsular fractures of the femoral neck in independently mobile patients remains open to debate. Successful fixation obviates the limitations of arthroplasty for this group of patients. However, with fixation failure rates as high as 30%, the outcome of revision surgery to salvage total hip arthroplasty (THA) must be considered. We carried out a systematic review to compare the outcomes of salvage THA and primary THA for intracapsular fractures of the femoral neck. PATIENTS AND METHODS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) compliant systematic review, using the PubMed, EMBASE and Cochrane libraries databases. A meta-analysis was performed where possible, and a narrative synthesis when a meta-analysis was not possible. RESULTS: Our analyses revealed a significantly increased risk of complications including deep infection, early dislocation and peri-prosthetic fracture with salvage THA when compared with primary THA for an intracapsular fracture of the femoral neck (overall risk ratio of 3.15). Functional outcomes assessment using EuroQoL (EQ)-5D were not significantly different (p = 0.3). CONCLUSION: Salvage THA carries a significantly higher risk of complications than primary THA for intracapsular fractured neck of femur. Current literature is still lacking well designed studies to provide a full answer to the question. TAKE HOME MESSAGE: Salvage THA is associated with more complications than primary THA for intracapsular neck of femur fractures

Status and trends of European pollinators. Key findings of the STEP project

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