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Aldehyde dehydrogenase enzymes (ALDHs) are widely studied for their roles in disease propagation and cell metabolism. Their use in biocatalysis applications, for the conversion of aldehydes to carboxylic acids, has also been recognized. Understanding the structural features and functions of both prokaryotic and eukaryotic ALDHs is key to uncovering novel applications of the enzyme and probing its role in disease propagation. The thermostable enzyme ALDHTt originating fromThermus thermophilus, strain HB27, possesses a unique extension of its C-terminus, which has been evolutionarily excluded from mesophilic counterparts and other thermophilic enzymes in the same genus. In this work, the thermophilic adaptation is studied by the expression and optimized purification of mutant ALDHTt-508, with a 22-amino acid truncation of the C-terminus. The mutant shows increased activity throughout production compared to native ALDHTt, indicating an opening of the active site upon C-terminus truncation and giving rationale into the evolutionary exclusion of the C-terminal extension from similar thermophilic and mesophilic ALDH proteins. Additionally, the C-terminus is shown to play a role in controlling substrate specificity of native ALDH, particularly in excluding catalysis of certain large and certain aromatic ortho-substituted aldehydes, as well as modulating the protein's pH tolerance by increasing surface charge. Dynamic light scattering and size-exclusion HPLC methods are used to show the role of the C-terminus in ALDHTt oligomeric stability at the cost of catalytic efficiency. Studying the aggregation rate of ALDHTt with and without a C-terminal extension leads to the conclusion that ALDHTt follows a monomolecular reaction aggregation mechanism.
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Aldehído Deshidrogenasa , Estabilidad de Enzimas , Thermus thermophilus , Thermus thermophilus/enzimología , Aldehído Deshidrogenasa/química , Aldehído Deshidrogenasa/metabolismo , Aldehído Deshidrogenasa/genética , Especificidad por Sustrato , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Multimerización de Proteína , Cinética , Dominio Catalítico , Secuencia de AminoácidosRESUMEN
The surface properties of biomaterials interact directly with biological systems, influencing cellular responses, tissue integration, and biocompatibility. Surface topography plays a critical role in cardiac tissue engineering by affecting electrical conductivity, cardiomyocyte alignment, and contractile function. Current methods for controlling surface properties and topography in cardiac tissue engineering scaffolds are limited, expensive, and lack precision. This study introduces a low-cost, one-step degradation process to create scaffolds with well-defined micro-grooves from multilayered 3D printed poly(lactic acid)/thermoplastic polyurethane composites. The approach provides control over erosion rate and surface morphology, allowing easy tuning of scaffold topographical cues for tissue engineering applications. The findings reported in this study provide a library of easily tuneable scaffold topographical cues. A strong dependence of neonatal rat cardiomyocyte (NRCM) contact guidance with the multilayers' dimension and shape in partially degraded polylactic acid (PLA)/thermoplastic polyurethane (TPU) samples is observed. NRCMs cultured on samples with a layer thickness of 13 ± 2 µm and depth of 4.7 ± 0.2 µm demonstrate the most regular contractions. Hence, the proposed fabrication scheme can be used to produce a new generation of biomaterials with excellent controllability determined by multilayer thickness, printing parameters, and degradation treatment duration.
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C5a peptidase, also known as ScpA, is a surface associated serine protease derived from Streptococcus pyogenes and has been described as an important factor in streptococcus virulence, capable of cleaving complement components C5a, C3 and C3a. Although the interactions of ScpA with complement components is well studied, extensive screening of ScpA activity against other pro-inflammatory cytokines is lacking. Here, ScpA's ability to cleave human pro-inflammatory cytokines was tested, revealing its ability to cleave human IFNγ, IFNλ1, IFNλ2, C5, IL-37 but with significantly reduced activities. The functional consequence of ScpA's cleavage of IFNγ in its signalling through the Jak-Stat pathway has also been evaluated in an in vitro RPE1 cell model. These newly identified targets for ScpA highlight the complexity of streptococcus infections and indeed, the potential for ScpA to have a therapeutic role in the progression of inflammatory diseases involving these cytokines.
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Interferón gamma , Interferones , Humanos , Interferones/metabolismo , Interferón gamma/metabolismo , Transducción de Señal , Streptococcus pyogenes/enzimología , Citocinas/metabolismo , Línea Celular , Interferón lambda , Proteínas Bacterianas/metabolismoRESUMEN
In this paper, we describe the development of a Dictyostelium discoideum strain deficient in frataxin protein (FXN). We investigated the conservation of function between humans and D. discoideum and showed that DdFXN can substitute the human version in the interaction and activation of the Fe-S assembly supercomplex. We edited the D. discoideum fxn locus and isolated a defective mutant, clone 8, which presents landmarks of frataxin deficiency, such as a decrease in Fe-S cluster-dependent enzymatic functions, growth rate reduction, and increased sensitivity to oxidative stress. In addition, the multicellular development is affected as well as growing on bacterial lawn. We also assessed the rescuing capacity of DdFXN-G122V, a version that mimics a human variant present in some FA patients. While the expression of DdFXN-G122V rescues growth and enzymatic activity defects, as DdFXN does, multicellular development defects were only partially rescued. The results of the study suggest that this new D. discoideum strain offers a wide range of possibilities to easily explore diverse FA FXN variants. This can facilitate the development of straightforward drug screenings to look for new therapeutic strategies.
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Posttranslational modifications of proteins can impact their therapeutic efficacy, stability, and potential for pharmaceutical development. The Group AStreptococcus pyogenesC5a peptidase (ScpA) is a multi-domain protein composed of an N-terminal signal peptide, a catalytic domain (including propeptide), three fibronectin domains, and cell membrane-associated domains. It is one of several proteins produced by Group AS. pyogenesknown to cleave components of the human complement system. After signal peptide removal, ScpA undergoes autoproteolysis and cleaves its propeptide for full maturation. The exact location and mechanism of the propeptide cleavage, and the impact of this cleavage on stability and activity, are not clearly understood, and the exact primary sequence of the final enzyme is not known. A form of ScpA with no autoproteolysis fragments of propeptide present may be more desirable for pharmaceutical development from a regulatory and a biocompatibility in the body perspective. The current study describes an in-depth structural and functional characterization of propeptide truncated variants of ScpA expressed inEscherichia colicells. All three purified ScpA variants, ScpA, 79ΔPro, and 92ΔPro, starting with N32, D79, and A92 positions, respectively, showed similar activity against C5a, which suggests a propeptide-independent activity profile of ScpA. CE-SDS and MALDI top-down sequencing analyses highlight a time-dependent propeptide autoproteolysis of ScpA at 37 °C with a distinct end point at A92 and/or D93. In comparison, all three variants of ScpA exhibit similar stability, melting temperatures, and secondary structure orientation. In summary, this work not only highlights propeptide localization but also provides a strategy to recombinantly produce a final mature and active form of ScpA without any propeptide-related fragments.
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Productos Biológicos , Streptococcus pyogenes , Humanos , Streptococcus pyogenes/metabolismo , Endopeptidasas/metabolismo , Señales de Clasificación de ProteínaRESUMEN
OBJECTIVE: To describe the surgical management and outcome of dogs undergoing laparoscopic pancreatic mass resection (LPMR). STUDY DESIGN: Retrospective study. ANIMALS: Twelve client-owned dogs. METHODS: Data collected from medical records of dogs that underwent LPMR between 2012 and 2023 included signalment, clinical signs, mass location within pancreas, preoperative diagnostic imaging, laparoscopic approach, number of portals and device type used for LPMR, operating time, complications and clinical outcome. RESULTS: Pancreatic tumors were located in the left lobe (7), in the right lobe (4) and in the body of the pancreas (1). A 3- or 4-port technique was used in nine and three dogs, respectively. LPMR was performed with the Ligasure in nine dogs, a harmonic scalpel in two dogs and an endoscopic stapler in one dog. The procedure was performed successfully, with no conversion to open laparotomy, in all cases with a median operating time of 69 min. Postoperative complications occurred in four dogs, which resolved with medical treatments. All dogs survived the surgical procedure, were discharged from the hospital and alive a minimum of 90 days postoperatively. The final follow-up time ranged between 105 and 245 days (median 147). Histopathological diagnosis included insulinoma (9) and pancreatic carcinoma (3). CONCLUSION: LPMR was performed successfully using a 3- or 4-port technique and was associated with a low complication rate and a good clinical outcome. CLINICAL SIGNIFICANCE: LPMR may be considered as an alternative to open celiotomy in dogs, particularly for small tumors located in the distal aspect of the pancreatic lobes.
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OBJECTIVE: To describe the technique, complications, and outcome of laparoscopic portosystemic shunt attenuation (LPSSA) in dogs. STUDY DESIGN: Retrospective study. ANIMALS: Twenty client-owned dogs. METHODS: Medical records were searched for dogs with a single congenital extrahepatic portosystemic shunt (CEPSS) that was treated with LPSSA. Signalment, clinical signs, CEPSS location, diagnostic imaging, laparoscopic approach, operative technique, complications, and clinical outcome were reviewed. RESULTS: Fourteen dogs with CEPSS located in the epiploic foramen had a right (13/14) or left (1/14) paramedian approach. In 6 dogs a CEPSS was not located in the epiploic foramen, and a left paramedian approach was used. A 3 or 4-port technique was used in 7 and 13 dogs, respectively. A thin film band was used for CEPSS attenuation in all dogs. The median operating time for LPSSA was 62 min (range 27-98 min). Intraoperative complications requiring conversion to an open technique occurred in 5 dogs. Mild perioperative self-limiting portal hypertension occurred in 3 dogs, while severe portal hypertension with surgical revision occurred in 1 case. The complications were resolved, and all dogs had a good outcome. CONCLUSION: Laparoscopic portosystemic shunt attenuation can be performed in dogs, in particular for a CEPSS located in the epiploic foramen using a right paramedian approach. For CEPSS not located in the epiploic foramen, a left paramedian approach is recommended. Conversion to open celiotomy was required in around a third of cases. CLINICAL SIGNIFICANCE: Laparoscopic attenuation of CEPSSs can be performed in dogs and has a good clinical outcome, particularly for CEPSS located in the epiploic foramen.
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Enfermedades de los Perros , Hipertensión Portal , Laparoscopía , Derivación Portosistémica Intrahepática Transyugular , Malformaciones Vasculares , Animales , Enfermedades de los Perros/congénito , Enfermedades de los Perros/cirugía , Perros , Hipertensión Portal/cirugía , Hipertensión Portal/veterinaria , Laparoscopía/veterinaria , Sistema Porta/anomalías , Sistema Porta/cirugía , Derivación Portosistémica Intrahepática Transyugular/veterinaria , Estudios Retrospectivos , Resultado del Tratamiento , Malformaciones Vasculares/cirugía , Malformaciones Vasculares/veterinariaRESUMEN
BACKGROUND: Suicide is a public health problem in the world. In Chile, suicide rates increased since 1990 with regional differences in rates. AIM: To analyze the geographical distribution of deaths due to suicide that occurred in the Region of Araucanía between the years 2004-2015. MATERIAL AND METHODS: The geographic distribution of suicide in the Araucania Region at district level (2004-2015) was analyzed using death data available at the web page of the Ministry of Health. Socio-demographic variables of suicide were characterized. The spatial distribution of suicide rates was represented using cartography, and suicide spatial clusters were identified through spatial-temporal exploration. RESULTS: There were 1,562 suicides, 86% in men, with a mean rate of 13.07 x105 inhabitants. The highest rates were registered in people aged over 70 years. Most individuals committing suicide were active workers. Hanging was the most common method to accomplish suicide. The territories from the coastal area in Cautín, and Nahuelbuta registered the highest suicide rates. Two statistically significant conglomerates with high incidence of suicide cases were identified. CONCLUSIONS: The use of geographic methods and the disaggregation of suicide cases at district level, allowed the identification of territorial variability in the distribution of suicide rates within the Araucanía Region. Spatial patterns of areas with high suicide risk were found.
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Suicidio , Anciano , Chile/epidemiología , Humanos , Incidencia , Masculino , Salud Pública , Distribución por SexoRESUMEN
Salmonella enterica serovar Paratyphi B variant Java sequence type 28 is prevalent in poultry and poultry meat. We investigated the evolutionary relatedness between sequence type 28 strains from Europe and Latin America using time-resolved phylogeny and principal component analysis. We sequenced isolates from Colombia, Guatemala, Costa Rica, and the Netherlands and complemented them with publicly available genomes from Europe, Africa, and the Middle East. Phylogenetic time trees and effective population sizes (Ne) showed separate clustering of strains from Latin America and Europe. The separation is estimated to have occurred during the 1980s. Ne of strains increased sharply in Europe around 1995 and in Latin America around 2005. Principal component analysis on noncore genes showed a clear distinction between strains from Europe and Latin America, whereas the plasmid gene content was similar. Regardless of the evolutionary separation, similar features of resistance to ß-lactams and quinolones/fluoroquinolones indicated parallel evolution of antimicrobial resistance in both regions.
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Salmonella enterica , Salmonella paratyphi B , África , Animales , Antibacterianos/farmacología , Colombia , Costa Rica , Farmacorresistencia Bacteriana , Farmacorresistencia Bacteriana Múltiple , Europa (Continente)/epidemiología , Guatemala , Indonesia , América Latina/epidemiología , Medio Oriente , Países Bajos , Filogenia , Aves de Corral , Salmonella enterica/genética , Salmonella paratyphi B/genéticaRESUMEN
Shigella spp. are a leading cause of human diarrheal disease worldwide, with Shigella flexneri being the most frequently isolated species in developing countries. This serogroup is presently classified into 19 serotypes worldwide. We report here a multicenter validation of a multiplex-PCR-based strategy previously developed by Q. Sun, R. Lan, Y. Wang, A. Zhao, et al. (J Clin Microbiol 49:3766-3770, 2011) for molecular serotyping of S. flexneri This study was performed by seven international laboratories, with a panel of 71 strains (researchers were blind to their identity) as well as 279 strains collected from each laboratory's own local culture collections. This collaborative work found a high extent of agreement among laboratories, calculated through interrater reliability (IRR) measures for the PCR test that proved its robustness. Agreement with the traditional method (serology) was also observed in all laboratories for 14 serotypes studied, while specific genetic events could be responsible for the discrepancies among methodologies in the other 5 serotypes, as determined by PCR product sequencing in most of the cases. This work provided an empirical framework that allowed the use of this molecular method to serotype S. flexneri and showed several advantages over the traditional method of serological typing. These advantages included overcoming the problem of availability of suitable antisera in testing laboratories as well as facilitating the analysis of multiple samples at the same time. The method is also less time-consuming for completion and easier to implement in routine laboratories. We recommend that this PCR be adopted, as it is a reliable diagnostic and characterization methodology that can be used globally for laboratory-based shigella surveillance.
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Reacción en Cadena de la Polimerasa Multiplex/métodos , Serotipificación/métodos , Shigella flexneri/clasificación , Técnicas de Tipificación Bacteriana/métodos , Técnicas de Tipificación Bacteriana/normas , ADN Bacteriano/genética , Humanos , Internacionalidad , Reacción en Cadena de la Polimerasa Multiplex/normas , Serogrupo , Shigella flexneri/inmunologíaRESUMEN
We address the assignment of ICD-10 codes for causes of death by analyzing free-text descriptions in death certificates, together with the associated autopsy reports and clinical bulletins, from the Portuguese Ministry of Health. We leverage a deep neural network that combines word embeddings, recurrent units, and neural attention, for the generation of intermediate representations of the textual contents. The neural network also explores the hierarchical nature of the input data, by building representations from the sequences of words within individual fields, which are then combined according to the sequences of fields that compose the inputs. Moreover, we explore innovative mechanisms for initializing the weights of the final nodes of the network, leveraging co-occurrences between classes together with the hierarchical structure of ICD-10. Experimental results attest to the contribution of the different neural network components. Our best model achieves accuracy scores over 89%, 81%, and 76%, respectively for ICD-10 chapters, blocks, and full-codes. Through examples, we also show that our method can produce interpretable results, useful for public health surveillance.
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Codificación Clínica/métodos , Minería de Datos/métodos , Certificado de Defunción , Clasificación Internacional de Enfermedades , Redes Neurales de la Computación , Autopsia/métodos , Registros Electrónicos de Salud , Humanos , Procesamiento de Lenguaje NaturalRESUMEN
PURPOSE OF REVIEW: Current preventive and treatment guidelines for type 2 diabetes have failed to decrease the incidence of comorbidities, such as dyslipidemia and ultimately heart disease. The goal of this review is to describe the physiological and metabolic lipid alterations that develop in patients with type 2 diabetes mellitus. Questions addressed include the differences in lipid and lipoprotein metabolism that characterize the dyslipidemia of insulin resistance and type 2 diabetes mellitus. We also examine the relevance of the new AHA/ADA treatment guidelines to dyslipidemic individuals. RECENT FINDINGS: In this review, we provide an update on the pathophysiology of diabetic dyslipidemia, including the role of several apolipoproteins such as apoC-III. We also point to new studies and new agents for the treatment of individuals with type 2 diabetes mellitus who need lipid therapies. Type 2 diabetes mellitus causes cardiovascular disease via several pathways, including dyslipidemia characterized by increased plasma levels of apoB-lipoproteins and triglycerides, and low plasma concentrations of HDL cholesterol. Treatments to normalize the dyslipidemia and reduce the risk for cardiovascular events include the following: lifestyle and medication, particularly statins, and if necessary, ezetimibe, to significantly lower LDL cholesterol. Other treatments, more focused on triglycerides and HDL cholesterol, are less well supported by randomized clinical trials and should be used on an individual basis. Newer agents, particularly the PCSK9 inhibitors, show a great promise for even greater lowering of LDL cholesterol, but we await the results of ongoing clinical trials.
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Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Dislipidemias/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lipoproteínas/sangre , Anticolesterolemiantes/uso terapéutico , Ezetimiba/uso terapéutico , Humanos , Resistencia a la Insulina , Estilo de Vida , Guías de Práctica Clínica como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The GMR editorial staff was alerted about two manuscripts that were found to be substantially equal. The Publisher and Editor decided to retract these articles in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation, there is strong reason to believe that the peer review process was failure and, after review and contacting the authors, the editors of Genetics and Molecular Research decided to retract the article. The authors and their institutions were advised of this serious breach of ethics. The retracted articles are: Li Q, Chen C-F, Wang D-Y, Lü Y-T, et al. (2015). Transplantation of umbilical cord blood mononuclear cells increases levels of nerve growth factor in the cerebrospinal fluid of patients with autism. Genet. Mol. Res. 14: 8725-8732. and Li Q, Chen C-F, Wang D-Y, Lü Y-T, et al. (2016). Changes in growth factor levels in the cerebrospinal fluid of autism patients after transplantation of human umbilical cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells. Genet. Mol. Res. 15: gmr.15027526. There is large-scale duplication of text from a previous publication by the authors in all sections of the articles and the Material and Methods section is identical for both manuscripts Li et al. (2015) and Li et al. (2016). Other major study, from where the text has been copied substantially, was found and can be accessed at https://translational-medicine.biomedcentral.com/ articles/10.1186/1479-5876-11-196.
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The aim of the present study was to assess the content and construct validity of the Canine Laparoscopic Simulator (CLS). Forty-two veterinarians were assigned to experienced (n=12), control (n=15), and training (n=15) groups, which were assessed while performing four laparoscopic tasks on the CLS. The initial and final assessments of all tasks were performed blindly by two experienced surgeons using the Global Operative Assessment of Laparoscopic Skills (GOALS) and a task-specific checklist. At the end of the study, the subjects completed an anonymous survey. The experienced group performed all of the tasks faster, with higher GOALS and checklist scores than the training and control groups (p≤.001). In the second assessment, the training group reduced the time needed to complete all of the tasks and obtained significantly higher GOALS and checklist scores than the control group. The participants perceived the CLS and its training program to be positive or very positive. The CLS and its training program demonstrated content and construct validity, supporting the suitability of the simulator for training and teaching and its ability to distinguish the degree of experience in laparoscopic surgery among veterinarians. In addition, face validity showed that the veterinarians fully accepted the CLS's usefulness for learning basic laparoscopic skills.
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Competencia Clínica , Simulación por Computador , Enfermedades de los Perros/cirugía , Educación en Veterinaria/métodos , Enfermedades Gastrointestinales/veterinaria , Laparoscopía/veterinaria , Enseñanza/métodos , Animales , Enfermedades de los Perros/diagnóstico , Perros , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/cirugía , Aprendizaje , Modelos Anatómicos , VeterinariosRESUMEN
BACKGROUND: Published comparisons of the different available laparoendoscopic single-site surgery (LESS) devices focused on its economic cost and technical aspects. With this study, we aimed to objectively compare the use of three different LESS access devices in controlled experimental tasks. MATERIALS AND METHODS: Twenty subjects participated in simulator trials. A cut and an intracorporeal suturing task were carried out. Three single access devices (SILS: SILS(TM) Port, GPN. GelPOINT Advanced Access Platform, and XCN: XCONE) were used according to a randomized nine-session schedule. Completion time was registered and performance objectively assessed with task-specific rating scales. Two blinded expert raters worked over video recordings of the hands-on sessions. RESULTS: Participants showed improvement with all devices on total cut completion times and significantly for SILS (P = 0.017). The GPN decreased its adapted Global Rating Scale score (P = 0.002) from the first (W1) to the last week (W9). On the suture task, XCN constituted the device with longer completion times compared with SILS (P < 0.001) and to GPN (P < 0.001). There was significant improvement in times from W1 to W9 with XCN (P < 0.001), SILS (P = 0.003), and GPN (P < 0.001). On average summative score, we observed significant improvement in performance with all devices from W1 to W9 (SILS: P = 0.003; GPN: P = 0.001; and XCN: P < 0.001). CONCLUSIONS: Although we advise surgeons to focus on the specific procedures and patient characteristics to select the most adequate access device to maintain procedural safety standards, single-use devices appear to confer an easier adaptation to LESS surgery.
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Educación Basada en Competencias/métodos , Simulación por Computador , Instrucción por Computador/métodos , Endoscopía/educación , Laparoscopía/educación , Técnicas de Sutura/educación , Instrucción por Computador/instrumentación , Educación de Postgrado en Medicina/métodos , Femenino , Humanos , Masculino , Estudios de Tiempo y Movimiento , Grabación en VideoRESUMEN
BACKGROUND: Over the past decades, minimally invasive surgery has undergone continuous development due to the demand for scarless results, with laparo-endoscopic single-site (LESS) surgery constituting one of today's most favored alternatives. In this study, we aim to assess the relative technical difficulty and performance benefits of dynamic articulating and pre-bent instruments, either combined with conventional laparoscopic tools or not, during the completion of two basic tasks hands-on simulator. METHODS: A total of 20 surgeons were included and performed two basic simulator tasks-coordination and cutting-carried out using four different combinations of LESS-designed and straight conventional laparoscopy instruments. Assessment took place before and after the completion of a 14-week training program. Performance data were objectively analyzed over video recordings with an adapted global rating scale (a-GRS) for performance evaluation, combined with a registry of total trial completion time. RESULTS: In the coordination task, the worst performance scores (p < 0.001) and longest completion times (p < 0.001 on first assessment and p < 0.01 on last assessment) were obtained with the two dynamic articulating tip instruments. On the cut trials, no significant differences between the different setups were found in a-GRS scores. The two dynamic articulating tip instruments also constituted the most time-demanding setup on both assessment trials (p < 0.05). The use of two dynamic articulating tip instruments showed significant improvement with training in all measured parameters except for performance in the cut task, in which the increase in a-GRS score was not significant. CONCLUSIONS: We conclude that the least adequate instrument set for initiation in LESS surgery is the one that combines two dynamic articulating tip instruments, as this has consistently obtained the worst results in all trials. Further data on more complex tasks and on a complete learning and skills-acquisition program must be obtained to confirm these findings.
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Competencia Clínica , Simulación por Computador , Educación Médica Continua/métodos , Evaluación Educacional/métodos , Endoscopía/instrumentación , Laparoscopía/instrumentación , Endoscopía/educación , Diseño de Equipo , Femenino , Humanos , Laparoscopía/educación , Masculino , Grabación en VideoRESUMEN
OBJECTIVES: This study aims to analyze the surgeons' hand spatial configuration during the use of two different instrument handles for laparoscopy, by obtaining information from the data glove CyberGlove®, and establishing existing risk levels for wrist disorders. MATERIAL AND METHODS: Fifty surgeons participated in this study and were distributed into three groups (novices, intermediate and experts). Each subject carried out suturing and dissection tasks on a physical simulator, using axial-handled or ring-handled instruments, respectively. Hand and wrist positions were registered by the CyberGlove® and a modified RULA method was applied to establish appropriate risk levels for wrist disorders. RESULTS: We found statistically significant differences in seven of the eleven glove sensors when comparing both tasks. RULA method showed that all subjects, with the exception of the experts using an axial-handled instrument, assume a prejudicial wrist posture during the practice of suturing and dissection tasks on the simulator. CONCLUSIONS: Data glove CyberGlove® allows for the distinction between two laparoscopic exercises performed with different instruments. Also, laparoscopic intracorporeal suturing when performed with an axial-handled needle holder entails a more ergonomic posture for the wrist joint. Previous minimally invasive surgical experience is a positive influencing factor on the surgeons' wrist postures during laparoscopy.
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Ergonomía , Mano , Laparoscopía/métodos , Movimiento (Física) , Muñeca , Trastornos de Traumas Acumulados/prevención & control , HumanosRESUMEN
Here, we report the complete genome of four S. enterica Infantis isolated in Costa Rica from human, poultry rinse, and raw chicken meat from 2017 to 2019. All genomes belonged to ST32 and carried a 310-kb plasmid with many antimicrobial resistance genes including the bla CTX-M65 gene.
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Approaches to safety culture assessment may have many limits if supported exclusively by quantitative methods. Based on this, a research team developed a quantitative-qualitative approach to assess the maturity of the safety culture on an oil platform. To that end, the team sought to develop and test a method consisting of an initial ethnographic phase followed by four other distinct phases: definition of homogeneous groups; production of customized questionnaires; quantitative evaluation; and qualitative assessment. The results show the emergence of trends, from pre-defined themes in safety culture to specific levels of maturity for each of the homogeneous groups. At the same time, it was perceived that the maturity level of the groups is defined from the daily work practices developed by each one of them. This experience allowed us to propose a framework for assessing the maturity levels of safety culture for the oil and gas industry.
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Industria del Petróleo y Gas , Administración de la Seguridad , Humanos , IndustriasRESUMEN
Cell-penetrating peptides (CPPs) are short chains of amino acids that have shown remarkable potential to cross the cell membrane and deliver coupled therapeutic cargoes into cells. Designing and testing different CPPs to target specific cells or tissues is crucial to ensure high delivery efficiency and reduced toxicity. However, in vivo/in vitro testing of various CPPs can be both time-consuming and costly, which has led to interest in computational methodologies, such as Machine Learning (ML) approaches, as faster and cheaper methods for CPP design and uptake prediction. However, most ML models developed to date focus on classification rather than regression techniques, because of the lack of informative quantitative uptake values. To address these challenges, we developed POSEIDON, an open-access and up-to-date curated database that provides experimental quantitative uptake values for over 2,300 entries and physicochemical properties of 1,315 peptides. POSEIDON also offers physicochemical properties, such as cell line, cargo, and sequence, among others. By leveraging this database along with cell line genomic features, we processed a dataset of over 1,200 entries to develop an ML regression CPP uptake predictor. Our results demonstrated that POSEIDON accurately predicted peptide cell line uptake, achieving a Pearson correlation of 0.87, Spearman correlation of 0.88, and r2 score of 0.76, on an independent test set. With its comprehensive and novel dataset, along with its potent predictive capabilities, the POSEIDON database and its associated ML predictor signify a significant leap forward in CPP research and development. The POSEIDON database and ML Predictor are available for free and with a user-friendly interface at https://moreiralab.com/resources/poseidon/ , making them valuable resources for advancing research on CPP-related topics. Scientific Contribution Statement: Our research addresses the critical need for more efficient and cost-effective methodologies in Cell-Penetrating Peptide (CPP) research. We introduced POSEIDON, a comprehensive and freely accessible database that delivers quantitative uptake values for over 2,300 entries, along with detailed physicochemical profiles for 1,315 peptides. Recognizing the limitations of current Machine Learning (ML) models for CPP design, our work leveraged the rich dataset provided by POSEIDON to develop a highly accurate ML regression model for predicting CPP uptake.