ABSTRACT
Antecedentes: La escala Teacher Emotion Inventory (TEI) es un instrumento que evalúa emociones discretas experimentadas por el profesorado en el proceso de enseñanza-aprendizaje. El objetivo de este estudio es examinar las propiedades psicométricas de la versión breve española de la escala Teacher Emotion Inventory (TEI-BSV) en una muestra de 567 profesores (65.5% son mujeres), con edades comprendidas entre 25 y 65 años (M = 46.04; DT = 9.09). Método: Tras su adaptación mediante traducción inversa, el profesorado completó una batería que incluía el TEI-BSV, un cuestionario de inteligencia emocional, dos escalas de bienestar subjetivo, una escala sobre burnout y una escala sobre engagement. Resultados: Los resultados mostraron una consistencia interna adecuada de las subescalas del TEI-BSV. Los análisis factoriales (exploratorio y confirmatorio) proporcionaron pruebas de que el TEI-BSV tiene una estructura de cuatro factores con un buen ajuste, frente a la estructura de cinco factores original. Se han hallado evidencias de validez convergente, así como de validez criterial e incremental del TEI-BSV. Conclusiones: el TEI-BSV podría ser una herramienta útil para la evaluación ecológica de las emociones discretas del profesorado en su contexto laboral.(AU)
Background: The Teacher Emotion Inventory (TEI) scale is an instrument that evaluates discrete emotions experienced by teachers in the teaching-learning process. The aim of this study was to examine the psychometric properties of the brief Spanish version of the Teacher Emotion Inventory scale (TEI-BSV) using a sample of 567 teachers (65.5% women), aged between 25 and 65 years (M= 46.04; SD= 9.09). Methods: After adaptation through back-translation, the teachers com-pleted a battery of tests included in the TEI-BSV: an emotional intelli-gence questionnaire, two subjective well-being scales, a burnout scale and a scale on engagement. Results: The data revealed adequate internal consistency of the TEI-BSV subscales, and exploratory and confirma-tory factor analyses provided evidence that the TEI-BSV has a four-factor structure with good adjustment, as opposed to the original five-factor structure proposed. There was evidence of convergent validity of the TEI-BSV, as well as criterion and incremental validity. Conclusions: The TEI-BSV could be a useful instrument for the ecological assess-ment of teachers' discrete emotions in the context of their workplace.(AU)
Subject(s)
Humans , Male , Female , Psychometrics , Emotions , Stress, Psychological , Burnout, Psychological , Emotional IntelligenceABSTRACT
Background: Cold agglutinin syndrome (CAS) is a hemolytic anemia mediated by antibodies, mainly IgM, whose maximum activity occurs at 4 °C. It happens secondary to infectious, autoimmune or neoplastic diseases, due to the formation of antibodies that cross-react against erythrocyte antigens, particularly of the I system. Here, we describe a case of CAS associated to Epstein-Barr virus (EBV) reactivation in a patient with primary human immunodeficiency virus (HIV) infection. Clinical case: 22-year old man with no medical history, hospitalized due to mononucleosis and anemic syndrome. Hemoglobin of 3.7 g/dL and elevation of lactate dehydrogenase were documented. In the peripheral blood smear it was observed spherocytosis, polychromasia and nucleated erythrocytes. EBV infection was confirmed with serology and viral load, as well as seronegative HIV infection with positive viral load. The C3d monospecific direct antiglobulin test was positive and an irregular antibody screening revealed the presence of an anti-I antibody. The patient received transfusion support and conservative treatment, with remission of the symptoms 2 weeks after admission. Conclusions: Cold agglutinin syndrome is a rare, potentially fatal complication of infectious mononucleosis, which should be considered in the face of findings suggestive of hemolysis in order to initiate support measures in a timely manner.
Introducción: el síndrome por aglutininas frías (SAF) es una anemia hemolítica mediada por anticuerpos principalmente de tipo IgM, cuya máxima actividad se da a 4 °C. Se presenta en el contexto de enfermedades infecciosas, autoinmunes o neoplásicas por la formación de anticuerpos que tienen reacción cruzada contra antígenos eritrocitarios, particularmente del sistema I. En este trabajo presentamos un caso de SAF asociado a reactivación del virus de Epstein-Barr (VEB) en un paciente con primoinfección por el virus de la inmunodeficiencia humana (VIH). Caso clínico: hombre de 22 años, sin antecedentes patológicos, hospitalizado por síndrome mononucleósico y anémico. Presentó hemoglobina de 3.7 g/dL y elevación de lactato deshidrogenasa. En el frotis de sangre periférica se observó esferocitosis, policromasia y eritrocitos nucleados. Se confirmó infección por VEB con serología y carga viral, así como infección por VIH seronegativa, con carga viral positiva. La prueba de antiglobulina directa monoespecífica a C3d fue positiva y el rastreo de anticuerpos irregulares demostró un anticuerpo anti-I. El paciente recibió soporte transfusional y tratamiento conservador, con remisión del cuadro a las 2 semanas de su ingreso. Conclusiones: el SAF es una complicación poco frecuente de la mononucleosis infecciosa, potencialmente mortal, la cual debe ser considerada ante hallazgos sugestivos de hemólisis con la finalidad de iniciar medidas de soporte de forma oportuna.
Subject(s)
Anemia, Hemolytic, Autoimmune , Infectious Mononucleosis , Humans , Male , Anemia, Hemolytic, Autoimmune/etiology , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/therapy , Anemia, Hemolytic, Autoimmune/virology , Infectious Mononucleosis/complications , Infectious Mononucleosis/diagnosis , Young AdultABSTRACT
With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate inter-study comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group-European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to i) account for gender-specific differences in determining hemoglobin levels for eligibility criteria, ii) revise definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices, and iii) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks prior to study enrollment) and hemoglobin thresholds for eligibility criteria (<10 g/dL for women and <11 g/dL for men). The revised document also provides separate (TDA vs. non-TDA) and graded (major vs. minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment.
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Human microbiota is known to influence immune and cerebral responses by direct and/or indirect mechanisms, including hypothalamic-pituitary-adrenal axis signaling, activation of neural afferent circuits to the brain, and by altering the peripheral immune responses (cellular and humoral immune function, circulatory inflammatory cells, and the production of several inflammatory mediators, such as cytokines, chemokines, and reactive oxygen species).â¯The inflammatory responses in the nasal mucosa (rhinitis) or paranasal sinuses (chronic rhinosinusitis) are dual conditions related with a greater risk for developing depression. In the nasal cavity, anatomic components of the olfactive function are in direct contact with the CNS through the olfactory receptors, neurons, and axons that end in the olfactory bulb and the entorhinal cortex. Local microbiome alterations (dysbiosis) are linked to transepithelial translocation of microorganisms and their metabolites, which disrupts the epithelial barrier and favors vascular permeability, increasing the levels of several inflammatory molecules (both cytokines and non-cytokine mediators: extracellular vesicles (exosomes) and neuropeptides), triggering local inflammation (rhinitis) and the spread of these components into the central nervous system (neuroinflammation). In this review, we discuss the role of microbiota-related immunity in conditions affecting the nasal mucosa (chronic rhinosinusitis and allergic rhinitis) and their relevance in major depressive disorders, focusing on the few mechanisms known to be involved and providing some hypothetical proposals on the pathophysiology of depression.
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PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.
Subject(s)
BCG Vaccine , Granulomatous Disease, Chronic , NADPH Oxidase 2 , Tuberculosis , Humans , Granulomatous Disease, Chronic/diagnosis , Granulomatous Disease, Chronic/epidemiology , Granulomatous Disease, Chronic/complications , BCG Vaccine/adverse effects , Male , Female , Child , Tuberculosis/epidemiology , Tuberculosis/immunology , Child, Preschool , Infant , Adolescent , NADPH Oxidase 2/genetics , Cohort Studies , Mycobacterium bovis , Mexico/epidemiology , Antitubercular Agents/therapeutic use , NADPH Oxidases/geneticsABSTRACT
BACKGROUND: Compared with conventional cigarettes, electronic cigarettes are less harmful in some studies. However, recent research may indicate the opposite. This study aimed to determine whether e-cigarette use is related to myocardial health in adults in the U.S. METHODS: This study used data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a cross-sectional survey of adult US residents aged 18 years or older. We examined whether e-cigarette use was related to myocardial infarction byapplying a logistic regression model to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The final analytical sample included 198,530 adults in the U.S. Logistic regression indicated that U.S. adults who reported being former and some days of e-cigarette use had 23% and 52% greater odds of ever having an MI, respectively, than did those who reported never using e-cigarettes (OR = 1.23, 95% CI 1.08-1.40, p = 0.001; OR = 1.52, 95% CI 1.10-2.09, p = 0.010). CONCLUSIONS: The results suggest that former and someday users of e-cigarettes probably have increased odds of myocardial infarction in adults in the U.S. Further research is needed, including long-term follow-up studies on e-cigarettes, since it is still unknown whether they should be discouraged.
Subject(s)
Behavioral Risk Factor Surveillance System , Myocardial Infarction , Vaping , Humans , Myocardial Infarction/epidemiology , Male , Female , Adult , United States/epidemiology , Middle Aged , Cross-Sectional Studies , Young Adult , Adolescent , Vaping/epidemiology , Vaping/adverse effects , Electronic Nicotine Delivery Systems/statistics & numerical data , Aged , Risk FactorsABSTRACT
Electrochemical SERS of pyridine adsorbed on a silver electrode has been analyzed by comparing the spectra to the calculated normal Raman and resonance Raman intensities of model systems of pyridine bonded to linear silver clusters with different densities of charge through the nitrogen (Ag-NPy) or flipped through the hydrogen in the para-position (Ag-HPy). The changes observed in the ν(CH) region of the SERS have been investigated for the first time and related to a molecular reorientation at negative surface excess of charge of the metal in such a way that the ν(CH) bands with the highest (mode 2) and lowest (mode 13) wavenumber dominate this spectral region at positive or negative electrode potentials, respectively. The calculations support that the ν(CH) region is dominated by a specific vibration depending on pyridine orientation and suggest that both species coexist in the SERS recorded at negative potentials. This conclusion is supported by the SERS of centrosymmetric pyrazine which do not show this behavior and remembers the predictions from the old propensity rules of the so-called electromagnetic mechanism of SERS.
ABSTRACT
Introduction. Colombia is home to 2 million indigenous people who live in conditions of poverty and with health deficiencies, making them vulnerable to contracting hepatitis B (HBV). Amazonas has a high virus prevalence, and there are barriers to accessing vaccination; thus, part of the population is susceptible to infection. Objective. To identify factors associated with HBV in Colombian indigenous people. Materials and Methods. A case-control study of people over 18 years from four departments of Colombia. Cases were identified through the national hepatitis B notification registry (2015-2022). Controls were selected and matched to cases (2:1) by age, sex, ethnicity, and department. Sociodemographic characteristics, factors associated with contact with body fluids, cultural practices, and vaccination history were identified by means of a survey. The ethics committee of the Universidad de Antioquia approved the project. Results. Seventy five cases and 150 controls from 13 ethnic groups were surveyed. Amazonas contributed 49% of participants, 83% were women, and the median age of cases was 30 years (IQ range: 27-37). The associated factors were a family history of hepatitis B [adjusted OR: 2.61 (95% CI: 1.09-6.27)] and, in women, the number of pregnancies [adjusted OR: 1.61 (95% CI 1.02- 2.54)]. The vaccination history showed a protective effect, but the association was not significant. Conclusion. Aspects associated with family life and unprotected sexual relations seem to be responsible for the potential transmission of the virus. It was not possible to identify associated cultural practices. Innovative and differential strategies are required for indigenous people to achieve a reduction of HBV.
Introducción. Colombia alberga dos millones de indígenas, que viven en condiciones de pobreza y tienen deficiencias en salud, por lo cual están expuestos a contraer infecciones virales como la hepatitis B. El departamento del Amazonas presenta una gran prevalencia del virus y barreras para acceder a la vacunación; por esto, parte de la población es propensa a la infección. Objetivo. Identificar factores asociados con la infección por el virus de la hepatitis B en indígenas colombianos. Materiales y métodos. Se llevó a cabo un estudio de casos y controles en mayores de 18 años de cuatro departamentos del país. Los casos se identificaron mediante el registro nacional de notificación de hepatitis B (2015-2022). Los controles seleccionados de manera concurrente fueron pareados con los casos por edad, sexo, etnia y departamento. En una encuesta se consignaron las características sociodemográficas, los factores asociados con el contacto con sangre y fluidos, las prácticas socioculturales y los antecedentes de vacunación. El proyecto fue aprobado por Comité de Ética de la Universidad de Antioquia. Resultados. Participaron 75 casos y 150 controles de 13 grupos étnicos. El departamento del Amazonas aportó el 49 % de los participantes (83 % mujeres) con una mediana de edad de 30 años (RIC = 27-37). Los factores asociados con una mayor probabilidad de contraer la infección fueron el antecedente de algún familiar infectado con el virus de la hepatitis B (OR ajustado = 2,61) (IC95%: 1,09-6,27) y número de embarazos en mujeres, (OR ajustado = 1,61) (IC95%: 1,02-2,54). La vacunación mostró un efecto protector sin asociación significativa. Conclusión. Los aspectos asociados con la convivencia familiar y el número de embarazos contribuyen a una potencial transmisión vertical y horizontal del virus. No se identificaron prácticas culturales asociadas. Se requieren estrategias novedosas y diferenciales para reducir la transmisión del virus de la hepatitis B en poblaciones indígenas.
Subject(s)
Hepatitis B , Humans , Colombia/epidemiology , Case-Control Studies , Adult , Female , Hepatitis B/epidemiology , Hepatitis B/transmission , Male , Indians, South American/statistics & numerical data , Risk Factors , Middle Aged , Young Adult , Adolescent , Hepatitis B Vaccines/administration & dosageABSTRACT
Sex differences may play a role in the etiopathogenesis and severity of metabolic dysfunction-associated steatotic liver disease (MASLD), a disorder characterized by excessive fat accumulation associated with increased inflammation and oxidative stress. We previously observed the development of steatosis specifically in female rats fed a high-fat diet enriched with liquid fructose (HFHFr) for 12 weeks. The aim of this study was to better characterize the observed sex differences by focusing on the antioxidant and cytoprotective pathways related to the KEAP1/NRF2 axis. The KEAP1/NRF2 signaling pathway, autophagy process (LC3B and LAMP2), and endoplasmic reticulum stress response (XBP1) were analyzed in liver homogenates in male and female rats that were fed a 12-week HFHFr diet. In females, the HFHFr diet resulted in the initial activation of the KEAP1/NRF2 pathway, which was not followed by the modulation of downstream molecular targets; this was possibly due to the increase in KEAP1 levels preventing the nuclear translocation of NRF2 despite its cytosolic increase. Interestingly, while in both sexes the HFHFr diet resulted in an increase in the levels of LC3BII/LC3BI, a marker of autophagosome formation, only males showed a significant upregulation of LAMP2 and XBP1s; this did not occur in females, suggesting impaired autophagic flux in this sex. Overall, our results suggest that males are characterized by a greater ability to cope with an HFHFr metabolic stimulus mainly through an autophagic-mediated proteostatic process while in females, this is impaired. This might depend at least in part upon the fine modulation of the cytoprotective and antioxidant KEAP1/NRF2 pathway resulting in sex differences in the occurrence and severity of MASLD. These results should be considered to design effective therapeutics for MASLD.
Subject(s)
Diet, High-Fat , Fructose , Kelch-Like ECH-Associated Protein 1 , NF-E2-Related Factor 2 , Sex Characteristics , Signal Transduction , Animals , NF-E2-Related Factor 2/metabolism , Female , Male , Diet, High-Fat/adverse effects , Signal Transduction/drug effects , Rats , Kelch-Like ECH-Associated Protein 1/metabolism , Autophagy/drug effects , X-Box Binding Protein 1/metabolism , X-Box Binding Protein 1/genetics , Disease Models, Animal , Fatty Liver/metabolism , Fatty Liver/pathology , Liver/metabolism , Liver/pathology , Liver/drug effects , Endoplasmic Reticulum Stress/drug effects , Rats, Wistar , Oxidative Stress/drug effects , Microtubule-Associated ProteinsABSTRACT
We used finite element analysis to study the mechanical stress distribution of a new intramedullary implant used for proximal interphalangeal joint (PIPJ) arthrodesis (PIPJA) to surgically correct the claw-hammer toe deformity that affects 20% of the population. After geometric reconstruction of the foot skeleton from claw toe images of a 36-year-old male patient, two implants were positioned, in the virtual model, one neutral implant (NI) and another one 10° angled (10°AI) within the PIPJ of the second through fourth HT during the toe-off phase of gait and results were compared to those derived for the non-surgical foot (NSF). A PIPJA was performed on the second toe using a NI reduced tensile stress at the proximal phalanx (PP) (45.83 MPa) compared to the NSF (59.44 MPa; p < 0.001). When using the 10°AI, the tensile stress was much higher at PP and middle phalanges (MP) of the same toe, measuring 147.58 and 160.58 MPa, respectively, versus 59.44 and 74.95 MPa at corresponding joints in the NSF (all p < 0.001). Similar results were found for compressive stresses. The NI reduced compressive stress at the second PP (-65.12 MPa) compared to the NSF (-113.23 MPa) and the 10°AI (-142 MPa) (all p < 0.001). The von Mises stresses within the implant were also significantly lower when using NI versus 10°AI (p < 0.001). Therefore, we do not recommend performing a PIPJA using the 10°AI due to the increase in stress concentration primarily at the second PP and MP, which could promote implant breakage.
Subject(s)
Arthrodesis , Finite Element Analysis , Hammer Toe Syndrome , Toe Joint , Humans , Male , Arthrodesis/methods , Adult , Toe Joint/surgery , Toe Joint/physiopathology , Hammer Toe Syndrome/surgery , Hammer Toe Syndrome/physiopathology , Biomechanical PhenomenaABSTRACT
Introduction: Corneal ulcers are common lesions in both human and veterinary medicine. However, only a few studies have evaluated the efficacy of cross-linked hyaluronic acid (X-HA) eye drops on corneal wound healing. To our knowledge, this is the first study to demonstrate and compare the efficacy of amniotic membrane extract eye drops (AMEED) and X-HA for corneal wound healing in rats. Material and methods: A total of 15 male Wistar rats (30 eyes) were used in this study. Then, 10 eyes were treated with X-HA, AMEED, or 0.9% saline. After general and topical anesthesia, a superficial corneal ulcer was created using a corneal trephine. The defect was further polished with a diamond burr. Three groups of 10 eyes each were treated with either one drop of 0.75% X-HA or AMEED or 0.9% saline (control), administered every 12 h for a duration of 72 h. The median epithelial defect area (MEDA), expressed as a percentage of the total corneal surface, was measured at 0, 12, 24, 36, 48, and 72 h. Re-epithelization time scores were also evaluated. The Kruskal-Wallis test was used to compare median times for re-epithelization and histopathologic scores between groups, while the Friedman test (for paired data) was employed to compare results from the serial analysis of MEDA and vascularization scores between groups. Results: MEDA was not significantly different between X-HA and AMEED. However, MEDA was significantly smaller in the X-HA group compared to the control group at 36 h (2.73 interquartile range (IQR) 5.52% x 9.95 IQR 9.10%, P=0.024) and 48 h (0.00 IQR 0.26% x 6.30 IQR 8.54%, P=0.030). The overall time for re-epithelization was significantly lower in the X-HA group (3.00 IQR 3.00) compared to the AMEED (6.5 IQR 3.00) and control (7.00 IQR 1.00) groups (P=0.035). Vascularization, hydropic degeneration, and epithelial-stromal separation were significantly less observed in samples in the X-HA-treated compared to samples in the AMEED- and saline-treated groups. Significantly more corneal epithelium cells were labeled for caspase3 in samples from the AMEED- and saline-treated groups compared to those from the X-HA-treated group. Discussion: Topical X-HA has been shown to accelerate corneal epithelial healing. AMEED did not decrease corneal re-epithelialization time. X-HA may also potentially be used as an adjunct therapy for treating corneal ulcers in clinical situations.
ABSTRACT
Malignant pleural effusion (MPE) has become an increasingly prevalent complication in oncological patients, negatively impacting their quality of life and casting a shadow over their prognosis. Owing to the pathophysiological mechanisms involved and the heterogeneous nature of the underlying disease, this entity is both a diagnostic and therapeutic challenge. Advances in the understanding of MPE have led to a shift in the treatment paradigm towards a more personalized approach. This article provides a comprehensive review and update on the pathophysiology of MPE and describes the diagnostic tools and the latest advances in the treatment of this complex clinical entity.
El derrame pleural maligno (DPM) se ha convertido en una complicación cada vez más prevalente en los pacientes oncológicos, empeorando la calidad de vida y ensombreciendo el pronóstico de los mismos. Debido a los mecanismos fisiopatológicos involucrados y a la naturaleza heterogénea de la enfermedad subyacente, esta entidad representa un desafío diagnóstico y terapéutico. Los avances en la comprensión del DPM han originado un cambio en el paradigma del tratamiento hacia un enfoque más personalizado. Este artículo proporciona una revisión exhaustiva y una actualización sobre la fisiopatología del DPM, y describe las herramientas diagnósticas y los últimos avances en el tratamiento de esta compleja entidad clínica.
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Introduction: The cognitive effects of video games have garnered increasing attention due to their potential applications in cognitive rehabilitation and evaluation. However, the underlying mechanisms driving these cognitive modifications remain poorly understood. Objectives: This study investigates the fundamental mnemonic processes of spatial navigation, pattern separation, and recognition memory, closely associated with the hippocampus. Our objective is to elucidate the interaction of these cognitive processes and shed light on rehabilitation mechanisms that could inform the design of video games aimed at stimulating the hippocampus. Method: In this study, we assessed 48 young adults, including both video game players and non-players. We utilized virtual reality and cognitive tasks such as the Lobato Virtual Water Maze and the Mnemonic Similarity Task to evaluate their cognitive abilities. Results: Our key findings highlight that gamers exhibit heightened pattern separation abilities and demonstrate quicker and more accurate spatial learning, attributed to the cognitive stimulation induced by video games. Additionally, we uncovered a significant relationship between spatial memory, guided by environmental cues, and pattern separation, which serves as the foundation for more efficient spatial navigation. Conclusions: These results provide valuable insights into the cognitive impact of video games and offer potential for monitoring changes in rehabilitation processes and early signs of cognitive decline through virtual reality-based assessments. Ultimately, we propose that examining the relationships between cognitive processes represents an effective method for evaluating neurodegenerative conditions, offering new possibilities for early diagnosis and intervention.
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B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer, with long-term overall survival rates of ~85%. However, B-ALL harboring rearrangements of the MLL gene (also known as KMT2A), referred to as MLLr B-ALL, is common in infants and is associated with poor 5-year survival (<30%), frequent relapses, and refractoriness to glucocorticoids (GCs). GCs are an essential part of the treatment backbone for B-ALL and GC resistance is a major clinical predictor of poor outcome. Elucidating the mechanisms of GC resistance in MLLr B-ALL is, therefore, critical to guide therapeutic strategies that deepen the response after induction therapy. Neuron-glial antigen-2 (NG2) expression is a hallmark of MLLr B-ALL and is minimally expressed in healthy hematopoietic cells. We recently reported that NG2 expression is associated with poor prognosis and that anti-NG2 immunotherapy strongly reduces/delays relapse in MLLr B-ALL xenograft models. Despite its contribution to MLLr B-ALL pathogenesis and its diagnostic utility, the role of NG2 in MLLr-mediated leukemogenesis/chemoresistance remains elusive. Here we show that NG2 is an epigenetically regulated direct target gene of the leukemic MLL-AF4 fusion protein. NG2 negatively regulates the expression of the GC receptor NR3C1 and confers GC resistance to MLLr B-ALL cells in vitro and in vivo. Mechanistically, NG2 interacts with FLT3 to render ligand-independent activation of FLT3 signaling (a hallmark of MLLr B-ALL) and downregulation of NR3C1 via AP-1-mediated trans-repression. Collectively, our study elucidates the role of NG2 in GC resistance in MLLr B-ALL through FLT3/AP-1-mediated downregulation of NR3C1, providing novel therapeutic avenues for MLLr B-ALL.
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A new variety of hornwort from northern Thailand, Phaeocerosperpusillusvar.scabrellus is described based on morphological characters and molecular phylogenetic analyses. In this study, phylogenetic analyses supported that the new variety is closely related to P.perpusillusvar.perpusillus. Morphologically, it is distinguished from the autonimic variety in nearly smooth spores under light microscope. A taxonomic description, illustrations, and light and scanning electron micrographs are provided. In addition, the new variety is assessed as Endangered (EN), demonstrating its rarity by being currently known from only three subpopulations.
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Neratinib is a tyrosine kinase inhibitor that is used for the therapy of patients with HER2+ breast tumors. However, despite its clinical benefit, resistance to the drug may arise. Here we have created cellular models of neratinib resistance to investigate the mechanisms underlying such resistance. Chronic neratinib exposure of BT474 human HER2+ breast cancer cells resulted in the selection of several clones resistant to the antiproliferative action of the drug. The clones were characterized biochemically and biologically using a variety of techniques. These clones retained HER2 levels similar to parental cells. Knockdown experiments showed that the neratinib-resistant clones retained oncogenic dependence on HER2. Moreover, the tyrosine phosphorylation status of BT474 and the resistant clones was equally sensitive to neratinib. Transcriptomic and Western analyses showed that peptidylarginine deiminase 3 was overexpressed in the three neratinib-resistant clones studied but was undetectable in BT474 cells. Experiments performed in the neratinib-resistant clones showed that reduction of PADI3 or inhibition of its function restored sensitivity to the antiproliferative action of neratinib. Moreover, overexpression of FLAG-tagged PADI3 in BT474 cells provoked resistance to the antiproliferative action of neratinib. Together, these results uncover a role of PADI3 in the regulation of sensitivity to neratinib in breast cancer cells overexpressing HER2 and open the possibility of using PADI3 inhibitors to fight resistance to neratinib.
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The hip is the location for many disorders, such as osteoarthritis, femoroacetabular impingement syndrome, avascular necrosis of the hip, and cartilage injuries, all of which cause chronic pain, disability, and limitation. It is estimated that 10% of the population ≥40 years of age will present with hip pain. The line of treatment goes from nonsteroidal anti-inflammatory drugs, physical therapy, lifestyle modification, intra-articular injections, and hip surgery. This will depend on the pathology, age, lifestyle, and sport activity of each patient. Currently, hip joint intra-articular injections represent a viable option for those patients who are not candidates for surgery or simply those who do not want surgery. Among the controversial indications for a hip injection is moderate-to-severe arthritis (grades III and IV). Hip injections are considered a diagnostic and therapeutic procedure, with a sensitivity of 87% and specificity of 100% reported, and will differentiate between an intra-articular pathology versus an extra-articular pathology and a neuropathic pain arising from the lumbar spine. Radiofrequency nerve ablation or neurectomy of the femoral and obturator nerve has been implemented more frequently not only for patients with mild-to-moderate osteoarthritis but also in those who present with femoroacetabular impingement syndrome and cartilage lesions who do not wish to undergo surgery.
ABSTRACT
INTRODUCTION AND OBJECTIVES: Worsening renal function (WRF) is a frequent complication in acute heart failure (AHF) with a controversial prognostic value. We aimed to study the usefulness of natriuresis to evaluate WRF. METHODS: We conducted an observational, prospective, multicenter study of patients with AHF who underwent a furosemide stress test. The patients were classified according to whether WRF was present or absent and according to the median natriuretic response. The main endpoint was the combination of mortality, rehospitalization due to HF, and heart transplant at 6 months of follow-up. RESULTS: One hundred and fifty-six patients were enrolled, and WRF occurred in 60 (38.5%). The patients were divided into 4 groups: a) 47 (30.1%) no WRF/low UNa (UNa ≤ 109 mEq/L); b) 49 (31.4%) no WRF/high UNa (UNa > 109 mEq/L); c) 31 (19.9%) WRF/low UNa and d) 29 (18.6%) WRF/high UNa. The parameters of the WRF/low UNa group showed higher clinical severity and worse diuretic and decongestive response. The development of WRF was associated with a higher risk of the combined event (HR, 1.88; 95%CI, 1.01-3.50; P = .046). When stratified by natriuretic response, WRF was associated with an increased risk of adverse events in patients with low natriuresis (HR, 2.28; 95%CI, 1.15-4.53; P = .019), but not in those with high natriuresis (HR, 1.18; 95%CI, 0.26-5.29; P = .826). CONCLUSIONS: Natriuresis could be a useful biomarker for interpreting and prognosticating WRF in AHF. WRF is associated with a higher risk of adverse events only in the context of low natriuresis.