Empiric flap coverage for the pneumonectomy stump: How protective is it? A single-institution cohort study.

OBJECTIVE: To evaluate the impact of empiric tissue flaps on bronchopleural fistula (BPF) rates after pneumonectomy. METHODS: Patients who underwent pneumonectomy between January 2001 and December 2019 were included. Primary end point was development of BPF. Secondary end points were impact of flap type on BPF rates, time to BPF development, and perioperative mortality. RESULTS: During the study period, 383 pneumonectomies were performed; 93 were extrapleural pneumonectomy. Most pneumonectomy cases had empiric flap coverage, with greater use in right-sided operations (right: 97%, 154/159; left: 80%, 179/224, P < .001). Empiric flaps harvested included intercostal, latissimus dorsi, serratus anterior, omentum, pectoralis major, pericardial fat/thymus, pericardium, and pleura. BPF occurred in 10.4% of the entire cohort but decreased to 6.6% when extrapleural pneumonectomy cases were excluded; 90% (36/40) of BPFs occurred on the right side (P < .001). Median time to develop BPF was 63 days, and 90-day mortality was greater in patients with BPF (12.5% BPF vs 7.4% non-BPF, P < .0001). Intercostal muscle had the lowest rate of BPF (4.5%), even in right-sided operations (8.7%). In contrast, larger muscle flaps such as latissimus dorsi (21%) and serratus anterior (33%) had greater rates of BPF, but the sample size was small in these cohorts. CONCLUSIONS: Empiric bronchial stump coverage should be performed in all right pneumonectomy cases due to greater risk of BPF. In our series, intercostal muscle flaps had low BPF rates, even in right-sided operations. Coverage of the left pneumonectomy stump is unnecessary due to low incidence of BPF in these cases.

Basolateral amygdala neuropeptide Y system modulates binge ethanol consumption.

Neuropeptide Y (NPY) signaling regulation of corticolimbic communication is known to modulate binge-like ethanol consumption in rodents. In this work we sought to assess the impact of intra-BLA NPY system modulation on binge-like ethanol intake and to assess the role of the NPY1R+ projection from the BLA to the mPFC in this behavior. We used "drinking-in-the-dark" (DID) procedures in C57BL6J mice to address these questions. First, the impact of intra-BLA administration of NPY on binge-like ethanol intake was assessed. Next, the impact of repeated cycles of DID intake on NPY1R expression in the BLA was assessed with use of immunohistochemistry (IHC). Finally, chemogenetic inhibition of BLA→mPFC NPY1R+ projections was assessed to determine if limbic communication with the mPFC was specifically involved in binge-like ethanol intake. Importantly, as both the BLA and NPY system are sexually dimorphic, both sexes were assessed in these studies. Intra-BLA NPY dose-dependently decreased binge-like ethanol intake in males only. Repeated DID reduced NPY1R expression in the BLA of both sexes. Silencing of BLA→mPFC NPY1R+ neurons significantly reduced binge-like ethanol intake in both sexes in a dose-dependent manner. We provide novel evidence that (1) intra-BLA NPY reduces binge-like ethanol intake in males; (2) binge-like ethanol intake reduces NPY1R levels in the BLA; and (3) chemogenetic inhibition of BLA→mPFC NPY1R+ neurons blunts binge-like drinking in male and female mice. These observations provide the first direct evidence that NPY signaling in the BLA, and specifically BLA communication with the mPFC, modulates binge-like ethanol consumption.

The mitigated carbon emissions of transitioning to virtual medical school and residency interviews: A survey-based study.

PURPOSE: Prior to COVID, thousands of medical school and residency applicants traversed their countries for in-person interviews each year. However, data on the greenhouse gas emissions from in-person interviews is limited. This study estimated greenhouse gas emissions associated with in-person medical school and residency interviews and explored applicant interview structure preferences. METHODS: From March to June 2022, we developed and distributed a nine-question, website-based survey to collect information on applicant virtual interview schedule, demographics and preference for future interview format. We calculated theoretical emissions for all interviews requiring air travel and performed a content analysis of interview preference explanations. RESULTS: We received responses from 258 first-year and 253 fourth-year medical students at 26 allopathic US medical schools who interviewed virtually in 2020-2021 and 2021-2022, respectively. Residency applicants participating in the study were interviewed at a mean of 15.3 programs (SD 5.4) and had mean theoretical emissions of 4.31 tons CO2 eq. Medical school applicants participating in the study were interviewed at a mean of 6.9 programs and had mean theoretical emissions of 2.19 tons CO2 eq. Ninety percent of medical school applicants and 91% of residency applicants participating in the study expressed a preference for hybrid or virtual interviews going forward. CONCLUSION: In-person medical training interviews have significant greenhouse gas emissions. Virtual and hybrid alternatives have a high degree of acceptability among applicants.

Extramural US Federal Research Grants For Health Outcomes Associated With Climate Change Inadequate, Too Narrow In Focus.

Climate change causes and exacerbates disease, creates and worsens health disparities, disrupts health care delivery, and imposes a significant disease burden in the US and globally. Critical knowledge gaps hinder an evidence-based response and are perpetuated by scarce federal research funds. We identified and described extramural US federal research funding (that is, grants provided to organizations and institutions outside of federal agencies) that both addressed health outcomes associated with climate change and was awarded between 2010 and 2020. During this eleven-year period, 102 grants met our criteria, totaling approximately $58.7 million, or approximately $5.3 million per year (2020 adjusted US dollars). Federal investments in climate change and health research during this period failed to address the breadth of climate-sensitive exposures, health outcomes, and impacts on vulnerable populations. Moving forward, in addition to increasing investment in climate and health research across all known hazards, critical attention should be placed on vulnerable populations and health equity. To achieve this, increased federal research coordination and cooperation are needed, as well as a mechanism to track this funding.

Role of protein aggregate structure on the strength and underwater performance of barnacle-inspired adhesives.

Nature employs protein aggregates when strong materials are needed to adhere surfaces in extreme environments, allowing organisms to survive conditions ranging from harsh intertidal coasts to open oceans. Amyloids and amyloid-like materials are prevalent and amongst the most densely bonded aggregate structures, though how they contribute to wet adhesion is not well understood. In this work, waterborne protein solutions of individual whey proteins are cured in place using varied temperature to produce model adhesives enriched in amyloid or non-amyloid aggregates. Dry adhesive strengths range from 0.2-1.5 MPa, while wet adhesive strengths range from 0-0.5 MPa across the tested proteins and processing conditions, highlighting that both proper protein selection and controlled aggregation extent are necessary for successful underwater performance. For bovine serum albumin, the amyloid-enriched adhesive was able to retain ca. 500 kPa bond strength underwater throughout extended immersion and thermal degradation testing, while the non-amyloid adhesive weakened by up to 80%. As freestanding gels, higher temperature processing improved underwater stability for all the protein materials, with amyloid-rich structures remaining mostly water-insoluble after 30 days submerged in water. Protein-based adhesives with a controlled aggregate structure shed light on the ability of amyloid-containing materials to remain adhered underwater, a necessary trait for the survival of many organisms.

A Narrative Review of Plastic Surgery and Climate Change: Context and Considerations.

Climate change poses significant threats to human health and society. Although healthcare will bear a large burden of the downstream effects of climate change, the healthcare industry is simultaneously a major contributor to climate change. Within hospitals, surgery is one of the most energy-intensive practices. There is a growing body of literature describing ways to mitigate and adapt to climate change in surgery. However, there is a need to better understand the unique implications for each surgical subspecialty. This review contextualizes plastic and reconstructive surgery within the climate change discussion. In particular, this review highlights the specific ways in which plastic surgery may affect climate change and how climate change may affect plastic surgery. In light of growing public demand for change and greater alignment between industries and nations with regard to climate change solutions, we also offer a conceptual framework to guide further work in this burgeoning field of research.

Public Perceptions of Climate Change and Plastic and Reconstructive Surgery.

Healthcare has a major impact on climate change, and surgery is among the most energy-intensive hospital practices. Although most Americans believe climate change is happening, little is known regarding public awareness of the impact of healthcare on climate change and how this may impact perceptions of plastic surgery. Methods: A cross-sectional survey was administered to adults in the United States using Amazon Mechanical Turk in December 2021 to assess public perceptions of climate change, healthcare, and plastic surgery. Incomplete responses were excluded from analysis. Multivariable logistic regression models were used to determine predictors of responses. Results: There were 890 complete responses. Most participants strongly agreed or agreed that climate change is happening (89%). Fewer believed that healthcare has an impact on climate change (62%), with greater odds among respondents with an associate's degree or higher (odds ratio 2.8, P < 0.001). After they were given information about the impact of healthcare on climate change, most respondents were more worried about the effects of cosmetic plastic surgery (64%). Many respondents would be willing to engage in personal climate change mitigation measures if undergoing surgery and pay higher professional fees to support sustainable hospital practices. Conclusions: Most Americans believe climate change is happening, but fewer believe healthcare has an impact on climate change. Knowledge regarding the impact of healthcare and surgery on climate change may make patients more worried about the effects of plastic surgery on climate change, but patients may be willing to personally mitigate climate impacts of surgery.

How Should We Respond to Health Sector Emissions That Exacerbate Climate Change and Inequity?

A warming climate poses substantial risk to public health and worsens existing health inequity. As a contributor to greenhouse gas emissions and air pollution, the health sector has obligations and ample opportunities to protect health by decreasing waste and motivating more system-wide sustainable clinical practices. Such efforts will have important ethical implications for health equity.

Examining the mental health of siblings of children with a mental disorder: A scoping review protocol.

INTRODUCTION: Mental disorders affect 1 in 5 children having consequences for both the child and their family. Indeed, the siblings of these children are not insulated from these consequences and may experience elevated levels of psychological distress, placing them at increased risk for developing mental disorders. This protocol describes the methodology for a scoping review that will examine how mental disorders in children impact the mental health of their sibling(s). Further, we aim to examine the role of sex, gender, birth order, age of each child, and familial factors (e.g., parent mental illness, family structure), in sibling mental health. The proposed review will also identify resources that aim to support the needs of siblings of children with mental disorders. Taken together, this proposed review aims to take a fundamental step towards determining intervention targets to reduce the transmission of risk between siblings. AIM: The proposed scoping review aims to address the following questions: i) how do mental disorders (in children <18 years of age) impact the mental health of their sibling(s) (also <18 years of age)? ii) Can we identify resources designed to address the needs of siblings of children with mental disorders? METHODS: We will conduct the proposed scoping review in keeping with the six-stage Arksey and O'Malley Framework and the scoping review methodology provided by the Joanna Briggs Institute. In section i) we outline our research questions. In section ii) we describe our process for identifying studies that examine the mental health of siblings of a child with a mental disorder and studies that provide evidence on resources directed specifically at these siblings. We will search peer-review and grey literature published between 2011 and 2022 from OVID MEDLINE, OVID EMBASE, CINAHL Complete, Proquest Nursing and Allied Health, PsycINFO (via APA platform), Proquest Sociology Collection and Web of Science Core Collection and Proquest Theses and Dissertations. Section iii) describes our process for selecting relevant studies. In sections iv and v, we describe our methods for charting and summarizing relevant data. Finally, in section vi) we describe our integrative knowledge translation plan that aims to include knowledge users in interpretating and translating evidence gathered from the proposed review.

The Connection between Climate Change, Surgical Care and Neglected Tropical Diseases.

The surgical burden of neglected tropical diseases (NTDs) is set to rise alongside average temperatures and drought. NTDs with surgical indications, including trachoma and lymphatic filariasis, predominantly affect people in low- and middle-income countries where the gravest effects of climate change are likely to be felt. Vectors sensitive to temperature and rainfall will likely expand their reach to previously nonendemic regions, while drought may exacerbate NTD burden in already resource-strained settings. Current NTD mitigation strategies, including mass drug administrations, were interrupted by COVID-19, demonstrating the vulnerability of NTD progress to global events. Without NTD programming that meshes with surgical systems strengthening, climate change may outpace current strategies to reduce the burden of these diseases.

High-Throughput Screening of Heterologous Functional Amyloids Using Escherichia coli.

Escherichia coli remains one of the most widely used workhorse microorganisms for the expression of heterologous proteins. The large number of cloning vectors and mutant host strains available for E. coli yields an impressively wide array of folded globular proteins in the laboratory. However, applying modern functional screening approaches to interrogate insoluble protein aggregates such as amyloids requires the use of nonstandard expression pathways. In this chapter, we detail the use of the curli export pathway in E. coli to express a library of gene fragments and variants of a functional amyloid protein to screen sequence traits responsible for aggregation and the formation of nanoscale materials.

A review on the biological, epidemiological, and statistical relevance of COVID-19 paired with air pollution.

This narrative review paper is aimed to critically evaluate recent studies of the associations between air pollution and the outcomes in the COVID-19 pandemic. The main air pollutants we have considered are carbon monoxide (CO), nitrogen dioxide (NO2), ground-level ozone (O3), particulate matter (PM2.5 and PM10), and sulfur dioxide (SO2). We, specifically, evaluated the influences of these pollutants, both individually and collaboratively, across various geographic areas and exposure windows. We further reviewed the proposed biological mechanisms underlying the association between air pollution and COVID-19. Ultimately, we aim to inform policy and public health practice regarding the implications of COVID-19 and air pollution.

Building sustainable and resilient surgical systems: A narrative review of opportunities to integrate climate change into national surgical planning in the Western Pacific region.

Five billion people lack access to surgical care worldwide; climate change is the biggest threat to human health in the 21st century. This review studies how climate change could be integrated into national surgical planning in the Western Pacific region. We searched databases (PubMed, Web of Science, and Global Health) for articles on climate change and surgical care. Findings were categorised using the modified World Health Organisation Health System Building Blocks Framework. 220 out of 2577 records were included. Infrastructure: Operating theatres are highly resource-intensive. Their carbon footprint could be reduced by maximising equipment longevity, improving energy efficiency, and renewable energy use. Service delivery Tele-medicine, outreaches, and avoiding desflurane could reduce emissions. Robust surgical systems are required to adapt to the increasing burden of surgically treated diseases, such as injuries from natural disasters. Finance: Climate change adaptation funds could be mobilised for surgical system strengthening. Information systems: Sustainability should be a key performance indicator for surgical systems. Workforce: Surgical providers could change clinical, institutional, and societal practices. Governance: Planning in surgical care and climate change should be aligned. Climate change mitigation is essential in the regional surgical care scale-up; surgical system strengthening is also necessary for adaptation to climate change.

National Evaluation of the Association Between Resident Labor Union Participation and Surgical Resident Well-being.

Importance: Labor unions are purported to improve working conditions; however, little evidence exists regarding the effect of resident physician unions. Objective: To evaluate the association of resident unions with well-being, educational environment, salary, and benefits among surgical residents in the US. Design, Setting, and Participants: This national cross-sectional survey study was based on a survey administered in January 2019 after the American Board of Surgery In-Training Examination (ABSITE). Clinically active residents at all nonmilitary US general surgery residency programs accredited by the American Council of Graduate Medical Education who completed the 2019 ABSITE were eligible for participation. Data were analyzed from December 5, 2020, to March 16, 2021. Exposures: Presence of a general surgery resident labor union. Rates of labor union coverage among non-health care employees within a region were used as an instrumental variable (IV) for the presence of a labor union at a residency program. Main Outcomes and Measures: The primary outcome was burnout, which was assessed using a modified version of the abbreviated Maslach Burnout Inventory and was defined as experiencing any symptom of depersonalization or emotional exhaustion at least weekly. Secondary outcomes included suicidality, measures of job satisfaction, duty hour violations, mistreatment, educational environment, salary, and benefits. Results: A total of 5701 residents at 285 programs completed the pertinent survey questions (response rate, 85.6%), of whom 3219 (56.5%) were male, 3779 (66.3%) were White individuals, 449 (7.9%) were of Hispanic ethnicity, 4239 (74.4%) were married or in a relationship, and 1304 (22.9%) had or were expecting children. Among respondents, 690 residents were from 30 unionized programs (10.5% of programs). There was no difference in burnout for residents at unionized vs nonunionized programs (297 [43.0%] vs 2175 [43.4%]; odds ratio [OR], 0.92 [95% CI, 0.75-1.13]; IV difference in probability, 0.15 [95% CI, -0.11 to 0.42]). There were no significant differences in suicidality, job satisfaction, duty hour violations, mistreatment, educational environment, salary, or benefits except that unionized programs more frequently offered 4 weeks instead of 2 to 3 weeks of vacation (27 [93.1%] vs 52 [30.6%]; OR, 19.18 [95% CI, 3.92-93.81]; IV difference in probability, 0.77 [95% CI, 0.09-1.45]) and more frequently offered housing stipends (10 [38.5%] vs 9 [16.1%]; OR, 2.15 [95% CI, 0.58-7.95]; IV difference in probability, 0.62 [95% CI 0.04-1.20]). Conclusions and Relevance: In this evaluation of surgical residency programs in the US, unionized programs offered improved vacation and housing stipend benefits, but resident unions were not associated with improved burnout, suicidality, job satisfaction, duty hour violations, mistreatment, educational environment, or salary.

Empowering Surgeons, Anesthesiologists, and Obstetricians to Incorporate Environmental Sustainability in the Operating Room.

OBJECTIVE: We review the existing research on environmentally sustainable surgical practices to enable SAO to advocate for improved environmental sustainability in operating rooms across the country. SUMMARY OF BACKGROUND DATA: Climate change refers to the impact of greenhouse gases emitted as a byproduct of human activities, trapped within our atmosphere and resulting in hotter and more variable climate patterns.1 As of 2013, the US healthcare industry was responsible for 9.8% of the country's emissions2; if it were itself a nation, US healthcare would rank 13th globally in emissions.3 As one of the most energy-intensive and wasteful areas of the hospital, ORs drive this trend. ORs are 3 to 6 times more energy intensive than clinical wards.4 Further, ORs and labor/delivery suites produce 50%-70% of waste across the hospital.5,6 Due to the adverse health impacts of climate change, the Lancet Climate Change Commission (2009) declared climate change "the biggest global health threat of the 21st century" and predicted it would exacerbate existing health disparities for minority groups, children and low socioeconomic patients.7. METHODS/RESULTS: We provide a comprehensive narrative review of published efforts to improve environmental sustainability in the OR while simultaneously achieving cost-savings, and highlight resources for clinicians interested in pursuing this work. CONCLUSION: Climate change adversely impacts patient health, and disproportionately impacts the most vulnerable patients. SAO contribute to the problem through their resource-intensive work in the OR and are uniquely positioned to lead efforts to improve the environmental sustainability of the OR.

Engineered Escherichia coli Biofilms Produce Adhesive Nanomaterials Shaped by a Patterned 43 kDa Barnacle Cement Protein.

Barnacles integrate multiple protein components into distinct amyloid-like nanofibers arranged as a bulk material network for their permanent underwater attachment. The design principle for how chemistry is displayed using adhesive nanomaterials, and fragments of proteins that are responsible for their formation, remains a challenge to assess and is yet to be established. Here, we use engineered bacterial biofilms to display a library of amyloid materials outside of the cell using full-length and subdomain sequences from a major component of the barnacle adhesive. A staggered charged pattern is found throughout the full-length sequence of a 43 kDa cement protein (AACP43), establishing a conserved sequence design evolved by barnacles to make adhesive nanomaterials. AACP43 domain deletions vary in their propensity to aggregate and form fibers, as exported extracellular materials are characterized through staining, immunoblotting, scanning electron microscopy, and atomic force microscopy. Full-length AACP43 and its domains have a propensity to aggregate into nanofibers independent of all other barnacle glue components, shedding light on its function in the barnacle adhesive. Curliated Escherichia coli biofilms are a compatible system for heterologous expression and the study of foreign functional amyloid adhesive materials, used here to identify the c-terminal portion of AACP43 as critical in material formation. This approach allows us to establish a common sequence pattern between two otherwise dissimilar families of cement proteins, laying the foundation to elucidate adhesive chemistries by one of the most tenacious marine fouling organisms in the ocean.

Structural Mimicry Drives HIV-1 Rev-Mediated HERV-K Expression.

Expression of the Human Endogenous Retrovirus Type K (HERV-K), the youngest and most active HERV, has been associated with various cancers and neurodegenerative diseases. As in all retroviruses, a fraction of HERV-K transcripts is exported from the nucleus in unspliced or incompletely spliced forms to serve as templates for translation of viral proteins. In a fraction of HERV-K loci (Type 2 proviruses), nuclear export of the unspliced HERV-K mRNA appears to be mediated by a cis-acting signal on the mRNA, the RcRE, and the protein Rec-these are analogous to the RRE-Rev system in HIV-1. Interestingly, the HIV-1 Rev protein is able to mediate the nuclear export of the HERV-K RcRE, contributing to elevated HERV-K expression in HIV-infected patients. We aimed to understand the structural basis for HIV Rev-HERV-K RcRE recognition. We examined the conformation of the RcRE RNA in solution using small-angle X-ray scattering (SAXS) and atomic force microscopy (AFM). We found that the 433-nt long RcRE can assume folded or extended conformations as observed by AFM. SAXS analysis of a truncated RcRE variant revealed an "A"-shaped topological structure similar to the one previously reported for the HIV-1 RRE. The effect of the overall topology was examined using several deletion variants. SAXS and biochemical analyses demonstrated that the "A" shape is necessary for efficient Rev-RcRE complex formation in vitro and nuclear export activity in cell culture. The findings provide insight into the mechanism of HERV-K expression and a structural explanation for HIV-1 Rev-mediated expression of HERV-K in HIV-infected patients. IMPORTANCE: Expression of the human endogenous retrovirus type K (HERV-K) has been associated with various cancers and autoimmune diseases. Nuclear export of both HIV-1 and HERV-K mRNAs is dependent on the interaction between a small viral protein (Rev in HIV-1 and Rec in HERV-K) and a region on the mRNA (RRE in HIV-1 and RcRE in HERV-K). HIV-1 Rev is able to mediate the nuclear export of RcRE-containing HERV-K mRNAs, which contributes to elevated production of HERV-K proteins in HIV-infected patients. We report the solution conformation of the RcRE RNA-the first three-dimensional topological structure for a HERV molecule-and find that the RcRE resembles the HIV-1 nuclear export signal, RRE. The finding reveals the structural basis for the increased HERV-K expression observed in HIV-infected patients. Elevated HERV expression, mediated by HIV infection or other stressors, can have various HERV-related biological consequences. The findings provide structural insight for regulation of HERV-K expression.

An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.

Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function of polycomb repressive complex 2 (PRC2) that mediates coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP), promoting evasion of T cell-mediated immunity. MHC-I APP gene promoters in MHC-I low cancers harbor bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine-induced upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological MHC-I silencing highlights a conserved mechanism by which cancers arising from these primitive tissues exploit PRC2 activity to enable immune evasion.

Molecular Recognition of Structures Is Key in the Polymerization of Patterned Barnacle Adhesive Sequences.

The permanent adhesive produced by adult barnacles is held together by tightly folded proteins that form amyloid-like materials distinct among marine foulants. In this work, we link stretches of alternating charged and noncharged linear sequences from a family of adhesive proteins to their role in forming fibrillar nanomaterials. Using recombinant proteins and short barnacle cement derived peptides (BCPs), we find a central sequence with charged motifs of the pattern [Gly/Ser/Val/Thr/Ala-X], where X are charged amino acids, to exert specific control over timing, structure, and morphology of fibril formation. While most BCPs remain dormant, the core segment demonstrates rapid polymerization as well as an ability to template other peptides with no propensity for self-assembly. Patterned charge domains assemble dormant peptides through a specific antiparallel ß-sheet structure as measured by FTIR. While charged domains favor an antiparallel structure, BCPs without charged domains switch fibril assembly to favor simpler parallel ß-sheet aggregates. In addition to activation, charged domains direct nanofibers to grow into discrete microns long fibrils similar to the natural adhesive, while segments without such domains only form short branched aggregates. The assembly of adhesive sequences through recognition of structured templates outlines a strategy used by barnacles to control physical mechanisms of underwater adhesive delivery, activation, and curing based on molecular recognition between proteins.