Evolutionary genetics: jumping into a new species.
A new study finds a dramatic increase in transposable element numbers in three new sunflower hybrid species, and may suggest a novel role for transposable elements in speciation.
Genetic Speciation↗
Biomedical subjects
Audrey S Chang
Publications and source records attributed to Audrey S Chang.
The intravenous ketamine test predicts subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients.
UNLABELLED: Fibromyalgia (FM) is a challenging pain syndrome for which no reliable pharmacologic treatment exists. Recent clinical studies suggest that N-methyl-D-aspartate receptors might play a role in the pathogenesis of this disorder. To determine whether an intravenous (IV) ketamine test predicts the response to a therapeutic trial with an oral N-methyl-D-aspartate receptor antagonist, we performed a low-dose (0.1 mg/kg) IV ketamine infusion on 34 consecutive patients with FM, which was subsequently followed by an oral dextromethorphan (DX) treatment regimen. As per previous guidelines, the cutoff value for a positive response to the IV ketamine test was designated to be 67% pain relief, and a positive response to DX treatment was 50% pain reduction at 4- to 6-week follow-up visits. The degree of correlation between pain relief with ketamine and DX was highly significant (Pearson correlation coefficient, 0.66; P < .001). Ten patients responded positively to both ketamine and DX, 19 responded to neither drug, 3 had a positive response to ketamine but not DX, and 2 obtained good pain relief with DX but not ketamine. The sensitivity of the IV ketamine test was 83%, the specificity was 86%, the positive predictive value was 77%, and the negative predictive value was 91%. An association was also found between the development of side effects to the two treatments. PERSPECTIVE: The response to an IV ketamine infusion was found to predict the subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients, with an observed agreement of 83%. Considering the refractory nature of fibromyalgia to conventional pain treatments, the IV ketamine test might enhance patient care by saving time and reducing unnecessary treatment trials.
Administration, Oral↗
A recombinational portrait of the Drosophila pseudoobscura genome.
Drosophila pseudoobscura has been intensively studied by evolutionary biologists for over 70 years. The recent publication of the genome sequence not only permits studies of comparative genomics with other dipterans but also opens the door to identifying genes associated with adaptive traits or speciation or testing for the signature of natural selection across the genome. Information on regional rates of recombination, localization of inversion breakpoints distinguishing it from its sibling species D. persimilis, and known polymorphic markers may be useful in such studies. Here, we present a molecular linkage map of four of the five major chromosome arms of D. pseudoobscura. In doing so, we order and orient several sequence contig groups, localize the inversion breakpoints on chromosome 2 to intervals of 200 kilobases, and identify one error in the published sequence assembly. Our results show that regional recombination rates in D. pseudoobscura are much higher than in D. melanogaster and significantly higher even than in D. persimilis. Furthermore, we detect a non-significant positive correlation between recombination rate and published DNA sequence variation. Finally, the online Appendix presents 200 primer sequence pairs for molecular markers that can be used for mapping of quantitative trait loci, of which 125 are known to be polymorphic within or between species.
Animals↗
What imaging studies are necessary for abdominal aortic endograft sizing? A prospective blinded study using conventional computed tomography, aortography, and three-dimensional computed tomography.
OBJECTIVE: Preoperative imaging modalities for endovascular abdominal aortic aneurysm repair (EVAR) include conventional computed tomography (CT), aortography with a marking catheter, and three-dimensional computed tomography (3D CT). Although each technique has advantages, to date no study has compared in a prospective manner the reproducibility of measurements and impact on graft selection of all three modalities. The objective of this study was to determine the most useful imaging studies in planning EVAR. METHODS: Twenty patients being considered for EVAR were enrolled prospectively to undergo a conventional CT scan and aortography. The CT scans were then reconstructed into 3D images using Preview Treatment Planning Software (Medical Media Systems, West Lebanon, NH). Four measurements of diameter and six of length were made from each modality in determining the proper graft for EVAR. RESULTS: Measurements from all three modalities were reproducible with intraobserver correlation coefficients of 0.79 to 1.0 for aortography, 0.87 to 1.0 for CT, and 0.96 to 1.0 for 3D CT. Measurements between observers were also similar from each modality; interobserver correlations were 0.70 to 0.97 for aortography, 0.76 to 0.97 for CT, and 0.73 to 0.99 for 3D CT. Significant differences ( P < .01) in diameter measurements were noted at D2 with aortography compared with 3D CT, whereas differences in length measurements were found between CT and 3D CT at L4 (nonaneurysmal right iliac) ( P < .01). The correlation between CT and 3D CT for most length measurements was acceptable (0.63 to 1.0). Aortography for diameters correlated poorly (0.35 to 0.67) with 3D CT. When the endograft selected by aortography/CT or 3D CT alone was compared with the actual endograft used, there was agreement in 11 of 11 patients when adjusted for +/- one size in diameter or length. CONCLUSION: Reproducible and comparable measures of diameter and length can be obtained by each of three imaging modalities available for endograft sizing. As a single imaging modality, 3D CT appears to have the best correlation for both diameters and lengths; however, the difference is not sufficient enough to alter endograft selection. Three-dimensional CT may be reserved for challenging aortic anatomy where small differences in measurements would affect patient or graft selection for EVAR.
Aged↗
Probing for thoracic pedicle screw tract violation(s): is it valid?
BACKGROUND: Preparation of the thoracic pedicle screw tract is a critical step prior to the placement of screws. The ability to detect pedicle wall violation(s) by probing prior to insertion of thoracic pedicles screws, however, has not been studied. The purpose of this study was to evaluate the inter- and intraobserver agreement and the accuracy in detecting thoracic pedicle screw tract violation(s) among surgeons at various levels of training. METHODS: With use of a straightforward trajectory, under direct visualization, 108 thoracic pedicle screw tracts (54 cadaveric thoracic vertebrae) were prepared in a standard fashion, followed by tapping with a 4.5-mm cannulated tap. A deliberate pedicle violation was randomly created by an independent investigator in either the anterior, the medial, or the lateral wall in 65 pedicles. Following this, four blinded, independent surgeons at various levels of training probed the specimens on three separate occasions to determine if a breach was present (1,296 discrete data points). Surgeon findings were then recorded as breach present or absent and, if present, breach location. The Cohen kappa correlation coefficient (kappa a) and 95% confidence interval were used to assess the accuracy of the observers and the inter- and intraobserver agreement. RESULTS: The mean accuracy over three iterations, the validity in detecting the breach location, and the intraobserver agreement varied by level of training and experience, with the most experienced observer (observer 1) scoring the best and the least experienced observer (observer 4) scoring the worst. The three most senior surgeons had good intraobserver agreement. Interobserver agreement was low between the four observers. CONCLUSIONS: An observer's ability to accurately detect the presence or absence of a pedicle tract violation and the breach location, if present, is dependent on the surgeon's level of training. Probing the pedicle tract prior to placement of pedicle screws in the thoracic spine is likely a learned skill that improves with repetition and experience.
Bone Screws↗
Conspecific sperm precedence in sister species of Drosophila with overlapping ranges.
Barriers to gene flow that act after mating but before fertilization are often overlooked in studies of reproductive isolation. Where species are sympatric, such "cryptic" isolating barriers may be important in maintaining species as distinct entities. Drosophila yakuba and its sister species D. santomea have overlapping ranges on the island of São Tomé, off the coast of West Africa. Previous studies have shown that the two species are strongly sexually isolated. However, the degree of sexual isolation observed in the laboratory cannot explain the low frequency (approximately 1%) of hybrids observed in nature. This study identifies two "cryptic" isolating barriers that may further reduce gene flow between D. yakuba and D. santomea where they are sympatric. First, noncompetitive gametic isolation has evolved between D. yakuba and D. santomea: heterospecific matings between the two species produce significantly fewer offspring than do conspecific matings. Second, conspecific sperm precedence (CSP) occurs when D. yakuba females mate with conspecific and heterospecific males. However, CSP is asymmetrical: D. santomea females do not show patterns of sperm usage consistent with CSP. Drosophila yakuba and D. santomea females also differ with respect to remating propensity after first mating with conspecific males. These results suggest that noncompetitive and competitive gametic isolating barriers may contribute to reproductive isolation between D. yakuba and D. santomea.
Animals↗
The intravenous ketamine test: a predictive response tool for oral dextromethorphan treatment in neuropathic pain.
IV infusion tests performed to predict subsequent response to oral analgesics are an increasingly popular method used to enhance medical care and conserve resources. Because no infusion test is completely accurate, the potential benefits of these tests must be weighed against the frustration and waste in resources encountered with false-positive results, and the failure to use a potentially beneficial treatment with false-negative results. In recent years, drugs that act antagonistically at N-methyl-d-aspartate receptors have been shown to be valuable adjuncts in the treatment of pain. To determine the predictive value of small-dose (0.1 mg/kg) IV ketamine on an oral dextromethorphan (DX) treatment regimen, we analyzed the analgesic response to these drugs in 25 patients at 2 tertiary care military treatment facilities, institutions at which DX is not readily accessible. When >/=50% response for both drugs was used as the outcome measure for success, the positive predictive value of the ketamine test was 64%, the negative predictive value 73%, and the observed agreement 68%. However, when >/=67% relief with ketamine was used as an outcome measure (as determined by a receiver operating characteristic curve), the positive predictive value was 90%, the negative predictive value 80%, and the observed agreement increased to 84%. Based on these results, we conclude that an IV ketamine test may be useful in predicting response to oral DX. More research is needed to determine the ideal candidates for such a test, and the optimal dose and cutoff value for the response to ketamine.
Administration, Oral↗
The causes of false-positive medial branch (facet joint) blocks in soldiers and retirees.
OBJECTIVE: The purpose of this study was to determine the factors associated with false-positive medial branch blocks (MBB), the nerve blocks used to diagnose facet arthropathy, in soldiers and retirees. METHODS: The study subjects were 78 patients with chronic low back pain who underwent diagnostic MBB to determine whether or not the facet joints were pain generators. Radiofrequency denervation of these nerves was performed in all patients with positive responses. Patients who failed to obtain pain relief after the blocks (negative blocks) and those who obtained temporary pain relief after MBB but failed radiofrequency denervation (false-positive blocks) then proceeded to undergo discography. Based on patients' responses to diagnostic blocks, discography results, the presence of radicular pain, and previous back surgery, the data were analyzed to determine whether any of these variables correlated with false-positive MBB. RESULTS: The presence of discogenic or radicular pain was not associated with a higher false-positive response rate to MBB. Conversely, the absence of discogenic pain was associated with a higher percentage of false-positive blocks. There was also a trend for patients with previous back surgery to have a higher false-positive rate than those who had not undergone previous surgery. CONCLUSIONS: Although a high incidence of epidural and foraminal spread occurs during the performance of MBB, this is unlikely to be a significant cause of false-positive blocks.
Adult↗
Sexual isolation between two sibling species with overlapping ranges: Drosophila santomea and Drosophila yakuba.
Drosophila yakuba is widespread in Africa, whereas D. santomea, its newly discovered sister species, is endemic to the volcanic island of São Tomé in the Gulf of Guinea. Drosophila santomea probably formed after colonization of the island by a D. yakuba-like ancestor. The species presently have overlapping ranges on the mountain Pico do São Tomé, with some hybridization occurring in this region. Sexual isolation between the species is uniformly high regardless of the source of the populations, and, as in many pairs of Drosophila species, is asymmetrical, so that hybridizations occur much more readily in one direction than the other. Despite the fact that these species meet many of the conditions required for the evolution of reinforcement (the elevation of sexual isolation by natural selection to avoid maladaptive interspecific hybridization), there is no evidence that sexual isolation between the species is highest in the zone of overlap. Sexual isolation is due to evolutionary changes in both female preference for heterospecific males and in the vigor with which males court heterospecific females. Heterospecific matings are also slower to take place than are homospecific matings, constituting another possible form of reproductive isolation. Genetic studies show that, when tested with females of either species, male hybrids having a D. santomea X chromosome mate much less frequently with females of either species than do males having a D. yakuba X chromosome, suggesting that the interaction between the D. santomea X chromosome and the D. yakuba genome causes behavioral sterility. Hybrid F1 females mate readily with males of either species, so that sexual isolation in this sex is completely recessive, a phenomenon seen in other Drosophila species. There has also been significant evolutionary change in the duration of copulation between these species; this difference involves genetic changes in both sexes, with at least two genes responsible in males and at least one in females.
Animals↗