Stepwise introduction of stabilizing mutations reveals nonlinear additive effects in de novo TIM barrels.

Over the past decades, the TIM-barrel fold has served as a model system for the exploration of how changes in protein sequences affect their structural, stability, and functional characteristics, and moreover, how this information can be leveraged to design proteins from the ground up. After numerous attempts to design de novo proteins with this specific fold, sTIM11 was the first validated de novo design of an idealized four-fold symmetric TIM barrel. Subsequent efforts to enhance the stability of this initial design resulted in the development of DeNovoTIMs, a family of de novo TIM barrels with various stabilizing mutations. In this study, we present an investigation into the biophysical and thermodynamic effects upon introducing a varying number of stabilizing mutations per quarter along the sequence of a four-fold symmetric TIM barrel. We compared the base design DeNovoTIM0 without any stabilizing mutations with variants containing mutations in one, two, three, and all four quarters-designated TIM1q, TIM2q, TIM3q, and DeNovoTIM6, respectively. This analysis revealed a stepwise and nonlinear change in the thermodynamic properties that correlated with the number of mutated quarters, suggesting positive nonadditive effects. To shed light on the significance of the location of stabilized quarters, we engineered two variants of TIM2q which contain the same number of mutations but positioned in different quarter locations. Characterization of these TIM2q variants revealed that the mutations exhibit varying effects on the overall protein stability, contingent upon the specific region in which they are introduced. These findings emphasize that the amount and location of stabilized interfaces among the four quarters play a crucial role in shaping the conformational stability of these four-fold symmetric TIM barrels. Analysis of de novo proteins, as described in this study, enhances our understanding of how sequence variations can finely modulate stability in both naturally occurring and computationally designed proteins.

Ultrasound in the Study of Thoracic Diseases: Innovative Aspects

Thoracic ultrasound (TU) has rapidly gained popularity over the past 10 years. This is in part because ultrasound equipment is available in many settings, more training programmes are educating trainees in this technique, and ultrasound can be done rapidly without exposure to radiation.The aim of this review is to present the most interesting and innovative aspects of the use of TU in the study of thoracic diseases.In pleural diseases, TU has been a real revolution. It helps to differentiate between different types of pleural effusions, guides the performance of pleural biopsies when necessary and is more cost-effective under these conditions, and assists in the decision to remove thoracic drainage after talc pleurodesis.With the advent of COVID19, the use of TU has increased for the study of lung involvement. Nowadays it helps in the diagnosis of pneumonias, tumours and interstitial diseases, and its use is becoming more and more widespread in the Pneumology ward.In recent years, TU guided biopsies have been shown to be highly cost-effective, with other advantages such as the absence of radiation and the possibility of being performed at bedside. The use of contrast in ultrasound to increase the cost-effectiveness of these biopsies is very promising.In the study of the mediastinum and peripheral pulmonary nodules, the introduction of echobronchoscopy has brought about a radical change. It is a fully established technique in the study of lung cancer patients. The introduction of elastography may help to further improve its cost-effectiveness.In critically-ill patients, diaphragmatic ultrasound helps in the assessment of withdrawal of mechanical ventilation, and is now an indispensable tool in the management of these patients. (AU)

Ultrasound in the Study of Thoracic Diseases: Innovative Aspects.

Thoracic ultrasound (TU) has rapidly gained popularity over the past 10 years. This is in part because ultrasound equipment is available in many settings, more training programmes are educating trainees in this technique, and ultrasound can be done rapidly without exposure to radiation. The aim of this review is to present the most interesting and innovative aspects of the use of TU in the study of thoracic diseases. In pleural diseases, TU has been a real revolution. It helps to differentiate between different types of pleural effusions, guides the performance of pleural biopsies when necessary and is more cost-effective under these conditions, and assists in the decision to remove thoracic drainage after talc pleurodesis. With the advent of COVID19, the use of TU has increased for the study of lung involvement. Nowadays it helps in the diagnosis of pneumonias, tumours and interstitial diseases, and its use is becoming more and more widespread in the Pneumology ward. In recent years, TU guided biopsies have been shown to be highly cost-effective, with other advantages such as the absence of radiation and the possibility of being performed at bedside. The use of contrast in ultrasound to increase the cost-effectiveness of these biopsies is very promising. In the study of the mediastinum and peripheral pulmonary nodules, the introduction of echobronchoscopy has brought about a radical change. It is a fully established technique in the study of lung cancer patients. The introduction of elastography may help to further improve its cost-effectiveness. In critically-ill patients, diaphragmatic ultrasound helps in the assessment of withdrawal of mechanical ventilation, and is now an indispensable tool in the management of these patients. In neuromuscular patients, ultrasound is a good predictor of impaired lung function. Currently, in Neuromuscular Disease Units, TU is an indispensable tool. Ultrasound study of the intercostal musculature is also effective in the study of respiratory function, and is widely used in Respiratory Rehabilitation. In Intermediate Care Units, thoracic ultrasound is indispensable for patient management. In these units there are ultrasound protocols for the management of patients with acute dyspnoea that have proven to be very effective.

Exploring the Protein Sequence Space with Global Generative Models.

Recent advancements in specialized large-scale architectures for training images and language have profoundly impacted the field of computer vision and natural language processing (NLP). Language models, such as the recent ChatGPT and GPT-4, have demonstrated exceptional capabilities in processing, translating, and generating human language. These breakthroughs have also been reflected in protein research, leading to the rapid development of numerous new methods in a short time, with unprecedented performance. Several of these models have been developed with the goal of generating sequences in novel regions of the protein space. In this work, we provide an overview of the use of protein generative models, reviewing (1) language models for the design of novel artificial proteins, (2) works that use non-transformer architectures, and (3) applications in directed evolution approaches.

Retracing the evolution of a modern periplasmic binding protein.

Investigating the evolution of structural features in modern multidomain proteins helps to understand their immense diversity and functional versatility. The class of periplasmic binding proteins (PBPs) offers an opportunity to interrogate one of the main processes driving diversification: the duplication and fusion of protein sequences to generate new architectures. The symmetry of their two-lobed topology, their mechanism of binding, and the organization of their operon structure led to the hypothesis that PBPs arose through a duplication and fusion event of a single common ancestor. To investigate this claim, we set out to reverse the evolutionary process and recreate the structural equivalent of a single-lobed progenitor using ribose-binding protein (RBP) as our model. We found that this modern PBP can be deconstructed into its lobes, producing two proteins that represent possible progenitor halves. The isolated halves of RBP are well folded and monomeric proteins, albeit with a lower thermostability, and do not retain the original binding function. However, the two entities readily form a heterodimer in vitro and in-cell. The x-ray structure of the heterodimer closely resembles the parental protein. Moreover, the binding function is fully regained upon formation of the heterodimer with a ligand affinity similar to that observed in the modern RBP. This highlights how a duplication event could have given rise to a stable and functional PBP-like fold and provides insights into how more complex functional structures can evolve from simpler molecular components.

GK-1 effectively reduces angiogenesis and prevents T cell exhaustion in a breast cancer murine experimental model.

Breast cancer is the leading malignancy in women worldwide, both in terms of incidence and mortality. Triple-negative breast cancer (TNBC) is the type with the worst clinical outcomes and with fewer therapeutic options than other types of breast cancer. GK-1 is a peptide that in the experimental model of the metastatic 4T1 breast cancer has demonstrated anti-tumor and anti-metastatic properties. Herein, GK-1 (5 mg/kg, i.v.) weekly administrated not only decreases tumor growth and the number of lung macro-metastases but also lung and lymph nodes micro-metastases. Histological analysis reveals that GK-1 reduced 57% of the intra-tumor vascular areas, diminished the leukemoid reaction's progression, and the spleens' weight and length. A significant reduction in VEGF-C, SDF-1, angiopoietin-2, and endothelin-1 angiogenic factors was induced. Moreover, GK-1 prevents T cell exhaustion in the tumor-infiltrating lymphocytes (TILs) decreasing PD-1 expression. It also increased IFN-γ and granzyme-B expression and the cytotoxic activity of CD8+ TILs cells against tumor cells. All these features were found to be associated with a better antitumor response and prognosis. Altogether, these results reinforce the potential of GK-1 to improve the clinical outcome of triple-negative breast cancer immunotherapy. Translation research is ongoing towards its evaluation in humans.

Active Surveillance of Antimicrobial Resistance and Carbapenemase-Encoding Genes According to Sites of Care and Age Groups in Mexico: Results from the INVIFAR Network.

We analyzed the antimicrobial resistance (AMR) data of 6519 clinical isolates of Escherichia coli (n = 3985), Klebsiella pneumoniae (n = 775), Acinetobacter baumannii (n = 163), Pseudomonas aeruginosa (n = 781), Enterococcus faecium (n = 124), and Staphylococcus aureus (n = 691) from 43 centers in Mexico. AMR assays were performed using commercial microdilution systems (37/43) and the disk diffusion susceptibility method (6/43). The presence of carbapenemase-encoding genes was assessed using PCR. Data from centers regarding site of care, patient age, and clinical specimen were collected. According to the site of care, the highest AMR was observed in E. coli, K. pneumoniae, and P. aeruginosa isolates from ICU patients. In contrast, in A. baumannii, higher AMR was observed in isolates from hospitalized non-ICU patients. According to age group, the highest AMR was observed in the ≥60 years age group for E. coli, E. faecium, and S. aureus, and in the 19-59 years age group for A. baumannii and P. aeruginosa. According to clinical specimen type, a higher AMR was observed in E. coli, K. pneumoniae, and P. aeruginosa isolates from blood specimens. The most frequently detected carbapenemase-encoding gene in E. coli was blaNDM (84%).

Academic stress, hair and saliva cortisol, and their relationship with body mass index and fat percentage in first year medical students.

Introduction: Although a large part of the population may be exposed to various pressures that can lead to mental or eating problems and increased perceived stress, the transition from adolescence to adulthood has been shown to be a crucial stage. Medical students are particularly vulnerable during the transition period as they must adapt to new circumstances, which may contribute to increased perceived stress. Cortisol plays an important role between stress, weight gain, and the development of obesity. We designed a study to investigate the association between stress, eating behaviour, cortisol, and body weight in a sample of first-year medical students. Methods: We determined 75 first-year medical students' hair and salivary cortisol concentrations by ELISA and related it to self-reported stress, eating behaviour, and anthropometric measurements throughout the academic period. The prevalence of overweight and obesity in females was 25% and 10%, and in males was 35% and 6%, respectively. We report an increase in hair cortisol, higher self-reported stress scores, and BMI mainly in females. Finally, we found evidence of positive associations between hair cortisol and BMI in females (r = 0.348) and males (r = 0.423). Conclusion: There is a low association between short-term single-point cortisol measures and long-term cortisol, mainly in males. Hence, short-term cortisol reactivity is moderately associated with long-term cortisol reactivity when both are evaluated simultaneously. These results support the previous evidence of positive associations between cortisol with body fat percentage and BMI, and finally, that eating behaviours are modified by academic stress perception, mainly in females.

Experiencias de docentes y estudiantes en la educación remota de emergencia: oportunidades para mejorar la educación del pregrado en medicina / Faculty and student experience during remote emergency education: opportunities for improving undergraduate medical education

Introducción: Los ciclos clínicos de pregrado representan los escenarios principales en los que los estudiantes de medicina consolidan los conocimientos. Sin embargo, a principios de 2020, la mayoría de los estudiantes fue confinada en sus domicilios debido a la pandemia por el SARS-CoV-2. Los procesos formativos continuaron desde los hogares por medio de la educación remota de emergencia, una modalidad de enseñanza basada en el uso intensivo de la tecnología que, a pesar de hacerse de manera improvisada, respondió a la situación educativa de urgencia. El propósito de este estudio fue indagar la experiencia educativa de estudiantes y docentes que se encontraban en los años clínicos de pregrado de la carrera de medicina con el fin de identificar las oportunidades de mejora en la enseñanza a partir de la crisis sanitaria vivida. Sujetos y métodos: Se realizó un estudio cualitativo de carácter descriptivo con la técnica de grupos focales. El análisis se basó en la reducción de datos, en la triangulación entre estamentos y en la bibliografía del tema. Resultados: Se realizaron 16 grupos focales con un total de 148 participantes. Se identificaron cuatro categorías generales: a) enseñanza y aprendizaje; b) evaluación de la práctica clínica; c) identidad profesional, y d) sugerencias en busca de mejoras en la formación de los médicos Conclusiones: Las reflexiones reconocen la necesidad de incorporar las tecnologías digitales de una manera planeada y diseñada en conjunto por expertos y docentes para adaptarlas a las necesidades de los contextos educativos, y continuar con modelos híbridos o combinados para mejorar la educación médica.(AU)

Introduction: During medical education, undergraduate clinical cycles represent the main scenarios where students consolidate knowledge. However, in the early 2020s, most students were confined to their homes due to the SARS-Cov-2 pandemic. In this situation, the digital network allowed the educational processes to continue from their homes through remote emergency education (REE), a teaching modality based on the intensive use of technology that, despite having been improvised, responded to the emergency educational situation. Therefore, this study aimed to investigate the educational experience of students and teachers in the undergraduate clinical years of the medical degree in order to identify opportunities for improvement in teaching after the health crisis. Subjects and methods: A descriptive qualitative study was carried out with a phenomenological approach through the focus group technique. The qualitative analysis was based on data reduction and triangulation between strata and subject literature. Results: Sixteen focus groups were integrated with a total of 148 participants. Four categories were identified: a) teaching and learning; b) evaluation of clinical practice; c) professional identity, and d) suggestions for improvement in the training of physicians. Conclusions: The reflections lead to recognizing the need to incorporate digital technology designed by experts and teachers to adapt them to the real needs of the educational contexts and to continue with a hybrid or combined model that supports the improvement of medical education.(AU)

Neutrophil to lymphocyte ratio and principal component analysis offer prognostic advantage for dogs with mammary tumors.

Introduction: In veterinary medicine, cancer is the leading cause of death in companion animals, and mammary gland tumors represent the most common neoplasm in female dogs. Several epidemiological risk factors, such as age, breed, hormones, diet, and obesity have been reported to be relevant for canine mammary tumors. Nowadays, the gold standard for diagnosis of canine mammary tumors is the pathological examination of the suspected tissue. However, tumor grade can only be assessed after surgical removal or biopsy of the altered tissue. Therefore, in cases of tumors that could be surgically removed, it would be very helpful to be able to predict the biological behavior of the tumor, before performing any surgery. Since, inflammation constitutes part of the tumor microenvironment and it influences each step of tumorigenesis, cellular and biochemical blood markers of systemic inflammation, such as the neutrophil to lymphocyte ratio (NLR) and the albumin to globulin ratio (AGR) have been proposed as prognostic factors for human cancer development. The NLR and the AGR have not been explored enough as prognostic factors for cancer development in veterinary medicine. Methods: To determine the prognostic value of NLR in canine mammary tumors, clinical records including biochemistry and hematological studies of female dogs with mammary tumors and of control healthy dogs, were used to determine the pre-treatment NLR and AGR. Other clinical data included age, breed, tumor size, histological tumor grade, and survival time after surgery. Results and discussion: It was found that a higher pre-treatment NLR value (NLR > 5) associates with less survival rate. In contrast, the AGR did not show any predictive value on the malignancy of the tumor. However, by combining the NLR with AGR, age of the dog, and tumor size in a principal component analysis (PCA), the grade of the tumor and survival after surgery could be appropriately predicted. These data strongly suggest that pre-treatment NLR values have a prognostic value for the survival rate after surgery of dogs with mammary tumors.

Thermodynamic and kinetic analysis of the LAO binding protein and its isolated domains reveal non-additivity in stability, folding and function.

Substrate-binding proteins (SBPs) are used by organisms from the three domains of life for transport and signalling. SBPs are composed of two domains that collectively trap ligands with high affinity and selectivity. To explore the role of the domains and the integrity of the hinge region between them in the function and conformation of SBPs, here, we describe the ligand binding, conformational stability and folding kinetics of the Lysine Arginine Ornithine (LAO) binding protein from Salmonella thiphimurium and constructs corresponding to its two independent domains. LAO is a class II SBP formed by a continuous and a discontinuous domain. Contrary to the expected behaviour based on their connectivity, the discontinuous domain shows a stable native-like structure that binds l-arginine with moderate affinity, whereas the continuous domain is barely stable and shows no detectable ligand binding. Regarding folding kinetics, studies of the entire protein revealed the presence of at least two intermediates. While the unfolding and refolding of the continuous domain exhibited only a single intermediate and simpler and faster kinetics than LAO, the folding mechanism of the discontinuous domain was complex and involved multiple intermediates. These findings suggest that in the complete protein the continuous domain nucleates folding and that its presence funnels the folding of the discontinuous domain avoiding nonproductive interactions. The strong dependence of the function, stability and folding pathway of the lobes on their covalent association is most likely the result of the coevolution of both domains as a single unit.

Whole genome analysis of Gram-negative bacteria using the EPISEQ CS application and other bioinformatic platforms.

OBJECTIVES: To determine genomic characteristics and molecular epidemiology of carbapenem non-susceptible Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa from medical centres of Mexico using whole genome sequencing data analysed with the EPISEQⓇ CS application and other bioinformatic platforms. METHODS: Clinical isolates collected from 28 centres in Mexico included carbapenem-non-susceptible K. pneumoniae (n = 22), E. coli (n = 24), A. baumannii (n = 16), and P. aeruginosa (n = 13). Isolates were subjected to whole genome sequencing using the Illumina (MiSeq) platform. FASTQ files were uploaded to the EPISEQⓇ CS application for analysis. Additionally, the tools Kleborate v2.0.4 and Pathogenwatch were used as comparators for Klebsiella genomes, and the bacterial whole genome sequence typing database was used for E. coli and A. baumannii. RESULTS: For K. pneumoniae, both bioinformatic approaches detected multiple genes encoding aminoglycoside, quinolone, and phenicol resistance, and the presence of blaNDM-1 explained carbapenem non-susceptibility in 18 strains and blaKPC-3 in four strains. Regarding E. coli, both EPISEQⓇ CS and bacterial whole genome sequence typing database analyses detected multiple virulence and resistance genes: 20 of 24 (83.3%) strains carried blaNDM, 3 of 24 (12.4%) carried blaOXA-232, and 1 carried blaOXA-181. Genes that confer resistance to aminoglycosides, tetracyclines, sulfonamides, phenicols, trimethoprim, and macrolides were also detected by both platforms. Regarding A. baumannii, the most frequent carbapenemase-encoding gene detected by both platforms was blaOXA-72, followed by blaOXA-66. Both approaches detected similar genes for aminoglycosides, carbapenems, tetracyclines, phenicols, and sulfonamides. Regarding P. aeruginosa, blaVIM, blaIMP, and blaGES were the more frequently detected. Multiple virulence genes were detected in all strains. CONCLUSION: Compared to the other available platforms, EPISEQⓇ CS enabled a comprehensive resistance and virulence analysis, providing a reliable method for bacterial strain typing and characterization of the virulome and resistome.

Structures of permuted halves of a modern ribose-binding protein.

Periplasmic binding proteins (PBPs) are a class of proteins that participate in the cellular transport of various ligands. They have been used as model systems to study mechanisms in protein evolution, such as duplication, recombination and domain swapping. It has been suggested that PBPs evolved from precursors half their size. Here, the crystal structures of two permuted halves of a modern ribose-binding protein (RBP) from Thermotoga maritima are reported. The overexpressed proteins are well folded and show a monomer-dimer equilibrium in solution. Their crystal structures show partially noncanonical PBP-like fold type I conformations with structural deviations from modern RBPs. One of the half variants forms a dimer via segment swapping, suggesting a high degree of malleability. The structural findings on these permuted halves support the evolutionary hypothesis that PBPs arose via a duplication event of a flavodoxin-like protein and further support a domain-swapping step that might have occurred during the evolution of the PBP-like fold, a process that is necessary to generate the characteristic motion of PBPs essential to perform their functions.

Diagnosis and Treatment of Pleural Effusion. Recommendations of the Spanish Society of Pulmonology and Thoracic Surgery. Update 2022

Pleural effusion (PE) is a common yet complex disease that requires specialized, multidisciplinary management. Recent advances, novel diagnostic techniques, and innovative patient-centered therapeutic proposals have prompted an update of the current guidelines. This document provides recommendations and protocols based on a critical review of the literature on the epidemiology, etiology, diagnosis, prognosis, and new therapeutic options in PE, and addresses some cost-effectiveness issues related to the main types of PE. (AU)

Diagnosis and Treatment of Pleural Effusion. Recommendations of the Spanish Society of Pulmonology and Thoracic Surgery. Update 2022.

Pleural effusion (PE) is a common yet complex disease that requires specialized, multidisciplinary management. Recent advances, novel diagnostic techniques, and innovative patient-centered therapeutic proposals have prompted an update of the current guidelines. This document provides recommendations and protocols based on a critical review of the literature on the epidemiology, etiology, diagnosis, prognosis, and new therapeutic options in PE, and addresses some cost-effectiveness issues related to the main types of PE.

Agglomeration: when folded proteins clump together.

Protein self-association is a widespread phenomenon that results in the formation of multimeric protein structures with critical roles in cellular processes. Protein self-association can lead to finite protein complexes or open-ended, and potentially, infinite structures. This review explores the concept of protein agglomeration, a process that results from the infinite self-assembly of folded proteins. We highlight its differences from other better-described processes with similar macroscopic features, such as aggregation and liquid-liquid phase separation. We review the sequence, structural, and biophysical factors influencing protein agglomeration. Lastly, we briefly discuss the implications of agglomeration in evolution, disease, and aging. Overall, this review highlights the need to study protein agglomeration for a better understanding of cellular processes.

Estudio proteomico diferencial entre liquidos pleurales secundarios a cáncer de pulmón versus mesotelioma / Differential proteomic study between pleural fluid secondary to lung cancer versus mesothelioma

Objetivo: Encontrar perfiles proteicos en líquido pleural que diferencien derrames pleurales secundarios a cáncer de pulmón (CP) versus mesotelioma pleural maligno (MPM).Metodología: Recogimos líquidos pleurales de 60 pacientes de tres grupos diferentes: MPM (N = 20), CP (N = 20) y derrames pleurales benignos (N = 20). Realizamos un análisis con proteómica diferencial con ITRAQ 4 plex (Applied Biosystem). Realizamos la identificación y cuantificación relativa de las proteínas con el programa Proteome Discoverer 1.4 (Termofisher Scientific). Construimos diagramas de Venn con las proteínas sobre/infra-expresadas en cada grupo. Realizamos una validación interna/externa mediante ELISA (Myobiosorce) añadiendo 25 muestras de CP y 14 de MPM.Resultados: Encontramos sobreexpresión de Pi3K en los derrames pleurales neoplásicos (16,86 +/- 25,83 ng/ml en CP; 20,66 +/- 17,26 ng/ml en MPM vs 5,92 +/- 0,99 ng/ml en controles). Hubo sobreexpresión de SPRM en MPM (30.702 +/- 30.310,53 ng/ml en el grupo MPM vs 10.404 +/- 10.157,72 ng/ml en el grupo CP vs 8.498 + /- 3.437,18 ng/ml en controles). Existió sobreexpresión de RhoB en CP (4,46 +/- 1,65 mg/ml en CP vs 1,65 +/- 2,65 mg/ml en MPM vs 0,92 +/- 1,6 mg/ml en controles). También encontramos sobreexpresión de PDGFR-alfa en derrames pleurales benignos (74,12 +/- 22,57 ng/ml en controles vs 43,05 +/- 23,96 ng/ml en CP vs 36,12 +/- 21,51 ng/ml en MPM).Conclusión: Existe un perfil diferencial proteico entre los derrames secundarios a CP (sobreexpresión de RhoB) y a MPM (sobrexpresión de SPRM). La sobrexpresión de Pi3K indica asociación a derrames pleurales malignos y la de PDGFR-alfa a derrames benignos. (AU)

Objetivo: Find protein profiles in pleural fluid that differentiate pleural effusions secondary to lung cancer (LC) versus malignant pleural mesothelioma (MPM).Metodología: We collected pleural fluids from 60 patients from three different groups: MPM (N = 20), CP (N = 20), and benign pleural effusions (N = 20). We performed differential proteomics analysis with ITRAQ 4 plex (Applied Biosystem). We performed the identification and relative quantification of the proteins with the Proteome Discoverer 1.4 program (Termofisher Scientific). We built Venn diagrams with the over/under-expressed proteins in each group. We performed an internal/external validation using ELISA (Myobiosorce) adding 25 CP and 14 MPM samples.Resultados: We found Pi3K overexpression in neoplastic pleural effusions (16.86 +/- 25.83 ng/ml in PC; 20.66 +/- 17.26 ng/ml in MPM vs 5.92 +/- 0.99 ng/ml in controls). There was overexpression of SPRM in MPM (30,702 +/- 30,310.53 ng/ml in the MPM group vs 10,404 +/- 10,157.72 ng/ml in the CP group vs 8,498 +/- 3,437.18 ng/ml in controls). There was overexpression of RhoB in CP (4.46 +/- 1.65 mg/ml in CP vs 1.65 +/- 2.65 mg/ml in MPM vs 0.92 +/- 1.6 mg/ml in controls). We also found overexpression of PDGFR-alpha in benign pleural effusions (74.12 +/- 22.57 ng/ml in controls vs 43.05 +/- 23.96 ng/ml in PC vs 36.12 +/- 21.51 ng/ml in MPM ).Conclusión: There is a differential protein profile between effusions secondary to CP (RhoB overexpression) and MPM (SPRM overexpression). Pi3K overexpression indicates association with malignant pleural effusions and PDGFR-alpha overexpression with benign effusions. (AU)

Inpatient Experience Surveys and Overall Hospital Rating: A Correlation Analysis for a Private Hospital in Central America.

Objectives: To validate the use of a patient experience survey composed of the Spanish version of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey and of questions locally created in our institution, a private hospital in Panama. To identify which domains of our patient experience survey have the strongest association with the overall inpatient hospital experience rating. Methods: A retrospective analysis of 1619 electronic survey results of adult inpatient experience data was performed using exploratory factor and Pearson correlation analyses. The data was collected between March 2018 and December 2019 from a web-survey application, accessible through a link sent by email after hospital discharge. Results: Results from analyses showed that questions grouping occurred under the same domains as the HCAHPS English version (factor loading 0.456 to 0.918) and that a new domain named administrative processes (0.818 to 0.846) arose for the newly created questions. Cronbach's alpha values ranged from 0.32 to 0.85, with an α of0.65 for the new local questions. Correlation analyses were higher for the domains of communication from nurses (0.670) and administrative processes (0.618). Conclusions: Our investigation validates the use of our patient experience survey, composed of questions from the Spanish version of the HCAHPS survey and locally created ones. In our institution, communication from nurses is most correlated with the inpatient hospital experience rating. Hospital administrative processes were also strongly associated with the overall inpatient hospital rating, and we argue that these later aspects should be addressed to improve the patient experience.

In Vitro Anthelmintic Activity of a Hydroalcoholic Extract from Guazuma ulmifolia Leaves against Haemonchus contortus.

The purpose of the present study was to assess the ovicidal and larvicidal activity of a hydroalcoholic extract (HAE) and their fractions (aqueous, Aq-F and organic, EtOAc-F) from Guazuma ulmifolia leaves using Haemonchus contortus as a biological model. The egg hatching inhibition (EHI) and larval mortality against infective larvae (L3) tests were used to determine the anthelmintic effect of the treatments. The extract and fractions were tested at different concentrations against eggs and L3. Additionally, distilled water and methanol were used as negative controls and ivermectin as a positive control. The extract and fractions were subjected to HPLC analysis to identify the major compounds. The HAE displayed the highest ovicidal activity (100% EHI at 10 mg/mL). Fractionation of the HA extract allowed increasing the nematicidal effect in the EtOAc-F (100% EHI at 0.62 mg/mL and 85.35% mortality at 25 mg/mL). The phytochemical analysis of the extract and fractions revealed the presence of kaempferol, ethyl ferulate, ethyl coumarate, flavonol, luteolin, ferulic acid, luteolin rhamnoside, apigenin rutinoside, coumaric acid derivative, luteolin glucoside, and quercetin glucoside. These results suggest that G. ulmifolia leaves could be potential candidates for the control of H. contortus or other gastrointestinal parasitic nematodes.

Charge Radii of

Nuclear charge radii of ^{55,56}Ni were measured by collinear laser spectroscopy. The obtained information completes the behavior of the charge radii at the shell closure of the doubly magic nucleus ^{56}Ni. The trend of charge radii across the shell closures in calcium and nickel is surprisingly similar despite the fact that the ^{56}Ni core is supposed to be much softer than the ^{48}Ca core. The very low magnetic moment µ(^{55}Ni)=-1.108(20) µ_{N} indicates the impact of M1 excitations between spin-orbit partners across the N,Z=28 shell gaps. Our charge-radii results are compared to ab initio and nuclear density functional theory calculations, showing good agreement within theoretical uncertainties.