2,607 research outputs found
Endovascular treatment for acute basilar artery occlusion: Descriptive analysis of the experience in a comprehensive stroke centre
Objectives: To describe the clinical and epidemiological characteristics of patients with basilar artery occlusion (BAO) treated with mechanical thrombectomy (MT) in Aragón, and to compare its anaesthetic management, technical effectivity, security, and prognosis with those of anterior circulation. Methods: 322 patients from the prospective registry of mechanical thrombectomies from Aragon were assessed: 29 with BAO and 293 with an anterior circulation large vessel occlusion. Baseline characteristics, procedural, clinical and safety outcomes variables were compared. Results: Out of 29 patients with BAO that underwent endovascular therapy (62.1% men; average age 69.8 ± 14.05 years) 18 (62.1%) received endovascular therapy (EVT) alone and 11 (37.9%) EVT plus intravenous thrombolysis. Atherothrombotic stroke was the most common etiology (41%). The BAO group had longer Door-to-groin (160 vs 141 min; P = 0.043) and Onset-to-reperfusion times (340 vs 297 min; P = 0.005), and higher use of general anaesthesia (60.7% vs 14.7%; P < 0.01). No statistically significant difference was found for Procedure time (60 vs 50 min; P = 0.231) nor the rate of successful recanalization (72.4% vs 82.7%; P = 0.171). Functional independence at 90 days was significantly worse in the BAO group (17.9% vs 38.2%; P < 0.01). Conclusions: Patients with basilar artery occlusion had higher morbimortality despite similar angiographic results. Mechanical thrombectomy for BAOs is a safe and effective procedure in selected patients. A consensus about the effect of anaesthesia has yet to be reached, for BAO general anaesthesia remains the most frequently used technique
Comparation of the new rebound tonometer IOPen and the Goldmann tonometer, and their relationship to corneal properties
Purpose To compare the intraocular pressures
(IOPs) obtained with the IOPen rebound
tonometer, Goldmann applanation tonometer
(GAT) and the ocular response analyzer (ORA)
and investigate the effects of corneal
biomechanical properties on IOPen
measurements.
Methods A total of 198 normal eyes were
included in this cross-sectional and
randomized study. Three measurements were
taken using IOPen. Agreement between
tonometers was calculated using the Bland
and Altman limits of agreement (LoA)
analysis.
Results The median IOPen IOP was 3mmHg
below the GAT (Po0.001), 3mmHg below
the ORA IOP similar to Goldmann (IOPg),
and 3mmHg below the ORA IOP corrected
using corneal parameters (IOPcc)(Po0.01).
The LoA width between the IOPen and GAT
IOPs varied between 13.92 (mean IOPen IOP)
and 15.99mmHg (third IOPen measurement).
The central corneal thickness (CCT) was
unrelated to IOPen measurements (P40.05).
Corneal hysteresis (CH) and corneal rigidity
factor (CRF) were correlated with IOPen
and GAT.
Conclusions IOPen underestimated the IOP
compared with GAT and ORA. The effect of
measurement quality or measurement order on
IOPen was low. CCT did not affect the IOPen,
but the CH and CRF did. The LoA width
between the IOPen and GAT IOPs was higher
than between the ORA IOPg or ORA IOPcc
and GAT IOPs
Bisphenol A Induces Accelerated Cell Aging in Murine Endothelium.
Bisphenol A (BPA) is a widespread endocrine disruptor affecting many organs and systems. Previous work in our laboratory demonstrated that BPA could induce death due to necroptosis in murine aortic endothelial cells (MAECs). This work aims to evaluate the possible involvement of BPA-induced senescence mechanisms in endothelial cells. The β-Gal assays showed interesting differences in cell senescence at relatively low doses (100 nM and 5 µM). Western blots confirmed that proteins involved in senescence mechanisms, p16 and p21, were overexpressed in the presence of BPA. In addition, the UPR (unfolding protein response) system, which is part of the senescent phenotype, was also explored by Western blot and qPCR, confirming the involvement of the PERK-ATF4-CHOP pathway (related to pathological processes). The endothelium of mice treated with BPA showed an evident increase in the expression of the proteins p16, p21, and CHOP, confirming the results observed in cells. Our results demonstrate that oxidative stress induced by BPA leads to UPR activation and senescence since pretreatment with N-acetylcysteine (NAC) in BPA-treated cells reduced the percentage of senescent cells prevented the overexpression of proteins related to BPA-induced senescence and reduced the activation of the UPR system. The results suggest that BPA participates actively in accelerated cell aging mechanisms, affecting the vascular endothelium and promoting cardiovascular diseases.post-print3206 K
Ischaemic Stroke in the Time of Coronavirus Disease 2019
Each year, between 1.1 and 1.5 million Europeans have a stroke1. Two to three out of 10 patients die as a consequence of it and about one third remains functionally dependent2. As we know, the likelihood of a favourable outcome in this disease relies heavily on patients presenting promptly after symptoms onset and on hospitals providing immediate access to optimized stroke care
Comparison of the renal effects of bisphenol A in mice with and without experimental diabetes. Role of sexual dimorphism.
Bisphenol-A (BPA), a chemical -xenoestrogen- used in the production of the plastic lining of food and beverage containers, is present in the urine of almost the entire population. Recent studies have shown that BPA exposure is associated with podocytopathy, increased urinary albumin excretion (UAE), and hypertension. Since these changes are characteristic of early diabetic nephropathy (DN), we explored the renal effects of BPA and diabetes including the potential role of sexual dimorphism. Male and female mice were included in the following animals' groups: control mice (C), mice treated with 21.2 mg/kg of BPA in the drinking water (BPA), diabetic mice induced by streptozotocin (D), and D mice treated with BPA (D + BPA). Male mice form the D + BPA group died by the tenth week of the study due probably to hydro-electrolytic disturbances.
Although BPA treated mice did not show an increase in serum creatinine, as observed in D and D + BPA groups, they displayed similar alteration to those of the D group, including increased in kidney damage biomarkers NGAL and KIM-1, UAE, hypertension, podocytopenia, apoptosis, collapsed glomeruli, as well as TGF-β, CHOP and PCNA upregulation. UAE, collapsed glomeruli, PCNA staining, TGF-β, NGAL and animal survival, significantly impaired in D + BPA animals. Moreover, UAE, collapsed glomeruli and animal survival also displayed a sexual dimorphism pattern.
In conclusion, oral administration of BPA is capable of promoting in the kidney alterations that resemble early DN. Further translational studies are needed to clarify the potential role of BPA in renal diseases, particularly in diabetic patients.pre-print3531 K
Brain structures identification based on feature descriptor
Traumatic Brain Injury -TBI- -1- is defined as an acute event that causes certain damage to areas of the brain. TBI may result in a significant impairment of an individuals physical, cognitive and psychosocial functioning. The main consequence of TBI is a dramatic change in the individuals daily life involving a profound disruption of the family, a loss of future income capacity and an increase of lifetime cost. One of the main challenges of TBI Neuroimaging is to develop robust automated image analysis methods to detect signatures of TBI, such as: hyper-intensity areas, changes in image contrast and in brain shape. The final goal of this research is to develop a method to identify the altered brain structures by automatically detecting landmarks on the image where signal changes and to provide comprehensive information to the clinician about them. These landmarks identify injured structures by co-registering the patient?s image with an atlas where landmarks have been previously detected. The research work has been initiated by identifying brain structures on healthy subjects to validate the proposed method. Later, this method will be used to identify modified structures on TBI imaging studies
Lipoic acid inhibits leptin secretion and Sp1 activity in adipocytes
Lipoic acid (LA) is an antioxidant with therapeutic potential on several diseases such as diabetes and obesity. Hyperleptinemia and oxidative stress play a major role in the development of obesity-linked diseases. The aim of this study was to examine in vivo and in vitro the effects of LA on leptin production, as well as to elucidate the mechanisms and signalling pathways involved in LA actions. Methods and results: Dietary supplementation with LA decreased both circulating leptin, and adipose tissue leptin mRNA in rats. Treatment of 3T3-L1 adipocytes with LA caused a concentration-dependent inhibition of leptin secretion and gene expression. Moreover, LA stimulated the anaerobic utilization of glucose to lactate, which negatively correlated with leptin secretion. Furthermore, LA enhanced phosphorylation of Sp1 and inhibited Sp1 transcriptional activity in 3T3-L1 adipocytes. Moreover, LA inhibited Akt phosphorylation, a downstream target of phosphatidylinositol 3-kinase (PI3K). Treatment with the PI3K inhibitor LY294002 mimicked LA actions, dramatically inhibiting both leptin secretion and gene expression and stimulating Sp1 phosphorylation. Conclusion: All of these data suggest that the phosphorylation of Sp1 and the accompanying reduced DNA-binding activity are likely to be involved in the inhibition of leptin induced by LA, which could be mediated in part by the abrogation of the PI3K/Akt pathway
Demographic history and population structure of Anopheles pseudopunctipennis in Argentina based on the mitochondrial COI gene
Background: Anopheles pseudopunctipennis is an important malaria vector in the Neotropical region and the only species involved in Plasmodium transmission in the Andean foothills. Its wide geographical distribution in America, high preference for biting humans and capacity to rest inside dwellings after feeding, are attributes contributing to its vector status. Previous reports have tried to elucidate its taxonomic status, distinguishing populations from North, Central and South America. In the present study we used a mitochondrial marker to examine the demographic history of An. pseudopunctipennis in northwestern Argentina.
Methods: Twelve localities were selected across 550 km of the distribution of this species in Argentina, including two near the Bolivian border and several in South Tucumán, for sampling. A fragment of the cytochrome oxidase I (COI) gene was sequenced and haplotype relationships were analyzed by a statistical parsimony network and a Neighbor-Joining (NJ) tree. Genetic differentiation was estimated with FS T. Historical demographic processes were evaluated using diversity measures, neutrality tests and mismatch distribution.
Results: Forty-one haplotypes were identified, of which haplotype A was the most common and widely distributed. Neither the network nor the NJ tree showed any geographic differentiation between northern and southern populations. Haplotype diversities, Tajima’s D T and Fu & Li’s F and D neutrality tests and mismatch distribution supported a scenario of Holocene demographic expansion.
Conclusion: The demographic pattern suggests that An. pseudopunctipennis has undergone a single colonization process, and the ancestral haplotype is shared by specimens from all localities, indicating mitochondrial gene flow. Genetic differentiation was minimal, observed only between one northern and one southern locality. The estimated time of the population expansion of this species was during the Holocene. These data suggest that regional vector control measures would be equally effective in both northern and southern localities sampled, but also that insecticide resistant genes may spread rapidly within this region.Fil: Dantur Juri, Maria Julia. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Superior de Entomología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Moreno, Marta. New York State Department of Health; Estados Unidos. State University Of New York; Estados Unidos. University Of California At San Diego; Estados UnidosFil: Prado Izaguirre, Mónica J.. Universidad Central de Venezuela; VenezuelaFil: Navarro, Juan C.. Universidad Central de Venezuela; VenezuelaFil: Zaidenberg, Mario O.. Ministerio de Salud de la Nación. Coordinación Nacional de Control de Vectores; ArgentinaFil: Almiron, Walter Ricardo. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Claps, Guillermo Luis. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Superior de Entomología; ArgentinaFil: Conn, Jan E.. New York State Department of Health; Estados Unidos. State University Of New York; Estados Unido
Noninvasive detection of microsatellite instability in patients with endometrial cancer
Endometrial cancer; Liquid biopsy; Uterine aspirateCàncer d'endometri; Biòpsia líquida; Aspirat uteríCáncer de endometrio; Biopsia líquida; Aspirado uterinoThe analysis of mismatch repair proteins in solid tissue is the standard of care (SoC) for the microsatellite instability (MSI) characterization in endometrial cancer (EC). Uterine aspirates (UAs) or circulating-DNA (cfDNA) samples capture the intratumor heterogeneity and provide a more comprehensive and dynamic molecular diagnosis. Thus, MSI analysis by droplet-digital PCR (ddPCR) in UAs and cfDNA can provide a reliable tool to characterize and follow-up the disease. The UAs, paraffin-embedded tumor tissue (FFPE) and longitudinal plasma samples from a cohort of 90 EC patients were analyzed using ddPCR panel and compared to the SoC. A high concordance (96.67%) was obtained between the analysis of MSI markers in UAs and the SoC. Three discordant cases were validated as unstable by ddPCR on FFPE samples. Besides, a good overall concordance (70.27%) was obtained when comparing the performance of the ddPCR assay on UAs and cfDNA in high-risk tumors. Importantly, our results also evidenced the value of MSI analysis to monitor the disease evolution. MSI evaluation in minimally invasive samples shows great accuracy and sensitivity and provides a valuable tool for the molecular characterization and follow-up of endometrial tumors, opening new opportunities for personalized management of EC.Centro de Investigación Biomédica en Red de Cáncer, Grant/Award Numbers: CB16/12/00295, CB16/12/00328; Fundación Científica Asociación Española Contra el Cáncer, Grant/Award Numbers: FC_AECC PROYE19036MOR, 2018-AECC, INVES20051COLA; Fundación Instituto de Investigación Sanitaria de Santiago de Compostela; Instituto de Salud Carlos III and FEDER, Grant/Award Numbers: CM19/00087, CP20/00119, PI20/00969, PI20/01566, PI21/00990; Spanish Ministry of Economy and Innovation, Grant/Award Number: PID2019-104644RB-I0
Cannabinoid receptor CB2 drives HER2 pro-oncogenic signaling in breast cancer
Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different models of cancer. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen and Freiburg between 1997 and 2010. CB2 mRNA expression was also analyzed in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the HER2 rat ortholog (neu) and lacks CB2, and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by co-localization, coimmunoprecipitation and proximity ligation assays. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis. We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade, and that an increased CB2 expression activates the HER2 prooncogenic signaling machinery at the level of the tyrosine kinase c-SRC. Finally, HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and suggest that CB2 may be a biomarker with prognostic value in these tumors
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