Ischemia is a limiting factor during distraction osteogenesis. The authors sought to determine the extent of ischemia in the distraction zone and whether endothelial progenitor cells home to the ...distraction zone and participate in local vasculogenesis.
Laser Doppler imaging was used to assess the extent of blood flow in the distraction zone in gradually distracted, immediately distracted, and osteotomized rat mandibles during activation and consolidation. Animals (n = 50; 25 rats with unilateral gradual distraction and contralateral osteotomy as an internal control, and 25 rats with unilateral immediate distraction) were examined on postoperative days 4, 6, and 8 of activation, and after 1 and 2 weeks of consolidation. Endothelial progenitor cells isolated from human peripheral blood were labeled with fluorescent DiI dye, and 0.5 x 10 cells were injected intra-arterially under direct vision into each carotid artery at the start of activation in nude rats (n = 18) that then underwent the distraction protocol outlined above.
Doppler flow analysis demonstrated relative ischemia during the activation period in the distraction osteogenesis group and increased blood flow in the osteotomized control group as compared with flow in a normal hemimandible normal, 1 (standardized); distraction osteogenesis, 0.58 +/- 0.05; control, 2.58 +/- 0.21; p < 0.05 for both results. We observed a significantly increased endothelial progenitor cell population at the generate site versus controls at midactivation and at 1 and 2 weeks of consolidation 25 +/- 1.9 versus 1 +/- 0.3 DiI-positive cells per high-power field (p < 0.05), 124 +/- 21 versus 8 +/- 4 DiI-positive cells per high-power field (p < 0.05), and 106 +/- 18 versus 9 +/- 3 DiI-positive cells per high-power field (p < 0.05), respectively.
These data suggest that the distraction zone becomes relatively ischemic during activation and that endothelial progenitor cells home to the ischemic generate site during the activation phase and remain during the consolidation phase. Selective expansion of these stem cells may be useful in overcoming ischemic limitations of distraction osteogenesis. Moreover, their homing capability may be used to effect site-specific transgene delivery to the generate.
The widespread distribution of lentiviruses among African primates, and the lack of severe pathogenesis in many of these natural reservoirs, are taken as evidence for long-term co-evolution between ...the simian immunodeficiency viruses (SIVs) and their primate hosts. Evidence for positive selection acting on antiviral restriction factors is consistent with virus-host interactions spanning millions of years of primate evolution. However, many restriction mechanisms are not virus-specific, and selection cannot be unambiguously attributed to any one type of virus. We hypothesized that the restriction factor TRIM5, because of its unique specificity for retrovirus capsids, should accumulate adaptive changes in a virus-specific fashion, and therefore, that phylogenetic reconstruction of TRIM5 evolution in African primates should reveal selection by lentiviruses closely related to modern SIVs. We analyzed complete TRIM5 coding sequences of 22 Old World primates and identified a tightly-spaced cluster of branch-specific adaptions appearing in the Cercopithecinae lineage after divergence from the Colobinae around 16 million years ago. Functional assays of both extant TRIM5 orthologs and reconstructed ancestral TRIM5 proteins revealed that this cluster of adaptations in TRIM5 specifically resulted in the ability to restrict Cercopithecine lentiviruses, but had no effect (positive or negative) on restriction of other retroviruses, including lentiviruses of non-Cercopithecine primates. The correlation between lineage-specific adaptations and ability to restrict viruses endemic to the same hosts supports the hypothesis that lentiviruses closely related to modern SIVs were present in Africa and infecting the ancestors of Cercopithecine primates as far back as 16 million years ago, and provides insight into the evolution of TRIM5 specificity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cranial vault remodeling procedures are carried out for both syndromic and nonsyndromic craniosynostosis as well as to correct some acquired deformities of the cranial vault. These procedures improve ...not only cosmesis but also neurological symptoms. The purpose of this study was to determine the incidence of "late" cephalohematoma, an underreported complication following these complex procedures.
A total of 113 patients underwent 127 cranial vault remodeling procedures using autogenous bone over a 6-year period. All patients who developed a late cephalohematoma 75 days or more after surgery were recorded. The time, size, and location of the cephalohematoma, the treatment performed, and the length of follow-up were also recorded. Ages at initial operation and postoperative follow-up were compared between patient groups for statistical differences.
Of the 113 patients, 17 developed 18 late cephalohematomas. The incidence for this complication was 15 percent. The median age at operation for all patients was 10 months, and most late cephalohematomas occurred 208 days later (range, 77 to 1416 days), at 12 to 24 months of age. Fronto-orbital advancement was the most commonly performed procedure, and 83.3 percent of late cephalohematomas occurred in the frontal region. No cephalohematomas became infected or required any operative intervention, but they were aspirated.
Surgeons should inform prospective parents of patients undergoing cranial vault remodeling procedures of this potential complication. This will improve parental awareness and possible avoidance strategies in future patients. Further evaluation and follow-up are required to determine the minimum length of postoperative time after which late cephalohematomas do not occur.
Objectives Patients who undergo lung resection surgery are at risk for postoperative morbidity and mortality. Appropriate selection of the surgical candidate is crucial in the treatment of lung ...cancer. Heart rate recovery is a measure of physical fitness. We aimed to investigate the association of impaired heart rate recovery with cardiopulmonary complications after lung resection surgery for treatment of lung cancer. Methods Data from consecutive patients who, between 2009 and 2013, underwent heart rate recovery evaluation after 6-minute walk tests before lung resection surgery were retrospectively reviewed. Impaired heart rate recovery was defined as a 12-beat or less decrease in peak heart rate at 1 minute after the 6-minute walk test. Postoperative cardiopulmonary complications were as defined by the Society of Thoracic Surgeons General Thoracic Surgery Database. Logistic regression was performed, including previously known risk factors for postoperative complications after lung resection surgery. Results A total of 96 patients had heart rate recovery evaluated within 6 months of lung resection surgery for treatment of lung cancer. Thirty-one patients had impaired heart rate recovery, 17 of whom (55%) had cardiopulmonary complications. A total of 65 patients had normal heart rate recovery, 17 of whom (26%) had cardiopulmonary complications. In multivariable logistic regression analysis, impaired heart rate recovery was significantly associated with postoperative cardiopulmonary complications (odds ratio, 4.97; confidence interval, 1.79-13.8; P = .002). No patient died within 30 days after surgery. Conclusions Impaired heart rate recovery after the 6-minute walk test is associated with postoperative cardiopulmonary complications in patients who underwent lung resection surgery for treatment of lung cancer.
Cellular restriction factors, which render cells intrinsically resistant to viruses, potentially impose genetic barriers to cross-species transmission and emergence of viral pathogens in nature. One ...such factor is APOBEC3G. To overcome APOBEC3G-mediated restriction, many lentiviruses encode Vif, a protein that targets APOBEC3G for degradation. As with many restriction factor genes, primate APOBEC3G displays strong signatures of positive selection. This is interpreted as evidence that the primate APOBEC3G locus reflects a long-term evolutionary "arms-race" between retroviruses and their primate hosts. Here, we provide direct evidence that APOBEC3G has functioned as a barrier to cross-species transmission, selecting for viral resistance during emergence of the AIDS-causing pathogen SIVmac in captive colonies of Asian macaques in the 1970s. Specifically, we found that rhesus macaques have multiple, functionally distinct APOBEC3G alleles, and that emergence of SIVmac and simian AIDS required adaptation of the virus to evade APOBEC3G-mediated restriction. Our evidence includes the first comparative analysis of APOBEC3G polymorphism and function in both a reservoir and recipient host species (sooty mangabeys and rhesus macaques, respectively), and identification of adaptations unique to Vif proteins of the SIVmac lineage that specifically antagonize rhesus APOBEC3G alleles. By demonstrating that interspecies variation in a known restriction factor selected for viral counter-adaptations in the context of a documented case of cross-species transmission, our results lend strong support to the evolutionary "arms-race" hypothesis. Importantly, our study confirms that APOBEC3G divergence can be a critical determinant of interspecies transmission and emergence of primate lentiviruses, including viruses with the potential to infect and spread in human populations.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Retroviral capsid recognition by Trim5 blocks productive infection. Rhesus macaques harbor three functionally distinct Trim5 alleles: Trim5αQ, Trim5αTFP and Trim5CypA. Despite the high degree of ...amino acid identity between Trim5αQ and Trim5αTFP alleles, the Q/TFP polymorphism results in the differential restriction of some primate lentiviruses, suggesting these alleles differ in how they engage these capsids. Simian immunodeficiency virus of rhesus macaques (SIVmac) evolved to resist all three alleles. Thus, SIVmac provides a unique opportunity to study a virus in the context of the Trim5 repertoire that drove its evolution in vivo. We exploited the evolved rhesus Trim5α resistance of this capsid to identify gain-of-sensitivity mutations that distinguish targets between the Trim5αQ and Trim5αTFP alleles. While both alleles recognize the capsid surface, Trim5αQ and Trim5αTFP alleles differed in their ability to restrict a panel of capsid chimeras and single amino acid substitutions. When mapped onto the structure of the SIVmac239 capsid N-terminal domain, single amino acid substitutions affecting both alleles mapped to the β-hairpin. Given that none of the substitutions affected Trim5αQ alone, and the fact that the β-hairpin is conserved among retroviral capsids, we propose that the β-hairpin is a molecular pattern widely exploited by Trim5α proteins. Mutations specifically affecting rhesus Trim5αTFP (without affecting Trim5αQ) surround a site of conservation unique to primate lentiviruses, overlapping the CPSF6 binding site. We believe targeting this site is an evolutionary innovation driven specifically by the emergence of primate lentiviruses in Africa during the last 12 million years. This modularity in targeting may be a general feature of Trim5 evolution, permitting different regions of the PRYSPRY domain to evolve independent interactions with capsid.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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