Species delimitation and integrative taxonomy of the Reithrodontomys mexicanus (Rodentia: Cricetidae) cryptic complex.

Species boundaries are difficult to establish in groups with very similar morphology. As an alternative, it has been suggested to integrate multiple sources of data to clarify taxonomic problems in taxa where cryptic speciation processes have been reported. This is the case of the harvest mouse Reithrodontomys mexicanus, which has a problematic taxonomy history as it is considered a complex species. Here, we evaluate the cryptic diversity of R. mexicanus using an integrative taxonomy approach in order to detect candidate lineages at the species level. The molecular analysis used one mitochondrial (cytb) and two nuclear (Fgb-I7 and IRBP) genes. Species hypotheses were suggested based on three molecular delimitation methods (mPTP, bGMYC, and STACEY) and cytb genetic distance values. Skull and environmental space differences between the delimited species were also tested to complement the discrimination of candidate species. Based on the consensus across the delimitation methods and genetic distance values, four species were proposed, which were mostly supported by morphometric and ecological data: R. mexicanus clade I, R. mexicanus clade IIA, R. mexicanus clade IIIA, and R. mexicanus clade IIIB. In addition, the evolutionary relationships between the species that comprise the R. mexicanus group were discussed from a phylogenetic approach. Our findings present important taxonomic implications for Reithrodontomys, as the number of known species for this genus increases. Furthermore, we highlight the importance of the use of multiple sources of data in systematic studies to establish robust delimitations between species considered taxonomically complex.

Molecular systematics of the Reithrodontomys tenuirostris group (Rodentia: Cricetidae) highlighting the Reithrodontomys microdon species complex.

The Reithrodontomys tenuirostris species group is considered "the most specialized" within the genus Reithrodontomys from morphological and ecological perspectives. Previous studies based on molecular data recommended changes in the taxonomy of the group. In particular, R. microdon has been the most taxonomically questioned, with the suggestion that it constitutes a complex of cryptic species. We analyzed the phylogenetic relationships of the R. tenuirostris species group using DNA sequences from the mitochondrial Cytochrome b gene and Intron 7 of the nuclear beta fibrinogen gene. In addition, divergence times were estimated, and possible new taxa delimited with three widely used species delimitation methods. Finally, possible connectivity routes based on shared haplotypes were tested among the R. microdon populations. All species were recovered as monophyletic with the exception of R. microdon, whose individuals were grouped into four different haplogroups, one of which included specimens of R. bakeri. Diversification within the R. tenuirostris species group began about 3 Ma, in the Pleistocene. The bGMYC and STACEY delimitation methods were congruent with each other, delimiting at the species-level each haplogroup within R. microdon, while the mPTP suggested a greater number of species. Moreover, none of the haplogroups showed potential connectivity routes between them, evidencing lack of gene flow. Our results suggest the existence of a higher number of species in the R. tenuirostris group, because we show that there are four species within what is currently recognized as R. microdon.

Dentro del género Reithrodontomys, el grupo de especies R. tenuirostris es considerado "el más especializado" morfológica y ecológicamente. Estudios moleculares previos recomendaron cambios en su taxonomía, proponiendo a R. microdon como un complejo de especies crípticas. Se analizaron las relaciones filogenéticas del grupo de especies R. tenuirostris con base en información de un gen mitocondrial, Citocromo b, y uno nuclear, el intrón 7 del beta fibrinógeno. Se estimaron los tiempos de divergencia, y se delimitó a posibles nuevos taxa aplicando tres métodos comúnmente utilizados, y se evaluaron posibles rutas de conectividad con base en los diferentes haplotipos identificados en las poblaciones de R. microdon. Todas las especies del grupo se recuperaron como monofiléticas excepto R. microdon, cuyos individuos formaron cuatro haplogrupos diferentes, uno de los cuales incluyó a especímenes de R. bakeri. Según la datación obtenida, la diversificación del grupo R. tenuirostris comenzó en el Pleistoceno, hace aproximadamente 3 Ma. Los métodos de análisis de delimitación de especies bGMYC y STACEY resultaron congruentes entre sí, logrando delimitar cada haplogrupo dentro de R. microdon a nivel de especie, mientras que con el método de mPTP se delimitó un número mayor de especies. No se identificaron rutas de conectividad entre haplogrupos, lo que resultaría en una ausencia de flujo génico. Se sugiere la existencia de un mayor número de especies en el grupo R. tenuirostris, ya que hay cuatro especies incluidas en lo que actualmente se reconoce como R. microdon.

Impact of transitioning to an online course - A report from the ESTRO gyn teaching course.

INTRODUCTION: In 2020, the ESTRO course on image-guided radiotherapy and chemotherapy in gynaecological cancer was converted into an online version due to the COVID-19 pandemic. This paper describes the change process and evaluates the impact on participants compared with previous live courses. METHODS AND MATERIALS: The 2019 live course contained 41 h of educational content, comprising 33 h of synchronous activities (lectures, interactive activities, videos) and 8 h of homework (contouring, dose planning). For the online course, the lectures were provided as pre-course material (11 mandatory, 22 optional). Contouring/dose planning homework was unchanged. The synchronous sessions were reconfigured as six 2-hour webinars (total educational content ~38 h).Participant numbers/characteristics, engagement and satisfaction for six live courses and the online course were compared. RESULTS: Participant numbers for the online and live courses were similar (90 vs. mean 96). There were more participants from outside Europe (28% vs. mean 18%) and more non-doctors (47% vs. mean 33%). Proportion of participants responding to the pre-course questionnaire was similar (77% vs. mean 78%) but post-course questionnaire response was lower (62% vs. mean 92%).43% participants viewed ≥75% of mandatory lectures before the webinars. 86% viewed the optional lectures. Submissions of contouring and dose planning homework was higher (contouring 77%-90% vs. 56%-69%, dose planning 74%-89% vs. 29%-57%).96% (47/49) participants rated the online course as Excellent (43%) or Good (53%). Overall satisfaction was similar (4.4 vs. mean 4.6). CONCLUSION: Participant satisfaction and engagement with the online course remained high despite less contact time with faculty.

Assessment of DNA Integrity From Trap-Captured Boll Weevil (Coleoptera: Curculionidae) for Use in a New PCR-Based Diagnostic Tool.

The boll weevil, Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae), is a major pest of commercial cotton (Gossypium hirsutum) in the southern United States and throughout Central and South America. Efforts are underway to develop a PCR-based diagnostic tool that can be used to rapidly and accurately differentiate boll weevils from other weevil species that are commonly captured in pheromone traps. However, the quantity and integrity of weevil DNA must be sufficient for a successful PCR assay. Currently, active eradication programs service traps weekly, but post-eradication programs service traps at 2- or 3-wk intervals. Consequently, captured weevils may be dead, dismembered, and exposed to environmental conditions for prolonged periods which may adversely affect the quantity and quality of weevil DNA. We documented DNA quantity and integrity in boll weevils and weevil body parts aged in traps over a 3-wk period under field conditions. The quantity of DNA extracted from whole weevils, heads, abdomens, and legs generally remained sufficient (> 1 ng/µl) for successful PCR amplification throughout the 21-d period. The integrity (fragment length) of extracted DNA declined over time but generally was sufficient (> 700 bp) for successful amplification. PCR amplification of three marker genes validated that the quality and integrity of DNA extracted from dead weevils and individual weevil body parts aged in traps up to 21 d remained at sufficient levels for the PCR-based assay. However, our data also suggested that rain events may accelerate degradation of weevil DNA.

Rice momilactone gene cluster: transcriptional response to barnyard grass (Echinochloa crus-galli).

Expression of genes involved in diterpene biosynthesis, especially momilactone and gibberellins (GAs), in rice plants (Oryza sativa L.) in response to barnyard grass (Echinochloa crus-galli) stress was examined. The three analyzed class II diterpene synthases had the highest fold change expression. Transcription patterns of genes for two homologs of momilactone synthases, OsMAS and OsMAS2, suggests their distinct roles in response to the presence of barnyard grass.

The role of Pleistocene climate change in the genetic variability, distribution and demography of Proechimys cuvieri and P. guyannensis (Rodentia: Echimyidae) in northeastern Amazonia.

The spiny rats, genus Proechimys, have the highest species richness within the Echimyidae family, as well as species with high genetic variability. The genus distribution includes tropical South America and Central America south to Honduras. In this study, we evaluate the phylogeographic histories of Proechimys guyannensis and P. cuvieri using cytochrome b, in a densely sampled area in northeastern Amazon where both species are found in sympatry in different environments. For each species, Bayesian and Maximum Likelihood phylogenetic analysis were congruent and recovered similar clades in the studied area. Bayesian phylogenetic analysis using a relaxed molecular clock showed that these clusters of haplotypes diversified during Pleistocene for both species. Apparently, the large rivers of the region did not act as barriers, as some clades include specimens collected from opposite banks of Oiapoque, Araguari and Jari rivers. Bayesian skyline plot analysis showed recent demographic expansion in both species. The Pleistocene climatic changes in concert with the geologic changes in the Amazon fan probably acted as drivers in the diversification that we detected in these two spiny rats. Proechimys cuvieri and P. guyannensis show genetic structure in the eastern part of the Guiana region. Greater genetic distances observed in P. guyannensis, associated with highly structured groups, suggest that more detailed studies of systematics and ecology should be directed to this species.

Evolutionary relationships and climatic niche evolution in the genus Handleyomys (Sigmodontinae: Oryzomyini).

Mesoamerica is considered a biodiversity hot spot with levels of endemism and species diversity likely underestimated. Unfortunately, the region continues to experience some of the highest deforestation rates in the world. For mammals, the evolutionary relationships of many endemic taxa are controversial, as it is the case for members of the genus Handleyomys. Estimation of a time-calibrated hypothesis for the evolution of these six genera (Euryoryzomys, Handleyomys, Hylaeamys, Nephelomys, Oecomys and Transandinomys) supported a monophyletic Handleyomys sensu lato. Based on their distinctive morphology and the amount of inter-generic genetic divergence, Handleyomys sensu stricto, H. alfaroi, the H. chapmani, and the H. melanotis species groups warrant recognition as separate genera. In addition, species delimitation documents the existence of cryptic species-level lineages within H. alfaroi and H. rostratus. Cryptic lineages within H. rostratus exhibited significant niche differentiation, but this was not the pattern among species-level clades within H. alfaroi. Similarly, age-range correlations revealed that niche evolution within Handleyomys is not correlated with evolutionary time, instead, ancestral climate tolerance reconstructions show niche disparities at specific diversification events within the chapmani and melanotis species groups, while the climatic niche of the rest of species of Handleyomys tended to be conservative.

The 25th anniversary of the retrograde suction decompression technique (Dallas technique) for the surgical management of paraclinoid aneurysms: historical background, systematic review, and pooled analysis of the literature.

OBJECTIVE: Paraclinoid internal carotid artery (ICA) aneurysms frequently require temporary occlusion to facilitate safe clipping. Brisk retrograde flow through the ophthalmic artery and cavernous ICA branches make simple trapping inadequate to soften the aneurysm. The retrograde suction decompression (RSD), or Dallas RSD, technique was described in 1990 in an attempt to overcome some of those treatment limitations. A frequent criticism of the RSD technique is an allegedly high risk of cervical ICA dissection. An endovascular modification was introduced in 1991 (endovascular RSD) but no studies have compared the 2 RSD variations. METHODS: The authors performed a systematic review of MEDLINE/PubMed and Web of Science and identified all studies from 1990-2016 in which either Dallas RSD or endovascular RSD was used for treatment of paraclinoid aneurysms. A pooled analysis of the data was completed to identify important demographic and treatment-specific variables. The primary outcome measure was defined as successful aneurysm obliteration. Secondary outcome variables were divided into overall and RSD-specific morbidity and mortality rates. RESULTS: Twenty-six RSD studies met the inclusion criteria (525 patients, 78.9% female). The mean patient age was 53.5 years. Most aneurysms were unruptured (56.6%) and giant (49%). The most common presentations were subarachnoid hemorrhage (43.6%) and vision changes (25.3%). The aneurysm obliteration rate was 95%. The mean temporary occlusion time was 12.7 minutes. Transient or permanent morbidity was seen in 19.9% of the patients. The RSD-specific complication rate was low (1.3%). The overall mortality rate was 4.2%, with 2 deaths (0.4%) attributable to the RSD technique itself. Good or fair outcome were reported in 90.7% of the patients.Aneurysm obliteration rates were similar in the 2 subgroups (Dallas RSD 94.3%, endovascular RSD 96.3%, p = 0.33). Despite a higher frequency of complex (giant or ruptured) aneurysms, Dallas RSD was associated with lower RSD-related morbidity (0.6% vs 2.9%, p = 0.03), compared with the endovascular RSD subgroup. There was a trend toward higher mortality in the endovascular RSD subgroup (6.4% vs 3.1%, p = 0.08). The proportion of patients with poor neurological outcome at last follow-up was significantly higher in the endovascular RSD group (15.4% vs 7.2%, p < 0.01). CONCLUSIONS: The treatment of paraclinoid ICA aneurysms using the RSD technique is associated with high aneurysm obliteration rates, good long-term neurological outcome, and low RSD-related morbidity and mortality. Review of the RSD literature showed no evidence of a higher complication rate associated with the Dallas technique compared with similar endovascular methods. On a subgroup analysis of Dallas RSD and endovascular RSD, both groups achieved similar obliteration rates, but a lower RSD-related morbidity was seen in the Dallas technique subgroup. Twenty-five years after its initial publication, RSD remains a useful neurosurgical technique for the management of large and giant paraclinoid aneurysms.

The use of unfixed bone marrow trephines for multicolour flow cytometry.

An adequate bone marrow aspirate is essential for a rapid diagnosis of acute leukaemia by multicolour flow cytometry enabling the simultaneous assessment of multiple antigens on the cell surface as well as intracellular or nuclear ones. In the context of acute leukaemia, it is important to have a diagnosis of the blasts lineage as soon as possible to decide the appropriate treatment. This is sometimes delayed due to difficulties in obtaining a bone marrow aspirate due to a "dry tap". In this study we evaluated retrospectively cell markers results by flow cytometry of unfixed bone marrow trephines of 65 patients with leukaemia at diagnosis and including a few after treatment. Our aims were: 1) To compare cell markers results between bone marrow trephine (BMT) and bone marrow aspirate (BMA) 24 cases and BMT with peripheral blood (PB) 14 cases in paired samples to establish if they were reproducible with results of the unfixed bone marrow trephine biopsies. 2) To ascertain a precise diagnosis in 27 (42%) of the cases in which only a bone marrow trephine was available. We demonstrated that unfixed bone marrow trephine provides an adequate and representative cell suspension for flow cytometry and it is a powerful tool when no other material (bone marrow aspirate or peripheral blood) is available to make a rapid diagnosis. Furthermore when marrow aspirate or peripheral blood paired samples were available, flow cytometry results obtained were identical across all the sample types. Applicability to the clinical laboratory: We described a method to obtain a cell suspension from core biopsies that can easily be implemented routinely in a laboratory that performs diagnostic flow cytometry immunophenotyping. This method is simple, inexpensive and it doesn't require extra equipment.

A new species of big-eared climbing rat, genus Ototylomys (Cricetidae: Tylomyinae), from Chiapas, Mexico.

An allopatric population of big-eared climbing rats (Ototylomys) from the Northern Highlands of Chiapas, Mexico, is described as a new species. The new taxon is part of a unique montane rainforest community that includes several other endemic species in the limited geographic range between the Río Grijalva and the Central Depression of Chiapas. Several cranial, external, and molecular characters distinguish this new species of big-eared climbing rat from its more widely distributed congener, Ototylomys phyllotis. We performed principal component and discriminate function analyses of cranial measurements, and found that specimens of the new species consistently could be distinguished from other Ototylomys with strong statistical support. Compared with exemplars of Ototylomys from elsewhere in their range, the new species possesses a karyotype that differs by 3 additional biarmed chromosome pairs, is fixed or nearly fixed for distinct electromorphs at 12 allozyme loci, and the mean genetic distance exceeds 14%, based on comparisons of the mitochondrial cytochrome b gene between the new species of Ototylomys and representatives of O. phyllotis. The restricted distribution in montane karst rainforest suggests that the species and its habitat may be a matter of conservation concern.

Una población alopátrica de rata orejuda trepadora (Ototylomys) de las Tierras Altas del Norte de Chiapas, México se describe como una nueva especie. El nuevo taxón es parte de una comunidad única de bosque lluvioso montano que incluye varias especies endémicas en el área de distribución geográfica limitada entre el Río Grijalva y la Depresión Central de Chiapas. Varios caracteres craneales, externos, y moleculares distinguen la nueva rata orejuda trepadora de su congénere más ampliamente distribuido, Ototylomys phyllotis. Se realizaron análisis de componentes principales y de función discriminante de los caracteres craneales, y se encontró que los especímenes de La Pera fueron consistentemente distinguidos de otros Ototylomys con un fuerte soporte estadístico. En comparación con ejemplares de Ototylomys del rango, la nueva especie posee un cariotipo que difiere por 3 pares adicionales de cromosomas biarmados, está fijo o casi fijo por distintos electromorfos en 12 loci alozímicos. Adicionalmente, la media de la distancia genética comparada del gen mitochondrial citocromo b entre la nueva especie de Ototylomys y representantes de O. phyllotis, excede el 14%. La distribución restringida en el bosque lluvioso montano kárstico sugiere que la especie y su hábitat pueden ser de importancia para la conservación.

Palliative care patients' perceptions of the work involved in understanding and managing the network of care provision surrounding them.

OBJECTIVE: To explore the work carried out for cancer palliative care patients in understanding and dealing with the often large network of care provision surrounding them. METHOD: Qualitative thematic analysis of interviews with 24 patients (aged 48-85 years) with 15 different types/sites of cancer and palliative care needs. RESULTS: The main theme of 'patient work-their strategies and project management' is presented. Subthemes included: being organised and keeping records; planning ahead and coordinating care; information gathering; understanding the hierarchy and knowing who the key people are; strategies to remember names and roles; understanding and 'working the system'. Insights are given into the work carried out on patients' behalf by family, although it was unclear who would do this work if no family was available. Some of the challenges faced by patients and families are identified. These included limited information; uncertainty when care is transferred between different teams or locations; deciding who to contact and how; and negotiating through gatekeepers. CONCLUSIONS: The number and variety of people contributing to the care of a cancer palliative care patient can be difficult for patients and family to comprehend. Work is required by patients or family on their behalf to achieve the level of understanding required to become accomplished at navigating the system and project managing their care organisation, and is probably influenced by role expectations and previous experience. Much of this additional, often hidden, workload for patients and family could probably be reduced with clear, timely information provision by health professionals.

Cotton (Gossypium hirsutum L.) boll rotting bacteria vectored by the brown stink bug, Euschistus servus (Say) (Hemiptera: Pentatomidae).

AIM: To determine the capacity of the brown stink bug (BSB) (Euschistus servus) to transmit an infective Pantoea agglomerans strain Sc 1-R into cotton (Gossypium hirsutum) bolls. METHODS AND RESULTS: A laboratory colony of BSB was maintained on fresh green beans. Either sterile or Sc 1-R contaminated beans were offered to adult insects. Strain Sc 1-R holds rifampicin resistance (Rif(r) ). Insects were then caged with unopened greenhouse-grown bolls. After 2 days, BSB were surface sterilized, ground, and then plated on media with and without Rif. Two weeks later, seed with lint were ground and plated on media with and without Rif. Microbes were recovered on nonselective media from all BSBs and from seed/lint at concentrations reaching 10(9)  CFU g(-1) tissue. Rif(r) bacteria were recovered strictly from insects exposed to Sc1-R and from diseased seed/lint of respective bolls. CONCLUSIONS: Euschistus servus was capable of transmitting strain Sc 1-R into bolls resulting in disease. Insects not exposed to the pathogen deposited bacteria yet the nonpathogenic microbes produced insignificant damage to the boll tissue. SIGNIFICANCE AND IMPACT OF STUDY: This is the first study to concretely show the capacity of the BSB to transmit an infective P. agglomerans strain resulting in boll disease.

Selection for pro-inflammatory mediators produces chickens more resistant to Clostridium perfringens-induced necrotic enteritis.

We developed a novel selection method based on an inherently high and low phenotype of pro-inflammatory mediators and produced "high" and "low" line chickens. We have shown high line birds are more resistant to Salmonella enterica serovar Enteritidis and Eimeria tenella compared to the low line. Clostridium perfringens is the fourth leading cause of bacterial-induced foodborne illness, and is also an economically important poultry pathogen and known etiologic agent of necrotic enteritis (NE). The objective of this study was to determine if high line birds were also more resistant to NE than low line birds using an established model. Birds were reared in floor pens and challenges were conducted twice (high line = 25/trial, 50 birds total; low line = 26/trial, 52 birds total). Day-old chicks were provided a 55% wheat-corn-based un-medicated starter diet. A bursal disease vaccine was administered at 10× the recommended dose via the ocular route at 14-d-of-age. Birds were challenged daily for 3 d beginning at 16-d-of-age by oral gavage (3 mL) with 10(7) colony forming units (cfu) of C. perfringens/mL then necropsied at 21-d-of-age. All birds had sections of the intestine examined and scored for lesions while the first 10 necropsied also had gut content collected for C. perfringens enumeration. Chickens from the high line were more resistant to C. perfringens-induced NE pathology compared to the low line, as indicated by reduced lesion scores. Ninety percent of the high line birds had lesions of zero or one compared to 67% of the low line birds. Wilcoxon rank sum test showed significantly higher lesion scores in the low line birds compared to the high line (P < 0.0001). There were no differences in the C. perfringens recovered (P = 0.83). These data provide additional validation and support selection based on elevated levels of pro-inflammatory mediators produces chickens with increased resistance against foodborne and poultry pathogens.

The networks of care surrounding cancer palliative care patients.

OBJECTIVES: This paper explicates the nature and extent of the networks of care surrounding patients with cancer palliative care needs. METHOD: Twenty-four patients with 15 different types/sites of cancer were recruited in one city in England, UK. During one in-depth interview patients identified who was 'involved in their care' and any known pathways of communication between them. One hundred of these people (35 doctors, 32 nurses, 17 professions allied to medicine, 8 family members and 8 others) were also interviewed. Maps of people/teams and the connections between them for each patient were then reconstructed using social networking software (PAJEK). RESULTS: The 24 patients identified a total of 619 people or teams (mean 26, median 22, range 9-45 per patient) contributing to their care. Selected care network maps are displayed, illustrating the extent and nature of the care networks supporting palliative care patients. Common members of care networks for patients with palliative care needs are revealed, but their individual and unique nature is also apparent. CONCLUSIONS: The possible clinical utility and challenges of mapping care networks are discussed. Exploring the care networks surrounding individual patients can be useful for illuminating the extent and complexity of individual patient's care networks; clarifying who is involved and who they communicate with; providing opportunities to see interaction routes that may otherwise be hidden, revealing potentially missing or weak connections; and highlighting overlaps or gaps in provision.

The utility of preoperative diffusion tensor imaging in the surgical management of brainstem cavernous malformations.

OBJECT: Resection of brainstem cavernous malformations (BSCMs) may reduce the risk of stepwise neurological deterioration secondary to hemorrhage, but the morbidity of surgery remains high. Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) are neuroimaging techniques that may assist in the complex surgical planning necessary for these lesions. The authors evaluate the utility of preoperative DTI and DTT in the surgical management of BSCMs and their correlation with functional outcome. METHODS: A retrospective review was conducted to identify patients who underwent resection of a BSCM between 2007 and 2012. All patients had preoperative DTI/DTT studies and a minimum of 6 months of clinical and radiographic follow-up. Five major fiber tracts were evaluated preoperatively using the DTI/DTT protocol: 1) corticospinal tract, 2) medial lemniscus and medial longitudinal fasciculus, 3) inferior cerebellar peduncle, 4) middle cerebellar peduncle, and 5) superior cerebellar peduncle. Scores were applied according to the degree of distortion seen, and the sum of scores was used for analysis. Functional outcomes were measured at hospital admission, discharge, and last clinic visit using modified Rankin Scale (mRS) scores. RESULTS: Eleven patients who underwent resection of a BSCM and preoperative DTI were identified. The mean age at presentation was 49 years, with a male-to-female ratio of 1.75:1. Cranial nerve deficit was the most common presenting symptom (81.8%), followed by cerebellar signs or gait/balance difficulties (54.5%) and hemibody anesthesia (27.2%). The majority of the lesions were located within the pons (54.5%). The mean diameter and estimated volume of lesions were 1.21 cm and 1.93 cm(3), respectively. Using DTI and DTT, 9 patients (82%) were found to have involvement of 2 or more major fiber tracts; the corticospinal tract and medial lemniscus/medial longitudinal fasciculus were the most commonly affected. In 2 patients with BSCMs without pial presentation, DTI/DTT findings were important in the selection of the surgical approach. In 2 other patients, the results from preoperative DTI/DTT were important for selection of brainstem entry zones. All 11 patients underwent gross-total resection of their BSCMs. After a mean postoperative follow-up duration of 32.04 months, all 11 patients had excellent or good outcome (mRS Score 0-3) at the time of last outpatient clinic evaluation. DTI score did not correlate with long-term outcome. CONCLUSIONS: Preoperative DTI and DTT should be considered in the resection of symptomatic BSCMs. These imaging studies may influence the selection of surgical approach or brainstem entry zones, especially in deep-seated lesions without pial or ependymal presentation. DTI/DTT findings may allow for more aggressive management of lesions previously considered surgically inaccessible. Preoperative DTI/DTT changes do not appear to correlate with functional postoperative outcome in long-term follow-up.

Management of intracranial aneurysms associated with arteriovenous malformations.

Intracranial or brain arteriovenous malformations (BAVMs) are some of the most interesting and challenging lesions treated by the cerebrovascular neurosurgeon. It is generally believed that the combination of BAVMs and intracranial aneurysms (IAs) is associated with higher hemorrhage rates at presentation and higher rehemorrhage rates and thus with a more aggressive course and natural history. There is wide variation in the literature on the prevalence of BAVM-associated aneurysms (range 2.7%-58%), with 10%-20% being most often cited in the largest case series. The risk of intracranial hemorrhage in patients with unruptured BAVMs and coexisting IAs has been reported to be 7% annually, compared with 2%-4% annually for those with BAVM alone. Several different classification systems have been applied in an attempt to better understand the natural history of this combination of lesions and implications for treatment. Independent of the classification used, it is clear that a few subtypes of aneurysms have a direct hemodynamic correlation with the BAVM itself. This is exemplified by the fact that the presence of a distal flow-related or an intranidal aneurysm appears to be associated with an increased hemorrhage risk, when compared with an aneurysm located on a vessel with no direct supply to the BAVM nidus. Debate still exists regarding the etiology of the association between those two vascular lesions, the subsequent implications for patients' risk of hemorrhagic stroke, and finally the determination of which patients warrant treatment and when. The ultimate goals of the treatment of a BAVM associated with an IA are to prevent hemorrhage, avoid stepwise neurological deterioration, and eliminate the mortality risk associated with recurrent hemorrhagic events. The treatment is only justifiable if the risks associated with an intervention are lower than or equivalent to the long-term risks of disability or mortality caused by the lesion itself. When faced with this difficult decision, a few questions need to be answered by the treating neu-rosurgeon: What is the mode of presentation? What is the symptomatic lesion? Which one of the lesions bled? What is the relationship between the BAVM and IA? Is it possible to safely treat both BAVM and IA? The objective of this review is to discuss the demographics, natural history, classification, and strategies for management of BAVMs associated with IAs.

In the wake of invasion: tracing the historical biogeography of the South American cricetid radiation (Rodentia, Sigmodontinae).

The Great American Biotic Interchange (GABI) was greatly influenced by the completion of the Isthmus of Panama and impacted the composition of modern faunal assemblages in the Americas. However, the contribution of preceding events has been comparatively less explored, even though early immigrants in the fossil records are evidence for waif dispersals. The cricetid rodents of the subfamily Sigmodontinae are a classic example of a species-rich South American radiation resulting from an early episode of North American invasion. Here, we provide a temporal and spatial framework to address key aspects of the historical biogeography and diversification of this diverse mammal group by using mitochondrial and nuclear DNA datasets coupled with methods of divergence time estimation, ancestral area reconstruction and comparative phylogenetics. Relaxed-clock time estimates indicate that divergence of the Sigmodontinae began in the middle-late Miocene (ca. 12-9 Ma). Dispersal-vicariance analyses point to the arrival of a single lineage of northern invaders with a widespread ancestral distribution and imply that the initial differentiation between Central and South America gave rise to the most basal groups within the subfamily. These two major clades diversified in the late Miocene followed by the radiation of main tribes until the early Pliocene. Within the Oryzomyalia, tribes diverged initially in eastern South America whereas multiple dispersals into the Andes promoted further diversification of the majority of modern genera. A comparatively uniform background tempo of diversification explains the species richness of sigmodontines across most nodes, except for two akodontine genera with recent increases in diversification rates. The bridging of the Central American seaway and episodes of low sea levels likely facilitated the invasion of South America long before the onset of the post-Isthmian phase of the GABI.

Lack of BDNF expression through promoter IV disturbs expression of monoamine genes in the frontal cortex and hippocampus.

Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of psychiatric conditions including major depression and schizophrenia. Mice lacking activity-driven BDNF expression through promoter IV (knock-in promoter IV: KIV) exhibit depression-like behavior, inflexible learning, and impaired response inhibition. Monoamine systems (serotonin, dopamine, and noradrenaline) are suggested to be involved in depression and schizophrenia since many of the current antidepressants and antipsychotics increase the brain levels of monoamines and/or act on monoamine receptors. To elucidate the impact of activity-driven BDNF on the monoamine systems, we examined mRNA levels for 30 monoamine-related genes, including receptors, transporters, and synthesizing enzymes, in KIV and control wild-type mice by using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). mRNA levels were measured in the frontal cortex and hippocampus, which are regions related to depression and schizophrenia and where promoter IV is active. The frontal cortex of KIV mice showed reduced levels of mRNA expression for serotonin receptors 1b, 2a, and 5b (5HTR1b, 5HTR2a, 5HTR5b), dopamine D2 receptors (DRD2), and adrenergic receptors alpha 1a and 1d (AdRα1a and AdRα1b), but increased levels for serotonin synthesizing enzyme, tryptophan hydroxylase (TPH), and dopamine D4 receptor (DRD4) when compared to control wild-type mice. The hippocampus of KIV mice showed decreased levels of 5HTR5b. Our results provide causal evidence that lack of promoter IV-driven BDNF disturbs expression of monoaminergic genes in the frontal cortex and hippocampus. These disturbed expression changes in the monoamine systems may mediate the depression- and schizophrenia-like behavior of KIV mice. Our results also suggest that antidepressant and antipsychotic treatments may actually interfere with and normalize the disturbed monoamine systems caused by reduced activity-dependent BDNF, while the treatment responses to these drugs may differ in the subject with reduced BDNF levels caused by stress and lack of neuronal activity.

Molecular phylogenetics and phylogeographic structure of Sumichrast's harvest mouse (Reithrodontomys sumichrasti: Cricetidae) based on mitochondrial and nuclear DNA sequences.

Sumichrast's harvest mouse (Reithrodontomys sumichrasti) is a montane rodent species widely distributed through the Mesoamerican highlands. We used sequence data from one mitochondrial (cytochrome b) and two nuclear (ß-fibrinogen and acid phosphatase type V) genes for a total of 1962 base pairs to estimate genealogical relationships and assess population genetic structure across the range of this taxon. Maximum likelihood and Bayesian approaches using cytochrome b resolved several major clades, revealing considerably more genetic diversity than observed in previous studies. The basal split in the tree topologies corresponded to the geographical separation among samples on either side of the Isthmus of Tehuantepec in México. We estimated an early Pleistocene or late Pliocene divergence between these two groups. We also recovered a well-supported clade south of the Nicaraguan Depression in Central America that we consider a separate biological species. The 12 networks generated using statistical parsimony (TCS) for cytochrome b sequence data were largely concordant with the phylogenetic analyses and we document the co-occurrence of two of these networks in central Veracurz. Phylogenies derived from ß-fibrinogen and acid phosphatase type V gene segments revealed less phylogenetic signal and did not separate samples of R. sumichrasti east and west of the Isthmus of Tehuantepec. The phylogeny estimated by combining the mitochondrial and nuclear sequence data was essentially identical to the cytochrome b gene tree.