Autologous microsurgical breast reconstruction and coronary artery bypass grafting: an anatomical study and clinical implications

OBJECTIVE: To identify possible avenues of sparing the internal mammary artery (IMA) for coronary artery bypass grafting (CABG) in women undergoing autologous breast reconstruction with deep inferior epigastric artery perforator (DIEP) flaps. BACKGROUND: Optimal autologous reconstruction of the breast and coronary artery bypass grafting (CABG) are often mutually exclusive as they both require utilisation of the IMA as the preferred arterial conduit. Given the prevalence of both breast cancer and coronary artery disease, this is an important issue for women's health as women with DIEP flap reconstructions and women at increased risk of developing coronary artery disease are potentially restricted from receiving this reconstructive option should the other condition arise. METHODS: The largest clinical and cadaveric anatomical study (n=315) to date was performed, investigating four solutions to this predicament by correlating the precise requirements of breast reconstruction and CABG against the anatomical features of the in situ IMAs. This information was supplemented by a thorough literature review. RESULTS: Minimum lengths of the left and right IMA needed for grafting to the left-anterior descending artery are 160.08 and 177.80 mm, respectively. Based on anatomical findings, the suitable options for anastomosis to each intercostals space are offered. In addition, 87-91% of patients have IMA perforator vessels to which DIEP flaps can be anastomosed in the first- and second-intercostal spaces. CONCLUSION: We outline five methods of preserving the IMA for future CABG: (1) lowering the level of DIEP flaps to the fourth- and fifth-intercostals spaces, (2) using the DIEP pedicle as an intermediary for CABG, (3) using IMA perforators to spare the IMA proper, (4) using and end-to-side anastomosis between the DIEP pedicle and IMA and (5) anastomosis of DIEP flaps using retrograde flow from the distal IMA. With careful patient selection, we hypothesize using the IMA for autologous breast reconstruction need not be an absolute contraindication for future CABG

Radiofrequency-based treatment in therapy-related clinical practice – a narrative review. Part I : acute conditions

This is an Accepted Manuscript of an article published by Taylor & Francis Group in Physical Therapy Reviews on 24 June 2015, available online at: https://www.tandfonline.com/doi/full/10.1179/1743288X15Y.0000000016Background: Radiofrequency electromagnetic field (RFEMF or simply RF)-based electrophysical agents (EPAs) have been employed in therapy-related clinical practice for several decades. They are used to reduce pain and inflammation and enhance tissue healing. Although these agents have generally become less popular in contemporary therapy practice, surveys have shown that some of these modalities are still reasonably widely used. Objective: To review the evidence for the use of non-invasive low frequency RFs (30 kHz–30 MHz) in therapy-related clinical practice. Major findings: All peer reviewed therapy-related clinical studies published in English and concerning low frequency RF were sought. Identified literature was divided into acute and chronic segments based on their clinical area and analysed to assess the volume and scope of current evidence. The studies on acute conditions were reviewed in detail for this paper. One hundred twenty clinical studies were identified, of which 30 related to acute conditions. The majority of studies employed Pulsed Shortwave Therapy (PSWT). Twenty-two studies out of 30 were related to conditions of pain and inflammation, seven to tissue healing and one to acute pneumothorax. No studies were identified on frequencies other than shortwave. Conclusions: Evidence for and against RF-based therapy is available. There is reasonable evidence in support of PSWT to alleviate postoperative pain and promote postoperative wound healing. Evidence for other acute conditions is sparse and conflicting. A general lack of research emphasis in the non-shortwave RF band is evident, with studies on acute conditions almost non-existent. Further and wider research in this area is warranted.Peer reviewe

Webinar Training: an acceptable, feasible and effective approach for multi-site medical record abstraction: the BOWII experience

<p>Abstract</p> <p>Background</p> <p>Abstractor training is a key element in creating valid and reliable data collection procedures. The choice between in-person vs. remote or simultaneous vs. sequential abstractor training has considerable consequences for time and resource utilization. We conducted a web-based (webinar) abstractor training session to standardize training across six individual Cancer Research Network (CRN) sites for a study of breast cancer treatment effects in older women (BOWII). The goals of this manuscript are to describe the training session, its participants and participants' evaluation of webinar technology for abstraction training.</p> <p>Findings</p> <p>A webinar was held for all six sites with the primary purpose of simultaneously training staff and ensuring consistent abstraction across sites. The training session involved sequential review of over 600 data elements outlined in the coding manual in conjunction with the display of data entry fields in the study's electronic data collection system. Post-training evaluation was conducted via Survey Monkey^©. Inter-rater reliability measures for abstractors within each site were conducted three months after the commencement of data collection.</p> <p>Ten of the 16 people who participated in the training completed the online survey. Almost all (90%) of the 10 trainees had previous medical record abstraction experience and nearly two-thirds reported over 10 years of experience. Half of the respondents had previously participated in a webinar, among which three had participated in a webinar for training purposes. All rated the knowledge and information delivered through the webinar as useful and reported it adequately prepared them for data collection. Moreover, all participants would recommend this platform for multi-site abstraction training. Consistent with participant-reported training effectiveness, results of data collection inter-rater agreement within sites ranged from 89 to 98%, with a weighted average of 95% agreement across sites.</p> <p>Conclusions</p> <p>Conducting training via web-based technology was an acceptable and effective approach to standardizing medical record review across multiple sites for this group of experienced abstractors. Given the substantial time and cost savings achieved with the webinar, coupled with participants' positive evaluation of the training session, researchers should consider this instructional method as part of training efforts to ensure high quality data collection in multi-site studies.</p

Mouse Embryonic Retina Delivers Information Controlling Cortical Neurogenesis

The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development [1]. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded [2], the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs) during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal). Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system

Automatic Design of Synthetic Gene Circuits through Mixed Integer Non-linear Programming

Automatic design of synthetic gene circuits poses a significant challenge to synthetic biology, primarily due to the complexity of biological systems, and the lack of rigorous optimization methods that can cope with the combinatorial explosion as the number of biological parts increases. Current optimization methods for synthetic gene design rely on heuristic algorithms that are usually not deterministic, deliver sub-optimal solutions, and provide no guaranties on convergence or error bounds. Here, we introduce an optimization framework for the problem of part selection in synthetic gene circuits that is based on mixed integer non-linear programming (MINLP), which is a deterministic method that finds the globally optimal solution and guarantees convergence in finite time. Given a synthetic gene circuit, a library of characterized parts, and user-defined constraints, our method can find the optimal selection of parts that satisfy the constraints and best approximates the objective function given by the user. We evaluated the proposed method in the design of three synthetic circuits (a toggle switch, a transcriptional cascade, and a band detector), with both experimentally constructed and synthetic promoter libraries. Scalability and robustness analysis shows that the proposed framework scales well with the library size and the solution space. The work described here is a step towards a unifying, realistic framework for the automated design of biological circuits

Eugene – A Domain Specific Language for Specifying and Constraining Synthetic Biological Parts, Devices, and Systems

BACKGROUND: Synthetic biological systems are currently created by an ad-hoc, iterative process of specification, design, and assembly. These systems would greatly benefit from a more formalized and rigorous specification of the desired system components as well as constraints on their composition. Therefore, the creation of robust and efficient design flows and tools is imperative. We present a human readable language (Eugene) that allows for the specification of synthetic biological designs based on biological parts, as well as provides a very expressive constraint system to drive the automatic creation of composite Parts (Devices) from a collection of individual Parts. RESULTS: We illustrate Eugene's capabilities in three different areas: Device specification, design space exploration, and assembly and simulation integration. These results highlight Eugene's ability to create combinatorial design spaces and prune these spaces for simulation or physical assembly. Eugene creates functional designs quickly and cost-effectively. CONCLUSIONS: Eugene is intended for forward engineering of DNA-based devices, and through its data types and execution semantics, reflects the desired abstraction hierarchy in synthetic biology. Eugene provides a powerful constraint system which can be used to drive the creation of new devices at runtime. It accomplishes all of this while being part of a larger tool chain which includes support for design, simulation, and physical device assembly

Thyroid Hormone T3 Counteracts STZ Induced Diabetes in Mouse

This study intended to demonstrate that the thyroid hormone T3 counteracts the onset of a Streptozotocin (STZ) induced diabetes in wild type mice. To test our hypothesis diabetes has been induced in Balb/c male mice by multiple low dose Streptozotocin injection; and a group of mice was contemporaneously injected with T3. After 48 h mice were tested for glucose tolerance test, insulin serum levels and then sacrified. Whole pancreata were utilized for morphological and biochemical analyses, while protein extracts and RNA were utilized for expression analyses of specific molecules. The results showed that islets from T3 treated mice were comparable to age- and sex-matched control, untreated mice in number, shape, dimension, consistency, ultrastructure, insulin and glucagon levels, Tunel positivity and caspases activation, while all the cited parameters and molecules were altered by STZ alone. The T3-induced pro survival effect was associated with a strong increase in phosphorylated Akt. Moreover, T3 administration prevented the STZ-dependent alterations in glucose blood level, both during fasting and after glucose challenge, as well as in insulin serum level. In conclusion we demonstrated that T3 could act as a protective factor against STZ induced diabetes

OptCircuit: An optimization based method for computational design of genetic circuits

<p>Abstract</p> <p>Background</p> <p>Recent years has witnessed an increasing number of studies on constructing simple synthetic genetic circuits that exhibit desired properties such as oscillatory behavior, inducer specific activation/repression, etc. It has been widely acknowledged that that task of building circuits to meet multiple inducer-specific requirements is a challenging one. This is because of the incomplete description of component interactions compounded by the fact that the number of ways in which one can chose and interconnect components, increases exponentially with the number of components.</p> <p>Results</p> <p>In this paper we introduce OptCircuit, an optimization based framework that automatically identifies the circuit components from a list and connectivity that brings about the desired functionality. Multiple literature sources are used to compile a comprehensive compilation of kinetic descriptions of promoter-protein pairs. The dynamics that govern the interactions between the elements of the genetic circuit are currently modeled using deterministic ordinary differential equations but the framework is general enough to accommodate stochastic simulations. The desired circuit response is abstracted as the maximization/minimization of an appropriately constructed objective function. Computational results for a toggle switch example demonstrate the ability of the framework to generate the complete list of circuit designs of varying complexity that exhibit the desired response. Designs identified for a genetic decoder highlight the ability of OptCircuit to suggest circuit configurations that go beyond the ones compatible with digital logic-based design principles. Finally, the results obtained from the concentration band detector example demonstrate the ability of OptCircuit to design circuits whose responses are contingent on the level of external inducer as well as pinpoint parameters for modification to rectify an existing (non-functional) biological circuit and restore functionality.</p> <p>Conclusion</p> <p>Our results demonstrate that OptCircuit framework can serve as a design platform to aid in the construction and finetuning of integrated biological circuits.</p

Mesenteric Resistance Arteries in Type 2 Diabetic db/db Mice Undergo Outward Remodeling

Resistance vessel remodeling is controlled by myriad of hemodynamic and neurohormonal factors. This study characterized structural and molecular remodeling in mesenteric resistance arteries (MRAs) in diabetic (db/db) and control (Db/db) mice.Structural properties were assessed in isolated MRAs from 12 and 16 wk-old db/db and Db/db mice by pressure myography. Matrix regulatory proteins were measured by Western blot analysis. Mean arterial pressure and superior mesenteric blood flow were measured in 12 wk-old mice by telemetry and a Doppler flow nanoprobe, respectively.Blood pressure was similar between groups. Lumen diameter and medial cross-sectional area were significantly increased in 16 wk-old db/db MRA compared to control, indicating outward hypertrophic remodeling. Moreover, wall stress and cross-sectional compliance were significantly larger in diabetic arteries. These remodeling indices were associated with increased expression of matrix regulatory proteins matrix metalloproteinase (MMP)-9, MMP-12, tissue inhibitors of matrix metalloproteinase (TIMP)-1, TIMP-2, and plasminogen activator inhibitor-1 (PAI-1) in db/db arteries. Finally, superior mesenteric artery blood flow was increased by 46% in 12 wk-old db/db mice, a finding that preceded mesenteric resistance artery remodeling.These data suggest that flow-induced hemodynamic changes may supersede the local neurohormonal and metabolic milieu to culminate in hypertrophic outward remodeling of type 2 DM mesenteric resistance arteries