Genome Digging: Insight into the Mitochondrial Genome of Homo

A fraction of the Neanderthal mitochondrial genome sequence has a similarity with a 5,839-bp nuclear DNA sequence of mitochondrial origin (numt) on the human chromosome 1. This fact has never been interpreted. Although this phenomenon may be attributed to contamination and mosaic assembly of Neanderthal mtDNA from short sequencing reads, we explain the mysterious similarity by integration of this numt (mtAncestor-1) into the nuclear genome of the common ancestor of Neanderthals and modern humans not long before their reproductive split.Exploiting bioinformatics, we uncovered an additional numt (mtAncestor-2) with a high similarity to the Neanderthal mtDNA and indicated that both numts represent almost identical replicas of the mtDNA sequences ancestral to the mitochondrial genomes of Neanderthals and modern humans. In the proteins, encoded by mtDNA, the majority of amino acids distinguishing chimpanzees from humans and Neanderthals were acquired by the ancestral hominins. The overall rate of nonsynonymous evolution in Neanderthal mitochondrial protein-coding genes is not higher than in other lineages. The model incorporating the ancestral hominin mtDNA sequences estimates the average divergence age of the mtDNAs of Neanderthals and modern humans to be 450,000-485,000 years. The mtAncestor-1 and mtAncestor-2 sequences were incorporated into the nuclear genome approximately 620,000 years and 2,885,000 years ago, respectively.This study provides the first insight into the evolution of the mitochondrial DNA in hominins ancestral to Neanderthals and humans. We hypothesize that mtAncestor-1 and mtAncestor-2 are likely to be molecular fossils of the mtDNAs of Homo heidelbergensis and a stem Homo lineage. The d(N)/d(S) dynamics suggests that the effective population size of extinct hominins was low. However, the hominin lineage ancestral to humans, Neanderthals and H. heidelbergensis, had a larger effective population size and possessed genetic diversity comparable with those of chimpanzee and gorilla

Indications for implant removal after fracture healing: a review of the literature

Introduction: The aim of this review was to collect and summarize published data on the indications for implant removal after fracture healing, since these are not well defined and guidelines hardly exist. Methods: A literature search was performed. Results: Though there are several presumed benefits of implant removal, such as functional improvement and pain relief, the surgical procedure can be very challenging and may lead to complications or even worsening of the complaints. Research has focused on the safety of metal implants (e.g., risk of corrosion, allergy, and carcinogenesis). For these reasons, implants have been removed routinely for decades. Along with the introduction of titanium alloy implants, the need for implant removal became a subject of debate in view of potential (dis)advantages since, in general, implants made of titanium alloys are more difficult to remove. Currently, the main indications for removal from both the upper and lower extremity are mostly 'relative' and patient-driven, such as pain, prominent material, or simply the request for removal. True medical indications like infection or intra-articular material are minor reasons. Conclusion: This review illustrates the great variety of view points in the literature, with large differences in opinions and practices about the indications for implant removal after fracture healing. Since some studies have described asymptomatic patients developing complaints after removal, the general advice nowadays is to remove implants after fracture healing only in symptomatic patients and after a proper informed consent. Well-designed prospective studies on this subject are urgently needed in order to form guidelines based on scientific evidence

Can Normal Fracture Healing Be Achieved When the Implant Is Retained on the Basis of Infection? An Experimental Animal Model

BACKGROUND: Infection after open fractures is a common complication. Treatment options for infections developed after intramedullary nailing surgery remain a topic of controversy. We therefore used a rat fracture model to evaluate the effects of infection on osseous union when the implant was maintained. QUESTIONS/PURPOSES: In a rat model, (1) does infection alter callus strength; (2) does infection alter the radiographic appearance of callus; and (3) does infection alter the histological properties of callus? METHODS: An open femoral fracture was created and fixed with an intramedullary Kirschner wire in 72 adult male Sprague-Dawley rats, which were divided into two study groups. In the infection group, the fracture site was contaminated with Staphylococcus aureus (36 animals), whereas in the control group, there was no bacterial contamination (36 animals). No antibiotics were used either for prophylaxis or for treatment. We performed biomechanical (maximum torque causing failure and stiffness), radiographic (Lane and Sandhu scoring for callus formation), and histologic (scoring for callus maturity) assessments at 3 and 6 weeks. The number of bacteria colonies on the femur, wire, and soft tissue inside knee were compared to validate that we successfully created an infection model. The number of bacteria colonies in the soft tissue inside the knee was higher in the infection group after 6 weeks than after the third week, demonstrating the presence of locally aggressive infection. RESULTS: Infection decreased callus strength at 6 weeks. Torque to failure (299.07 ± 65.53 Nmm versus 107.20 ± 88.81, mean difference with 95% confidence interval, 192 [43–340]; p = 0.007) and stiffness at 6 weeks (11.28 ± 2.67 Nmm versus 2.03 ± 1.68, mean difference with 95% confidence interval, 9 [3–16]; p = 0.004) both were greater in the control group than in the group with infection. Radiographic analysis at 6 weeks demonstrated the fracture line was less distinct (Lane and Sandhu score of 2–3) in the infection group and complete union was observed (Lane and Sandhu score of 3–4) in the control group (p = 0.001). Semiquantitative histology scores were not different between the noninfected controls and the rats with infection (score 10 versus 9). CONCLUSIONS: Retaining an implant in the presence of an underlying infection without antibiotic treatment leads to weaker callus and impedes callus maturation compared with noninfected controls in a rat model. Future studies might evaluate whether antibiotic treatment would modify this result. CLINICAL RELEVANCE: This model sets the stage for further investigations that might study the influence of different interventions on fracture healing in implant-associated osteomyelitis. Future observational studies might also evaluate the histological properties of callus in patients with osteomyelitis