Cancer stem cells in malignant peripheral nerve sheath tumor: Biology and therapeutic ramifications [abstract]

Neuroscience - Vision and Functional Brain Imaging Poster SessionAlthough monoclonal in origin, most tumors appear to contain heterogeneous populations of cancer cells. One possible explanation of this tumor heterogeneity is that human tumors are not merely monoclonal expansions of a single transformed cell, but rather caricatures of normal tissues, and their growth is sustained by cancer stem cells (CSCs). This conceptual shift has important implications, not only for understanding tumor biology but also for developing and evaluating effective anticancer therapies. These CSCs are thought to be more resistant to apoptosis, to survive therapy and to eventually give rise to second-line tumors, which are harder to eliminate by the first-line therapy. In this proposal, we are introducing our data in detection of CSCs in malignant peripheral nerve sheath tumors (MPNSTs) for the first time, and explain our plans for studying the biology of these cells in order to develop a therapeutic strategy for targeting them. We have identified a sub-population of cells in primary human MPNST cells which are positive for CD133 (a well-known marker for CSCs) and other stem cell markers. We have also studied the characteristics of Ras signaling pathway in these cells showing enhanced activation of Ras, Ral, PI3K and ERK. Now, we plan to not only study the biological characteristics of these cells further but also intend to “custom design” a new protocol for targeting them on the basis of specific characteristics of Ras pathway in these cells. If MPNST CSCs could be targeted, it can result in an efficient regression of tumors and enhancement of therapeutic success in MPNST patients

Levels of Sustainability Awareness in Spanish University Students of Nautical Activities as Future Managers of Sports and Active Tourism Programmes

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).Abstract: University students will play an important role in making decisions that will affect the environment, as future leaders of our society. Their level of sensitivity and environmental knowledge will play an important role in adequately facing future challenges. This article aims to measure the sustainability awareness of a sample of future graduates in Physical Activity and Sport Sciences in Spain. The literature supports that the sensitivity of these students can be estimated by using the Spanish adaptation of the SCQ-S. This allows for establishing the level of knowledge, attitudes and behaviour pertaining to sustainability in three dimensions: environmental, social and economic. The sample consisted of 170 students (58.8% males; 41.2% females) with a mean age of 20.5 years (±4.039). The overall Cronbach’s alpha showed a fairly good value (α = 0.836). The same was true for the Kaiser–Meyer–Olkin test values (KMO = 0.816) and Bartlett’s sphericity test (p < 0.001). The knowledge construct (4.56 ± 0.53) was the highest descriptive, followed by attitude (4.12 ± 0.59). The lowest value was behaviour (3.79 ± 0.66). By gender, girls obtained the highest sensitivity indexes. In addition, the place of habitual residence and physical activity in the natural environment were related to the overall behaviour of the university students. It is concluded that being in active contact with the natural environment allows us to have a higher level of awareness

Ground calcium carbonate as a low cost and biosafety excipient for solubility and dissolution improvement of praziquantel

Calcium carbonate is an abundant mineral with several advantages to be a successful carrier to improve oral bioavailability of poorly water-soluble drugs, such as praziquantel. Praziquantel is an antiparasitic drug classified in group II of the Biopharmaceutical Classification System hence characterized by high-permeability and low-solubility. Therefore, the dissolution rate is the limiting factor for the gastrointestinal absorption that contributes to the low bioavailability. Consequently, the therapeutic dose of the praziquantel must be high and big tablets and capsules are required, which are difficult to swallow, especially for pediatric and elderly patients. Mixtures of praziquantel and calcium carbonate using solid-solid physical mixtures and solid dispersions were prepared and characterized using several techniques (X-ray diffraction differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, laser diffraction, Fourier transform infrared and Raman spectroscopies). Solubility of these formulations evidenced that the solubility of praziquantel-calcium carbonate interaction product increased in physiological media. In vitro dissolution tests showed that the interaction product increased the dissolution rate of the drug in acidic medium. Theoretical models were studied to understand this experimental behavior. Cytotoxicity and cell cycle studies were performed, showing that praziquantel-calcium carbonate physical mixture and interaction product were biocompatible with the HTC116 cells, because it did not produce a decrease in cell viability or alterations in the cell cycle

COVID-19 pandemic on coronary artery and cerebrovascular diseases in Southern Spain: interrupted time series analysis

Objective: Healthcare systems have been put under intense pressure by the COVID-19 pandemic, although some studies have shown a decline in hospital admissions for cardiovascular and cerebrovascular diseases during the first and second wave of the pandemic. In addition, studies analyzing gender and procedural differences are scarce. The present study aimed to determine the impact of the pandemic on hospital admissions for acute myocardial infarction (AMI) and cerebrovascular disease (CVD) in Andalusia (Spain) and analyzed differences by gender and by percutaneous coronary interventions performed. Patients and methods: An interrupted time series analysis of AMI and CVD hospital admissions in Andalusia (Spain) was carried out to measure the impact of the COVID-19 outbreak. AMI and CVD cases admitted daily in public hospitals of Andalusia between January 2018 and December 2020 were included. Results: During the pandemic, significant reductions in AMI [-19%; 95% confidence interval (CI): (-29%, -9%), p&lt;0.001] and CVD [-17%; 95% CI: (-26%, -9%); p&lt;0.01] in daily hospital admissions were observed. Differences were also produced according to the diagnosis (ST-Elevation Myocardial Infarction, Non-ST-Elevation Myocardial Infarction, other AMI and stroke), with a greater reduction in females for AMI and in males for CVD. Although there were more percutaneous coronary interventions during the pandemic, no significant reductions were observed. Conclusions: A decline in AMI and CVD daily hospital admissions during the first and second wave of COVID-19 pandemic was noted. Gender differences were observed, but no clear impact was observed in percutaneous interventions

Un caso de Síndrome de Wünderlich y revisión de la bibliografía / A case of Wünderlich syndrome and literature review

El diagnóstico y terapéutica de las malformaciones congénitas todavía hoy constituye una problemática universal. El presente trabajo corresponde al estudio de un caso de una adolescente de 14 años de edad, paciente del Hospital Oncológico Dr. Julio Villacreses Colmont de Manabí (SOLCA), Ecuador, que a partir del mes de septiembre de 2014 inicia con cuadro clínico de dolor pélvico mantenido, leucorrea persistente y fétida, sin menarquia y sin respuesta a tratamiento específico. Realizadas la Ecografía y Resonancia Magnética, se definen múltiples malformaciones congénitas, obteniéndose el diagnóstico del Síndrome de Wünderlich; una patología rara, con frecuencia de un 40%. El objetivo de este trabajo consiste en demostrar la elevada frecuencia de esta morbilidad para disminuir tratamientos quirúrgicos innecesarios (Histerectomía), un factor agravante para su eventual compromiso reproductivo. En Ecuador no reportan estadísticas del síndrome, o existe un subregistro de esta entidad. Abstract The diagnosis and treatment of congenital malformations is still a universal problem nowadays. The present work is a study of a case of a 14-year-old patient at the Cancer Hospital Dr. Julio Villacreces Colmont (SOLCA) in Manabí, Ecuador, that from September 2014 begins with clinical symptoms of steady pelvic pain, a persistent and fetid leukorrhea without menarche and response to a specific treatment. Once carried ultrasound and MRI, multiple congenital malformations are defined to give the diagnosis Wünderlich Syndrome; a rare disease, which is frequent at a 40%. The objective of this work is to demonstrate the high frequency of this disease to reduce unnecessary surgical treatment (hysterectomy), which is an aggravating factor for possible reproductive status. In Ecuador there is no statistical report of this syndrome, or there is underreporting of this disease

A Second Generation 2-Methoxyestradiol Prodrug Is Effective Against Barrett's Adenocarcinoma in a Mouse Xenograft Model

This is the author's accepted manuscript. The original is available at http://mct.aacrjournals.org/content/12/3/2552-Methoxyestradiol (2-ME2) is an endogenous metabolite of estradiol. In preclinical models, 2-ME2 is effective against different types of tumors. Unfortunately, only low systemic concentrations of 2-ME2 can be achieved following oral administration, even after very high doses are administered to patients. In an effort to solve this problem we have now synthesized and tested a new prodrug of 2-ME2 that is water soluble due to a bio-reversible hydrophilic group added at the 3-position and more effectively resists metabolic inactivation due to an ester moiety added to mask the 17-position alcohol. We are reporting here for the first time that this double prodrug of 2-ME2 is effective as an antiproliferative and anti-cancer agent for both in vitro and in vivo studies against Barrett's esophageal adenocarcinoma (BEAC), and provided greater potency than 2-ME2 in inhibiting the growth of BEAC xenografts. Finally, studies indicate that, like 2-ME2, the 2-ME2-PD1 exhibits anticancer effect through possible disruption of microtubule-network

Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion

Genetic variants that result in truncation in desmoplakin (DSP) are a known cause of arrhythmogenic cardiomyopathy (AC). In homozygous carriers, the combined involvement of skin and heart muscle is well defined, however, this is not the case in heterozygous carriers. The aim of this work is to describe cutaneous findings and analyze the molecular and ultrastructural cutaneous changes in this group of patients. Four women and eight men with a mean age of 48 ± 14 years were included. Eight met definitive criteria for AC, one was borderline and three were silent carriers. No relevant macroscopic changes in skin and hair were detected. However, significantly lower skin temperature (29.56 vs. 30.97 ◦C, p = 0.036) and higher transepidermal water loss (TEWL) (37.62 vs. 23.95 g m 2 h 1, p = 0.028) were observed compared to sex- and age-matched controls. Histopathology of the skin biopsy showed widening of intercellular spaces and acantholysis of keratinocytes in the spinous layer. Immunohistochemistry showed a strongly reduced expression of DSP in all samples. Trichogram showed regular nodules (thickening) compatible with pseudomonilethrix. Therefore, regardless of cardiac involvement, heterozygous patients with truncation-type variants in DSP have lower skin temperature and higher TEWL, constant microscopic skin involvement with specific patterns and pseudomonilethrix in the trichogram.Andalusian Society of Cardiology with a “beca de Investigación general

Hypertrophic cardiomyopathy mutations in the calponin-homology domain of ACTN2 affect actin binding and cardiomyocyte Z-disc incorporation

α-Actinin-2 (ACTN2) is the only muscle isoform of α-actinin expressed in cardiac muscle. Mutations in this protein have been implicated in mild to moderate forms of hypertrophic cardiomyopathy (HCM). We have investigated the effects of two mutations identified from HCM patients, A119T and G111V, on the secondary and tertiary structure of a purified actin binding domain (ABD) of ACTN2 by circular dichroism and X-ray crystallography, and show small but distinct changes for both mutations. We also find that both mutants have reduced F-actin binding affinity, although the differences are not significant. The full length mEos2 tagged protein expressed in adult cardiomyocytes shows that both mutations additionally affect Z-disc localization and dynamic behaviour. Overall, these two mutations have small effects on structure, function and behaviour, which may contribute to a mild phenotype for this disease