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OBJECTIVES: The absorption of biostimulatory particulate matter following its application to fractional skin defects remains poorly understood, and even less is known about its in vivo impact in terms of tissue integration. The objectives of this study are twofold: (1) to evaluate the potential of calcium hydroxylapatite (CaHA) to penetrate through skin treated with a fractional laser; and (2) to assess the effectiveness of clinical laser scanning microscopy technologies in monitoring the effects of such treatment over time. METHODS: One area on a volunteer's arm was treated with a fractional erbium laser (Sciton Inc., Palo Alto, CA), while a second area received the same laser treatment followed by CaHA topical application. We used reflectance confocal microscopy (RCM) and multiphoton microscopy (MPM) to noninvasively image beneath the surface of the treated skin to study and monitor the effects of these treatments within 1 h of treatment and at four additional time points over a 6-week period. RESULTS: One hour posttreatment, at different depths beneath the skin surface, MPM and RCM provided similar visualizations of laser-induced channels. In skin treated by both laser and CaHA, these two imaging methods provided complementary information. RCM captured the lateral and depth distribution of CaHA microspheres and were seen as bright spheres as they became incorporated into the healing tissue. MPM, meanwhile, visualized the CaHA microparticles as dark shadow spheres within the laser-induced channels and encroaching healing tissue. Furthermore, MPM provided critical information about collagen regeneration around the microspheres, with the collagen visually marked by its distinct second harmonic generation (SHG) signal. CONCLUSIONS: This observational pilot study demonstrates that CaHA, a collagen stimulator used as a dermal filler, can not only be inserted into the dermis after fractional laser treatment but remains in the healing skin for at least 6 weeks posttreatment. The noninvasive imaging techniques RCM and MPM successfully captured the presence of CaHA microspheres mid-dermis during the healing phase. They also demonstrated new collagen production around the microspheres, highlighting the effectiveness of these imaging approaches in monitoring such treatment over time.
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Much of the evolutionary ecology of toxic algal blooms (TABs) remains unclear, including the role of algal toxins in the adaptive 'strategies' of TAB-forming species. Most eukaryotic TABs are caused by mixotrophs that augment autotrophy with organic nutrient sources, including competing algae (intraguild predation). We leverage the standing diversity of TABs formed by the toxic, invasive mixotroph Prymnesium parvum to identify cell-level behaviours involved in toxin-assisted predation using direct observations as well as comparisons between genetically distinct low- and high-toxicity isolates. Our results suggest that P. parvum toxins are primarily delivered at close range and promote subsequent prey capture/consumption. Surprisingly, we find opposite chemotactic preferences for organic (prey-derived) and inorganic nutrients between differentially toxic isolates, respectively, suggesting behavioural integration of toxicity and phagotrophy. Variation in toxicity may, therefore, reflect broader phenotypic integration of key traits that ultimately contribute to the remarkable flexibility, diversity, and success of invasive populations.
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Haptophyta , Toxinas Biológicas , Animales , Conducta Predatoria , Eutrofización , Evolución BiológicaRESUMEN
BACKGROUND: The traditional paradigm of hospital surgical ward care consists of episodic bedside visits by providers with periodic perusals of the patient's electronic health record (EHR). Vital signs and laboratory results are directly pushed to the EHR but not to providers themselves. Results that require intervention may not be recognized for hours. Remote surveillance programs continuously monitor electronic data and provide automatic alerts that can be routed to multidisciplinary providers. Such programs have not been explored in surgical general care wards. METHODS: We performed a quality improvement observational study of otolaryngology and ophthalmology patients on a general care ward from October 2017 to March 2019 during nighttime hours (17:00-07:00). The study was initiated due to the loss of on-site anesthesiology resources that historically helped respond to acute physiologic deterioration events. We implemented a remote surveillance software program to continuously monitor patients for severe vital signs and laboratory abnormalities and automatically alert the ward team and a remote critical care anesthesiology team. The primary end point was the true positive rate, defined as the proportion of alerts that were associated with a downstream action that changed the care of the patient. This was determined using systematic chart review. The secondary end point, as a measure of alarm fatigue, was the average number of alerts per clinician shift. RESULTS: The software monitored 3926 hospital visits and analyzed 1,560,999 vitals signs and 16,635 laboratories. It generated 151 alerts, averaging 2.6 alerts per week. Of these, 143 (94.7%) were numerically accurate and 8 (5.3%) were inaccurate. Hypoxemia with oxygen saturation <88% was the most common etiology (92, 63%) followed by tachycardia >130 beats per minute (19, 13.3%). Among the accurate alerts, 133 (88.1%) were true positives with an associated clinical action. Actions included a change in management 113 (67.7%), new diagnostic test 26 (15.6%), change in discharge planning 20 (12.0%), and change in level of care to the intensive care unit (ICU) 8 (4.8%). As a measure of alarm fatigue, there were 0.4 alerts per clinician shift. CONCLUSIONS: In a surgical general care ward, a remote surveillance software program that continually and automatically monitors physiologic data streams from the EHR and alerts multidisciplinary providers for severe derangements provided highly actionable alarms at a rate that is unlikely to cause alarm fatigue. Such programs are feasible and could be used to change the paradigm of monitoring.
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Alarmas Clínicas , Registros Electrónicos de Salud , Pacientes Internos , Monitoreo Fisiológico , Procedimientos Quirúrgicos Oftalmológicos/efectos adversos , Procedimientos Quirúrgicos Otorrinolaringológicos/efectos adversos , Programas Informáticos , Telemedicina , Técnicas de Laboratorio Clínico , Estudios de Factibilidad , Cirugía General , Unidades Hospitalarias , Humanos , Valor Predictivo de las Pruebas , Mejoramiento de la Calidad , Indicadores de Calidad de la Atención de Salud , Resultado del Tratamiento , Signos VitalesRESUMEN
BACKGROUND: Manual processes for verifying patient identification before blood transfusion and documenting this pretransfusion safety check are prone to errors, and compliance with manual systems is especially poor in urgent operating room settings. An automated, electronic barcode scanner system would be expected to improve pretransfusion verification and documentation. METHODS: Audits were conducted of blood transfusion documentation under a manual paper system from January to October 2014. An electronic barcode scanning system was developed to streamline transfusion safety checking and automate documentation. This system was implemented in 58 operating rooms between October and December 2014, with follow-up compliance audits through December 2015. The association of barcode scanner implementation with transfusion documentation compliance was assessed using an interrupted time series analysis. Anesthesia providers were surveyed regarding their opinions on the electronic system. In mid-2016, the scanning system was modified to transfer from the Metavision medical record system to Epic OpTime. Follow-up analysis assessed performance of this system within Epic during 2017. RESULTS: In an interrupted time series analysis, the proportion of units with compliant documentation was estimated to be 19.6% (95% confidence interval [CI], 10.7-25.6) the week before scanner implementation, and 74.4% (95% CI, 59.4-87.4) the week after implementation. There was a significant postintervention level change (odds ratio 10.80, 95% CI, 6.31-18.70; P < .001) and increase in slope (odds ratio 1.14 per 1-week increase, 95% CI, 1.11-1.17; P < .001). After implementation, providers chose to use the new electronic system for 98% of transfusions. Across the 2 years analyzed (15,997 transfusions), the electronic system detected 45 potential transfusion errors in 27 unique patients, and averted transfusion of 36 mismatched blood products into 20 unique patients. A total of 69%, 86%, and 88% of providers reported the electronic system improved patient safety, blood transfusion workflow, and transfusion documentation, respectively. When providers used the barcode scanner, no transfusion errors or reactions were reported. The scanner system was successfully transferred from Metavision to Epic without retraining staff or changing workflows. CONCLUSIONS: A barcode-based system designed for easy integration to different commonly used anesthesia information management systems was implemented in a large urban academic hospital. The system allows a single user with the assistance of a software system to perform and document pretransfusion safety verification. The system improved transfusion documentation compliance, averted potential transfusion errors, and became the preferred method of blood transfusion safety checking.
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Transfusión Sanguínea/métodos , Procesamiento Automatizado de Datos , Registros Electrónicos de Salud/organización & administración , Quirófanos/organización & administración , Adulto , Documentación , Adhesión a Directriz , Humanos , Análisis de Series de Tiempo Interrumpido , Errores Médicos/prevención & control , Seguridad del Paciente , Mejoramiento de la Calidad , Flujo de TrabajoRESUMEN
The convergence of multiple recent developments in health care information technology and monitoring devices has made possible the creation of remote patient surveillance systems that increase the timeliness and quality of patient care. More convenient, less invasive monitoring devices, including patches, wearables, and biosensors, now allow for continuous physiological data to be gleaned from patients in a variety of care settings across the perioperative experience. These data can be bound into a single data repository, creating so-called data lakes. The high volume and diversity of data in these repositories must be processed into standard formats that can be queried in real time. These data can then be used by sophisticated prediction algorithms currently under development, enabling the early recognition of patterns of clinical deterioration otherwise undetectable to humans. Improved predictions can reduce alarm fatigue. In addition, data are now automatically queriable on a real-time basis such that they can be fed back to clinicians in a time frame that allows for meaningful intervention. These advancements are key components of successful remote surveillance systems. Anesthesiologists have the opportunity to be at the forefront of remote surveillance in the care they provide in the operating room, postanesthesia care unit, and intensive care unit, while also expanding their scope to include high-risk preoperative and postoperative patients on the general care wards. These systems hold the promise of enabling anesthesiologists to detect and intervene upon changes in the clinical status of the patient before adverse events have occurred. Importantly, however, significant barriers still exist to the effective deployment of these technologies and their study in impacting patient outcomes. Studies demonstrating the impact of remote surveillance on patient outcomes are limited. Critical to the impact of the technology are strategies of implementation, including who should receive and respond to alerts and how they should respond. Moreover, the lack of cost-effectiveness data and the uncertainty of whether clinical activities surrounding these technologies will be financially reimbursed remain significant challenges to future scale and sustainability. This narrative review will discuss the evolving technical components of remote surveillance systems, the clinical use cases relevant to the anesthesiologist's practice, the existing evidence for their impact on patients, the barriers that exist to their effective implementation and study, and important considerations regarding sustainability and cost-effectiveness.
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Anestesiología/métodos , Manejo de Datos/métodos , Informática Médica/métodos , Calidad de la Atención de Salud , Tecnología de Sensores Remotos/métodos , Anestesiología/economía , Anestesiología/normas , Análisis Costo-Beneficio/métodos , Análisis Costo-Beneficio/normas , Manejo de Datos/economía , Manejo de Datos/normas , Humanos , Informática Médica/economía , Informática Médica/normas , Calidad de la Atención de Salud/economía , Calidad de la Atención de Salud/normas , Tecnología de Sensores Remotos/economía , Tecnología de Sensores Remotos/normas , Factores de TiempoRESUMEN
The importance of 'eco-evolutionary feedbacks' in natural systems is currently unclear. Here, we advance a general hypothesis for a particular class of eco-evolutionary feedbacks with potentially large, long-lasting impacts in complex ecosystems. These eco-evolutionary feedbacks involve traits that mediate important interactions with abiotic and biotic features of the environment and a self-driven reversal of selection as the ecological impact of the trait varies between private (small scale) and public (large scale). Toxic algal blooms may involve such eco-evolutionary feedbacks due to the emergence of public goods. We review evidence that toxin production by microalgae may yield 'privatised' benefits for individual cells or colonies under pre- and early-bloom conditions; however, the large-scale, ecosystem-level effects of toxicity associated with bloom states yield benefits that are necessarily 'public'. Theory predicts that the replacement of private with public goods may reverse selection for toxicity in the absence of higher level selection. Indeed, blooms often harbor significant genetic and functional diversity: bloom populations may undergo genetic differentiation over a scale of days, and even genetically similar lineages may vary widely in toxic potential. Intriguingly, these observations find parallels in terrestrial communities, suggesting that toxic blooms may serve as useful models for eco-evolutionary dynamics in nature. Eco-evolutionary feedbacks involving the emergence of a public good may shed new light on the potential for interactions between ecology and evolution to influence the structure and function of entire ecosystems.
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Evolución Biológica , Eutrofización , Microalgas/fisiología , Retroalimentación , Modelos BiológicosRESUMEN
BACKGROUND: Process improvement in healthcare delivery settings can be difficult, even when there is consensus among clinicians about a clinical practice or desired outcome. Airway management is a medical intervention fundamental to the delivery of anesthesia care. Like other medical interventions, a detailed description of the management methods should be documented. Despite this expectation, airway documentation is often insufficient. The authors hypothesized that formal adoption of process improvement methods could be used to increase the rate of "complete" airway management documentation. METHODS: The authors defined a set of criteria as a local practice standard of "complete" airway management documentation. The authors then employed selected process improvement methodologies over 13 months in three iterative and escalating phases to increase the percentage of records with complete documentation. The criteria were applied retrospectively to determine the baseline frequency of complete records, and prospectively to measure the impact of process improvements efforts over the three phases of implementation. RESULTS: Immediately before the initial intervention, a retrospective review of 23,011 general anesthesia cases over 6 months showed that 13.2% of patient records included complete documentation. At the conclusion of the 13-month improvement effort, documentation improved to a completion rate of 91.6% (P<0.0001). During the subsequent 21 months, the completion rate was sustained at an average of 90.7% (SD, 0.9%) across 82,571 general anesthetic records. CONCLUSION: Systematic application of process improvement methodologies can improve airway documentation and may be similarly effective in improving other areas of anesthesia clinical practice.
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Manejo de la Vía Aérea/métodos , Documentación/métodos , Documentación/normas , Mejoramiento de la Calidad , Anestesia General , Adhesión a Directriz , Humanos , Gestión de la InformaciónRESUMEN
Convergent evolution is central in the origins of multicellularity. Identifying the basis for convergent multicellular evolution is challenging because of the diverse evolutionary origins and environments involved. Haploid Kluyveromyces lactis populations evolve multicellularity during selection for increased settling in liquid media. Strong genomic and phenotypic convergence is observed between K. lactis and previously selected S. cerevisiae populations under similar selection, despite their >100-million-year divergence. We find K. lactis multicellularity is conferred by mutations in genes ACE2 or AIM44, with ACE2 being predominant. They are a subset of the six genes involved in the S. cerevisiae multicellularity. Both ACE2 and AIM44 regulate cell division, indicating that the genetic convergence is likely due to conserved cellular replication mechanisms. Complex population dynamics involving multiple ACE2/AIM44 genotypes are found in most K. lactis lineages. The results show common ancestry and natural selection shape convergence while chance and contingency determine the degree of divergence.
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Kluyveromyces , Kluyveromyces/genética , Kluyveromyces/fisiología , Saccharomyces cerevisiae/genética , Genoma Fúngico , Mutación , Evolución Molecular , Adaptación Fisiológica/genética , Selección Genética , Evolución Biológica , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Genómica/métodosRESUMEN
Our goal in this study was to develop decision support systems for resident operating room (OR) assignments using anesthesia information management system (AIMS) records and Accreditation Council for Graduate Medical Education (ACGME) case logs and evaluate the implementations. We developed 2 Web-based systems: an ACGME case-log visualization tool, and Residents Helping in Navigating OR Scheduling (Rhinos), an interactive system that solicits OR assignment requests from residents and creates resident profiles. Resident profiles are snapshots of the cases and procedures each resident has done and were derived from AIMS records and ACGME case logs. A Rhinos pilot was performed for 6 weeks on 2 clinical services. One hundred sixty-five requests were entered and used in OR assignment decisions by a single attending anesthesiologist. Each request consisted of a rank ordered list of up to 3 ORs. Residents had access to detailed information about these cases including surgeon and patient name, age, procedure type, and admission status. Success rates at matching resident requests were determined by comparing requests with AIMS records. Of the 165 requests, 87 first-choice matches (52.7%), 27 second-choice matches (16.4%), and 8 third-choice matches (4.8%) were made. Forty-three requests were unmatched (26.1%). Thirty-nine first-choice requests overlapped (23.6%). Full implementation followed on 8 clinical services for 8 weeks. Seven hundred fifty-four requests were reviewed by 15 attending anesthesiologists, with 339 first-choice matches (45.0%), 122 second-choice matches (16.2%), 55 third-choice matches (7.3%), and 238 unmatched (31.5%). There were 279 overlapping first-choice requests (37.0%). The overall combined match success rate was 69.4%. Separately, we developed an ACGME case-log visualization tool that allows individual resident experiences to be compared against case minimums as well as resident peer groups. We conclude that it is feasible to use ACGME case-log data in decision support systems for informing resident OR assignments. Additional analysis will be necessary to assess the educational impact of these systems.
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Acreditación/normas , Servicio de Anestesia en Hospital/normas , Anestesiología/educación , Anestesiología/normas , Técnicas de Apoyo para la Decisión , Educación de Postgrado en Medicina/normas , Internado y Residencia/normas , Sistemas de Información en Quirófanos/normas , Sistemas de Información para Admisión y Escalafón de Personal/normas , Admisión y Programación de Personal/normas , Competencia Clínica/normas , Estudios de Factibilidad , Humanos , Proyectos Piloto , Evaluación de Programas y Proyectos de Salud , Diseño de Software , Factores de Tiempo , Carga de Trabajo/normasRESUMEN
Harmful algal blooms of the toxic haptophyte Prymnesium parvum are a recurrent problem in many inland and estuarine waters around the world. Strains of P. parvum vary in the toxins they produce and in other physiological traits associated with harmful algal blooms, but the genetic basis for this variation is unknown. To investigate genome diversity in this morphospecies, we generated genome assemblies for 15 phylogenetically and geographically diverse strains of P. parvum, including Hi-C guided, near-chromosome-level assemblies for two strains. Comparative analysis revealed considerable DNA content variation between strains, ranging from 115 to 845 Mbp. Strains included haploids, diploids, and polyploids, but not all differences in DNA content were due to variation in genome copy number. Haploid genome size between strains of different chemotypes differed by as much as 243 Mbp. Syntenic and phylogenetic analyses indicate that UTEX 2797, a common laboratory strain from Texas, is a hybrid that retains two phylogenetically distinct haplotypes. Investigation of gene families variably present across the strains identified several functional categories associated with metabolic and genome size variation in P. parvum, including genes for the biosynthesis of toxic metabolites and proliferation of transposable elements. Together, our results indicate that P. parvum comprises multiple cryptic species. These genomes provide a robust phylogenetic and genomic framework for investigations into the eco-physiological consequences of the intra- and inter-specific genetic variation present in P. parvum and demonstrate the need for similar resources for other harmful algal-bloom-forming morphospecies.
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Haptophyta , Toxinas Biológicas , Floraciones de Algas Nocivas/fisiología , Filogenia , Haptophyta/genética , ADN/genéticaRESUMEN
Bacteria rely on a range of extracellular metabolites to suppress competitors, gain access to resources, and exploit plant or animal hosts. The GacS/GacA two-component regulatory system positively controls the expression of many of these beneficial external products in pseudomonad bacteria. Natural populations often contain variants with defective Gac systems that do not produce most external products. These mutants benefit from a decreased metabolic load but do not appear to displace the wild type in nature. How could natural selection maintain the wild type in the presence of a mutant with enhanced growth? One hypothesis is that Gac mutants are "cheaters" that do not contribute to the public good, favored within groups but selected against between groups, as groups containing more mutants lose access to ecologically important external products. An alternative hypothesis is that Gac mutants have a mutualistic interaction with the wild type, so that each variant benefits by the presence of the other. In the biocontrol bacterium Pseudomonas chlororaphis strain 30-84, Gac mutants do not produce phenazines, which suppress competitor growth and are critical for biofilm formation. Here, we test the predictions of these alternative hypotheses by quantifying interactions between the wild type and the phenazine- and biofilm-deficient Gac mutant within growing biofilms. We find evidence that the wild type and Gac mutants interact mutualistically in the biofilm context, whereas a phenazine-defective structural mutant does not. Our results suggest that the persistence of alternative Gac phenotypes may be due to the stabilizing role of local mutualistic interactions.
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Proteínas Bacterianas/genética , Genes Reguladores , Mutación , Pseudomonas/crecimiento & desarrollo , Pseudomonas/genética , Factores de Transcripción/genética , Animales , Biopelículas/crecimiento & desarrollo , Variación Genética , Fenazinas/metabolismo , Selección GenéticaRESUMEN
BACKGROUND: Efforts to assure high-quality, safe, clinical care depend upon capturing information about near-miss and adverse outcome events. Inconsistent or unreliable information capture, especially for infrequent events, compromises attempts to analyze events in quantitative terms, understand their implications, and assess corrective efforts. To enhance reporting, we developed a secure, electronic, mandatory system for reporting quality assurance data linked to our electronic anesthesia record. METHODS: We used the capabilities of our anesthesia information management system (AIMS) in conjunction with internally developed, secure, intranet-based, Web application software. The application is implemented with a backend allowing robust data storage, retrieval, data analysis, and reporting capabilities. We customized a feature within the AIMS software to create a hard stop in the documentation workflow before the end of anesthesia care time stamp for every case. The software forces the anesthesia provider to access the separate quality assurance data collection program, which provides a checklist for targeted clinical events and a free text option. After completing the event collection program, the software automatically returns the clinician to the AIMS to finalize the anesthesia record. RESULTS: The number of events captured by the departmental quality assurance office increased by 92% (95% confidence interval [CI] 60.4%-130%) after system implementation. The major contributor to this increase was the new electronic system. This increase has been sustained over the initial 12 full months after implementation. Under our reporting criteria, the overall rate of clinical events reported by any method was 471 events out of 55,382 cases or 0.85% (95% CI 0.78% to 0.93%). The new system collected 67% of these events (95% confidence interval 63%-71%). CONCLUSION: We demonstrate the implementation in an academic anesthesia department of a secure clinical event reporting system linked to an AIMS. The system enforces entry of quality assurance information (either no clinical event or notification of a clinical event). System implementation resulted in capturing nearly twice the number of events at a relatively steady case load.
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Servicio de Anestesia en Hospital/estadística & datos numéricos , Anestesia/efectos adversos , Anestesiología/estadística & datos numéricos , Sistemas de Registros Médicos Computarizados/estadística & datos numéricos , Sistemas de Información en Quirófanos/estadística & datos numéricos , Evaluación de Procesos y Resultados en Atención de Salud/estadística & datos numéricos , Garantía de la Calidad de Atención de Salud/estadística & datos numéricos , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Boston , Lista de Verificación , Hospitales Generales/estadística & datos numéricos , Humanos , Seguridad del Paciente/estadística & datos numéricos , Evaluación de Programas y Proyectos de Salud , Programas Informáticos , Flujo de TrabajoRESUMEN
Arachidonoyl amino acids are a class of endogenous lipid messengers that are expressed in the mammalian central nervous system and peripherally. While several of their prominent pharmacologic effects have been documented, the mechanism by which arachidonoyl amino acids are biosynthesized has not been defined. We have previously observed that the mitochondrial protein, cytochrome c, is capable of catalyzing the formation of the prototypic arachidonoyl amino acid, arachidonoyl glycine, utilizing arachidonoyl CoA and glycine as substrates, in the presence of hydrogen peroxide. Here we report that cytochrome c is similarly able to catalyze the formation of N-arachidonoyl serine, N-arachidonoyl alanine, and N-arachidonoyl gamma aminobutyric acid from arachidonoyl CoA and the respective amino acids. The identities of the arachidonoyl amino acid products were verified by mass spectral fragmentation pattern analysis. The synthetic reactions exhibited Michaelis-Menten kinetics and continued favorably at physiologic temperature and pH. Spectral data indicate that both cytochrome c protein structure and a +3 heme iron oxidation state are required for the reaction mechanism to proceed optimally. Reactions designed to catalyze the formation of N-arachidonoyl dopamine were not efficient due to the rapid oxidation of dopamine substrate by hydrogen peroxide, consuming both reactants. Finally, under standard assay conditions, arachidonoyl CoA and ethanolamine were found to react spontaneously to form anandamide, independent of cytochrome c and hydrogen peroxide. Accordingly, it was not possible to demonstrate a potential role for cytochrome c in the biosynthetic mechanism for either arachidonoyl dopamine or anandamide. However, the ability of cytochrome c to effectively catalyze the formation of N-arachidonoyl serine, N-arachidonoyl alanine, and N-arachidonoyl gamma aminobutyric acid in vitro highlights its potential role for the generation of these lipid messengers in vivo.
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Aminoácidos/biosíntesis , Aminoácidos/química , Ácido Araquidónico/biosíntesis , Ácido Araquidónico/química , Citocromos c/metabolismo , Acilcoenzima A/metabolismo , Aminobutiratos/química , Aminobutiratos/metabolismo , Animales , Ácidos Araquidónicos/metabolismo , Biocatálisis , Bovinos , Citocromos c/química , Dopamina/metabolismo , Endocannabinoides , Etanolamina/metabolismo , Peróxido de Hidrógeno/metabolismo , Concentración de Iones de Hidrógeno , Hierro/metabolismo , Oxidación-Reducción , Alcamidas Poliinsaturadas/metabolismo , TemperaturaRESUMEN
α-Amidation is a terminal modification in peptide biosynthesis that can itself be rate limiting in the overall production of bioactive α-amidated peptides. More than half of the known neural and endocrine peptides are α-amidated and in most cases this structural feature is essential for receptor recognition, signal transduction, and thus biologic function. This chapter describes methods for developing and using analytical tools to study the biology of α-amidated peptides. The principal analytical method used to quantify α-amidated peptides is the radioimmunoassay (RIA). Detailed protocols are provided for (1) primary antibody production and characterization; (2) radiolabeling of RIA peptides; (3) sample preparation; and (4) performance of the RIA itself. Techniques are also described for the identification and verification of α-amidated peptides. Lastly, in vivo models used for studying the biology of α-amidation are discussed.
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Péptidos/química , Péptidos/metabolismo , Amidas/química , Radioinmunoensayo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Long chain fatty acyl glycines are an emerging class of biologically active molecules that occur naturally and produce a wide array of physiological effects. Their biosynthetic pathway, however, remains unknown. Here we report that cytochrome c catalyzes the synthesis of N-arachidonoyl glycine (NAGly) from arachidonoyl coenzyme A and glycine in the presence of hydrogen peroxide. The identity of the NAGly product was verified by isotope labeling and mass analysis. Other heme-containing proteins, hemoglobin and myoglobin, were considerably less effective in generating arachidonoyl glycine as compared to cytochrome c. The reaction catalyzed by cytochrome c in vitro points to its potential role in the formation of NAGly and other long chain fatty acyl glycines in vivo.
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Acilcoenzima A/química , Ácidos Araquidónicos/síntesis química , Citocromos c/química , Glicina/análogos & derivados , Glicina/química , Peróxido de Hidrógeno/química , Catálisis , Activación Enzimática , Glicina/síntesis química , Especificidad por SustratoRESUMEN
alpha-Amidation is a terminal modification in peptide biosynthesis that can itself be rate-limiting in the overall production of bioactive alpha-amidated peptides. More than half of the known neural and endocrine peptides are alpha-amidated and in most cases, this structural feature is essential for receptor recognition, signal transduction, and thus, biologic function. This chapter describes methods for developing and using analytical tools to study the biology of alpha-amidated peptides. The principle analytical method used to quantify alpha-amidated peptides is the radioimmunoassay (RIA). Detailed protocols are provided for 1) primary antibody production and characterization; 2) radiolabeling of RIA peptides; 3) sample preparation; and 4) the performance of the RIA itself. Techniques are also described for the identification and verification of alpha-amidated peptides. Lastly, in vivo models used for studying the biology of alpha-amidation are discussed.
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Amidas/química , Péptidos/química , Especificidad de Anticuerpos , Cromatografía Líquida de Alta Presión , Radioinmunoensayo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Programmed cell death (PCD) occurs in both unicellular and multicellular organisms. While PCD plays a key role in the development and maintenance of multicellular organisms, explaining why single-celled organisms would evolve to actively commit suicide has been far more challenging. Here, we explore the potential for PCD to act as an accessory to microbial bet-hedging strategies that utilize stochastic phenotype switching. We consider organisms that face unpredictable and recurring disasters, in which fitness depends on effective phenotypic diversification. We show that when reproductive opportunities are limited by carrying capacity, PCD drives population turnover, providing increased opportunities for phenotypic diversification through stochastic phenotype switching. The main cost of PCD, providing resources for growth to a PCD(-) competitor, is ameliorated by genetic assortment in spatially structured populations. Using agent -based simulations, we explore how basic demographic factors, namely bottlenecks and local dispersal, can generate sufficient spatial structure to favor the evolution of high PCD rates.
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A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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BACKGROUND: Studies of the accuracy and completeness of handwritten anesthesia records demonstrate deficiencies in documentation, suggesting that the quality of anesthesia records can be improved. METHODS: We reviewed all electronic anesthesia records generated during a 1-month period at our institution to ascertain completion rates for six clinical documentation elements: allergies, IV access, electrocardiogram rhythm, ease of mask ventilation, laryngoscopic grade of view, and insertion depth of the endotracheal tube. RESULTS: Of 2838 records, 64% had the necessary free text remark in the allergy element. The free text required to complete endotracheal tube depth documentation appeared in 538 of 918 cases in which the patient was tracheally intubated (59%). Free text documentation of the electrocardiogram rhythm diagnosis appeared at least once in 86% of records. Documentation of mask ventilation characteristics was entered by touch screen from a pick list and was expected in 781 records but appeared in 664 records (85%). Laryngoscopic grade of view documentation was also selected by touch screen and expected in 883 records but present in 811 cases (92%). Any notation of IV access appeared in 84% of records. CONCLUSIONS: We found that electronic clinical anesthesia documentation was often incomplete. Dependence on free text remarks and the record keeping system's inability to automatically present entries in logical sequences consistent with workflow were associated with incomplete data entry. Our results suggest that the user interface for data entry, and the logic that an electronic system uses for preventing omissions and inconsistencies, merit further study and development in order to facilitate clinically useful documentation.
Asunto(s)
Anestesia/normas , Sistemas de Información Administrativa/normas , Sistemas de Registros Médicos Computarizados/normas , Servicio de Anestesia en Hospital/normas , Sistemas de Información en Hospital/normas , Humanos , Estudios RetrospectivosRESUMEN
The cause of the awareness under general anesthesia often cannot be definitely determined from retrospective reviews of handwritten records, examinations of equipment, or interviews with clinicians. Failure to deliver the intended concentrations of anesthetic agents to the patient is one possible contributing cause for awareness. An advantage of an automated Anesthesia Information Management System (AIMS) is its ability to electronically capture and preserve case data that might otherwise be lost. We reviewed the AIMS records of 3 anesthetics in which intraoperative awareness was felt to have probably occurred. The details of the reported awareness event were temporally correlated with the anesthetic gas concentrations in an effort to determine if low concentrations were contributing factors. The data captured by the AIMS revealed low levels of inspired or expired inhalation agents during the intervals correlating with apparent patient recall. The findings suggest that failure to deliver sufficient concentrations of anesthetic gases permitted awareness events in these cases. Thus data from automated anesthesia information management in the operating room may help identify causes of awareness, and means to prevent awareness can be instituted.