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1.
Front Public Health ; 12: 1392894, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100951

RESUMEN

The Preparedness and Resilience for Emerging Threats (PRET) initiative takes an innovative mode-of-transmission approach to pandemic planning by advocating for integrated preparedness and response systems and capacities for groups of pathogens with common transmission pathways. The World Health Organization (WHO) launched this initiative in 2023 with the publication of PRET Module 1 addressing respiratory pathogens. Exercise PanPRET-1 is a customizable tabletop simulation exercise (TTX) package developed to complement PRET Module 1. The exercise scenario focuses on strengthening capacities for multisectoral coordination, risk communication and community engagement, and the triggers for operational decision-making. This article reports on the experiences of the first four countries to implement Exercise PanPRET-1: Cook Islands, Costa Rica, Lebanon and Mongolia. Exercise outcomes demonstrated that PanPRET-1 can be an effective tool for testing pandemic plans in a multisectoral forum and identifying opportunities to improve preparedness and response in key domains. In quantitative evaluations in Cook Islands, Costa Rica and Mongolia, high proportions of exercise participants indicated that multiple aspects of the exercise were well-designed and were beneficial for improving health emergency preparedness. Exercise participants in Lebanon provided qualitative feedback indicating that they found the exercise to be beneficial. Conducting a TTX and monitoring the implementation of action plans based on exercise findings facilitates a country-owned whole-of-society vision for pandemic planning. Countries are encouraged to incorporate TTX such as Exercise PanPRET-1 into a continuous cycle of activity to improve pandemic preparedness.


Asunto(s)
Pandemias , Humanos , Líbano/epidemiología , Costa Rica/epidemiología , Pandemias/prevención & control , Mongolia/epidemiología , Entrenamiento Simulado , Planificación en Desastres , Infecciones del Sistema Respiratorio/prevención & control , Infecciones del Sistema Respiratorio/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control
2.
J. pediatr. (Rio J.) ; 100(4): 343-349, July-Aug. 2024. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1564747

RESUMEN

Abstract Objectives: Identify potential barriers, delays, and missed opportunities in the prevention and diagnosis of childhood TB. Methods: Scoping review according to the PRISMA extension. The definitions considered for the selection followed the acronym PCC where the population (P) is children under 18years of age with TB disease, the concept (C) refers to missed opportunities for prevention and diagnosis, and context (C) is defined as a diagnosis of TB disease. The authors searched systematically in the databases; VHL/Lilacs, Medline via PubMed, Cochrane, Scopus, and Web of Science, without date or language limitation. Results: Seven studies were included. In developed countries, with low disease burden, the main shortcoming is the delay in diagnosing bacilliferous adults in contact with young children. This problem is concentrated in the portion of the population with socioeconomic vulnerability. In underdeveloped countries, with a high burden of disease, the biggest challenge is tracking children who come into contact with bacilliferous patients. Conclusions: There are still many missed opportunities in the prevention and diagnosis of childhood TB. The positive legacy of the COVID-19 pandemic should be taken advantage of and the encouragement of scientific development in the management of infectious diseases should be taken.

3.
An Pediatr (Engl Ed) ; 101(1): 46-57, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38987075

RESUMEN

Mycoplasma pneumoniae (M. pneumoniae) is a bacterium with particular characteristics that give rise to a broad clinical spectrum, being respiratory infection the most frequent presentation. Infection by M. pneumoniae occurs in cyclical epidemics, and paediatricians in Spain have noticed an increase in cases since January 2024, establishing hospital registers to collect surveillance data (as it is not a notifiable disease in Spain). The diagnosis of infection by M. pneumoniae is made through serological testing and/or the detection of genetic material by means of polymerase chain reaction (PCR). Neither methods can differentiate between colonization and active infection, so a precise diagnosis is not possible and testing should only be requested in the case of high clinical suspicion. The role of antibiotherapy in infection by M. pneumoniae in its different clinical variants is not well defined. Most infections are self-limiting and mild, and there is insufficient evidence to support the use of antibiotherapy in these cases. Antibiotic treatment is justified in patients with risk factors for the development of severe disease (Down syndrome, anatomical or functional asplenia, immunosuppression), in hospitalized patients with respiratory infection and in patients with moderate or severe extrapulmonary forms. Taking into account aspects concerning the rational use of antimicrobials, the treatment of choice would be clarithromycin, with azithromycin as an alternative, reserving the use of doxycycline and levofloxacin for cases of antimicrobial resistance and/or infections of the central nervous system.


Asunto(s)
Antibacterianos , Mycoplasma pneumoniae , Neumonía por Mycoplasma , Humanos , Neumonía por Mycoplasma/diagnóstico , Neumonía por Mycoplasma/tratamiento farmacológico , Neumonía por Mycoplasma/epidemiología , Antibacterianos/uso terapéutico , Niño , España/epidemiología , Mycoplasma pneumoniae/aislamiento & purificación
4.
Sci Rep ; 14(1): 16587, 2024 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-39025897

RESUMEN

Drug repurposing aims to find new therapeutic applications for existing drugs in the pharmaceutical market, leading to significant savings in time and cost. The use of artificial intelligence and knowledge graphs to propose repurposing candidates facilitates the process, as large amounts of data can be processed. However, it is important to pay attention to the explainability needed to validate the predictions. We propose a general architecture to understand several explainable methods for graph completion based on knowledge graphs and design our own architecture for drug repurposing. We present XG4Repo (eXplainable Graphs for Repurposing), a framework that takes advantage of the connectivity of any biomedical knowledge graph to link compounds to the diseases they can treat. Our method allows methapaths of different types and lengths, which are automatically generated and optimised based on data. XG4Repo focuses on providing meaningful explanations to the predictions, which are based on paths from compounds to diseases. These paths include nodes such as genes, pathways, side effects, or anatomies, so they provide information about the targets and other characteristics of the biomedical mechanism that link compounds and diseases. Paths make predictions interpretable for experts who can validate them and use them in further research on drug repurposing. We also describe three use cases where we analyse new uses for Epirubicin, Paclitaxel, and Predinisone and present the paths that support the predictions.


Asunto(s)
Reposicionamiento de Medicamentos , Reposicionamiento de Medicamentos/métodos , Humanos , Inteligencia Artificial , Algoritmos
5.
mBio ; 15(8): e0166724, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39037272

RESUMEN

Severe COVID-19 has been associated with coinfections with bacterial and fungal pathogens. Notably, patients with COVID-19 who develop Staphylococcus aureus bacteremia exhibit higher rates of mortality than those infected with either pathogen alone. To understand this clinical scenario, we collected and examined S. aureus blood and respiratory isolates from a hospital in New York City during the early phase of the pandemic from both SARS-CoV-2+ and SARS-CoV-2- patients. Whole genome sequencing of these S. aureus isolates revealed broad phylogenetic diversity in both patient groups, suggesting that SARS-CoV-2 coinfection was not associated with a particular S. aureus lineage. Phenotypic characterization of the contemporary collection of S. aureus isolates from SARS-CoV-2+ and SARS-CoV-2- patients revealed no notable differences in several virulence traits examined. However, we noted a trend toward overrepresentation of S. aureus bloodstream strains with low cytotoxicity in the SARS-CoV-2+ group. We observed that patients coinfected with SARS-CoV-2 and S. aureus were more likely to die during the acute phase of infection when the coinfecting S. aureus strain exhibited high or low cytotoxicity. To further investigate the relationship between SARS-CoV-2 and S. aureus infections, we developed a murine coinfection model. These studies revealed that infection with SARS-CoV-2 renders mice susceptible to subsequent superinfection with low cytotoxicity S. aureus. Thus, SARS-CoV-2 infection sensitizes the host to coinfections, including S. aureus isolates with low intrinsic virulence. IMPORTANCE: The COVID-19 pandemic has had an enormous impact on healthcare across the globe. Patients who were severely infected with SARS-CoV-2, the virus causing COVID-19, sometimes became infected with other pathogens, which is termed coinfection. If the coinfecting pathogen is the bacterium Staphylococcus aureus, there is an increased risk of patient death. We collected S. aureus strains that coinfected patients with SARS-CoV-2 to study the disease outcome caused by the interaction of these two important pathogens. We found that both in patients and in mice, coinfection with an S. aureus strain lacking toxicity resulted in more severe disease during the early phase of infection, compared with infection with either pathogen alone. Thus, SARS-CoV-2 infection can directly increase the severity of S. aureus infection.


Asunto(s)
COVID-19 , Coinfección , SARS-CoV-2 , Infecciones Estafilocócicas , Staphylococcus aureus , COVID-19/complicaciones , COVID-19/microbiología , Coinfección/microbiología , Coinfección/virología , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidad , Infecciones Estafilocócicas/microbiología , Humanos , Animales , Ratones , SARS-CoV-2/genética , Filogenia , Femenino , Ciudad de Nueva York/epidemiología , Masculino , Virulencia , Persona de Mediana Edad , Secuenciación Completa del Genoma , Bacteriemia/microbiología , Modelos Animales de Enfermedad , Anciano
6.
Am J Orthopsychiatry ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38976392

RESUMEN

Although Black women face disproportionately high rates of gun violence and incarceration loss, there is a scarcity of culturally relevant interventions for this population. The aims of this study were to (a) examine the need for a culturally responsive, trauma-informed, and evidence-based grief intervention and to (b) identify key program components and considerations. Using a community-based participatory research framework, co-collaborators interviewed and surveyed 13 Black women who experienced gun violence and/or incarceration loss. Thematic analysis of interview data confirmed a need for this type of intervention due to the traumatic impact of losing a loved one, the inadequacy of available resources, and the personal and communal importance of addressing their grief. Critical intervention components included relationships and social support, help in "moving beyond" the experience, opportunities for emotional expression and validation, acknowledgment of spirituality and self-care, personal freedom in the grieving process, and addressing "underlying issues." The participants also completed a survey with 24 proposed intervention activities. The 22 they identified as "very important" largely corresponded with interview codes. Barriers to treatment included judgment and invalidation, lack of trust, disinterest, feeling stuck, mental health stigma, and lack of knowledge. Opinions about combining women with different types of loss in the same group and the importance of the group developers' lived experience were mixed. Overall, our findings support the need for culturally relevant, trauma-informed interventions in this population and provide a foundation for developing such an intervention. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

7.
Cell Death Dis ; 15(7): 534, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39068166

RESUMEN

Lymphoid tumor patients often exhibit resistance to standard therapies or experience relapse post-remission. Relapse is driven by Tumor Initiating Cells (TICs), a subset of tumor cells capable of regrowing the tumor and highly resistant to therapy. Growing cells in 3D gels is a method to discern tumorigenic cells because it strongly correlates with tumorigenicity. The finding that TICs, rather than differentiated tumor cells, grow in 3D gels offers a unique opportunity to unveil TIC-specific signaling pathways and therapeutic targets common to various cancer types. Here, we show that culturing lymphoid cells in 3D gels triggers reactive oxygen species (ROS) production, leading to non-tumor lymphoid cell death while enabling the survival and proliferation of a subset of lymphoma/leukemia cells, TICs or TIC-like cells. Treatment with the antioxidant N-acetylcysteine inhibits this lethality and promotes the growth of primary non-tumor lymphoid cells in 3D gels. A subset of lymphoma cells, characterized by an increased abundance of the antioxidant glutathione, escape ROS-induced lethality, a response not seen in non-tumor cells. Reducing glutathione production in lymphoma cells, either through pharmacological inhibition of glutamate cysteine ligase (GCL), the enzyme catalyzing the rate-limiting step in glutathione biosynthesis, or via knockdown of GCLC, the GCL catalytic subunit, sharply decreased cell growth in 3D gels and xenografts. Tumor cells from B-cell lymphoma/leukemia patients and λ-MYC mice, a B-cell lymphoma mouse model, overproduce glutathione. Importantly, pharmacological GCL inhibition hindered lymphoma growth in female λ-MYC mice, suggesting that this treatment holds promise as a therapeutic strategy for female lymphoma/leukemia patients.


Asunto(s)
Glutatión , Linfoma , Células Madre Neoplásicas , Especies Reactivas de Oxígeno , Animales , Humanos , Femenino , Linfoma/patología , Linfoma/metabolismo , Linfoma/tratamiento farmacológico , Glutatión/metabolismo , Ratones , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Masculino , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Carcinogénesis/patología , Carcinogénesis/efectos de los fármacos , Carcinogénesis/metabolismo
8.
Nutrients ; 16(14)2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-39064653

RESUMEN

The introduction of closed-loop systems in the pediatric population has been a revolution in the management and evolution of diabetes. However, there are not many published studies in situations in which the feeding, schedules, and activities of the children deviate from the routine for which the systems were programmed, as in the case of a summer camp for children and adolescents with diabetes, where the specific programming of this device is not well known. It was a single-center prospective preliminary study. A total of twenty-seven patients (mean age 11.9 ± 1.9 years, 40% male, duration of diabetes 6.44 ± 2.83 years) were included (twenty with Medtronic MiniMed 780G system and seven with Tandem Control-IQ). Glucometric variables and pump functionality were monitored during the 7-day camp and in the following 3 weeks. There was no decrease from the objective TIR 70% at any moment. The worst results in Time Below Range were at 72 h from starting the camp, and the worst results in Time Above Range were in the first 24 h, with a progressive improvement after that. No episodes of level 3 hypoglycemia or ketoacidosis occurred. The use of specific programming in two integrated systems, with complex blood glucose regulation algorithms and not-prepared-for situations with increased levels of physical activity or abrupt changes in feeding routines, did not result in an increased risk of level 3 hypoglycemia and ketoacidosis for our pediatric type 1 diabetes (T1D) patients, regardless of the closed-loop device.


Asunto(s)
Glucemia , Diabetes Mellitus Tipo 1 , Sistemas de Infusión de Insulina , Insulina , Humanos , Niño , Masculino , Adolescente , Femenino , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/sangre , Estudios Prospectivos , Insulina/administración & dosificación , Automonitorización de la Glucosa Sanguínea/instrumentación , Hipoglucemiantes/administración & dosificación , Acampada , Control Glucémico/métodos , Algoritmos , Hipoglucemia/prevención & control
9.
J Comp Physiol B ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995419

RESUMEN

With climate change increasing not just mean temperatures but the frequency of cold snaps and heat waves, animals occupying thermally variable areas may be faced with thermal conditions for which they are not prepared. Studies of physiological adaptations of temperate resident birds to such thermal variability are largely lacking in the literature. To address this gap, we acclimated winter-phenotype house sparrows (Passer domesticus) to stable warm, stable cold, and fluctuating cold temperatures. We then measured several metrics of the oxidative stress (OS) system, including enzymatic and non-enzymatic antioxidants and lipid oxidative damage, in brain (post-mitotic), kidney (mitotic), liver (mitotic) and pectoralis muscle (post-mitotic). We predicted that high metabolic flexibility could be linked to increases in reactive oxygen damage. Alternatively, if variation in ROS production is not associated with metabolic flexibility, then we predict no antioxidant compensation with thermal variation. Our data suggest that ROS production is not associated with metabolic flexibility, as we found no differences across thermal treatment groups. However, we did find differences across tissues. Brain catalase activity demonstrated the lowest values compared with kidney, liver and muscle. In contrast, brain glutathione peroxidase (GPx) activities were higher than those in kidney and liver. Muscle GPx activities were intermediate to brain and kidney/liver. Lipid peroxidation damage was lowest in the kidney and highest in muscle tissue.

10.
ACS Appl Mater Interfaces ; 16(28): 36735-36744, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38952105

RESUMEN

The piezoelectric properties of two-dimensional semiconductor nanobubbles present remarkable potential for application in flexible optoelectronic devices, and the piezoelectric field has emerged as an efficacious pathway for both the separation and migration of photogenerated electron-hole pairs, along with inhibition of recombination. However, the comprehension and control of photogenerated carrier dynamics within nanobubbles still remain inadequate. Hence, this study is dedicated to underscore the importance of in situ detection and detailed characterization of photogenerated electron-hole pairs in nanobubbles to enrich understanding and strategic manipulation in two-dimensional semiconductor materials. Utilizing frequency modulation kelvin probe force microscopy (FM-KPFM) and strain gradient distribution techniques, the existence of a piezoelectric field in monolayer WS2 nanobubbles was confirmed. Combining w/o and with illumination FM-KPFM, second-order capacitance gradient technique and in situ nanoscale tip-enhanced photoluminescence characterization techniques, the interrelationships among the piezoelectric effect, interlayer carrier transfer, and the funneling effect for photocarrier dynamics process across various nanobubble sizes were revealed. Notably, for a WS2/graphene bubble height of 15.45 nm, a 0 mV surface potential difference was recorded in the bubble region w/o and with illumination, indicating a mutual offset of piezoelectric effect, interlayer carrier transfer, and the funneling effect. This phenomenon is prevalent in transition metal dichalcogenides materials exhibiting inversion symmetry breaking. The implication of our study is profound for advancing the understanding of the dynamics of photogenerated electron-hole pair in nonuniform strain piezoelectric systems, and offers a reliable framework for the separation and modulation of photogenerated electron-hole pair in flexible optoelectronic devices and photocatalytic applications.

11.
Pediatr Infect Dis J ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38920379

RESUMEN

BACKGROUND: Since the end of 2023, an elevated incidence and severity of Mycoplasma pneumoniae infections among children in Asia has been noted. Subsequently, this trend was observed in several European countries although limited data are currently available. We conducted a national study to delineate the ongoing M. pneumoniae outbreak in our country. METHODS: A multicenter retrospective observational study was conducted across 32 hospitals in Spain, encompassing patients under 18 years old hospitalized for M. pneumoniae infection from January 2023 to March 2024. Infection was confirmed by positive polymerase chain reaction and/or by 2 serological tests. RESULTS: A total of 623 children were included, with 79% of cases diagnosed in the final 3 months of the study period. Pneumonia was the most common diagnosis (87%). Respiratory symptoms were present in 97% of cases, with 62% requiring oxygen supplementation and 14% requiring admission to the pediatric intensive care unit (PICU). Risk factors for PICU admission included the presence of neurological symptoms, hypoxemia and a history of prematurity. Children admitted to the PICU exhibited significantly higher neutrophil counts upon admission. CONCLUSIONS: We have observed a notable increase in hospital admissions, including PICU support by up to 14%, due to M. pneumoniae infection in our country since November 2023, indicative of a more severe clinical course associated with this pathogen.

14.
Parasitol Res ; 123(4): 196, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38662084

RESUMEN

Many pathogens are related to carcinogenesis. Chronic inflammation, as a result of persistent infection, leads to DNA damage, higher expression of oncogenes, decreased apoptosis and immunosuppression, which are some of the reasons for cancer induction. Among parasites, Schistosoma, Opistorchis and Clonorchis are recognised as infectious agents which contribute to cancer. A relationship between Anisakis and cancer was hypothesised because cellular responses to Anisakis products could result in inflammation and DNA damage. Previous research has shown a decrease in CD8+ γδ T-cells and an increase in αß and γδ T-cell apoptosis in colon cancer (CC) samples. Ninety-two CC patients and 60 healthy subjects were recruited. γδ and αß T-cells were analysed, and their apoptosis was evaluated. Anti-Anisakis antibodies were tested in sera from CC patients and controls. Anti-Anisakis IgG, IgM, IgA and IgE antibodies were significantly higher in CC patients. A significant increase in anti-Anisakis IgA levels was observed in patients with angiolymphatic invasion. The number of all γδ T-cells, as well as CD3+ CD4+ αß T-cells, was significantly lower in CC patients. The apoptosis of all T-cells was significantly increased in patients with CC. We observed a significantly higher percentage of anti-Anisakis IgE positive patients having a deficit of CD3+ γδ T-cells. Our results suggest a relationship between Anisakis and CC.


Asunto(s)
Anisakis , Anticuerpos Antihelmínticos , Neoplasias del Colon , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Antihelmínticos/sangre , Anticuerpos Antihelmínticos/inmunología , Femenino , Neoplasias del Colon/inmunología , Neoplasias del Colon/parasitología , Anciano , Animales , Anisakis/inmunología , Adulto , Apoptosis , Anciano de 80 o más Años , Subgrupos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Linfocitos T/inmunología
15.
Lett Appl Microbiol ; 77(5)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38684470

RESUMEN

In this study, we evaluated the antimicrobial activity of bacteria isolated from the marine sponges Hymeniacidon perlevis and Halichondria panicea against seven Acinetobacter baumannii strains, the majority of which were clinically relevant carbapenem-resistant A. baumannii strains. We observed the inhibitory activity of 18 (out of 114) sponge-isolated bacterial strains against all A. baumanii strains using medium-throughput solid agar overlay assays. These inhibitory strains belonged to the genera Lactococcus, Pseudomonas, and Vagococcus. In addition, this antimicrobial activity was validated through a liquid co-cultivation challenge using an inhibitory strain of each genus and a green fluorescent protein-tagged A. baumanii strain. Fluorescence measurements indicated that the growth of A. baumanii was inhibited by the sponge isolates. In addition, the inability of A. baumanii to grow after spreading the co-cultures on solid medium allowed us to characterize the activity of the sponge isolates as bactericidal. In conclusion, this study demonstrates that marine sponges are a reservoir of bacteria that deserves to be tapped for antibiotic discovery against A. baumanii.


Asunto(s)
Acinetobacter baumannii , Antibacterianos , Carbapenémicos , Pruebas de Sensibilidad Microbiana , Poríferos , Animales , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/crecimiento & desarrollo , Acinetobacter baumannii/aislamiento & purificación , Poríferos/microbiología , Antibacterianos/farmacología , Carbapenémicos/farmacología , Antibiosis
16.
Biomark Res ; 12(1): 38, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594765

RESUMEN

BACKGROUND & AIMS: Metallothionein-3 (hMT3) is a structurally unique member of the metallothioneins family of low-mass cysteine-rich proteins. hMT3 has poorly characterized functions, and its importance for hepatocellular carcinoma (HCC) cells has not yet been elucidated. Therefore, we investigated the molecular mechanisms driven by hMT3 with a special emphasis on susceptibility to sorafenib. METHODS: Intrinsically sorafenib-resistant (BCLC-3) and sensitive (Huh7) cells with or without up-regulated hMT3 were examined using cDNA microarray and methods aimed at mitochondrial flux, oxidative status, cell death, and cell cycle. In addition, in ovo/ex ovo chick chorioallantoic membrane (CAM) assays were conducted to determine a role of hMT3 in resistance to sorafenib and associated cancer hallmarks, such as angiogenesis and metastastic spread. Molecular aspects of hMT3-mediated induction of sorafenib-resistant phenotype were delineated using mass-spectrometry-based proteomics. RESULTS: The phenotype of sensitive HCC cells can be remodeled into sorafenib-resistant one via up-regulation of hMT3. hMT3 has a profound effect on mitochondrial respiration, glycolysis, and redox homeostasis. Proteomic analyses revealed a number of hMT3-affected biological pathways, including exocytosis, glycolysis, apoptosis, angiogenesis, and cellular stress, which drive resistance to sorafenib. CONCLUSIONS: hMT3 acts as a multifunctional driver capable of inducing sorafenib-resistant phenotype of HCC cells. Our data suggest that hMT3 and related pathways could serve as possible druggable targets to improve therapeutic outcomes in patients with sorafenib-resistant HCC.

17.
Methods Mol Biol ; 2798: 205-212, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38587745

RESUMEN

Superoxide and hydrogen peroxide are reactive oxygen species (ROS) involved in the oxidation of multiple biological molecules and the signaling processes during plant growth and stress response. Thus, control of ROS is fundamental for cell survival and development, with superoxide dismutase (EC 1.15.1.1, SOD) being one of the main enzymes involved. Different isoforms of SOD catalyze the dismutation of superoxide (O2.-) to hydrogen peroxide (H2O2) and oxygen (O2), such as Mn-SODs, Cu,Zn-SODs, and Fe-SODs. Using non-denaturing polyacrylamide gel electrophoresis (PAGE) combined with a specific staining method for SOD activity, the protocol describes the identification of different SOD isozymes, based on their differential inhibition by KCN and H2O2, in different organs and plant species such as pea (Pisum sativum L.) leaves and pepper (Capsicum annuum L.) fruits.


Asunto(s)
Isoenzimas , Superóxido Dismutasa , Superóxidos , Peróxido de Hidrógeno , Especies Reactivas de Oxígeno , Frutas , Oxígeno , Pisum sativum
18.
Neuropsychologia ; 198: 108867, 2024 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-38518888

RESUMEN

Cardiac interoception, the ability to sense and process cardiac afferent signals, has been shown to improve after a single session of acute physical exercise. However, it remains unclear whether repetitive engagement in physical exercise over time leads to long-term changes in cardiac interoceptive accuracy. It is also unknown whether those changes affect the neural activity associated with the processing of afferent cardiac signals, assessed by the heart-evoked potential (HEP). In this study, we aimed to investigate this hypothesis through two cross-sectional studies, categorizing participants as active or inactive based on physical fitness (Study I; N = 45) or self-reported physical activity levels (Study II; N = 60). Interoception was assessed at rest using the HEP (Studies I and II), the Heartbeat Counting task (Study II), and the Rubber Hand Illusion (RHI) (Study II). Study I showed strong evidence of better cardiovascular fitness in the active group than in the inactive group as well as robust between-group differences in electrocardiogram (ECG) recordings. Study 2 replicated the clear differences in ECG as a function of regular physical activity. Those results were expected due to clear differences in physical activity habits. In contrast, our analysis revealed no robust differences between groups across cardiac interoception tasks and the RHI, although the direct relevance of these measures to interoception remains under investigation. In sum, our results do not provide convincing evidence to support a strong version of the notion that regular physical exercise is associated with an enhanced in cardiac interoception.


Asunto(s)
Electrocardiografía , Ejercicio Físico , Frecuencia Cardíaca , Interocepción , Humanos , Interocepción/fisiología , Masculino , Femenino , Ejercicio Físico/fisiología , Estudios Transversales , Adulto , Adulto Joven , Frecuencia Cardíaca/fisiología , Corazón/fisiología , Potenciales Evocados/fisiología , Electroencefalografía
19.
J Exp Zool A Ecol Integr Physiol ; 341(5): 606-614, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38511570

RESUMEN

Regulation of internal body temperature (Tb), or thermoregulation, is an evolutionarily conserved trait that places demand on basal metabolic rate of endothermic animals. Across species, athletes generate increased quantities of heat in comparison to their nonathletic counterparts and, therefore, must mediate physiological unbalance by upregulating the effectiveness of their heat dissipation abilities. Canine athletes are no exception to this phenomenon, however, with literature denoting body temperatures lower than nonathletic canines, it is clear they must possess adaptations to mitigate this demand. With VO2 max measurements of more than 200 mL/kg/min in sled dogs with mild training to 300 mL/kg/min in highly trained animals, sled dogs are a prime example of athleticism in canines. Seeking to determine correlations between Tear and body mass, morphology, and age of canine athletes, core body temperature (Tb) was measured with an instant ear thermometer, using Tear as a correlate before and after a 2-mile run. In addition, we employed thermal imaging analysis to capture body-wide heat dissipation patterns in sled dogs, and focused on thermal variation of mouth (Tmouth), nose (Tnose), and eyes (Teye). Furthermore, we looked at correlations between thermal variability across these four tissues and head morphology of each dog. Tear was consistently the highest temperature across all tissues measured, with a 1.5°C increase between pre- to postexercise (p < 0.001). Thermal imaging revealed significant positive correlations between Tmouth and body mass 15 min postexercise (p = 0.0023) as well as significantly negative correlations between Tnose and body mass at before exercise (p = 0.0468), Teye and nose length after run (p = 0.0076), and Tmouth and nose length after run (p = 0.0110). As body temperature rises during exercise, it becomes increasingly important to regulate blood flow throughout the body to supply working tissues with oxygen. This demand is offset by the role of the snout in evaporative cooling through panting, functioning as a prime location for heat dissipation and therefore maintaining significant relationships with many other vascularized tissues.


Asunto(s)
Regulación de la Temperatura Corporal , Condicionamiento Físico Animal , Animales , Perros/fisiología , Regulación de la Temperatura Corporal/fisiología , Condicionamiento Físico Animal/fisiología , Masculino , Femenino , Temperatura Corporal/fisiología , Lágrimas/fisiología
20.
Case Rep Ophthalmol ; 15(1): 202-211, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38487796

RESUMEN

Introduction: The term white dot syndromes has been used to refer conditions that differ in their morphology and prognosis. We report three cases of different pathologies encompassed within the white dot syndromes. Case Presentations: Case 1: A 26-year-old female presented with scotoma in her right eye. Fundus examination revealed multiple white dots that demonstrated early hyperfluorescence with late staining on FA. OCT showed discontinuities in inner segment-outer segment junction associated with columnar-shaped outer retinal hyperreflective bands. AF revealed multiple hyperautofluorescent dots around the posterior pole, compatible with multiple evanescent white dot syndrome. The symptoms improved without treatment. Case 2: A 16-year-old male presented with retinal lesions compatible with punctate inner choroidopathy in his right eye. OCT showed lesion in the outer retinal layer. FAF revealed parafoveal hypoautofluorescent dots with early hyperfluorescence and late staining on FFA. After oral corticotherapy, they progress to atrophic scars. Case 3: A 65-year-old male presented with scotoma and decreased vision in his right eye. OCT showed hyperreflectivity in the outer layer that progresses to a large atrophic plaque with foveal affectation. FAF demonstrated hyperautofluorescent placoid lesion occupying macular area, compatible with acute posterior multifocal placoid pigment epitheliopathy. Retinal lesions improved with systemic corticosteroids. Conclusion: The FAF pattern helps know the distribution of the lesions. It represents a noninvasive method that has been shown to be useful in the diagnosis and monitoring of white dot syndromes.

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