State-independent inhibition of the oncogenic Kv10.1 channel by desethylamiodarone, a comparison with amiodarone.

Kv10.1 is a voltage-dependent K channel whose ectopic expression is associated with several human cancers. Additionally, Kv10.1 has structure-function properties which are not yet well understood. We are using drugs of clinical importance in an attempt to gain insight on the relationship between pharmacology and characteristic functional properties of this channel. Herein, we report the interaction of desethylamiodarone (desAd), the active metabolic product of the antiarrhythmic amiodarone with Kv10.1: desAd binds to both closed and open channels, with most inhibition taking place from the open state, with affinity ~ 5 times smaller than that of amiodarone. Current inhibition by desAd and amiodarone is not synergistic. Upon repolarization desAd becomes trapped in Kv10.1 and thereafter dissociates slowly from closed-and-blocked channels. The addition of the Cole-Moore shift plus desAd open-pore-block time courses yields an increasing phase on the steady-state inhibition curve (H∞) at hyperpolarized holding potentials. In contrast to amiodarone, desAd does not inhibit the Kv10.1 Cole-Moore shift, suggesting that a relevant hydrophobic interaction between amiodarone and Kv10.1 participates in the inhibition of the Cole-Moore shift, which is lost with desAd.

Developing Bioactive Dental Resins for Restorative Dentistry.

Despite its reputation as the most widely used restorative dental material currently, resin-based materials have acknowledged shortcomings. As most systematic survival studies of resin composites and dental adhesives indicate, secondary caries is the foremost reason for resin-based restoration failure and life span reduction. In subjects with high caries risk, the microbial community dominated by acidogenic and acid-tolerant bacteria triggers acid-induced deterioration of the bonding interface and/or bulk material and mineral loss around the restorations. In addition, resin-based materials undergo biodegradation in the oral cavity. As a result, the past decades have seen exponential growth in developing restorative dental materials for antimicrobial applications addressing secondary caries prevention and progression. Currently, the main challenge of bioactive resin development is the identification of efficient and safe anticaries agents that are detrimental free to final material properties and show satisfactory long-term performance and favorable clinical translation. This review centers on the continuous efforts to formulate novel bioactive resins employing 1 or multiple agents to enhance the antibiofilm efficacy or achieve multiple functionalities, such as remineralization and antimicrobial activity antidegradation. We present a comprehensive synthesis of the constraints and challenges encountered in the formulation process, the clinical performance-related prerequisites, the materials' intended applicability, and the current advancements in clinical implementation. Moreover, we identify crucial vulnerabilities that arise during the development of dental materials, including particle aggregation, alterations in color, susceptibility to hydrolysis, and loss of physicomechanical core properties of the targeted materials.

Fulvifomes wrightii (Hymenochaetales), a new species related to F. robiniae from Argentina and Paraguay.

Morphological revision and phylogenetic analysis based on nITS and nLSU of specimens previously considered to be a species related to Fulvifomes robiniae from South America revealed a new species of Fulvifomes, i.e. Fulvifomes wrightii. It grows on Libidibia paraguariensis, a Fabaceae distributed in the Chaco Region. The new species is characterised by a perennial, ungulate basidioma with a rimose pileal surface, 6-7 pores per mm, a homogenous context, indistinct stratified tubes and abundant crystals in tube trama and hymenia. Illustrations, taxonomic analyses and a key to the Fulvifomes species recorded from the Americas is provided. Citation: Martínez M, Salvador-Montoya CA, de Errasti A, Popoff OF, Rajchenberg M (2023). Fulvifomes wrightii (Hymenochaetales), a new species related to F. robiniae from Argentina and Paraguay. Fungal Systematics and Evolution 12: 47-57. doi: 10.3114/fuse.2023.12.03.

Two novel endophytic Tolypocladium species identified from native pines in south Florida.

This study investigated the incidence and diversity of Tolypocladium within trunks of south Florida slash pines (Pinus densa). Thirty-five isolates were recovered from trunk tissue including living phloem, cambium, and sapwood. Two novel species of Tolypocladium (T. subtropicale and T. trecense) are described here based on morphological and molecular analysis of concatenated LSU, ITS, tef-1, tub, and RPB1 sequences. Our findings expand our understanding of the distribution, diversity, and ecology of this genus and confirm that it is widely spread as an endophyte across ecosystems and hosts. Strains collected in this survey will be used in future bioassays to determine their potential ecological roles as mycoparasites or entomopathogens. Citation: Soares JM, Karlsen-Ayala E, Salvador-Montoya CA, Gazis R (2023). Two novel endophytic Tolypocladium species identified from native pines in south Florida. Fungal Systematics and Evolution 11: 51-61. doi: 10.3114/fuse.2023.11.04.

[P300 cognitive event-related potentials in the diagnosis and classification of possible Alzheimer-type neurocognitive disorders]. / Potencial relacionado con eventos cognitivos P300 en el diagnóstico y clasificación del trastorno neurocognitivo debido a enfermedad de Alzheimer posible.

INTRODUCTION: The value of the P300 cognitive event-related potential in the diagnosis of Alzheimer subtype neurocognitive disorders is still incipient. Recent studies suggest that combining it with neuropsychological tests by cognitive domains would allow an objective and early characterisation of the cognitive impairment in its initial stages. AIMS: To characterise the electrophysiological patterns in the P300 potential that obtain a discriminatory value for the diagnosis and classification of the neurocognitive disorders with a possible Alzheimer-type aetiology. SUBJECTS AND METHODS: This study examines 39 patients classified, according to the DSM-5, with possible Alzheimer-type minor and major neurocognitive disorders, aged between 50 and 85 years, and 53 control subjects with normal cognitive functions. The P300 potential is registered in the auditory mode, oddball paradigm and centroparietal recording. RESULTS: P300 latency is significantly prolonged in subjects with neurocognitive disorder; there are significant differences in the mean values and confidence intervals between healthy controls and patients. No significant differences are obtained in P300 latency between groups with minor and major neurocognitive disorder. The mean amplitude value decreases in neurocognitive disorder, and the P300 amplitude logarithm of the control groups and those with minor and major neurocognitive disorder reaches significantly different mean values and confidence intervals. CONCLUSIONS: The parameters quantified in the P300 potential can be used as complementary biomarkers to classify the presence and level of cognitive dysfunction with a possible Alzheimer-type aetiology.

TITLE: Potencial relacionado con eventos cognitivos P300 en el diagnóstico y clasificación del trastorno neurocognitivo debido a enfermedad de Alzheimer posible.Introducción. El valor del potencial relacionado con eventos cognitivos P300 en el diagnóstico de los trastornos neurocognitivos subtipo Alzheimer es aún incipiente. Estudios recientes sugieren que su combinación con tests neuropsicológicos por dominios cognitivos permitiría caracterizar de forma objetiva y precoz el déficit cognitivo en sus etapas iniciales. Objetivo. Caracterizar los patrones electrofisiológicos en el potencial P300 que obtengan un valor discriminativo para el diagnóstico y clasificación de los trastornos neurocognitivos de etiología enfermedad de Alzheimer posible. Sujetos y métodos. Se estudia a 39 pacientes clasificados, según el DSM-5, con trastorno neurocognitivo menor y mayor debido a enfermedad de Alzheimer posible, en un rango de edad de 50-85 años, y a 53 sujetos control con funciones cognitivas normales. Se registra el potencial P300 en la modalidad auditiva, paradigma de oddball y registro centroparietal. Resultados. La latencia P300 se prolonga significativamente en los sujetos con trastorno neurocognitivo; sus valores medios e intervalos de confianza son significativamente diferentes entre los controles sanos y los pacientes. No se obtienen diferencias significativas de latencia P300 entre los grupos con trastorno neurocognitivo menor y mayor. El valor medio de amplitud disminuye en el trastorno neurocognitivo, y el logaritmo de amplitud P300 obtiene valores medios e intervalos de confianza significativamente diferentes entre los grupos control y con trastorno neurocognitivo menor y mayor. Conclusiones. Los parámetros cuantificados en el potencial P300 pueden utilizarse como biomarcadores complementarios clasificadores de la presencia y del nivel de la disfunción cognitiva de etiología enfermedad de Alzheimer posible.

Epigenetic control of the EWS­FLI1 promoter in Ewing's sarcoma.

Ewing sarcoma (ES) is a primary bone marrow tumor that very rarely develops in extra­osseous tissues, such as lung. The hallmark of ES tumors is a translocation between chromosomes 11 and 22, resulting in a fusion protein, commonly referred to as EWS­FLI1. The epigenetic profile (histone acetylation and methylation enrichment of the promoter region) that may regulate the expression of the aberrant transcription factor EWS­FLI1, remains poorly studied and understood. Knowledge of epigenetic patterns associated with covalent histone modification and expression of enzymes associated with this process, can contribute to the understanding of the molecular basis of the disease, as well as to the identification of possible molecular targets involved in expression of the EWS­FLI1 gene, so that therapeutic strategies may be improved in the future. In the present study, the transcriptional activation and repression of the EWS­FLI1 fusion gene in ES was accompanied by selective deposition of histone markers on its promoter. The EWS­FLI1 fusion gene was evaluated in two patients with ES using conventional cytogenetic, fluorescence in situ hybridization and nested PCR assays, which revealed that the aberrant expression of the EWS­FLI1 gene is accompanied by enrichment of H3K4Me3, H3K9ac and H3K27ac at the promoter region.

Revisión de las últimas novedades en el manejo del paciente con urticaria crónica: Consenso multidisciplinar de la comunidad autónoma de Andalucía / A Review of the Latest Recommendations on the Management of Chronic Urticaria: A Multidisciplinary Consensus Statement from Andalusia, Spain

La urticaria crónica es una enfermedad de la piel difícil de tratar que presenta un alto impacto negativo en la calidad de vida de los pacientes. La última actualización de la guía europea para el manejo del paciente con urticaria se publicó en 2018. Con el actual contexto, presentamos un enfoque multidisciplinar para la aplicación del nuevo algoritmo de tratamiento propuesto por la guía en el territorio español, más concretamente, en la comunidad autónoma de Andalucía

Chronic urticaria is a difficult-to-treat skin disorder that has a major impact on patient quality of life. The latest update of the European guideline on the management of urticaria was published in 2018. In this consensus statement, produced in the autonomous community of Andalusia, Spain, we describe a multidisciplinary approach for applying the new treatment algorithm proposed by the European guideline in our región

A Review of the Latest Recommendations on the Management of Chronic Urticaria: A Multidisciplinary Consensus Statement from Andalusia, Spain. / Revisión de las últimas novedades en el manejo del paciente con urticaria crónica: Consenso multidisciplinar de la comunidad autónoma de Andalucía.

Chronic urticaria is a difficult-to-treat skin disorder that has a major impact on patient quality of life. The latest update of the European guideline on the management of urticaria was published in 2018. In this consensus statement, produced in the autonomous community of Andalusia, Spain, we describe a multidisciplinary approach for applying the new treatment algorithm proposed by the European guideline in our region.

Dronedarone blockage of the tumor-related Kv10.1 channel: a comparison with amiodarone.

Kv10.1 (Eag1, or KCNH1) is a human potassium-selective channel associated with tumor development. In this work, we study the interaction of the drug dronedarone with Kv10.1. Dronedarone presents two chemical modifications aimed to lessen side effects produced by its parent molecule, the antiarrhythmic amiodarone. Hence, our observations are discussed within the framework of a previously reported interaction of amiodarone with Kv10.1. Additionally, we show new data regarding the interaction of amiodarone with the channels. We found that, unexpectedly, the effect of dronedarone on Kv10.1 differs both quantitatively and qualitatively to that of amiodarone. Among other observations, we found that dronedarone seems to be an open-pore blocker, in contrast to the reported behavior of amiodarone, which seems to inhibit from both open and closed states. Additionally, herein we provide evidence showing that, in spite of their chemical similarity, these molecules inhibit the K+ conductance by binding to non-overlapping, independent (non-allosterically related) sites. Also, we show that, while amiodarone inhibits the Cole-Moore shift, dronedarone is unable to inhibit this voltage-dependent characteristic of Kv10.1.

Enfermedad de Grover tipo poroqueratósico: más allá de un patrón acantolítico / Porokeratosis-Like Grover Disease: More Than an Acantholytic Pattern

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Growth of Candida norvegensis (strain Levazoot 15) with different energy, nitrogen, vitamin, and micromineral sources.

To examine the growth of Candida norvegensis (strain Levazoot 15), four experiments were conducted with different sources of energy, nitrogen, vitamins, and microminerals. Optical density was used as an indirect measure of strain growth in a fully randomized factorial design, in which principal factor A was the source of energy, nitrogen, vitamins, or microminerals and principal factor B was the measurement time point (0, 20, or 40 h). The results showed that the yeast strain used glucose (primarily sucrose and lactose) as the energy source and tryptone as the nitrogen source. The addition of B-complex vitamins or microminerals was not necessary for strain growth. It is concluded that the strain Levazoot 15 preferentially utilizes glucose as a source of energy, tryptone as a source of nitrogen and manganese as a mineral source, and that no vitamin source was necessary for growth.

Correction to: Inhibition of the K+ conductance and Cole-Moore shift of the oncogenic Kv10.1 channel by amiodarone.

The original publication of this article contained multiple technical errors that occurred during its production and printing. These errors included sentences and paragraphs with parts missing. The Publisher regrets these mistakes.

Inhibition of the K+ conductance and Cole-Moore shift of the oncogenic Kv10.1 channel by amiodarone.

The ectopic overexpression of the voltage-dependent Eag1 (Kv10.1) K+ channel is associated with the cancerous phenotype in about 70% of human cancers and tumor cell lines. Recent reports showed that, compared with the canonical Shaker-related Kv family, Kv10.1 presents unique structural and functional properties. Herein, we report the interaction of the class III anti-arrhythmic compound amiodarone with Kv10.1. Using whole-cell patch clamp, we found that amiodarone inhibits Kv10.1 channel conductance with nanomolar affinity. Additionally, and interestingly, we also report that amiodarone inhibits the characteristic Cole-Moore shift of Eag1 channels. Our observations are interpreted considering the structural-functional characteristics of these channels. We conclude that amiodarone possibly binds with high affinity to the voltage sensor module, altering the gating of Kv10.1.