Biomechanics associated with tibial stress fracture in runners: A systematic review and meta-analysis.

BACKGROUND: Tibial stress fracture (TSF) is an overuse running injury with a long recovery period. While many running studies refer to biomechanical risk factors for TSF, only a few have compared biomechanics in runners with TSF to controls. The aim of this systematic review and meta-analysis was to evaluate biomechanics in runners with TSF compared to controls. METHODS: Electronic databases PubMed, Web of Science, SPORTDiscus, Scopus, Cochrane, and CINAHL were searched. Risk of bias was assessed and meta-analysis conducted for variables reported in 3 or more studies. RESULTS: The search retrieved 359 unique records, but only the 14 that compared runners with TSF to controls were included in the review. Most studies were retrospective, 2 were prospective, and most had a small sample size (5-30 per group). Many variables were not significantly different between groups. Meta-analysis of peak impact, active, and braking ground reaction forces found no significant differences between groups. Individual studies found larger tibial peak anterior tensile stress, peak posterior compressive stress, peak axial acceleration, peak rearfoot eversion, and hip adduction in the TSF group. CONCLUSION: Meta-analysis indicated that discrete ground reaction force variables were not statistically significantly different in runners with TSF compared to controls. In individual included studies, many biomechanical variables were not statistically significantly different between groups. However, many were reported by only a single study, and sample sizes were small. We encourage additional studies with larger sample sizes of runners with TSF and controls and adequate statistical power to confirm or refute these findings.

Comparison of lower limb muscle architecture and geometry in distance runners with rearfoot and forefoot strike pattern.

We examined the association between footfall pattern and characteristics of lower limb muscle function and compared lower limb muscle function between forefoot and rearfoot runners. Fifteen rearfoot and 16 forefoot runners were evaluated using ultrasonography of the gastrocnemii and tibialis anterior while strike index and heel strike angle quantified footfall pattern. Higher strike index was associated with lower medial gastrocnemius echo intensity (p = 0.05), lower lateral gastrocnemius echo intensity (p = 0.04), smaller tibialis anterior pennation angle (p = 0.05), and longer lateral gastrocnemius fascicle length (p = 0.04). Larger heel strike angle was associated with smaller medial gastrocnemius cross-sectional area (p = 0.04), shorter lateral gastrocnemius fascicle length (p < 0.01), and lower plantar flexion moment (p < 0.01). Larger plantar flexion moment was associated with lesser medial gastrocnemius echo intensity (p = 0.04), lesser lateral gastrocnemius echo intensity (p = 0.03), and greater lateral gastrocnemius fascicle length (p = 0.02). A smaller plantar flexion moment, larger heel strike angle, lower tibialis anterior echo intensity, larger tibialis anterior pennation angle, and smaller lateral gastrocnemius pennation angle were observed in rearfoot compared to forefoot runners (p < 0.05). Lower limb muscle architecture is associated with footfall pattern and ankle mechanics during running. Abbreviation: EMG: electromyographic; MG: medial gastrocnemius; LG: lateral gastrocnemius; TA: tibialis anterior; EI: echo intensity; CSA: cross-sectional area; PA: pennation angle; FL: fascicle length; FT: fat thickness.

The landscape of inherited and de novo copy number variants in a Plasmodium falciparum genetic cross.

BACKGROUND: Copy number is a major source of genome variation with important evolutionary implications. Consequently, it is essential to determine copy number variant (CNV) behavior, distributions and frequencies across genomes to understand their origins in both evolutionary and generational time frames. We use comparative genomic hybridization (CGH) microarray and the resolution provided by a segregating population of cloned progeny lines of the malaria parasite, Plasmodium falciparum, to identify and analyze the inheritance of 170 genome-wide CNVs. RESULTS: We describe CNVs in progeny clones derived from both Mendelian (i.e. inherited) and non-Mendelian mechanisms. Forty-five CNVs were present in the parent lines and segregated in the progeny population. Furthermore, extensive variation that did not conform to strict Mendelian inheritance patterns was observed. 124 CNVs were called in one or more progeny but in neither parent: we observed CNVs in more than one progeny clone that were not identified in either parent, located more frequently in the telomeric-subtelomeric regions of chromosomes and singleton de novo CNVs distributed evenly throughout the genome. Linkage analysis of CNVs revealed dynamic copy number fluctuations and suggested mechanisms that could have generated them. Five of 12 previously identified expression quantitative trait loci (eQTL) hotspots coincide with CNVs, demonstrating the potential for broad influence of CNV on the transcriptional program and phenotypic variation. CONCLUSIONS: CNVs are a significant source of segregating and de novo genome variation involving hundreds of genes. Examination of progeny genome segments provides a framework to assess the extent and possible origins of CNVs. This segregating genetic system reveals the breadth, distribution and dynamics of CNVs in a surprisingly plastic parasite genome, providing a new perspective on the sources of diversity in parasite populations.

Imaging professionals' beliefs on overutilization of CT and MRI exams.

The intent of an independent study was to see if radiologists, administrators, and technologists would agree that there is a problem with CT and MRI overutilization. Another goal was to see if they are doing anything about this issue, to determine if there are best practices in place, and to set the basis for future studies. A literature review uncovered United States utilization rates compared to the global community. It also revealed economic concerns and relevance to an increase in healthcare costs. The recognition of overutilization exists; however, many still have not put a program in place to help with mitigation.

Chloroquine susceptibility and reversibility in a Plasmodium falciparum genetic cross.

Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT) are major determinants of verapamil (VP)-reversible CQ resistance (CQR). In the presence of mutant PfCRT, additional genes contribute to the wide range of CQ susceptibilities observed. It is not known if these genes influence mechanisms of chemosensitization by CQR reversal agents. Using quantitative trait locus (QTL) mapping of progeny clones from the HB3 × Dd2 cross, we show that the P. falciparum multidrug resistance gene 1 (pfmdr1) interacts with the South-East Asia-derived mutant pfcrt haplotype to modulate CQR levels. A novel chromosome 7 locus is predicted to contribute with the pfcrt and pfmdr1 loci to influence CQR levels. Chemoreversal via a wide range of chemical structures operates through a direct pfcrt-based mechanism. Direct inhibition of parasite growth by these reversal agents is influenced by pfcrt mutations and additional loci. Direct labelling of purified recombinant PfMDR1 protein with a highly specific photoaffinity CQ analogue, and lack of competition for photolabelling by VP, supports our QTL predictions. We find no evidence that pfmdr1 copy number affects CQ response in the progeny; however, inheritance patterns indicate that an allele-specific interaction between pfmdr1 and pfcrt is part of the complex genetic background of CQR.

Regulatory hotspots in the malaria parasite genome dictate transcriptional variation.

The determinants of transcriptional regulation in malaria parasites remain elusive. The presence of a well-characterized gene expression cascade shared by different Plasmodium falciparum strains could imply that transcriptional regulation and its natural variation do not contribute significantly to the evolution of parasite drug resistance. To clarify the role of transcriptional variation as a source of stain-specific diversity in the most deadly malaria species and to find genetic loci that dictate variations in gene expression, we examined genome-wide expression level polymorphisms (ELPs) in a genetic cross between phenotypically distinct parasite clones. Significant variation in gene expression is observed through direct co-hybridizations of RNA from different P. falciparum clones. Nearly 18% of genes were regulated by a significant expression quantitative trait locus. The genetic determinants of most of these ELPs resided in hotspots that are physically distant from their targets. The most prominent regulatory locus, influencing 269 transcripts, coincided with a Chromosome 5 amplification event carrying the drug resistance gene, pfmdr1, and 13 other genes. Drug selection pressure in the Dd2 parental clone lineage led not only to a copy number change in the pfmdr1 gene but also to an increased copy number of putative neighboring regulatory factors that, in turn, broadly influence the transcriptional network. Previously unrecognized transcriptional variation, controlled by polymorphic regulatory genes and possibly master regulators within large copy number variants, contributes to sweeping phenotypic evolution in drug-resistant malaria parasites.