Marine transmissible cancer navigates urbanized waters, threatening spillover.

Inter-individual transmission of cancer cells represents a unique form of microparasites increasingly reported in marine bivalves. In this study, we sought to understand the ecology of the propagation of Mytilus trossulus Bivalve Transmissible Neoplasia 2 (MtrBTN2), a transmissible cancer affecting four Mytilus mussel species worldwide. We investigated the prevalence of MtrBTN2 in the mosaic hybrid zone of M. edulis and M. galloprovincialis along the French Atlantic coast, sampling contrasting natural and anthropogenic habitats. We observed a similar prevalence in both species, probably due to the spatial proximity of the two species in this region. Our results showed that ports had higher prevalence of MtrBTN2, with a possible hotspot observed at a shuttle landing dock. No cancer was found in natural beds except for two sites close to the hotspot, suggesting spillover. Ports may provide favourable conditions for the transmission of MtrBTN2, such as high mussel density, stressful conditions, sheltered and confined shores or buffered temperatures. Ships may also spread the disease through biofouling. Our results suggest ports may serve as epidemiological hubs, with maritime routes providing artificial gateways for MtrBTN2 propagation. This highlights the importance of preventing biofouling on docks and ship hulls to limit the spread of marine pathogens hosted by fouling species.

Gradual Correction of Valgus Deformities of the Tibia Using a Monolateral External Fixator.

Objective: To present a review of patients subjected to gradual correction of a valgus deformity of the tibia using a monolateral external fixator. Method: This retrospective review included patients from January 2012 to May 2022 who met the following inclusion criteria: deviation of mechanical axis of the limb due to valgus deformity of the tibia; tibial deformity in the coronal plane on radiographic examination; a documented outpatient pre-operative evaluation by an orthopaedic surgeon and age between 10 and 70 years. The following exclusion criteria were applied: the presence of another tibia deformity preventing gradual correction using the proposed assembly; skin conditions incompatible with the surgical procedure; inadequate pre- or post-operative radiological evaluation; and insufficient information in the medical records. Results: The mean age of patients with a valgus deformity of the tibia was 30.8 ± 15.9 years. These patients had a body mass index (BMI) of 26.1 ± 5.5 kg/m2. A congenital or developmental aetiology was attributed to 58.3% of the cases. Most commonly, the deformity was found in the middle third of the tibia with a mean deformity of 14.7 ± 6.6 degrees. The total external fixator time ranged from 73 to 229 days (average 149.7 ± 36.1 days). The mean medial proximal and lateral distal tibial angles differed significantly for pre- and post-operative measurements (p ≤ 0.05). There were complications in eight cases; five cases of pin site infections, two cases of medial cortical fracture and one case of peroneal nerve neuropraxia. Conclusion: The proposed correction technique produces a satisfactory angular correction and with similar outcomes as described in the literature. How to cite this article: Motta DP, Faria JLR, Couto A, et al. Gradual Correction of Valgus Deformities of the Tibia Using a Monolateral External Fixator. Strategies Trauma Limb Reconstr 2023;18(2):123-132.

Inhibitory Effect of 5-Aminoimidazole-4-Carbohydrazonamides Derivatives Against Candida spp. Biofilm on Nanohydroxyapatite Substrate.

Candida can adhere and form biofilm on biomaterials commonly used in medical devices which is a key attribute that enhances its ability to cause infections in humans. Furthermore, biomaterial-related infections represent a major therapeutic challenge since Candida biofilms are implicated in antifungal therapies failure. The goals of the present work were to investigate the effect of three 5-aminoimidazole-4-carbohydrazonamides, namely (Z)-5-amino-1-methyl-N'-aryl-1H-imidazole-4-carbohydrazonamides [aryl = phenyl (1a), 4-fluorophenyl (1b), 3-fluorophenyl (1c)], on Candida albicans and Candida krusei biofilm on nanohydroxyapatite substrate, a well-known bioactive ceramic material. To address these goals, both quantitative methods (by cultivable cell numbers) and qualitative evaluation (by scanning electron microscopy) were used. Compounds cytocompatibility towards osteoblast-like cells was also evaluated after 24 h of exposure, through resazurin assay. The three tested compounds displayed a strong inhibitory effect on biofilm development of both Candida species as potent in vitro activity against C. albicans sessile cells. Regarding cytocompatibility, a concentration-dependent effect was observed. Together, these findings indicated that the potent activity of imidazole derivatives on Candida spp. biofilms on nanohydroxyapatite substrate, in particular compound 1c, is worth further investigating.

Graphene field-effect transistor array with integrated electrolytic gates scaled to 200 mm.

Ten years have passed since the beginning of graphene research. In this period we have witnessed breakthroughs both in fundamental and applied research. However, the development of graphene devices for mass production has not yet reached the same level of progress. The architecture of graphene field-effect transistors (FET) has not significantly changed, and the integration of devices at the wafer scale has generally not been sought. Currently, whenever an electrolyte-gated FET (EGFET) is used, an external, cumbersome, out-of-plane gate electrode is required. Here, an alternative architecture for graphene EGFET is presented. In this architecture, source, drain, and gate are in the same plane, eliminating the need for an external gate electrode and the use of an additional reservoir to confine the electrolyte inside the transistor active zone. This planar structure with an integrated gate allows for wafer-scale fabrication of high-performance graphene EGFETs, with carrier mobility up to 1800 cm(2) V(-1) s(-1). As a proof-of principle, a chemical sensor was achieved. It is shown that the sensor can discriminate between saline solutions of different concentrations. The proposed architecture will facilitate the mass production of graphene sensors, materializing the potential of previous achievements in fundamental and applied graphene research.

Genetic structure in the Amazonian catfish Brachyplatystoma rousseauxii: influence of life history strategies.

The Dorado or Plateado (Gilded catfish) Brachyplatystoma rousseauxii (Pimelodidae, Siluriformes) is a commercially valuable migratory catfish performing the largest migration in freshwaters: from the Amazonian headwaters in the Andean foothills (breeding area) to the Amazon estuary (nursery area). In spite of its importance to inform management and conservation efforts, the genetic variability of this species has only recently begun to be studied. The aim of the present work was to determine the population genetic structure of B. rousseauxii in two regions: the Upper Madera Basin (five locations in the Bolivian Amazon) and the Western Amazon Basin (one regional sample from the Uyucalí-Napo-Marañon-Amazon basin, Peru). Length polymorphism at nine microsatellite loci (284 individuals) was used to determine genetic variability and to identify the most probable panmictic units (using a Bayesian approach), after a significant departure from Hardy-Weinberg equilibrium was observed in the overall dataset (Western Amazon + Upper Madera). Bayesian analyses revealed at least three clusters in admixture in the five locations sampled in the Bolivian Amazon, whereas only two of these clusters were observed in the Western Amazon. Considering the migratory behaviour of B. rousseauxii, different life history strategies, including homing, are proposed to explain the cluster distribution. Our results are discussed in the light of the numerous threats to the species survival in the Madera basin, in particular dam and reservoir construction.

Miconazole-loaded nanostructured lipid carriers (NLC) for local delivery to the oral mucosa: improving antifungal activity.

Miconazole is a widely used antifungal agent with poor aqueous solubility, which requires the development of drug delivery systems able to improve its therapeutic activity. For this purpose, a miconazole-loaded nanostructured lipid carriers (NLC) dispersion was prepared and characterized. Further, the dispersion was used to prepare a NLC-based hydrogel formulation proposed as an alternative system to improve the local delivery of miconazole to the oral mucosa. NLC dispersion showed particles in the nanometer range (≈ 200 nm) with low polidispersity index (<0.3), good physical stability and high encapsulation efficiency (>87%). A controlled miconazole release was observed from NLC and NLC-based hydrogel formulations, in contrast to a commercial oral gel formulation, which demonstrated a faster release. Additionally, it was observed that the encapsulation of miconazole in the NLC improved its antifungal activity against Candida albicans. Therefore, it was demonstrated that the encapsulation of miconazole in NLC allows for obtaining the same therapeutic effect of a commercial oral gel formulation, using a 17-fold lower dose of miconazole.

Nanocomposite metal amorphous-carbon thin films deposited by hybrid PVD and PECVD technique.

Carbon based films can combine the properties of solid lubricating graphite structure and hard diamond crystal structure, i.e., high hardness, chemical inertness, high thermal conductivity and optical transparency without the crystalline structure of diamond. Issues of fundamental importance associated with nanocarbon coatings are reducing stress, improving adhesion and compatibility with substrates. In this work new nanocomposite coatings with improved toughness based in nanocrystalline phases of metals and ceramics embedded in amorphous carbon matrix are being developed within the frame of a research project: nc-MeNxCy/a-C(Me) with Me = Mo, Si, Al, Ti, etc. Carbide forming metal/carbon (Me/C) composite films with Me = Mo, W or Ti possess appropriate properties to overcome the limitation of pure DLC films. These novel coating architectures will be adopted with the objective to decrease residual stress, improve adherence and fracture toughness, obtain low friction coefficient and high wear-resistance. Nanocomposite DLC's films were deposited by hybrid technique using a PVD-Physically Vapor Deposition (magnetron sputtering) and Plasma Enhanced Chemical Vapor Deposition (PECVD), by the use of CH4 gas. The parameters varied were: deposition time, substrate temperature (180 degrees C) and dopant (Si + Mo) of the amorphous carbon matrix. All the depositions were made on silicon wafers and steel substrates precoated with a silicon inter-layer. The characterisation of the film's physico-mechanical properties will be presented in order to understand the influence of the deposition parameters and metal content used within the a-C matrix in the thin film properties. Film microstructure and film hybridization state was characterized by Raman Spectroscopy. In order to characterize morphology SEM and AFM will be used. Film composition was measured by Energy-Dispersive X-ray analysis (EDS) and by X-ray photoelectron spectroscopy (XPS). The contact angle for the produced DLC's on silicon substrates were also measured. Thin film adherence was studied by micro-scratch test. Residual stresses in the produced coatings will be analysed by bending technique.

Demoting redundant features to improve the discriminatory ability in cancer data.

The identification of a set of relevant but not redundant features is an important first step in building predictive and diagnostic models from biomedical data sets. Most commonly, individual features are ranked in terms of a quality criterion, out of which the best (first) k features are selected. However, feature ranking methods do not sufficiently account for interactions and correlations between the features. Thus, redundancy is likely to be encountered in the selected features. We present a new algorithm, termed Redundancy Demoting (RD), that takes an arbitrary feature ranking as input, and improves this ranking by identifying redundant features and demoting them to positions in the ranking in which they are not redundant. Redundant features are those that are correlated with other features and not relevant in the sense that they do not improve the discriminatory ability of a set of features. Experiments on two cancer data sets, one melanoma image data set and one lung cancer microarray data set, show that our algorithm greatly improves the feature rankings provided by the methods information gain, ReliefF and Student's t-test in terms of predictive power.

The natural prenylated flavone artelastin is an inhibitor of ROS and NO production.

Artelastin, a prenylated flavone previously isolated from Artocarpus elasticus, was evaluated for its effect on the production of reactive oxygen species (ROS) by human polymorphonuclear neutrophils (PMNs) and nitric oxide (NO) by J774 murine macrophage cell line. Artelastin showed to be an inhibitor of ROS production due to a strong O2- scavenging activity. No effect was observed on the activity of myeloperoxidase (MPO). Artelastin showed also to be an inhibitor of NO production without NO scavenging activity. This flavone seems to interfere with the expression of the inducible nitric oxide synthase (iNOS) immediately after LPS-IFNgamma-macrophage stimulation.

Effect of abietane diterpenes from Plectranthus grandidentatus on T- and B-lymphocyte proliferation.

Five known abietane diterpenes of the royleanone and coleon type, namely, fatty acid esters of 7alpha-acyloxy-6beta-hydroxyroyleanone (1), grandidone A (2), 7alpha-acetoxy-6beta-hydroxyroyleanone (3), 6beta,7alpha-dihydroxyroyleanone (4) and coleon U (5), isolated from Plectranthus grandidentatus, were evaluated for their effect on the proliferation of human lymphocytes induced by the mitogen PHA. All except 4, showed a dose-dependent suppressor effect, with 3 yielding the most potent antiproliferative activity, followed by 5. These two compounds, that represent diterpenes of the royleanone and coleon type respectively, were also shown to be potent inhibitors of mouse splenocyte proliferation induced by ConA or LPS mitogens. However, the sensitivity of ConA-stimulated splenocytes to their suppressive effect was higher, suggesting a preferential inhibition of T-lymphocyte proliferation. The antiproliferative activity of 3 seemed to be exerted without affecting the expression of the lymphocyte activation marker CD69. On the contrary, 5 was shown to reduce the expression of CD69 of TCD8(+) and B-cells, suggesting a relationship between its antiproliferative effect and the expression of this early marker of activation on these cell populations. The capacity of 5 to induce apoptosis on ConA-stimulated splenocytes could also be related with its antiproliferative activity.

Inhibition of lymphocyte proliferation by prenylated flavones: artelastin as a potent inhibitor.

Eight natural prenylated flavones, previously isolated from Artocarpus elasticus, were evaluated for their effect on the mitogenic response of human lymphocytes to PHA. They all exhibited a dose-dependent suppression effect. An interesting relationship was observed between their antiproliferative activity and their chemical structure. Indeed, the most potent flavones possessed a 3,3-dymethylallyl group (prenyl) at C-8, such as artelastin, which exhibited the highest antiproliferative activity. Studies of the mechanism underlying its effect revealed that artelastin had an irreversible inhibitory effect on the PHA-induced lymphocyte proliferation and could affect the course of the ongoing mitogenic response either at the initial induction phase or at the late phase of proliferation. This prenylated flavone was also shown to be a potent inhibitor of both T- and B-lymphocyte mitogen induced proliferation although B-mitogenic response was the more sensitive one. Artelastin did not affect either the basal levels of the early marker of activation CD69 on non-stimulated splenocytes or its expression on ConA- or LPS-stimulated splenocytes. However, it decreased the production of IFN-gamma, IL-2, IL-4 and IL-10 in ConA-stimulated splenocytes. Furthermore, artelastin had no effect on apoptosis of splenocytes.

Catechols from abietic acid synthesis and evaluation as bioactive compounds.

Catechols from abietic acid were prepared by a short and good yielding chemical process and further evaluated for several biological activities namely, antifungal, antitumoral, antimutagenic, antiviral, antiproliferative and inhibition of nitric oxide. Their properties were compared with those of carnosic acid (6), a naturally occurring catechol with an abietane skeleton and known to possess potent antioxidant activity, as well as anticancer and antiviral properties. From all the synthetic catechols tested compound 2 showed the best activities, stronger than carnosic acid.

Synthetic secofriedelane and friedelane derivatives as inhibitors of human lymphocyte proliferation and growth of human cancer cell lines in vitro.

Controlled silylation of friedelin (1) from cork smoker wash solids, a byproduct generated during processing of corkboard by steam baking, gave 3-trimethylsiloxyfriedel-2-ene (3) in high yields. Oxidation of 3 with OsO(4)/NMMO produced 2alpha-hydroxyfriedelan-3-one (cerin) (5), from which the new 2,3-secofriedelan-2-al-3-oic acid (6) was obtained quantitatively by periodic acid oxidation. Oxidation of 3 with DDQ afforded friedel-1-en-3-one (8). Reductive ozonolysis of 3 gave 2alpha,3beta-dihydroxyfriedelane, pachysandiol A (7). Compound 6 proved to be a potent inhibitor of human lymphocyte proliferation (IC(50) = 10.7 microM) and of the growth of a human cancer cell line (GI(50) = 5.4-17.2 microM). (13)C NMR data for compounds (3, 4, 5, 6a,7, and 8) are described for the first time.

Mini-sternotomy for the treatment of aortic valve lesions.

OBJECTIVE: To compare inverted-L mini-sternotomy performed above the sternal furcula with conventional sternotomy in patients with aortic valve diseases who undergo surgical treatment. METHODS: We operated upon 30 patients who had aortic valve lesions that had clinical and hemodynamic findings. All patients underwent inverted-L sternotomy, which extended from above the manubrium of the sternum to the 3rd right intercostal space, without opening the pleural cavity. Their ages ranged from 32 to 76 years, and 18 were males and 12 were females. We used negative pressure in a venous 1/4-inch cannula, and the patients were maintained in Trendelemburg's position. Twenty-seven patients received bioprostheses with diameters ranging from 23 to 29mm. Three patients underwent only removal of the calcifications of the aortic valve leaflets and aortic commissurotomy. RESULTS: The mean duration of anoxic cardiac arrest was 63.11min. Access was considered good in all patients. One death was due to pulmonary and renal problems not related to the incision. All patients had a better recovery in the intensive care unit, got out of bed sooner, coughed more easily, and performed prophylactic physiotherapeutic maneuvers for respiratory problems more easily and with less pain in the incision. Early ambulation was more easily carried out by all patients. CONCLUSION: Mini-sternotomy proved to be better than the conventional sternotomy because it provided more comfort for the patients in the early postoperative period, with less pain and greater desire for early ambulation and all its inherent advantages.

Myosin thick filaments from adult rabbit skeletal muscles.

Myosin subfragment 1 (S1) forms dimers in the presence of Mg(2+) or MgADP or MgATP. The entire myosin molecule forms head-head dimers in the presence of MgATP. The angle between the two subunits in the S1 dimer is 95 degrees. Assuming that the length of the globular part of S1 is approximately 12 nm and that the S1/S2 joint (lever arm approximately 7 nm) is clearly bent, the cylinder tangent to this dimer should have a diameter of approximately 18 nm, close to the approximately 16-20 nm suggested by many studies for the diameter of thick filaments in situ. These conclusions led us to re-examine our previous model, according to which two heads from two opposite myosin molecules are inserted into the filament core and interact as dimers. We studied synthetic filaments by electron microscopy, enzyme activity assays, controlled digestion and filament-filament interaction analysis. Synthetic filaments formed by rapid dilution in the presence of 1 mM EDTA at room temperature ( approximately 22 degrees C) had all their myosin heads outside the backbone. These filaments are called superfilaments (SF). Synthetic filaments formed by slow dilution, in the presence of either 2 mM Mg(2+) or 0.5 mM MgATP and at low temperature ( approximately 0 degrees C) had one myosin head outside the backbone and one head inside. These filaments are called filaments (F). Synthetic filaments formed by slow dilution, in the presence of 4 mM MgATP at low temperature ( approximately 0 degrees C) had most of their heads inserted in the filament core. These filaments are called antifilaments (AF). These experimental results provide important new information about myosin synthetic filaments. In particular, we found that myosin heads were involved in filament assembly and that filament-filament interactions can occur via the external heads. Native filaments (NF) from rabbit psoas muscle were also studied by enzyme assays. Their structure depended on the age of the rabbit. NF from 4-month-old rabbits were three-stranded, i.e. six myosin heads per crown, two of which were inside the core and four outside. NF from 18-month-old rabbits were two-stranded (similar to F).