The Tiger Rattlesnake genome reveals a complex genotype underlying a simple venom phenotype.

Variation in gene regulation is ubiquitous, yet identifying the mechanisms producing such variation, especially for complex traits, is challenging. Snake venoms provide a model system for studying the phenotypic impacts of regulatory variation in complex traits because of their genetic tractability. Here, we sequence the genome of the Tiger Rattlesnake, which possesses the simplest and most toxic venom of any rattlesnake species, to determine whether the simple venom phenotype is the result of a simple genotype through gene loss or a complex genotype mediated through regulatory mechanisms. We generate the most contiguous snake-genome assembly to date and use this genome to show that gene loss, chromatin accessibility, and methylation levels all contribute to the production of the simplest, most toxic rattlesnake venom. We provide the most complete characterization of the venom gene-regulatory network to date and identify key mechanisms mediating phenotypic variation across a polygenic regulatory network.

Phylogenetically diverse diets favor more complex venoms in North American pitvipers.

The role of natural selection in the evolution of trait complexity can be characterized by testing hypothesized links between complex forms and their functions across species. Predatory venoms are composed of multiple proteins that collectively function to incapacitate prey. Venom complexity fluctuates over evolutionary timescales, with apparent increases and decreases in complexity, and yet the causes of this variation are unclear. We tested alternative hypotheses linking venom complexity and ecological sources of selection from diet in the largest clade of front-fanged venomous snakes in North America: the rattlesnakes, copperheads, cantils, and cottonmouths. We generated independent transcriptomic and proteomic measures of venom complexity and collated several natural history studies to quantify dietary variation. We then constructed genome-scale phylogenies for these snakes for comparative analyses. Strikingly, prey phylogenetic diversity was more strongly correlated to venom complexity than was overall prey species diversity, specifically implicating prey species' divergence, rather than the number of lineages alone, in the evolution of complexity. Prey phylogenetic diversity further predicted transcriptomic complexity of three of the four largest gene families in viper venom, showing that complexity evolution is a concerted response among many independent gene families. We suggest that the phylogenetic diversity of prey measures functionally relevant divergence in the targets of venom, a claim supported by sequence diversity in the coagulation cascade targets of venom. Our results support the general concept that the diversity of species in an ecological community is more important than their overall number in determining evolutionary patterns in predator trait complexity.

Sequence Divergence in Venom Genes Within and Between Montane Pitviper (Viperidae: Crotalinae: Cerrophidion) Species is Driven by Mutation-Drift Equilibrium.

Snake venom can vary both among and within species. While some groups of New World pitvipers-such as rattlesnakes-have been well studied, very little is known about the venom of montane pitvipers (Cerrophidion) found across the Mesoamerican highlands. Compared to most well-studied rattlesnakes, which are widely distributed, the isolated montane populations of Cerrophidion may facilitate unique evolutionary trajectories and venom differentiation. Here, we describe the venom gland transcriptomes for populations of C. petlalcalensis, C. tzotzilorum, and C. godmani from Mexico, and a single individual of C. sasai from Costa Rica. We explore gene expression variation in Cerrophidion and sequence evolution of toxins within C. godmani specifically. Cerrophidion venom gland transcriptomes are composed primarily of snake venom metalloproteinases, phospholipase A[Formula: see text]s (PLA[Formula: see text]s), and snake venom serine proteases. Cerrophidion petlalcalensis shows little intraspecific variation; however, C. godmani and C. tzotzilorum differ significantly between geographically isolated populations. Interestingly, intraspecific variation was mostly attributed to expression variation as we did not detect signals of selection within C. godmani toxins. Additionally, we found PLA[Formula: see text]-like myotoxins in all species except C. petlalcalensis, and crotoxin-like PLA[Formula: see text]s in the southern population of C. godmani. Our results demonstrate significant intraspecific venom variation within C. godmani and C. tzotzilorum. The toxins of C. godmani show little evidence of directional selection where variation in toxin sequence is consistent with evolution under a model of mutation-drift equilibrium. Cerrophidion godmani individuals from the southern population may exhibit neurotoxic venom activity given the presence of crotoxin-like PLA[Formula: see text]s; however, further research is required to confirm this hypothesis.

RESUMEN: El veneno de las serpientes puede variar entre y dentro de las especies. Mientras algunos grupos de viperidos del Nuevo Mundo­como las cascabeles­han sido bien estudiadas, muy poco se sabe acerca del veneno de las nauyacas de frío (Cerrophidion) que se encuentran en las zonas altas de Mesoamérica. Comparadas con las extensamente estudiadas cascabeles, que estan ampliamente distribuidas, las poblaciones de Cerrophidion, aisladas en montañas, pueden poseer trayectorias evolutivas y diferenciación en su veneno unicos. En el presente trabajo, describimos el transcriptoma de las glándulas de veneno de poblaciones de C. petlalcalensis, C. tzotzilorum, y C. godmani de México, y un individuo de C. sasai de Costa Rica. Exploramos la variación en la expresión de toxinas en Cerrophidion y la evolución en las secuencias geneticas en C. godmani específicamente. El transcriptoma de la glándula de veneno de Cerrophidion esta compuesto principalmente de Metaloproteinasas de Veneno de Serpiente, Fosfolipasas A[Formula: see text] (PLA[Formula: see text]s), y Serin Proteasas de Veneno de Serpiente. Cerrophidion petlalcalensis presenta poca variación intraespecífica; sin embargo, los transcriptomas de la glandula de veneno de C. godmani y C. tzotzilorum difieren significativamente entre poblaciones geográficamente aisladas. Curiosamente, la variación intraespecífica estuvo atribuida principalmente a la expresión de las toxinas ya que no encontramos señales de selección en las toxinas de C. godmani. Adicionalmente, encontramos miotoxinas similares a PLA[Formula: see text] en todas las especies excepto C. petlalcalensis, y PLA[Formula: see text]s similares a crotoxina en la población sureña de C. godmani. Nuestros resultados demuestran la presencia de variacion intraespecífica presente en el veneno de C. godmani y C. tzotzilorum. Las toxinas de Cerrophidion godmani muestran poca evidencia de selección direccional, y la variación en la secuencias de las toxinas es consistente con evolucion bajo un modelo de equilibrio de mutación-deriva. Algunos individuos de C. godmani de la población del sur potencialmente tienen un veneno neurotóxico dada la presencia de PLA[Formula: see text]s similares a la crotoxina, sin embargo, se necesita más evidencia para corroborar esta hipótesis.

Intraspecific sequence and gene expression variation contribute little to venom diversity in sidewinder rattlesnakes ( Crotalus cerastes).

Traits can evolve rapidly through changes in gene expression or protein-coding sequences. However, these forms of genetic variation can be correlated and changes to one can influence the other. As a result, we might expect traits lacking differential expression to preferentially evolve through changes in protein sequences or morphological adaptation. Given the lack of differential expression across the distribution of sidewinder rattlesnakes ( Crotalus cerastes), we tested this hypothesis by comparing the coding regions of genes expressed in the venom gland transcriptomes and fang morphology. We calculated Tajima's D and FST across four populations comparing toxin and nontoxin loci. Overall, we found little evidence of directional selection or differentiation between populations, suggesting that changes to protein sequences do not underlie the evolution of sidewinder venom or that toxins are under extremely variant selection pressures. Although low-expression toxins do not have higher sequence divergence between populations, they do have more standing variation on which selection can act. Additionally, we found significant differences in fang length among populations. The lack of differential expression and sequence divergence suggests sidewinders-given their generalist diet, moderate gene flow and environmental variation-are under stabilizing selection which functions to maintain a generalist phenotype. Overall, we demonstrate the importance of examining the relationship between gene expression and protein-coding changes to understand the evolution of complex traits.

Epidural venous thrombosis as differential diagnosis in back pain patients.

Epidural venous thrombosis is a rare clinical entity with a characteristic constellation of findings in contrast-enhanced MRI, which should be considered in the differential diagnosis in the case of clinical symptoms that are initially indicative of disc herniation. The most important distinctive feature between epidural venous thrombosis and disc herniation is their topographical location in relation to the vertebral venous plexus. Particularly where morphological imaging shows a space-occupying lesion in close proximity to the internal vertebral venous plexus and a central contrast medium defect, epidural venous thrombosis should be taken into consideration.

Origins and biogeography of the Anolis crassulus subgroup (Squamata: Dactyloidae) in the highlands of Nuclear Central America.

BACKGROUND: Recent studies have begun to reveal the complex evolutionary and biogeographic histories of mainland anoles in Central America, but the origins and relationships of many taxa remain poorly understood. One such group is the Anolis (Norops) crassulus species subgroup, which contains ten morphologically similar highland taxa, the majority of which have restricted distributions. The nominal taxon A. crassulus has a disjunct distribution from Chiapas, Mexico, through Guatemala, in the highlands of El Salvador, and in the Chortís Highlands of Honduras. We test the relationships of these species using multiple mitochondrial and nuclear loci in concatenated and multispecies coalescent frameworks, in an effort to both resolve long-standing taxonomic confusion and present new insights into the evolution and biogeography of these taxa. RESULTS: Sequences of multiple mitochondrial and nuclear loci were generated for eight of the ten species of the Anolis crassulus species subgroup. We analyzed phylogenetic relationships and estimated divergence times and ancestral ranges of the subgroup, recovering a monophyletic subgroup within Anolis. Within the nominal taxon Anolis crassulus, we recovered multiple genetically distinct lineages corresponding to allopatric populations, and show that the Chortís Highland lineage split from the others over 13 MYA. Additionally, distinct mitochondrial lineages are present within the taxa A. heteropholidotus and A. morazani, and importantly, samples of A. crassulus and A. sminthus previously used in major anole phylogenetic analyses are not recovered as conspecific with those taxa. We infer a Chortís Highland origin for the ancestor of this subgroup, and estimate cladogenesis of this subgroup began approximately 22 MYA. CONCLUSIONS: Our results provide new insights into the evolution, biogeography, and timing of diversification of the Anolis crassulus species subgroup. The disjunctly distributed Anolis crassulus sensu lato represents several morphologically conserved, molecularly distinct anoles, and several other species in the subgroup contain multiple isolated lineages.

Collateral vessels in proximal middle cerebral artery occlusion: the ENDOSTROKE study.

PURPOSE: To determine the impact of collateral vessel status on clinical and imaging outcomes in patients undergoing endovascular therapy (EVT) for proximal middle cerebral artery (MCA) occlusion. MATERIALS AND METHODS: There were 160 patients with proximal MCA occlusion at six centers in this institutional review board-approved multicenter EVT registry. Angiograms were analyzed at a blinded core laboratory, and collateral vessel status was assessed by using the American Society of Interventional and Therapeutic Neuroradiology (ASITN)/Society of Interventional Radiology (SIR) collateral vessel grading system, while reperfusion was assessed by using the Thrombolysis in Cerebral Infarction (TICI) scale. Good outcome was defined as a modified Rankin Scale score of 0-2 at follow-up. Binary logistic regression analysis was performed by using parameters with P < .2 in univariate analysis. RESULTS: Good clinical outcome was attained in 62 (39%) of the 160 patients, and TICI 2b-3 reperfusion was achieved in 94 (59%) patients. Nineteen patients had ASITN/SIR collateral vessel grades of 0 or 1, 63 patients had a grade of 2, and 78 patients had grades of 3 or 4. Better collateral vessels were associated with higher reperfusion rates (21%, 48%, and 77% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P < .001), a higher proportion of infarcts smaller than one-third of the MCA territory (32%, 48%, and 69% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P < .001), and a higher proportion of good clinical outcome (11%, 35%, and 49% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P = .007). At multivariable analysis, collateral vessel status independently predicted reperfusion, final infarct size, and clinical outcome. Within an onset-to-treatment time (OTT) of 0-3 hours, collateral vessel status predicted final infarct size and reperfusion. Within an OTT of 3-6 hours, it additionally predicted clinical outcome, with 53% of patients with ASITN/SIR grades of 3 or 4 having a good outcome, as compared with 0% of patients with grades of 0 or 1 and 27% of patients with a grade of 2 (P = .008). CONCLUSION: In this patient population, collateral vessel status independently predicted the pivotal outcome parameters of reperfusion, infarct size, and clinical outcome. These data underscore the utility of patient selection for EVT on the basis of collateral vessel status.

Clinical High-Resolution Imaging of the Inner Ear by Using Magnetic Resonance Imaging (MRI) and Cone Beam Computed Tomography (CBCT).

PURPOSE: Imaging of the delicate inner ear morphology has become more and more precise owing to the rapid progress in magnetic resonance imaging (MRI). However, in clinical practice, the interpretation of imaging findings is hampered by a limited knowledge of anatomical details which are frequently obscured by artifacts. Corresponding review articles are as rare in journals as they are in reference books. This shortness prompted us to perform a direct comparison of imaging with anatomical whole-mount sections as a reference. It was the intention of this paper to compare the microscopic anatomy of a human inner ear as shown on anatomical whole-mount sections with high-resolution MRI and cone beam computed tomography (CBCT). Both are available in clinical routine and depict the structures with maximum spatial resolution. It was also a goal of this work to clarify if structures that were observed on MRI in a regular manner correlate with factual inner ear anatomy or correspond with artifacts typical for imaging. METHODS: A fresh human anatomical specimen was examined on a clinical 3-Tesla MRI scanner using a dedicated surface coil. The same specimen was then studied with CBCT. In each imaging modality, high-resolution 3D data sets which enabled multiplanar reformatting were created. In the second step, anatomical whole-mount sections of the specimen were cut and stained. This process enabled a direct comparison of imaging with anatomical conditions. RESULTS: Clinical MRI was able to depict the inner ear with remarkable anatomical precision. Strongly T2-weighted imaging protocols are exquisitely capable of showing the fluid-filled components of the inner ear. The macular organs, ampullar crests and cochlear aqueduct were clearly visible. Truncation artifacts are prone to be confused with the delicate membrane separating the endolymphatic from the perilymphatic compartment. However, it was not possible to directly depict this borderline. CONCLUSIONS: With the maximum resolution of magnetic resonance tomography, commonly used in everyday clinical practice, even the smallest details of the inner ear structures can be reliably displayed. However, it is important to distinguish between truncation artifacts and true anatomical structures. Therefore, this study can be useful as a reference for image analysis.

Periprocedural aspects in mechanical recanalization for acute stroke: data from the ENDOSTROKE registry.

INTRODUCTION: The ENDOSTROKE registry aims to accompany the spreading use of endovascular stroke treatment (EVT) in academic and non-academic hospitals. This analysis focuses on preprocedural imaging, patient handling and referral, as well as on different treatment modalities in mechanical recanalization. METHODS: Data for this study were from observational registry study in 12 stroke centers in Germany and Austria with online assessment of prespecified variables concerning endovascular stroke therapy. RESULTS: Data from 734 patients undergoing EVT were analyzed. Preferred imaging modality prior to EVT was CT (83 %) and CTA (78 %). In 95 %, EVT was performed under general anesthesia. In 55 % of patients, a combination of intravenous (IV) thrombolysis and EVT was used, followed by pure EVT (25 %), intra-arterial (IA) thrombolysis plus EVT (13 %) and IV + IA thrombolysis plus EVT (7 %). Intrahospital time delay until start of EVT was 91 and 99 min in anterior and vertebrobasilar circulation stroke, respectively. Average duration of EVT was 60 min. Overall thrombolysis in myocardial infarction grade 2/3 recanalization rate was 85 %. Stent retrievers were used in 75 %, being associated with higher recanalization rates than non-stent retrievers. Hemorrhagic complications (symptomatic and asymptomatic) occurred in 12 %. Overall vessel occlusion time was approximately 60 min longer in patients being referred from a primary care hospital for EVT. CONCLUSION: This study gives an overview of procedure-related factors in current EVT practice. It gives estimates on preprocedural imaging modalities, periprocedural handling, and treatment combinations used for EVT. Patient referral for EVT from primary care hospitals is associated with longer vessel occlusion times.

Endovascular intervention in treatment of refractory epistaxis.

Objective: Angiographic embolization is an established method of treating intractable cases of posterior epistaxis. This study aimed to test the effectiveness and safety of this method in treating cases refractory to conservative methods. Methods: A descriptive retrospective analysis of consecutive cases referred to the department of interventional radiology with refractory epistaxis from January 2001 to December 2018 and received a selective angiographic embolization of the sphenopalatine artery was done. Only epistaxis of idiopathic origin was included in the study. Results: During this period, 98 embolizations were performed. The success rate reached 81.6%. Minor complications were registered in 5%, with no single major complication. The length of stay was 10.5 ± 5.6. Conclusion: Selective angiographic embolization is an effective, safe, and minimally invasive method in treating refractory epistaxis.

Auditory Brainstem Implants-Hearing Restoration in Congenitally Deaf Children.

BACKGROUND: Children who are born deaf can learn to hear and to speak with the aid of a cochlear implant (CI). If the implantation of a CI is not possible for anatomical reasons, an auditory brainstem implant (ABI) is the only surgical option for auditory rehabilitation. It is estimated that about 5 to 45 children could potentially benefit from this treatment in Germany each year. In this article, we present and discuss the current state of the scientific evidence. METHODS: The PubMed and Embase databases were searched for relevant publications from 2010 onward. 15 articles reporting at least 10 cases with at least one year of auditory follow-up were included in the analysis. The results, including CAP ("categories of auditory performance") scores on a scale of 0 to 7, are presented and compared with the authors' own findings in a series of 38 patients. RESULTS: All of the publications show that children who do not suffer from impairments of other kinds hear significantly better with an ABI than those with additional handicaps. Early implantation is advantageous, under the age of three years if possible. The results vary widely across publications and from patient to patient. The mean CAP score in all publications is 3.57 (standard deviation [SD], 1.04). 38.24% of the patients (SD 18.68) achieved the ability to understand spoken language (CAP ≥= 5), more specifically, the ability to communicate in everyday life without lip reading, in person and some even succeed in conversing over the telephone. CONCLUSION: ABI is a safe and effective treatment for sensorineural deafness in congenitally deaf children who cannot be treated with a cochlear implant. In particular, children without any other impairments have a good chance of developing the ability to understand spoken language, especially if the implantation is performed early.

VenomMaps: Updated species distribution maps and models for New World pitvipers (Viperidae: Crotalinae).

Beyond providing critical information to biologists, species distributions are useful for naturalists, curious citizens, and applied disciplines including conservation planning and medical intervention. Venomous snakes are one group that highlight the importance of having accurate information given their cosmopolitan distribution and medical significance. Envenomation by snakebite is considered a neglected tropical disease by the World Health Organization and venomous snake distributions are used to assess vulnerability to snakebite based on species occurrence and antivenom/healthcare accessibility. However, recent studies highlighted the need for updated fine-scale distributions of venomous snakes. Pitvipers (Viperidae: Crotalinae) are responsible for >98% of snakebites in the New World. Therefore, to begin to address the need for updated fine-scale distributions, we created VenomMaps, a database and web application containing updated distribution maps and species distribution models for all species of New World pitvipers. With these distributions, biologists can better understand the biogeography and conservation status of this group, researchers can better assess vulnerability to snakebite, and medical professionals can easily discern species found in their area.

Duvernoy's Gland Transcriptomics of the Plains Black-Headed Snake, Tantilla nigriceps (Squamata, Colubridae): Unearthing the Venom of Small Rear-Fanged Snakes.

The venoms of small rear-fanged snakes (RFS) remain largely unexplored, despite increased recognition of their importance in understanding venom evolution more broadly. Sequencing the transcriptome of venom-producing glands has greatly increased the ability of researchers to examine and characterize the toxin repertoire of small taxa with low venom yields. Here, we use RNA-seq to characterize the Duvernoy's gland transcriptome of the Plains Black-headed Snake, Tantilla nigriceps, a small, semi-fossorial colubrid that feeds on a variety of potentially dangerous arthropods including centipedes and spiders. We generated transcriptomes of six individuals from three localities in order to both characterize the toxin expression of this species for the first time, and to look for initial evidence of venom variation in the species. Three toxin families-three-finger neurotoxins (3FTxs), cysteine-rich secretory proteins (CRISPs), and snake venom metalloproteinases (SVMPIIIs)-dominated the transcriptome of T. nigriceps; 3FTx themselves were the dominant toxin family in most individuals, accounting for as much as 86.4% of an individual's toxin expression. Variation in toxin expression between individuals was also noted, with two specimens exhibiting higher relative expression of c-type lectins than any other sample (8.7-11.9% compared to <1%), and another expressed CRISPs higher than any other toxin. This study provides the first Duvernoy's gland transcriptomes of any species of Tantilla, and one of the few transcriptomic studies of RFS not predicated on a single individual. This initial characterization demonstrates the need for further study of toxin expression variation in this species, as well as the need for further exploration of small RFS venoms.

[Quantitative MR-Spectroscopy: implementation and quality assurance on a clinical MR-scanner]. / Quantitative MR-Spektroskopie: Implementierung und Qualitätssicherung an einem klinischen MR-Tomografen.

The aim of this study was the implementation of quantitative MR-Spectroscopy with external reference signals on a Philips Gyroscan Intera 1,5 T MR-Scanner for routine clinical use. We established measurements for quality assurance of the used phantoms and methods. In detail we analyzed the dependence of the signal on concentration and volume as well as on the local variation within the coil and the impact of these factors on quantification. Furthermore we established measurements for routine constancy checks. The method as well as the software for concentration calculation was checked by an in vitro measurement. In a blinded measurement the concentrations of NAA, Cho and Kr in the PTB reference phantom 10614mM were determined correctly within their error limits.

Imaging of cerebrospinal fluid leaks.

The present article provides an overview of epidemiology, clinical signs and symptoms, imaging techniques and specific imaging findings in cerebrospinal fluid leaks. Imaging protocols are supplemented with practical hints for invasive techniques. Emphasis is on the full scope of imaging findings in traumatic and nontraumatic cranial and spinal leaks.

Cryptic Diversity, but to What Extent? Discordance Between Single-Locus Species Delimitation Methods Within Mainland Anoles (Squamata: Dactyloidae) of Northern Central America.

Single-locus molecular barcoding is a useful method for identifying overlooked and undescribed biodiversity, providing the groundwork for further systematic study and taxonomic investigation. A variety of methods for delimiting species from barcoding libraries have been developed and applied, allowing for rapid estimates of species diversity in a broad range of taxa. However, tree-based and distance-based analyses can infer different group assignments, potentially over- or underestimating the number of putative species groups. Here, we explore diversity of mainland species of anole lizards from the Chortís Block biogeographical province of northern Central America using a DNA barcoding approach, generating and analyzing cytochrome oxidase subunit I (COI) sequences for over 400 samples assignable to 33 of 38 (86.8%) native and one introduced mainland species. We subsequently tested the effects different models of nucleotide substitution, different species-delimitation algorithms, and reducing our dataset had on species delimitation estimates. We performed of two distance-based (ABGD, RESL) and three tree-based (bPTP, mPTP, GMYC) analyses on both the full dataset and a dataset consisting only of unique halotypes. From 34 nominal taxa, analyses of the full dataset recovered between 34 and 64 operational taxonomic units (OTUs), while analyses of the reduced dataset inferred between 36 and 59. Reassigning individuals to either mPTP-inferred or ABGD clustered (7.2% threshold) groups improved the detection of a barcoding gap across three different models of nucleotide substitution, removing overlap between intra- and interspecific distances. Our results highlight the underestimated diversity of mainland Chortís Block anoles, but the lack of congruence between analyses demonstrates the importance of considering multiple analytical methods when dealing with single-locus datasets. We recommend future studies consider the effects of different models of nucleotide substitution on proposed barcoding gaps, as well as the effect reducing a dataset to unique haplotypes may have on proposed diversity estimates.

Postoperative Cochlear Obliteration after Retrosigmoid Approach in Patients with Vestibular Schwannoma.

Objective Vestibular schwannomas (VSNs) account for the vast majority of lesions located in the cerebellopontine angle (CPA). The goals of VSN surgery are possible total tumor removal, intact facial nerve function, and preservation of cochlear nerve function. In cases of pre- or postoperative deafness, restoration of hearing with auditory brainstem implant (ABI) or cochlear implant (CI) is a promising treatment option with normally better results in CI than in ABI. The aim of this retrospective study is to evaluate cochlear ossification or obliteration secondary to a retrosigmoid approach, which is important for later CI, especially in single-sided deafness. Materials and Methods We retrospectively reviewed data from our suboccipital retrosigmoid operation database for the period from January 2008 to February 2015. A total of 65 patients with VSN could be analyzed retrospectively. The patient's data (age, gender, side of operation, tumor entities, and the duration of follow-up) were evaluated. The most recent T2-weigted MRI exams were taken into account for the evaluation of cochlea. To compare left and right sides, the coronal reformatted images were reconstructed in a symmetrical way. Results Twenty-two out of 65 (33%) patients had cochlear obliteration in our survey. The cochlear obliteration was more common in females (44 vs. 20% in males). The median follow-up was 28 months. The size and the intrameatal extension of tumors could not be considered as factors influencing the cochlear obliteration rate. According to our survey, 33% of suboccipital approaches manifested cochlear obliteration to some extent. It was more common in females. The intrameatal extension of tumors played statistically no role in the occurrence of postoperative cochlear obliteration. Whether the prohibition of cochlear ossification can be best achieved by retrosigmoid approaches, compared to other approaches to the CPA, or not could be a subject of future studies.

Comparative venom-gland transcriptomics and venom proteomics of four Sidewinder Rattlesnake (Crotalus cerastes) lineages reveal little differential expression despite individual variation.

Changes in gene expression can rapidly influence adaptive traits in the early stages of lineage diversification. Venom is an adaptive trait comprised of numerous toxins used for prey capture and defense. Snake venoms can vary widely between conspecific populations, but the influence of lineage diversification on such compositional differences are unknown. To explore venom differentiation in the early stages of lineage diversification, we used RNA-seq and mass spectrometry to characterize Sidewinder Rattlesnake (Crotalus cerastes) venom. We generated the first venom-gland transcriptomes and complementary venom proteomes for eight individuals collected across the United States and tested for expression differences across life history traits and between subspecific, mitochondrial, and phylotranscriptomic hypotheses. Sidewinder venom was comprised primarily of hemorrhagic toxins, with few cases of differential expression attributable to life history or lineage hypotheses. However, phylotranscriptomic lineage comparisons more than doubled instances of significant expression differences compared to all other factors. Nevertheless, only 6.4% of toxins were differentially expressed overall, suggesting that shallow divergence has not led to major changes in Sidewinder venom composition. Our results demonstrate the need for consensus venom-gland transcriptomes based on multiple individuals and highlight the potential for discrepancies in differential expression between different phylogenetic hypotheses.

Renal cell cancer presented with leptomeningeal carcinomatosis effectively treated with sorafenib.

BACKGROUND: Sorafenib has been approved in the U.S. and the European Union for patients with advanced renal cell cancer (RCC). There is evidence that treatment with sorafenib can achieve partial remissions in patients with brain metastases of RCC. CASE REPORT: We report of a patient with leptomeningeal carcinomatosis of RCC, who 10 days after initiation of sorafenib therapy showed a noticeable decrease in contrast enhancement of the tumor in a magnetic resonance imaging (MRI) scan of the brain. This partial response was verified by an MRI scan on day 74. DISCUSSION: Results of a sub-evalution of a randomized phase III trial show that sorafenib offers encouraging activity in the treatment of patients with RCC and brain metastases. CONCLUSION: This case shows that sorafenib can achieve rapid tumor response in a patient with leptomeningeal carcinomatosis of RCC. This partial remission can persist for at least 10 weeks.