Human monkeypox virus in a tertiary hospital in Madrid, Spain: An observational study of the clinical and epidemiological characteristics of 53 cases.

A new outbreak of monkeypox virus (MPXV) infection, a zoonotic infection endemic in Central and West Africa, is spreading throughout the world with new epidemiology and clinical features. Our aim was to characterize patients presenting to Dermatology emergency room with a MPXV infection between 15 May and 30 June 2022 in a tertiary hospital in Madrid, Spain. We collected 53 patients and describe their clinical, demographic and epidemiological characteristics and followed their evolution. Most of the patients were men who had sex with men with high-risk sexual practices and no recent travels abroad. Most of them (91%) had had a sexually transmitted infection before. All patients had typical skin lesions consisting of vesicular-pustular rash with central umbilication which was localized or disseminated. The most frequent extracutaneous symptoms were fever, painful regional lymphadenopathy and asthenia. Proctitis was present in more than one third of patients. All patients were diagnosed by real time polymerase chain reaction of samples obtained from skin lesions. Pharyngeal and/or rectal exudates demonstrated MPXV in 74% of patients. The current worldwide outbreak of MPXV infections shows epidemiological and clinical differences from previous ones. Clinicians should be aware of these characteristics to correctly diagnose this emerging disease.

Position Measurements Using Magnetic Sensors for a Shape Memory Alloy Linear Actuator.

This article presents the design and implementation of a linear actuator based on NiTi Shape Memory Alloys with temperature and position measurements based on a magnetic sensor array and a set of thermistors. The position instrumentation is contact free to avoid friction perturbations; the position signal conditioning is carried out through the calculation of the response of each magnetic sensor, selecting the closest sensor to ensure accurate results on the full range of movement. Experimental results validate the accuracy of the position sensing with a competitive behaviour.

Over-expression of Isu1p and Jac1p increases the ethanol tolerance and yield by superoxide and iron homeostasis mechanism in an engineered Saccharomyces cerevisiae yeast.

The ethanol stress response in ethanologenic yeast during fermentation involves the swishing of several adaptation mechanisms. In Saccharomyces cerevisiae, the Jac1p and Isu1p proteins constitute the scaffold system for the Fe-S cluster assembly. This study was performed using the over-expression of the Jac1p and Isu1p in the industrially utilized S. cerevisiae UMArn3 strain, with the objective of improving the Fe-S assembly/recycling, and thus counteracting the toxic effects of ethanol stress during fermentation. The UMArn3 yeast was transformed with both the JAC1-His and ISU1-His genes-plasmid contained. The Jac1p and Isu1p His-tagged proteins over-expression in the engineered yeasts was confirmed by immunodetection, rendering increases in ethanol tolerance level from a DL50 = ~ 4.5% ethanol (v/v) to DL50 = ~ 8.2% ethanol (v/v), and survival up 90% at 15% ethanol (v/v) comparing to ~ 50% survival in the control strain. Fermentation by the engineered yeasts showed that the ethanol production was increased, producing 15-20% more ethanol than the control yeast. The decrease of ROS and free-iron accumulation was observed in the engineered yeasts under ethanol stress condition. The results indicate that Jac1p and Isu1p over-expression in the S. cerevisiae UMArn3.3 yeast increased its ethanol tolerance level and ethanol production by a mechanism that involves ROS and iron homeostasis related to the biogenesis/recycling of Fe-S clusters dependent proteins.

The Antiproliferative Effect of Cyclodipeptides from Pseudomonas aeruginosa PAO1 on HeLa Cells Involves Inhibition of Phosphorylation of Akt and S6k Kinases.

Pseudomonas aeruginosa PAO1, a potential pathogen of plants and animals, produces the cyclodipeptides cyclo(l-Pro-l-Tyr), cyclo(l-Pro-l-Phe), and cyclo(l-Pro-l-Val) (PAO1-CDPs), whose effects have been implicated in inhibition of human tumor cell line proliferation. Our purpose was to investigate in depth in the mechanisms of HeLa cell proliferation inhibition by the PAO1-CDPs. The results indicate that PAO1-CDPs, both purified individually and in mixtures, inhibited HeLa cell proliferation by arresting the cell cycle at the G0-G1 transition. The crude PAO1-CDPs mixture promoted cell death in HeLa cells in a dose-dependent manner, showing efficacy similar to that of isolated PAO1-CDPs (LD50 of 60-250 µM) and inducing apoptosis with EC50 between 0.6 and 3.0 µM. Moreover, PAO1-CDPs showed a higher proapoptotic activity (~10³-105 fold) than their synthetic analogs did. Subsequently, the PAO1-CDPs affected mitochondrial membrane potential and induced apoptosis by caspase-9-dependent pathway. The mechanism of inhibition of cells proliferation in HeLa cells involves inhibition of phosphorylation of both Akt-S473 and S6k-T389 protein kinases, showing a cyclic behavior of their expression and phosphorylation in a time and concentration-dependent fashion. Taken together our findings indicate that PI3K-Akt-mTOR-S6k signaling pathway blockage is involved in the antiproliferative effect of the PAO1-CDPs.

Daam1a mediates asymmetric habenular morphogenesis by regulating dendritic and axonal outgrowth.

Although progress has been made in resolving the genetic pathways that specify neuronal asymmetries in the brain, little is known about genes that mediate the development of structural asymmetries between neurons on left and right. In this study, we identify daam1a as an asymmetric component of the signalling pathways leading to asymmetric morphogenesis of the habenulae in zebrafish. Daam1a is a member of the Formin family of actin-binding proteins and the extent of Daam1a expression in habenular neuron dendrites mirrors the asymmetric growth of habenular neuropil between left and right. Local loss and gain of Daam1a function affects neither cell number nor subtype organisation but leads to a decrease or increase of neuropil, respectively. Daam1a therefore plays a key role in the asymmetric growth of habenular neuropil downstream of the pathways that specify asymmetric cellular domains in the habenulae. In addition, Daam1a mediates the development of habenular efferent connectivity as local loss and gain of Daam1a function impairs or enhances, respectively, the growth of habenular neuron terminals in the interpeduncular nucleus. Abrogation of Daam1a disrupts the growth of both dendritic and axonal processes and results in disorganised filamentous actin and α-tubulin. Our results indicate that Daam1a plays a key role in asymmetric habenular morphogenesis mediating the growth of dendritic and axonal processes in dorsal habenular neurons.

Protective effects of dietary avocado oil on impaired electron transport chain function and exacerbated oxidative stress in liver mitochondria from diabetic rats.

Electron transport chain (ETC) dysfunction, excessive ROS generation and lipid peroxidation are hallmarks of mitochondrial injury in the diabetic liver, with these alterations also playing a role in the development of non-alcoholic fatty liver disease (NAFLD). Enhanced mitochondrial sensitivity to lipid peroxidation during diabetes has been also associated to augmented content of C22:6 in membrane phospholipids. Thus, we aimed to test whether avocado oil, a rich source of C18:1 and antioxidants, attenuates the deleterious effects of diabetes on oxidative status of liver mitochondria by decreasing unsaturation of acyl chains of membrane lipids and/or by improving ETC functionality and decreasing ROS generation. Streptozocin-induced diabetes elicited a noticeable increase in the content of C22:6, leading to augmented mitochondrial peroxidizability index and higher levels of lipid peroxidation. Mitochondrial respiration and complex I activity were impaired in diabetic rats with a concomitant increase in ROS generation using a complex I substrate. This was associated to a more oxidized state of glutathione, All these alterations were prevented by avocado oil except by the changes in mitochondrial fatty acid composition. Avocado oil did not prevented hyperglycemia and polyphagia although did normalized hyperlipidemia. Neither diabetes nor avocado oil induced steatosis. These results suggest that avocado oil improves mitochondrial ETC function by attenuating the deleterious effects of oxidative stress in the liver of diabetic rats independently of a hypoglycemic effect or by modifying the fatty acid composition of mitochondrial membranes. These findings might have also significant implications in the progression of NAFLD in experimental models of steatosis.

Reactive oxygen species production induced by ethanol in Saccharomyces cerevisiae increases because of a dysfunctional mitochondrial iron-sulfur cluster assembly system.

Ethanol accumulation during fermentation contributes to the toxic effects in Saccharomyces cerevisiae, impairing its viability and fermentative capabilities. The iron-sulfur (Fe-S) cluster biogenesis is encoded by the ISC genes. Reactive oxygen species (ROS) generation is associated with iron release from Fe-S-containing enzymes. We evaluated ethanol toxicity, ROS generation, antioxidant response and mitochondrial integrity in S. cerevisiae ISC mutants. These mutants showed an impaired tolerance to ethanol. ROS generation increased substantially when ethanol accumulated at toxic concentrations under the fermentation process. At the cellular and mitochondrial levels, ROS were increased in yeast treated with ethanol and increased to a higher level in the ssq1∆, isa1∆, iba57∆ and grx5∆ mutants - hydrogen peroxide and superoxide were the main molecules detected. Additionally, ethanol treatment decreased GSH/GSSG ratio and increased catalase activity in the ISC mutants. Examination of cytochrome c integrity indicated that mitochondrial apoptosis was triggered following ethanol treatment. The findings indicate that the mechanism of ethanol toxicity occurs via ROS generation dependent on ISC assembly system functionality. In addition, mutations in the ISC genes in S. cerevisiae contribute to the increase in ROS concentration at the mitochondrial and cellular level, leading to depletion of the antioxidant responses and finally to mitochondrial apoptosis.

Apocynin Attenuates Diabetes-Induced Skeletal Muscle Dysfunction by Mitigating ROS Generation and Boosting Antioxidant Defenses in Fast-Twitch and Slow-Twitch Muscles.

In response to diabetes mellitus, skeletal muscle is negatively affected, as is evident by reduced contractile force production, increased muscle fatigability, and increased levels of oxidative stress biomarkers. Apocynin is a widely used NADPH oxidase inhibitor, with antioxidant and anti-inflammatory potential. It has been effective for amelioration of a variety of disorders, including diabetic complications. Therefore, the present study was conducted to evaluate the effects and action mechanisms of apocynin in slow- and fast-twitch diabetic rat muscles. Male Wistar rats were rendered diabetic by applying intraperitoneally a single dose of streptozotocin (45 mg/kg). Apocynin treatment (3 mg/kg/day) was administered over 8 weeks. Fasting blood glucose (FBG), insulin tolerance and body weight gain were measured. Both slow (soleus) and fast (extensor digitorum longus, EDL) skeletal muscles were used for muscle function evaluation, oxidative stress markers, and evaluating gene expression using qRT-PCR. Treatment with apocynin significantly reduced FBG levels and enhanced insulin tolerance. Apocynin also prevented muscle contractile dysfunction in EDL muscle but had no significant effect on this parameter in soleus muscles. However, in both types of muscles, apocynin mitigated the oxidative stress by decreasing ROS levels and increasing total glutathione levels and redox state. Concomitantly, apocynin also statistically enhanced Nrf-2 and GLU4 mRNA expression and downregulated NOX2, NOX4, and NF-κB mRNA. Collectively, apocynin exhibits properties myoprotective in diabetic animals. These findings indicate that apocynin predominantly acts as an antioxidant in fast-twitch and slow-twitch muscles but has differential impact on contractile function.

Emergency medicine questions on the entrance examination for medical internships and residency training in Spain: analysis of changes between 2010 and 2019. / Presencia de la Medicina de Urgencias y Emergencias en el examen de médico interno residente (MIR) en España: análisis evolutivo durante el periodo 2010-2019.

OBJECTIVES: To investigate the presence of fundamental concepts in emergency medicine on the entrance examination taken by candidates for medical internships and residency training in Spain, and to identify changes over time. MATERIAL AND METHODS: Longitudinal retrospective study. Three independent researchers reviewed questions on the entrance examinations of the past 10 years (2010-2019) and classified them as directly, indirectly, or not related to emergency medicine. The topics of directly related questions were also classified according to the categories listed in Tintinalli's Emergency Medicine and subject areas in the Citation Index Expanded (SCIE) of the Web of Science. Changes in the number of questions and range of topics were analyzed with simple linear regression models. RESULTS: A total of 2300 questions were reviewed; 487 (22%) were directly related to emergency medicine, and 313 of them specifically referred to an emergency or urgent care setting. The proportion of directly related questions held steady over the 10-year period (P=.172). The most frequently mentioned categories listed by Tintinalli were cardiovascular (12.2%), infectious (11.1%), and gastrointestinal (10.9%) emergencies, and no significant differences were noted over time. However, proportions assigned to the SCIE categories did change over time, as follows. Questions about emergency care in general (11.9% during the period overall) increased significantly with time (P=.005) whereas cardiovascular questions (11.3%) decreased (P=.037). The proportion of infectious disease topics remained the same (10.7%). CONCLUSION: Even though emergency medicine is not a recognized specialty for medical residency training in the public health system, questions on emergencies are considered important for evaluating candidates, judging by the high percentage of questions on the examinations.

OBJETIVO: Investigar la presencia del cuerpo doctrinal de la Medicina de Urgencias y Emergencias (MUE) en el examen de acceso a médico interno residente (MIR) en España y su evolución en el tiempo. METODO: Estudio longitudinal retrospectivo. Tres investigadores revisaron independientemente las preguntas de los exámenes MIR de los últimos 10 años (2010-2019) y las clasificaron por acuerdo mayoritario como directamente, indirectamente o no relacionadas con la MUE. La temática de las preguntas directamente relacionadas con la MUE se clasificó según el índice del libro de texto de MUE de Tintinalli y según la clasificación de las áreas de la base Science Citation Index Expanded (SCIE) de la Web of Science. La evolución temporal de la presencia y la temática de la MUE se analizó mediante regresión lineal simple. RESULTADOS: Se revisaron 2.300 preguntas: 487 (22%) estaban directamente relacionadas con la MUE (313 citaban específicamente el escenario de urgencias o emergencias). La presencia de preguntas directamente relacionadas con la MUE se mantuvo constante entre 2010-2019 (p = 0,172). Siguiendo la clasificación de Tintinalli, las temáticas más frecuentes de estas preguntas fueron urgencias cardiovasculares (12,2%), infecciosas (11,1%) y gastrointestinales (10,9%), sin cambios significativos entre 2010-2019, mientras que siguiendo la clasificación del SCIE, estas temáticas fueron urgencias (11,9%, que aumentó significativamente durante el periodo, p = 0,005), cardiovascular (11,3%, que descendió, p = 0,037) y enfermedades infecciosas (10,7%, sin cambios durante el periodo). CONCLUSIONES: La MUE, a pesar de no estar reconocida como una especialidad formativa por la vía MIR, tiene una elevada relevancia para la administración sanitaria a la hora de seleccionar a los MIR, que inician su formación especializada en el sistema público de salud, a juzgar por su elevada presencia en el examen anual al que se somete a los candidatos.

Presencia de la Medicina de Urgencias y Emergencias en el examen de médico interno residente (MIR) en España: análisis evolutivo durante el periodo 2010-2019 / Emergency medicine questions on the entrance examination for medical internships and residency training in Spain: analysis of changes between 2010 and 2019

OBJETIVO: Investigar la presencia del cuerpo doctrinal de la Medicina de Urgencias y Emergencias (MUE) en el examen de acceso a médico interno residente (MIR) en España y su evolución en el tiempo. MÉTODO: Estudio longitudinal retrospectivo. Tres investigadores revisaron independientemente las preguntas de los exámenes MIR de los últimos 10 años (2010-2019) y las clasificaron por acuerdo mayoritario como directamente, indirectamente o no relacionadas con la MUE. La temática de las preguntas directamente relacionadas con la MUE se clasificó según el índice del libro de texto de MUE de Tintinalli y según la clasificación de las áreas de la base Science Citation Index Expanded (SCIE) de la Web of Science. La evolución temporal de la presencia y la temática de la MUE se analizó mediante regresión lineal simple. RESULTADOS: Se revisaron 2.300 preguntas: 487 (22%) estaban directamente relacionadas con la MUE (313 citaban específicamente el escenario de urgencias o emergencias). La presencia de preguntas directamente relacionadas con la MUE se mantuvo constante entre 2010-2019 (p = 0,172). Siguiendo la clasificación de Tintinalli, las temáticas más frecuentes de estas preguntas fueron urgencias cardiovasculares (12,2%), infecciosas (11,1%) y gastrointestinales (10,9%), sin cambios significativos entre 2010-2019, mientras que siguiendo la clasificación del SCIE, estas temáticas fueron urgencias (11,9%, que aumentó significativamente durante el periodo, p = 0,005), cardiovascular (11,3%, que descendió, p = 0,037) y enfermedades infecciosas (10,7%, sin cambios durante el periodo). CONCLUSIÓN: La MUE, a pesar de no estar reconocida como una especialidad formativa por la vía MIR, tiene una elevada relevancia para la administración sanitaria a la hora de seleccionar a los MIR, que inician su formación especializada en el sistema público de salud, a juzgar por su elevada presencia en el examen anual al que se somete a los candidatos

OBJETIVE: To investigate the presence of fundamental concepts in emergency medicine on the entrance examination taken by candidates for medical internships and residency training in Spain, and to identify changes over time. METHODS: Longitudinal retrospective study. Three independent researchers reviewed questions on the entrance examinations of the past 10 years (2010-2019) and classified them as directly, indirectly, or not related to emergency medicine. The topics of directly related questions were also classified according to the categories listed in Tintinalli's Emergency Medicine and subject areas in the Citation Index Expanded (SCIE) of the Web of Science. Changes in the number of questions and range of topics were analyzed with simple linear regression models. RESULTS: A total of 2300 questions were reviewed; 487 (22%) were directly related to emergency medicine, and 313 of them specifically referred to an emergency or urgent care setting. The proportion of directly related questions held steady over the 10-year period (P=.172). The most frequently mentioned categories listed by Tintinalli were cardiovascular (12.2%), infectious (11.1%), and gastrointestinal (10.9%) emergencies, and no significant differences were noted over time. However, proportions assigned to the SCIE categories did change over time, as follows. Questions about emergency care in general (11.9% during the period overall) increased significantly with time(P=.005) whereas cardiovascular questions (11.3%) decreased (P=.037). The proportion of infectious disease topics remained the same (10.7%). CONCLUSION: Even though emergency medicine is not a recognized specialty for medical residency training in the public health system, questions on emergencies are considered important for evaluating candidates, judging by the high percentage of questions on the examinations

The thermochromism of the ET(30) betaine in a micro-heterogeneous medium: a spectral and dynamics simulation study.

A spectral investigation of the thermochromic behavior of Reichardt's E(T)(30) betaine in aqueous solutions of block copolymers ("poloxamers") P407, P237 and P105 was carried out as a function of temperature and concentration. The betaine microenvironment at various stages of the micellization process in these systems was mimicked with the aid of molecular dynamics simulations of model systems. These consisted of the E(T)(30) probe in boxes of water molecules, in the presence of an isolated block copolymer of formula (PEO)(11)-(PPO)(16)-(PEO)(11), and of a micelle formed of 50 of these unimers.