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We describe splenomegaly and bilateral grade 2 Baker breast capsular contracture in a woman who had undergone augmentation mammoplasty. This case represents the first documented instance of splenic marginal zone lymphoma, and is among the rare reports of B-cell lymphoma, arising in a patient with breast implants.

Debated topics and new and evolving techniques in breast surgery are discussed in this chapter. Antibiotics and the use of closed-suction drains vary among surgeons, but the existing evidence favours discontinuation of antibiotics within 24 hours in most cases, and the indications for drains are limited but include breast reconstruction with acellular dermal matrix (ADM). ADM is a biological tissue substitute with many applications in breast surgery. The product selected and surgical technique used are often case specific; cost and patient anatomy play major roles. Although not suitable for all patients, ADM is an asset to prosthetic breast reconstruction. In addition, ADM is useful in the correction of breast surgery complications, including malpositioning and capsular contracture. It may be combined with fat grafting to mask rippling. Fat grafting, or lipomodelling, is an evolving science with promising results. Technique is critical for good results, and is described in this chapter. Radiographic changes after fat grafting are usually discernible from suspicious lesions, and growing evidence supports the oncological safety of this procedure

Implant-based breast reconstruction has become the predominant type of breast reconstruction, consisting of two-stage immediate, two-stage delayed, and direct-to-implant reconstruction. Both preoperative and intraoperative considerations guide appropriate choice among these reconstructive options and are discussed. Outside of the United States, greater diversity exists for both tissue expanders and breast implants. Techniques including total submuscular and partial subpectoral pocket creation, acellular dermal matrix use, SPY Elite™ use, pocket and inframammary fold revisions, and timing of reconstructive steps are discussed. With expanding criteria for post-mastectomy radiation, consideration of effects and timing of radiation treatment is essential. Other risk factors associated with complications, such as obesity, smoking, and age, should be utilized for risk stratification and reconstructive decision-making. The future of implant-based breast reconstruction will rely on minimizing costs without sacrificing aesthetics, as well as continued research on fat grafting and biological scaffolds.

Vascular compromise and blindness are reported but rare complications of facial soft tissue filler injections. Stroke is an even rarer complication resulting from intraarterial injection of fillers. We present a case of a patient suffering all 3 complications following hyaluronic acid filler injection: forehead skin vascular compromise, unilateral blindness, and ipsilateral subclinical strokes. Were it not for a stroke workup protocol, the incidental strokes may have otherwise gone undetected, suggesting the incidence of stroke from intraarterial injection may be higher than reported. Further, we review the literature and recommendations for prevention and management of threatened tissue ischemia and vision loss from facial filler injection. Level of Evidence: 5

High follow-up rates are critical for robust research with minimal bias, and are particularly important for breast implant Core Studies seeking U.S. Food and Drug Administration approval. The Core Study for IDEAL IMPLANT, the most recently U.S. Food and Drug Administration-approved breast implant, used a novel incentive payment model to achieve higher follow-up rates than in previous breast implant trials.At enrollment, $3500 was deposited into an independent, irrevocable trust for each of the 502 subjects and invested in a diversified portfolio. If a follow-up visit is missed, the subject is exited from the study and compensated for completed visits, but the remainder of her share of the funds stay in the trust. At the conclusion of the 10-year study, the trust will be divided among those subjects who completed all required follow-up visits. For primary and revision augmentation cohorts, the U.S. Food and Drug Administration published follow-up rates from Core Studies were compared for all currently available breast implants.Five-year follow-up rates for the IDEAL IMPLANT Core Study are higher for both primary augmentation and revision augmentation cohorts (94.9 percent and 96.7 percent, respectively) when compared to all other trials that have used U.S. Food and Drug Administration standardized follow-up reporting (MemoryShape, Allergan 410, and Sientra Core Studies).This trial demonstrates the utility of a novel incentive strategy to maximize follow-up in cosmetic surgery patients. This strategy may benefit future cosmetic surgery trials and perhaps any prospective research trial by providing more complete data.Therapeutic, IV.

The rectus abdominis flap is a versatile, workhorse flap. It is ideal for head and neck reconstruction requiring large, soft tissue bulk without bony reconstruction, particularly for defects of the tongue, orbits, maxilla, cheek, posterior mandible, and cranial base. Its ability to be folded upon itself and harvested with multiple skin paddles makes it versatile for complex three-dimensional and multilaminar defects. Its pedicle size and length and consistent vascular anatomy make the flap a reliable choice for head and neck reconstruction. Its indications in head and neck reconstruction and technique in harvest are elaborated in this chapter.

Although the upper extremity is the most commonly injured part of the body, many studies have indicated that there is a lack of emergency hand coverage in the United States. In 2010, our laboratory evaluated on-call hand coverage in Tennessee (TN) and found that only 7% of hospitals had a hand surgeon on call for emergency cases at all times. In 2014, the Affordable Care Act (ACA) was implemented with the goal of increasing overall access to care and decreasing health care costs. Hand surgeons were surveyed on their attitudes toward the ACA, and the majority of surgeons surveyed disagreed or strongly disagree that the ACA would improve access to emergent hand surgery. This study aimed to determine if there has been an increase in emergency hand coverage in TN since the implementation of the ACA. A survey was administered to all hospitals in TN with both an emergency department and operating room to determine the percentage of TN hospitals offering elective hand surgery and on-call emergency hand coverage. With 94% of TN hospitals responding to the emergency department survey, we determined that there has been a 138% significant increase in the percentage of hospitals reporting 24/7 emergency hand coverage by a hand specialist since our last study in 2010. There has also been a significant increase in elective hand coverage in TN, although much smaller at 13% since 2010. This study suggests that there has been an overall increase in access to hand care in TN since the implementation of the ACA, most profoundly seen in the increase in hand specialists available for emergent cases.

Chromatographic separation of the enantiomers of parent compounds dimethyl α-hydroxyallyl phosphonate and 1-(dimethoxyphosphoryl) allyl methyl carbonate was demonstrated by high-performance liquid chromatography (HPLC) using Chiralpak AS-H and ad-H chiral stationary phases (CSP), respectively, using a combination of UV, polarimetric, and refractive index detectors. A comparison was made of the separation efficiency and elution order of enantiomeric α-hydroxyallyl phosphonates and their carbonate derivatives on commercially available polysaccharide AS, ad, OD, IC-3, and Whelk-O 1 CSPs. In general, the α-hydroxyallyl phosphonates were resolved on the AS-H CSP, whereas the carbonate derivatives and were preferentially resolved on the ad-H CSP. The impact of aryl substitution on the resolution of analytes and was evaluated. Thermodynamic parameters determined for enantioselective adsorption hydroxyphosphonates and on the AS-H CSP and carbonate on the ad-H CSP demonstrated enthalpic control for separation of the enantiomers. Chirality 28:656-662, 2016. © 2016 Wiley Periodicals, Inc.

Background Given emerging focus on competency-based surgical training and work-hour limitations, surgical skills laboratories play an increasingly important role in resident education. This study was designed to investigate educational opportunities in microsurgery across integrated residency programs. Methods Senior residents (PGY 4–6) at integrated plastic surgery programs were surveyed during the 2016 to 2017 academic year to determine each program's access to: training microscopes and anastomosis models, video-based skills assessment, pre-requisite skills exams, flap courses, or a formal microsurgical training curriculum. Programs were stratified based on large size (>18 residents) and presence of microsurgery fellows. Chi-squared analysis was performed with p Results Survey responses were collected from 32 of 60 eligible programs (53% response rate). Sixty-nine percent provide access to one to two training microscopes, 25% provide three or more, and 6% provide none. Sixty-nine percent of programs train anastomosis with nonliving prosthetics, 66% with living biologics, and 50% with nonliving biologics. Large program size or having microsurgical fellows was not associated with increased access to training microscopes or specific anastomosis models. Programs without microsurgery fellows reported more often that a formal microsurgery curriculum would be helpful (90 vs. 58% of programs with fellows, p = 0.0003). Respondents who indicated that creating a formal curriculum would not be helpful elaborated that their program already has a formal curriculum or a high volume of microsurgery cases. Conclusion This study demonstrates the current variation in microsurgery training at integrated plastic surgery residency programs. A formal microsurgical training curriculum is commonly viewed as being helpful, particularly at programs without microsurgery fellows.

The primary goal of belt lipectomy surgery is to improve the contour of the inferior truncal circumferential unit and to place the resultant scar in natural junctions. Excessive intra-abdominal content is a contraindication for belt lipectomy. The higher the presenting patient's body mass index (BMI), the higher the risk of postoperative complications and the less impressive the results. The converse is also true: the lower the BMI, the lower the risk of complications and the better the results. The most common complications are small wound separations and seromas.

Conditions in the Democratic Republic of the Congo provide an ideal environment for leptospirosis and plague, both of which can cause severe pulmonary manifestations. In December 2004, an outbreak of lethal pneumonia occurred in a local mining camp, affecting 130 persons and killing 57 of them. Clinical signs, fast disease spread, and initial laboratory investigations suggested pneumonic plague. While leptospirosis had not recently been described in the region, it was considered as a differential diagnosis. Anti-Leptospira antibodies were detected by microscopic agglutination test (MAT). A confirmed case of leptospirosis was defined as having consistent clinical signs and any one of the following: seroconversion or four-fold increase in MAT titre for paired serum samples, or a MAT titre ≥ 1:400 for acute-phase serum samples. Twenty-nine of the 54 patients or convalescents tested for leptospirosis were seropositive. Two cases showed a confirmed infection for both plague and leptospirosis. While evidence supports the plague nature of this outbreak, the results suggest that some of the suspected plague cases might be due to leptospirosis. In any case, this diagnosis will have to be evoked in the future if a similar outbreak occurs in this region of Africa.

In order to implement effective burn prevention strategies, the WHO has called for improved data collection to better characterize burn injuries in low and middle income countries (LMIC). This study was designed to gather information on burn injury in Kenya and to test a model for such data collection.The study was designed as a retrospective case series study utilizing an electronic data collection tool to assess the scope of burn injuries requiring operation at Kijabe Hospital from January 2006 to May 2010. Data were entered into a web-based tool to test its utility as the potential Kenya Burn Repository (KBR).174 patients were included. The median age was 10 years. There was a male predominance (59% vs. 41%). Findings included that timing of presentation was associated with burn etiology (p=0.009). Length of stay (LOS) was associated with burn etiology (p0.001). Etiology differed depending on the age group, with scald being most prominent in children (p=0.002).Burn injuries in Kenya show similarities with other LMIC in etiology and pediatric predominance. Late presentation for care and prolonged LOS are areas for further investigation. The web-based database is an effective tool for data collection and international collaboration.

Chromatographic separation of the enantiomers of parent compounds dimethyl α-hydroxyallyl phosphonate and 1-(dimethoxyphosphoryl) allyl methyl carbonate was demonstrated by high-performance liquid chromatography (HPLC) using Chiralpak AS-H and ad-H chiral stationary phases (CSP), respectively, using a combination of UV, polarimetric, and refractive index detectors. A comparison was made of the separation efficiency and elution order of enantiomeric α-hydroxyallyl phosphonates and their carbonate derivatives on commercially available polysaccharide AS, ad, OD, IC-3, and Whelk-O 1 CSPs. In general, the α-hydroxyallyl phosphonates were resolved on the AS-H CSP, whereas the carbonate derivatives and were preferentially resolved on the ad-H CSP. The impact of aryl substitution on the resolution of analytes and was evaluated. Thermodynamic parameters determined for enantioselective adsorption hydroxyphosphonates and on the AS-H CSP and carbonate on the ad-H CSP demonstrated enthalpic control for separation of the enantiomers. Chirality 28:656-662, 2016. © 2016 Wiley Periodicals, Inc.

The solution structure of the cold-shock-like protein from R. rickettsii, the causative agent of Rocky Mountain spotted fever, is reported., Rocky Mountain spotted fever is caused by Rickettsia rickettsii infection. R. rickettsii can be transmitted to mammals, including humans, through the bite of an infected hard-bodied tick of the family Ixodidae. Since the R. rickettsii genome contains only one cold-shock-like protein and given the essential nature of cold-shock proteins in other bacteria, the structure of the cold-shock-like protein from R. rickettsii was investigated. With the exception of a short α-helix found between β-strands 3 and 4, the solution structure of the R. rickettsii cold-shock-like protein has the typical Greek-key five-stranded β-barrel structure found in most cold-shock domains. Additionally, the R. rickettsii cold-shock-like protein, with a ΔG of unfolding of 18.4 kJ mol−1, has a similar stability when compared with other bacterial cold-shock proteins.

Previously, we showed that the HNK-1 carbohydrate epitope is expressed on aggrecan synthesized in the notochord but not in mature cartilage. In the present study, we demonstrate that in immature cartilage (embryonic day 6) the HNK-1 epitope is also expressed predominantly on aggrecan proteoglycan molecules. This finding was verified by using an aggrecan-deficient mutant, the nanomelic chick, which lacks HNK-1 immunostaining in the extracellular matrix of dividing and hypertrophic chondrocytes as late as embryonic day 12. By using both biochemical and immunologic approaches, the initially prominent expression of the HNK-1 epitope is down-regulated as development of limb and vertebral cartilage proceeds, so that by embryonic day 14 no HNK-1 is detectable. Localization changes with development and the HNK-1-aggrecan matrix becomes restricted to dividing and hypertrophic chondrocytes and is particularly concentrated in the intraterritorial matrix. Concomitant with the temporal and spatial decreases in HNK-1, there is a significant increase in keratan-sulfate content and the aggrecan-borne HNK-1 epitope is closely associated with proteolytic peptides that contain keratan sulfate chains, rather than chondroitin sulfate chains or carbohydrate-free domains. Lastly, the diminution in HNK-1 expression is consistent with a reduction in mRNA transcripts specific for at least one of the key enzymes in HNK-1 oligosaccharide biosynthesis, the HNK-1 sulfotransferase. These findings indicate that the HNK-1 carbohydrate may be a common modifier of several proteoglycans (such as aggrecan) that are usually expressed early in development, and that HNK-1 addition to these molecules may be regulated by tissue- and temporal-specific expression of requisite sulfotransferases and glycosyltransferases.

OBJECTIVES/SPECIFIC AIMS: The goal of the eResearch platform is to make consenting for clinical trials more convenient, accessible, and faster while retaining an ethical and informed consenting process. eResearch e-consent also allows for enhanced standardization and efficiency for research collaborations across academic research institutions, which, ultimately, helps drive discovery of better health care for our patients and communities. METHODS/STUDY POPULATION: The UMN’s CTSI and AHC Information Systems developed software, called eResearch Suite, for electronic consenting. The eResearch Suite includes viewing a consent, a “Check Your Understanding” quiz to assess comprehension of critical study details, and a signature block that captures the participant signature electronically and with an automatic date and time stamp. The eResearch Suite also has the capability to randomize participants, track participants via a master list, collect participant data, collect internal study data, and generate emails to participants. The eResearch Suite platform is written in Ruby on Rails. RESULTS/ANTICIPATED RESULTS: We have pilot tested the eResearch platform with one study thus far. Preliminary results of the study show that all participants consented via eResearch, with 64% of participants consenting remotely via eResearch before their first study visit. Participants e-consented using various devices including desktop computers, tablets, and smart phones. Participants also filled out surveys and questionnaires before their study visits, which saved the study team time and money. DISCUSSION/SIGNIFICANCE OF IMPACT: eResearch electronic consenting (e-consenting) changes the way potential participants consent for studies. e-Consenting is important because it allows individuals, or their Legally Authorized Representatives, to consent remotely. This may be faster, more convenient for people, reduce coercion, increase comprehension, and allow for consenting information or process to be shared with an individual’s family/friends. In acute and emergent settings we anticipate eResearch e-consenting will result in significant reduction of consent time by replacing faxed and paper consent with e-consent available via email and mobile devices. This allows legally authorized representatives to sign consent remotely, reduces the time physicians spend faxing consents, and allow them to avert more focus back on their patients. Time savings, whether for consent or study visits, may also result in a cost savings for studies.

Background Hand trauma is the most frequently treated injury in emergency departments, but presently there is a crisis of insufficient emergency coverage. This study evaluates the discrepancy of emergent and elective hand care trends based on socioeconomic factors in the state of Tennessee. Method We identified 119 hospitals in Tennessee that contained operating and emergency room facilities. Of these, 111 hospitals participated in a survey to determine the availability of elective and emergency hand surgery. Wilcoxon rank-sum test or permutation chi-square test and logistic regression were used to analyze reported measures. Results Our results revealed that hospitals in counties with the lowest per capita income and median household income are less likely to have hand specialists or offer hand call. There are also significantly fewer hospitals that have hand specialists and offer hand call that are located in medically underserved areas. In the state of TN, level 1 trauma facilities are required by the Tennessee Department of Health to have staffed hand specialists and 24/7 hand call. Our study revealed that while 7/8 (87.5 %) level 1 trauma facilities have hand specialists, only 2/8 (25 %) provide 24/7 hand specialist call. Conclusion Our results strongly suggest the presence of a health care disparity for hand trauma in counties with a low income and in medically underserved areas.

Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO., National Institutes of Health (U.S.) (DC010998), National Institutes of Health (U.S.) (NIH DC010231), Harvard College (1780- ), Sarah Fuller Foundation for Little Deaf Children

Wrist, hand, and finger trauma are the most common injuries presenting to emergency departments. Shortage of emergency hand care is an emerging problem, as on-call hand coverage declines. This study evaluates the availability of elective and emergency hand surgery services in Tennessee, with the use of telephone surveys administered to emergency department and operating facility management. One hundred eleven Tennessee hospitals completed the surveys (93% response rate). In all, 77% of hospitals offer elective hand surgery, 58% offer basic emergency hand services, 18% offer occasional hand specialist call coverage and only 7% of hospitals have 24/7 hand specialist call coverage. Hospitals with hand specialists have significantly more payer charges from commercial insurance than hospitals without hand specialists (26.1% vs. 16.1%, P0.001). Our results strongly support the need for increased emergency hand coverage. Solutions include creating multihospital coordinated call schedules, increasing incentives for call coverage, and training more hand specialists.

p53 binding protein 1 (53BP1) was identified in a yeast two-hybrid screen as a protein that binds to the central DNA binding domain of the tumor suppressor protein p53 (15). It contains two tightly packed tudor domains and a C-terminal tandem BRCT motif (9, 19). BRCT domains are thought to be protein-protein interaction domains and are found in many DNA damage response proteins (5, 19). The observation that, upon exposure of cells to ionizing radiation (IR), 53BP1 rapidly localizes in a dose-dependent manner to discrete nuclear foci supported the proposed role of 53BP1 in the DNA damage response (2, 16, 25, 29, 36). Moreover, following irradiation, 53BP1 interacts with and becomes phosphorylated by ataxia telangiectasia mutated (ATM), a central kinase in the DNA double-strand break (DSB) response (2, 25, 36). Colocalization of 53BP1 foci with those of phosphorylated histone H2AX and the Mre-11/Nbs1/Rad50 complex mapped the IR-induced accumulation of 53BP1 to regions of DNA DSBs (2, 25, 29). Subsequent studies using small interfering RNAs indicated that 53BP1 is involved in DNA damage checkpoint control by facilitating the phosphorylation of ATM substrates like Chk2 or SMC1 (12, 31). Moreover, 53BP1 was reported to be required for p53 accumulation in response to IR (31). Defects in DNA damage checkpoint control were also observed in cells derived from 53BP1 knockout mice (13); however, the more striking observations obtained with these mice were of sensitivity towards ionizing radiation and greatly impaired class switch recombination (CSR) combined with immunodeficiency and an increased lymphoma predisposition (23, 24, 33, 34). Since CSR involves the generation and rejoining of DNA DSBs, a function of 53BP1 in DSB repair has been proposed (23, 34). It is well established that defects in the joining of DSBs can lead to chromosome translocations and gene amplifications that promote tumorigenesis, particularly in the context in which p53-dependent apoptosis is abrogated (11, 37). In this study, we address how 53BP1 contributes to genomic stability by analyzing tumorigenesis in p53-null mice that express various amounts of 53BP1.

Expression of the extracellular proteoglycan aggrecan is both cell-specific and developmentally regulated. Previous studies identified six functionally defined cis elements in the aggrecan promoter region which were shown to repress aggrecan gene expression (1). Using competition electrophoretic mobility shift assays (EMSAs) we have now identified in nuclear extracts a functional repressor cis element, (T/C)TCCCCT(A/C)RRC, which occurs at multiple locations within the chick aggrecan regulatory region. We purified the factor that binds to this cis element and established that it, APBP-1 (aggrecan promoter-binding protein-1), is a 19-kDa protein that has significant homology to CIRP (cold inducible RNA-binding protein). Recombinantly expressed APBP-1 mimics the native cis element-trans factor interaction in EMSAs. In situ hybridization demonstrates that aggrecan and APBP-1 RNA expression are restricted to complementary tissues in the developing limb, and Northern blot analysis of chick limb bud mRNA shows that APBP-1 mRNA expression is inversely correlated with aggrecan mRNA expression. Functional analyses by transient transfections and Northern blot analyses suggest APBP-1 has the capacity to repress aggrecan expression, indicating that this factor may be important regulator of aggrecan gene expression.