West Nile Virus Encephalitis in Haematological Setting: Report of Two Cases and a Brief Review of the Literature

West Nile virus is a zoonotic agent causing life-threatening encephalitis in a proportion of infected patients. Older age, immunosuppression, and mutations in specific host genes (e.g., CCR5 delta-32 mutation) predispose to neuroinvasive infection. We report on two cases of severe West Nile encephalitis in recently-treated, different-aged, chronic lymphocytic leukemia patients. Both patients developed high-grade fever associated with severe neurological impairment. The younger one harboured germ-line CCR5 delta-32 mutation, which might have played a role in the pathogenesis of its neuroinvasive manifestations

In vitro description of a new technique for stapled side-to-side jejunocecal anastomosis in horses and CT scan anatomical comparison with other techniques

BACKGROUND: Stapled jejunocecal anastomoses are commonly performed in equine abdominal surgery. They carry higher complication rates compared to handsewn techniques. In human surgery various causes likely to lead to failure of stapled techniques have been evaluated, including staple line failure. Recently Freeman proposed a technique to perform a stapled jejunocecal anastomosis in horses while avoiding blind pouch formation. The aim of this study is to describe a method for stapled side-to-side jejunocecal anastomosis in horses and to compare it with other techniques with computed tomography to assess stomal area, shape and blind pouch size. METHODS: Intestinal specimens comprising the cecum, ileum and jejunum from 18 horses were collected and were divided into three groups. In Group S a standard stapled side-to-side jejunocecal anastomosis was performed. In Group F the anastomosis was performed using a modified technique proposed by Freeman. In Group G the anastomosis was performed with a modified technique proposed by the authors. Inflated bowel segments were CT scanned to obtain a MultiPlanar Reconstruction of the stoma and afferent small intestine before calculating the cross-sectional area of each of these regions. The ratio of the measured areas was compared between the three techniques. The volume of the blind-end pouch was measured and its ratio with the intestinal area compared between techniques. The cecum was opened and the length of the stoma measured with a caliper and compared to the intended initial length. RESULTS: The stomal/intestinal area ratio was not significantly different between techniques. No statistically significant difference was found in the stomal ideal/real perimeter ratio. There was no statistically significant difference in the intended/real stomal length ratio, and all techniques featured an increase in stomal length ranging from 2 to 12 %. Blind pouch formation was a consistent finding in Group S and was virtually absent in Groups F and G. CONCLUSIONS: Both the Freeman and the new (G) technique were comparable to the standard technique in terms of stomal area, stomal shape and difference in stomal elongation. They consistently produced a smaller blind pouch and allowed easier placement of the staplers

Ex Vivo Anatomical Characterization of Handsewn or Stapled Jejunocecal Anastomosis in Horses by Computed Tomography Scan

The aim of this study is to compare handsewn and stapled jejunocecal anastomosis with different stomal lengths in terms of anatomical differences. Group 1 underwent a two-layer handsewn jejunocecal side-to-side anastomosis (HS); Group 2 received a stapled jejunocecal side-to-side anastomosis (GIA). Each group was divided into two subgroups (HS80 and HS100, GIA80 and GIA100). Specimens were inflated and CT scanned. The stomal/jejunal area ratio and blind end pouch volume/area were measured and compared. Effective length of the stoma was measured and compared with the initial length. Stomal/jejunal area ratio was 1.1 for both 80 techniques, 1.6 for the GIA100, and 1.9 for the HS100 technique. Both HS and GIA techniques produced a blind end pouch and exhibited a mean increase of the final stomal length ranging from 6 to 11% greater than the original stomal length. All techniques will exhibit a length increase of the final stomal length compared to the intended stomal length, with a consequent increase in stomal area. Stapled techniques consistently produced a large distal blind end pouch. Length of a jejunocecal anastomosis should be selected in accordance with the diameter of afferent jejunum, and the 80 mm stomal length could be deemed sufficient in horses

Climate change in the temperature and precipitation at two contrasting sites of the Argentinean wheat region

Global climate change is shifting temperature and precipitation regimes, which is modifying the environments that define wheat yield and quality. The current work characterises the changes that have occurred in the thermal and hydric environment in two contrasting sites of the wheat-growing region of Argentina, allowing comparison between sites for these changes and for how the changes are accelerating. Temperature and precipitation variables were analysed by regression and trend testing (Mann Kendall), and future projections were made based upon significant relationships. The two sites compared were in the zones around the cities of Azul in the Province of Buenos Aires and Marcos Juárez in the Province of Córdoba, located approximately 500 km apart. The climate data analysed covered the period 1931–2014 for Azul and 1952–2014 for Marcos Juárez. At both sites, temperatures increased significantly in mean and extreme values over these periods, where the rate of change accelerated during the first years of the twenty-first century. The changes observed were in general more pronounced in Marcos Juárez than in Azul. Furthermore, in Marcos Juárez, mean precipitation increased from September to December and there was a higher frequency of extremes of precipitation greater than 100 mm in September and October during the early twenty-first century. Evidence was found for temperature rise and the occurrence of extreme temperature and precipitation events occurring differently between sites, as well as for its acceleration rate in the early twenty-first century. The projected future changes made implied that wheat yield is expected to suffer losses over the coming century.Fil: Basile, Silvana Marisol Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnolológico Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología. Laboratorio de Biología Funcional y Biotecnología; ArgentinaFil: Tognetti, Jorge Alberto. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Laboratorio de Fisiología Vegetal; ArgentinaFil: Gandini, Marcelo Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnolológico Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología. Laboratorio de Biología Funcional y Biotecnología; Argentina. Laboratorio de Investigación y Servicios En Teledetecci; ArgentinaFil: Rogers, William John. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnolológico Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología. Laboratorio de Biología Funcional y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Seasonal diet of Magellanic Penguin (Spheniscus magellanicus) juveniles revealed with a stable isotopes analysis of claws

Se realizó un análisis de isótopos estables en uñas para evaluar la composición de la dieta y el uso estacional de los recursos tróficos en individuos juveniles de Pingüino Patagónico (Spheniscus magellanicus) provenientes de las costas de Brasil. El análisis se llevó a cabo sobre las porciones basal y distal de las uñas, correspondientes a la temporada invernal y a la reproductiva, respectivamente, en función del tiempo de integración de la señal isotópica determinado por la tasa de crecimiento de la uña y la fecha de colecta. Se observaron diferencias significativas en las señales isotópicas de las dietas correspondientes a las temporadas reproductiva e invernal, sugiriendo diferencias en las contribuciones relativas de las presas. Durante la temporada invernal en Brasil hubo una alta contribución del calamar Loligo sanpaulensis y de la anchoíta, mientras que durante la temporada reproductiva la contribución de presas fue más diversa, con una alta proporción de peces. Esto se reflejó en una mayor amplitud de nicho isotópico en la dieta reproductiva que en la invernal, indicando un uso más amplio de los recursos tróficos en áreas reproductivas. El consumo de anchoíta es mayor al previamente reportado para individuos juveniles en áreas invernales.We carried out a stable isotopes analysis on claws to evaluate the diet and the use of trophic resources of Magellanic Penguin (Spheniscus magellanicus) juveniles off Brazil coasts. The analysis was performed on the basal and distal portions of the claws which correspond to wintering and reproductive seasons, respectively, according to the integration time of the isotopic signature based on the growth rate of claws and sample collection date. We found differences in the isotopic signals between winter and reproductive diets, suggesting differences in the relative contribution of different prey. During the wintering season in Brazil there was a high contribution of Loligo sanpaulensis and anchoita, whereas during the breeding season there was a more diverse contribution of prey items, with an important presence of fishes. Consequently, the isotopic niche breadth was higher in reproductive birds which indicates a broader use of trophic resources in breeding areas. We report a higher consumption of anchoita for juvenile individuals in wintering areas compared to previous studies.Fil: Silva, Laura Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Siles, Laura. Universidad de Barcelona; EspañaFil: Cardona, Luis. Universidad de Barcelona; EspañaFil: Tavares, Mauricio. Universidade Federal do Rio Grande do Sul; BrasilFil: Crespo, Enrique Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Gandini, Patricia Alejandra. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Centro de Investigaciones Puerto Deseado; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Arrival of Paleo-Indians to the Southern Cone of South America: New Clues from Mitogenomes

With analyses of entire mitogenomes, studies of Native American mitochondrial DNA (mtDNA) variation have entered the final phase of phylogenetic refinement: the dissection of the founding haplogroups into clades that arose in America during and after human arrival and spread. Ages and geographic distributions of these clades could provide novel clues on the colonization processes of the different regions of the double continent. As for the Southern Cone of South America, this approach has recently allowed the identification of two local clades (D1g and D1j) whose age estimates agree with the dating of the earliest archaeological sites in South America, indicating that Paleo-Indians might have reached that region from Beringia in less than 2000 years. In this study, we sequenced 46 mitogenomes belonging to two additional clades, termed B2i2 (former B2l) and C1b13, which were recently identified on the basis of mtDNA control-region data and whose geographical distributions appear to be restricted to Chile and Argentina. We confirm that their mutational motifs most likely arose in the Southern Cone region. However, the age estimate for B2i2 and C1b13 (11–13,000 years) appears to be younger than those of other local clades. The difference could reflect the different evolutionary origins of the distinct South American-specific sub-haplogroups, with some being already present, at different times and locations, at the very front of the expansion wave in South America, and others originating later in situ, when the tribalization process had already begun. A delayed origin of a few thousand years in one of the locally derived populations, possibly in the central part of Chile, would have limited the geographical and ethnic diffusion of B2i2 and explain the present-day occurrence that appears to be mainly confined to the Tehuelche and Araucanian-speaking grou

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration

The mortality rate for malignant melanoma (MM) is very high, since it is highly invasive and resistant to chemotherapeutic treatments. The modulation of some transcription factors affects cellular processes in MM. In particular, a higher expression of the osteogenic master gene RUNX2 has been reported in melanoma cells, compared to normal melanocytes. By analyzing public databases for recurrent RUNX2 genetic and epigenetic modifications in melanoma, we found that the most common RUNX2 genetic alteration that exists in transcription upregulation is, followed by genomic amplification, nucleotide substitution and multiple changes. Additionally, altered RUNX2 is involved in unchecked pathways promoting tumor progression, Epithelial Mesenchymal Transition (EMT), and metastasis. In order to investigate further the role of RUNX2 in melanoma development and to identify a therapeutic target, we applied the CRISPR/Cas9 technique to explore the role of the RUNT domain of RUNX2 in a melanoma cell line. RUNT-deleted cells showed reduced proliferation, increased apoptosis, and reduced EMT features, suggesting the involvement of the RUNT domain in different pathways. In addition, del-RUNT cells showed a downregulation of genes involved in migration ability. In an in vivo zebrafish model, we observed that wild-type melanoma cells migrated in 81% of transplanted fishes, while del-RUNT cells migrated in 58%. All these findings strongly suggest the involvement of the RUNT domain in melanoma metastasis and cell migration and indicate RUNX2 as a prospective target in MM therapy

Two novel C-terminus RUNX2 mutations in two cleidocranial dysplasia (CCD) patients impairing p53 expression

Cleidocranial dysplasia (CCD), a dominantly inherited skeletal disease, is characterized by a variable phenotype ranging from dental alterations to severe skeletal defects. Either de novo or inherited mutations in the RUNX2 gene have been identified in most CCD patients. Transcription factor RUNX2, the osteogenic master gene, plays a central role in the commitment of mesenchymal stem cells to osteoblast lineage. With the aim to analyse the effects of RUNX2 mutations in CCD patients, we investigated RUNX2 gene expression and the osteogenic potential of two CCD patients’ cells. In addition, with the aim to better understand how RUNX2 mutations interfere with osteogenic differentiation, we performed string analyses to identify proteins interacting with RUNX2 and analysed p53 expression levels. Our findings demonstrated for the first time that, in addition to the alteration of downstream gene expression, RUNX2 mutations impair p53 expression affecting osteogenic maturation. In conclusion, the present work provides new insights into the role of RUNX2 mutations in CCD patients and suggests that an in-depth analysis of the RUNX2-associated gene network may contribute to better understand the complex molecular and phenotypic alterations in mutant subjects

Treatment reduces the incidence of newly appearing multiple sclerosis lesions evolving into chronic active, slowly expanding lesions: A retrospective analysis

Background and purpose: Newly appearing lesions in multiple sclerosis (MS) may evolve into chronically active, slowly expanding lesions (SELs), leading to sustained disability progression. The aim of this study was to evaluate the incidence of newly appearing lesions developing into SELs, and their correlation to clinical evolution and treatment. // Methods: A retrospective analysis of a fingolimod trial in primary progressive MS (PPMS; INFORMS, NCT 00731692) was undertaken. Data were available from 324 patients with magnetic resonance imaging scans up to 3 years after screening. New lesions at year 1 were identified with convolutional neural networks, and SELs obtained through a deformation-based method. Clinical disability was assessed annually by Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test, Timed 25-Foot Walk, and Paced Auditory Serial Addition Test. Linear, logistic, and mixed-effect models were used to assess the relationship between the Jacobian expansion in new lesions and SELs, disability scores, and treatment status. // Results: One hundred seventy patients had ≥1 new lesions at year 1 and had a higher lesion count at screening compared to patients with no new lesions (median = 27 vs. 22, p = 0.007). Among the new lesions (median = 2 per patient), 37% evolved into definite or possible SELs. Higher SEL volume and count were associated with EDSS worsening and confirmed disability progression. Treated patients had lower volume and count of definite SELs (β = −0.04, 95% confidence interval [CI] = −0.07 to −0.01, p = 0.015; β = −0.36, 95% CI = −0.67 to −0.06, p = 0.019, respectively). // Conclusions: Incident chronic active lesions are common in PPMS, and fingolimod treatment can reduce their number