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The pathogenic fungus Aspergillus fumigatus utilizes a cyclic ferrioxamine E (FOXE) siderophore to acquire iron from the host. Biomimetic FOXE analogues were labeled with gallium-68 for molecular imaging with PET. [68Ga]Ga(III)-FOXE analogues were internalized in A. fumigatus cells via Sit1. Uptake of [68Ga]Ga(III)-FOX 2-5, the most structurally alike analogue to FOXE, was high by both A. fumigatus and bacterial Staphylococcus aureus. However, altering the ring size provoked species-specific uptake between these two microbes: ring size shortening by one methylene unit (FOX 2-4) increased uptake by A. fumigatus compared to that by S. aureus, whereas lengthening the ring (FOX 2-6 and 3-5) had the opposite effect. These results were consistent both in vitro and in vivo, including PET imaging in infection models. Overall, this study provided valuable structural insights into the specificity of siderophore uptake and, for the first time, opened up ways for selective targeting and imaging of microbial pathogens by siderophore derivatization.
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Aspergilose , Aspergillus fumigatus , Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons , Sideróforos , Staphylococcus aureus , Aspergillus fumigatus/metabolismo , Aspergillus fumigatus/química , Tomografia por Emissão de Pósitrons/métodos , Sideróforos/química , Sideróforos/metabolismo , Animais , Staphylococcus aureus/metabolismo , Aspergilose/diagnóstico por imagem , Aspergilose/microbiologia , Radioisótopos de Gálio/química , Especificidade da Espécie , Camundongos , Compostos Férricos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Desferroxamina/química , Peptídeos CíclicosRESUMO
The mold Aspergillus fumigatus employs two high-affinity uptake systems, reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA), for the acquisition of the essential trace element iron. SIA has previously been shown to be crucial for virulence in mammalian hosts. Here, we show that a lack of AcuK or AcuM, transcription factors required for the activation of gluconeogenesis, decreases the production of both extra- and intracellular siderophores in A. fumigatus. The lack of AcuM or AcuK did not affect the expression of genes involved in RIA and SIA, suggesting that these regulators do not directly regulate iron homeostasis genes, but indirectly affect siderophore production through their influence on metabolism. Consistent with this, acetate supplementation reversed the intracellular siderophore production defect of ΔacuM and ΔacuK. Moreover, ΔacuM and ΔacuK displayed a similar growth defect under iron limitation and iron sufficiency, which suggests they have a general role in carbon metabolism apart from gluconeogenesis. In agreement with a potential role of the glyoxylate cycle in adaptation to iron starvation, transcript levels of the malate synthase-encoding acuE were found to be upregulated by iron limitation that is partially dependent on AcuK and AcuM. Together, these data demonstrate the influence of iron availability on carbon metabolism.
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Attention Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder in childhood that often persists into adulthood. Objectively diagnosing ADHD can be challenging due to the reliance on subjective questionnaires in clinical assessment. Fortunately, recent advancements in artificial intelligence (AI) have shown promise in providing objective diagnoses through the analysis of medical images or activity recordings. These AI-based techniques have demonstrated accurate ADHD diagnosis; however, the growing complexity of deep learning models has introduced a lack of interpretability. These models often function as black boxes, unable to offer meaningful insights into the data patterns that characterize ADHD. OBJECTIVE: This paper proposes a methodology to interpret the output of an AI-based diagnosis system for combined ADHD in age and gender-stratified populations. METHODS: Our system is based on the analysis of 24 hour-long activity records using Convolutional Neural Networks (CNNs) to classify spectrograms of activity windows. These windows are interpreted using occlusion maps to highlight the time-frequency patterns explaining ADHD activity. RESULTS: Significant differences in the frequency patterns between ADHD and controls both in diurnal and nocturnal activity were found for all the populations. Temporal dispersion also presented differences in the male population. CONCLUSION: The proposed interpretation techniques for CNNs highlighted gender- and age-related differences between ADHD patients and controls. Leveraging these differences could potentially lead to improved diagnostic accuracy, especially if a larger and more balanced dataset is utilized. SIGNIFICANCE: Our findings pave the way for the development of an AI-based diagnosis system for ADHD that offers interpretability, thereby providing valuable insights into the underlying etiology of the disease.
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Transtorno do Deficit de Atenção com Hiperatividade , Aprendizado Profundo , Humanos , Masculino , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Inteligência Artificial , Redes Neurais de ComputaçãoRESUMO
Sub-nanometer metal clusters have special physical and chemical properties, significantly different from those of nanoparticles. However, there is a major concern about their thermal stability and susceptibility to oxidation. In situ X-ray Absorption spectroscopy and Near Ambient Pressure X-ray Photoelectron spectroscopy results reveal that supported Cu5 clusters are resistant to irreversible oxidation at least up to 773â K, even in the presence of 0.15â mbar of oxygen. These experimental findings can be formally described by a theoretical model which combines dispersion-corrected DFT and first principles thermochemistry revealing that most of the adsorbed O2 molecules are transformed into superoxo and peroxo species by an interplay of collective charge transfer within the network of Cu atoms and large amplitude "breathing" motions. A chemical phase diagram for Cu oxidation states of the Cu5 -oxygen system is presented, clearly different from the already known bulk and nano-structured chemistry of Cu.
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Pesticides are an environmental problem. The search for new pest control methods has focused on compounds with low or no toxic effects in non-target organisms. Analogs of the juvenile hormone (JH) interfere endocrine system of arthropods. However, the lack of effect on non-target species requires confirmation. This article analyzes the impact of Fenoxycarb, an analog of JH, on Physella acuta, an aquatic gastropod. For 1 week, animals were exposed to 0.01, 1, and 100 µg/L and the RNA was isolated to analyze the gene expression by retrotranscription and Real-Time PCR. Forty genes related to the endocrine system, the DNA repair mechanisms, the detoxification mechanisms, oxidative stress, the stress response, the nervous system, hypoxia, energy metabolism, the immune system, and apoptosis were analyzed. Three of the genes, AchE, HSP17.9, and ApA, showed responses to the presence of Fenoxycarb at 1 µg/L, with no statistically significant responses in the rest of the genes and at the remaining concentrations. From the results, it can be concluded that Fenoxycarb shows a weak response at the molecular level in P. acuta in the tested time and concentrations. However, Aplysianin-A, a gene related to immunity, was altered so the long-term effect could be relevant. Therefore, additional research is required to confirm the safety of Fenoxycarb in non-arthropod species in the long term.
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Praguicidas , Animais , Hormônios Juvenis , Caramujos/genética , Expressão GênicaRESUMO
This review was conducted to evaluate the efficacy of light-emitting diode (LED) phototherapy as compared with the conventional phototherapy in neonates with unconjugated hyperbilirubinemia and their adverse effects. We searched the following databases right from their inception till April, 2021: MEDLINE, EMBASE, Cochrane Library, and LILACS. Randomized clinical trials (RCTs) comparing the LED phototherapy with other light sources, which enrolled newborns (term and preterm) with unconjugated hyperbilirubinemia were included. We included 21 articles in this review. The treatment with the LED light therapy had a lower failure rate as compared with the non-LED one (RR = 0.60, 95% CI: 0.39-0.94). The mean duration of phototherapy was significantly shorter in the group with the LED light source as compared with the one with the non-LED light source (mean difference [hours]: -8.07, 95% CI: -8.45 to -7.68), regardless of the type of non-LED units. However, the rate of bilirubin showed a comparable decline (mean difference [mg/dL/h]: 0.01, 95% CI: -0.00, 0.03) in both the light sources, irrespective of irradiance or distance. No studies reported primary outcomes related to the neurotoxicity effects of hyperbilirubinemia in neonates. The LED light devices caused a significantly higher risk of hypothermia. Neonates were at a lower risk of developing hyperthermia and skin rash with the LED light therapy. Our findings provide support for the use of LED light source phototherapy due to its better clinical efficacy, which is evidenced by its shorter duration and lower rate of treatment failure, as compared with the non-LED light sources. KEY POINTS: · The efficacy of phototherapy is dependent on specific characteristics of light sources of phototherapy devices.. · LED phototherapy demonstrated better efficacy with shorter duration and lower rate of treatment failure.. · Adverse effects of phototherapy devices such as hypothermia, hyperthermia, and skin rash should be monitored..
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Exantema , Hiperbilirrubinemia Neonatal , Hipotermia , Recém-Nascido , Humanos , Hiperbilirrubinemia Neonatal/terapia , Hiperbilirrubinemia Neonatal/etiologia , Hipotermia/etiologia , Bilirrubina , Fototerapia/efeitos adversos , Exantema/etiologiaRESUMO
Siderophores play an important role in fungal virulence, serving as trackers for in vivo imaging and as biomarkers of fungal infections. However, siderophore uptake is only partially characterized. As the major cause of aspergillosis, Aspergillus fumigatus is one of the most common airborne fungal pathogens of humans. Here, we demonstrate that this mold species mediates the uptake of iron chelated by the secreted siderophores triacetylfusarinine C (TAFC) and fusarinine C by the major facilitator-type transporters MirB and MirD, respectively. In a murine aspergillosis model, MirB but not MirD was found to be crucial for virulence, indicating that TAFC-mediated uptake plays a dominant role during infection. In the absence of MirB, TAFC becomes inhibitory by decreasing iron availability because the mutant is not able to recognize iron that is chelated by TAFC. MirB-mediated transport was found to tolerate the conjugation of fluorescein isothiocyanate to triacetylfusarinine C, which might aid in the development of siderophore-based antifungals in a Trojan horse approach, particularly as the role of MirB in pathogenicity restrains its mutational inactivation. Taken together, this study identified the first eukaryotic siderophore transporter that is crucial for virulence and elucidated its translational potential as well as its evolutionary conservation. IMPORTANCE Aspergillus fumigatus is responsible for thousands of cases of invasive fungal disease annually. For iron uptake, A. fumigatus secretes so-called siderophores, which are taken up after the binding of environmental iron. Moreover, A. fumigatus can utilize siderophore types that are produced by other fungi or bacteria. Fungal siderophores raised considerable interest due to their role in virulence and their potential for the diagnosis and treatment of fungal infections. Here, we demonstrate that the siderophore transporter MirB is crucial for the virulence of A. fumigatus, which reveals that its substrate, triacetylfusarinine C, is the most important siderophore during infection. We found that in the absence of MirB, TAFC becomes inhibitory by decreasing the availability of environmental iron and that MirB-mediated transport tolerates the derivatization of its substrate, which might aid in the development of siderophore-based antifungals. This study significantly improved the understanding of fungal iron homeostasis and the role of siderophores in interactions with the host.
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Aspergilose , Micoses , Humanos , Animais , Camundongos , Sideróforos/metabolismo , Aspergillus fumigatus/metabolismo , Virulência , Antifúngicos/metabolismo , Aspergilose/microbiologia , Ferro/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Isotiocianatos/metabolismo , FluoresceínasRESUMO
Resumen El botulismo del lactante (BL), es la forma más frecuente del botulismo humano en la actualidad, es una enfermedad "rara" o "huérfana" ya que afecta a menos del 0,05 % de la población. El objetivo del presente trabajo es determinar la Incidencia del BL en la Argentina, evaluar el diagnóstico y tratamiento realizado, comparar la evolución y las secuelas al alta en pacientes con y sin tratamiento específico y, considerar las características climáticas (precipitaciones y vientos) y los estudios de muestras de suelos de las provincias con mayor cantidad de casos de BL. Presentamos un estudio multicéntrico, de cohorte (longitudinal) observacional, retrospectivo analizando las historias clínicas de los pacientes con BL, que ingresaron a Unidades de Cuidados Intensivos Pediátricos con asistencia respiratoria mecánica, desde el 1 de enero de 2010 hasta 31 de diciembre de 2013. Se consideró: edad, sexo, días previos al ingreso hasta diagnóstico por laboratorio, total internación en Unidades de Cuidados Intensivos Pediátricos con asistencia respiratoria mecánica, alimentación por sonda nasogástrica, tratamiento y secuelas. En Argentina entre 2010 al 2013 se registraron 216 casos de BL. En este trabajo se analizaron 79 pacientes provenientes de 11 provincias, que ingresaron a Unidades de Cuidados Intensivos Pediátricos. La edad promedio de los pacientes ingresados fue de 4 meses, de los cuales 90% recibía alimentación materna. Dieciocho pacientes de seis provincias recibieron antitoxina botulínica equina. El promedio de días de enfermedad previos al ingreso fue de 2 días en los pacientes que recibieron tratamiento con antitoxina botulínica equina y 4 días en los pacientes no tratados. Diagnóstico de laboratorio (Toxina A y Clostridium botulinum) a los 5 días en los tratados con antitoxina botulínica equina, y a los 11,5 en los no tratados. En los pacientes tratados con antitoxina botulínica equina, el promedio de días de internación fue de 30 versus 70 días en los no tratados (p=0,0001). El promedio días en las Unidades de Cuidados Intensivos Pediátricos de los pacientes tratados fue de 20 versus 54 días en los no tratados (p=0,0001). Los días de asistencia respiratoria mecánica en los tratados fue de 16 versus 43 días en los no tratados (p=0,0001) y los tratados requirieron 29 días de alimentación por sonda nasogástrica versus 70 días en los no tratados (p=0,0001). El 40% de los pacientes tratados presentaron neumonía asociada a respirador versus el 56% de los no tratados (p=0,0038), sepsis el 11% versus el 34% (p=0,005) y secuelas al alta 6% versus 64% (p=0,0001), respectivamente. En zonas con mayor número de casos, se observó una alta frecuencia de esporas en los suelos, asociado a clima seco y ventoso. Los resultados sugieren que el tratamiento precoz con antitoxina botulínica equina es una alternativa hasta disponer de inmuno-globulina botulínica humana. Los climas secos y ventosos favorecen la enfermedad.
Abstract Infant botulism (BL), the most common form of human botulism today, is a "rare" or "orphan" disease as it affects less than 0.05% of the population. The objective of this work is to determine the incidence of BL in Argentina. Evaluate the diagnosis and treatment performed. To compare evolution and sequelae at discharge in patients with and without specific treatment. Consider the climatic characteristics (precipitations and winds) and the studies of soil samples from the provinces with the highest number of BL cases. We present a retrospective, observational, multicenter, cohort (longitudinal) study analyzing the medical records of patients with BL, who were admitted to Pediatric Intensive Care Units with mechanical ventilation, from January 1,2010 to December 31,2013. The following were considered: age, sex, days prior to admission, until laboratory diagnosis, Pediatric Intensive Care Units, me-chanical respiratory assistance, average hospital days, nasogastric tube feeding, treatment and sequelae. In the country, 216 cases of BL were registered between 2010 and 2013. We analyzed 79 who were admitted to Pediatric Intensive Care Units from 11 provinces. Average age 4 months. Maternal nutrition 90%. Eighteen patients (6 provinces) received equine botulinum antitoxin .Mean days of illness prior to admission: 2 in those treated with equine botulinum antitoxin and 4 in those not treated. Laboratory diagnosis (Toxin A and Clostridium botulinum) at 5 days in treated with equine botulinum antitoxin, at 11.5 in untreated. Patients with equine botulinum antitoxin average hospital days 30 vs 70 in untreated patients (p=0.0001). Mean Pediatric Intensive Care Unit days 20 vs 54 (p=0.0001) of mechanical respiratory assistance 16 vs 43 (p=0.0001) and nasogastric tube feeding 29 vs 70 (p=0.0001). Those treated presented ventilator-associated pneumonia 40% vs 56% (p=0.0038) and sepsis 11% vs 34% (p=0.005). Sequelae at discharge 6% vs 64% (p=0.0001) in those not treated. In areas with a higher number of cases, high frequency of spores in soils, dry and windy weather. The results suggest that early treatment with equine botulinum antitoxin is an alternative until human botulinum immunoglobulin is available. The dry and windy climates favor the disease.
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Humanos , Lactente , Botulismo/diagnóstico , Botulismo/tratamento farmacológico , Antitoxina Botulínica/uso terapêutico , Toxinas Botulínicas Tipo A , Argentina/epidemiologiaRESUMO
By replacing a phenolic ring of (E)-resveratrol with an 1,3,4-oxadiazol-2(3H)-one heterocycle, new resveratrol-based multitarget-directed ligands (MTDLs) were obtained. They were evaluated in several assays related to oxidative stress and inflammation (monoamine oxidases, nuclear erythroid 2-related factor, quinone reductase-2, and oxygen radical trapping) and then in experiments of increasing complexity (neurogenic properties and neuroprotection vs okadaic acid). 5-[(E)-2-(4-Methoxyphenyl)ethenyl]-3-(prop-2-yn-1-yl)-1,3,4-oxadiazol-2(3H)-one (4e) showed a well-balanced MTDL profile: cellular activation of the NRF2-ARE pathway (CD = 9.83 µM), selective inhibition of both hMAO-B and QR2 (IC50s = 8.05 and 0.57 µM), and the best ability to promote hippocampal neurogenesis. It showed a good drug-like profile (positive in vitro central nervous system permeability, good physiological solubility, no glutathione conjugation, and lack of PAINS or Lipinski alerts) and exerted neuroprotective and antioxidant actions in both acute and chronic Alzheimer models using hippocampal tissues. Thus, 4e is an interesting MTDL that could stimulate defensive and regenerative pathways and block early events in neurodegenerative cascades.
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Monoaminoxidase , Fármacos Neuroprotetores , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Ligantes , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Resveratrol/farmacologiaRESUMO
Objectives. Several studies have shown that one of the most common causes of collision is driver fatigue since fatigue causes drowsiness while driving and this decreases the driver's ability to maneuver the vehicle and increases the probability of their nodding off and falling asleep at the wheel. This may be due to a variety of personal reasons and specific factors connected to working conditions. In the present work we therefore intend to develop a predictive model for fatigue in professional drivers using the following indicators: age, gender, personality, burnout, characteristics and job content. Method. The participants were 516 professional drivers from different transport sectors, obtained through non-probabilistic sampling. SPSS version 25.0 was used for data analysis. Results. The predictive capacity of a number of variables that affect drivers by causing fatigue is determined. Fatigue can be predicted through certain variables, with the best predictor being exhaustion (48.8%). Conclusions. This research contributes to a greater knowledge of the factors that produce fatigue in professional drivers. It highlights the importance of designing interventions to reduce the incidence of fatigue, resulting in greater well-being for the driver and a lower incidence of collisions.
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Condução de Veículo , Esgotamento Profissional , Humanos , Esgotamento Profissional/epidemiologia , Fadiga/epidemiologia , Personalidade , Satisfação no Emprego , Inquéritos e QuestionáriosRESUMO
Objectives. Professional drivers drive for many hours without rest. This factor, in addition to the characteristics of the job, the vehicle, the environment and the driver, causes driver fatigue. Fatigue is one of the most common risk factors when driving because it causes drowsiness, decreases drivers' attention and may make them fall asleep at the wheel. In this article we propose a predictive model for professional drivers using the following variables: age, number of children, time spent at work, time spent inside the vehicle, personality, job characteristics (JDS), job content (JCQ) and burnout. Method. Participants were 509 professional drivers from various transport sectors recruited by non-probabilistic sampling. SPSS version 25.0 was used for statistical analysis. Results. The predictive capacity of variables that cause driver fatigue was determined. Exhaustion best predicts fatigue positively, while openness to experience best predicts it negatively. Burnout and certain personality characteristics are good predictors, whereas other variables, such as JCQ and JDS, are weak predictors. Conclusions. This study extends our knowledge of the factors that cause fatigue in professional drivers and underlines the importance of designing interventions aimed at reducing the incidence of fatigue, promoting greater driver well-being and lowering the incidence of accidents.
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Condução de Veículo , Esgotamento Profissional , Acidentes de Trânsito , Esgotamento Profissional/epidemiologia , Criança , Fadiga/epidemiologia , Humanos , Ocupações , PersonalidadeRESUMO
The study objective is to create a scale specifically for measuring driver fatigue and to analyze the scale's psychometric properties. The participants were 518 Spanish drivers. We carried out an exploratory factor analysis (EFA) and the first subsample obtained a single-item solution (eight items). We then performed a confirmatory factor analysis (CFA) with a second subsample. The results were root mean square error of approximation (rmsea) = 0.05, comparative fit index (CFI) = 0.94 and Tucker-Lewis index (TLI) = 0.92, which corroborates the previous results and maintains the same number of elements. The resulting dimension shows good reliability. The scale scores were then related to several external correlates and other scales, and showed good convergence and criteria validity. The results indicate that the scale for assessing work fatigue specifically in professional drivers - driver fatigue (DF-8) - is a reliable and valid instrument.
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Condução de Veículo , Fadiga , Análise Fatorial , Fadiga/diagnóstico , Humanos , Psicometria , Reprodutibilidade dos Testes , Espanha , Inquéritos e QuestionáriosRESUMO
Objectives. Stress maintained over time leads to a state of exhaustion known as burnout syndrome. This syndrome constitutes an occupational health problem, leading to high absenteeism. It can also mean that workers come to the workplace feeling unwell, which increases occupational collisions and injuries at work. In this study, we developed a predictive model of burnout in professional drivers using the following indicators: age, hours worked, seniority, educational level, fatigue, personality, attitudes toward driving, safety behaviors in the vehicle, and work characteristics and content. Method. A total of 523 professional drivers from different transport sectors, obtained through non-probability sampling, participated in the study. We used SPSS version 25.0 to analyze the data. Results. We determined the predictive capacity of certain variables that affect drivers and cause burnout. Exhaustion can be predicted with fatigue (48.8%), professional efficiency with emotional stability (39.8%) and cynicism with lack of motivation (28%) as the best predictors. Conclusions. The results contribute to a better knowledge of those factors that cause burnout in professional drivers. It is important to design individual interventions to reduce burnout, which would help reduce sick leave and possible collisions, in addition to providing greater well-being for drivers.
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Esgotamento Profissional , Doenças Profissionais , Absenteísmo , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Fadiga/epidemiologia , Humanos , Doenças Profissionais/psicologia , Ocupações , Inquéritos e Questionários , Local de Trabalho/psicologiaRESUMO
Plastic pollution is one of the leading environmental problems. Phthalates are widely used plastic additives released into the environment. Although the effects of phthalates on vertebrates have been extensively studied, there is a knowledge gap regarding their effects on invertebrates. This work analyzes the impact of three phthalates, diethyl phthalate (DEP), benzyl butyl phthalate (BBP), and bis-(2-ethylhexyl) phthalate (DEHP), on the gastropod Physella acuta at the molecular level to establish the putative pathways involved in its response to them. By real-time PCR, we obtained the expression profile of 30 genes in animals exposed for 1 week to 0.1, 10, and 1000 µg/L of each phthalate. The genes cover DNA repair, detoxification, apoptosis, oxidative and stress responses, immunity, energy reserves, and lipid transport. The results show that while DEP and DEHP did not alter the mRNA levels, BBP modulated almost all the analyzed genes. It can be concluded that the impact of BBP is extensive at the molecular level. However, it cannot be dismissed that the increase in transcriptional activity is a general response due to this compound's well-known role as an endocrine disruptor. Additional research is needed to elucidate the differences observed in the impact of these compounds on the gastropod P. acuta.
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Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Moluscos , Ácidos Ftálicos/toxicidade , Transcriptoma/efeitos dos fármacos , Animais , Moluscos/efeitos dos fármacos , Moluscos/metabolismoRESUMO
Dispersion-corrected density functional theory (DFT-D3) is applied to model iron triade (Fe, Co, and Ni) surfaces upon exchange of surface atoms with atomic gold. One first goal is to analyze the contact problem at the triade surface-Au interface and to correlate our findings with recent observations on iron triade nanoparticles (with diameters of around 5 nm) passivated by a few layers of gold. For this purpose, we analyze: (1) the energies of substitution; (2) the restructuring of the iron triade surfaces upon the atomic exchange; (3) the density of the orbitals bearing the largest projection on d(Au) atomic orbitals and, particularly, their overlap with orbitals from neighboring atoms of the triade surfaces; (4) the modification of the electronic density of states; and (5) the redistribution of the electronic density upon intermixing of Au and triade atoms. Inspite of the similarities between Ni, Co, and Fe in the condensed phase, significant differences are found in the features characterizing the exchange process. In particular, we find a better integration of the Au atom on the substitutional site of the Ni(001) surface than on those of the Fe(001) and Co(001) surfaces. This is in agreement with the fact that the electronic density of states is almost indistinguishable before and after Ni-Au intermixing. This outcome is correlated with the experimental observation on the allowing transition of Ni-Au core-shell nanoparticles before reaching the melting temperature. Our second objective is to explore the Au-triade atom intermixing process in sub-nanometric clusters, finding that it is energetically more favored than at solid surfaces yet endothermic at 0 K. This feature is explained as the result of the structural fluxionality characterizing clusters at the sub-nanometer scale. Entropy contributions make mixed Au-Ni clusters more stable than the unmixed counterpart already at 650 K while unmixed Co clusters remain energetically more favored up to 1295 K and iron clusters are predicted to be stable against intermixing over the experimentally relevant range of temperatures (up to 1100 °C). Remarkably, the net charge donated from the three triade atoms to atomic gold upon intermixing is similar in triade sub-nanometeric clusters and at extended triade surfaces. Gold clusters are prone to host Fe, Co, and Ni atoms at the center of their structures and the exchange process is predicted to be exothermic at 0 K even for a small cluster made of 13 atoms. More generally, our work highlights the importance of the polarity of the chemical bond between unlike metal atoms in alloys.
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RESUMEN Introducción: el hipotiroidismo puede asociarse a la insuficiencia renal crónica, solapándose sus síntomas. Objetivo: determinar la frecuencia y características clínicas de los trastornos tiroideos silentes en pacientes adultos con insuficiencia renal crónica. Metodología: estudio observacional, correlacional, prospectivo, multicéntrico. Se incluyeron varones y mujeres, mayores de edad, portadores de insuficiencia renal crónica, que asistieron al Hospital Nacional (Itauguá) y Hospital Militar (Asunción) durante 2020. Los sujetos que dieron su consentimiento fueron sometidos a la determinación del perfil tiroideo. Se incluyeron a sujetos en terapia predialítica y dialítica, se excluyeron a conocidos portadores de enfermedades tiroideas. Se midieron variables demográficas y clínicas. Los datos fueron sometidos a estadística descriptiva y analítica. El protocolo fue aprobado por el Comité de Ética de la Universidad Privada del Este. Resultados: ingresaron al estudio 103 mujeres y 115 varones, con edad media 58 y 57 años, respectivamente. Se halló sobrepeso en 52,4 % y obesidad en 16,6 %. El 66 % se encontraba en estadio 5 de insuficiencia renal y predominó la etiología diabética e hipertensiva. La anemia se encontró en 90 %. Respecto al perfil tiroideo, se encontró 20,2 % en rango normal, 12,4 % en hipotiroidismo clínico, 15,6 % en hipotiroidismo subclínico, 20,2 % con síndrome del enfermo eutiroideo y 31,6 % con síndrome T3 bajo. Se halló asociación significativa entre la depuración de creatinina y los estados tiroideos. Conclusión: en 28 % se halló algún grado de hipotiroidismo. Se recomienda el tamizaje del funcionamiento tiroideo en pacientes con insuficiencia renal crónica.
ABSTRACT Introduction: hypothyroidism can be associated with chronic kidney failure and its symptoms can overlap Objectives: to determine the frequency and clinical characteristics of silent thyroid disorders in adult patients with chronic renal failure. Methodology: we conducted an observational, correlational, prospective, multicenter study. We included adults' men and women, with chronic kidney failure, who attended the National Hospital (Itauguá) and the Military Hospital (Asunción) during 2020. The subjects who gave their consent were invited to the determination of the serum thyroid profile. Subjects in predialytic and dialytic therapy were included. Known carriers of thyroid diseases were excluded. Demographic and clinical variables were measured. We applied descriptive and analytical statistics. The protocol was approved by the Ethics Committee of the Private University of the East. Results: we included 103 women and 115 men, with a mean age of 58 and 57 years, respectively. Overweight was found in 52.4 % and obesity in 16.6 %. In 66 % of the cases the patients were in stage 5 of renal failure. Diabetic and hypertensive origin was the predominated etiology. Anemia was found in 90 %. Regarding the thyroid profile, 20.2 % were found in the normal range, 12.4 % in clinical hypothyroidism, 15.6 % in subclinical hypothyroidism, 20.2 % with euthyroid sick syndrome and 31.6 % with low T3 syndrome. A significant association was found between creatinine clearance and thyroid status. Conclusion: 28 % had some degree of hypothyroidism. Thyroid function screening is recommended in patients with chronic renal failure.
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This study aims to evaluate the costs of informal care for children with neuromuscular disease and evaluate how physical and psychological health is associated with socio-demographic variables. A cross sectional design was used with a convenience sample of 110 carers that participated in this study. Participants were recruited from Spanish hospitals and rare diseases organizations. Economic costs and sociodemographic aspects were assessed using the economic costs questionnaire and the sociodemographic questionnaire. Physical and psychological health was evaluated using the CarerQol-7D, PHQ-15, Barthel Index, Zarit Overload Scale and Satisfaction with Life Scale. Carers of children with neuromuscular disease spent a large percentage of their annual income in physical therapy, psychological care and speech therapy. Informal costs differed according to the degree of dependency of the child. These were higher in those caregivers whose child under their care presented low functional independence. The loss of work productivity was related to marital status, use of professional services and the child's dependency. Finally, carers who were female, single or separated and without a job showed worse physical and psychological health. The results highlighted that carers have to face a number of high costs because of the non-existence of social protection and due to the child's diagnosis.
Assuntos
Cuidadores , Doenças Neuromusculares , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
Rare neuromuscular diseases (RNMDs) are a group of pathologies characterized by a progressive loss of muscular strength, atrophy, fatigue, and other muscle-related symptoms, which affect quality of life (QoL) levels. The low prevalence, high geographical dispersion and disability of these individuals involve difficulties in accessing health and social care services. Teleassistance is presented as a useful tool to perform psychosocial interventions in these situations. The main aim of this research is to assess the effects of a teleassistance psychosocial program on the QoL levels of people with RNMDs who have different levels of disability. A sample of 73 participants was divided into an experimental group (n = 40), which participated in the intervention, and a control wait list group (n = 33). QoL was evaluated through the SIP and the SF-36, and disability through the WHO-DAS II. The participants with a moderate to severe level of disability were those who most benefited from the intervention. The results also revealed that the psychosocial teleassistance program was suitable to improve physical and psychosocial aspects of people suffering from a rare neuromuscular disease with a moderate level of disability, but just psychosocial aspects in those with a severe level of disability.
RESUMO
Of the seven currently known botulinum neurotoxin-producing species of Clostridium, C. parabotulinum, or C. botulinum Group I, is the species associated with the majority of human botulism cases worldwide. Phylogenetic analysis of these bacteria reveals a diverse species with multiple genomic clades. The neurotoxins they produce are also diverse, with over 20 subtypes currently represented. The existence of different bont genes within very similar genomes and of the same bont genes/gene clusters within different bacterial variants/species indicates that they have evolved independently. The neurotoxin genes are associated with one of two toxin gene cluster types containing either hemagglutinin (ha) genes or orfX genes. These genes may be located within the chromosome or extrachromosomal elements such as large plasmids. Although BoNT-producing C parabotulinum bacteria are distributed globally, they are more ubiquitous in certain specific geographic regions. Notably, northern hemisphere strains primarily contain ha gene clusters while southern hemisphere strains have a preponderance of orfX gene clusters. OrfX C. parabotulinum strains constitute a subset of this species that contain highly conserved bont gene clusters having a diverse range of bont genes. While much has been written about strains with ha gene clusters, less attention has been devoted to those with orfX gene clusters. The recent sequencing of 28 orfX C. parabotulinum strains and the availability of an additional 91 strains for analysis provides an opportunity to compare genomic relationships and identify unique toxin gene cluster characteristics and locations within this species subset in depth. The mechanisms behind the independent processes of bacteria evolution and generation of toxin diversity are explored through the examination of bacterial relationships relating to source locations and evidence of horizontal transfer of genetic material among different bacterial variants, particularly concerning bont gene clusters. Analysis of the content and locations of the bont gene clusters offers insights into common mechanisms of genetic transfer, chromosomal integration, and development of diversity among these genes.
RESUMO
BACKGROUND: Numerous studies have noted the presence of a dysexecutive component of the ALS-FTD. The most widely replicated result refers to the significantly reduced verbal fluency of ALS patients when compared to healthy people. As ALS patients have motor alterations that interfere with production, qualitative studies have the advantage of being independent of the degree of motor disability and revealing patients' cognitive state. This study examined the production differences between 42 ALS patients who presented with different degrees of dementia and motor impairment and 42 healthy people. Production processes were studied by extending the administration time of a letter fluency task to 2 minutes for the phonemic verbal fluency (PVF) and semantic verbal fluency (SVF) categories. This ensured that the qualitative aspects of verbal fluency were addressed, paying special attention to the new perseverations and intrusions, as well as any clinical correlates that may exist. RESULTS: The ALS patients produced a significantly lower number of responses in PVF (p = .017) and SVF (p = .008). The rest of the indicators for frontal lobe alteration also suggested the existence of a dysfunction. The most remarkable results were the number of intrusions on the PVF task, which was much higher in the ALS group (p = .002). However, the number of perseverations did not differ significantly. CONCLUSIONS: This study highlights the value of intrusions in addressing cognitive deterioration in ALS patients. This deterioration seems to be independent of the degree of motor impairment and of behavioural alterations. Therefore, the value of the intromissions on the verbal fluency task was highlighted as an indicator of a new cognitive alteration, which can be easily evaluated, even retrospectively.