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OBJECTIVE: The aim of this study was to examine the association between race, experience of microaggressions, and implicit bias in surgical training. BACKGROUND: There is persistent underrepresentation of specific racial and ethnic groups in the field of surgery. Prior research has demonstrated significant sex differences among those who experience microaggressions during training. However, little research has been conducted on the association between race and experiences of microaggressions and implicit bias among surgical trainees. METHODS: A 46-item survey was distributed to general surgery residents and residents of surgical subspecialties through the Association of Program Directors in Surgery listserv and social media platforms. The questions included general information/demographic data and information about experiencing, witnessing, and responding to microaggressions during surgical training. The primary outcome was the prevalence of microaggressions during surgical training by self-disclosed race. Secondary outcomes were predictors of and adverse effects of microaggressions. RESULTS: A total of 1624 resident responses were obtained. General surgery residents comprised 825 (50.8%) responses. The female-to-male ratio was nearly equal (815:809). The majority of respondents identified as non-Hispanic White (63.4%), of which 5.3% of residents identified as non-Hispanic Black, and 9.5% identified as Hispanic. Notably, 91.9% of non-Hispanic Black residents (n=79) experienced microaggressions. After adjustment for other demographics, non-Hispanic Black residents were more likely than non-Hispanic White residents to experience microaggressions [odds ratio (OR): 8.81, P <0.001]. Similar findings were observed among Asian/Pacific Islanders (OR: 5.77, P <0.001) and Hispanic residents (OR: 3.35, P <0.001). CONCLUSIONS: Race plays an important role in experiencing microaggressions and implicit bias. As the future of our specialty relies on the well-being of the pipeline, it is crucial that training programs and institutions are proactive in developing formal methods to address the bias experienced by residents.
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Viés Implícito , Cirurgia Geral , Internato e Residência , Microagressão , Feminino , Humanos , Masculino , Etnicidade , Hispânico ou Latino , Negro ou Afro-AmericanoRESUMO
BACKGROUND: Large Language Models (LLMs) provide clinical guidance with inconsistent accuracy due to limitations with their training dataset. LLMs are "teachable" through customization. We compared the ability of the generic ChatGPT-4 model and a customized version of ChatGPT-4 to provide recommendations for the surgical management of gastroesophageal reflux disease (GERD) to both surgeons and patients. METHODS: Sixty patient cases were developed using eligibility criteria from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) & United European Gastroenterology (UEG)-European Association of Endoscopic. Surgery (EAES) guidelines for the surgical management of GERD. Standardized prompts were engineered for physicians as the end-user, with separate layperson prompts for patients. A customized GPT was developed to generate recommendations based on guidelines, called the GERD Tool for Surgery (GTS). Both the GTS and generic ChatGPT-4 were queried July 21st, 2024. Model performance was evaluated by comparing responses to SAGES & UEG-EAES guideline recommendations. Outcome data was presented using descriptive statistics including counts and percentages. RESULTS: The GTS provided accurate recommendations for the surgical management of GERD for 60/60 (100.0%) surgeon inquiries and 40/40 (100.0%) patient inquiries based on guideline recommendations. The Generic ChatGPT-4 model generated accurate guidance for 40/60 (66.7%) surgeon inquiries and 19/40 (47.5%) patient inquiries. The GTS produced recommendations based on the 2021 SAGES & UEG-EAES guidelines on the surgical management of GERD, while the generic ChatGPT-4 model generated guidance without citing evidence to support its recommendations. CONCLUSION: ChatGPT-4 can be customized to overcome limitations with its training dataset to provide recommendations for the surgical management of GERD with reliable accuracy and consistency. The training of LLM models can be used to help integrate this efficient technology into the creation of robust and accurate information for both surgeons and patients. Prospective data is needed to assess its effectiveness in a pragmatic clinical environment.
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BACKGROUND: Large language model (LLM)-linked chatbots may be an efficient source of clinical recommendations for healthcare providers and patients. This study evaluated the performance of LLM-linked chatbots in providing recommendations for the surgical management of gastroesophageal reflux disease (GERD). METHODS: Nine patient cases were created based on key questions addressed by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) guidelines for the surgical treatment of GERD. ChatGPT-3.5, ChatGPT-4, Copilot, Google Bard, and Perplexity AI were queried on November 16th, 2023, for recommendations regarding the surgical management of GERD. Accurate chatbot performance was defined as the number of responses aligning with SAGES guideline recommendations. Outcomes were reported with counts and percentages. RESULTS: Surgeons were given accurate recommendations for the surgical management of GERD in an adult patient for 5/7 (71.4%) KQs by ChatGPT-4, 3/7 (42.9%) KQs by Copilot, 6/7 (85.7%) KQs by Google Bard, and 3/7 (42.9%) KQs by Perplexity according to the SAGES guidelines. Patients were given accurate recommendations for 3/5 (60.0%) KQs by ChatGPT-4, 2/5 (40.0%) KQs by Copilot, 4/5 (80.0%) KQs by Google Bard, and 1/5 (20.0%) KQs by Perplexity, respectively. In a pediatric patient, surgeons were given accurate recommendations for 2/3 (66.7%) KQs by ChatGPT-4, 3/3 (100.0%) KQs by Copilot, 3/3 (100.0%) KQs by Google Bard, and 2/3 (66.7%) KQs by Perplexity. Patients were given appropriate guidance for 2/2 (100.0%) KQs by ChatGPT-4, 2/2 (100.0%) KQs by Copilot, 1/2 (50.0%) KQs by Google Bard, and 1/2 (50.0%) KQs by Perplexity. CONCLUSIONS: Gastrointestinal surgeons, gastroenterologists, and patients should recognize both the promise and pitfalls of LLM's when utilized for advice on surgical management of GERD. Additional training of LLM's using evidence-based health information is needed.
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Inteligência Artificial , Refluxo Gastroesofágico , Refluxo Gastroesofágico/cirurgia , Humanos , Tomada de Decisão Clínica , Adulto , Guias de Prática Clínica como Assunto , MasculinoRESUMO
BACKGROUND: Minimally invasive surgery has been used for both de novo insertion and salvage of peritoneal dialysis (PD) catheters. Advanced laparoscopic, basic laparoscopic, open, and image-guided techniques have evolved as the most popular techniques. The aim of this guideline was to develop evidence-based guidelines that support surgeons, patients, and other physicians in decisions on minimally invasive peritoneal dialysis access and the salvage of malfunctioning catheters in both adults and children. METHODS: A guidelines committee panel of the Society of American Gastrointestinal and Endoscopic Surgeons reviewed the literature since the prior guideline was published in 2014 and developed seven key questions in adults and four in children. After a systematic review of the literature, by the panel, evidence-based recommendations were formulated using the Grading of Recommendations Assessment, Development and Evaluation approach. Recommendations for future research were also proposed. RESULTS: After systematic review, data extraction, and evidence to decision meetings, the panel agreed on twelve recommendations for the peri-operative performance of laparoscopic peritoneal dialysis access surgery and management of catheter dysfunction. CONCLUSIONS: In the adult population, conditional recommendations were made in favor of: staged hernia repair followed by PD catheter insertion over simultaneous and traditional start over urgent start of PD when medically possible. Furthermore, the panel suggested advanced laparoscopic insertion techniques rather than basic laparoscopic techniques or open insertion. Conditional recommendations were made for either advanced laparoscopic or image-guided percutaneous insertion and for either nonoperative or operative salvage. A recommendation could not be made regarding concomitant clean-contaminated surgery in adults. In the pediatric population, conditional recommendations were made for either traditional or urgent start of PD, concomitant clean or clean-contaminated surgery and PD catheter placement rather than staged, and advanced laparoscopic placement rather than basic or open insertion.
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Falência Renal Crônica , Laparoscopia , Diálise Peritoneal , Adulto , Criança , Humanos , Cateterismo/métodos , Cateteres de Demora , Diálise Peritoneal/métodos , PeritônioRESUMO
OBJECTIVE: To examine the prevalence, nature, and source of microaggressions experienced by surgical residents during training. SUMMARY AND BACKGROUND DATA: The role of microaggressions in contributing to workplace culture, individual performance, and professional satisfaction has become an increasingly studied topic across various fields. Little is known about the prevalence and impact of microaggressions during surgical training. METHODS: A 46-item survey distributed to current surgical residents in training programs across the United States via the Association of Program Directors in Surgery listserv and social media platforms between January and May 2020. Survey questions explored the frequency and extent of events of experiencing, witnessing, and responding to microaggressions in the workplace. The primary outcome was the occurrence of microaggressions experienced by surgical residents. Secondary outcomes included the nature, impact, and responses to these events. RESULTS: A total of 1624 responses were collected, with an equal distribution by self-identified gender (female, n = 815; male, n = 809). The majority of trainees considered themselves heterosexual (n = 1490, 91.7%) and White (n = 1131, 69.6%). A majority (72.2%, n = 1173) of respondents reported experiencing microaggressions, most commonly from patients (64.1%), followed by staff (57.5%), faculty (45.3%), and co-residents (38.8%). Only a small proportion (n = 109, 7.0%) of residents reported these events to graduate medical education office/program director. Nearly one third (30.8%) of residents said they experienced retaliation due to reporting of micro-aggressions. CONCLUSIONS: Based on this large, national survey of general surgery and surgical subspecialty trainees, microaggressions appear to be pervasive in surgical training. Microaggressions are rarely reported to program leadership, and when reported, can result in retaliation.
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Viés Implícito , Internato e Residência , Humanos , Masculino , Feminino , Estados Unidos , Microagressão , Educação de Pós-Graduação em Medicina , Inquéritos e Questionários , DocentesRESUMO
OBJECTIVE: To summarize state-of-the-art artificial intelligence-enabled decision support in surgery and to quantify deficiencies in scientific rigor and reporting. BACKGROUND: To positively affect surgical care, decision-support models must exceed current reporting guideline requirements by performing external and real-time validation, enrolling adequate sample sizes, reporting model precision, assessing performance across vulnerable populations, and achieving clinical implementation; the degree to which published models meet these criteria is unknown. METHODS: Embase, PubMed, and MEDLINE databases were searched from their inception to September 21, 2022 for articles describing artificial intelligence-enabled decision support in surgery that uses preoperative or intraoperative data elements to predict complications within 90 days of surgery. Scientific rigor and reporting criteria were assessed and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. RESULTS: Sample size ranged from 163-2,882,526, with 8/36 articles (22.2%) featuring sample sizes of less than 2000; 7 of these 8 articles (87.5%) had below-average (<0.83) area under the receiver operating characteristic or accuracy. Overall, 29 articles (80.6%) performed internal validation only, 5 (13.8%) performed external validation, and 2 (5.6%) performed real-time validation. Twenty-three articles (63.9%) reported precision. No articles reported performance across sociodemographic categories. Thirteen articles (36.1%) presented a framework that could be used for clinical implementation; none assessed clinical implementation efficacy. CONCLUSIONS: Artificial intelligence-enabled decision support in surgery is limited by reliance on internal validation, small sample sizes that risk overfitting and sacrifice predictive performance, and failure to report confidence intervals, precision, equity analyses, and clinical implementation. Researchers should strive to improve scientific quality.
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Inteligência Artificial , Humanos , Curva ROCRESUMO
PDMS (polydimethylsiloxane) is a cheap, optically clear polymer that is elastic and can be easily and quickly fabricated into a wide array of microscale and nanoscale architectures, making it a versatile substrate for biophysical experiments on cell membranes. It is easy to imagine many new experiments will be devised that require a bilayer to be placed upon a substrate that is flexible or easily cast into a desired geometry, such as in lab-on-a-chip, organ-on-chip, and microfluidic applications, or for building accurate membrane models that replicate the surface structure and elasticity of the cytoskeleton. However, PDMS has its limitations, and the extent to which the behavior of membranes is affected on PDMS has not been fully explored. We use AFM and fluorescence optical microscopy to investigate the use of PDMS as a substrate for the formation and study of supported lipid bilayers (SLBs). Lipid bilayers form on plasma-treated PDMS and show free diffusion and normal phase transitions, confirming its suitability as a model bilayer substrate. However, lipid-phase separation on PDMS is severely restricted due to the pinning of domains to surface roughness, resulting in the cessation of lateral hydrodynamic flow. We show the high-resolution porous structure of PDMS and the extreme smoothing effect of oxygen plasma treatment used to hydrophilize the surface, but this is not flat enough to allow domain formation. We also observe bilayer degradation over hour timescales, which correlates with the known hydrophobic recovery of PDMS, and establish a critical water contact angle of 30°, above which bilayers degrade or not form at all. Care must be taken as incomplete surface oxidation and hydrophobic recovery result in optically invisible membrane disruption, which will also be transparent to fluorescence microscopy and lipid diffusion measurements in the early stages.
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Bicamadas Lipídicas , Água , Bicamadas Lipídicas/química , Elasticidade , Microscopia de FluorescênciaRESUMO
BACKGROUND: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee develops evidence-based guidelines for practicing surgeons using standard methodology. Our objective was to survey the SAGES membership regarding guidelines' quality, use, and value and identify topics of interest for new guideline development. METHODS: An anonymous online survey was emailed in October 2019 to SAGES members. Respondents were asked 18 questions on their use and evaluation of SAGES guidelines and SAGES reviews and to provide suggestions for new guideline topics and areas of improvement. The survey was open for 6 weeks with a 3-week reminder. RESULTS: Of 548 responders, most were minimally invasive (41%) or general surgeons (33%). There was an even distribution between academic (46%) and non-academic practice (24% private practice, 23% hospital employed). Most used SAGES guidelines frequently (22%) or occasionally (68%) and found them to be of value (83%), above average quality (86%), and easy to use (74%). While most stated it was important (35%) or very important (58%) that SAGES continues to follow "rigorous guidelines development processes," common suggestions were for more timely updates and improved web access. Of 442 overlapping topic suggestions, 60% fell into overarching categories of hernia, bariatric, robotic, HPB, and colorectal surgery. CONCLUSIONS: The SAGES guidelines are used frequently and valued by its users for their quality and content. Topics proposed by SAGES members and valuable insight from this survey can guide creation of new guidelines and refinement of established guidelines and processes.
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Procedimentos Cirúrgicos do Sistema Digestório/métodos , Guias como Assunto , Humanos , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: The mission of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) is to innovate, educate, and collaborate to improve patient care. A critical element in meeting this mission is the publishing of trustworthy and current guidelines for the practicing surgeon. METHODS: In this manuscript, we outline the steps of developing high quality practice guidelines using a completely volunteer-based professional organization. RESULTS: SAGES has developed a standardized approach to train volunteer surgeons and trainees alike to develop clinically pertinent guidelines in a timely manner, without sacrificing quality. CONCLUSIONS: This methodology can be used more widely by volunteer organizations to efficiently develop effective tools for practicing physicians.
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Sociedades Médicas , Cirurgiões , Endoscopia , Humanos , Editoração , Estados UnidosRESUMO
BACKGROUND: Gastroesophageal reflux disease (GERD) has a high worldwide prevalence in adults and children. There is uncertainty regarding medical versus surgical therapy and different surgical techniques. This review assessed outcomes of antireflux surgery versus medical management of GERD in adults and children, robotic versus laparoscopic fundoplication, complete versus partial fundoplication, and minimal versus maximal dissection in pediatric patients. METHODS: PubMed, Embase, and Cochrane databases were searched (2004-2019) to identify randomized control and non-randomized comparative studies. Two independent reviewers screened for eligibility. Random effects meta-analysis was performed on comparative data. Study quality was assessed using the Cochrane Risk of Bias and Newcastle Ottawa Scale. RESULTS: From 1473 records, 105 studies were included. Most had high or uncertain risk of bias. Analysis demonstrated that anti-reflux surgery was associated with superior short-term quality of life compared to PPI (Std mean difference = - 0.51, 95%CI - 0.63, - 0.40, I2 = 0%) however short-term symptom control was not significantly superior (RR = 0.75, 95%CI 0.47, 1.21, I2 = 82%). A proportion of patients undergoing operative treatment continue PPI treatment (28%). Robotic and laparoscopic fundoplication outcomes were similar. Compared to total fundoplication, partial fundoplication was associated with higher rates of prolonged PPI usage (RR = 2.06, 95%CI 1.08, 3.94, I2 = 45%). There was no statistically significant difference for long-term symptom control (RR = 0.94, 95%CI 0.85, 1.04, I2 = 53%) or long-term dysphagia (RR = 0.73, 95%CI 0.52, 1.02, I2 = 0%). Ien, minimal dissection during fundoplication was associated with lower reoperation rates than maximal dissection (RR = 0.21, 95%CI 0.06, 0.67). CONCLUSIONS: The available evidence regarding the optimal treatment of GERD often suffers from high risk of bias. Additional high-quality randomized control trials may further inform surgical decision making in the treatment of GERD.
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Refluxo Gastroesofágico , Laparoscopia , Adulto , Criança , Fundoplicatura , Refluxo Gastroesofágico/cirurgia , Humanos , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Gastroesophageal Reflux Disease (GERD) is an extremely common condition with several medical and surgical treatment options. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians, patients, and others in decisions regarding the treatment of GERD with an emphasis on evaluating different surgical techniques. METHODS: Literature reviews were conducted for 4 key questions regarding the surgical treatment of GERD in both adults and children: surgical vs. medical treatment, robotic vs. laparoscopic fundoplication, partial vs. complete fundoplication, and division vs. preservation of short gastric vessels in adults or maximal versus minimal dissection in pediatric patients. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Recommendations for future research were also proposed. RESULTS: The panel provided seven recommendations for adults and children with GERD. All recommendations were conditional due to very low, low, or moderate certainty of evidence. The panel conditionally recommended surgical treatment over medical management for adults with chronic or chronic refractory GERD. There was insufficient evidence for the panel to make a recommendation regarding surgical versus medical treatment in children. The panel suggested that once the decision to pursue surgical therapy is made, adults and children with GERD may be treated with either a robotic or a laparoscopic approach, and either partial or complete fundoplication based on surgeon-patient shared decision-making and patient values. In adults, the panel suggested either division or non-division of the short gastric vessels is appropriate, and that children should undergo minimal dissection during fundoplication. CONCLUSIONS: These recommendations should provide guidance with regard to surgical decision-making in the treatment of GERD and highlight the importance of shared decision-making and patient values to optimize patient outcomes. Pursuing the identified research needs may improve future versions of guidelines for the treatment of GERD.
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Esofagoplastia , Refluxo Gastroesofágico , Laparoscopia , Adulto , Criança , Fundoplicatura , Refluxo Gastroesofágico/cirurgia , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Minimally invasive splenectomy (MIS) is increasingly favored for the treatment of benign and malignant diseases of the spleen over open access approaches. While many studies cite the superiority of MIS in terms of decreased morbidity and length of stay over a traditional open approach, the comparative effectiveness of specific technical and peri-operative approaches to MIS is unclear. OBJECTIVE: To develop evidence-based guidelines that support clinicians, patients, and others in decisions on the peri-operative performance of MIS. METHODS: A guidelines committee panel of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) including methodologists used the Grading of Recommendations Assessment, Development and Evaluation approach to grade the certainty of evidence and formulate recommendations. RESULTS: Informed by a systematic review of the evidence, the panel agreed on eight recommendations for the peri-operative performance of MIS for adults and children in elective situations addressing six key questions. CONCLUSIONS: Conditional recommendations were made in favor of lateral positioning for non-hematologic disease, intra-operative platelet administration for patients with idiopathic thrombocytopenic purpura instead of preoperative administration, and the use of mechanical devices to control the splenic hilum. Further, a conditional recommendation was made against routine intra-operative drain placement.
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Laparoscopia , Púrpura Trombocitopênica Idiopática , Adulto , Criança , Procedimentos Cirúrgicos Eletivos , Humanos , Púrpura Trombocitopênica Idiopática/cirurgia , Baço , Esplenectomia , Resultado do TratamentoRESUMO
BACKGROUND: The increase in female surgeons has resulted in scrutiny of widely variable parental leave policies. We hypothesized that academic and private practice surgeons have different experiences based on difference in workplace expectations. METHODS: A 25-question survey was disseminated via social media and through the Association of Women Surgeons social media platforms from June 1 to September 15, 2017. An analysis of attending surgeons working in the USA in an academic or private practice setting was performed. RESULTS: Of 1115 total respondents, 477 were attending surgeons practicing in the USA. Practice distribution was 34% private and 47% academic. There was no difference in marital status, work status, or the number who report having been pregnant between the groups. Compared to academic surgeons, private practice surgeons were statistically less likely to have paid leave (p < 0.001) and were more likely to continue to pay benefits while on leave (p < 0.001). Private practitioners were more likely to return to work sooner than desired due to financial (p = 0.022) and supervisor (p = 0.004) pressures and were more likely to leave a job (p = 0.01). Academic surgeons were more likely to experience a delay in job advancement (p = 0.031). On multivariate analysis, more than two pregnancies were associated with an increased risk of perception of a bias and discrimination against pregnancy in the workplace. CONCLUSIONS: Parental leave policies and attitudes vary between academic and private practice, creating unique challenges for female surgeons and different issues for family planning depending on employment model.
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Licença Parental , Médicas , Cirurgiões , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Políticas , Gravidez , Local de TrabalhoRESUMO
The sepsis order set at our institution was created with the intent to facilitate the prompt initiation of appropriate sepsis care. Once clinical features meeting criteria for systemic inflammatory response syndrome (SIRS) are identified and an infectious source is considered, a "sepsis huddle" is concomitantly initiated. The sepsis huddle was implemented in March of 2016 in order to increase compliance with the sepsis bundles. The sepsis huddle is called via overhead paging system in the emergency department (ED) to notify all staff that there is a patient present who meets SIRS criteria with concern for sepsis requiring immediate attention. The sepsis order set is utilized for these patients and includes laboratory testing, treatment, and monitoring items to meet sepsis "bundle" compliance. In addition, it suggests antibiotic options to be administered based on the presumed source of infection. Each team member responding to a sepsis huddle has a pre-established role outlined to facilitate timely treatment. The Centers for Medicare & Medicaid Services, (CMS), is part of the Department of Health and Human Services (HHS). CMS sepsis guidelines call for periodic patient reassessment, including repeat vital signs, pertinent physical examination findings, and timed lactic acid measurement to determine a patient's response to resuscitation efforts. Our established order set has automated some of these reassessment features to facilitate compliance. Sepsis huddle initiation also triggers a department staff member to track the timing and completion of serial blood draws. Utilizing and adhering to the guidelines of this methodology in the management of these patients has enabled our hospital to improve benchmarking compliance from previously underperforming at the 31st and 49th percentiles in 2015, prior to initiation of the huddle, to a peak compliance at the 81st and 91st percentiles in 2016 and 65th and 83rd percentiles in 2017 for the 3-hour and 6-hour bundles respectively.
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Benchmarking/normas , Serviço Hospitalar de Emergência/tendências , Sepse/classificação , Benchmarking/métodos , Benchmarking/estatística & dados numéricos , Serviço Hospitalar de Emergência/organização & administração , Fidelidade a Diretrizes , Humanos , New York , Estudos Retrospectivos , Sepse/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/classificação , Síndrome de Resposta Inflamatória Sistêmica/diagnósticoRESUMO
Supported lipid bilayers are model membranes formed at solid substrate surfaces. This architecture renders the membrane experimentally accessible to surface-sensitive techniques used to study their properties, including atomic force microscopy, optical fluorescence microscopy, quartz crystal microbalance, and X-ray/neutron reflectometry, and allows integration with technology for potential biotechnological applications such as drug screening devices. The experimental technique often dictates substrate choice or treatment, and it is anecdotally recognized that certain substrates are suitable for a particular experiment, but the exact influence of the substrate has not been comprehensively investigated. Here, we study the behavior of a simple model bilayer, phase-separating on a variety of commonly used substrates, including glass, mica, silicon, and quartz, with drastically different results. The distinct micron-scale domains observed on mica, identical to those seen in free-floating giant unilamellar vesicles, are reduced to nanometer-scale domains on glass and quartz. The mechanism for the arrest of domain formation is investigated, and the most likely candidate is nanoscale surface roughness, acting as a drag on the hydrodynamic motion of small domains during phase separation. Evidence was found that the physicochemical properties of the surface have a mediating effect, most likely because of the changes in the lubricating interstitial water layer between the surface and bilayer.
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Silicatos de Alumínio/química , Vidro/química , Bicamadas Lipídicas/química , Microdomínios da Membrana/química , Quartzo/química , Silício/química , 1,2-Dipalmitoilfosfatidilcolina/química , Difusão , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Propriedades de SuperfícieRESUMO
Halophilic organisms have adapted to survive in high salt environments, where mesophilic organisms would perish. One of the biggest challenges faced by halophilic proteins is the ability to maintain both the structure and function at molar concentrations of salt. A distinct adaptation of halophilic proteins, compared to mesophilic homologues, is the abundance of aspartic acid on the protein surface. Mutagenesis and crystallographic studies of halophilic proteins suggest an important role for solvent interactions with the surface aspartic acid residues. This interaction, between the regions of the acidic protein surface and the solvent, is thought to maintain a hydration layer around the protein at molar salt concentrations thereby allowing halophilic proteins to retain their functional state. Here we present neutron diffraction data of the monomeric zwitterionic form of aspartic acid solutions at physiological pH in 0.25 M and 2.5 M concentration of potassium chloride, to mimic mesophilic and halophilic-like environmental conditions. We have used isotopic substitution in combination with empirical potential structure refinement to extract atomic-scale information from the data. Our study provides structural insights that support the hypothesis that carboxyl groups on acidic residues bind water more tightly under high salt conditions, in support of the residue-ion interaction model of halophilic protein stabilisation. Furthermore our data show that in the presence of high salt the self-association between the zwitterionic form of aspartic acid molecules is reduced, suggesting a possible mechanism through which protein aggregation is prevented.
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Ácido Aspártico/química , Cloreto de Potássio/química , Cloreto de Sódio/química , Solventes/química , Adaptação Fisiológica , Estabilidade ProteicaRESUMO
Extremophiles are organisms which survive and thrive in extreme environments. The proteins from extremophilic single-celled organisms have received considerable attention as they are structurally stable and functionally active under extreme physical and chemical conditions. In this short article, we provide an introduction to extremophiles, the structural adaptations of proteins from extremophilic organisms and the exploitation of these proteins in industrial applications. We provide a review of recent developments which have utilized single molecule force spectroscopy to mechanically manipulate proteins from extremophilic organisms and the information which has been gained about their stability, flexibility and underlying energy landscapes.
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Adaptação Fisiológica/genética , Metabolismo Energético/genética , Meio Ambiente , Proteínas/química , Estabilidade Proteica , Proteínas/genética , Proteínas/metabolismo , Análise Espectral , Sulfolobus acidocaldarius/química , Sulfolobus acidocaldarius/metabolismoRESUMO
PURPOSE: This pilot study of a diet and physical activity intervention (HEALTH4CLL) was conducted to reduce fatigue and improve physical function (PF) in patients with chronic lymphocytic leukemia (CLL). METHODS: The HEALTH4CLL study used a randomized factorial design based on the multiphase optimization strategy (MOST). Patients received diet, exercise, and body weight management instructional materials plus a Fitbit and were randomized to undergo one of 16 combinations of 4 evidence-based mHealth intervention strategies over 16 weeks. Patients' fatigue, PF, health-related quality of life, behavior changes, and program satisfaction and retention were assessed. Paired t-tests were used to examine changes in outcomes from baseline to follow-up among patients. Factorial analysis of variance examined effective intervention components and their combinations regarding improvement in fatigue and PF scores. RESULTS: Among 31 patients, we observed significant improvements in fatigue (+ 11.8; t = 4.08, p = 0.001) and PF (+ 2.6; t = 2.75, p = 0.01) scores. The combination of resistance and aerobic exercise with daily self-monitoring was associated with improved fatigue scores (ß = 3.857, SE = 1.617, p = 0.027). Analysis of the individual components of the MOST design demonstrated greater improvement in the PF score with resistance plus aerobic exercise than with aerobic exercise alone (ß = 2.257, SE = 1.071, p = 0.048). CONCLUSIONS: Combined aerobic and resistance exercise and daily self-monitoring improved PF and reduced fatigue in patients with CLL. IMPLICATIONS FOR CANCER SURVIVORS: This pilot study supported the feasibility of a low-touch mHealth intervention for survivors of CLL and provided preliminary evidence that exercising, particularly resistance exercise, can improve their symptoms and quality of life.
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BACKGROUND: The Bleeding Control Basics (B-Con) Course was developed to teach lifesaving hemorrhage control techniques to the public. Currently, medical students (MS) without prior clinical experience (CE) may not act as autonomous instructors, limiting the instructor pool. PURPOSE: To assess the bleeding control knowledge of MS (phase I) and compare the knowledge of students taught by a certified instructor vs a medical student (phase II). METHODS: Phase I: 20 MS, 6 with prior CE and 14 without clinical experience (NCE) completed a pre-course and post-course knowledge assessment. Results were assessed by independent sample t-tests. Phase II: 91 first-year MS were taught the B-Con Course by either a third-year MS (n = 45) or certified instructor (n = 46). An analysis of covariance (ANCOVA) was performed to compare scores by instructor type (certified vs MS) using prior CE and pretest scores as confounding variables. RESULTS: In Phase I, the CE group scored higher on the pretest assessment compared to the NCE group (P = .003). All students improved in posttest scoring, and there was no difference in posttest scores between the groups (P = .597). In Phase II, despite no difference in pretest scores between groups, the MS taught learners scored significantly higher on the posttest compared to the certified instructor group (P < .01). Prior CE did not correlate to posttest scores (P = .719). DISCUSSION: Medical students are as effective as certified instructors at conveying the B-Con learning objectives. Based on near-perfect assimilation of content by students, MS should be permitted to teach B-Con Courses.
Assuntos
Estudantes de Medicina , Humanos , Hemorragia/prevenção & controle , Currículo , Respiração ArtificialRESUMO
The anticancer complexes cisplatin and carboplatin target the DNA major groove, forming intrastrand and interstrand cross-links between guanine bases through their N7 atoms, causing distortion of the DNA helix and apoptotic cell death. A major side effect of these drugs is toxicity, which is caused via binding to many proteins in the body. A range of crystallographic studies have been carried out involving the cocrystallization of hen egg-white lysozyme (HEWL) as a test protein with cisplatin and carboplatin in aqueous and dimethyl sulfoxide (DMSO) conditions. Different cryoprotectants, glycerol and Paratone, were used for each of the cisplatin and carboplatin cocrystallization cases, while silicone oil was used for studies involving N-acetylglucosamine (NAG). Both cisplatin and carboplatin do not bind to HEWL in aqueous media on the timescales of the conditions used here, but upon addition of DMSO two molecules of cisplatin or carboplatin bind either side of His15, which is the only His residue in lysozyme and is assumed to be an imidazolyl anion or a chemical resonance moiety, i.e. both imidazole N atoms are chemically reactive. To identify the platinum-peak positions in the 'with DMSO conditions', anomalous scattering maps were calculated as a cross-check with the F(o) - F(c) OMIT maps. Platinum-occupancy σ values were established using three different software programs in each case. The use of EVAL15 to process all of the diffraction data sets provided a consistent platform for a large ensemble of data sets for the various protein and platinum-compound model refinements with REFMAC5 and then SHELXTL. Overall, this extensive set of crystallization and cryoprotectant conditions allowed a systematic evaluation of cisplatin and carboplatin binding to lysozyme as a test protein via detailed X-ray crystal structure characterizations. DMSO is used as a super-solvent for drug delivery as it is deemed to cause no effect upon drug binding. However, these results show that addition of DMSO causes the platinum anticancer drugs to bind to HEWL. This effect should be considered in toxicity assessments of these drugs and perhaps more widely.