RESUMEN

The study aims to evaluate corneal healing post amniotic membrane transplantation in controlled corneal defects, justifying its application in routine ophthalmology practice. The objective is to establish a reliable method for assessing the repair process. In three groups of six adult New Zealand rabbits, keratectomy and a monolayer transplant of dehydrated human amniotic membrane (AM) were conducted in the left eye (OS) with the right eye (OD) serving as the control eye. Clinical signs were assessed, and both eyes were enucleated at 1, 2, and 4 weeks for optical coherence tomography (OCT) measurements and histological analysis, collecting data from different epithelium, stroma, and limbus regions. This study was conducted using a formula that combines histologic data categorizing their presence and/or type as beneficial for corneal repair. No statistically significant differences were found between the experimental and control eyes regarding all clinical signs and OCT measurements. However, a linear model using histopathological results showed a period-implant mode interaction with statistical significance (p=0.010). The use of the single-layer amniotic membrane resulted in improved corneal recovery with the stromal side showing better performance in the first week and the epithelial side proving to be more effective than the stromal side in the long term. For the first time, a statistical formula employing histopathological data is introduced to determine corneal recovery, potentially offering a more accurate and reliable method compared with the observation of clinical signs and corneal measurements with OCT.

RESUMEN

Clofazimine is included in drug regimens to treat rifampicin/drug-resistant tuberculosis (DR-TB), but there is little information about its interaction with other drugs in DR-TB regimens. We evaluated the pharmacokinetic interaction between clofazimine and isoniazid, linezolid, levofloxacin, and cycloserine, dosed as terizidone. Newly diagnosed adults with DR-TB at Klerksdorp/Tshepong Hospital, South Africa, were started on the then-standard treatment with clofazimine temporarily excluded for the initial 2 weeks. Pharmacokinetic sampling was done immediately before and 3 weeks after starting clofazimine, and drug concentrations were determined using validated liquid chromatography-tandem mass spectrometry assays. The data were interpreted with population pharmacokinetics in NONMEM v7.5.1 to explore the impact of clofazimine co-administration and other relevant covariates on the pharmacokinetics of isoniazid, linezolid, levofloxacin, and cycloserine. Clofazimine, isoniazid, linezolid, levofloxacin, and cycloserine data were available for 16, 27, 21, 21, and 6 participants, respectively. The median age and weight for the full cohort were 39 years and 52 kg, respectively. Clofazimine exposures were in the expected range, and its addition to the regimen did not significantly affect the pharmacokinetics of the other drugs except levofloxacin, for which it caused a 15% reduction in clearance. A posteriori power size calculations predicted that our sample sizes had 97%, 90%, and 87% power at P < 0.05 to detect a 30% change in clearance of isoniazid, linezolid, and cycloserine, respectively. Although clofazimine increased the area under the curve of levofloxacin by 19%, this is unlikely to be of great clinical significance, and the lack of interaction with other drugs tested is reassuring.

Asunto(s)

Antituberculosos , Clofazimina , Cicloserina , Interacciones Farmacológicas , Isoniazida , Levofloxacino , Linezolid , Tuberculosis Resistente a Múltiples Medicamentos , Clofazimina/farmacocinética , Clofazimina/uso terapéutico , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Antituberculosos/farmacocinética , Antituberculosos/uso terapéutico , Masculino , Femenino , Linezolid/farmacocinética , Linezolid/uso terapéutico , Isoniazida/farmacocinética , Isoniazida/uso terapéutico , Levofloxacino/farmacocinética , Levofloxacino/uso terapéutico , Cicloserina/farmacocinética , Cicloserina/uso terapéutico , Persona de Mediana Edad , Sudáfrica , Adulto Joven , Quimioterapia Combinada

RESUMEN

The latest advances in technology and materials science have catalyzed a transformative shift towards the adoption of environmentally conscious and lightweight materials across key sectors such as aeronautics, biomedical, and automotive industries. Noteworthy among these innovations are the magnesium-aluminum (Mg-Al) alloys employed in aeronautical applications, contributing to the overall reduction in aircraft weight and subsequently diminishing fuel consumption and mitigating atmospheric emissions. The present work delves into a study of the anti-corrosive properties inherent in various sol-gel coatings, leveraging a range of environmentally friendly corrosion inhibitors, specifically tailored for samples of the AZ61 alloy. Methodologically, the work involves the synthesis and application of sol-gel coatings on AZ61 alloy containing eco-friendly inhibitors: L-cysteine, N-acetyl-cysteine, curcumin and methylene blue. Subsequently, an accelerated corrosion test in a simulated saline environment is performed. Through microstructural and compositional analyses, the best inhibitors responses are achieved with inhibitors containing S, N heteroatoms and conjugated double bonds in their structure, probably due to the creation of a continuous MgCl2 layer. This research contributes to the ongoing discourse on protective eco-coatings, aligning with the broader paradigm shift towards sustainable and lightweight materials in key industries.

RESUMEN

Preclinical and clinical studies suggest that hypothyroidism might cause hepatic endocrine and metabolic disturbances with features that mimic deficiencies of testosterone and/or GH. The absence of physiological interactions between testosterone and GH can be linked to male differentiated liver diseases. Testosterone plays relevant physiological effects on somatotropic-liver axis and liver composition and the liver is a primary organ of interactions between testosterone and GH. However, testosterone exerts many effects on liver through complex and poorly understood mechanisms. Testosterone impacts liver functions by binding to the Androgen Receptor, and, indirectly, through its conversion to estradiol, and cooperation with GH. However, the role of testosterone, and its interaction with GH, in the hypothyroid liver, remains unclear. In the present work, the effects of testosterone, and how they impact on GH-regulated whole transcriptome and lipid composition in the liver, were studied in the context of adult hypothyroid-orchiectomized rats. Testosterone replacement positively modulated somatotropic-liver axis and impacted liver transcriptome involved in lipid and glucose metabolism. In addition, testosterone enhanced the effects of GH on the transcriptome linked to lipid biosynthesis, oxidation-reduction, and metabolism of unsaturated and long-chain fatty acids (FA). However, testosterone decreased the hepatic content of cholesterol esters and triacylglycerols and increased fatty acids whereas GH increased neutral lipids and decreased polar lipids. Biological network analysis of the effects of testosterone on GH-regulated transcriptome confirmed a close connection with crucial proteins involved in steroid and fatty acid metabolism. Taken together, this comprehensive analysis of gene expression and lipid profiling in hypothyroid male liver reveals a functional interplay between testosterone and pulsed GH administration.

Asunto(s)

Hormona del Crecimiento , Hipotiroidismo , Animales , Masculino , Ratas , Ácidos Grasos/metabolismo , Perfilación de la Expresión Génica , Hormona del Crecimiento/metabolismo , Hipotiroidismo/complicaciones , Hipotiroidismo/genética , Hipotiroidismo/metabolismo , Hígado/metabolismo , Testosterona/metabolismo , Transcriptoma

RESUMEN

Leishmaniasis is a zoonotic disease caused by a parasite of the genus Leishmania endemic in 102 countries around the world. Clinical features can be classified as cutaneous, mucocutaneous, and visceral leishmaniasis; this will depend on the species of leishmania responsible for the disease and the immunologic response of the host. We present the case of a 14-year-old male who started with a small papular lesion in the helix of the left ear, which later spread to the rest of the helix, tragus, and part of the auricular concha. On physical examination, an erythematous plaque with a scale that deforms the auricular surface was observed. In histopathology, acute and chronic inflammatory processes were observed with an accumulation of macrophages that contain amastigotes inside (Leishman Donovan bodies). The diagnosis of leishmaniasis represents a challenge in non-endemic regions. It is important to ask about travel history to endemic areas and perform assays to confirm the diagnosis and initiate treatment to prevent mortality and morbidity.

RESUMEN

The first people considered digital natives, the millennials, have already entered the teaching profession. As a result, we are faced with a remarkable generational diversity. This survey aimed to explore the generational change in teachers and the beginning of the incorporation of the first millennials (digital natives) into teaching. It was carried out through a qualitative study using focus groups and interviews with a total of 147 teachers. The main results found establish a generational clash between migrants and digital natives. This difference is present in the use and understanding of ICTs in the teaching task across the different teaching generations and in a generational diversity within the educational centres that has not been seen so far. However, this difference between teachers is also a condition that facilitates exchange between teachers of different generations. Junior teachers help veteran teachers in the use of ICTs and veteran teachers provide the expertise that new recruits lack.

RESUMEN

Today's environmental needs require the reduction of the weight of vehicles, thus reducing fuel consumption and associated emissions. For this reason, the use of light alloys is being studied, which, due to their reactivity, must be protected before use. In this work, the effectiveness of a hybrid sol-gel coating doped with various organic environmentally friendly corrosion inhibitors applied to an AA2024 lightweight aluminium alloy is evaluated. Some of the inhibitors tested are pH indicators, acting as both corrosion inhibitors and optical sensors for the surface of the alloy. Samples are subjected to a corrosion test in a simulated saline environment and characterised before and after the test. The experimental results regarding their best inhibitor performance for their potential application in the transport industry are evaluated.

RESUMEN

INTRODUCTION: BRAFV600E mutations have been associated with papillary thyroid carcinoma (PTC) histological types including tall-cell and classical, peritumoral infiltration, and nuclear signs, whereas cytological features such as plump cells and sickle nuclei have also been associated with favorable thyroid fine needle aspiration (FNA) results for this tumor. BRAF and RAS are considered early driver mutations that contribute to the development of BRAF-like PTCs and RAS-like PTCs. Our aim was to assess the possible association between all Bethesda System cytological features and thyroid FNAs for PTC and their potential predictive value for future BRAFV600E-related biopsies. METHODS: Our study analyzed 63 cases of PTCs operated on at our hospital over a 5-year period between 2005 and 2017 that had previously undergone FNA and had been classified by the Bethesda System. BRAFV600E was identified by pyrosequencing paraffin-embedded tissues and comparing the cytological signs with the Bethesda System. In addition, a statistical and predictive study of the diagnostic factors "non-follicular," "non-round nuclei," and "non-clear chromatin" was performed to discriminate BRAF-like signs from other hypothetical RAS-like follicular signs. RESULTS: BRAFV600E was detected in 43/63 cases (68.2%). Histological types were significant (p < 0.001), with the classical variant being the most prevalent 31/63 (49.2%) and independent by multivariate analysis odds ratio of 10.58 [2.67; 41.97]. Follicular cytological signs are negatively associated with BRAFV600E: follicular structure (p < 0.001), round nuclei (p = 0.015), and clear chromatin (p = 0.049), while the diagnostic factors: "non-follicular" (positive predictive value [PPV] 82.9, sensitivity 79.1, negative predictive value [NPV] 59.1, specificity 65.0), "non-round nuclei" (PPV 76.6, sensitivity 83.7, NPV 56.3, specificity 45.0), and "non-clear chromatin" (PPV 75.6, sensitivity 79.1, NPV 50.0, specificity 45.0) have predictive value for the mutation. There was no individual significance for the remaining cytological features. CONCLUSIONS: Our study found no association between cytomorphological signs of thyroid FNA and BRAFV600E mutation. Considering the Bethesda System, there is an association (p = 0.045) with numerous cases of mutated PTC in categories V and VI. Our results indicate, however, that the presence of signs referred to as "non-follicular," "non-round nuclei," and "non-clear chromatin" in biopsy of papillary thyroid carcinoma is predictive of BRAF type mutation, whereas follicular signs indicate a RAS type PTC, according to published literature. These results need to be confirmed or modified by further research.

Asunto(s)

Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Biopsia con Aguja Fina , Proteínas Proto-Oncogénicas B-raf/genética , Carcinoma Papilar/genética , Carcinoma Papilar/patología , Mutación , Cromatina

RESUMEN

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, but the precise intracellular mechanisms underlying the progression of this inflammation associated cancer are not well established. SOCS2 protein plays an important role in the carcinogenesis of different tumors by regulating cytokine signalling through the JAK/STAT axis. However, its role in HCC is unclear. Here, we investigate the role of SOCS2 in HCC progression and its potential as HCC biomarker. The effects of SOCS2 in HCC progression were evaluated in an experimental model of diethylnitrosamine (DEN)-induced HCC in C57BL/6 and SOCS2 deficient mice, in cultured hepatic cells, and in liver samples from HCC patients. Mice lacking SOCS2 showed higher liver tumor burden with increased malignancy grade, inflammation, fibrosis, and proliferation than their controls. Protein and gene expression analysis reported higher pSTAT5 and pSTAT3 activation, upregulation of different proteins involved in survival and proliferation, and increased levels of proinflammatory and pro-tumoral mediators in the absence of SOCS2. Clinically relevant, downregulated expression of SOCS2 was found in neoplasia from HCC patients compared to healthy liver tissue, correlating with the malignancy grade. In summary, our data show that lack of SOCS2 increases susceptibility to chemical-induced HCC and suggest the tumor suppressor role of this protein by regulating the oncogenic and inflammatory responses mediated by STAT5 and STAT3 in the liver. Hence, SOCS2 emerges as an attractive target molecule and potential biomarker to deepen in the study of HCC treatment.

Asunto(s)

Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Ratones Endogámicos C57BL , Proliferación Celular , Dietilnitrosamina/toxicidad , Proteínas Supresoras de la Señalización de Citocinas/genética , Proteínas Supresoras de la Señalización de Citocinas/metabolismo

RESUMEN

This letter aims to reply to Bratchenko and Bratchenko's comment on our paper "Feasibility of Raman spectroscopy as a potential in vivo tool to screen for pre-diabetes and diabetes." Our paper analyzed the feasibility of using in vivo Raman measurements combined with machine learning techniques to screen diabetic and prediabetic patients. We argued that this approach yields high overall accuracy (94.3%) while retaining a good capacity to distinguish between diabetic (area under the receiver-operating curve [AUC] = 0.86) and control classes (AUC = 0.97) and a moderate performance for the prediabetic class (AUC = 0.76). Bratchenko and Bratchenko's comment focuses on the possible overestimation of the proposed classification models and the absence of information on the age of participants. In this reply, we address their main concerns regarding our previous manuscript.

Asunto(s)

Diabetes Mellitus , Estado Prediabético , Humanos , Estado Prediabético/diagnóstico , Espectrometría Raman/métodos , Estudios de Factibilidad , Diabetes Mellitus/diagnóstico , Aprendizaje Automático

RESUMEN

The introduction of digital information and communication technologies has influenced many aspects of the teaching profession. In addition to their changing use in the classroom, these technologies have strongly impacted the work and professional development of teachers. In this study, which was framed within the R+D+i project DePrInEd, we analyzed the perceptions, beliefs, opinions, and attitudes of teachers on this subject. We conducted a qualitative study through interviews, with a thematic analysis addressing the duality of technology and change. The results indicated that these produced benefits and created difficulties in the teaching task, with the latter being more demanding. Teachers stated that one of the main difficulties they encountered was related to the evolution of students as a result of technology, both in the school and social contexts. This highlights the risk that its extensive use did not lead to the acquisition of other key competencies, including digital and media competencies, in the school environment. Finally, other dimensions that impacted the corporate intelligence of educational centers included the continuous adaptation and mastery of digital competence required by teachers regarding the changes in their tasks, as well as the excessive bureaucratization that technologies have necessitated.

Asunto(s)

Humanos , Algoritmos , Índice de Masa Corporal , Carcinoma Endometrioide , Neoplasias Endometriales/patología , Fenotipo , Inestabilidad de Microsatélites , Obesidad/genética

RESUMEN

In this article, we investigated the feasibility of using Raman spectroscopy and multivariate analysis method to noninvasively screen for prediabetes and diabetes in vivo. Raman measurements were performed on the skin from 56 patients with diabetes, 19 prediabetic patients and 32 healthy volunteers. These spectra were collected along with reference values provided by the standard glycated hemoglobin (HbA1c) assay. A multiclass principal component analysis and support vector machine (PCA-SVM) model was created from the labeled Raman spectra and was validated through a two-layer cross-validation scheme. Classification accuracy of the model was 94.3% with an area under the receiver operating characteristic curve AUC of 0.76 (0.65-0.84) for the prediabetic group, 0.86 (0.71-0.93) for the diabetic group and 0.97(0.93-0.99) for the control group. Our results suggest the feasibility of using Raman spectroscopy for the classification of prediabetes and diabetes in vivo.

Asunto(s)

Diabetes Mellitus , Estado Prediabético , Diabetes Mellitus/diagnóstico , Estudios de Factibilidad , Humanos , Estado Prediabético/diagnóstico , Análisis de Componente Principal , Espectrometría Raman/métodos , Máquina de Vectores de Soporte

RESUMEN

PURPOSE: In endometrial cancer, the incidence of mutations in mismatch repair genes (MMR) is estimated at 17-30%. Patients with alterations at this level (MSI) are known to have different clinical and anatomopathological characteristics than those without this genetic alteration (MSS). In this study, we aim to identify the MSI phenotype in patients who underwent hysterectomy for endometrial cancer. We assessed the correlation of this phenotype with anatomoclinical parameters such as obesity and histological subtype. METHODS/PATIENTS: Clinical and anatomopathological data were collected from 147 patients diagnosed with endometrial cancer and an immunohistochemical study of MMR system proteins was performed. PMS2 and MSH6 proteins were evaluated as primary screening and subsequent evaluation of MLH1 and MSH6, respectively, if the former were negative. Statistical association between the anatomopathological data and the immunohistochemical result was analyzed. RESULTS AND CONCLUSIONS: 22.4% of our patients were MSI phenotype. We obtained statistically significant differences by multivariate analysis between endometrioid subtype and higher FIGO classification grade with MSI phenotype and obesity with MSS phenotype. Given these statistical results, we propose a function for predicting the probability of being MSI phenotype taking into account the histological subtype (endometrioid/non-endometrioid carcinoma) and FIGO grade as well as obesity. This prediction may be useful prior to hysterectomy, for genetic study of the MLH1 promoter and subsequent genetic counseling.

Asunto(s)

Carcinoma Endometrioide , Neoplasias Endometriales , Algoritmos , Índice de Masa Corporal , Neoplasias Endometriales/patología , Femenino , Humanos , Inestabilidad de Microsatélites , Homólogo 1 de la Proteína MutL/genética , Homólogo 1 de la Proteína MutL/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Obesidad/genética , Fenotipo

RESUMEN

Physiological human fluid is a natural corrosive environment and can lead to serious corrosion and mechanical damages to light Mg-Al alloys used in prosthetics for biomedical applications. In this work, organic-inorganic hybrid coatings doped with various environmentally friendly and non-toxic corrosion inhibitors have been prepared by the sol-gel process for the corrosion protection of AZ61 magnesium alloys. Effectiveness has been evaluated by pH measurements, optical microscopy, and SEM during a standard corrosion test in a Hanks' Balanced Salt Solution. The results showed that the addition of an inhibitor to the sol-gel coating can improve significantly the corrosion performance, being an excellent barrier for the L-cysteine-doped hybrid sol-gel films. The incorporation of TiO2 nanoparticles, 2-Aminopyridine and quinine organic molecules slowed down the corrosion rate of the Mg-Al alloy. Graphene oxide seemed to have the same response to corrosion as the hybrid sol-gel coating without inhibitors.

RESUMEN

Linezolid is an oxazolidinone used to treat multidrug-resistant tuberculosis (MDR-TB), including in the recently-endorsed shorter 6-month treatment regimens. Due to its narrow therapeutic index, linezolid is often either dose-adjusted or discontinued due to intolerance or toxicity during treatment, and the optimal balance between linezolid efficacy and toxicity remains unclear. India carries a significant burden of MDR-TB cases in the world, but limited information on the pharmacokinetics of linezolid and minimum inhibitory concentration (MIC) distribution is available from Indian MDR-TB patients. We enrolled participants from a tertiary care centre in Mumbai, India, treated for MDR-TB and receiving linezolid daily doses of 600 or 300 mg. Pharmacokinetic visits were scheduled between 1 and 15 months after treatment initiation to undergo intensive or sparse blood sampling. Linezolid concentration versus time data were analysed using non-linear mixed-effects modelling, with simulations to evaluate doses for different scenarios. We enrolled 183 participants (121 females), with a median age of 26 years (interquartile range [IQR] 21-35), weight 55.0 kg (IQR 45.6-65.8), and fat-free mass 38.7 kg (IQR 32.7-46.0). Linezolid pharmacokinetics was best described by a one-compartment model with first-order elimination allometrically scaled by fat-free mass and transit compartment absorption. The typical clearance value was 3.81 L/h. Simulations predicted that treatment with 300 mg daily achieves a high probability of target attainment (PTA) when linezolid MIC was ≤0.25 mg/L (61.5% of participant samples tested), while 600 mg daily would be required if MIC were 0.5 mg/L (29% of samples). While linezolid 300 mg daily is predicted to achieve effective targets for the majority of adults with MDR-TB, it failed to achieve the therapeutic target for 21% participants. A dose of 600 mg had a PTA >90% for all susceptible samples, but with a higher likelihood of exceeding toxicity thresholds (31% vs 9.6%). These data suggest potential benefit to individualized dosing taking host and microbial characteristics into account to improve the likelihood of treatment efficacy while minimizing risk of toxicity from linezolid for the treatment of MDR-TB. Further prospective evaluation in different clinical settings is urgently needed to inform safety and efficacy of these lower doses.

RESUMEN

El pólipo fibroide inflamatorio gástrico es una entidad clínico-patológica rara, la cual representa una incidencia del 0,1 % de todos los pólipos gástricos.Con mayor frecuencia afecta a adultos en un amplio rango de edad, cuyo pico de incidencia es entre la sexta y séptima décadas de la vida. Las lesiones son predominantemente asintomáticas y se detectan incidentalmente en la endoscopia o en las imágenes realizadas por causas no relacionadas. Ocasionalmente, los pólipos fibroides provocan sintomatología, ya sea por su gran tamaño que causa obstrucción de la salida gástrica, o por la erosión de la mucosa que se presenta con sangrado gastrointestinal superior manifiesto u oculto.

---

The gastric inflammatory fibroid polyp is a rare clinical-pathological entity, representing an incidence of 0.1% of all gastric polyps. It most frequently affects adults in a wide age range, and its incidence peak is between the sixth and seventh decades of life. The lesions remain predominantly asymptomatic and are detected incidentally on endoscopy or imaging for unrelated causes. Occasionally, fibroid polyps cause symptoms due to their large size causing gastric outlet obstruction, or due to mucosal erosion presenting with overt or occult upper gastrointestinal bleeding.

Asunto(s)

Antro Pilórico , Tomografía Computarizada por Rayos X , Dispepsia