Rapid Shifts in Mitochondrial tRNA Import in a Plant Lineage with Extensive Mitochondrial tRNA Gene Loss.

In most eukaryotes, transfer RNAs (tRNAs) are one of the very few classes of genes remaining in the mitochondrial genome, but some mitochondria have lost these vestiges of their prokaryotic ancestry. Sequencing of mitogenomes from the flowering plant genus Silene previously revealed a large range in tRNA gene content, suggesting rapid and ongoing gene loss/replacement. Here, we use this system to test longstanding hypotheses about how mitochondrial tRNA genes are replaced by importing nuclear-encoded tRNAs. We traced the evolutionary history of these gene loss events by sequencing mitochondrial genomes from key outgroups (Agrostemma githago and Silene [=Lychnis] chalcedonica). We then performed the first global sequencing of purified plant mitochondrial tRNA populations to characterize the expression of mitochondrial-encoded tRNAs and the identity of imported nuclear-encoded tRNAs. We also confirmed the utility of high-throughput sequencing methods for the detection of tRNA import by sequencing mitochondrial tRNA populations in a species (Solanum tuberosum) with known tRNA trafficking patterns. Mitochondrial tRNA sequencing in Silene revealed substantial shifts in the abundance of some nuclear-encoded tRNAs in conjunction with their recent history of mt-tRNA gene loss and surprising cases where tRNAs with anticodons still encoded in the mitochondrial genome also appeared to be imported. These data suggest that nuclear-encoded counterparts are likely replacing mitochondrial tRNAs even in systems with recent mitochondrial tRNA gene loss, and the redundant import of a nuclear-encoded tRNA may provide a mechanism for functional replacement between translation systems separated by billions of years of evolutionary divergence.

Predicting Surgical Intervention in Cerebellar Stroke: A Quantitative Retrospective Analysis.

BACKGROUND: Debate still exists regarding whether preventive surgical decompression should be offered to high-risk patients experiencing cerebellar stroke. This study aimed to predict neurologic decline based on risk factors, volumetric analysis, and imaging characteristics. METHODS: This retrospective cohort study comprised patients ≥18 years who presented with acute cerebellar ischemic stroke (CIS) between January 2011 and December 2016. Diagnostic imaging was used to calculate metrics based on individual stroke, cerebellar, and posterior fossa volumes. Head computed tomography scans on presentation and day of peak swelling were used to tabulate a CIS score. RESULTS: The study included 86 patients; most were male and African American. Posterior inferior communicating artery stroke was most common (50%). On initial presentation imaging, 18.6% had documented hydrocephalus, 20.9% had brainstem compression, 22.1% had brainstem stroke, and 39.5% had stroke in another vascular territory. Cardioembolic stroke was the most common etiology, followed by cryptogenic stroke. Overall, patients who underwent surgical intervention had larger stroke volumes on presentation. Patients undergoing surgical intervention also experienced faster cerebellar swelling compared with patients without intervention. Total CIS scores were statistically significant and remained significant on the peak day of swelling. CIS score was independently associated with neurosurgical intervention; patients in this group with delayed interventions (median CIS score, 6; range, 4-8) later deteriorated and required emergent surgical decompression. Eleven patients without intervention had CIS score >6; 4 patients died of stroke complications. CONCLUSIONS: Volumetric studies and CIS score are objective measures that may help predict decline on imaging before clinical deterioration.

Treatment-related calvarial lesions in pediatric brain tumor survivors.

BACKGROUND: Despite improved survival, many pediatric brain tumor survivors receiving radiation therapy (RT) experience late effects. PROCEDURE: To study calvarial lesions in this population, we retrospectively reviewed records of patients undergoing neurosurgical evaluation for calvarial bone lesions detected in posttreatment follow-up imaging at St. Jude Children's Research Hospital. Primary tumor diagnosis, treatment, imaging, surgical intervention, and histopathology from patients with radiographic evidence of lesions followed for ≥2 years post-RT were studied. RESULTS: For 17 patients with 18 index lesions, median time to lesion manifestation was 2.34 years. Medulloblastoma patients developed lesions at a shorter interval from RT than ependymoma patients (P = .05). Twelve of 14 lesions requiring surgery were benign fibro-osseous or sclerotic. Two malignant lesions distinct from the primary tumor had genetic predisposition to malignancy. CONCLUSION: Most calvarial lesions arising post-RT are benign and fibro-osseous. Serial imaging is recommended, and high index of suspicion for malignant lesions is warranted for patients genetically predisposed to cancer.

Application of the Preventable Shunt Revision Rate to an Adult Population.

BACKGROUND: The preventable shunt revision rate (PSRR) was recently introduced in pediatric hydrocephalus as a quality metric for shunt surgery. We evaluated the PSRR in an adult hydrocephalus population. METHODS: All ventricular shunt operations (January 1, 2013 to March 31, 2018) performed at a university-based teaching hospital were included. For any index surgery (de novo or revision) resulting in reoperation within 90 days, the index surgery details were collected, and a consensus decision was reached regarding whether the failure had been potentially avoidable. Preventable failure was defined as failure due to infection, malposition, disconnection, migration, or kinking. The 90-day shunt failure rate and PSRR were calculated. Bivariate analyses were performed to evaluate the individual effects of each independent variable on preventable shunt failure. RESULTS: A total of 318 shunt operations had been performed in 245 patients. Most patients were women (62%), with a median age of 48.2 years (interquartile range, 31.2-63.2 years). Most had had ventriculoperitoneal shunts placed (86.5%), and just more than one half were new shunts (51.6%). A total of 53 cases (16.7%) in 42 patients experienced shunt failure within 90 days of the index operation. Of these, 27 failures (8.5% of the total cases; 51% of the failures) were considered potentially preventable. The most common reasons were infection (37%; n = 10) and malposition of the proximal and distal catheters (both 25.9%; n = 7). Age was the only statistically significant difference between the 2 groups, with the patients experiencing preventable shunt failure older than those without preventable shunt failure (51.4 vs. 37.1 years; P = 0.017). CONCLUSIONS: The 90-day PSRR can be applied to an adult population and serve as a quality metric.

Ecological contributions to body shape evolution in salamanders of the genus Eurycea (Plethodontidae).

BACKGROUND: Body shape can be both a consequence and cause of a species' evolution and ecology. There are many examples of phenotypes associated with specific ecological niches, likely as a result of specific selective regimes. A classic example of this is the phenotypic change associated with colonization of caves, including body and limb elongation. However, studies explicitly testing for differences in body shape between cave-dwelling and non-cave-dwelling lineages have been limited and so the role of the cave environment in determining morphological characteristics is still not completely understood. Here we examine variation in body shape among 405 individuals representing 20 species in the salamander genus Eurycea (Plethodontidae) and select outgroups exhibiting great diversity in morphology, ecological niche, and life history. RESULTS: After analyzing morphometric data in a phylogenetic context using phylogenetic MANOVA and examination of the phylomorphospace, we found significant differences in body shape among cave-dwelling and non-cave-dwelling species and between aquatic and terrestrial species. Notably, limb elongation and reduced body and tail size characterized cave-dwelling species. Terrestrial species also exhibited elongation of the limbs and digits. We also observed differences in shape variance among paedomorphic and biphasic species. Our results suggest that the functional limitations imposed by habitat and life history played a key role in the evolution of body shape in this group in the context of their phylogenetic history.

Effect of the anther-smut fungus Microbotryum on the juvenile growth of its host Silene latifolia.

PREMISE OF THE STUDY: Plant pathogens that form persistent systemic infections within plants have the potential to affect multiple plant life history traits, yet we tend to focus only on visible symptoms. Anther smut of Silene latifolia caused by the fungus Microbotryum lychnidis-dioicae induces the anthers of its host to support fungal spore production instead of pollen, and the pathogen is primarily transmitted among flowering plants by pollinators. Nevertheless, most of its life cycle is spent in the asymptomatic vegetative phase, and spores falling on seedlings or nonflowering plants can also infect the host. The purpose of this study was to ask whether the fungus also had an effect on its host plant in the juvenile vegetative phase before flowering as this is important for the disease dynamics in species where infection of seedlings is commonplace. METHODS: Leaf length and leaf number of inoculated and uninoculated juvenile plants were compared in greenhouse experiments, and in one experiment, disease status of the plants at flowering was determined. KEY RESULTS: Inoculated plants had shorter but more leaves, and reduced root mass at the early juvenile (preflowering) stage. Some of these effects were detectable in plants that were inoculated but showed no disease symptoms at flowering. CONCLUSIONS: These results show that pathogenic fungi can have endophyte-like effects even in the total absence of their typical and more charismatic symptoms, and conversely that the assessment of endophyte effects on the fitness of their hosts should include all stages of the host life cycle.

Taking the next step in publication productivity analysis in pediatric neurosurgery.

OBJECTIVE There has been an increasing interest in the quantitative analysis of publishing within the field of neurosurgery at the individual, group, and institutional levels. The authors present an updated analysis of accredited pediatric neurosurgery training programs. METHODS All 28 Accreditation Council for Pediatric Neurosurgery Fellowship programs were contacted for the names of pediatric neurosurgeons who were present each year from 2011 through 2015. Faculty names were queried in Scopus for publications and citations during this time period. The 5-year institutional Hirsch index [i h(5)-index] and revised 5-year institutional h-index [i r(5)-index] were calculated to rank programs. Each publication was reviewed to determine authorship value, tier of research, clinical versus basic science research, subject matter, and whether it was pediatrics-specific. A unique 3-tier article classification system was introduced to stratify clinical articles by quality and complexity, with tier 3 being the lowest tier of publication (e.g., case reports) and tier 1 being the highest (e.g., randomized controlled trials). RESULTS Among 2060 unique publications, 1378 (67%) were pediatrics-specific. The pediatrics-specific articles had a mean of 15.2 citations per publication (median 6), whereas the non-pediatrics-specific articles had a mean of 23.0 citations per publication (median 8; p < 0.0001). For the 46% of papers that had a pediatric neurosurgeon as first or last author, the mean number of citations per publication was 12.1 (median 5.0) compared with 22.5 (median 8.0) for those in which a pediatric neurosurgeon was a middle author (p < 0.0001). Seventy-nine percent of articles were clinical research and 21% were basic science or translational research; however, basic science and translational articles had a mean of 36.9 citations per publication (median 15) compared with 12.6 for clinical publications (median 5.0; p < 0.0001). Among clinical articles, tier 1 papers had a mean of 15.0 citations per publication (median 8.0), tier 2 papers had a mean of 18.7 (median 8.0), and tier 3 papers had a mean of 7.8 (median 3.0). Neuro-oncology papers received the highest number of citations per publication (mean 25.7). The most common journal was the Journal of Neurosurgery: Pediatrics (20%). MD/PhD faculty members had significantly more citations per publication than MD faculty members (mean 26.7 vs 14.0; p < 0.0001) and also a higher number of publications per author (mean 38.6 vs 20.8). The median i h(5)- and i r(5)-indices per program were 14 (range 5-48) and 10 (range 5.6-37.2), respectively. The mean i r(5)/i h(5)-index ratio was 0.8. The top 5 fellowship programs (in descending order) as ranked by the i h(5)-index corrected for number of faculty members were The Hospital for Sick Children, Toronto; Children's Hospital of Pittsburgh; University of California, San Francisco Benioff Children's Hospital; Seattle Children's Hospital; and St. Louis Children's Hospital. CONCLUSIONS About two-thirds of publications authored by pediatric neurosurgeons are pediatrics-specific, although non-pediatrics-specific articles averaged more citations. Most of the articles authored by pediatric neurosurgeons are clinical, with basic and translational articles averaging more citations. Neurosurgeons with PhD degrees averaged more total publications and more citations per publication. In all, this is the most advanced and informative analysis of publication productivity in pediatric neurosurgery to date.

A Review of Industry Funding in Randomized Controlled Trials Published in the Neurosurgical Literature-The Elephant in the Room.

OBJECTIVE: To analyze the role of industry sponsorship of randomized controlled trials (RCTs) published exclusively in 3 major North American neurosurgical journals. METHODS: Our primary objective was to determine whether an association exists between study conclusion(s) in favor of industry sponsored drugs, devices/implants, or surgical techniques and industry sponsorship. The secondary objective was to describe the quality/quantity of these neurosurgical RCTs. RESULTS: A total of 110 RCTs were analyzed, the majority were published in the Journal of Neurosurgery (85%) and were international in origin (55%). The most common subspecialty was spine (n = 29) and drug study was the most common type (n = 49). Overall quality was good with median Jadad and Detsky scores of 4 (range, 1-5) and 18 (range, 8-21), respectively. There was a statistically significant difference in RCTs with industry funding (31/40, 78%) versus those without (9/70, 13%) that published a favorable conclusion of the new drug, device/implant, or surgical technique (odds ratio [OR], 23.35; P < .0001). Multiple binomial logistic regression analysis identified "number of authors" as mildly protective (OR, 0.79; 95% confidence interval, 0.69-0.91; P = .001) and "industry funding" strongly predictive (OR, 12.34; 95% confidence interval, 2.97-51.29; P = .001) of a positive trial. CONCLUSION: Industry funding was associated with a much greater chance of positive findings in RCTs published in neurosurgical journals. Further efforts are needed to define the relationship between the authors and financial sponsors of neurosurgical research and explore the reasons for this finding.

Positive Selection in Rapidly Evolving Plastid-Nuclear Enzyme Complexes.

Rates of sequence evolution in plastid genomes are generally low, but numerous angiosperm lineages exhibit accelerated evolutionary rates in similar subsets of plastid genes. These genes include clpP1 and accD, which encode components of the caseinolytic protease (CLP) and acetyl-coA carboxylase (ACCase) complexes, respectively. Whether these extreme and repeated accelerations in rates of plastid genome evolution result from adaptive change in proteins (i.e., positive selection) or simply a loss of functional constraint (i.e., relaxed purifying selection) is a source of ongoing controversy. To address this, we have taken advantage of the multiple independent accelerations that have occurred within the genus Silene (Caryophyllaceae) by examining phylogenetic and population genetic variation in the nuclear genes that encode subunits of the CLP and ACCase complexes. We found that, in species with accelerated plastid genome evolution, the nuclear-encoded subunits in the CLP and ACCase complexes are also evolving rapidly, especially those involved in direct physical interactions with plastid-encoded proteins. A massive excess of nonsynonymous substitutions between species relative to levels of intraspecific polymorphism indicated a history of strong positive selection (particularly in CLP genes). Interestingly, however, some species are likely undergoing loss of the native (heteromeric) plastid ACCase and putative functional replacement by a duplicated cytosolic (homomeric) ACCase. Overall, the patterns of molecular evolution in these plastid-nuclear complexes are unusual for anciently conserved enzymes. They instead resemble cases of antagonistic coevolution between pathogens and host immune genes. We discuss a possible role of plastid-nuclear conflict as a novel cause of accelerated evolution.

Cyto-nuclear discordance suggests complex evolutionary history in the cave-dwelling salamander, Eurycea lucifuga.

Our understanding of the evolutionary history and ecology of cave-associated species has been driven historically by studies of morphologically adapted cave-restricted species. Our understanding of the evolutionary history and ecology of nonrestricted cave species, troglophiles, is limited to a few studies, which present differing accounts of troglophiles' relationship with the cave habitat, and its impact on population dynamics. Here, we used phylogenetics, demographic statistics, and population genetic methods to study lineage divergence, dates of divergence, and population structure in the Cave Salamander, Eurycea lucifuga, across its range. In order to perform these analyses, we sampled 233 individuals from 49 populations, using sequence data from three gene loci as well as genotyping data from 19 newly designed microsatellite markers. We find, as in many other species studied in a phylogeographic context, discordance between patterns inferred from mitochondrial relationships and those inferred by nuclear markers indicating a complicated evolutionary history in this species. Our results suggest Pleistocene-based divergence among three main lineages within E. lucifuga corresponding to the western, central, and eastern regions of the range, similar to patterns seen in species separated in multiple refugia during climatic shifts. The conflict between mitochondrial and nuclear patterns is consistent with what we would expect from secondary contact between regional populations following expansion from multiple refugia.

Investigating past range dynamics for a weed of cultivation, Silene vulgaris.

Since the last glacial maximum (LGM), many plant and animal taxa have expanded their ranges by migration from glacial refugia. Weeds of cultivation may have followed this trend or spread globally following the expansion of agriculture or ruderal habitats associated with human-mediated disturbance. We tested whether the range expansion of the weed Silene vulgaris across Europe fit the classical model of postglacial expansion from southern refugia, or followed known routes of the expansion of human agricultural practices. We used species distribution modeling to predict spatial patterns of postglacial expansion and contrasted these with the patterns of human agricultural expansion. A population genetic analysis using microsatellite loci was then used to test which scenario was better supported by spatial patterns of genetic diversity and structure. Genetic diversity was highest in southern Europe and declined with increasing latitude. Locations of ancestral demes from genetic cluster analysis were consistent with areas of predicted refugia. Species distribution models showed the most suitable habitat in the LGM on the southern coasts of Europe. These results support the typical postglacial northward colonization from southern refugia while refuting the east-to-west agricultural spread as the main mode of expansion for S. vulgaris. We know that S. vulgaris has recently colonized many regions (including North America and other continents) through human-mediated dispersal, but there is no evidence for a direct link between the Neolithic expansion of agriculture and current patterns of genetic diversity of S. vulgaris in Europe. Therefore, the history of range expansion of S. vulgaris likely began with postglacial expansion after the LGM, followed by more recent global dispersal by humans.

Elevational divergence and clinal variation in floral color and leaf chemistry in Silene vulgaris.

PREMISE OF STUDY: Environmental heterogeneity over a species range can lead to divergent selection among populations, leading to phenotypic differences. The plant flavonoid pathway controls key reproductive and defense-related traits and responds to selection and environmental stressors, allowing for hypotheses about phenotypic divergence across environmental gradients. We hypothesized that with increasing elevation, more flavonoids would be produced as a response to increased UV radiation and that plants would be better defended against herbivores. METHODS: We measured floral color, flavonoids, and herbivory in natural populations of Silene vulgaris (Caryophyllaceae) along elevational transects in the French Alps. We correlated phenotypes with environmental variables and calculated genotypic divergence (FST) to compare with phenotypic divergence (PST). KEY RESULTS: We found significant phenotypic variation in S. vulgaris along elevational gradients. Strong positive correlations were observed between floral color, leaf non-anthocyanidin flavonoid concentration, and elevation. Floral anthocyanin and leaf non-anthocyanidin flavonoid phenotypes negatively covaried with temperature and precipitation seasonality. Comparisons of PST to FST provided evidence for stabilizing selection on floral color among transects and divergent selection along the elevational gradient. CONCLUSIONS: Flavonoid production increases along elevational gradients in S. vulgaris, with clinal variation in calyx anthocyanins and increasing leaf non-anthocyanin flavonoid concentrations. Despite the photoprotective and antiherbivore properties of some flavonoids, flavonoid production in flowers and leaves was correlated with population microclimatic variables: temperature and precipitation. Taken together, the results suggest that different flavonoid groups are targeted by selection in different tissues and provide evidence for divergent patterns of selection for flavonoids between high and low elevations.

Five-Year Institutional Bibliometric Profiles for 119 North American Neurosurgical Residency Programs: An Update.

BACKGROUND: We recently performed a comprehensive bibliometric analysis of 103 U.S. neurosurgical departments and found the ih(5)-index as meaningful and reproducible using public data. The present report expands this analysis by adding 14 Canadian and 2 additional U.S. programs. METHODS: Departments were included if listed in the American Association of Neurological Surgeons Residency Directory. Each institution was considered a single entity, and original research articles with authors who were neurosurgeon faculty were counted only once per institution, although a single article may have been credited toward multiple institutions, if applicable. The following bibliometric indices were calculated and used to rank departments: ih(5), ig(5), ie(5), and i10(5). In addition, intradepartmental comparison of productivity among faculty members was analyzed by computing Gini coefficients for publications and citations. RESULTS: The top 5 most academically productive North American neurosurgical programs based on ih(5)-index were found to be the University of Toronto, University of California at San Francisco, University of California at Los Angeles, University of Pittsburgh, and Brigham and Women's Hospital. The top 5 Canadian programs were the University of Toronto, University of Calgary, McGill University, University of Sherbrooke, and University of British Columbia. The median ih(5)-index for U.S. and Canadian programs was 12 and 10.5, respectively. CONCLUSIONS: This is the most accurate comprehensive analysis to date of contemporary bibliometrics among North American neurosurgery departments. Using the ih(5)-index for institutional ranking allows for informative comparison of recent scholarly efforts.

Scale dependence of sex ratio in wild plant populations: implications for social selection.

Social context refers to the composition of an individual's social interactants, including potential mates. In spatially structured populations, social context can vary among individuals within populations, generating the opportunity for social selection to drive differences in fitness functions among individuals at a fine spatial scale. In sexually polymorphic plants, the local sex ratio varies at a fine scale and thus has the potential to generate this opportunity. We measured the spatial distribution of two wild populations of the gynodioecious plant Silene vulgaris and show that there is fine-scale heterogeneity in the local distribution of the sexes within these populations. We demonstrate that the largest variance in sex ratio is among nearest neighbors. This variance is greatly reduced as the spatial scale of social interactions increases. These patterns suggest the sex of neighbors has the potential to generate fine-scale differences in selection differentials among individuals. One of the most important determinants of social interactions in plants is the behavior of pollinators. These results suggest that the potential for selection arising from sex ratio will be greatest when pollen is shared among nearest neighbors. Future studies incorporating the movement of pollinators may reveal whether and how this fine-scale variance in sex ratio affects the fitness of individuals in these populations.

Five-year institutional bibliometric profiles for 103 US neurosurgical residency programs.

OBJECT: Various bibliometric indices based on the citations accumulated by scholarly articles, including the h-index, g-index, e-index, and Google's i10-index, may be used to evaluate academic productivity in neurological surgery. The present article provides a comprehensive assessment of recent academic publishing output from 103 US neurosurgical residency programs and investigates intradepartmental publishing equality among faculty members. METHODS: Each institution was considered a single entity, with the 5-year academic yield of every neurosurgical faculty member compiled to compute the following indices: ih(5), cumulative h, ig(5), ie(5), and i10(5) (based on publications and citations from 2009 through 2013). Intradepartmental comparison of productivity among faculty members yielded Gini coefficients for publications and citations. National and regional comparisons, institutional rankings, and intradepartmental publishing equality measures are presented. RESULTS: The median numbers of departmental faculty, total publications and citations, ih(5), summed h, ig(5), ie(5), i10(5), and Gini coefficients for publications and citations were 13, 82, 716, 12, 144, 23, 16, 17, 0.57, and 0.71, respectively. The top 5 most academically productive neurosurgical programs based on ih(5)-index were University of California, San Francisco, University of California, Los Angeles, University of Pittsburgh, Brigham & Women's Hospital, and Johns Hopkins University. The Western US region was most academically productive and displayed greater intradepartmental publishing equality (median ih[5]-index = 18, median Ginipub = 0.56). In all regions, large departments with relative intradepartmental publishing equality tend to be the most academically productive. Multivariable logistic regression analysis identified the ih(5)-index as the only independent predictor of intradepartmental publishing equality (Ginipub ≤ 0.5 [OR 1.20, 95% CI 1.20-1.40, p = 0.03]). CONCLUSIONS: The ih(5)-index is a novel, simple, and intuitive metric capable of accurately comparing the recent scholarly efforts of neurosurgical programs and accurately predicting intradepartmental publication equality. The ih(5)-index is relatively insensitive to factors such as isolated highly productive and/or no longer academically active senior faculty, which tend to distort other bibliometric indices and mask the accurate identification of currently productive academic environments. Institutional ranking by ih(5)-index may provide information of use to faculty and trainee applicants, research funding institutions, program leaders, and other stakeholders.

The massive mitochondrial genome of the angiosperm Silene noctiflora is evolving by gain or loss of entire chromosomes.

Across eukaryotes, mitochondria exhibit staggering diversity in genomic architecture, including the repeated evolution of multichromosomal structures. Unlike in the nucleus, where mitosis and meiosis ensure faithful transmission of chromosomes, the mechanisms of inheritance in fragmented mitochondrial genomes remain mysterious. Multichromosomal mitochondrial genomes have recently been found in multiple species of flowering plants, including Silene noctiflora, which harbors an unusually large and complex mitochondrial genome with more than 50 circular-mapping chromosomes totaling ∼7 Mb in size. To determine the extent to which such genomes are stably maintained, we analyzed intraspecific variation in the mitochondrial genome of S. noctiflora. Complete genomes from two populations revealed a high degree of similarity in the sequence, structure, and relative abundance of mitochondrial chromosomes. For example, there are no inversions between the genomes, and there are only nine SNPs in 25 kb of protein-coding sequence. Remarkably, however, these genomes differ in the presence or absence of 19 entire chromosomes, all of which lack any identifiable genes or contain only duplicate gene copies. Thus, these mitochondrial genomes retain a full gene complement but carry a highly variable set of chromosomes that are filled with presumably dispensable sequence. In S. noctiflora, conventional mechanisms of mitochondrial sequence divergence are being outstripped by an apparently nonadaptive process of whole-chromosome gain/loss, highlighting the inherent challenge in maintaining a fragmented genome. We discuss the implications of these findings in relation to the question of why mitochondria, more so than plastids and bacterial endosymbionts, are prone to the repeated evolution of multichromosomal genomes.

Tumor pseudoprogression of spinal metastasis after radiosurgery: a novel concept and case reports.

Radiosurgery for primary and metastatic tumors of the central nervous system is increasing in utility and intensity. Known complications in the brain include radiation necrosis and the well-documented phenomenon of pseudoprogression. Known complications of radiosurgery to spinal column tumors include radiation myelopathy and delayed vertebral compression fractures; however, the concept of pseudoprogression of spinal column tumors has not been previously described. The authors review 2 cases of spinal metastasis treated with stereotactic radiosurgery (SRS) and attempt to define the concept of spine tumor pseudoprogression. Two patients who had undergone SRS to the spine for metastatic disease presented in early follow-up (3 and 7 weeks) with symptomatic complaints consisting of axial pain, radicular pain, or evidence of cord compression. In both patients, MRI revealed evidence of tumor enlargement. In one patient, the lesion had grown by 9 mm and 7.7 mm in the axial and sagittal planes, respectively. In the other patient, the tumor growth resulted in a 5-mm decrease in spinal canal diameter with epidural compression and right foraminal encroachment. Because of the absence of progressive neurological deficit, myelopathy, mechanical symptomatology of instability, or vertebral compression fracture, the first patient was treated expectantly with a corticosteroid taper and had improvement of symptoms at 1 month and near-total radiographic resolution of the tumor. In the second patient, worsening symptoms suggested a need for surgical intervention to address presumed radiosurgical failure and tumor progression. During surgery, only necrotic tumor cells were observed, without viable tumor. Follow-up imaging over 1 year showed ongoing local control. To their knowledge, the authors report the first description of pseudoprogression involving spinal column metastasis in the literature and aim to alert the treating physician to this clinical situation. Unlike brain tumor pseudoprogression, spine tumor pseudoprogression is a relatively early posttreatment phenomenon, measured in days to 2 months. The authors believe that the acute inflammatory response associated with tumor necrosis and disruption of the tumor capillary integrity caused by radiotherapy is an important component in the development of pseudoprogression. Future studies will be fundamental in assigning clinical significance, defining the incidence and predictors, and affecting future management of this phenomenon.

Intensive blood pressure control during the hyperacute phase of intracerebral hemorrhage in patients at risk for resistant hypertension: a retrospective cohort study.

INTRODUCTION: There are limited data evaluating intensive systolic blood pressure (SBP) control during the hyperacute phase of intracerebral hemorrhage (ICH) in patients with multiple risk factors for resistant hypertension. We evaluated the feasibility and safety of this intervention in a primary population that includes patients with multiple risk factors for resistant hypertension. MATERIALS AND METHODS: We conducted a retrospective analysis of ICH patients for which intensive SBP control (<140 mm Hg)- i.e. less than or equal to 140 was targeted. All patients possessed at least 2 risk factors that have been associated with resistant hypertension. Our primary objective was to determine the percentage of patients who achieved goal SBP within 1 hour of ICH diagnosis. Secondary objectives included identifying predictors of achieving goal SBP within 6 hours. RESULTS: Goal SBP within 1 hour was achieved in 8.1% of patients. The total number of risk factors a patient possessed was found to negatively predict ability to achieve goal SBP. For each risk factor possessed, the odds of achieving goal SBP within 6 hours are reduced by 31% (odds ratio, 0.69 [95% confidence interval, 0.54-0.89]). CONCLUSION: Intensive SBP control after ICH was difficult to achieve within 1 hour in those with risk factors for resistant hypertension. Patients' total risk factors were found to reduce the odds of achieving goal SBP within 6 hours.