Brief report: perioperative analgesic efficacy and plasma concentrations of S+ -ketamine in continuous epidural infusion during thoracic surgery.

BACKGROUND: In our study, we evaluated the analgesic effect and plasma level time course of subanesthetic doses of intraoperative S(+)-ketamine administered by continuous epidural infusion for postthoracotomic pain. METHODS: A study population of 140 patients undergoing thoracic surgery was randomly assigned to either S(+)-ketamine or ropivacaine by continuous epidural infusion. The outcome measures were as follows: (a) intraoperative fentanyl requirements; (b) postoperative pain intensity; and (c) postoperative rescue analgesics. RESULTS: Intraoperative fentanyl consumption was significantly lower (median of difference: -58.6 µg; 95% confidence interval [CI], -97.2 to -19.6 µg; P = 0.0032) in patients in the ketamine group than those in the ropivacaine group. Postoperative visual analog scale scores were significantly lower in the ketamine group than in controls (Wilcoxon-Mann-Whitney odds at 24 hours = 6.25; 95% CI, 4.07 to 1.97; P < 0.0001). Rescue analgesics were required more frequently in controls than in the ketamine group (percentage difference: 58.6%; 95% CI, 43.3% to 69.6%; P < 0.0001). The mean plasma level of ketamine declined rapidly during continuous epidural infusion and decayed slowly after it had stopped. CONCLUSIONS: Our data show that epidural infusion of subanesthetic doses of S(+)-ketamine during thoracic surgery provides better postoperative analgesia than epidural ropivacaine.

Engineering Efforts to Refine Compatibility and Duration of Aortic Valve Replacements: An Overview of Previous Expectations and New Promises.

The absence of pharmacological treatments to reduce or retard the progression of cardiac valve diseases makes replacement with artificial prostheses (mechanical or bio-prosthetic) essential. Given the increasing incidence of cardiac valve pathologies, there is always a more stringent need for valve replacements that offer enhanced performance and durability. Unfortunately, surgical valve replacement with mechanical or biological substitutes still leads to disadvantages over time. In fact, mechanical valves require a lifetime anticoagulation therapy that leads to a rise in thromboembolic complications, while biological valves are still manufactured with non-living tissue, consisting of aldehyde-treated xenograft material (e.g., bovine pericardium) whose integration into the host fails in the mid- to long-term due to unresolved issues regarding immune-compatibility. While various solutions to these shortcomings are currently under scrutiny, the possibility to implant fully biologically compatible valve replacements remains elusive, at least for large-scale deployment. In this regard, the failure in translation of most of the designed tissue engineered heart valves (TEHVs) to a viable clinical solution has played a major role. In this review, we present a comprehensive overview of the TEHVs developed until now, and critically analyze their strengths and limitations emerging from basic research and clinical trials. Starting from these aspects, we will also discuss strategies currently under investigation to produce valve replacements endowed with a true ability to self-repair, remodel and regenerate. We will discuss these new developments not only considering the scientific/technical framework inherent to the design of novel valve prostheses, but also economical and regulatory aspects, which may be crucial for the success of these novel designs.

Luminal endothelialization of small caliber silk tubular graft for vascular constructs engineering.

The constantly increasing incidence of coronary artery disease worldwide makes necessary to set advanced therapies and tools such as tissue engineered vessel grafts (TEVGs) to surpass the autologous grafts [(i.e., mammary and internal thoracic arteries, saphenous vein (SV)] currently employed in coronary artery and vascular surgery. To this aim, in vitro cellularization of artificial tubular scaffolds still holds a good potential to overcome the unresolved problem of vessel conduits availability and the issues resulting from thrombosis, intima hyperplasia and matrix remodeling, occurring in autologous grafts especially with small caliber (<6 mm). The employment of silk-based tubular scaffolds has been proposed as a promising approach to engineer small caliber cellularized vascular constructs. The advantage of the silk material is the excellent manufacturability and the easiness of fiber deposition, mechanical properties, low immunogenicity and the extremely high in vivo biocompatibility. In the present work, we propose a method to optimize coverage of the luminal surface of silk electrospun tubular scaffold with endothelial cells. Our strategy is based on seeding endothelial cells (ECs) on the luminal surface of the scaffolds using a low-speed rolling. We show that this procedure allows the formation of a nearly complete EC monolayer suitable for flow-dependent studies and vascular maturation, as a step toward derivation of complete vascular constructs for transplantation and disease modeling.

Enhancing Cubes with Models to Describe Multidimensional Data.

The Intentional Analytics Model (IAM) has been recently envisioned as a new paradigm to couple OLAP and analytics. It relies on two basic ideas: (i) letting the user explore data by expressing her analysis intentions rather than the data she needs, and (ii) returning enhanced cubes, i.e., multidimensional data annotated with knowledge insights in the form of interesting model components (e.g., clusters). In this paper we contribute to give a proof-of-concept for the IAM vision by delivering an end-to-end implementation of describe, one of the five intention operators introduced by IAM. Among the research challenges left open in IAM, those we address are (i) automatically tuning the size of models (e.g., the number of clusters), (ii) devising a measure to estimate the interestingness of model components, (iii) selecting the most effective chart or graph for visualizing each enhanced cube depending on its features, and (iv) devising a visual metaphor to display enhanced cubes and interact with them. We assess the validity of our approach in terms of user effort for formulating intentions, effectiveness, efficiency, and scalability.

Lithotripsy of Calcified Aortic Valve Leaflets by a Novel Ultrasound Transcatheter-Based Device.

The increasing incidence of calcific aortic valve disease necessitates the elaboration of new strategies to retard the progression of the pathology with an innovative solution. While the increasing diffusion of the transcatheter aortic valve replacements (TAVRs) allows a mini-invasive approach to aortic valve substitution as an alternative to conventional surgical replacement (SAVR) in an always larger patient population, TAVR implantation still has contraindications for young patients. In addition, it is liable to undergo calcification with the consequent necessity of re-intervention with conventional valve surgery or repeated implantation in the so-called TAVR-in-TAVR procedure. Inspired by applications for non-cardiac pathologies or for vascular decalcification before stenting (i.e., coronary lithotripsy), in the present study, we show the feasibility of human valve treatment with a mini-invasive device tailored to deliver shockwaves to the calcific leaflets. We provide evidence of efficient calcium deposit ruptures in human calcified leaflets treated ex vivo and the safety of the treatment in pigs. The use of this device could be helpful to perform shockwaves valvuloplasty as an option to retard TAVR/SAVR, or as a pretreatment to facilitate prosthesis implantation and minimize the occurrence of paravalvular leak.

Environmental Distribution of AR Class 1 Integrons in Upper Adige River Catchment (Northern Italy).

The source of antibiotic residuals can be directly related to the presence of municipal or industrial wastewater and agricultural activities. Antibiotics can trigger the dissemination of antibiotic resistance genes within bacterial communities. The mobile genetic elements Class 1 integrons (intl1 region) has been already found to be correlated with a wide range of pollutants (i.e., antibiotics, heavy metals), and hence, it has been proposed as a proxy for environmental health. This study aimed to assess the presence of intl1 in different environmental matrices, including agricultural and forest soils, freshwater and unpolluted sediments in the upper Adige River catchment (N Italy), in order to identify the spread of pollutants. Intl1 was detected by direct PCR amplification at different frequencies. The urban and agricultural areas revealed the presence of intl1, except for apple orchards, where it was below the detection limit. Interestingly, intl1 was found in a presumed unpolluted environment (glacier moraine), maybe because of the high concentration of metal ions in the mineral soil. Finally, intl1 was absent in forest fresh-leaf litter samples and occurred with low rates in soil. Our results provide new data in supporting the use of intl1 to detect the environmental health of different land-use systems.

Harnessing Mechanosensation in Next Generation Cardiovascular Tissue Engineering.

The ability of the cells to sense mechanical cues is an integral component of "social" cell behavior inside tissues with a complex architecture. Through "mechanosensation" cells are in fact able to decrypt motion, geometries and physical information of surrounding cells and extracellular matrices by activating intracellular pathways converging onto gene expression circuitries controlling cell and tissue homeostasis. Additionally, only recently cell mechanosensation has been integrated systematically as a crucial element in tissue pathophysiology. In the present review, we highlight some of the current efforts to assess the relevance of mechanical sensing into pathology modeling and manufacturing criteria for a next generation of cardiovascular tissue implants.

Culture Into Perfusion-Assisted Bioreactor Promotes Valve-Like Tissue Maturation of Recellularized Pericardial Membrane.

Derivation of tissue-engineered valve replacements is a strategy to overcome the limitations of the current valve prostheses, mechanical, or biological. In an effort to set living pericardial material for aortic valve reconstruction, we have previously assessed the efficiency of a recellularization strategy based on a perfusion system enabling mass transport and homogenous distribution of aortic valve-derived "interstitial" cells inside decellularized pericardial material. In the present report, we show that alternate perfusion promoted a rapid growth of valve cells inside the pericardial material and the activity of a proliferation-supporting pathway, likely controlled by the YAP transcription factor, a crucial component of the Hippo-dependent signaling cascade, especially between 3 and 14 days of culture. Quantitative mass spectrometry analysis of protein content in the tissue constructs showed deposition of valve proteins in the decellularized pericardium with a high variability at day 14 and a reproducible tissue maturation at 21 days. These results represent a step forward in the definition of strategies to produce a fully engineered tissue for replacing the calcified leaflets of failing aortic valves.

Plasmopara viticola infection affects mineral elements allocation and distribution in Vitis vinifera leaves.

Plasmopara viticola is one of the most important pathogens infecting Vitis vinifera plants. The interactions among P. viticola and both susceptible and resistant grapevine plants have been extensively characterised, at transcriptomic, proteomic and metabolomic levels. However, the involvement of plants ionome in the response against the pathogen has been completely neglected so far. Therefore, this study was aimed at investigating the possible role of leaf ionomic modulation during compatible and incompatible interactions between P. viticola and grapevine plants. In susceptible cultivars, a dramatic redistribution of mineral elements has been observed, thus uncovering a possible role for mineral nutrients in the response against pathogens. On the contrary, the resistant cultivars did not present substantial rearrangement of mineral elements at leaf level, except for manganese (Mn) and iron (Fe). This might demonstrate that, resistant cultivars, albeit expressing the resistance gene, still exploit a pathogen response mechanism based on the local increase in the concentration of microelements, which are involved in the synthesis of secondary metabolites and reactive oxygen species. Moreover, these data also highlight the link between the mineral nutrition and plants' response to pathogens, further stressing that appropriate fertilization strategies can be fundamental for the expression of response mechanisms against pathogens.