Nanoscopic surface inspection by analyzing the linear polarization degree of the scattered light

We present an optical method for the nanoscopic inspection of surfaces. The method is based on the spectral and polarization analysis of the light scattered by a probe nanoparticle close to the inspected surface. We explore the sensitivity to changes either in the probe–surface distance or in the refractive index of the surface

Regulation of pancreatic cancer aggressiveness by stromal stiffening

No abstract available

Caveolin-1 is required for TGF-β-induced transactivation of the EGF receptor pathway in hepatocytes through the activation of the metalloprotease TACE/ADAM17

Transforming growth factor-beta (TGF-β) plays a dual role in hepatocytes, inducing both pro- and anti-apoptotic responses, whose balance decides cell fate. Survival signals are mediated by the epidermal growth factor receptor (EGFR) pathway, which is activated by TGF-β in these cells. Caveolin-1 (Cav1) is a structural protein of caveolae linked to TGF-β receptors trafficking and signaling. Previous results have indicated that in hepatocytes, Cav1 is required for TGF-β-induced anti-apoptotic signals, but the molecular mechanism is not fully understood yet. In this work, we show that immortalized Cav1(-/-) hepatocytes were more sensitive to the pro-apoptotic effects induced by TGF-β, showing a higher activation of caspase-3, higher decrease in cell viability and prolonged increase through time of intracellular reactive oxygen species (ROS). These results were coincident with attenuation of TGF-β-induced survival signals in Cav1(-/-) hepatocytes, such as AKT and ERK1/2 phosphorylation and NFκ-B activation. Transactivation of the EGFR pathway by TGF-β was impaired in Cav1(-/-) hepatocytes, which correlated with lack of activation of TACE/ADAM17, the metalloprotease responsible for the shedding of EGFR ligands. Reconstitution of Cav1 in Cav1(-/-) hepatocytes rescued wild-type phenotype features, both in terms of EGFR transactivation and TACE/ADAM17 activation. TACE/ADAM17 was localized in detergent-resistant membrane (DRM) fractions in Cav1(+/+) cells, which was not the case in Cav1(-/-) cells. Disorganization of lipid rafts after treatment with cholesterol-binding agents caused loss of TACE/ADAM17 activation after TGF-β treatment. In conclusion, in hepatocytes, Cav1 is required for TGF-β-mediated activation of the metalloprotease TACE/ADAM17 that is responsible for shedding of EGFR ligands and activation of the EGFR pathway, which counteracts the TGF-β pro-apoptotic effects. Therefore, Cav1 contributes to the pro-tumorigenic effects of TGF-β in liver cancer cells.This work was supported by grants from: (1) the Ministry of Economy and Competitiveness (MINECO), Spain (BFU2012-35538 and ISCIII-RTICC: RD12-0036-0029 to IF; SAF2013-43713 to PM-S; BFU2012-33932 to GE; SAF2011-25047 and CSD2009-00016 to MAdP); (2) AGAUR-Generalitat de Catalunya (2009SGR-312 to IF); and (3) People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. PITN-GA-2012-316549 (IT LIVER) to IF JM-C and RM-V were recipients of pre-doctoral fellowships from the FPU program (Ministry of Education, Culture and Sport, Spain) and the FPI program (associated to SAF201125047, MINECO, Spain), respectively. We acknowledge the review and suggestions of Dr. Christoph Meyer (University of Heidelberg, Mannheim, Germany).S

Finding answers in lipid profile in COVID-19 patients

Introduction: A small percentage of patients will develop a severe form of COVID-19 caused by SARS-CoV-2 infection. Thus, it is important to predict the potential outcomes identifying early markers of poor prognosis. In this context, we evaluated the association of SARS-CoV-2 infection with lipid abnormalities and their role in prognosis. Methods: Single-center, retrospective, observational study of COVID-19 patients admitted from March to October 2020. Clinical and laboratory data, comorbidities, and treatments for COVID-19 were evaluated. Main outcomes including intensive care unit (ICU) admission and mortality were analyzed with a multivariable Cox proportional hazards regression model. Results: We selected 1489 from a total of 2038 consecutive patients with confirmed COVID-19, who had a complete lipid profile before ICU admission. During the follow-up performed in 1109 patients, we observed a decrease in T-c, HDL-c, and LDL-c in 28.6%, 42.9%, and 30.4% of patients, respectively, and an increase in TG in 76.8%. The decrease of both T-c and HDL- c was correlated with a decrease in albumin levels (r = 0.39 and r = 0.37, respectively). Kaplan–Meier survival curves found an increased ICU admission in patients with lower T-c (HR 0.55, CI 0.36–0.86), HDL-c (HR 0.61, CI 0.45–0.84), and LDL-c (HR 0.85, CI 0.74–0.97). Higher values of T-c (HR 0.45, CI 0.36–0.57), HDL-c (HR 0.66, CI 0.54–0.81), and LDL-c (HR 0.86, CI 0.78–0.94) showed a protective effect on mortality. Conclusions: Abnormalities in lipid profile are a frequent complication of SARS-CoV-2 infection and might be related to morbidity and mortalityThis work was supported by the following grants: Proyectos de Investigación en Salud (FIS) PI16-02091 and PI19-00584 (funded by Instituto de Salud Carlos III), TIRONET2-CM, B2017/BMD-3724 (funded by Comunidad de Madrid) and cofinanced by FEDER funds to M.M

Comparison of autologous bone marrow and adipose tissue derived mesenchymal stem cells, and platelet rich plasma, for treating surgically induced lesions of the equine superficial digital flexor tendon

Several therapies have been investigated for equine tendinopathies, but satisfactory long term results have not been achieved consistently and a better understanding of the healing mechanism elicited by regenerative therapies is needed. The aim of this study was to assess the separate effects of autologous bone marrow (BM) and adipose tissue (AT) derived mesenchymal stem cells (MSCs), and platelet rich plasma (PRP), for treating lesions induced in the superficial digital flexor tendon (SDFT) of horses. Lesions were created surgically in both SDFTs of the forelimbs of 12 horses and were treated with BM-MSCs (six tendons), AT-MSCs (six tendons) or PRP (six tendons). The remaining six tendons received lactated Ringer''s solution as control. Serial ultrasound assessment was performed prior to treatment and at 2, 6, 10, 20 and 45 weeks post-treatment. At 45 weeks, histopathology and gene expression analyses were performed. At week 6, the ultrasound echogenicity score in tendons treated with BM-MSCs suggested earlier improvement, whilst all treatment groups reached the same level at week 10, which was superior to the control group. Collagen orientation scores on histological examination suggested a better outcome in treated tendons. Gene expression was indicative of better tissue regeneration after all treatments, especially for BM-MSCs, as suggested by upregulation of collagen type I, decorin, tenascin and matrix metalloproteinase III mRNA. Considering all findings, a clear beneficial effect was elicited by all treatments compared with the control group. Although differences between treatments were relatively small, BM-MSCs resulted in a better outcome than PRP and AT-MSCs

Management of Patients with Suspected or Confirmed Antibiotic Allergy. Executive Summary of Guidance from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Allergy and Clinical Immunology (SEAIC), the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Intensive Medicine and Coronary Care Units (SEMICYUC)

Suspected or confirmed antibiotic allergy is a frequent clinical circumstance that influences antimicrobial prescription and often leads to the avoidable use of less efficacious and/or more toxic or costly drugs than first-line antimicrobials. Optimizing antimicrobial therapy in patients with antibiotic allergy labels has become one of the priorities of antimicrobial stewardship programs in several countries. These guidelines aim to make recommendations for the systematic approach to patients with suspected or confirmed antibiotic allergy based on current evidence. An expert panel (11 members of various scientific societies) formulated questions about the management of patients with suspected or confirmed antibiotic allergy. A systematic literature review was performed by a medical librarian. The questions were distributed among panel members who selected the most relevant references, summarized the evidence, and formulated graded recommendations when possible. The answers to all the questions were finally reviewed by all panel members. A systematic approach to patients with suspected or confirmed antibiotic allergy was recommended to improve antibiotic selection and, consequently, clinical outcomes. A clinically oriented, 3-category risk-stratification strategy was recommended for patients with suspected antibiotic allergy. Complementary assessments should consider both clinical risk category and preferred antibiotic agent. Empirical therapy recommendations for the most relevant clinical syndromes in patients with suspected or confirmed ss-lactam allergy were formulated, as were recommendations on the implementation and monitoring of the impact of the guidelines. Antimicrobial stewardship programs and allergists should design and implement activities that facilitate the most appropriate use of antibiotics in these patients

Transanal total mesorectal excision: a pure NOTES approach for selected patients

Background: The concept of natural orifice transluminal endoscopic surgery (NOTES) has stimulated the development of various “incisionless” procedures. One of the most popular is the transanal approach for rectal lesions. The aims of this study were to report how we standardized NOTES technique for transanal mesorectal excision without abdominal assistance, discuss the difficulties and surgical outcomes of this technique and report its feasibility in a small group of selected patients. Methods: Three consecutive female patients underwent transanal NOTES rectal resection without transabdominal laparoscopic assistance for rectal lesions. Functional results were assessed with the Fecal Incontinence Quality of Life scale and the Wexner score. Results: The technical steps are described in details and complemented with a video. All procedures were completed without transabdominal laparoscopic help. The mesorectal plane was entirely dissected without any disruption, and distal and circumferential margins were tumor-free. No major complications were observed. Functional results show a significant impairment after surgery with improvement at 6 months to levels near those of the preoperative period. Conclusions: The performance and publication of NOTES procedures are subject to much discussion. Despite the small number of patients, this procedure appears feasible and can be accomplished maintaining fecal continence and respecting oncologic principles

Compilation of parameterized seismogenic sources in Iberia for the SHARE European-scale seismic source model.

Abstract: SHARE (Seismic Hazard Harmonization in Europe) is an EC-funded project (FP7) that aims to evaluate European seismic hazards using an integrated, standardized approach. In the context of SHARE, we are compiling a fully-parameterized active fault database for Iberia and the nearby offshore region. The principal goal of this initiative is for fault sources in the Iberian region to be represented in SHARE and incorporated into the source model that will be used to produce seismic hazard maps at the European scale. The SHARE project relies heavily on input from many regional experts throughout the Euro-Mediterranean region. At the SHARE regional meeting for Iberia, the 2010 Working Group on Iberian Seismogenic Sources (WGISS) was established; these researchers are contributing to this large effort by providing their data to the Iberian regional integrators in a standardized format. The development of the SHARE Iberian active fault database is occurring in parallel with IBERFAULT, another ongoing effort to compile a database of active faults in the Iberian region. The SHARE Iberian active fault database synthesizes a wide range of geological and geophysical observations on active seismogenic sources, and incorporates existing compilations (e.g., Cabral, 1995; Silva et al., 2008), original data contributed directly from researchers, data compiled from the literature, parameters estimated using empirical and analytical relationships, and, where necessary, parameters derived using expert judgment. The Iberian seismogenic source model derived for SHARE will be the first regional-scale source model for Iberia that includes fault data and follows an internationally standardized approach (Basili et al., 2008; 2009). This model can be used in both seismic hazard and risk analyses and will be appropriate for use in Iberian- and European-scale assessments