Skin-reducing mastectomy and one-stage implant reconstruction with a myodermal flap: A safe and effective technique in risk-reducing and therapeutic mastectomy

Introduction: Immediate reconstruction following mastectomy for breast cancer has been shown to be oncologically safe and associated with improved psychosocial outcomes for patients. Bostwick described a technique for one-stage implant based reconstruction, combining skin-sparing mastectomy with concurrent reduction of the skin envelope. This report reviews the experience of a single centre using skin-reducing mastectomy and one-stage implant reconstruction in both early stage breast cancer and risk-reducing mastectomy, with specific reference to frequency of complications, implant loss and oncological outcomes.

Methods and results: A retrospective review was undertaken to identify women who had undergone skin-reducing mastectomy and one-stage implant reconstruction using a de-epithelialised dermal flap, between October 2008 and October 2012. One hundred and four consecutive mastectomies, with reconstruction, were performed by two surgeons on 64 patients. No complications were seen in 43.8% of patients. At three months, four implants were lost (3.8% of breast reconstructions, 6.3% of patients), due to either peri-implant infection or mastectomy skin flap necrosis. One patient required unplanned return to theatre for evacuation of a haematoma. Minor mastectomy skin flap necrosis was seen in 10 breasts (9.6% of reconstructed breasts) and superficial wound infection in 8 breasts (7.7% of reconstructed breasts). All of these complications were managed conservatively and none required operative intervention. At a median follow up of 35 months (4-53 months) there had been one episode of ipsilateral axillary nodal recurrence.

Conclusion: One-stage implant reconstruction using a myo-dermal flap technique following skin-reducing mastectomy is safe and should be considered in selected patients. Most complications are minor and will resolve with conservative management. Major complications such as implant failure or immediate reoperation, were relatively uncommon (6.3% patients, 3.8% of reconstructed breasts). Early follow-up suggests that oncological outcomes are satisfactory, but longer follow-up is required to substantiate this. (C) 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Unspliced X-box-binding Protein 1 (XBP1) Protects Endothelial Cells from Oxidative Stress through Interaction with Histone Deacetylase 3

It is well-known that atherosclerosis occurs geographically at branch points where disturbed flow predisposes to the development of plaque via triggering of oxidative stress and inflammatory reactions. In this study, we found that disturbed flow activated anti-oxidative reactions via up-regulating heme oxygenase 1 (HO-1) in an X-box binding protein 1 (XBP1) and histone deacetylase 3 (HDAC3)-dependent manner. Disturbed flow concomitantly up-regulated the unspliced XBP1 (XBP1u) and HDAC3 in a vascular endothelial growth factor receptor (VEGFR) and PI3K/Akt dependent manner. The presence of XBP1 was essential for the up-regulation of HDAC3 protein. Over-expression of XBP1u and/or HDAC3 activated Akt1 phosphorylation, Nrf2 protein stabilization and nuclear translocation, and HO-1 expression. Knockdown of XBP1u decreased the basal level and disturbed flow-induced Akt1 phosphorylation, Nrf2 stabilization and HO-1 expression. Knockdown of HDAC3 ablated XBP1u-mediated effects. The mammalian target of rapamycin complex 2 (mTORC2) inhibitor, AZD2014, ablated XBP1u or HDAC3 or disturbed flow-mediated Akt1 phosphorylation, Nrf2 nuclear translocation and HO-1 expression. Neither actinomycin D nor cycloheximide affected disturbed flow-induced up-regulation of Nrf2 Protein. Knockdown of Nrf2 abolished XBP1u or HDAC3 or disturbed flow-induced HO-1 up-regulation. Co-immunoprecipitation assays demonstrated that XBP1u physically bound to HDAC3 and Akt1. The region of amino acids 201 to 323 of the HDAC3 protein was responsible for the binding to XBP1u. Double immunofluorescence staining revealed that the interactions between Akt1 and mTORC2, Akt1 and HDAC3, Akt1 and XBP1u, HDAC3 and XBP1u occurred in the cytosol. Thus, we demonstrate that XBP1u and HDAC3 exert a protective effect on disturbed flow-induced oxidative stress via up-regulation of mTORC2-dependent Akt1 phosphorylation and Nrf2-mediated HO-1 expression.

Containing the Nanometer "Pandora-Box": Cross-Layer Design Techniques for Variation Aware Low Power Systems

The demand for richer multimedia services, multifunctional portable devices and high data rates can only been visioned due to the improvement in semiconductor technology. Unfortunately, sub-90 nm process nodes uncover the nanometer Pandora-box exposing the barriers of technology scaling-parameter variations, that threaten the correct operation of circuits, and increased energy consumption, that limits the operational lifetime of today's systems. The contradictory design requirements for low-power and system robustness, is one of the most challenging design problems of today. The design efforts are further complicated due to the heterogeneous types of designs ( logic, memory, mixed-signal) that are included in today's complex systems and are characterized by different design requirements. This paper presents an overview of techniques at various levels of design abstraction that lead to low power and variation aware logic, memory and mixed-signal circuits and can potentially assist in meeting the strict power budgets and yield/quality requirements of future systems.

Safe moving and handling of patients: an inter-professional approach

A gap in the medical undergraduate curriculum on safe moving and handling of patients was identified, and a project to enhance moving and handling education for undergraduates in various healthcare disciplines was undertaken. A team of nurses, doctors, physiotherapists and e-learning professionals developed a cross-discipline e-learning resource, piloted with medical and nursing students at Queen’s University Belfast. One outcome of the project was the development of a deeper recognition of the common curriculum across healthcare disciplines.

The struggle for safe staffing levels in the USA: A political economy of evidence-based practice

This paper examines the debate over nursing staff to patient ratios through the lens of Marxist political economy, arguing that the owners and controllers of healthcare in the USA have a vested interest in opposing mandated minimum ratios, while those involved in carrying out nursing care have a vested interest in their implementation, which coincides with the interests of patients. We examine how evidence-based practice articulates with social power, and proceed to interrogate the research methods used to generate evidence for practice, noting that randomised controlled trials are not suitable for evaluating nurse/patient ratios, which means that observational studies are the primary source of evidence. Representatives of nursing managers have used the fact that observational studies, while demonstrating an association between high ratios and poor outcomes, have not established a causal relationship, to support their argument that there is not sufficient evidence for the imposition of mandatory ratios. We argue that the precautionary principle provides firm justification for mandatory ratios, unless and until a causal relationship has been disproved. We conclude that those involved in the generation of evidence have to choose between technical arguments about the inferiority of observational studies, or emphasising their sufficiency in triggering the precautionary principle.

Can Safe Clinical Thinking be Taught?

OBJECTIVES: To determine if: (a) safe clinical decision making can be taught to undergraduate final year medical students and (b) if such students can be taught to specifically recognise illness severity from nominal clinical data. 
METHODS: 115 final year undergraduate medical students completed a 3 hour interactive Safe Thinking Workshop which focussed entirely on nontechnical skills such as potential perceptive pitfalls, attention to detail, teamwork and safe clinical decision making. The study involved students inspecting and interpreting a set of arterial blood gas results relating to a patient with acute respiratory distress, then answering a short questionnaire addressing biochemical diagnosis, clinical diagnosis and effective management. A separate question was embedded in the questionnaire to determine if astute students could determine the severity of the illness from the CO2 value provided. The study group (n = 58) completed the questionnaire immediately after the Safe Thinking Workshop, whilst the control group (n = 57) completed the questionnaire prior to the Workshop.
RESULTS: The mean total score for study students was 80.51%, with a mean total score of 63.86% for the control group (Student’s t-test; p<0.05). Correct classification of illness severity was observed in 10.35% of study students, compared with 3.51% of control students (p<0.05). 
CONCLUSION: These results suggest that safe clinical decision making and recognition of illness severity can be fostered by specific teaching in the nontechnical skill areas described above.

DEAD-box helicase DP103 defines metastatic potential of human breast cancers

Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β-activated kinase-1 (TAK1) phosphorylation of NF-κB-activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB-mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment.

STARTEC: Novel processing technologies in the development of a decision support tool to ensure safe and nutritious Ready-To-Eat foods

Ready-to-eat (RTE) foods can be readily consumed with minimum or without any further preparation; their processing is complex—involving thorough decontamination processes— due to their composition of mixed ingredients. Compared with conventional preservation technologies, novel processing technologies can enhance the safety and quality of these complex products by reducing the risk of pathogens and/ or by preserving related health-promoting compounds. These novel technologies can be divided into two categories: thermal and non-thermal. As a non-thermal treatment, High Pressure Processing is a very promising novel methodology that can be used even in the already packaged RTE foods. A new “volumetric” microwave heating technology is an interesting cooking and decontamination method directly applied to foods. Cold Plasma technology is a potential substitute of chlorine washing in fresh vegetable decontamination. Ohmic heating is a heating method applicable to viscous products but also to meat products. Producers of RTE foods have to deal with challenging decisions starting from the ingredients suppliers to the distribution chain. They have to take into account not only the cost factor but also the benefits and food products’ safety and quality. Novel processing technologies can be a valuable yet large investment for several SME food manufacturers, but they need support data to be able to make adequate decisions. Within the FP7 Cooperation funded by the European Commission, the STARTEC project aims to develop an IT decision supporting tool to help food business operators in their risk assessment and future decision making when producing RTE foods with or without novel preservation technologies.

Phytoremediation assessment of Gomphrena globosa and Zinnia elegans grown in arsenic-contaminated hydroponic conditions as a safe and feasible alternative to be applied in arsenic-contaminated soils of the Bengal Delta

Several agricultural fields show high contents of arsenic because of irrigation with arsenic- contaminated groundwater. Vegetables accumulate arse- nic in their edible parts when grown in contaminated soils. Polluted vegetables are one of the main sources of arsenic in the food chain, especially for people living in rural arsenic endemic villages of India and Bangladesh. The aim of this study was to assess the feasibility of floriculture in the crop rotation system of arsenic en- demic areas of the Bengal Delta. The effects of different arsenic concentrations (0, 0.5, 1.0, and 2.0 mg As L−1) and types of flowering plant (Gomphrena globosa and Zinnia elegans) on plant growth and arsenic accumula- tion were studied under hydroponic conditions. Total arsenic was quantified using atomic absorption spec- trometer with hydride generation (HG-AAS). Arsenic was mainly accumulated in the roots (72 %), followed by leaves (12 %), stems (10 %), and flowers (<1 %). The flowering plants studied did not show as high phytoremediation capacities as other wild species, suchas ferns. However, they behaved as arsenic tolerant plants and grew and bloomed well, without showing any phytotoxic signs. This study proves that floriculture could be included within the crop rotation system in arsenic-contaminated agricultural soils, in order to im- prove food safety and also food security by increasing farmer’s revenue.