The Potential Use of Mitochondrial Extracellular Vesicles as Biomarkers or Therapeutical Tools.

The mitochondria play a crucial role in cellular metabolism, reactive oxygen species (ROS) production, and apoptosis. Aberrant mitochondria can cause severe damage to the cells, which have established a tight quality control for the mitochondria. This process avoids the accumulation of damaged mitochondria and can lead to the release of mitochondrial constituents to the extracellular milieu through mitochondrial extracellular vesicles (MitoEVs). These MitoEVs carry mtDNA, rRNA, tRNA, and protein complexes of the respiratory chain, and the largest MitoEVs can even transport whole mitochondria. Macrophages ultimately engulf these MitoEVs to undergo outsourced mitophagy. Recently, it has been reported that MitoEVs can also contain healthy mitochondria, whose function seems to be the rescue of stressed cells by restoring the loss of mitochondrial function. This mitochondrial transfer has opened the field of their use as potential disease biomarkers and therapeutic tools. This review describes this new EVs-mediated transfer of the mitochondria and the current application of MitoEVs in the clinical environment.

Extracellular Vesicles: The Future of Diagnosis in Solid Organ Transplantation?

Solid organ transplantation (SOT) is a life-saving treatment for end-stage organ failure, but it comes with several challenges, the most important of which is the existing gap between the need for transplants and organ availability. One of the main concerns in this regard is the lack of accurate non-invasive biomarkers to monitor the status of a transplanted organ. Extracellular vesicles (EVs) have recently emerged as a promising source of biomarkers for various diseases. In the context of SOT, EVs have been shown to be involved in the communication between donor and recipient cells and may carry valuable information about the function of an allograft. This has led to an increasing interest in exploring the use of EVs for the preoperative assessment of organs, early postoperative monitoring of graft function, or the diagnosis of rejection, infection, ischemia-reperfusion injury, or drug toxicity. In this review, we summarize recent evidence on the use of EVs as biomarkers for these conditions and discuss their applicability in the clinical setting.

Small extracellular vesicles from senescent stem cells trigger adaptive mechanisms in young stem cells by increasing antioxidant enzyme expression.

Extracellular vesicles' biogenesis, shedding, and uptake are redox-sensitive. Indeed, oxidative stress conditions influence extracellular vesicles' release and content, which can modulate the redox status of the receiving cells. In this study, we aimed to assess the effect of extracellular vesicles from human dental pulp stem cells cultured under 21% O2 (senescent stem cells) on human dental pulp stem cells cultured under 3% O2 (young stem cells). Extracellular vesicles were isolated by ultracentrifugation from senescent stem cells and prepared for the treatment of young stem cells at a final concentration of 10 µg/mL. Cells were analyzed for antioxidant gene expression, mitochondrial bioenergetic parameters, ROS production, culture kinetics, and apoptosis. The results show that extracellular vesicles from senescent stem cells induce overexpression of antioxidant genes (MnSOD, CAT, and GPx) in young stem cells, which show an increased non-mitochondrial oxygen consumption, accompanied by reduced maximal respiration and spare respiratory capacity without altering mitochondrial membrane potential. This is accompanied by improved cell proliferation, viability, and migration rates and a reduction of apoptosis. In conclusion, extracellular vesicles from senescent stem cells trigger an adaptive response in young stem cells which improves their antioxidant defenses and their proliferation, migration, and survival rates. This suggests that extracellular vesicles can modulate the cells' microenvironment and the balance between proliferation and senescence.

Extracellular Vesicles as Therapeutic Resources in the Clinical Environment.

The native role of extracellular vesicles (EVs) in mediating the transfer of biomolecules between cells has raised the possibility to use them as therapeutic vehicles. The development of therapies based on EVs is now expanding rapidly; here we will describe the current knowledge on different key points regarding the use of EVs in a clinical setting. These points are related to cell sources of EVs, isolation, storage, and delivery methods, as well as modifications to the releasing cells for improved production of EVs. Finally, we will depict the application of EVs therapies in clinical trials, considering the impact of the COVID-19 pandemic on the development of these therapies, pointing out that although it is a promising therapy for human diseases, we are still in the initial phase of its application to patients.

Extracellular Vesicles and Cellular Ageing.

Ageing is a complex process characterized by deteriorated performance at multiple levels, starting from cellular dysfunction to organ degeneration. Stem cell-based therapies aim to administrate stem cells that eventually migrate to the injured site to replenish the damaged tissue and recover tissue functionality. Stem cells can be easily obtained and cultured in vitro, and display several qualities such as self-renewal, differentiation, and immunomodulation that make them suitable candidates for stem cell-based therapies. Current animal studies and clinical trials are being performed to assess the safety and beneficial effects of stem cell engraftments for regenerative medicine in ageing and age-related diseases.Since alterations in cell-cell communication have been associated with the development of pathophysiological processes, new research is focusing on the modulation of the microenvironment. Recent research has highlighted the important role of some microenvironment components that modulate cell-cell communication, thus spreading signals from damaged ageing cells to neighbor healthy cells, thereby promoting systemic ageing. Extracellular vesicles (EVs) are small-rounded vesicles released by almost every cell type. EVs cargo includes several bioactive molecules, such as lipids, proteins, and genetic material. Once internalized by target cells, their specific cargo can induce epigenetic modifications and alter the fate of the recipient cells. Also, EV's content is dependent on the releasing cells, thus, EVs can be used as biomarkers for several diseases. Moreover, EVs have been proposed to be used as cell-free therapies that focus on their administration to slow or even reverse some hallmarks of physiological ageing. It is not surprising that EVs are also under study as next-generation therapies for age-related diseases.

The Double-Edged Role of Extracellular Vesicles in the Hallmarks of Aging.

The exponential growth in the elderly population and their associated socioeconomic burden have recently brought aging research into the spotlight. To integrate current knowledge and guide potential interventions, nine biochemical pathways are summarized under the term hallmarks of aging. These hallmarks are deeply inter-related and act together to drive the aging process. Altered intercellular communication is particularly relevant since it explains how damage at the cellular level translates into age-related loss of function at the organismal level. As the main effectors of intercellular communication, extracellular vesicles (EVs) might play a key role in the aggravation or mitigation of the hallmarks of aging. This review aims to summarize this role and to provide context for the multiple emerging EV-based gerotherapeutic strategies that are currently under study.

Therapeutic Potential of Extracellular Vesicles in Aging and Age-Related Diseases.

Aging is associated with an alteration of intercellular communication. These changes in the extracellular environment contribute to the aging phenotype and have been linked to different aging-related diseases. Extracellular vesicles (EVs) are factors that mediate the transmission of signaling molecules between cells. In the aging field, these EVs have been shown to regulate important aging processes, such as oxidative stress or senescence, both in vivo and in vitro. EVs from healthy cells, particularly those coming from stem cells (SCs), have been described as potential effectors of the regenerative potential of SCs. Many studies with different animal models have shown promising results in the field of regenerative medicine. EVs are now viewed as a potential cell-free therapy for tissue damage and several diseases. Here we propose EVs as regulators of the aging process, with an important role in tissue regeneration and a raising therapy for age-related diseases.

Advanced MRI Protocols to Discriminate Glioma From Treatment Effects: State of the Art and Future Directions.

In the follow-up treatment of high-grade gliomas (HGGs), differentiating true tumor progression from treatment-related effects, such as pseudoprogression and radiation necrosis, presents an ongoing clinical challenge. Conventional MRI with and without intravenous contrast serves as the clinical benchmark for the posttreatment surveillance imaging of HGG. However, many advanced imaging techniques have shown promise in helping better delineate the findings in indeterminate scenarios, as posttreatment effects can often mimic true tumor progression on conventional imaging. These challenges are further confounded by the histologic admixture that can commonly occur between tumor growth and treatment-related effects within the posttreatment bed. This review discusses the current practices in the surveillance imaging of HGG and the role of advanced imaging techniques, including perfusion MRI and metabolic MRI.

Hardware Acceleration of EEG-Based Emotion Classification Systems: A Comprehensive Survey.

Recent years have witnessed a growing interest in EEG-based wearable classifiers of emotions, which could enable the real-time monitoring of patients suffering from neurological disorders such as Amyotrophic Lateral Sclerosis (ALS), Autism Spectrum Disorder (ASD), or Alzheimer's. The hope is that such wearable emotion classifiers would facilitate the patients' social integration and lead to improved healthcare outcomes for them and their loved ones. Yet in spite of their direct relevance to neuro-medicine, the hardware platforms for emotion classification have yet to fill up some important gaps in their various approaches to emotion classification in a healthcare context. In this paper, we present the first hardware-focused critical review of EEG-based wearable classifiers of emotions and survey their implementation perspectives, their algorithmic foundations, and their feature extraction methodologies. We further provide a neuroscience-based analysis of current hardware accelerators of emotion classifiers and use it to map out several research opportunities, including multi-modal hardware platforms, accelerators with tightly-coupled cores operating robustly in the near/supra-threshold region, and pre-processing libraries for universal EEG-based datasets.

Limiting the stroke of a Schmitt trigger with multiplicative noise.

We have devised an experiment whereby a bistable system is confined away from its deterministic attractors by means of multiplicative noise. Together with previous numerical results, our experimental results validate the hypothesis that the higher the slope of the noise's multiplicative factor, the more it shifts the stationary states.

The top 100 cited articles published in emergency medicine journals.

INTRODUCTION: Our objective was to identify trends and examine the characteristics of the top 100 cited articles in emergency medicine (EM) journals. METHODS: Scopus Library database was queried to determine the citations of the top 100 EM articles. A second database (Google Scholar) was used to gather the following information: number of authors, publication year, journal name, impact factor, country of origin, and article type (original article, review article, conference paper, or editorial). The top 100 cited articles were selected and analyzed by 2 independent investigators. RESULTS: We identified 100 top-cited articles published in 6 EM journals, led by Annals of Emergency Medicine (65) and American Journal of Emergency Medicine (15). All top-cited articles were published between 1980 and 2009. The common areas of study were categorized as cardiovascular medicine, emergency department administration, toxicology, pain medicine, pediatrics, traumatology, and resuscitation. A statistically significant association was found between the journal impact factor and the number of top 100 cited articles (P < .005). CONCLUSION: The top-cited articles published in EM journals help us recognize the quality of the works, discoveries, and trends steering EM. Our analysis provides an insight to the prevalent areas of study being cited within our field of practice.

Afrontamiento y Adapatación de Pacientes en Hemodiálisis y Diálisis. Cartagena 2010 / Coping and Adaptation of Patients in Hemodialysis and Dialysis. Cartagena 2010 / Enfrentamento e Adaptação de Pacientes em Hemodiálise e Diálise. Cartagena 2010

Objetivo: Describir y contrastar el afrontamiento y la adaptación de los pacientes en hemodiálisis y diálisis peritoneal continua ambulatoria en dos unidades renales en Cartagena. Metodología: Estudio descriptivo con abordaje cuantitativo. Participaron 277 adultos, 243 en tratamiento de hemodiálisis y 34 diálisis peritoneal en unidades renales en el primer periodo del 2010. El afrontamiento y adaptación, se cuantificó con la Escala del Proceso de Afrontamiento y Adaptación de Roy. Los datos se analizaron mediante estadística descriptiva. Resultados: La edad promedio de los pacientes en diálisis fue de 55,6 años y para los hemodializados de 56 años de edad, el sexo masculino se observó en mayor proporción en los pacientes con diálisis 55.9%. Los pacientes bajo tratamiento mostraron alta capacidad de afrontamiento y adaptación en un mayor grado en los hemodializados en 78,2%, la capacidad alta de afrontamiento se evidenció en ser enfocados con 76,1% y en bajo grado al realizar procesamientos sistemático con 56,8%, para los que reciben diálisis el factor con mayor capacidad de afrontamiento y adaptación fue en estar alerta con 76,5% y el más bajo en relación con tener reacciones físicas y enfocadas con 58,8%. Conclusión: Existe una capacidad de afrontamiento y adaptación alta en pacientes en tratamiento de hemodiálisis y diálisis, mostrando tendencias estables en el uso de estrategias de afrontamiento para sí mismo y para otros a nivel cognitivo, comportamental y emocional.

Objective: Describe and contrast the coping and adaptation of patients in hemodialysis and continuous ambulatory peritoneal dialysis in Cartagena city. Methodology: Descriptive study with quantitative approach. Involved 277 adults, 243 on hemodialysis and 34 peritoneal dialysis attending renal units in the first quarter of 2010. The coping and adaptation, was quantified with the Scale of Coping and Adaptation Process of Roy. The data were expressed using descriptive statistics as percentages. Results: The average age of dialysis patients was 55.6 years and for those on hemodialysis, 56 years of age, male sex was observed in greater proportion in dialysis patients 55.9%. Patients under treatment showed good coping and adaptation to a greater extent in those on hemodialysis in 78.2%, in hemodialysis patients treated by high coping ability was evident to be focused with 76.1% and low-grade to make systematic processing 56.8% for those receiving dialysis the main factor coping and adaptation was being alert to 76.5% and the lowest in relation to have physical reactions and focused with 58.8%. Conclusion: There is a capacity for high active coping style in patients treated with hemodialysis and peritoneal dialysis, which show stable trends in the use of coping strategies for themselves and others at the three domains of cognitive, behavioral and emotional.

Objetivo: Descrever e aferir o enfrentamento e a adaptação dos pacientes em hemodiálise e diálise peritoneal ambulatorial contínua em duas unidades renais em Cartagena. Metodologia: Estudo descritivo com abordagem quantitativo. 277 adultos participaram; 243 em tratamento de hemodiálise, e 34 em diálise peritoneal comparecendo em unidades renais no primeiro período de 2010. O enfrentamento e adaptação foram quantificados com a Escala de Enfrentamento e Processo de Adaptação de Roy. A data foi analisada mediante estatística descritiva. Resultados: A média das idades nos pacientes em diálise foi 55,6 anos, e para os pacientes de 56 anos de idade com hemodiálise, o sexo masculino apresentou maior proporção nos pacientes com diálise, 55.9%. Os pacientes com tratamentos de hemodiálise apresentaram elevada resposta de enfrentamento e adaptação em maior grau: 78,2%. A capacidade elevada de enfrentamento foi evidente ao serem enfocados com 76,1%, e em baixo nível ao realizar processamentos sistemáticos com 56,8%. Para os que recebem diálise, o fator com maior capacidade de enfrentamento e adaptação foi estar vigilantes com 76,5%, e o mais baixo no que diz respeito a apresentar reação física e focada com 58,8%. Conclusão: Os pacientes em tratamento de hemodiálise e diálise apresentam capacidade e adaptação elevada, evidenciando tendências estáveis no uso de estratégias de enfrentamento para si mesmo e para outros no nível cognitivo, comportamental e emocional.

Quick method for mean frontal QRS axis determination.

BACKGROUND: ECGs are the recording of the electrical activity of the heart. The direction of it's current in the frontal plane can be determined by analyzing the QRS direction and magnitude in limb leads. Several methods for determination of the QRS frontal axis have been proposed, however most of them require memorization of the exact location of the leads in the frontal plane with pen and paper calculations. METHODS: a new method of estimating the frontal mean QRS axis in the standard 12 lead ECG is proposed. This method consists of assigning pre-determined values to each frontal lead in ECGs, which have a positive or isoelectric QRS complexes in lead, I. The mnemonic "+/- 90, -30, +30, -60, +60, and 0" is obtained by plotting only the value of the axis which is perpendicular to the each lead on the left side of the hexaxial system. The right-sided perpendiculars are not considered since lead I indicates a left sided axis. The most isoelectric lead will have only one value plotted and that will be the mean QRS axis in the frontal plane. By finding the most equiphasic lead(s) and matching the corresponding pre-determined value we can estimate the frontal mean QRS axis in most of the cases. Interpolation between two leads is allowed if no single isoelectric lead is identified. We reviewed the standard 12 lead electrocardiograms of 155 patients who underwent open-heart coronary revascularization procedures at the VA Caribbean Health Center from 2003 to 2006. Frontal mean QRS axis was determined by the proposed new methodology and the results were compared to the QRS axis determined by the GE Marquette 5000 electrocardiographer utilized in all the reviewed ECG's. Simple regression analysis was used to determine the proposed methods predictive accuracy. RESULTS: We obtained a high coefficient of determination R2= 0.9505, p<0.001. The derived linear equation was obtained as follow: y = 1.0007 + 0.9580x (Where independent x= QRS axis estimated by the new method, dependent y = QRS axis estimated by ECG machine). CONCLUSION: The proposed new method is simple and is able to estimate accurately the ECG frontal axis as compared with the GE Marquette 5000 electrocardiographer in most of the cases.

Tumores del estroma gastrointestinal: resultados del tratamiento / Gastrointestinal stromal tumors: incidence and treatment results

Revisar nuestra experiencia en el Servicio de Medicina Interna Oncológica en el tratamiento con imatinib en los tumores del estroma gastrointestinal. Se analizaron 9 pacientes con diagnostico de tumor del estroma gastrointestinal entre los años 2000 y 2004. Se evaluaron factores tales como edad, sexo, fecha del diagnostico, duración del tratamiento, sitio de presentación, inmunohistoquimica, presencia de metástasis, recidiva, toxicidades y mediana de sobrevida. El promedio de seguimiento fue de 17 meses. Tres pacientes eran del sexo masculino (33,3 por ciento) y seis pacientes el sexo femenino (66,6 por ciento) con una media de edad de 43,1 años. Seis pacientes recibieron imatinib. Los sitios anatómicos de presentación fueron estómago en 3 casos e intestino delgado, colon transverso respectivamente. Todos os pacientes fueron previamente a laparotomía explorada. Dos pacientes recibieron quimioterapia previa. Todos los pacientes recibieron una dosis inicial de imatinib de 400 mg O.D. Se observo respuesta clínica de 2 a 4 semanas, dada por disminución del volumen abdominal. Toxicidades frecuentes: edema en miembros inferiores en 3 pacientes (50 por ciento), mialgias, calambres musculares en 2 pacientes (33,3 por ciento) y gastritis en 2 pacientes (33,3 por cinto). Se recomienda el tratamiento con imatinib a una dosis de 400 mg o 600 mg del día en los pacientes con tumores del estroma gastrointestinal con toxicidad manejable

Perforación uterina y localización vesical de un dispositivo intrauterino y cistolitiasis: comunicación de un caso y revisión de la literatura / Uterine perforation and vesical localization of an device and cystolithiasis: a case presentation an literature review

Se describe el caso de una perforación uterina por un dispositivo intrauterino y su presencia en la cavidad vesical con la formación de un cálculo, en una paciente de 39 años de edad con dos embarazos posteriores a la colocación del mismo. La paciente presentó posteriormente sintomatología urinaria caracterizada por disuria, hematuria, polaquiuria y tenesmo vesical sin sintomatología uterina. El caso fue visto en julio de 1993 en el Hospital General Regional "Vicente Guerrero" de Acapulco. En la literatura solamente se han comunicado 19 casos de migraciones de dispositivos hacia la vejiga con la formación agregada de cistolitiasis. Se efectúa la revisión de la literatura y se disculte la clínico-radiológica