Physiological response of Metarhizium rileyi with linoleic acid supplementation.

Metarhizium rileyi has a broad biocontrol spectrum but is highly sensitive to abiotic factors. A Colombian isolate M. rileyi Nm017 has shown notorious potential against Helicoverpa zea. However, it has a loss of up to 22 % of its conidial germination after drying, which limits its potential as a biocontrol agent and further commercialization. Conidial desiccation resistance can be enhanced by nutritional supplements, which promotes field adaptability and facilitates technological development as a biopesticide. In this study, the effect of culture medium supplemented with linoleic acid on desiccation tolerance in Nm017 conidia was evaluated. Results showed that using a 2 % linoleic acid-supplemented medium increased the relative germination after drying by 41 % compared to the control treatment, without affecting insecticidal activity on H. zea. Also, the fungus increased the synthesis of trehalose, glucose, and erythritol during drying, independently of linoleic acid use. Ultrastructural analyses of the cell wall-membrane showed a loss of thickness by 22 % and 25 %, in samples obtained from 2 % linoleic acid supplementation and the control, respectively. Regarding its morphological characteristics, conidia inner area from both treatments did not change after drying. However, conidia from the control had a 24 % decrease in length/width ratio, whereas there was no alteration in conidia from acid linoleic. The average value of dry conidia elasticity coefficient from linoleic acid treatment was 200 % above the control. Medium supplementation with linoleic acid is a promising fermentation strategy for obtaining more tolerant conidia without affecting production and biocontrol parameters, compatible solutes synthesis, or modifying its cell configuration.

Noninvasive assessment of liver fibrosis can predict clinical outcomes at late follow-up after a sustained virological response in HCV patients?

OBJECTIVES: The primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. METHODS: A total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. RESULTS: At 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. CONCLUSION: Transient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.

Mechanical Characterization of the Erythrocyte Membrane Using a Capacitor-Based Technique.

Pathological processes often change the mechanical properties of cells. Increased rigidity could be a marker of cellular malfunction. Erythrocytes are a type of cell that deforms to squeeze through tiny capillaries; changes in their rigidity can dramatically affect their functionality. Furthermore, differences in the homeostatic elasticity of the cell can be used as a tool for diagnosis and even for choosing the adequate treatment for some illnesses. More accurate types of equipment needed to study biomechanical phenomena at the single-cell level are very costly and thus out of reach for many laboratories around the world. This study presents a simple and low-cost technique to study the rigidity of red blood cells (RBCs) through the application of electric fields in a hand-made microfluidic chamber that uses a capacitor principle. As RBCs are deformed with the application of voltage, cells are observed under a light microscope. From mechanical force vs. deformation data, the elastic constant of the cells is determined. The results obtained with the capacitor-based method were compared with those obtained using optical tweezers, finding good agreement. In addition, P. falciparum-infected erythrocytes were tested with the electric field applicator. Our technique provides a simple means of testing the mechanical properties of individual cells.

Multiparametric magnetic resonance imaging of the liver and spleen in Gaucher disease.

PURPOSE: To assess liver and spleen characteristics of a population with Gaucher disease (GD) using multiparametric MRI and MR elastography (MRE) for evaluation of diffuse liver and spleen disease, which includes liver fat fraction, liver and spleen volume and iron deposition, and liver and spleen stiffness correlated with DS3 Severity Scoring System for Gaucher disease (GD-DS3). METHODS: We prospectively evaluated 41 patients with type 1 Gaucher disease using a 3.0 T MRI and MRE between January 2019 and February 2020. Clinical, laboratory, and imaging data was collected. Mann-Whitney, Kruskal-Wallis, and Spearman's correlation were applied to evaluate liver and spleen MRI and MRE, clinical and laboratory variables, and GD-DS3. ERT and SRT treatment groups were compared. RESULTS: Hepatomegaly was seen in 15% and splenomegaly in 42% of the population. Moderate and strong and correlations were found between liver and spleen iron overload (rho = 0.537; p = 0.002); between liver and spleen volume (rho = 0.692, p < 0.001) and between liver and spleen stiffness (rho = 0.453, p = 0.006). Moderate correlations were found between liver stiffness and GD-DS3 (rho = 0.559; p < 0.001) and between splenic volume and GD-DS3 (rho = 0.524; p = 0.001). CONCLUSION: The prevalence of hepatosplenomegaly, liver fibrosis, and liver iron overload in treated patients with GD is low, which may be related to the beneficial effect of treatment. Liver MRE and splenic volume correlate with severity score and may be biomarkers of disease severity.

Quantitative ultrasonography reveals skeletal muscle abnormalities in carriers of DMD pathogenic variants.

INTRODUCTION/AIMS: Carriers of DMD pathogenic variants may become symptomatic and develop muscle-related manifestations. Despite that, few studies have attempted to characterize changes in the muscles of these carriers using imaging tools, particularly muscle ultrasound (MUS). The aim of this study was to compare lower limb MUS findings in carriers of DMD pathogenic variants (cDMD) vs healthy controls. METHODS: Twenty-eight women (15 cDMD and 13 controls) underwent clinical evaluation and MUS. We collected information about muscle-related symptoms and assessed muscle strength. MUS was performed by a single physician (blind to the genetic status of subjects). The following muscles were assessed: rectus femoris, sartorius, tibialis anterior, and medial gastrocnemius. For each site, we computed data on muscle thickness, cross-sectional area, sound attenuation index, and elastography. Between-group comparisons were assessed using nonparametric tests and p-values <.05 were deemed significant. RESULTS: None of the subjects had objective muscle weakness, but exercise intolerance/fatigue was reported by four cDMDs and only one control. Regarding MUS, sound attenuation indices were significantly higher among carriers for all muscles tested. Longitudinal and axial deep echo intensities for the rectus femoris and tibialis anterior were also higher in the cDMD group compared with controls. No significant between-group differences were noted for elastography values, muscle area, or mean echo intensities. DISCUSSION: cDMD have skeletal muscle abnormalities that can be detected using quantitative MUS. Further studies are needed to determine whether such abnormalities are related to muscle symptoms in these patients.

Noninvasive assessment of liver fibrosis can predict clinical outcomes at late follow-up after a sustained virological response in HCV patients?

Abstract Objectives The primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. Methods A total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. Results At 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. Conclusion Transient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.

Impact of plasticization temperature on the mechanical properties of sports mouthguards / Impacto da temperatura de plastificação nas propriedades mecânicas de protetores bucais esportivo

Objective: Mouthguards can reduce or even prevent orofacial injuries. These devices are responsible for absorbing part of the energy of an impact force, while the remaining part is dissipated. The present study aimed to evaluate how the plasticization temperature of the sports mouthguards' manufacturing process influences their mechanical properties and protective potential. Material and Methods: Specimens were made according to different plasticization temperatures (85°C, 103°C, 121°C and 128°C) and different dental brands of EVA sheets (Bio-art and FGM). Plasticization temperatures were measured using a culinary thermometer (Term; TP300). The mechanical properties evaluated were: energy absorption capacity, deformation, and modulus of elasticity. Compression testing was carried out in the Emic universal testing machine with a speed of 600 mm/min to simulate a punch. Results: EVA sheets submitted to the highest temperatures (121°C and 128°C) had their energy absorption capacity reduced. In addition, the samples that plasticized at the lowest temperature (85°C) showed higher absorption capacity, lower elastic modulus, and less variation in its dimensions. It proved to be the most effective in protection and with greater durability. Conclusion: The plasticization temperature proved to be an influential factor in the absorption capacity of mouthguards, so the increase in temperature led to a reduction in this property, especially when higher than 120°C. In addition, the plasticization temperature may vary depending on the sheet brand used. Finally, the kitchen thermometer used proved to be efficient and practical, thanks to its easy-to-read display and wide availability on the market. (AU)

Objetivo: Os protetores bucais são capazes de reduzir ou mesmo prevenir lesões orofaciais. Esses dispositivos são responsáveis por absorver parte da energia de uma força de impacto, enquanto a parte restante é dissipada. Este estudo teve como objetivo avaliar como a temperatura de plastificação de protetores bucais esportivos influencia em suas propriedades mecânicas e no seu potencial protetivo. Material e Métodos: Foram confeccionados modelos de trabalho segundo diferentes temperaturas de plastificação (85°C, 103°C, 121°C e 128°C) e distintas marcas odontológicas de placas de EVA (Bio-art e FGM). As temperaturas de plastificação foram medidas com termômetro culinário da marca Term/TP300. As propriedades mecânicas avaliadas foram capacidade de absorção de energia, deformação e módulo de elasticidade. O teste de compressão foi realizado na máquina de ensaios universal Emic com velocidade de 600 mm/min, a fim de simular um soco. Resultados: As placas de EVA submetidas às mais altas temperaturas (121°C e 128°C) tiveram sua capacidade de absorção de energia reduzida. Além disso, as amostras que plastificaram na temperatura mais baixa (85°C) apresentaram maior capacidade de absorção, menor módulo de elasticidade e menor variação em suas dimensões. Assim, mostraram-se a mais eficaz na proteção e com maior durabilidade. Conclusão: A temperatura de plastificação demonstrou ser um fator influente na capacidade de absorção dos protetores bucais, de modo que o aumento da temperatura levou a uma redução desta propriedade, principalmente quando superior a 120°C. Além disso, a temperatura de plastificação pode variar dependendo da marca comercial utilizada. Por fim, o termômetro culinário utilizado mostrou-se eficiente e prático, pela facilidade de leitura e por ser facilmente encontrado no mercado (AU)

Shear wave elastography for extracranial carotid atherosclerotic plaques: technical principles and how to do it.

In the wake of studies targeting atherosclerotic plaques and searching for quantifiable variables that contribute additional information to therapeutic decision-making, plaque assessment using Shear Wave Elastography (SWE) is emerging as a reproducible and promising alternative. We used a single Logiq S8 device (General Electric, Boston, Massachusetts, United States) with an 8.5-11MHz multifrequency linear transducer at 10MHz in longitudinal section. We considered relevant criteria for image acquisition: adequate longitudinal insonation, differentiation of the intima-media complex, delineation of proximal and distal tunica adventitia and the vascular lumen, good visualization of the atherosclerotic plaque, cardiac cycle in ventricular diastole, and absence of incongruous changes. SWE is an emerging and extremely promising method for assessment of carotid plaques that may contribute to therapeutic decision-making based on characteristics related to the atherosclerotic plaque, with inter-device and inter-examiner reproducibility.

The Importance of Ultrasonography in the Evaluation of Mammary Tumors in Bitches.

The high incidence of mammary tumors in small animals is concerning. Patient history, clinical examination, physical evaluation, and imaging studies are important for clinical staging. Ultrasonography is commonly applied to investigate the presence of abdominal metastasis. However, it has been shown to provide important information regarding mammary tumors' architecture and advanced sonographic techniques can provide information regarding neovascularization, stiffness, and perfusion. Different techniques have been investigated to determine accuracy to predict the lesions' histological classification. This paper reviews the information regarding each sonographic technique in the evaluation of mammary tumors, describing the most common findings and their potential to accurately assess and predict malignancy. Even though the gold standard for the diagnosis of mammary lesions is the histopathological examination, some ultrasonographic features described can predict the potential of a lesion being malignant. Among the different sonographic techniques, elastography can be considered the most reliable modality to accurately differentiate benign from malignant tumors when malignant lesions present increased stiffness. However, the combination of all sonographic techniques can provide important information that can lead to a better therapeutic approach and clinical staging. Furthermore, the potential of the sonographic study, especially CEUS to monitor therapeutic progression, demonstrate the need of further studies.

Comportamiento Mecánico de un Premolar Humano Sano Sometido a Fuerzas Funcionales y Disfuncionales en un MEF / Mechanical Behavior of a Healthy Human Premolar Subjected to Functional and Dysfunctional Forces in a FEM

El propósito de este estudio fue analizar el comportamiento mecánico de la estructura dental sana de un primer premolar inferior humano sometido a fuerzas funcionales y disfuncionales en diferentes direcciones. Se buscó comprender, bajo las variables contempladas, las zonas de concentración de esfuerzos que conllevan al daño estructural de sus constituyentes y tejidos adyacentes. Se realizó el modelo 3D de la reconstrucción de un archivo TAC de un primer premolar inferior, que incluyó esmalte, dentina, ligamento periodontal y hueso alveolar considerando tres variables: dirección, magnitud y área de la fuerza aplicada. La dirección fue dirigida en tres vectores (vertical, tangencial y horizontal) bajo cuatro magnitudes, una funcional de 35 N y tres disfuncionales de 170, 310 y 445 N, aplicadas sobre un área de la cara oclusal y/o vestibular del premolar que involucró tres contactos estabilizadores (A, B y C) y dos paradores de cierre. Los resultados obtenidos explican el fenómeno de combinar tres vectores, cuatro magnitudes y un área de aplicación de la fuerza, donde los valores de esfuerzo efectivo equivalente Von Mises muestran valores máximos a partir de los 60 MPa. Los valores de tensión máximos se localizan, bajo la carga horizontal a 170 N y en el proceso masticatorio en la zona cervical, cuando la fuerza pasa del 60 %. Sobre la base de los hallazgos de este estudio, se puede concluir que la reacción de los tejidos a fuerzas funcionales y disfuncionales varía de acuerdo con la magnitud, dirección y área de aplicación de la fuerza. Los valores de tensión resultan ser más altos bajo la aplicación de fuerzas disfuncionales tanto en magnitud como en dirección, produciendo esfuerzos tensiles significativos para la estructura dental y periodontal cervical, mientras que, bajo las cargas funcionales aplicadas en cualquier dirección, no se generan esfuerzos lesivos. Esto supone el reconocimiento del poder de detrimento estructural del diente y periodonto frente al bruxismo céntrico y excéntrico.

SUMMARY: The purpose of this study was to analyze the mechanical behavior of the healthy dental structure of a human mandibular first premolar subjected to functional and dysfunctional forces in different directions. It was sought to understand, under the contemplated variables, the areas of stress concentration that lead to structural damage of its constituents and adjacent tissues. The 3D model of the reconstruction of a CT file of a lower first premolar was made, which included enamel, dentin, periodontal ligament and alveolar bone considering three variables: direction, magnitude and area of the applied force. The direction was directed in three vectors (vertical, tangential and horizontal) under four magnitudes, one functional of 35 N and three dysfunctional of 170, 310 and 445 N, applied to an area of the occlusal and/or buccal face of the premolar that involved three stabilizing contacts (A, B and C) and two closing stops. The results obtained explain the phenomenon of combining three vectors, four magnitudes and an area of force application, where the values of effective equivalent Von Mises stress show maximum values from 60 MPa. The maximum tension values are located under the horizontal load at 170 N and in the masticatory process in the cervical area, when the force exceeds 60%. Based on the findings of this study, it can be concluded that the reaction of tissues to functional and dysfunctional forces varies according to the magnitude, direction, and area of application of the force. The stress values turn out to be higher under the application of dysfunctional forces both in magnitude and in direction, producing significant tensile stresses for the dental and cervical periodontal structure, while under functional loads applied in any direction, no damaging stresses are generated. This supposes the recognition of the power of structural detriment of the tooth and periodontium against centric and eccentric bruxism.

Risk Factors for Liver Fibrosis in Diabetic Patients with End-stage Renal Disease

Introduction: Liver cirrhosis is the fourth cause of death in the world. Fatty liver disease is the most common cause of chronic liver disease (CKD) in most countries. Identifying risk factors for liver fibrosis in a population with end-stage renal disease (ESRD) may facilitate early diagnosis of this complication and allow the activation of follow-up protocols to reduce morbidity and mortality in these patients. Materials and methods: A cross-sectional and analytical study was carried out. Patients on hemodialysis, older than 18 years with a diagnosis of diabetes mellitus and ESRD were included. The hypotheses were contrasted through the chi-square test and Student's T-test, as appropriate. Statistical significance was established at a p-value = 0.05. Results: A prevalence of significant liver fibrosis and cirrhosis of 17% was found. Factors associated with liver fibrosis were a history of cerebrovascular disease, peripheral vascular disease, body mass index (BMI), total cholesterol, glycosylated hemoglobin, sodium, and aspartate aminotransferase (AST). No relationship was observed between the NAFLD (non-alcoholic fatty liver disease) score, the APRI index (AST to Platelet Ratio Index), and fibrosis. Conclusion: The prevalence of significant liver fibrosis in patients with diabetes and ESRD is similar to that reported in other populations of patients with diabetes. However, some factors, such as BMI, could behave differently and favor the appearance of liver injury with lower degrees of obesity than previously reported in the literature.

Introducción: la cirrosis hepática es la cuarta causa de muerte en el mundo. Actualmente, la enfermedad hepática por depósito de grasa es la causa más frecuente de hepatopatía crónica en la mayoría de los países. La identificación de factores de riesgo para la presencia de fibrosis hepática en una población con enfermedad renal crónica terminal puede facilitar el diagnóstico temprano de esta complicación y permitir la activación de protocolos de seguimiento para disminuir la morbimortalidad en estos pacientes. Metodología: se realizó un estudio de corte transversal y analítico. Se incluyeron pacientes en hemodiálisis, mayores de 18 años con diagnóstico de diabetes mellitus y de enfermedad renal crónica terminal. El contraste de hipótesis se realizó a través de la prueba de chi cuadrado y la T de Student, según correspondiera. La significación estadística se estableció con un valor p = 0,05. Resultados: se observó una prevalencia de fibrosis hepática significativa y cirrosis del 17%. Los factores asociados a la presencia de fibrosis hepática fueron los antecedentes de enfermedad cerebrovascular, la enfermedad vascular periférica, el índice de masa corporal (IMC), el colesterol total, la hemoglobina glicosilada, el sodio y el aspartato-aminotransferasa (AST). No se observó relación entre el puntaje de NAFLD (enfermedad del hígado graso no alcohólico), el índice APRI (AST to Platelet Ratio Index) y la presencia de fibrosis. Conclusión: la prevalencia de fibrosis hepática significativa en pacientes con diabetes y ERCT es similar a la reportada en otras poblaciones de pacientes con diabetes. Sin embargo, algunos factores, como el IMC, podrían comportarse de forma diferente y favorecer la aparición de lesión hepática con grados menores de obesidad a los reportados previamente en la literatura.

Marsupial position on life-history continua and the potential contribution of life-history traits to population growth.

Previous studies have suggested that mammal life history varies along the fast-slow continuum and that, in eutherians, this continuum is linked to variation in the potential contribution of survival and reproduction to population growth rate (λ). Fast eutherians mature early, have large litters and short lifespans, and exhibit high potential contribution of age at first reproduction and fertility to λ, while slow eutherians show high potential contribution of survival to λ. However, marsupials have typically been overlooked in comparative tests of mammalian life-history evolution. Here, we tested whether the eutherian life-history pattern extends to marsupials, and show that marsupial life-history trade-offs are organized along two major axes: (i) the reproductive output and dispersion axis, and (ii) the fast-slow continuum, with an additional association between adult survival and body mass. Life-history traits that potentially drive changes in λ are similar in eutherians and marsupials with slow life histories, but differ in fast marsupials; age at first reproduction is the most important trait contributing to λ and fertility contributes little. Marsupials have slower life histories than eutherians, and differences between these clades may derive from their contrasting reproductive modes; marsupials have slower development, growth and metabolism than eutherians of equivalent size.

Diagnostic Performance of 2D Shear Wave (2D-SWE) for Liver Fibrosis in Adults Undergoing Bariatric Surgery.

BACKGROUND: Among the most recent methods to diagnose liver fibrosis is 2D shear wave elastography (2D-SWE). However, the evidence in the Latin population is limited, and there is no consensus on the cutoff points for each stage of fibrosis. AIM: To evaluate the diagnostic performance of 2D-SWE for liver fibrosis in adults with obesity who underwent bariatric surgery (BS). METHODS: We conducted a cross-sectional study on patients with obesity who underwent BS between 2020 and 2021. Liver stiffness measurement was reported as the mean of valid measurements in kilopascals made with the 2D-SWE. The outcome was biopsy-proven liver fibrosis. ROC curves were constructed for significant fibrosis (F≥2) and advanced fibrosis (F≥3), with their respective area under the curve (AUC). To obtain the best cutoff point for each scenario, we used the Youden index. The 95% confidence intervals (95% CI) for each cutoff point were estimated by bootstrap with 1000 replications. RESULTS: We analyzed data from 227 patients. The mean age was 37.8 ± 11.1 years and 65.2% were women. Overall, the AUC for significant and advanced fibrosis was 0.54 (95% CI: 0.47-0.62) and 0.73 (95% CI: 0.60-0.87), respectively. For advanced fibrosis, higher AUCs were found among women (AUC: 0.82; 95% CI: 0.59-1.00) and among patients with morbid obesity (AUC: 0.78; 95% CI: 0.61-0.99). CONCLUSION: The 2D-SWE appears to be a valuable tool for screening advanced liver fibrosis in candidates for BS, mainly in the female population and in adults with morbid obesity.

Effect of Reducing the Size and Number of Faces of Polyhedral Specimen on Wood Characterization by Ultrasound.

The complete characterization of wood, with the determination of the 12 elastic constants that represent its orthotropy, is greatly relevant in applications employing structural calculation software programs. Ultrasound allows for such characterization with relative simplicity when compared to other methods. The polyhedron is considered the most appropriate specimen format for allowing the 12 constants to be calculated with a single specimen, and the traditionally used one is the 26-sided polyhedron, which, to be produced manually with more precision in directing the main directions of the wood, needs larger faces. The accuracy of this technique tends to be reduced when increasing the growth rings' inclination since the waves deviate from the main directions of orthotropy. This research aimed to verify whether it is possible to reduce the polyhedra dimension without affecting the results of the elastic parameters obtained in wood characterization by ultrasound. The results indicate that the dimension of the polyhedron can be reduced without prejudice to the results of the elastic parameters obtained by the ultrasound test and that, in the manual production process of the specimen, the best way to make this reduction is to eliminate the faces unused in the test, changing the polyhedron to 18 faces instead of 26. Reducing the number of faces simplifies the manufacturing process and thus increases the possibility of producing specimens with straighter growth rings and better-directed symmetry axes.

Lower prevalence of elevated liver stiffness measurements in people with type 2 diabetes taking sodium-glucose co-transporter 2 inhibitors or glucagon-like peptide-1 receptor agonists.

INTRODUCTION AND OBJECTIVES: Among people with type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD) is very common and has an increased risk of clinically significant liver disease. The use of sodium-glucose co-transporter 2 (SGLT2i) inhibitors and glucagon-like peptide-1 (GLP-1a) receptor agonists is endorsed to reduce major cardiovascular events and/or progression of chronic kidney disease. Their prevalence of use in people with T2D and co-existent NAFLD remains unclear. We sought to determine the prevalence of use of these medications at two different time periods, and their association with prevalence of clinically significant liver disease. MATERIALS AND METHODS: Consecutive people with type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) were recruited from diabetes clinics between Jun-2021 and Jun-2022 ('current' cohort). Liver stiffness measurements (LSM) using FibroScan were performed. Medication data were collected prospectively at recruitment and verified with the dispensing pharmacy or general practitioner medical records. Data for a historical cohort with NAFLD and T2D recruited from the same clinics during 2015-2017 ('historical' cohort) were available. Logistic regression was used to evaluate factors associated with LSM <8.0 or ≥8 kPa (clinically significant fibrosis). RESULTS: There were 292 participants, 177 in the historical cohort and 115 in the current cohort. In the current cohort, 57.4% of patients with T2D and NAFLD were taking a GLP-1a and 42.6% were taking a SGLT2i; a 2.6 to 3.4-fold higher prevalence than in 2015-2017. A lower proportion of the current cohort (23.9% compared to 38.4%) had clinically significant fibrosis (LSM ≥8 kPa; p = 0.012). When the cohorts were pooled and differences adjusted for in multivariable logistic regression analysis, patients taking a GLP-1a or a SGLT2i were 2 times more likely to have a lower LSM (<8 kPa) compared to patients not taking these drugs (OR=2.05, 95%CI 1.07-3.94, p = 0.03 and OR 2.07 95%CI 1.04-4.11, p = 0.04, respectively). CONCLUSIONS: The observation of a lower LSM in people taking SGLT2i and/or GLP-1a following adjustment for other relevant clinico-demographic variables provides support for clinical trials to assess their efficacy in reducing the progression of NAFLD.

Bezafibrate reduces the damage, activation and mechanical properties of lung fibroblast cells induced by hydrogen peroxide.

In pulmonary fibrosis, the proliferation of fibroblasts and their differentiation into myofibroblasts is often caused by tissue damage, such as oxidative damage caused by reactive oxygen species, which leads to progressive rupture and thus destruction of the alveolar architecture, resulting in cell proliferation and tissue remodeling. Bezafibrate (BZF) is an important member of the peroxisome proliferator-activated receptor (PPARs) family agonists, used in clinical practice as antihyperlipidemic. However, the antifibrotic effects of BZF are still poorly studied. The objective of this study was to evaluate the effects of BZF on pulmonary oxidative damage in lung fibroblast cells. MRC-5 cells were treated with hydrogen peroxide (H2O2) to induce oxidative stress activation and BZF treatment was administered at the same moment as H2O2 induction. The outcomes evaluated were cell proliferation and cell viability; oxidative stress markers such as reactive oxygen species (ROS), catalase (CAT) levels and thiobarbituric acid reactive substances (TBARS); col-1 and α-SMA mRNA expression and cellular elasticity through Young's modulus analysis evaluated by atomic force microscopy (AFM). The H2O2-induced oxidative damage decreased the cell viability and increased ROS levels and decreased CAT activity in MRC-5 cells. The expression of α-SMA and the cell stiffness increased in response to H2O2 treatment. Treatment with BZF decreased the MRC-5 cell proliferation, ROS levels, reestablished CAT levels, decreased the mRNA expression of type I collagen protein (col-1) and α-smooth muscle actin (α-SMA), and cellular elasticity even with H2O2 induction. Our results suggest that BZF has a potential protective effect on H2O2-induced oxidative stress. These results are based on an in vitro experiment, derived from a fetal lung cell line and may emerge as a possible new therapy for the treatment of pulmonary fibrosis.

Hepatic fibrosis: a manifestation of the liver disease evolution in patients with Ataxia-telangiectasia.

BACKGROUND: Ataxia-telangiectasia (A-T) is a DNA repair disorder characterized by changes in several organs and systems. Advances in clinical protocols have resulted in increased survival of A-T patients, however disease progression is evident, mainly through metabolic and liver changes. OBJECTIVE: To identify the frequency of significant hepatic fibrosis in A-T patients and to verify the association with metabolic alterations and degree of ataxia. METHODS: This is a cross-sectional study that included 25 A-T patients aged 5 to 31 years. Anthropometric data, liver, inflammatory, lipid metabolism and glucose biomarkers (oral glucose tolerance test with insulin curve-OGTT) were collected. The Cooperative Ataxia Rating Scale was applied to assess the degree of ataxia. The following were calculated: Homeostasis Model Assessment-Insulin Resistance, Homeostasis Model Assessment-Adiponectin (HOMA-AD), Matsuda index, aspartate aminotransferase (AST): platelet ratio index, nonalcoholic fatty liver disease fibrosis score and BARD score. Liver ultrasonography and transient liver elastography by FibroScan® were performed. RESULTS: Significant hepatic fibrosis was observed in 5/25 (20%). Patients in the group with significant hepatic fibrosis were older (p < 0.001), had lower platelet count values (p = 0.027), serum albumin (p = 0.019), HDL-c (p = 0.013) and Matsuda index (p = 0.044); and high values of LDL-c (p = 0.049), AST (p = 0.001), alanine aminotransferase (p = 0.002), gamma-glutamyl transferase (p = 0.001), ferritin (p = 0.001), 120-min glycemia by OGTT (p = 0.049), HOMA-AD (p = 0.016) and degree of ataxia (p = 0.009). CONCLUSIONS: A non-invasive diagnosis of significant hepatic fibrosis was observed in 20% of A-T patients associated with changes in liver enzymes, ferritin, increased HOMA-AD, and the severity of ataxia in comparison with patients without hepatic fibrosis.

Anisotropic behavior of mechanical properties for thea- andc-domains in a (001) BaTiO3single crystal.

Barium titanate (BaTiO3) single crystal with a tetragonal phase was characterized by nanoindentation. Elastic and elastic-plastic deformation regimes were obtained. The main objective was the evaluation of the anisotropic behavior related to mechanical properties associated with the cross-section of the ferroelectrica- andc-domains (In-plane and out-of-plane) in (001) configuration domains. This behavior was evaluated along a line perpendicular to the between domains, which demonstrated that the mechanical properties of the BaTiO3single crystal depend on the distance from due to the effect of the influence of the neighbor domain. A three-dimensional (3D) finite element (FE) model was developed to simulate mechanical effects revealed by the nanoindentations test. The FE simulation demonstrated that there is no simple isotropic mechanical behavior associated with the domain type. Numerical simulations and experiments performed to study ferroelastic switching domains in BaTiO3crystals revealed the interaction of the 90°-cadomain with the indentation position.

Systematic review and meta-analysis: Transient elastography compared to liver biopsy for staging of liver fibrosis in primary biliary cholangitis.

INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) is an autoimmune liver disease, with 60% of patients being asymptomatic at diagnosis and 30% progressing rapidly into liver fibrosis. Liver biopsy is standard for staging fibrosis, but performance of non-invasive methods such as transient elastography (TE) have not been evaluated. We conducted a meta-analysis of articles up to May 2022 to evaluate the performance of TE compared with liver biopsy in adult patients with PBC. MATERIALS AND METHODS: Two reviewers performed the search and assessed which articles were included. The quality of each study was evaluated according to QUADAS-2 and NOS. Meta-analysis of sensitivity and specificity was conducted with a bivariate random-effects model. The protocol was registered in PROSPERO, ID CRD42020199915. RESULTS: Four studies involving 377 patients were included. Only stages F3 and F4 were computed in the meta-analysis. TE had a pooled sensitivity of 68% and specificity of 92% for stage F3 and a pooled sensitivity of 90% and specificity of 94% for stage F4. The AUROC curves were 0.91 (95% Confidence Interval (CI) 0.88-0.93) and 0.97 (95% CI 0.96-0.98) for stages F3 and F4, respectively. The mean cut-off points of TE for stage F3 were 9.28 kPa (95% CI 4.98-13.57) and for stage F4 were 15.2 kPa (95% CI 7.02-23.37). CONCLUSIONS: TE performance compared with liver biopsy in adult patients with PBC was excellent for staging liver fibrosis and was able to rule out cirrhosis in clinical practice.

Role of galectin-3 in the elastic response of radial growth phase melanoma cancer cells.

Melanoma is originated from the malignant transformation of the melanocytes and is characterized by a high rate of invasion, the more serious stage compromising deeper layers of the skin and eventually leading to the metastasis. A high mortality due to melanoma lesion persists because most of melanoma lesions are detected in advanced stages, which decreases the chances of survival. The identification of the principal mechanics implicated in the development and progression of melanoma is essential to devise new early diagnosis strategies. Cell mechanics is related with a lot of cellular functions and processes, for instance motility, differentiation, migration and invasion. In particular, the elastic modulus (Young's modulus) is a very explored parameter to describe the cell mechanical properties; most cancer cells reported in the literature smaller elasticity modulus. In this work, we show that the elastic modulus of melanoma cells lacking galectin-3 is significantly lower than those of melanoma cells expressing galectin-3. More interestingly, the gradient of elastic modulus in cells from the nuclear region towards the cell periphery is more pronounced in shGal3 cells. RESEARCH HIGHLIGHTS: AFM imaging and force spectroscopy were used to investigate the morphology and elasticity properties of healthy HaCaT cells and melanoma cells WM1366, with (shSCR) and without (shGal3) expression of galectin-3. It is shown the effect of galectin-3 protein on the elastic properties of cells: the cells without expression of galectin-3 presents lower elastic modulus. By the results, we suggest here that galectin-3 could be used as an effective biomarker of malignancy in both melanoma diagnostic and prognosis.