The 1693 Catania earthquake, which caused 60000 deaths in eastern Sicily and generated a 5–10 m high tsunami, is investigated. GPS data indicate ESE‐WNW convergence in the Calabrian arc at 4–5 mm/yr. ...New high‐resolution seismic data image active compression at the toe of the accretionary wedge. The lack of instrumentally recorded thrust earthquakes suggests the presence of a locked subduction fault plane. Thermal modeling is applied to calculate the limits of the seismogenic zone. Tsunami modeling is performed to test the hypothesis that the 1693 earthquake occurred on the subduction fault plane (160 × 120 km in size) with 2 m of mean co‐seismic slip. This source successfully reproduces historical observations with regard to polarity and predicts 1–3 m high amplitudes. It is likely that only the SW segment of the subduction fault plane ruptured in 1693 and 1169, implying a recurrence interval of roughly 500 years for similar events.
The Eurasia–Nubia plate boundary between the Azores and the Strait of Gibraltar has been the place of large tsunamigenic earthquakes. The tectonic regime is extensional in the Azores, transcurrent ...along the Gloria Fault, and compressional in the Strait of Gibraltar. Here, the plate boundary is not clearly defined. The knowledge of past events that occurred in the area constitutes an essential contribution to the evaluations of seismic and tsunami hazard in the North-East Atlantic. In this study, we present an overview of the six major events in the area and show the use of tsunami data to add some constraints on their source. The historical events occurred in the eighteenth-century between 1722 and 1761, while the twentieth-century events occurred between 1941 and 1975. We speculate that major tsunamigenic earthquakes that occur in the Iberia-Maghreb area take place at the boundaries of a lithospheric block approximately defined by the location the six events summarized here, which role and dynamics are not yet understood.
Abstract Although the majority of peripheral-nerve regeneration studies are carried out on the sciatic nerve, lesions of the upper extremities are more common in humans and usually lead to ...significant physical disabilities. The present study was driven by the hypothesis that a combination of strategies, namely grafts of mesenchymal stem cells (MSC) and resorbable polycaprolactone (PCL) conduits would improve median-nerve regeneration after transection. Mouse median nerves were transected and sutured to PCL tubes that were filled with either green fluorescent protein (GFP+ ) MSC in DMEM or with DMEM alone. During the post-operative period, animals were tested weekly for flexor digitorum muscle function by means of the grasping test. After 8 weeks, the proximal and middle portions of the PCL tube and the regenerating nerves were harvested and processed for light and electron microscopy. The flexor digitorum muscle was weighed and subjected to biochemical analysis for creatine phosphokinase (CK) levels. Scanning electron microscopy of the PCL tube 8 weeks after implantation showed clear signs of wall disintegration. MSC-treated animals showed significantly larger numbers of myelinated and unmyelinated nerve fibers and blood vessels compared with DMEM-treated animals. The flexor digitorum muscle CK levels were significantly higher in the MSC-treated animals, but muscle weight values did not differ between the groups. Compared with the DMEM-treated group, MSC-treated animals showed, by the grasping test, improved functional performance throughout the period analyzed. Immunofluorescence for S-100 and GFP showed, in a few cases, double-labeled cells, suggesting that transplanted cells may occasionally transdifferentiate into Schwann cells. Our data demonstrate that the polycaprolactone conduit filled with MSC is capable of significantly improving the median-nerve regeneration after a traumatic lesion.
Objectives
To identify clinical, angiographic and hemodynamic predictors of discordance between instantaneous wave‐free ratio (iFR) and fractional flow reserve (FFR).
Background
The iFR was found to ...be non‐inferior to the gold‐standard FFR for guiding coronary revascularization, although it is discordant with FFR in 20% of cases. A better understanding of the causes of discordance may enhance application of these indices.
Methods
Both FFR and iFR were measured in the prospective multicenter CONTRAST study. Clinical, angiographic and hemodynamic variables were compared between patients with concordant values of FFR and iFR (cutoff ≤0.80 and ≤0.89, respectively).
Results
Out of the 587 patients included, in 466 patients (79.4%) FFR and iFR agreed: both negative, n = 244 (41.6%), or positive, n = 222 (37.8%). Compared with FFR, iFR was negative discordant (FFR+/iFR‐) in 69 (11.8%) patients and positive discordant (FFR‐/iFR+) in 52 (8.9%) patients. On multivariate regression, stenosis location (left main or proximal left anterior descending) (OR: 3.301.68;6.47), more severe stenosis (OR: 1.771.35;2.30), younger age (OR: 0.930.90;0.97), and slower heart rate (OR: 0.590.42;0.75) were predictors of a negative discordant iFR. Absence of a beta‐blocker (OR: 0.410.22;0.78), older age (OR: 1.041.00;1.07), and less severe stenosis (OR: 0.690.53;0.89) were predictors of a positive discordant iFR.
Conclusions
During iFR acquisition, stenosis location, stenosis degree, heart rate, age and use of beta blockers influence concordance with FFR and should be taken into account when interpreting iFR.
Condensed
iFR‐guided revascularization is non‐inferior to FFR at 1 year, despite being discordant with FFR in 20% of cases. In 587 patients, we studied predictive factors for this discordance. Stenosis location involving the left main or proximal left anterior descending coronary, more severe stenosis, younger age and slower heart rate were significant predictors of a negative discordant iFR (FFR+/iFR‐). Lack of use of a beta‐blocker, older age, and less severe stenosis were significant predictors of a positive discordant iFR (FFR‐/iFR+). Clinical, angiographic and hemodynamic conditions during iFR acquisition influence concordance with FFR and must be taken into account when interpreting iFR.
Breast cancer is the main cause of mortality among women. The disease presents high recurrence mainly due to incomplete efficacy of primary treatment in killing all cancer cells. Photodynamic therapy ...(PDT), an approach that causes tissue destruction by visible light in the presence of a photosensitizer (Ps) and oxygen, appears as a promising alternative therapy that could be used adjunct to chemotherapy and surgery for curing cancer. However, the efficacy of PDT to treat breast tumours as well as the molecular mechanisms that lead to cell death remain unclear.
In this study, we assessed the cell-killing potential of PDT using methylene blue (MB-PDT) in three breast epithelial cell lines that represent non-malignant conditions and different molecular subtypes of breast tumours. Cells were incubated in the absence or presence of MB and irradiated or not at 640 nm with 4.5 J/cm
. We used a combination of imaging and biochemistry approaches to assess the involvement of classical autophagic and apoptotic pathways in mediating the cell-deletion induced by MB-PDT. The role of these pathways was investigated using specific inhibitors, activators and gene silencing.
We observed that MB-PDT differentially induces massive cell death of tumour cells. Non-malignant cells were significantly more resistant to the therapy compared to malignant cells. Morphological and biochemical analysis of dying cells pointed to alternative mechanisms rather than classical apoptosis. MB-PDT-induced autophagy modulated cell viability depending on the cell model used. However, impairment of one of these pathways did not prevent the fatal destination of MB-PDT treated cells. Additionally, when using a physiological 3D culture model that recapitulates relevant features of normal and tumorous breast tissue morphology, we found that MB-PDT differential action in killing tumour cells was even higher than what was detected in 2D cultures.
Finally, our observations underscore the potential of MB-PDT as a highly efficient strategy which could use as a powerful adjunct therapy to surgery of breast tumours, and possibly other types of tumours, to safely increase the eradication rate of microscopic residual disease and thus minimizing the chance of both local and metastatic recurrence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Aims
The gap between patients on transplant waiting lists and available donor organs is steadily increasing. Human organoids derived from leucine‐rich repeat‐containing G ...protein‐coupled receptor 5 (LGR5)–positive adult stem cells represent an exciting new cell source for liver regeneration; however, culturing large numbers of organoids with current protocols is tedious and the level of hepatic differentiation is limited.
Approach and Results
Here, we established a method for the expansion of large quantities of human liver organoids in spinner flasks. Due to improved oxygenation in the spinner flasks, organoids rapidly proliferated and reached an average 40‐fold cell expansion after 2 weeks, compared with 6‐fold expansion in static cultures. The organoids repopulated decellularized liver discs and formed liver‐like tissue. After differentiation in spinner flasks, mature hepatocyte markers were highly up‐regulated compared with static organoid cultures, and cytochrome p450 activity reached levels equivalent to hepatocytes.
Conclusions
We established a highly efficient method for culturing large numbers of LGR5‐positive stem cells in the form of organoids, which paves the way for the application of organoids for tissue engineering and liver transplantation.
Lipid peroxidation (LPO) plays a key role in many age-related neurodegenerative conditions and other disorders. Light irradiation can initiate LPO through various mechanisms and is of importance in ...retinal and dermatological pathologies. The introduction of deuterated polyunsaturated fatty acids (D-PUFA) into membrane lipids is a promising approach for protection against LPO. Here, we report the protective effects of D-PUFA against the photodynamically induced LPO, using illumination in the presence of the photosensitizer trisulfonated aluminum phthalocyanine (AlPcS3) in liposomes and giant unilamellar vesicles (GUV), as assessed in four experimental models: 1) sulforhodamine B leakage from liposomes, detected with fluorescence correlation spectroscopy (FCS); 2) formation of diene conjugates in liposomal membranes, measured by absorbance at 234 nm; 3) membrane leakage in GUV assessed by optical phase-contrast intensity observations; 4) UPLC-MS/MS method to detect oxidized linoleic acid (Lin)-derived metabolites. Specifically, in liposomes or GUV containing H-PUFA (dilinoleyl-sn-glycero-3-phosphatidylcholine), light irradiation led to an extensive oxidative damage to bilayers. By contrast, no damage was observed in lipid bilayers containing 20% or more D-PUFA (D2-Lin or D10-docosahexanenoic acid). Remarkably, addition of tocopherol increased the dye leakage from liposomes in H-PUFA bilayers compared to photoirradiation alone, signifying tocopherol's pro-oxidant properties. However, in the presence of D-PUFA the opposite effect was observed, whereby adding tocopherol increased the resistance to LPO. These findings suggest a method to augment the protective effects of D-PUFA, which are currently undergoing clinical trials in several neurological and retinal diseases that involve LPO.
•Light induced lipid peroxidation and membrane protection by D-PUFA and α-tocopherol were investigated.•Trisulfonated aluminum phthalocyanine damaged membranes by type I and type II photosensitized oxidation mechanisms.•The presence of D-PUFA strongly inhibits the photoinduced lipid oxidation.•α-tocopherol augment the protective effects of D-PUFAs.•In certain conditions, α-tocopherol increases membrane damage by the tocopherol-mediated peroxidation.
Performance development in international soccer is undergoing a silent revolution fueled by the rapidly increasing availability of athlete quantification data and advanced analytics. Objective ...performance data from teams and individual players are increasingly being collected automatically during practices and more recently also in matches after FIFA's 2015 approval of wearables in electronic performance and tracking systems. Some clubs have even started collecting data from players outside of the sport arenas. Further algorithmic analysis of these data might provide vital insights for individual training personalization and injury prevention, and also provide a foundation for evidence-based decisions for team performance improvements. This paper presents our experiences from using a detailed radio-based wearable positioning data system in an elite soccer club. We demonstrate how such a system can detect and find anomalies, trends, and insights vital for individual athletic and soccer team performance development. As an example, during a normal microcycle (6 days) full backs only covered 26% of the sprint distance they covered in the next match. This indicates that practitioners must carefully consider to proximity size and physical work pattern in microcycles to better resemble match performance. We also compare and discuss the accuracy between radio waves and GPS in sampling tracking data. Finally, we present how we are extending the radio-based positional system with a novel soccer analytics annotation system, and a real-time video processing system using a video camera array. This provides a novel toolkit for modern forward-looking soccer coaches that we hope to integrate in future studies.
To address if corneal biomechanical behavior has a predictive value for the presence of glaucomatous optical neuropathy in eyes with high myopia.
This observational cross-sectional study included 209 ...eyes from 108 consecutive patients, divided into four groups: high myopia and primary open-angle glaucoma (POAG) - HMG, n = 53; high myopia without POAG - HMNG, n = 53; non-myopic with POAG - POAG, n = 50; non-myopic and non-POAG- NMNG, n = 53. Biomechanical assessment was made through a Scheimpflug-camera-based technology. Receiver operating characteristic curves were made for the discrimination between groups. Multivariable logistic regression models were performed to address the predictive value of corneal biomechanics for the presence of glaucoma.
Areas Under the Receiver Operating Characteristic (AUROCs) above 0.6 were found in 6 parameters applied to discriminate between HMG and HMNG and six parameters to discriminate between POAG and NMNG. The biomechanical models with the highest power of prediction for the presence of glaucoma included 5 parameters with an AUROC of 0.947 for eyes with high myopia and 6 parameters with an AUROC of 0.857 for non-myopic eyes. In the final model, including all eyes, and adjusted for the presence of high myopia, the highest power of prediction for the presence of glaucoma was achieved including eight biomechanical parameters, with an AUROC of 0.917.
Corneal biomechanics demonstrated differences in eyes with glaucoma and mainly in myopic eyes. A biomechanical model based on multivariable logistic regression analysis and adjusted for high myopia was built, with an overall probability of 91.7% for the correct prediction of glaucomatous damage.
HTLV-1/2 are transmitted sexually, by whole cell blood products and from mother-to-child (MTC), mainly through breastfeeding. HTLV-1/2 prevalence in pregnant women is high in Rio de Janeiro, however ...there were no local studies addressing the rate of adverse pregnancy outcomes (APO) and MTC transmission. The aim was to study sociodemographic characteristics which may be associated to HTLV-1/2 infection and describe pregnancy outcomes and MTC transmission in HTLV-1/2-positive women. The cross-sectional study screened 1,628 pregnant women in of Rio de Janeiro (2012-2014) and found 12 asymptomatic carrier mothers (prevalence = 0.74%). Pregnancy outcome information was retrieved from medical records. Sociodemographic characteristics were similar between the positive and negative groups except for maternal age, which was higher in carrier mothers. The incidence of adverse pregnancy outcomes was similar in infected and non-infected patients (p = 0.33), however there was a high rate of premature rupture of membranes (PROM) amid infected mothers (3/12). Multilevel logistic regression found that for each additional year of age, the chance of being HTLV-1/2-positive increased 11% and that having another sexually transmitted infection (STI) increased 9 times the chance of being infected. Carrier mothers had more antenatal visits (OR = 5.26). Among the children of HTLV-1/2-positive mothers there was one fetal death, one infant death and one loss of follow-up. After two years of follow-up there was one case of MTC transmission (1/9). The mother reported breastfeeding for one month only. Knowledge about factors associated to HTLV-1/2 infection, its impact on pregnancy outcomes and the MTC transmission rate is important to guide public health policies on antenatal screening and management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK