Validation of plasma fibrinogen as a marker of carotid atherosclerosis in subjects free of clinical cardiovascular disease

BACKGROUND AND OBJECTIVES: Fibrinogen has been found to be an independent risk factor for cardiovascular disease. The aim of this study was to validate the measurement of plasma fibrinogen as a marker of subclinical atherosclerosis in a series of asymptomatic subjects (n=519, median age 55.5 years, 80% men). DESIGN AND METHODS: All individuals had a complete clinical examination, lipid profile (cholesterol and its high and low density lipoprotein fractions and triglycerides), global vascular risk assessment (PROCAM), and B-mode ultrasonography of the carotid arteries to determine the intima-media thickness (IMT) and the presence of atheroma plaques. C-reactive protein (CRP), and von Willebrand factor (vWF) were also measured in all subjects as markers of inflammation/endothelial damage. RESULTS: In the univariate model, a positive relationship was found between plasma fibrinogen concentration and carotid IMT (p<0.001). Fibrinogen concentration also correlated positively with age (p<0.001), systolic blood pressure (p<0.001), smoking (p<0.05), diabetes (p<0.05), PROCAM (p<0.001), CRP and vWF (p<0.001). In the multivariate analysis, the association of fibrinogen with carotid IMT remained significant (p=0.008) after adjustment for all parameters analyzed. INTERPRETATION AND CONCLUSIONS: In a population sample of adults without clinically overt atherosclerotic disease, elevated fibrinogen levels was related to carotid IMT independently of a wide range of important confounding variables. Plasma fibrinogen may represent a systemic marker of carotid atherosclerosis

A Decade of GRB Follow-Up by BOOTES in Spain (2003–2013)

This article covers ten years of GRB follow-ups by the Spanish BOOTES stations: 71 follow-ups providing 23 detections. Follow-ups by BOOTES-1B from 2005 to 2008 were given in a previous article and are here reviewed and updated, and additional detection data points are included as the former articlemerely stated their existence. The all-sky cameras CASSANDRA have not yet detected any GRB optical afterglows, but limits are reported where available.The authors appreciate the auspices of INTA, IHSM-UMA/CSIC, and UMA as well as the financial support by the Junta de Andaluca and the Spanish Ministry of Economy and Competitiveness through the Research Projects P07-TIC-03094, P12-TIC2839, AYA2009-14000-C03-01, AYA 2010-39727-C03-01, and AYA-2015-71718-R. Martin Jelinek was supported by the postdoctoral fellowship of the Czech Academy of Sciences. This study was carried out in the framework of the Unidad Asociada IAA-CSIC at the Group of Planetary Science of ETSI-UPV/EHU. This work was supported by the Ikerbasque Foundation for Science. The Czech CVUT FEL team acknowledges the support by GA CR Grant 13-33324S

Divisibility patterns within Pascal divisibility networks

The Pascal triangle is so simple and rich that it has always attracted the interest of professional and amateur mathematicians. Their coefficients satisfy a myriad of properties. Inspired by the work of Shekatkar et al., we study the divisibility patterns within the elements of the Pascal triangle, through its decomposition into Pascal’s matrices, from the perspective of network science. Applying Kolmogorov–Smirnov test, we determine that the degree distribution of the resulting network follows a power-law distribution. We also study degrees, global and local clustering coefficients, stretching graph, averaged path length and the mixing assortative

High Levels of Proinflammatory Cytokines, but Not Markers of Tissue Injury, in Unaffected Intestinal Areas from Patients with IBD

Intestinal alterations in IBD are triggered and maintained by an overexpression of proinflammatory cytokines. Additionally, increased immune activation has been found in the adjacent intestinal areas without displaying any apparent histological alterations, however, the regulatory environment is not well established. Biopsy specimens from patients with ulcerative colitis (UC) and Crohn's disease (CD), from both affected and unaffected areas, and also from a group of colonic biopsies from healthy controls, were included in our study. Cytokines and markers of mucosal damage were analyzed by real-time PCR, and some of the results confirmed by western-blot and ELISA. Levels of IFNγ, TNFα, IL-6, IL-15, IL-18, and IL-23 were increased (above healthy controls) in both affected and unaffected areas from IBD. IL-1β, IL-6, IL-12, and IL-27 were higher in affected areas compared to unaffected ones in UC but not CD. In general, a correlation was observed between mRNA levels of these cytokines and both iNOS and Granzyme B. SOCS-2 and SOCS-3 were also increased in the affected areas. In conclusion, the unaffected areas from IBD show increased levels of a restricted set of cytokines that may exert immune activating roles in these areas without being able to trigger tissue damage

Totally Laparoscopic Roux-en-Y Duct-to-Mucosa Pancreaticojejunostomy After Middle Pancreatectomy A Consecutive Nine-case Series at a Single Institution

To present the results of a series of laparoscopic middle pancreatectomies with roux-en-Y duct-to-mucosa pancreaticojejunostomy. SUMMARY OF BACKGROUND DATA: Middle pancreatectomy makes it possible to preserve pancreatic parenchyma in the resection of lesions that traditionally have been treated by distal splenopancreatectomy or cephalic duodenopancreatectomy. The laparoscopic approach could minimize the invasiveness of the procedure and enhance the benefits of middle pancreatectomy. METHODS: From March 2005 to October 2007, 9 consecutive patients with benign or low malignant potential lesions in the pancreatic neck or body underwent surgery. Laparoscopic middle pancreatectomy with a roux-en-Y duct-to-mucosa pancreaticojejunostomy was planned on all of them. In the first 2 patients, the pancreas was transected by endostapler; in the last 7, the staple line was reinforced with absorbable polymer membrane. RESULTS: The intervention was concluded laparoscopically in every case except 1 (laparoscopic-assisted) in which pancreaticojejunostomy was performed by means of minilaparotomy. Mortality was 0% and perioperative morbidity was 33%, (fistula of the cephalic stump in the first 2 patients (22%)). The pancreaticojejunostomy fistula rate was 0%. The median postoperative hospital stay was 5 days (range, 3-41). In the last 7 patients, in which pancreas was transected with staple line reinforcement material there were no stump fistulas; morbidity decreased to 14% and the median hospital stay was 4 days (range, 3-30). CONCLUSIONS: Laparoscopic middle pancreatectomy is feasible and safe. Duct-to-mucosa pancreaticojejunostomy can be performed safely using this approach. The method of pancreatic transection seems to be decisive in the incidence of cephalic stump fistulas

Development and Implementation of an Assessment Model in a Sophomore Electromechanical Systems Design Laboratory for the ETAC-ABET Accreditation

In the field of assessment in higher education, practitioners regularly mention two features as key for success at implementing a sustainable assessment model, i) it has to be faculty-driven, and ii) it has to become part of the curriculum. This paper describes an assessment model incorporating these features. The model was developed and implemented for assessing both the ETAC-ABET Program Criteria for an associate degree in Electromechanical Engineering Technology program and the new ETAC-ABET (2019-2020) student outcome (2), which regards students\u27 ability to design systems, components, or processes for well-defined engineering technology problems appropriate to the discipline. This paper describes the implementation of our assessment model, including a description of the performance indicators used for assessment of criteria mentioned above, the structure of course selected for the assessment, the details of the laboratory experiments and final design project used as assessment tools, a summary of the collected data and a discussion of the assessment results, and the arrangements we made in response to the COVID-19 pandemic. We believe that our method of incorporating assessment as regular course activities helps achieve the ultimate objective of education, i.e., continuous and constant improvement of students\u27 competencies and learning experiences

A decade of GRB follow-up by BOOTES in Spain (2003-2013)

This article covers ten years of GRB follow-ups by the Spanish BOOTES stations: 71 follow-ups providing 23 detections. Follow-ups by BOOTES-1B from 2005 to 2008 were given in the previous article, and are here reviewed, updated, and include additional detection data points as the former article merely stated their existence. The all-sky cameras CASSANDRA have not yet detected any GRB optical afterglows, but limits are reported where available

Transient and intensive pharmacological immunosuppression fails to improve AAV-based liver gene transfer in non-human primates

BACKGROUND: Adeno-associated vectors (rAAV) have been used to attain long-term liver gene expression. In humans, the cellular immune response poses a serious obstacle for transgene persistence while neutralizing humoral immunity curtails re-administration. Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria) benefits from liver gene transfer in mouse models and clinical trials are about to begin. In this study, we sought to study in non-human primates the feasibility of repeated gene-transfer with intravenous administration of rAAV5 vectors under the effects of an intensive immunosuppressive regimen and to analyze its ability to circumvent T-cell immunity and thereby prolong transgene expression. METHODS: Three female Macaca fascicularis were intravenously injected with 1x1013 genome copies/kg of rAAV5 encoding the human PBGD. Mycophenolate mofetil (MMF), anti-thymocyte immunoglobulin, methylprednisolone, tacrolimus and rituximab were given in combination during 12 weeks to block T- and B-cell mediated adaptive immune responses in two macaques. Immunodeficient and immunocompetent mice were intravenously injected with 5x1012 genome copies/kg of rAAV5-encoding luciferase protein. Forty days later MMF, tacrolimus and rituximab were daily administrated to ascertain whether the immunosuppressants or their metabolites could interfere with transgene expression. RESULTS: Macaques given a rAAV5 vector encoding human PBGD developed cellular and humoral immunity against viral capsids but not towards the transgene. Anti-AAV humoral responses were attenuated during 12 weeks but intensely rebounded following cessation of the immunosuppressants. Accordingly, subsequent gene transfer with a rAAV5 vector encoding green fluorescent protein was impossible. One macaque showed enhanced PBGD expression 25 weeks after rAAV5-pbgd administration but overexpression had not been detected while the animal was under immunosuppression. As a potential explanation, MMF decreases transgene expression in mouse livers that had been successfully transduced by a rAAV5 several weeks before MMF onset. Such a silencing effect was independent of AAV complementary strand synthesis and requires an adaptive immune system. CONCLUSIONS: These results indicate that our transient and intensive pharmacological immunosuppression fails to improve AAV5-based liver gene transfer in non-human primates. The reasons include an incomplete restraint of humoral immune responses to viral capsids that interfere with repeated gene transfer in addition to an intriguing MMF-dependent drug-mediated interference with liver transgene expression