SPINT2 mutations in the Kunitz domain 2 found in SCSD patients inactivate HAI-2 as prostasin inhibitor via abnormal protein folding and N-glycosylation.

Mutations in the Kunitz-type serine protease inhibitor HAI-2, encoded by SPINT2, are responsible for the pathogenesis of syndromic congenital sodium diarrhea (SCSD), an intractable secretory diarrhea of infancy. Some of the mutations cause defects in the functionally required Kunitz domain 1 and/or subcellular targeting signals. Almost all SCSD patients, however, harbor SPINT2 missense mutations that affect the functionally less important Kunitz domain 2. How theses single amino acid substitutions inactivate HAI-2 was, here, investigated by the doxycycline-inducible expression of three of these mutants in HAI-2-knockout Caco-2 human colorectal adenocarcinoma cells. Examining protein expressed from these HAI-2 mutants reveals that roughly 50% of the protein is synthesized as disulfide-linked oligomers that lose protease inhibitory activity due to the distortion of the Kunitz domains by disarrayed disulfide bonding. Although the remaining protein is synthesized as monomers, its glycosylation status suggests that the HAI-2 monomer remains in the immature, lightly glycosylated form, and is not converted to the heavily glycosylated mature form. Heavily glycosylated HAI-2 possesses full anti-protease activity and appropriate subcellular targeting signals, including the one embedded in the complex-type N-glycan. As predicted, these HAI-2 mutants cannot suppress the excessive prostasin proteolysis caused by HAI-2 deletion. The oligomerization and glycosylation defects have also been observed in a colorectal adenocarcinoma line that harbors one of these SPINT2 missense mutations. Our study reveals that the abnormal protein folding and N-glycosylation can cause widespread HAI-2 inactivation in SCSD patents.

Effect of mindfulness-based programmes on elite athlete mental health: a systematic review and meta-analysis.

OBJECTIVE: To determine the effectiveness of mindfulness-based programmes (MBPs) on the mental health of elite athletes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eight online databases (Embase, PsycINFO, SPORTDiscus, MEDLINE, Scopus, Cochrane CENTRAL, ProQuest Dissertations & Theses and Google Scholar), plus forward and backward searching from included studies and previous systematic reviews. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they were randomised controlled trials (RCTs) that compared an MBP against a control, in current or former elite athletes. RESULTS: Of 2386 articles identified, 12 RCTs were included in this systematic review and meta-analysis, comprising a total of 614 elite athletes (314 MBPs and 300 controls). Overall, MBPs improved mental health, with large significant pooled effect sizes for reducing symptoms of anxiety (hedges g=-0.87, number of studies (n)=6, p=0.017, I 2=90) and stress (g=-0.91, n=5, p=0.012, I 2=74) and increasing psychological well-being (g=0.96, n=5, p=0.039., I 2=89). Overall, the risk of bias and certainty of evidence was moderate, and all findings were subject to high estimated levels of heterogeneity. CONCLUSION: MBPs improved several mental health outcomes. Given the moderate degree of evidence, high-quality, adequately powered trials are required in the future. These studies should emphasise intervention fidelity, teacher competence and scalability within elite sport. PROSPERO REGISTRATION NUMBER: CRD42020176654.

Automated Real-Time Eddy Current Array Inspection of Nuclear Assets.

Inspection of components with surface discontinuities is an area that volumetric Non-Destructive Testing (NDT) methods, such as ultrasonic and radiographic, struggle in detection and characterisation. This coupled with the industrial desire to detect surface-breaking defects of components at the point of manufacture and/or maintenance, to increase design lifetime and further embed sustainability in their business models, is driving the increased adoption of Eddy Current Testing (ECT). Moreover, as businesses move toward Industry 4.0, demand for robotic delivery of NDT has grown. In this work, the authors present the novel implementation and use of a flexible robotic cell to deliver an eddy current array to inspect stress corrosion cracking on a nuclear canister made from 1.4404 stainless steel. Three 180-degree scans at different heights on one side of the canister were performed, and the acquired impedance data were vertically stitched together to show the full extent of the cracking. Axial and transversal datasets, corresponding to the transmit/receive coil configurations of the array elements, were simultaneously acquired at transmission frequencies 250, 300, 400, and 450 kHz and allowed for the generation of several impedance C-scan images. The variation in the lift-off of the eddy current array was innovatively minimised through the use of a force-torque sensor, a padded flexible ECT array and a PI control system. Through the use of bespoke software, the impedance data were logged in real-time (≤7 ms), displayed to the user, saved to a binary file, and flexibly post-processed via phase-rotation and mixing of the impedance data of different frequency and coil configuration channels. Phase rotation alone demonstrated an average increase in Signal to Noise Ratio (SNR) of 4.53 decibels across all datasets acquired, while a selective sum and average mixing technique was shown to increase the SNR by an average of 1.19 decibels. The results show how robotic delivery of eddy current arrays, and innovative post-processing, can allow for repeatable and flexible surface inspection, suitable for the challenges faced in many quality-focused industries.

Representation of Women on Plastic Surgery Journal Editorial Boards in the United States.

BACKGROUND: During the past decade, a growing number of women have pursued medical careers, including in plastic surgery. However, female physicians have tended to be underrepresented in a variety of leadership roles in their respective specialties. OBJECTIVES: The authors sought to evaluate the representation of female plastic surgeons on the editorial boards of high-impact plastic surgery journals. METHODS: The gender of editorial board members on 3 high-impact plastic surgery journals was evaluated from 2009 and 2018. The number of women on each editorial board was then compared with the number of board-certified female plastic surgeons (BCFPS) and board-certified female academic plastic surgeons (BCFAPS), a subgroup of BCFPS. RESULTS: There were 555 unique editorial board members from Plastic and Reconstructive Surgery, Aesthetic Surgery Journal, and Annals of Plastic Surgery from 2009 to 2018. During that period, 72 editors (13.0%) were women. At the beginning of the study, there were significantly fewer female editors than expected based on proportionate representation of BCFPS and BCFAPS to all board-certified plastic surgeons (P = 0.007 and 0.007, respectively). During the study, there was a 177% increase in women holding editorial board positions. At study end, women were adequately represented on all 3 editorial boards compared with their population data (BCFPS and BCFAPS). CONCLUSIONS: During the 10 years of this study (2009-2018), editorial boards have overcome the underrepresentation of women on, and female plastic surgeons are currently adequately represented on the top 3 high-impact journal editorial boards.

Pyoderma Gangrenosum: A Rare Disease With Dire Consequences in Facial Aesthetic Surgery Patients.

Pyoderma gangrenosum (PG) is a rare, inflammatory dermatologic condition characterized by painful cutaneous ulcerations. Herein, we describe the third documented case of PG arising in an elective plastic surgery patient who had undergone an otherwise uncomplicated facelift. We describe the course of her diagnosis and management of PG, which involved her face and neck and then progressed to her lower extremities. Although the etiology remains unknown, PG often arises in a host with another autoimmune disease. In the case described, the patient was diagnosed with an immunoglobulin A gammopathy shortly after she developed PG. Following the case report, the pathogenesis, diagnosis, and treatment strategy of PG is briefly reviewed. Level of Evidence: 5.

3D Nipple-Areolar Tattoo: It's Technique, Outcomes, and Utilization.

BACKGROUND: Three-dimensional (3D) nipple-areolar tattoo is a novel approach to nipple-areolar complex reconstruction for which little data exist. Our aim was to evaluate 3D nipple-areolar tattoo outcomes and investigate if patient factors, payer status, surgeries, or therapies affect tattoo utilization. METHODS: Patients pursuing skin-sparing (SSM) or attempted nipple-sparing mastectomy (NSM) with breast reconstruction from 2008 to 2019 were reviewed. Outcomes included frequency of 3D tattoo, post-procedure complications (infections, or other local adverse sequelae), and rates, indications, and timing of revisions. Patient factors, payer status, surgeries, and adjuvant therapies underwent univariate analysis comparing rates of 3D tattoo and revisions. RESULTS: A total of 191 patients were identified; median follow-up was 4 years. The majority of patients were white (165, 86%), married (146, 76%), and post-menopausal (97, 51%), with private insurance (156, 81%). Surgeries included SSM (172, 90%) or attempted NSM (19, 10%) with implant (154, 81%) or autologous reconstruction (37, 19%). Sixty-two patients (32%) underwent 3D nipple-areolar tattooing. No post-procedure complications occurred. After tattooing, 20 patients (32%) pursued revisions, the majority due to color fading (12, 60%). Average time from tattoo to completion of revisions was 5.6 months. Patients undergoing autologous reconstruction had a higher rate of 3D tattooing (p < 0.001). Adjuvant radiation led to a higher rate of revisions (p = 0.02). Patient factors, payer status, index mastectomy, and chemotherapy did not significantly affect rates of 3D tattooing or revisions. CONCLUSIONS: 3D nipple-areolar tattoo utilization is likely unaffected by age, marriage, menopause, or payer status. Radiotherapy and color fading can lead to more revisions. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Aesthetic Surgery Research Funding: Where Does It Come From and to Whom Does It Go?

BACKGROUND: Recent data show that aesthetic surgery research is lagging compared with reconstructive surgery: research funding and institutional disparities within aesthetic surgery are potential factors in this trend. OBJECTIVES: The authors sought to determine if disparities exist in aesthetic surgery research based on funding sources or practice settings. METHODS: The authors reviewed Aesthetic Surgery Journal articles from 2009 to 2019. Chi-square, t test, bivariate, and multivariate regression analyses were employed to evaluate research trends. RESULTS: A total of 2262 publications were identified, with 318 funded articles meeting inclusion criteria. The majority of studies (294, 92%) received external funding, with 281 (88%) being supported solely by external funds. Externally funded studies were financed by private industry (194, 66%), foundations/societies (53, 18%), government grants (23, 8%), or a combination of agencies (24, 8%). The majority of funded studies were at academic institutions (266, 84%), followed by private practice (46, 14%) and private industry (6, 2%). Analysis of annual publications revealed a rising percentage of academic-based research, which correlated with decreasing research from private practice (r = -0.95, r2 = 0.89, P < 0.001). Compared with academic institutions, private practice relied more heavily on industry funding (55% vs 87%, respectively, P = 0.001), exhibiting lower rates of foundational/societal (20% vs 2%), governmental (9% vs 0%), combined (8% vs 7%), and internal department funding (8% vs 4%). Article citations and level of evidence were unaffected by funding source, agency, or practice setting. CONCLUSIONS: Lack of diversity in research funding among private practice surgeons may explain the reported discrepancies that currently exist between aesthetic and reconstructive surgery research.

Does Prior Breast Augmentation Affect Outcomes After Mastectomy With Reconstruction? An Analysis of Postoperative Complications and Reoperations.

BACKGROUND: The purpose of this study is to evaluate how prior breast augmentation impacts rates of complications and risk for reoperation after mastectomy with concurrent breast reconstruction. METHODS: Patients undergoing nipple-sparing, skin-sparing, or simple mastectomy with implant-based reconstruction from 2008 to 2018 were identified in a prospective database. Postoperative complications and reoperations were then analyzed comparing patients with prior augmentation to patients without history of previous breast surgery. RESULTS: A total of 468 patients were identified with a median follow-up of 4 years. Of these, 72 had prior augmentation mammoplasty. These patients underwent nipple-sparing (52, 72%), skin-sparing (15, 21%), or simple (5, 7%) mastectomy with immediate direct-to-implant (46, 61%) or tissue expander (26, 35%) reconstruction. On univariate analysis, this cohort had a lower body mass index (23.3 vs 25.3, P = 0.003), a higher rate of nipple-sparing mastectomy (72% vs 54%, P = 0.01), and a higher prevalence of stage I disease (44% vs 33%, P = 0.04). Differences in age, comorbidities, reconstructive techniques, tumor size, and neoadjuvant/adjuvant therapies were not significant. Overall complication rate between patients with or without prior augmentation did not significantly differ (51% vs 50%, P = 0.83); no significant differences in rates of surgical site infection, hematoma, mastectomy skin flap/wound necrosis, nipple complications, implant loss, or capsular contracture were found. Analysis of reoperations between patients with and without prior augmentation revealed no significant differences in average number of subsequent planned, unplanned, or total reoperations. On multivariate analysis, prior breast augmentation was found to be associated with significantly increased risk for undergoing ≥1 unplanned reoperation (odds ratio, 2.28; 95% confidence interval, 1.28-4.05, P = 0.005). CONCLUSIONS: Prior augmentation mammoplasty does not significantly affect rates of postoperative complications after mastectomy with concurrent reconstruction. Although prior augmentation does not affect number of subsequent reoperations on average, it does increase the risk of experiencing 1 or more unplanned reoperation after mastectomy with reconstruction.

Venous Thromboembolism Prophylaxis in Aesthetic Surgery: A Survey of Plastic Surgeons' Practices.

BACKGROUND: Deep venous thrombosis and pulmonary embolism, collectively known as venous thromboembolism (VTE), are among the most feared yet preventable surgical complications. Although many recommendations exist to reduce the risk of VTE, the actual VTE prophylaxis practices of aesthetic plastic surgeons remain unknown. OBJECTIVES: The primary aim of this study was to elucidate plastic surgeons' experiences with VTE, preferred VTE prophylaxis practices, and areas in which VTE prevention may be improved. METHODS: Members of The Aesthetic Society were queried via a 55-question electronic survey regarding their experience with VTE as well as their VTE prophylaxis practices. Anonymous responses were collected and analyzed by the Mayo Clinic Survey Research Center. RESULTS: The survey was sent to 1729 of The Aesthetic Society members, of whom 286 responded. Fifty percent, 38%, and 6% of respondents reported having had a patient develop a deep venous thrombosis, pulmonary embolism, or death secondary to VTE, respectively. Procedures performed on the back or trunk were associated with the highest rate of VTE. Lower extremity procedures were associated with a significantly higher rate of VTE than expected. Over 90% of respondents reported utilizing a patient risk stratification assessment tool. Although at least one-half of respondents reported that the surgical facility in which they operate maintains some form of VTE prophylaxis protocol, 39% self-reported nonadherence with these protocols. CONCLUSIONS: Considerable variability exists in VTE prophylaxis practices among The Aesthetic Society responders. Future efforts should simplify guidelines and tailor prophylaxis recommendations to the aesthetic surgery population. Furthermore, education of plastic surgeons performing aesthetic surgery and more diligent surgical venue supervision is needed to narrow the gap between current recommendations and actual practices.

Author Disclosures in Plastic Surgery Journals Compared With Information Reported in the Open Payments Database: How Open Are We?

BACKGROUND: Relationships between companies in the biomedical industry and authors submitting scientific articles for publication has been an issue of some concern for many years. It has been frequently demonstrated that these financial relationships can influence the manner in which research findings are presented. The National Physician Payment Transparency Program, also known as the Open Payment Program or the Sunshine Act, was legislated to expose potential conflicts of interest (COIs). Likewise, most peer-reviewed journals require disclosure of any potential COIs. OBJECTIVES: The purpose of this paper was to compare the information published in the Open Payment Database to authors' self-disclosed COIs in their published articles. METHODS: An analysis was performed by one of the authors (P.S.B.) of all articles published in Aesthetic Surgery Journal (ASJ) and Plastic and Reconstructive Surgery (PRS) from August 2013 through December 2016. Financial disclosures reported in these articles were compared with the physician payment information provided by the biomedical industry and published in the Open Payments Database in 2013 and 2018. RESULTS: A total of 1346 articles were included in the study, from which 320 authors and 899 total authorships were eligible for analysis. Out of 782 authorships with noted discrepancies, 96% were related to potential COIs found in the Open Payments database but not disclosed in the journal publication. CONCLUSIONS: Our data suggest major discordance between authors' self-reported COIs in the plastic surgery literature and industry payments published in the Open Payments database.

Variables That Impact Medical Malpractice Claims Involving Plastic Surgeons in the United States.

BACKGROUND: Medical malpractice lawsuits contribute directly and indirectly to the cost of healthcare in the United States. Reducing medical malpractice claims represents an often unrecognized opportunity for improving both the quality and affordability of healthcare. OBJECTIVES: The aim of this study was to better understand variables of the informed consent process that may contribute to reducing malpractice claims in plastic surgery. METHODS: A prospective multiple choice questionnaire was distributed via email to all of the 1694 members of the American Society for Aesthetic Plastic Surgery (ASAPS) to evaluate attitudes and practices of informed consent in relation to medical malpractice. RESULTS: A total of 129 questionnaires obtained from plastic surgeons were eligible for analysis (response rate 7.6%). Respondents who provided procedure-specific brochures to their patients were significantly less likely to be sued for medical malpractice (P = 0.004) than those who did not. Plastic surgeons that participated in malpractice carrier-required courses on avoiding medical malpractice litigation had a similarly significantly reduced likelihood of lawsuits. (P = 0.04). CONCLUSIONS: Variables that may reduce malpractice claims, and thereby both improve the quality and affordability of healthcare, include: (1) the use of procedure-specific patient education brochures; and (2) physician participation in malpractice insurance carrier-required courses. These findings should be of interest to physicians, hospitals, and insurance companies.

Use of a secure social media platform to facilitate reflection in a residency program.

BACKGROUND: Reflective writing is used to promote learning and professional growth in medical education. Sharing reflections with peers and supervisors facilitates feedback that enhances understanding. OBJECTIVE: We explored the feasibility of using a secure social media platform to share reflections and promote reflective discussions in an emergency medicine residency program. METHODS: This was a prospective pilot investigation evaluated with a poststudy opinion survey. Reflective discussions were also described using basic quantitative and qualitative methods. RESULTS: The 2-month, voluntary, pilot study included 21 faculty and 36 residents. Faculty posted reflections and replies (n  =  146) more frequently than residents did (n  =  48). Survey data suggested both groups found the platform engaging and easy to use, valued the security of the platform, and felt the conversations were valuable to their professional development. CONCLUSIONS: Secure social media offers a feasible option for sharing reflections and facilitating reflective discussions in medical education.

In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers.

BACKGROUND: DNA-based vaccines have been safe but weakly immunogenic in humans to date. METHODS AND FINDINGS: We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines. CONCLUSIONS: This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate. TRIAL REGISTRATION: ClinicalTrials.gov NCT00545987.