Charge density waves tuned by biaxial tensile stress.

The precise arrangement and nature of atoms drive electronic phase transitions in condensed matter. To explore this tenuous link, we developed a true biaxial mechanical deformation device working at cryogenic temperatures, compatible with x-ray diffraction and transport measurements, well adapted to layered samples. Here we show that a slight deformation of TbTe3 can have a dramatic influence on its Charge Density Wave (CDW), with an orientational transition from c to a driven by the a/c parameter, a tiny coexistence region near a = c, and without space group change. The CDW transition temperature Tc displays a linear dependence with a / c - 1 while the gap saturates out of the coexistence region. This behaviour is well accounted for within a tight-binding model. Our results question the relationship between gap and Tc in RTe3 systems. This method opens a new route towards the study of coexisting or competing electronic orders in condensed matter.

Trombosis venosa cerebral / Cerebral venous thrombosis

La trombosis venosa cerebral forma parte de las llamadas trombosis en sitios inusuales. Se define como una oclusión en el territorio venoso cerebral. Su incidencia se encuentra en aumento progresivo, especialmente en países en vías de desarrollo. Se observa con más frecuencia en mujeres jóvenes, siendo los factores hormonales, como el embarazo o la anticoncepción hormonal, factores de riesgo principales en el desarrollo de esta afección. La clínica va a depender fundamentalmente de la topografía de la trombosis, con un diagnóstico de confirmación basado principalmente en las pruebas de imagen. El tratamiento consiste generalmente en la anticoagulación, pudiendo plantearse otras opciones según la gravedad del cuadro. En general, el pronóstico es mejor que el de otros trastornos vasculares intracraneales. En esta revisión se describe la evidencia actual disponible acerca de la trombosis venosa cerebral.(AU)

Cerebral venous thrombosis is part of the so-called thrombosis in unusual sites. It is defined as an occlusion in the cerebral venous territory. Its incidence is progressively increasing, especially in developing countries. It is more frequently observed in young women, with hormonal factors such as pregnancy or hormonal contraception being significant risk factors in the development of this condition. The clinical presentation will depend fundamentally on the topography of the thrombosis, with a confirmatory diagnosis based mainly on imaging tests. The treatment generally consists of anticoagulation, and other options may be considered depending on the severity of the case. Overall, the prognosis is better than that of other intracranial vascular disorders. This review describes the current evidence available regarding cerebral venous thrombosis.(AU)

Cerebral venous thrombosis.

Cerebral venous thrombosis is part of the so-called thrombosis in unusual sites. It is defined as an occlusion in the cerebral venous territory. Its incidence is progressively increasing, especially in developing countries. It is more frequently observed in young women, with hormonal factors such as pregnancy or hormonal contraception being significant risk factors in the development of this condition. The clinical presentation will depend fundamentally on the topography of the thrombosis, with a confirmatory diagnosis based mainly on imaging tests. The treatment generally consists of anticoagulation, and other options may be considered depending on the severity of the case. Overall, the prognosis is better than that of other intracranial vascular disorders. This review describes the current evidence available regarding cerebral venous thrombosis.

Osteogenic-angiogenic coupled response of cobalt-containing mesoporous bioactive glasses in vivo.

The incorporation of cobalt ions into the composition of bioactive glasses has emerged as a strategy of interest for bone regeneration purposes. In the present work, we have designed a set of bioactive mesoporous glasses SiO2-CaO-P2O5-CoO (Co-MBGs) with different amounts of cobalt. The physicochemical changes introduced by the Co2+ ion, the in vitro effects of Co-MBGs on preosteoblasts and endothelial cells and their in vivo behaviour using them as bone grafts in a sheep model were studied. The results show that Co2+ ions neither destroy mesoporous ordering nor inhibit in vitro bioactive behaviour, exerting a dual role as network former and modifier for CoO concentrations above 3 % mol. On the other hand, the activity of Co-MBGs on MC3T3-E1 preosteoblasts and HUVEC vascular endothelial cells is dependent on the concentration of CoO present in the glass. For low Co-MBGs concentrations (1mg/ml) cell viability is not affected, while the expression of osteogenic (ALP, RUNX2 and OC) and angiogenic (VEGF) genes is stimulated. For Co-MBGs concentration of 5 mg/ml, cell viability decreases as a function of the CoO content. In vivo studies show that the incorporation of Co2+ ions to the MBGs improves the bone regeneration activity of these materials, despite the deleterious effect that this ion has on bone-forming cells for any of the Co-MBG compositions studied. This contradictory effect is explained by the marked increase in angiogenesis that takes place inside the bone defect, leading to an angiogenesis-osteogenesis coupling that compensates for the partial decrease in osteoblast cells. STATEMENT OF SIGNIFICANCE: The development of new bone grafts implies to address the need for osteogenesis-angiogenesis coupling that allows bone regeneration with viable tissue in the long term. In this sense the incorporation of cobalt ions into the composition of bioactive glasses has emerged as a strategy of great interest in this field. Due to the potential cytotoxic effect of cobalt ions, there is an important controversy regarding the suitability of their incorporation in bone grafts. In this work, we address this controversy after the implantation of cobalt-doped mesoporous bioactive glasses in a sheep model. The incorporation of cobalt ions in bioactive glasses improves the bone regeneration ability of these bone grafts, due to enhancement of the angiogenesis-osteogenesis coupling.

HIF-1 inactivation empowers HIF-2 to drive hypoxia adaptation in aggressive forms of medulloblastoma.

Medulloblastoma (MB) is the most prevalent brain cancer in children. Four subgroups of MB have been identified; of these, Group 3 is the most metastatic. Its genetics and biology remain less clear than the other groups, and it has a poor prognosis and few effective treatments available. Tumor hypoxia and the resulting metabolism are known to be important in the growth and survival of tumors but, to date, have been only minimally explored in MB. Here we show that Group 3 MB tumors do not depend on the canonical transcription factor hypoxia-inducible factor-1α (HIF-1α) to mount an adaptive response to hypoxia. We discovered that HIF-1α is rendered inactive either through post-translational methylation, preventing its nuclear localization specifically in Group 3 MB, or by a low expression that prevents modulation of HIF-target genes. Strikingly, we found that HIF-2 takes over the role of HIF-1 in the nucleus and promotes the activation of hypoxia-dependent anabolic pathways. The exclusion of HIF-1 from the nucleus in Group 3 MB cells enhances the reliance on HIF-2's transcriptional role, making it a viable target for potential anticancer strategies. By combining pharmacological inhibition of HIF-2α with the use of metformin, a mitochondrial complex I inhibitor to block respiration, we effectively induced Group 3 MB cell death, surpassing the effectiveness observed in Non-Group 3 MB cells. Overall, the unique dependence of MB cells, but not normal cells, on HIF-2-mediated anabolic metabolism presents an appealing therapeutic opportunity for treating Group 3 MB patients with minimal toxicity.

Correlación entre la sensibilidad al contraste y las características morfológicas obtenidas por OCT en pacientes con degeneración macular relacionada con la edad avanzada tratados con dosis de carga de inhibidores del factor de crecimiento endotelial vascular / Correlation between contrast sensitivity and morphological features obtained by OCT in patients with age-related macular degeneration treated with a loading dose of vascular endothelial growth factor inhibitors

Objetivo Determinar la correlación entre la sensibilidad al contraste y las características morfológicas obtenidas por tomografía de coherencia óptica en pacientes con degeneración macular relacionada con la edad avanzada tratados con dosis de carga de inhibidores del factor de crecimiento endotelial vascular (anti-VEGF). Diseño Se trata de un estudio ambispectivo (prospectivo+retrospectivo) observacional y analítico. Participantes Todos los pacientes de 55 años o más con degeneración macular relacionada con la edad que acudieron al departamento de Retina del servicio de Oftalmología y cumplieron con los criterios de inclusión entre marzo-mayo de 2022. Métodos Se recolectaron los datos por medio de la revisión de expedientes. Se analizaron los estudios de tomografía de coherencia óptica previa a la aplicación de inyecciones intravítreas de los pacientes que se encontraban en el mes posterior a la última dosis. Se incluyeron un total de 33 sujetos y un total de 30 continuaron seguimiento. Se realizaron pruebas de normalidad (Shapiro y Bartlett) entre los grupos de estudio, dando como resultado grupos no normales no homocedásticos. Los sujetos fueron sometidos a una nueva evaluación oftalmológica y nueva toma de mediciones retinianas. Resultados Se realizó un análisis de regresión lineal comparando los valores logarítmicos de la agudeza visual y la sensibilidad al contraste, obteniendo una relación significativa entre ambos valores posterior a la aplicación del tratamiento (p<0,0001). Asimismo, se demostró una correlación entre la disminución de los valores de la sensibilidad al contraste y todas las características evaluadas en el tomografía de coherencia óptica. Conclusiones Las estrategias de antiangiogénesis pueden conducir a mejores resultados en la función visual global, impactando positivamente en la sensibilidad al contraste (AU)

Objective To determine the correlation between contrast sensitivity and morphological characteristics obtained by optical coherence tomography in patients with age-related macular degeneration treated with a loading dose of vascular endothelial growth factor inhibitors (anti-VEGF). Design This is an ambispective (prospective+retrospective) observational, cross-sectional, and analytical study. Participants All patients over 55 years of age with age-related macular degeneration who attended the Retina service of the Ophthalmology department and met the inclusion criteria between March-May 2022. Methods Data collection was carried out by reviewing the records of patients.Optical coherence tomography studies prior to the application of intravitreal injections of patients who were currently in the first month after the last dose of anti-VEGF were analyzed. A total of 33 subjects were included, of which 30 continued follow-ups. Normality tests (Shapiro and Bartlett) were performed where a nonparametric data distribution was demonstrated. The subjects underwent a new ophthalmological evaluation and new retinal measurements of the affected eye. Results A linear regression analysis was performed comparing the logarithmic values of both visual acuity and contrast sensitivity, obtaining a significant relationship between both values after the application of treatment (P<.0001). Likewise, correlation was demonstrated between the decrease in contrast sensitivity values and all the characteristics evaluated in the patients’ optical coherence tomography. Conclusions Antiangiogenesis strategies can lead to better results in global visual function, positively impacting contrast sensitivity (AU)

Correlation between contrast sensitivity and morphological features obtained by OCT in patients with age-related macular degeneration treated with a loading dose of vascular endothelial growth factor inhibitors.

OBJECTIVE: To determine the correlation between contrast sensitivity and morphological characteristics obtained by Optical Coherence Tomography (OCT) in patients with Age-Related Macular Degeneration treated with a loading dose of vascular endothelial growth factor inhibitors (anti-VEGF). DESIGN: This is an ambispective (prospective + retrospective) observational, cross-sectional, and analytical study. PARTICIPANTS: All patients over 55 years of age with Age-Related Macular Degeneration who attended the Retina service of the Ophthalmology department and met the inclusion criteria between March-May 2022. METHODS: Data collection was carried out by reviewing the records of patients diagnosed with Age-Related Macular Degeneration of the neovascular variety treated with the loading dose of anti-VEGF. OCT studies obtained by Optovue® iVue80 prior to the application of intravitreal injections of patients who met the inclusion criteria and were currently in the first month after the last dose of anti-VEGF were analyzed. A total of 33 subjects were included, of which 30 continued follow-ups. The subjects underwent a new ophthalmological evaluation and new retinal measurements of the affected eye. Normality tests (Shapiro‒Wilk) were performed where a nonparametric data distribution was demonstrated. RESULTS: A linear regression analysis was performed comparing the logarithmic values of both visual acuity and contrast sensitivity, obtaining a significant relationship between both values after the application of treatment (P = <.0001***). Likewise, correlation was demonstrated between the decrease in contrast sensitivity values and all the characteristics evaluated in the patients' OCT. CONCLUSIONS: Antiangiogenesis strategies can lead to better results in global visual function, positively impacting contrast sensitivity.

Is off-label thrombolysis safe and effective in a real-life primary stroke center? A retrospective analysis of data from a 5-year prospective database.

BACKGROUND: Intravenous thrombolysis (IVT) use for acute ischemic stroke (AIS) varies among countries, partly due to guidelines and product labeling changes. The study aim was to identify the characteristics of patients with AIS treated with off-label IVT and to determine its safety when performed in a primary stroke center (PSC). METHODS: This observational, single-center study included all consecutive patients admitted to Perpignan PSC for AIS and treated with IVT and patients transferred for EVT, between January 1, 2015 and December 31, 2019. Data of patients treated with IVT according to ("in-label group") or outside ("off-label") the initial guidelines and manufacturer's product specification were compared. Safety was assessed using symptomatic intracerebral hemorrhage (SIH) as the main adverse event. RESULTS: Among the 892 patients in the database (834 screened by MRI, 93.5%), 746 were treated by IVT: 185 (24.8%) "in-label" and 561 (75.2%) "off-label". In the "off-label" group, 316 (42.4% of the cohort) had a single criterion for "off-label" use, 197 (26.4%) had two, and 48 (6.4%) had three or more criteria, without any difference in IVT safety pattern among them. SIH rates were comparable between the "off-label" and "in-label" groups (2.7% vs. 1.1%, P=0.21); early neurological deterioration and systematic adverse event due to IVT treatment were similar in the 2 groups. "Off-label" patients had higher in-hospital (8.7% vs. 3.8%, P=0.05) and 3-month mortality rates (12.1% vs 5.4%, P<0.01), but this is explained by confounding factors as they were older (76 vs 67 years, P<0.0001) and more dependent (median modified Rankin scale score 0.4 vs 0.1, P<0.0001) at admission. CONCLUSIONS: "Off-label" thrombolysis for AIS seems to be safe and effective in the routine setting of a primary stroke center.

Injectable mesoporous bioactive nanoparticles regenerate bone tissue under osteoporosis conditions.

The osteogenic capability of mesoporous bioactive nanoparticles (MBNPs) in the SiO2CaO system has been assessed in vivo using an osteoporotic rabbit model. MBNPs have been prepared using a double template method, resulting in spherical nanoparticles with a porous core-shell structure that has a high surface area and the ability to incorporate the anti-osteoporotic drug ipriflavone. In vitro expression of the pro-inflammatory genes NF-κB1, IL-6, TNF-α, P38 and NOS2 in RAW-264.7 macrophages, indicates that these nanoparticles do not show adverse inflammatory effects. An injectable system has been prepared by suspending MBNPs in a hyaluronic acid-based hydrogel, which has been injected intraosseously into cavitary bone defects in osteoporotic rabbits. The histological analyses evidenced that MBNPs promote bone regeneration with a moderate inflammatory response. The incorporation of ipriflavone into these nanoparticles resulted in a higher presence of osteoblasts and enhanced angiogenesis at the defect site, but without showing significant differences in terms of new bone formation. STATEMENT OF SIGNIFICANCE: Mesoporous bioactive glass nanoparticles have emerged as one of the most interesting materials in the field of bone regeneration therapies. For the first time, injectable mesoporous bioactive nanoparticles have been tested in vivo using an osteoporotic animal model. Our findings evidence that MBG nanoparticles can be loaded with an antiosteoporotic drug, ipriflavone, and incorporated in hyaluronic acid to make up an injectable hydrogel. The incorporation of MBG nanoparticles promotes bone regeneration even under osteoporotic conditions, whereas the presence of IP enhances angiogenesis as well as the presence of osteoblast cells lining in the newly formed bone. The injectable device presented in this work opens new possibilities for the intraosseous treatment of osteoporotic bone using minimally invasive surgery.

Unravelling groundwater and surface water sources in the Esteros del Iberá Wetland Area: An isotopic approach.

In the Esteros del Iberá Wetland Area (EIWA, NE Argentina), the southern sector of the transboundary Guarani Aquifer System (SAG) is overlain by the Ramsar listed Iberá Wetlands and several rivers, that combined extend across 37,930 km2 and represent one of the largest freshwater systems on the South American continent. Previous hydrogeological studies encompassing the entire SAG proposed preferential discharge of groundwater of various origins and ages to the EIWA. In this study, a multi-tracer study using major ionic species, δ18O, δ2H and 222Rn was conducted in lagoons, rivers, wells, and boreholes in the EIWA to confirm if discharge from the transboundary SAG is contributing to the surface water system. End-member Mixing Analysis (EMMA) determined the existence of four main end-members: groundwater from the SAG, more saline groundwater from the deeper Pre-SAG, and two poorly mineralised end-members from shallow, Post-SAG. EMMA calculations clearly illustrated complex binary and ternary mixing patterns involving the four end-members and highlighted the role of geological structures, specifically regional steep faults, in controlling the mixing patterns. 222Rn activities allowed in-situ identification of preferential deep groundwater discharge into both surface waters and shallow groundwaters. These findings provide strong evidence for the widespread existence of upward flows along major faults in this sector of the SAG, inducing complex mixing flow patterns and explaining the presence of old groundwater in shallow aquifers. Mapping the sources of water and the hydrological interactions are relevant for improving water balance estimates and develop management policies towards the preservation of these wetlands.

Water stable isotopes reveal a complex rainfall to groundwater connectivity in central Honduras.

The inter-mountainous region of central Honduras has been experiencing abrupt urban drinking water shortages during the last decade. Land use fragmentation and rainfall deficits have rapidly reduced surface water quality and quantity in this region. Here we present a 3-yr (2018-2020) tracer study within the headwaters of the Choluteca River basin (2949 km2). We sampled rainfall (weekly N = 156; daily N = 270), drilled wells (N = 166; up to ~300 m depth), boreholes (N = 70; ~4-12 m depth), and springs (N = 128) to assess the spatiotemporal connectivity between rainfall and mean groundwater recharge elevations (MREs). Clear W-shaped incursions characterized rainfall isotopic seasonality from the dry to the wet season. Air mass back trajectory analysis revealed three primary moisture sources: 73 % (east, Caribbean Sea), 17 % (southwest, Pacific Ocean), and 10 % (north; Gulf of Mexico). Groundwater sources exhibited a strong meteoric origin with evidence of secondary evaporation evolution, characterized by low d-excess values. MREs for the drilled wells ranged from 821 to 2018 m asl with a mean value of 1570 ± 150 m asl. Seasonal isotopic variability during dry-wet transitions and the influence of rapid infiltration limited the performance of the MRE method in springs and boreholes. MREs coincided primarily with coniferous forests, pasture, and crop areas, within regions of moderate to high transmissivity. These results are intended to guide the mapping and delineation of critical recharge areas in central Honduras to enhance municipal water regulations, effective environmental protection, and long-term conservation practices.

Cuidados de enfermería en la elefantisis verrucosa nostra. A propósito de un caso / Nursing care in the treatment of elephantiasis nostras verrucosa and myiasis with 20% trichloroacetic acid: A case report

Introducción: La elefantiasis verrucosa nostra es una afección dermatológica deformante poco frecuente asociada al linfedema crónico. Se caracteriza por presentar edema de la parte afectada con fibrosis progresiva de aspecto leñoso de la dermis y el tejido subcutáneo, hiperqueratosis de la epidermis y lesiones papilomatosas y verrucosas que dan una apariencia de empedrado a la piel.Presentación del caso:La paciente, además de sufrir elefantisis verrucosa nostra en ambas extremidades, también sufría colonización por larvas de díptero, úlceras por presión en ambos talones y un estado general de salud muy deteriorado. Se realizó un plan de atención de enfermería (PAE), valorando a la paciente según las 14 Necesidades Básicas Humanas de Virginia Henderson, seguida de una fase diagnóstica según la North American Nursing Diagnosis Association (NANDA) realizando una planificación de objetivos basándonos en la Nursing Outcomes Classification (NOC) y llevando a cabo una serie de intervenciones con actividades específicas apoyándonos en la Nursing Interventions Classification (NIC), realizando una evaluación constante de la evolución de la paciente.Para apreciar la evolución del PAE focalizando en un mismo diagnóstico NANDA, “Deterioro de la integridad cutánea”, a lo largo de todo el proceso hospitalario de la paciente y como el tratamiento de la afección con ácido tricloracético al 20% (TCA 20%) mejoró el estado de la piel.Conclusiones:El tratamiento con ácido tricloroacético al 20% ha resultado efectivo frente a la elefantisis verrucosa nostra, reduciendo la hiperqueratosis hasta obtener una piel aceptablemente sana. El seguimiento del plan de atención a enfermería a lo largo del todo el proceso garantiza los cuidados necesarios para una correcta recuperación del paciente. (AU)

Introduction: Elephantiasis Verrucosa Nostra is a rare deforming dermatologic condition associated with chronic lymphedema. It is characterized by edema of the affected area with progressive woody fibrosis of the dermis and the subcutaneous tissue, hyperkeratosis of the epidermis, and papillomatous and verrucous lesions that give the skin a cobblestone appearance.Case presentation:The patient, in addition to suffering from elephantitisis verrucosa nostra on both limbs, also suffered from dipteran larvae colonisation, pressure ulcers on both heels and aexceptionally deteriorated health condition.A Nursing Care Plan (PAE) was carried out, Assessing the patient according to Virginia Henderson's 14 Basic Human Needs, followed by a diagnostic phase according to the North American Nursing Diagnosis Association (NANDA), carrying out a planning of objectives based on the Nursing Outcomes Classification (NOC) and accomplishing a series of interventions with specific activities based on the Nursing Interventions Classification (NIC), getting a constant evaluation of thepatient's evolution. In order to appreciate the PAE's evolution focusing on the same NANDA diagnosis, “Deterioration of Skin Integrity”, throughout the entire hospital process and how thedisease's treatment with 20% trichloroacetic acid (TCA 20%) improved the condition of the skin.Conclusions:Treatment with 20% trichloroacetic acid has been effective against elephantiasis verrucosa nostra, reducing hyperkeratosis to an acceptably healthy skin. The monitoring of the nursing care plan throughout the entire process guarantees the necessary care for the correct recovery of the patient. (AU)

Activating stress memory: eustressors as potential tools for plant breeding.

Plants are continuously exposed to stress conditions, such that they have developed sophisticated and elegant survival strategies, which are reflected in their phenotypic plasticity, priming capacity, and memory acquisition. Epigenetic mechanisms play a critical role in modulating gene expression and stress responses, allowing malleability, reversibility, stability, and heritability of favourable phenotypes to enhance plant performance. Considering the urgency to improve our agricultural system because of going impacting climate change, potential and sustainable strategies rely on the controlled use of eustressors, enhancing desired characteristics and yield and shaping stress tolerance in crops. However, for plant breeding purposes is necessary to focus on the use of eustressors capable of establishing stable epigenetic marks to generate a transgenerational memory to stimulate a priming state in plants to face the changing environment.

Venous thromboembolism incidence in cancer patients with germline BRCA mutations

BackgroundGermline BRCA (gBRCA) mutations predispose to an increased risk of breast and ovarian cancer among other neoplasms. Recently, several genomic alterations such as ALK and ROS-1 rearrangements have been described as molecular drivers of venous thromboembolism (VTE). The association of gBRCA mutations and VTE is unknown.Materials and methodsWe performed an observational, retrospective, single-center study to determine the VTE incidence in consecutive patients with gBRCA mutations and cancer diagnosis attended in the multidisciplinary heredofamiliar cancer unit (HFCU) of Hospital General Universitario Gregorio Marañón, Spain, from 2010 to 2019.ResultsOne-hundred and forty-one patients were included in the analysis. The overall VTE incidence was 12.8%. The highest incidence was reported in ovarian cancer patients (20.0%), followed by patients with both ovarian and breast cancers (16.6%) and the lowest was found in breast cancer (4.9%). No difference in the type of gBRCA mutation (1 or 2) in terms of VTE rate was observed. Sixty one percent of the patients were receiving anti-cancer therapy at the time of VTE diagnosis and the majority of the events (83.3%) were diagnosed in ambulatory setting. Khorana score was of limited value to detect high-risk patients.ConclusionsThe VTE incidence observed in our study is consistent with prior data described in general population of breast and ovarian cancer. The risk of VTE in these patients seems to be driven by the type of cancer. We have not observed any significant interaction of gBRCA mutation status and cancer-associated thrombosis.

Delivery of Anti-IFNAR1 shRNA to Hepatic Cells Decreases IFNAR1 Gene Expression and Improves Adenoviral Transduction and Transgene Expression.

Chronic liver injury leads to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Genetical cell treatment related to the use of adenovirus (Ads) has proven to be beneficial and efficient in the recovery of hepatic diseases. Nevertheless, they are highly immunogenic and trigger an immune response where interferons type 1 (IFN-I) play a very important role. Three shRNAs against the Interferon-1 receptor (IFNAR1) were designed and cloned in pENTR/U6 plasmid and amplified in DH5α cells. Huh7 cells were transfected with these plasmids in the presence or absence of 1 × 109 viral particles/ml of adenovirus containing the green fluorescent protein gene used as a reporter. Transfection with the shRNA plasmids partially inhibited the IFNAR1 expression. This inhibition substantially decreased antiviral response, demonstrated by the decrease of IFNAR1, IFN-α, and TNF-α gene expression, and the decrease at protein levels of IFNAR1, Protein kinase RNA-activated (PKR), and phosphorylated STAT1, allowing higher adenoviral transduction and transgene expression. Interestingly it was seen shRNA inhibited macrophage activation. These results suggest that the inhibition of the IFN-I pathway could be a strategy to minimize the immune response against Adenoviral vectors allowing higher Adenovirus transduction extending the transgene expression.

Venous thromboembolism incidence in cancer patients with germline BRCA mutations.

BACKGROUND: Germline BRCA (gBRCA) mutations predispose to an increased risk of breast and ovarian cancer among other neoplasms. Recently, several genomic alterations such as ALK and ROS-1 rearrangements have been described as molecular drivers of venous thromboembolism (VTE). The association of gBRCA mutations and VTE is unknown. MATERIALS AND METHODS: We performed an observational, retrospective, single-center study to determine the VTE incidence in consecutive patients with gBRCA mutations and cancer diagnosis attended in the multidisciplinary heredofamiliar cancer unit (HFCU) of Hospital General Universitario Gregorio Marañón, Spain, from 2010 to 2019. RESULTS: One-hundred and forty-one patients were included in the analysis. The overall VTE incidence was 12.8%. The highest incidence was reported in ovarian cancer patients (20.0%), followed by patients with both ovarian and breast cancers (16.6%) and the lowest was found in breast cancer (4.9%). No difference in the type of gBRCA mutation (1 or 2) in terms of VTE rate was observed. Sixty one percent of the patients were receiving anti-cancer therapy at the time of VTE diagnosis and the majority of the events (83.3%) were diagnosed in ambulatory setting. Khorana score was of limited value to detect high-risk patients. CONCLUSIONS: The VTE incidence observed in our study is consistent with prior data described in general population of breast and ovarian cancer. The risk of VTE in these patients seems to be driven by the type of cancer. We have not observed any significant interaction of gBRCA mutation status and cancer-associated thrombosis.

Strontium and oxygen isotopes to trace mobility routes during the Bell Beaker period in the north of Spain.

Strontium and oxygen isotopes of individuals from El Hundido and Valdescusa (north of Spain) sites, corresponding to the Bell Beaker culture, were analysed in order to determine mobility patterns and provenance areas. Strontium and oxygen isotope ratios in three teeth from two individuals at El Hundido and two teeth from the five individuals at Valdescusa were studied. The analyses were performed in both dentine and enamel fractions. 87Sr/86Sr ratios of El Hundido individuals indicate one was of foreign origin and the other was local whereas at Valdescusa were all of foreign provenance. Calculated δ18Ow values of El Hundido suggest a provenance from the geographical area close to the site while the Valdescusa would come from a warmer region. The comparison of oxygen and strontium isotope signatures indicate the west of the Iberian Peninsula (Zamora or the east of Leon regions) as the provenance area for the foreign individual at El Hundido and southwest France (Garonne basin) as the region of provenance for the Valdescusa.

Research opportunities: Traditional fermented beverages in Mexico. Cultural, microbiological, chemical, and functional aspects.

In Mexico, close to 200 fermented products have been described, of which, approximately 20 are beverages. They were obtained through rustic and ancestral fermentation methods by different indigenous Mexican communities; most of them were used in ceremonies, agricultural work, and other occasions. For their elaboration, different substrates obtained from plants are used, where uncontrolled and low-scale spontaneous anaerobic fermentation occurs. In Mexico, some of these products are considered as nutritional sources and functional beverages; the study of those products has revealed the presence of multiple compounds of biological importance. Additionally, elder generations attribute healing properties against diverse illnesses to these beverages. The aim of this review is to highlight the available information on twelve traditional Mexican fermented beverages, their traditional uses, and their fermentation processes along with toxicological, chemical, nutritional, and functional studies as seen from different areas of investigation. In the literature, pulque, cocoa, and pozol were the beverages with the greatest amount of described health properties; sendechó and guarapo were less characterized. Polyphenols, gallic and ferulic acid, anthocyanins and saponins were the most abundant molecules in all beverages. Finally, it is important to continue this research in order to determine the microorganisms that are involved in the fermentation process, as well as the organoleptic and beneficial properties they lend to the traditional Mexican fermented beverages.