Radiation exposure and breast cancer: lessons from Chernobyl.

The lessons learned from the Chernobyl disaster have become increasingly important after the second anniversary of the Fukushima, Japan nuclear accident. Historically, data from the Chernobyl reactor accident 27 years ago demonstrated a strong correlation with thyroid cancer, but data on the radiation effects of Chernobyl on breast cancer incidence have remained inconclusive. We reviewed the published literature on the effects of the Chernobyl disaster on breast cancer incidence, using Medline and Scopus from the time of the accident to December of 2010. Our findings indicate limited data and statistical flaws. Other confounding factors, such as discrepancies in data collection, make interpretation of the results from the published literature difficult. Re-analyzing the data reveals that the incidence of breast cancer in Chernobyl-disaster-exposed women could be higher than previously thought. We have learned little of the consequences of radiation exposure at Chernobyl except for its effects on thyroid cancer incidence. Marking the 27th year after the Chernobyl event, this report sheds light on a specific, crucial and understudied aspect of the results of radiation from a gruesome nuclear power plant disaster.

Pretraining and posttraining assessment of residents' performance in the fourth accreditation council for graduate medical education competency: patient communication skills.

HYPOTHESIS: Structured communication curricula will improve surgical residents' ability to communicate effectively with patients. DESIGN AND SETTING: A prospective study approved by the institutional review board involved 44 University of Connecticut general surgery residents. Residents initially completed a written baseline survey to assess general communication skills awareness. In step 1 of the study, residents were randomized to 1 of 2 simulations using standardized patient instructors to mimic patients receiving a diagnosis of either breast or rectal cancer. The standardized patient instructors scored residents' communication skills using a case-specific content checklist and Master Interview Rating Scale. In step 2 of the study, residents attended a 3-part interactive program that comprised (1) principles of patient communication; (2) experiences of a surgeon (role as physician, patient, and patient's spouse); and (3) role-playing (3-resident groups played patient, physician, and observer roles and rated their own performance). In step 3, residents were retested as in step 1, using a crossover case design. Scores were analyzed using Wilcoxon signed rank test with a Bonferroni correction. RESULTS: Case-specific performance improved significantly, from a pretest content checklist median score of 8.5 (65%) to a posttest median of 11.0 (84%) (P = .005 by Wilcoxon signed rank test for paired ordinal data)(n = 44). Median Master Interview Rating Scale scores changed from 58.0 before testing (P = .10) to 61.5 after testing (P = .94). Difference between overall rectal cancer scores and breast cancer scores also were not significant. CONCLUSIONS: Patient communication skills need to be taught as part of residency training. With limited training, case-specific skills (herein, involving patients with cancer) are likely to improve more than general communication skills.

Phagocytosis of fungal agents and yeast via macrophage cell surface scavenger receptors.

BACKGROUND: Macrophages mediate phagocytosis via cell-surface pattern-recognition-receptors (PRRs) known to recognize certain fixed patterns on pathogens. Of these PRRs, scavenger receptors class A I and II (SR-A I and II) are known to mediate the binding and internalization of a large variety of Gram +ve and Gram -ve bacteria. Their role in phagocytic clearance of fungal agents has not been described. METHODS: Fluorescence microscopy and phagocytosis assays were used on murine macrophage cell lines RAW264.7. Chinese hamster ovarian cell lines (CHO) transfected with SR-A-I or SRA-II and known ligands that block SRA-uptake were used to test the ability of these cells to bind fungal agents. Macrophages from mice genetically deficient in SRA (MSR-knockouts) were used to establish whether absence of these receptors affects fungal uptake. RESULTS: We show for the first time that the SR-A I and II on macrophages are involved in both the binding and phagocytosis of S. cerevisiae and Candida albicans. SRA-mediated binding and internalization of these pathogens is specifically inhibited by known ligands of SRA (Fucoidan and Poly G) in a dose-titratable manner. Further, CHO cells transfected with either SR-A-I or SRA-II show an increased ability to bind and internalize S. cerevisiae compared with the non-transfected parental cells. In contrast, the macrophages that are deficient in the scavenger receptor (obtained from MSR-/- mice) do not show a decreased ability to phagocytose fungal agents. CONCLUSIONS: Scavenger receptors mediate phagocytosis of fungal agents, representing perhaps an alternative, fall back mechanism.

Topical herbal remedies: research opportunities for plastic surgeons.

The use of topical herbal remedies (THRs) among plastic surgery patients is rampant, sometimes indiscriminately, and expanding rapidly. Supporting scientific evidence is low, and most patients who use THRs believe firmly that being 'natural', these agents are 'safe'. The federal regulation of THRs is not uniform. The research potential of these remedies is underexplored, creating a vast opportunity for plastic surgeons to harvest its clinical benefits and help create a regulatory structure that promotes patient safety. This article delineates the critical aspects: essential steps in starting research in THRs, organisational structure to support this work including funding sources, intellectual property and patent protection, federal regulation and patient education and advocacy. These steps create a platform for plastic surgeons to pursue this research work and translate it into the clinical setting effectively.

Phagocytosis: reemerging roles for a primitive function.

BACKGROUND: Described by Metchnikoff, it has been 100 years since the discovery of phagocytosis was awarded the Nobel Prize. Since then, advances in phagocytosis research have vastly expanded its potential clinical application to health and disease. In this article, the authors revisit this process of evolution and chart out its relevance to plastic surgery. METHODS: The discovery and evolution of the concept of phagocytosis are described. Its role in innate and adaptive immune responses is reviewed in the light of converging new discoveries in allied fields. Lastly, how the Rubicon of phagocytosis research could specifically address brittle plastic surgical problems is examined and currently available research tools that would specifically facilitate this work are described. RESULTS: Phagocytosis is centrally important in an expanded repertoire of plastic surgical problems. These include aging, wherein a rapid rate of elimination of apoptotic elements could slow chronologic damage. Other examples include problematic wound repair; skin cancers including melanoma; in radiation and metabolic tissue insult; keloid and hypertrophic scarring; burns and antibiotic-resistant infections; transplantation immunology; regenerative medicine; and lastly "cosmeceuticals," wherein nanoparticle-based drug delivery systems could be explored using novel phagocytic carriers. CONCLUSIONS: For plastic surgeons, phagocytosis research is an attractive opportunity to solve some tough clinical problems. For biologists, the collaboration with plastic surgeons opens a vista of novel translational research. It holds the robust promise of developing a new class of drugs with which to address vast unmet clinical needs. For phagocytosis, its reemergence is a well-deserved encore. Lastly, for Metchnikoff, it is a befitting 100-year anniversary.

Cutaneous myiasis.

Cutaneous myiasis is a unique disease, endemic in tropical areas, and uncommon in the Western world, making its diagnosis difficult for physicians that are unfamiliar with the disease process. Larvae of a two-winged fly are inoculated through normal skin by a mosquito bite. The larvae grow in the subcutaneous tissues, feed off the surrounding tissues and develop into a fly. A patient with a seemingly commonplace cutaneous lesion which was a harbinger of a much more sinister, unique disease process, is presented. Salient features that characterise these lesions, the difficulty in accurate (and timely) diagnosis, treatment and a review of the literature are discussed with the aim of overcoming limitations of diagnosis and management.

Improving surgical residents' performance on written assessments of cultural competency.

CONTEXT: The pressure to implement cultural-competency training at the level of GME is high. The rapidly diversifying American population and the ACGME demand it, and cultural competency is recognized as a core competency under "Professionalism." OBJECTIVES: The objectives for this study were (1) to assess residents' baseline levels of cultural competence, (2) define barriers to skill-acquisition, and (3) examine efficacy of educational programs in improving cultural competence. SETTING & PARTICIPANTS: In all, 43 residents from the University of Connecticut School of Medicine participated in a prospective, Institutional Review Board (IRB)-approved study. DESIGN: During Step 1 (pretest), baseline performance was recorded using 3 assessments: (1) Healthcare Cultural Competency Test (HCCT), (2) Cultural skills acquisition (CSA), and (3) Clinical Scenarios Test (CSE). During Step 2 (Educational Intervention), a 2-part lecture that focused on principles of cultural competency and continued self-learning was presented. Last, for Step 3 (posttest), the post-program evaluation was administered as in Step 1. MAIN OUTCOME MEASURES: Answers for Step 1 (pretest) and Step 3 (posttest) were compared using a paired t-test for HCCT and CSE and the chi-square test for CSA. RESULTS: Thirty-five replies were evaluated. Every resident performed better on the posttest than the pretest. Specifically, participants showed 88% improvement in their scores on the HCCT (pretest: 360, posttest: 696; p < 0.01), 2-fold improvement on the CSA (pretest: 6, posttest: 12; p < 0.009), and 40% improvement in CSE (pretest mean score = 23.3, posttest = 34.6; p < 0.01). Commonly identified barriers to learning included inadequate teaching tools and absence of formal training. CONCLUSIONS: Surgery residents tested for 3 aspects of cultural competence prior to and after teaching sessions showed marked improvement on all 3 assessment measures after this brief intervention.

Pasteur's Quadrant: preparing training programs for "use-inspired" surgical research.

Ensuring that scientific research is an integral element of surgical residency training is critical to the future viability of the field. The ability to nurture surgeon-scientists, invoke them to ask pertinent questions, design experiments, and translate these findings into clinical applications will set this specialty apart from competing fields. Involving residents and younger faculty in this process of translational research is crucial to develop academic leaders and improve patient care. It is as critical as it is complex. Here, we propose that this objective can be attained only if academic departments of surgery recognize its value, create a solid framework of support, encourage partnerships, and above all provide the patient and essential mentorship that residents and young faculty need to pursue meaningful surgical research. To provide usable frameworks, a unique 2-dimensional quadrant termed "Pasteur's Quadrant" is generated based on the original work of Stokes. Briefly, it creates 4 quadrants that separate pure basic science or discovery (X-axis) from applied research or innovation (Y-axis). In doing so, it also defines a median-research that satisfies both goals: scientific advancement AND clinical improvement. This novel use-inspired method of categorizing research provides guidelines to select research programs prudently. Using the Pasteur's Quadrant approach to the conduct of resident-performed surgical research offers several advantages: It is clinically applicable; it advances goals of fundamental scientific research; it is provocative, productive, and retains high visibility; and it makes it attractive to funding agencies and industry alike. Lastly, it charts a vibrant course for their main beneficiaries, residents and academic surgical programs.

Cost-aware care: critical core competency.

HYPOTHESIS: Resident core competence can be improved by learning to accurately estimate the costs of postoperative complications. DESIGN: Prospective, institutional review board-approved study. In step 1, residents were provided 3 clinical vignettes detailing specific treatment measures for postsurgical complications and asked to assign total cost estimates for the treatment for each vignette; in step 2 they were given a pocket-sized cost card listing hospital costs, and in step 3, after 2 weeks, they were retested using the same clinical vignettes as in step 1. SETTING: University of Connecticut, Farmington, and the Yale University School of Medicine, New Haven. PARTICIPANTS: Fifty-three general surgery residents. MAIN OUTCOME MEASURES: Cost estimates for steps 1 and 3 were compared using the paired t test and analysis of variance to examine whether there is a difference between the baseline cost estimates and the actual cost; whether introduction of the cost card improves performance; and whether responses correlate to postgraduate year level or to the clinical vignette. RESULTS: There was a statistically significant difference between the baseline cost estimates (before introduction of the cost card) and the actual cost of the treatment (P = .03). Introduction of the cost card resulted in a statistically significant improvement between the cost estimates before and after the intervention (P = .002), with a drop in average percentage error by 35% (range, 32%-38%). Level of postgraduate training or type of test vignette (at analysis of variance) did not seem to be a significant factor. CONCLUSIONS: There is a lack of awareness among surgical residents of the cost of treatment of postoperative complications. Introduction of a simple educational tool such as a cost card measurably improves their overall understanding of the cost of care and can be easily incorporated into the residency curriculum.

Dynamics of hospital-based plastic surgery.

BACKGROUND: Legislative regulations, decreasing reimbursements for office procedures, and malpractice premiums have transformed plastic surgery from an office-based specialty into a hospital-based one. Simultaneously, hospital economics has altered, wherein the "business model" has all but subsumed the old "medical care" model. Integration between plastic surgeons and the new hospital structure has been difficult for both. Limited understanding of the financial dynamics of hospital-based practices, unfamiliarity with the administrative processes, and resistance to accept and assimilate changes by both sides pose hurdles, in some situations even forcing plastic surgeons out of hospital settings. METHODS: Using well-defined financial terminology, changing national development in health care policy, and hospital-based administrative strategies as a backdrop, this study finds common ground for the plastic surgery specialty to coapt with the hospital. RESULTS: Key missing elements in the interaction between plastic surgeons and hospital administrations and ways of integrating these components are identified. To do so effectively, plastic surgeons must first understand the basic tenets of management that drive hospital administrators, participate at every level they can in guiding these processes, and assume leadership roles that will ultimately dictate the way they work and conduct their professional lives. CONCLUSIONS: It is critical that plastic surgeons engage in important processes that govern the economics of hospital-based health care delivery. This commitment will also ensure that all three groups (the patients, physicians, and hospital administrators) achieve a degree of satisfaction. The message to plastic surgeons is clear: be proactive and lead a campaign of change.

HSP70 enhances macrophage phagocytosis by interaction with lipid raft-associated TLR-7 and upregulating p38 MAPK and PI3K pathways.

BACKGROUND: Exogenous Heat Shock Protein-70 (HSP70), a product of necrotic cell death, binds the lipid raft microdomains of macrophages and, within minutes, stimulates the phagocytosis and presentation of internalized antigens. The aim of this study was to identify (a) the receptor on the lipid raft microdomain that interacts with HSP70 and (b) the subsequent signaling pathways that mediate HSP70-enhanced phagocytosis. METHODS: Cells including RAW264.7, bone-marrow-derived macrophages from TLR7-/- mice or controls and cells subjected to genetic methods reducing the mRNA expression of TLR7 were used to examine the interaction of HSP70 with TLR7. The effect of HSP70-TLR7 interaction on phagocytosis was assessed using phagocytosis assays described earlier. RESULTS: HSP70 binds Toll-like receptor-7 (TLR7) on the lipid raft microdomain of macrophage plasma membrane. Subsequent signaling is mediated through phosphoinositide 3-kinase (PI3K) and the up-regulation of the p38 MAP kinase pathways, both known activators of the phagocytic mechanisms. Reduced expression of TLR7 either via short interfering RNA for TLR7 (siRNA-TLR7) or using bone-marrow derived macrophages from TLR7-/- mice show that, as macrophages lose expression of TLR7, their ability to mediate HSP70-induced phagocytosis undergoes a corresponding diminution. Similarly, disruption of lipid rafts or blocking HSP70-TLR7-interaction or treatment with wortmannin and SB203580, inhibitors of PI3K or p38 MAPK, respectively, abrogates HSP70-induced macrophage phagocytosis. CONCLUSIONS: The interaction of HSP70 and LR-associated TLR7, two phylogenetically conserved molecules, activates a rapid, membrane-bound signaling pathway that enhances phagocytosis, a vital innate defense mechanism. This study elucidates critical mechanistic elements that mediate HSP70-enhanced phagocytosis by macrophages.

'Fish-incision' brachioplasty.

Upper arm deformities are common after massive weight loss following bariatric surgery. In patients with enormous amount of soft tissue excess and skin, the sheer volume and its laxity can be anatomically disorienting. Soft tissue landmarks are blurred, axis points hard to locate and bony landmarks are over-padded. Many corrective procedures have been described and yet, the surgical outcomes are often marred by poor preoperative planning and preparation--leading to poor contour correction, webbing of the axillae, widened scars some of which require revision surgery. We describe a surgical approach using careful mathematical measurements of the deformity that allows the preoperative marking of the incision in the shape of a fish. This incision is specially designed to offset the problems routinely faced in brachioplasty. Mathematical measurements, anatomic marking and conduct of the operation have been described in detail. The 'fish-incision' brachioplasty provides a usable, simple method that is easy to follow and optimises aesthetic results.

In vivo delivery of heat shock protein 70 accelerates wound healing by up-regulating macrophage-mediated phagocytosis.

Injury causes tissue breakdown, which releases large quantities of intracellular contents into the extracellular space. Some of these materials are well-established activators of the immune system and include heat shock proteins (HSPs), uric acid, nucleotides, High Mobility Group Box-1 protein (HMGB-1), and DNA. Here, we show that in vivo delivery of HSPs into BALB/cJ mice with full-thickness wounds accelerates the rate of wound closure by 60% as compared with control-treated mice. The onset is rapid and the effect is sustained, dose dependent, and protein specific. Adoptive transfer of RAW264 macrophages pretreated with HSP70 into naïve recipients with a wound transfers the HSP-mediated effect on the rate of wound closure. Further, we demonstrate that part of the mechanism by which HSP70 accelerates wound closure is through the stimulation of macrophage-mediated phagocytosis of wound debris. Disabling the HSP70-mediated enhancement of phagocytosis abrogates the HSP-mediated acceleration of the healing process. These findings create two opportunities: one, therapeutic, wherein HSP70 could be used in the clinical management of wounds; and two, pathophysiologic, to decode signals by which the host defenses recognize and respond to injury.