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Latin American region is a high-burden setting for tuberculosis where multidrug-resistant tuberculosis (MDR-TB) is among the main challenge to move forward the End TB Strategy goals. It has been shown that MDR-TB is associated to certain Mycobacterium tuberculosis (MTB) lineages like L2-Beijing sublineage or L4-LAM. Although L2-Beijing is present in South America, the L4 lineage is the most prevalent with values ranging from 75% to 99% depending on the country. Within L4, Latin American-Mediterranean (LAM) family is the most prevalent. Moreover, within LAM, RDRio subfamily is present in high prevalence in several countries in South America like Venezuela or Brazil. RDRio has been associated to MDR-TB in several studies in Brazil but more epidemiological information is needed for South America. Here we discuss the problem of MDR-TB in Latin America and the potential threat that RDRio could represent. At this time, more molecular epidemiology studies are necessary to improve TB surveillance programs in Latin America by tracking MTB strains potentially responsible for MDR-TB spread.
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Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Humanos , América Latina/epidemiología , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Prevalencia , Farmacorresistencia Bacteriana MúltipleRESUMEN
The objective of this study was to develop and characterize a novel hyaluronic acid (HA) 3D scaffold integrated with gelatin microparticles for sustained-delivery applications. To achieve this goal, the delivery microparticles were synthesized and thoroughly characterized, focusing on their crosslinking mechanisms (vanillin and genipin), degradation profiles, and release kinetics. Additionally, the cytotoxicity of the system was assessed, and its impact on the cell adhesion and distribution using mouse fibroblasts was examined. The combination of both biomaterials offers a novel platform for the gradual release of various factors encapsulated within the microparticles while simultaneously providing cell protection, support, and controlled factor dispersion due to the HA 3D scaffold matrix. Hence, this system offers a platform for addressing injure repair by continuously releasing specific encapsulated factors for optimal tissue regeneration. Additionally, by leveraging the properties of HA conjugates with small drug molecules, we can enhance the solubility, targeting capabilities, and cellular absorption, as well as prolong the system stability and half-life. As a result, this integrated approach presents a versatile strategy for therapeutic interventions aimed at promoting tissue repair and regeneration.
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Polycaprolactone (PCL) scaffolds have demonstrated an effectiveness in articular cartilage regeneration due to their biomechanical properties. On the other hand, alginate hydrogels generate a 3D environment with great chondrogenic potential. Our aim is to generate a mixed PCL/alginate scaffold that combines the chondrogenic properties of the two biomaterials. Porous PCL scaffolds were manufactured using a modified salt-leaching method and embedded in a culture medium or alginate in the presence or absence of chondrocytes. The chondrogenic capacity was studied in vitro. Type II collagen and aggrecan were measured by immunofluorescence, cell morphology by F-actin fluorescence staining and gene expression of COL1A1, COL2A1, ACAN, COL10A1, VEGF, RUNX1 and SOX6 by reverse transcription polymerase chain reaction (RT-PCR). The biocompatibility of the scaffolds was determined in vivo using athymic nude mice and assessed by histopathological and morphometric analysis. Alginate improved the chondrogenic potential of PCL in vitro by increasing the expression of type II collagen and aggrecan, as well as other markers related to chondrogenesis. All scaffolds showed good biocompatibility in the in vivo model. The presence of cells in the scaffolds induced an increase in vascularization of the PCL/alginate scaffolds. The results presented here reinforce the benefits of the combined use of PCL and alginate for the regeneration of articular cartilage.
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INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.
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Enfermedades Inflamatorias del Intestino , Pancreatitis , Sistema de Registros , Humanos , Femenino , Pancreatitis/inducido químicamente , Pancreatitis/genética , Masculino , Adulto , Estudios de Casos y Controles , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Persona de Mediana Edad , Predisposición Genética a la Enfermedad , Factores de Riesgo , Variación Genética , Mercaptopurina/efectos adversos , Mercaptopurina/uso terapéuticoRESUMEN
INTRODUCTION: Wilson's disease (WD) is associated with a variety of movement disorders and progressive neurological dysfunction. The aim of this study was to correlate baseline brain magnetic resonance imaging (MRI) features with clinical phenotype and long-term outcomes in chronically treated WD patients. METHODS: Patients were retrospectively selected from an institutional database. Two experienced neuroradiologists reviewed baseline brain MRI. Functional assessment was performed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) scale, and disease severity was classified using the Global Assessment Scale for Wilson's Disease (GASWD). RESULTS: Of 27 patients selected, 14 were female (51.9%), with a mean (standard deviation [SD]) age at onset of 19.5 (7.1) years. Neurological symptoms developed in 22 patients (81.5%), with hyperkinetic symptoms being the most common (70.4%). Baseline brain MRI showed abnormal findings in 18 cases (66.7%), including T2 hyperintensities in 59.3% and atrophy in 29.6%. After a mean (SD) follow-up of 20.9 (11.0) years, WD patients had a mean score of 19.2 (10.2) on WHODAS 2.0 and 6.4 (5.7) on GASWD. The presence of hyperkinetic symptoms correlated with putaminal T2 hyperintensities (p = 0.003), putaminal T2 hypointensities (p = 0.009), and mesencephalic T2 hyperintensities (p = 0.009). Increased functional disability was associated with brain atrophy (p = 0.007), diffusion abnormalities (p = 0.013), and burden of T2 hyperintensities (p = 0.002). A stepwise regression model identified atrophy as a predictor of increased WHODAS 2.0 (p = 0.023) and GASWD (p = 0.007) scores. CONCLUSIONS: Atrophy and, to a lesser extent, deep T2 hyperintensity are associated with functional disability and disease severity in long-term follow-up of WD patients.
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Encéfalo , Degeneración Hepatolenticular , Imagen por Resonancia Magnética , Fenotipo , Humanos , Femenino , Degeneración Hepatolenticular/diagnóstico por imagen , Degeneración Hepatolenticular/fisiopatología , Degeneración Hepatolenticular/patología , Masculino , Adulto Joven , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatología , Adulto , Estudios Retrospectivos , Adolescente , Neuroimagen/métodos , Índice de Severidad de la Enfermedad , Evaluación de la Discapacidad , Niño , Estudios de Seguimiento , Atrofia/patologíaRESUMEN
Accurate DNA replication and transcription elongation are crucial for preventing the accumulation of unreplicated DNA and genomic instability. Cells have evolved multiple mechanisms to deal with impaired replication fork progression, challenged by both intrinsic and extrinsic impediments. The bacterium Bacillus subtilis, which adopts multiple forms of differentiation and development, serves as an excellent model system for studying the pathways required to cope with replication stress to preserve genomic stability. This review focuses on the genetics, single molecule choreography, and biochemical properties of the proteins that act to circumvent the replicative arrest allowing the resumption of DNA synthesis. The RecA recombinase, its mediators (RecO, RecR, and RadA/Sms) and modulators (RecF, RecX, RarA, RecU, RecD2, and PcrA), repair licensing (DisA), fork remodelers (RuvAB, RecG, RecD2, RadA/Sms, and PriA), Holliday junction resolvase (RecU), nucleases (RnhC and DinG), and translesion synthesis DNA polymerases (PolY1 and PolY2) are key functions required to overcome a replication stress, provided that the fork does not collapse.
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Bacillus subtilis , Proteínas de Escherichia coli , Bacillus subtilis/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Replicación del ADN/genética , ADN/metabolismo , Proteínas de Escherichia coli/genéticaRESUMEN
BACKGROUND: Patients on hemodialysis are particularly vulnerable to COVID-19 and may have a reduced response to vaccination because of a decreased immune response. The nutritional status before or during the infection could also impact on the clinical effectiveness of vaccination. OBJECTIVES: We aim to describe the evolution of clinical and nutritional biomarkers of hemodialysis patients infected with SARS-CoV-2 and to assess their association with vaccination status. METHODS: An observational, analytic, longitudinal, retrospective multicenter study was carried out in 82 patients on hemodialysis with SARS-CoV-2 infection. Nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI), anthropometry, and biochemical parameters. The association of the vaccine doses with clinical- and nutritional-related variables was also evaluated. RESULTS: The percentage of vaccinated patients was similar to that of nonvaccinated patients. Before infection, most of the patients were malnourished. They presented lower albumin, creatinine, and urea levels than the well-nourished patients. Significant deterioration of nutritional status after infection was evidenced considering GNRI score, dry weight, and body mass index. Albumin and creatinine also decreased significantly after infection, whereas C-reactive protein increased in the acute phase. Significant inverse correlation was found between the variation of post-pre GNRI scores and basal albumin and C-reactive protein at 7 days. In addition, we observed the opposite trend between albumin at 30 days and basal cholesterol. A negative value in the GNRI variation was associated with bilateral pneumonia, need for hospitalization, and nutritional support. Vaccinated patients presented substantially less bilateral pneumonia and hospitalization. No significant effects were observed between vaccine doses and the variation in nutritional status, although a positive correlation was detected with the albumin at 7 days and C-reactive protein before infection and the number of vaccine doses received. DISCUSSION: COVID-19 is associated with affectations in the nutritional status and biomarkers in hemodialysis patients. In this study, vaccines have shown a protective effect against the clinical consequences of COVID. However, they have shown limitations in preventing the deterioration of nutritional status after infection. The results highlight the importance of promoting the vaccination in these patients as well as incorporating nutritional assessment before, during, and after the infection.
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COVID-19 , Vacunas , Humanos , Anciano , SARS-CoV-2 , Proteína C-Reactiva , Creatinina , COVID-19/prevención & control , Estado Nutricional , Diálisis Renal/efectos adversos , Biomarcadores , VacunaciónRESUMEN
The endometrium plays a vital role in fertility, providing a receptive environment for embryo implantation and development. Understanding the endometrial physiology is essential for developing new strategies to improve reproductive healthcare. Human endometrial organoids (hEOs) are emerging as powerful models for translational research and personalized medicine. However, most hEOs are cultured in a 3D microenvironment that significantly differs from the human endometrium, limiting their applicability in bioengineering. This study presents a hybrid endometrial-derived hydrogel that combines the rigidity of PuraMatrix (PM) with the natural scaffold components and interactions of a porcine decellularized endometrial extracellular matrix (EndoECM) hydrogel. This hydrogel provides outstanding support for hEO culture, enhances hEO differentiation efficiency due to its biochemical similarity with the native tissue, exhibits superior in vivo stability, and demonstrates xenogeneic biocompatibility in mice over a 2-week period. Taken together, these attributes position this hybrid endometrial-derived hydrogel as a promising biomaterial for regenerative treatments in reproductive medicine.
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OBJECTIVE: A common consultation since the beginning of the vaccination campaign against COVID-19 was related to people with a history of allergy to drugs or other vaccines. The objective of the study was to describe what happened after the administration of the vaccine against COVID-19 in people with a history of moderate and severe allergy, vaccinated against COVID-19 in a Primary Care Emergency Center (PCEC). METHODS: Observational descriptive study with sixty-four people with a history of moderate and severe allergy was carried out, vaccinated in PCEP, between May and October 2021, in the Barcelonés Nord and Maresme (Barcelona province), after assessment by primary care pharmacologists and pharmacists. The percentage of people with adverse events that occurred after vaccination during their stay in the PCEP, the types detected and severity were calculated. Subsequently, a telephone survey was conducted to determine patient satisfaction. A descriptive analysis (calculation of proportions) was performed. RESULTS: The mean age of 49.7 years (from twelve to ninety-four years) and 90.6% were women. 87.5% of the administered vaccines were Comirnaty®. Adverse events occurring after vaccination were detected in fifteen patients (23.4%), of whom four (6.25%) were manifestations of hypersensitivity, all classified as mild. The reasons for vaccination were a history of allergy to NSAIDs (45.3%), antibiotics (32.8%), analgesics (17.2%), vaccines (28.1%), other substances (40.6%) and anaphylaxis (26.6%). The degree of general satisfaction was 9.11 (out of 10). CONCLUSIONS: The percentage of patients with a history of anaphylaxis and allergic drug reactions who present hypersensitivity reactions to COVID-19 vaccines is 6.25% and all are mild.
OBJETIVO: Una consulta habitual desde el inicio de la campaña de vacunación frente a la COVID-19 fue la relacionada con personas que tienen antecedentes de alergia a fármacos u otras vacunas. El objetivo del estudio fue describir lo ocurrido tras la administración de la vacuna frente a la COVID-19 en personas con antecedentes de alergia moderada y grave, en un Centro de Urgencias de Atención Primaria (CUAP). METODOS: Se realizó un estudio observacional descriptivo con sesenta y cuatro personas que tenían antecedentes de alergia moderada y grave, vacunadas en CUAP, entre mayo y octubre de 2021, en el Barcelonés Nord i Maresme (provincia de Barcelona), previa valoración por farmacólogos y farmacéuticos de Atención Primaria. Se calculó el porcentaje de personas con acontecimientos adversos ocurridos tras la vacunación en el transcurso de su estancia en el CUAP, los tipos detectados y la gravedad. Posteriormente, se realizó una encuesta telefónica para conocer la satisfacción de los pacientes. Se realizó un análisis descriptivo (cálculo de proporciones). RESULTADOS: La media de edad de las personas participantes fue de 49,7 años (de doce a noventa y cuatro años) y el 90,6% fueron mujeres. El 87,5% de las vacunas administradas fue Comirnaty®. Se detectaron acontecimientos adversos ocurridos tras la vacunación en quince pacientes (23,4%), de los que en cuatro casos (6,25%) fueron manifestaciones de hipersensibilidad, todas catalogadas como leves. Los motivos de vacunación fueron antecedentes de alergia a AINE (45,3%), antibióticos (32,8%), analgésicos (17,2%), vacunas (28,1%), otras sustancias (40,6%) y anafilaxia (26,6%). El grado de satisfacción general fue de 9,11 (sobre 10). CONCLUSIONES: El porcentaje de pacientes con antecedentes de anafilaxia y reacciones alérgicas a medicamentos que presentan reacciones de hipersensibilidad a las vacunas frente a la COVID-19 es del 6,25% y todas son leves.
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Anafilaxia , Vacunas contra la COVID-19 , COVID-19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anafilaxia/inducido químicamente , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , España , Niño , Adolescente , Adulto Joven , Adulto , Anciano , Anciano de 80 o más AñosRESUMEN
The most prevalent genetic form of inherited arrhythmogenic cardiomyopathy (ACM) is caused by mutations in desmosomal plakophilin-2 (PKP2). By studying pathogenic deletion mutations in the desmosomal protein PKP2, here we identify a general mechanism by which PKP2 delocalization restricts actomyosin network organization and cardiac sarcomeric contraction in this untreatable disease. Computational modeling of PKP2 variants reveals that the carboxy-terminal (CT) domain is required for N-terminal domain stabilization, which determines PKP2 cortical localization and function. In mutant PKP2 cells the expression of the interacting protein MYH10 rescues actomyosin disorganization. Conversely, dominant-negative MYH10 mutant expression mimics the pathogenic CT-deletion PKP2 mutant causing actin network abnormalities and right ventricle systolic dysfunction. A chemical activator of non-muscle myosins, 4-hydroxyacetophenone (4-HAP), also restores normal contractility. Our findings demonstrate that activation of MYH10 corrects the deleterious effect of PKP2 mutant over systolic cardiac contraction, with potential implications for ACM therapy.
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Displasia Ventricular Derecha Arritmogénica , Cardiomiopatías , Humanos , Displasia Ventricular Derecha Arritmogénica/genética , Displasia Ventricular Derecha Arritmogénica/metabolismo , Actomiosina/genética , Mutación , Cardiomiopatías/genética , Placofilinas/genética , Placofilinas/metabolismoRESUMEN
Fundamentos: Una consulta habitual desde el inicio de la campaña de vacunación frente a la COVID-19 fue la relacionada con personas que tienen antecedentes de alergia a fármacos u otras vacunas. El objetivo del estudio fue describir lo ocurrido tras la administración de la vacuna frente a la COVID-19 en personas con antecedentes de alergia moderada y grave, en un Centro de Urgencias de Atención Primaria (CUAP). Métodos: Se realizó un estudio observacional descriptivo con sesenta y cuatro personas que tenían antecedentes de alergia moderada y grave, vacunadas en CUAP, entre mayo y octubre de 2021, en el Barcelonés Nord i Maresme (provincia de Barcelona), previa valoración por farmacólogos y farmacéuticos de Atención Primaria. Se calculó el porcentaje de personas con acontecimientos adversos ocurridos tras la vacunación en el transcurso de su estancia en el CUAP, los tipos detectados y la gravedad. Posteriormente, se realizó una encuesta telefónica para conocer la satisfacción de los pacientes. Se realizó un análisis descriptivo (cálculo de proporciones). Resultados: La media de edad de las personas participantes fue de 49,7 años (de doce a noventa y cuatro años) y el 90,6% fueron mujeres. El 87,5% de las vacunas administradas fue Comirnaty ®. Se detectaron acontecimientos adversos ocurridos tras la vacunación en quince pacientes (23,4%), de los que en cuatro casos (6,25%) fueron manifestaciones de hipersensibilidad, todas catalogadas como leves. Los motivos de vacunación fueron antecedentes de alergia a AINE (45,3%), antibióticos (32,8%), analgésicos (17,2%), vacunas (28,1%), otras sustancias (40,6%) y anafilaxia (26,6%). El grado de satisfacción general fue de 9,11 (sobre 10). Conclusiones: El porcentaje de pacientes con antecedentes de anafilaxia y reacciones alérgicas a medicamentos que presentan reacciones de hipersensibilidad a las vacunas frente a la COVID-19 es del 6,25% y todas son leves.(AU)
Background: A common consultation since the beginning of the vaccination campaign against COVID-19 was related to people with a history of allergy to drugs or other vaccines. The objective of the study was to describe what happened after the administration of the vaccine against COVID-19 in people with a history of moderate and severe allergy, vaccinated against COVID-19 in a Primary Care Emergency Center (PCEC). Methods/ Observational descriptive study with sixty-four people with a history of moderate and severe allergy was carried out, vaccinated in PCEP, between May and October 2021, in the Barcelonés Nord and Maresme (Barcelona province), after assessment by primary care pharmacologists and pharmacists. The percentage of people with adverse events that occurred after vaccination during their stay in the PCEP, the types detected and severity were calculated. Subsequently, a telephone survey was conducted to determine patient satisfaction. A descriptive analysis (calculation of proportions) was performed. Results: The mean age of 49.7 years (from twelve to ninety-four years) and 90.6% were women. 87.5% of the administered vaccines were Comirnaty ® . Adverse events occurring after vaccination were detected in fifteen patients (23.4%), of whom four (6.25%)were manifestations of hypersensitivity, all classified as mild. The reasons for vaccination were a history of allergy to NSAIDs (45.3%), antibiotics (32.8%), analgesics (17.2%), vaccines (28.1%), other substances (40.6%) and anaphylaxis (26.6%). The degree of generalsatisfaction was 9.11 (out of 10). Conclusions: The percentage of patients with a history of anaphylaxis and allergic drug reactions who present hypersensitivityreactions to COVID-19 vaccines is 6.25% and all are mild.(AU)
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Humanos , Masculino , Femenino , /complicaciones , /efectos adversos , Hipersensibilidad a las Drogas , Hipersensibilidad , Anafilaxia , Vacunación , /epidemiología , /inmunología , Vacunas/efectos adversos , Programas de Inmunización , Encuestas y Cuestionarios , Estudios Retrospectivos , Epidemiología DescriptivaRESUMEN
Brain manganese (Mn) accumulation is a key feature in patients with acquired hepatocerebral degeneration (AHD). The role of trace elements other than Mn in AHD needs to be clarified. In this study, using inductively coupled plasma mass spectrometry, we aimed to evaluate blood levels of trace elements in patients with AHD before and after liver transplantation (LT). Trace element levels in the AHD group were also compared with those of healthy controls (blood donors, n = 51). Fifty-one AHD patients were included in the study (mean age: 59.2 ± 10.6 years; men: 72.5%). AHD patients had higher levels of Mn, Li, B, Ni, As, Sr, Mo, Cd, Sb, Tl and Pb and a higher Cu/Se ratio, and lower levels of Se and Rb. Six patients (two women; mean age 55 ± 8.7 years) underwent LT, and there was an improvement in neurological symptoms, a significant increase in the Zn, Se and Sr levels, and a decrease in the Cu/Zn and Cu/Se ratios. In summary, several trace element imbalances were identified in AHD patients. Liver transplantation resulted in the improvement of neurological manifestations and the oxidant/inflammatory status. It is possible that observed changes in trace element levels may play a role in the pathophysiology and symptomatology of AHD.
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Controlled drug release systems are the subject of many investigations to achieve the therapeutic effect of drugs. They have numerous advantages, such as localized effects, lower side effects, and less onset of action. Among drug-delivery systems, electrospinning is a versatile and cost-effective method for biomedical applications. Furthermore, electrospun nanofibers are promising as drug carrier candidates due to their properties that mimic the extracellular matrix. In this work, electrospun fibers were made of Poly-L-lactic acid (PLA), one of the most widely tested materials, which has excellent biocompatible and biodegradable properties. A curcuminoid, bisdemethoxycurcumin (BDMC) was added in order to complete the drug delivery system. The PLA/BDMC membranes were characterized, and biological characteristics were examined in vitro. The results show that the average fiber diameter was reduced with the drug, which was mainly released during the first 24 h by a diffusion mechanism. It was seen that the use of our membranes loaded with BDMC enhanced the rate of proliferation in Schwann cells, the main peripheral neuroglial cells, and modulated inflammation by reducing NLRP3 inflammasome activation. Considering the results, the prepared PLA/BDMC membranes hold great potential for being used in tissue engineering applications.
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Nanofibras , Poliésteres , Sistemas de Liberación de Medicamentos , Diarilheptanoides , Antiinflamatorios/farmacologíaRESUMEN
Metabolic adaptations are a hallmark of cancer and may be exploited to develop novel diagnostic and therapeutic tools. Only about 50% of the patients who undergo thyroidectomy due to suspicion of thyroid cancer actually have the disease, highlighting the diagnostic limitations of current tools. We explored the possibility of using non-invasive blood tests to accurately diagnose thyroid cancer. We analyzed blood and thyroid tissue samples from two independent cohorts of patients undergoing thyroidectomy at the Hospital Universitario 12 de Octubre (Madrid, Spain). As expected, histological comparisons of thyroid cancer and hyperplasia revealed higher proliferation and apoptotic rates and enhanced vascular alterations in the former. Notably, they also revealed increased levels of membrane-bound phosphorylated AKT, suggestive of enhanced glycolysis, and alterations in mitochondrial sub-cellular distribution. Both characteristics are common metabolic adaptations in primary tumors. These data together with reduced mtDNA copy number and elevated levels of the mitochondrial antioxidant PRX3 in cancer tissue samples suggest the presence of mitochondrial oxidative stress. In plasma, cancer patients showed higher levels of cfDNA and mtDNA. Of note, mtDNA plasma levels inversely correlated with those in the tissue, suggesting that higher death rates were linked to lower mtDNA copy number. In PBMCs, cancer patients showed higher levels of PGC-1α, a positive regulator of mitochondrial function, but this increase was not associated with a corresponding induction of its target genes, suggesting a reduced activity in cancer patients. We also observed a significant difference in the PRDX3/PFKFB3 correlation at the gene expression level, between carcinoma and hyperplasia patients, also indicative of increased systemic metabolic stress in cancer patients. The correlation of mtDNA levels in tissue and PBMCs further stressed the interconnection between systemic and tumor metabolism. Evaluation of the mitochondrial gene ND1 in plasma, PBMCs and tissue samples, suggested that it could be a good biomarker for systemic oxidative metabolism, with ND1/mtDNA ratio positively correlating in PBMCs and tissue samples. In contrast, ND4 evaluation would be informative of tumor development, with ND4/mtDNA ratio specifically altered in the tumor context. Taken together, our data suggest that metabolic dysregulation in thyroid cancer can be monitored accurately in blood samples and might be exploited for the accurate discrimination of cancer from hyperplasia.
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Mitocondrias , Neoplasias de la Tiroides , Humanos , Hiperplasia/metabolismo , Mitocondrias/genética , Mitocondrias/metabolismo , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , GlucólisisRESUMEN
Liberfarb syndrome is an extremely rare mitochondrial multisystem disorder, recently described and characterized by early-onset retinal degeneration and sensorineural hearing loss, spondyloepimetaphyseal dysplasia, joint laxity, short stature, microcephaly, developmental delay and intellectual disability, but clinical variability has been observed. We report a case that presented to the hospital with a flare-up of the disease. We describe the brain magnetic resonance imaging findings, which are still not well characterized, to raise awareness of this diagnosis.
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Enfermedades Cerebelosas , Discapacidad Intelectual , Humanos , Enfermedades Cerebelosas/patología , Nervio Óptico , Discapacidad Intelectual/patología , Atrofia/patología , NeuroimagenRESUMEN
Electroconductive materials based on poly(lactic acid) (PLA) electrospinning membranes grafted with carbon nanotubes (CNTs) functionalized with the carboxylic group R-COOH have been obtained. PLA electrospun membranes were modified with sulfuric acid (H2SO4) to oxidize its surface to subsequently graft the CNTs, the treatment time and drying of the membranes before grafting with CNTs being critical, influencing the final properties of the materials. SEM images showed that CNTs presented a uniform distribution on the surface of the PLA nanofibers, while FTIR spectra of PLA-CNTs materials revealed characteristic hydroxyl groups, as evidenced by absorption peaks of CNTs. Thanks to the grafting with CNTs, the resulting PLA-CNTs membranes present an improvement of the mechanical and conductive properties when compared with PLA membranes. On the one hand, grafting with CNTs causes the nanofibers to have greater rigidity, so they are more manipulable and can more easily preserve their conformation when stress is exerted. On the other hand, grafting with CNTs allows elimination of the insulating barrier of the PLA, reducing the resistivity and providing high electrical conductivity to the PLA-CNTs membranes. The incorporation of CNTs into PLA electrospun membranes is expected to offer greater functionalities to electrospun composite nanofibers for medical and industrial applications.
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The aim of the present research was to analyse modifications in the autonomic stress response of Physiotherapy students undergoing a 12-scenario Objective Structured Clinical Evaluation (OSCE). A total of 86 last year students of the Physiotherapy bachelor's degree (27.29 years (SD = 6.66); 36 females and 50 males) randomly assigned were monitored during the complete OSCE to measure heart rate variability (HRV) in temporal, frequency, and non-linear domains. The HRV analysed showed a large anticipatory stress response of students maintained during the entire evaluation. The stress response varied regarding OSCE station complexity and demands and the highest sympathetic response was not found in higher emotional scenarios.The autonomic modulation monitoring allows teachers to design OSCE scenarios more adapted to the students, limiting the effect of the stress response to allow a better performance.
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Competencia Clínica , Evaluación Educacional , Femenino , Humanos , Masculino , Frecuencia Cardíaca , Modalidades de Fisioterapia , EstudiantesRESUMEN
Neural progenitor cells (NPCs) have been shown to serve as an efficient therapeutic strategy in different cell therapy approaches, including spinal cord injury treatment. Despite the reported beneficial effects of NPC transplantation, the low survival and differentiation rates constrain important limitations. Herein, a new methodology has been developed to overcome both limitations by applying a combination of wireless electrical and magnetic stimulation to NPCs seeded on aligned poly(lactic acid) nanofibrous scaffolds for in vitro cell conditioning prior transplantation. Two stimulation patterns were tested and compared, continuous (long stimulus applied once a day) and intermittent (short stimulus applied three times a day). The results show that applied continuous stimulation promotes NPC proliferation and preferential differentiation into oligodendrocytic and neuronal lineages. A neural-like phenotypic induction was observed when compared to unstimulated NPCs. In contrast, intermittent stimulation patterns did not affect NPC proliferation and differentiation to oligodendrocytes or astrocytes morphology with a detrimental effect on neuronal differentiation. This study provides a new approach of using a combination of electric and magnetic stimulation to induce proliferation and further neuronal differentiation, which would improve therapy outcomes in disorders such as spinal cord injury.