Diversity Drives Representation: An Internal Audit of Gender Representation in Citation Practices of a Single Surgical Laboratory.

Background: Large-scale retrospective studies have identified implicit gender bias in citation behaviors across multiple medical fields. There are minimal resources to directly assess one's own citation behavior before publication at a laboratory level. In this study, we performed an internal audit of our own citation practices and behavior, looking at the representation of authors by gender in our own bibliographies. Methods: Bibliographies were collated from our laboratory's publications between 2015 and 2022 with a single senior author, who was excluded from participating in this study. Bibliographies were run through a simulation originally constructed and used by authors from the University of Pennsylvania that categorized authors of each article by gender: man or woman, according to external database records. Results: Of the 1697 citations, the first and last authorship sequences displayed to be 60.8% male/male, 10.1% male/female, 16.3% female/male and 12.8% female/female. Men-led articles within our laboratory cited 67.4% male/male articles in their bibliographies compared with women-led articles citing 53.9%. All laboratory bibliographies consisted of 77.1% male senior authors compared with 22.9% female senior authors. Conclusions: Our data confirm that a gender bias in citation practices exists at the laboratory level. Promisingly, these data also indicate that diversity within an individual laboratory group leads to diversity in representation; therefore, diversifying a team of researchers is prone to improve the overall work and success of the laboratory. We encourage laboratory groups to challenge their own biases by replicating their own results and discovering how these biases might be impacting their publications.

Blue-Blood Pig Thorax Model Increases Residents' Confidence in Internal Mammary Dissection.

BACKGROUND: Preparation of the recipient vessels is a crucial step in autologous breast reconstruction, with limited opportunity for resident training intraoperatively. The Blue-Blood-infused porcine chest wall-a cadaveric pig thorax embedded in a mannequin shell, connected to a saline perfusion system-is a novel, cost-effective ($55) simulator of internal mammary artery (IMA) dissection and anastomosis intended to improve resident's comfort, safety, and expertise with all steps of this procedure. The purpose of this study was to assess the effect of the use of this chest wall model on resident's confidence in performing dissection and anastomosis of the IMA, as well as obtain resident's and faculty's perspectives on model realism and utility. METHODS: Plastic surgery residents and microsurgery faculty at the University of Wisconsin were invited to participate. One expert microsurgeon led individual training sessions and performed as the microsurgical assistant. Participants anonymously completed surveys prior to and immediately following their training session to assess their change in confidence performing the procedure, as well as their perception of model realism and utility as a formal microsurgical training tool on a five-point scale. RESULTS: Every participant saw improvement in confidence after their training session in a minimum of one of seven key procedural steps identified. Of participants who had experience with this procedure in humans, the majority rated model anatomy and performance of key procedural steps as "very" or "extremely" realistic as compared with humans. 100% of participants believed practice with this model would improve residents' ability to perform this operation in the operating room and 100% of participants would recommend this model be incorporated into the microsurgical training curriculum. CONCLUSION: The Blue-Blood porcine chest wall simulator increases trainee confidence in performing key steps of IMA dissection and anastomosis and is perceived as valuable to residents and faculty alike.

Breast Implants: Common Questions and Answers.

Breast implants are used for a wide range of cosmetic and reconstructive purposes. In addition to breast augmentation, implants can be used for postmastectomy breast reconstruction, correction of congenital breast anomalies, breast or chest wall deformities, and male-to-female top surgery. Breast implants may confer significant benefits to patients, but several factors are important to consider preoperatively, including the impact on mammography, future lactation, and potential long-term implant complications (e.g., infection, capsular contracture, rupture, and the need for revision, replacement, or removal). A fundamental understanding of implant monitoring is also paramount to implant use. Patients with silicone breast implants should undergo routine screening for implant rupture with magnetic resonance imaging or ultrasonography completed five to six years postoperatively and then every two to three years thereafter. With the exception of complications, there are no formal recommendations regarding the timing of breast implant removal or exchange. Women with unilateral breast swelling should be evaluated with ultrasonography for an effusion that might indicate breast implant-associated anaplastic large cell lymphoma. There are no specific breast cancer screening recommendations for patients with breast implants, but special mammographic views are indicated to enhance accuracy. Although these discussions are a routine component of consultation and postoperative follow-up for plastic surgeons performing these procedures, family physicians should have a working knowledge of implant indications, characteristics, and complications to better counsel their patients, to ensure appropriate screening, and to coordinate care after surgery.

Evaluation of Racial Disparities in Postoperative Outcomes Following Breast Reconstruction at a Single Institution in Wisconsin.

INTRODUCTION: Breast cancer is the most common cancer in women in Wisconsin. Evidence demonstrates that non-White racial minorities in the United States exhibit a higher mortality rate and more advanced or aggressive presentations of the disease than their White counterparts. Postmastectomy breast reconstruction remains essential to the treatment and recovery of these patients; however, racial disparities in the receipt of reconstruction are evident. This study evaluates the presence of racial disparities in postoperative outcomes of breast reconstruction at a single institution in Wisconsin. METHODS: An institutional review board-exempt retrospective study of postoperative outcomes was performed using a single institution's National Surgical Quality Improvement Program Registry to identify patients who underwent autologous or prosthesis-based breast reconstruction following mastectomy. Patient demographic, preoperative, operative, and postoperative variables were recorded. Postoperative outcomes in relation to self-reported race were evaluated using univariate analysis and propensity score matching. RESULTS: A total of 1,140 patients were included (1,092 White vs 48 non-White), with fewer non-White patients undergoing reconstruction. Patients of non-White race demonstrated a higher incidence of morbid obesity (4.4% White vs 12.5% non-White, P = 0.010) and bleeding disorders (0.3% White vs 4.2% non-White, P < 0.001). No association between self-reported race and postoperative complication was found. CONCLUSION: This study did not reveal racial disparities in postoperative outcomes of breast reconstruction at a single institution in Wisconsin; however, non-White patients were less likely to undergo reconstruction. Further research into the underlying causes of unequal access to care, influence of insurance, effect of structural racism, and impact of physician- and patient-associated factors is warranted.

Multispecialty Microsurgical Course Utilizing the Blue-Blood Chicken Thigh Model Significantly Improves Resident Comfort, Confidence, and Attitudes in Multiple Domains.

BACKGROUND: The high level of technical skill required by microsurgical procedures has prompted the development of in vitro educational models. Current models are cost-ineffective, unrealistic, or carry ethical implications and are utilized as isolated experiences within single surgical specialties. The purpose of this study was to assess the educational and interprofessional effect of a microsurgical training course utilizing the nonliving "Blue-Blood" chicken thigh model (BBCTM) in a multidisciplinary environment. METHODS: A 10-hour course was developed integrating didactic lectures, case presentations, and one-on-one practical sessions utilizing hydrogel microvessels and the BBCTM. Pre- and postcourse surveys were administered assessing participants' self-reported comfort and confidence within fundamental microsurgical domains, assessments of the models utilized, and the effects of a multidisciplinary environment on the experience. RESULTS: A total of 19 residents attended the course on two separate occasions (n = 10 and n = 9, respectively). Respondents varied from postgraduate year-2 (PGY-2) to PGY-6+ and represented plastic and reconstructive surgery (n = 10), urology (n = 6), and otolaryngology (n = 3). On average, each participant performed 4.3 end-to-end, 1.3 end-to-side, and 0.4 coupler-assisted anastomoses. Following the course, participants felt significantly more comfortable operating a microscope and handling microsurgical instruments. They felt significantly more confident handling tissues, manipulating needles, microdissecting, performing end-to-end anastomoses, performing end-to-side anastomoses, using an anastomotic coupler, and declaring anastomoses suitable (all p < 0.05). The majority of participants believed that the use of live animals in the course would have minimally improved their learning. All but two respondents believed the course improved their awareness of the value of microsurgery in other specialties "very much" or "incredibly." CONCLUSION: A microsurgical training course utilizing nonliving models such as the "BBCTM significantly improves resident comfort and confidence in core operative domains and offers an in vivo experience without the use of live animals. Multispecialty training experiences in microsurgery are beneficial, desired, and likely underutilized.

Cell proliferation and invasion are regulated differently by EGFR and MRP1 in T-DM1-resistant breast cancer cells.

We recently reported that T-DM1-resistant JIMT1 (T-DM1R-JIMT1) cells exhibited high invasive activity via EGFR and integrin cooperated pathways and gained cross-resistance to doxorubicin. Here, we show that EGFR positively coordinates with MRP1 in T-DM1R-JIMT1 cells to contribute to cross-resistance to doxorubicin. Downregulating EGFR and MRP1 inhibits T-DM1R-JIMT1 cell growth and re-sensitizes T-DM1R cells to doxorubicin, suggesting that dual targeting EGFR and MRP1 could serve as a therapeutic approach to overcome T-DM1 resistance. However, it increases cell invasion activity of T-DM1R-JIMT1 cells with molecular and cellular phenotypes similar to the breast cancer cells that express low levels of HER2 (MDA-MB-231 and BT-549 cells). Importantly, the invasion activity of MDA-MB-231 and BT-549 cells is also significantly increased after chronically exposed to T-DM1 although cell growth of MDA-MB-231 and BT-549 cells is not inhibited by T-DM1. These results highlight the importance of HER2 heterogenicity in HER-positive breast cancers treated with T-DM1. Our study also provides evidence demonstrating that proliferation and invasion activities of T-DM1R-JIMT1, and MDA-MB-231 and BT-549 cells are regulated by different mechanisms and that different aspects of cancer cell behaviors affected by targeted-therapeutics should be fully characterized in order to overcome T-DM1-resistant disease and to prevent cancer metastasis.

Whole-Proteome Analysis of Human Craniosynostotic Tissue Suggests a Link between Inflammatory Signaling and Osteoclast Activation in Human Cranial Suture Patency.

BACKGROUND: The pathophysiology of nonsyndromic craniosynostosis remains poorly understood. The authors seek to understand the cause of this condition with a specific focus on how osteoclasts may contribute to craniosynostosis. Here, the authors characterize proteins differentially expressed in patent and fused cranial sutures by comparing their respective proteomes. METHODS: Fused and patent suture samples were obtained from craniosynostotic patients undergoing surgery at a single academic medical center. Extracted protein from samples was interrogated using mass spectrometry. Differential protein expression was determined using maximum likelihood-based G-test with a q-value cutoffs of 0.5 after correction for multiple hypothesis testing. Immunolocalization of lead protein candidates was performed to validate proteomic findings. In addition, quantitative polymerase chain reaction analysis of corresponding gene expression of proteins of interest was performed. RESULTS: Proteins differentially expressed in patent versus fused sutures included collagen 6A1 (Col6A1), fibromodulin, periostin, aggrecan, adipocyte enhancer-binding protein 1, and osteomodulin (OMD). Maximum likelihood-based G-test suggested that Col6A1, fibromodulin, and adipocyte enhancer-binding protein 1 are highly expressed in patent sutures compared with fused sutures, whereas OMD is up-regulated in fused sutures compared with patent sutures. These results were corroborated by immunohistochemistry. Quantitative polymerase chain reaction data point to an inverse relationship in proteins of interest to RNA transcript levels, in prematurely fused and patent sutures that potentially describes a feedback loop mechanism. CONCLUSIONS: Proteome analysis validated by immunohistochemistry may provide insight into the mechanism of cranial suture patency and disease from an osteoclast perspective. The authors results suggest a role of inflammatory mediators in nonsyndromic craniosynostosis. Col6A1 may aid in the regulation of suture patency, and OMD may be involved in premature fusion. Additional validation studies are required.

Parental leave policies in graduate medical education: A systematic review.

BACKGROUND: A thorough understanding of attitudes toward and program policies for parenthood in graduate medical education (GME) is essential for establishing fair and achievable parental leave policies and fostering a culture of support for trainees during GME. METHODS: A systematic review of the literature was completed. Non-cohort studies, studies completed or published outside of the United States, and studies not published in English were excluded. Studies that addressed the existence of parental leave policies in GME were identified and were the focus of this study. RESULTS: Twenty-eight studies addressed the topic of the existence of formal parental leave policies in GME, which was found to vary across time and ranged between 22 and 90%. Support for such policies persisted across time. CONCLUSIONS: Attention to formal leave policies in GME has traditionally been lacking, but may be increasing. Negative attitudes towards parenthood in GME persist. Active awareness of the challenges faced by parent-trainees combined with formal parental leave policy implementation is important in supporting parenthood in GME.

Pulmonary Tuberculosis.

This review on pulmonary tuberculosis includes an introduction that describes how the lung is the portal of entry for the tuberculosis bacilli to enter the body and then spread to the rest of the body. The symptoms and signs of both primary and reactivation tuberculosis are described. Routine laboratory tests are rarely helpful for making the diagnosis of tuberculosis. The differences between the chest X ray in primary and reactivation tuberculosis is also described. The chest computed tomography appearance in primary and reactivation tuberculosis is also described. The criteria for the diagnosis of pulmonary tuberculosis are described, and the differential is discussed. The pulmonary findings of tuberculosis in HIV infection are described and differentiated from those in patients without HIV infection. The occurrence of tuberculosis in the elderly and in those patients on anti-tumor necrosis factor alpha inhibitors is described. Pleural tuberculosis and its diagnosis are described. Efforts to define the activity of tuberculosis and the need for respiratory isolation are discussed. The complications of pulmonary tuberculosis are also described.

Alterations in B-cell subsets in pediatric patients with early atopic dermatitis.

BACKGROUND: B cells undergo maturation and class-switching in response to antigen exposure and T-cell help. Early B-cell differentiation has not been defined in patients with early-onset atopic dermatitis (AD). OBJECTIVE: We sought to define the frequency of B-cell subsets associated with progressive B-cell maturation and IgE class-switching. METHODS: We studied 27 children and 34 adults with moderate-to-severe AD (mean SCORAD score, 55 and 65, respectively) and age-matched control subjects (15 children and 27 adults). IgD/CD27 and CD24/CD38 core gating systems and an 11-color flow cytometric panel were used to determine the frequencies of circulating B-cell subsets. Serum total and allergen-specific IgE (sIgE) levels were measured by using ImmunoCAP. RESULTS: Compared with adults, children showed T-cell predominance in the skin. Circulating CD19+CD20+ B-cell counts were lower in patients with pediatric AD than in control subjects (24% vs 33%, P = .04), whereas CD3+ T-cell counts were higher (62% vs 52%, P = .05). A decreased B-cell/T-cell lymphocyte ratio with age was observed only in pediatric control subjects (r = -0.48, P = .07). In pediatric patients with AD, a positive correlation was observed between B-cell/T-cell ratio and nonswitched memory B-cell counts (r = 0.42, P = .03). Higher frequencies of positive sIgE levels were seen in pediatric patients with AD (P < .0001). Diverse sIgE levels correlated with SCORAD scores and age of pediatric patients with AD (P < .01). Positive correlations were observed between activated B-cell and memory T-cell counts (P < .02). In patients with AD, IgE sensitization to most allergens clustered with age, TH1, TH2, total IgE levels, and B-cell memory subsets. CONCLUSIONS: Peripheral B and T cells are altered in pediatric patients with early AD, but T cells predominate in skin lesions.

Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin.

BACKGROUND: Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only TH2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. OBJECTIVE: We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD. METHODS: Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects. RESULTS: In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3+, CD11c+, and FcεRI+) than adults with AD. Similar to adults, strong activation of the TH2 (IL-13, IL-31, and CCL17) and TH22 (IL-22 and S100As) axes and some TH1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of TH17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), TH9/IL-9, IL-33, and innate markers (IL-8) than adults (P < .02). Despite the characteristic downregulation in adult patients with AD, filaggrin expression was similar in children with AD and healthy children. Nonlesional skin in pediatric patients with AD showed higher levels of inflammation (particularly IL-17A and the related molecules IL-19 and LL37) and epidermal proliferation (keratin 16 and S100As) markers (P < .001). CONCLUSION: The skin phenotype of new-onset pediatric AD is substantially different from that of adult AD. Although excess TH2 activation characterizes both, TH9 and TH17 are highly activated at disease initiation. Increases in IL-19 levels might link TH2 and TH17 activation.

Osteoprotegerin deficiency results in disruption of posterofrontal suture closure in mice: implications in nonsyndromic craniosynostosis.

BACKGROUND: Little is known about the role of osteoclasts in cranial suture fusion. Osteoclasts are predominantly regulated by receptor activator of nuclear factor kappa B and receptor activator of nuclear factor kappa B ligand, both of which lead to osteoclast differentiation, activation, and survival; and osteoprotegerin, a soluble inhibitor of receptor activator of nuclear factor kappa B. The authors' work examines the role of osteoprotegerin in this process using knockout technology. METHODS: Wild-type, osteoprotegerin-heterozygous, and osteoprotegerin-knockout mice were imaged by serial micro-computed tomography at 3, 5, 7, 9, and 16 weeks. Suture density measurements and craniometric analysis were performed at these same time points. Posterofrontal sutures were harvested from mice after the week-16 time point and analyzed by means of histochemistry. RESULTS: Micro-computed tomographic analysis of the posterofrontal suture revealed reduced suture fusion in osteoprotegerin-knockout mice compared with wild-type and heterozygous littermates. Osteoprotegerin deficiency resulted in a statistically significant decrease in suture bone density in knockout mice. There was no reduction in the density of non-suture-containing calvarial bone between wild-type and osteoprotegerin-knockout mice. Histochemistry of suture sections supported these micro-computed tomographic findings. Finally, osteoprotegerin-knockout mice had reduced anteroposterior skull distance at all time points and an increased interorbital distance at the week-16 time point. CONCLUSION: The authors' data suggest that perturbations in the expression of osteoprotegerin and subsequent changes in osteoclastogenesis lead to alterations in murine cranial and posterofrontal suture morphology.

Twelve-hour days in the brain and behavior of split hamsters.

Hamsters will spontaneously 'split' and exhibit two rest-activity cycles each day when housed in constant light (LL). The suprachiasmatic nucleus (SCN) is the locus of a brain clock organizing circadian rhythmicity. In split hamsters, the right and left SCN oscillate 12 h out of phase with each other, and the twice-daily locomotor bouts alternately correspond to one or the other. This unique configuration of the circadian system is useful for investigation of SCN communication to efferent targets. To track phase and period in the SCN and its targets, we measured wheel-running and FOS expression in the brains of split and unsplit hamsters housed in LL or light-dark cycles. The amount and duration of activity before splitting were correlated with latency to split, suggesting behavioral feedback to circadian organization. LL induced a robust rhythm in the SCN core, regardless of splitting. The split hamsters' SCN exhibited 24-h rhythms of FOS that cycled in antiphase between left and right sides and between core and shell subregions. In contrast, the medial preoptic area, paraventricular nucleus of the hypothalamus, dorsomedial hypothalamus and orexin-A neurons all exhibited 12-h rhythms of FOS expression, in-phase between hemispheres, with some detectable right-left differences in amplitude. Importantly, in all conditions studied, the onset of FOS expression in targets occurred at a common phase reference point of the SCN oscillation, suggesting that each SCN may signal these targets once daily. Finally, the transduction of 24-h SCN rhythms to 12-h extra-SCN rhythms indicates that each SCN signals both ipsilateral and contralateral targets.

Investigating the effect of increasing charge density on the hemolytic activity of synthetic antimicrobial polymers.

The current study is aimed at investigating the effect of fine-tuning the cationic character of synthetic mimics of antimicrobial peptides (SMAMPs) on the hemolytic and antibacterial activities. A series of novel norbornene monomers that carry one, two, or three Boc-protected amine functionalities was prepared. Ring-opening metathesis polymerization (ROMP) of the monomers, followed by deprotection of the amine groups resulted in cationic antimicrobial polynorbornenes that carry one, two, and three charges per monomer repeat unit. Increasing the number of amine groups on the most hydrophobic polymer reduced its hemolytic activity significantly. To understand the membrane activity of these polymers, we conducted dye leakage experiments on lipid vesicles that mimic bacteria and red blood cell membranes, and these results showed a strong correlation with the hemolysis data.

Alcohol consumption and HIV disease progression: are they related?

BACKGROUND: The relationship between alcohol consumption and HIV disease progression has received limited attention in the era of highly active antiretroviral therapy (HAART). METHODS: We assessed CD4 cell count, HIV RNA levels, and alcohol consumption in the past month, defined as none, moderate, and at risk, in 349 HIV-infected people with a history of alcohol problems. We investigated the relationship between alcohol consumption and HIV disease markers CD4 cell count and HIV RNA level, stratified by HAART use, using multivariable regression. RESULTS: No significant differences in CD4 cell count or HIV RNA level were found across the categories of alcohol consumption for patients who were not receiving HAART. However, among patients who were receiving HAART, log HIV RNA levels were significantly higher in those with moderate (2.17 copies/ml) and at-risk (2.73 copies/ml) alcohol use compared with none (1.73 copies/ml; p = 0.006). CD4 cell counts in those with moderate (368 cells/microl) and at-risk (360 cells/microl) alcohol use were lower than for subjects who reported none (426 cells/microl; p = 0.07). CONCLUSION: Among patients who have a history of alcohol problems and are receiving antiretroviral treatment, alcohol consumption was associated with higher HIV RNA levels and lower CD4 counts. No comparable association was found for similar patients who were not receiving HAART. Addressing alcohol use in HIV-infected patients, especially those who are receiving HAART, may have a substantial impact on HIV disease progression.