Differential scanning calorimetry in drug-membrane interactions.

Differential Scanning Calorimetry (DSC) is a central technique in investigating drug - membrane interactions, a critical component of pharmaceutical research. DSC measures the heat difference between a sample of interest and a reference as a function of temperature or time, contributing essential knowledge on the thermally induced phase changes in lipid membranes and how these changes are affected by incorporating pharmacological substances. The manuscript discusses the use of phospholipid bilayers, which can form structures like unilamellar and multilamellar vesicles, providing a simplified yet representative membrane model to investigate the complex dynamics of how drugs interact with and penetrate cellular barriers. The manuscript consolidates data from various studies, providing a comprehensive understanding of the mechanisms underlying drug - membrane interactions, the determinants that influence these interactions, and the crucial role of DSC in elucidating these components. It further explores the interactions of specific classes of drugs with phospholipid membranes, including non-steroidal anti-inflammatory drugs, anticancer agents, natural products with antioxidant properties, and Alzheimer's disease therapeutics. The manuscript underscores the critical importance of DSC in this field and the need for continued research to improve our understanding of these interactions, acting as a valuable resource for researchers.

Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway.

The integrated stress response (ISR) regulates cell fate during conditions of stress by leveraging the cell's capacity to endure sustainable and efficient adaptive stress responses. Protein phosphatase 2A (PP2A) activity modulation has been shown to be successful in achieving both therapeutic efficacy and safety across various cancer models; however, the molecular mechanisms driving its selective antitumor effects remain unclear. Here, we show for the first time that ISR plasticity relies on PP2A activation to regulate drug response and dictate cellular fate under conditions of chronic stress. We demonstrate that genetic and chemical modulation of the PP2A leads to chronic proteolytic stress and triggers an ISR to dictate cell fate. More specifically, we uncovered that the PP2A-TFE3-ATF4 pathway governs ISR cell plasticity during endoplasmic reticular and cellular stress independent of the unfolded protein response. We further show that normal cells reprogram their genetic signatures to undergo ISR-mediated adaptation and homeostatic recovery thereby successfully avoiding toxicity following PP2A-mediated stress. Conversely, oncogenic specific cytotoxicity induced by chemical modulation of PP2A is achieved by activating chronic and irreversible ISR in cancer cells. Our findings propose that a differential response to chemical modulation of PP2A is determined by intrinsic ISR plasticity, providing a novel biological vulnerability to selectively induce cancer cell death and improve targeted therapeutic efficacy.

A new tissue-agnostic microfluidic device to model physiology and disease: the lattice platform.

To accurately phenocopy human biology in vitro, researchers have been reducing their dependence on standard, static two-dimensional (2D) cultures and instead are moving towards three-dimensional (3D) and/or multicellular culture techniques. While these culture innovations are becoming more commonplace, there is a growing body of research that illustrates the benefits and even necessity of recapitulating the dynamic flow of nutrients, gas, waste exchange and tissue interactions that occur in vivo. However, cost and engineering complexity are two main factors that hinder the adoption of these technologies and incorporation into standard laboratory workflows. We developed LATTICE, a plug-and-play microfluidic platform able to house up to eight large tissue or organ models that can be cultured individually or in an interconnected fashion. The functionality of the platform to model both healthy and diseased tissue states was demonstrated using 3D cultures of reproductive tissues including murine ovarian tissues and human fallopian tube explants (hFTE). When exogenously exposed to pathological doses of gonadotropins and androgens to mimic the endocrinology of polycystic ovarian syndrome (PCOS), subsequent ovarian follicle development, hormone production and ovulation copied key features of this endocrinopathy. Further, hFTE cilia beating decreased significantly only when experiencing continuous media exchanges. We were then able to endogenously recreate this phenotype on the platform by dynamically co-culturing the PCOS ovary and hFTE. LATTICE was designed to be customizable with flexibility in 3D culture formats and can serve as a powerful automated tool to enable the study of tissue and cellular dynamics in health and disease in all fields of research.

Small-Molecule-Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death.

High-grade serous carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP inhibitors (PARPi) have become the mainstay of HGSC-targeted therapy, given that these tumors are driven by a high degree of genomic instability (GI) and homologous recombination (HR) defects. Nonetheless, approximately 30% of patients initially respond to treatment, ultimately relapsing with resistant disease. Thus, despite recent advances in drug development and an increased understanding of genetic alterations driving HGSC progression, mortality has not declined, highlighting the need for novel therapies. Using a small-molecule activator of protein phosphatase 2A (PP2A; SMAP-061), we investigated the mechanism by which PP2A stabilization induces apoptosis in patient-derived HGSC cells and xenograft (PDX) models alone or in combination with PARPi. We uncovered that PP2A genes essential for cellular transformation (B56α, B56γ, and PR72) and basal phosphatase activity (PP2A-A and -C) are heterozygously lost in the majority of HGSC. Moreover, loss of these PP2A genes correlates with worse overall patient survival. We show that SMAP-061-induced stabilization of PP2A inhibits the HR output by targeting RAD51, leading to chronic accumulation of DNA damage and ultimately apoptosis. Furthermore, combination of SMAP-061 and PARPi leads to enhanced apoptosis in both HR-proficient and HR-deficient HGSC cells and PDX models. Our studies identify PP2A as a novel regulator of HR and indicate PP2A modulators as a therapeutic therapy for HGSC. In summary, our findings further emphasize the potential of PP2A modulators to overcome PARPi insensitivity, given that targeting RAD51 presents benefits in overcoming PARPi resistance driven by BRCA1/2 mutation reversions.

In vitro evaluation of the protective effect of crocin on human erythrocytes.

The interactions and the protective effect of the carotenoid crocin (CRO) on human erythrocytes (RBC) and molecular models of its membrane were investigated. The latter consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the RBC membrane, respectively. X-ray diffraction, differential scanning calorimetry (DSC) and electronic paramagnetic resonance spectroscopy (EPR) showed that CRO produced structural perturbations in DMPC bilayers and in isolated unsealed human erythrocyte membranes. On the other hand, scanning electron microscopy (SEM) showed that CRO induced shape changes in the RBC from their normal discoid form to echinocytes. This result indicates that the CRO molecules were mainly localized in the outer monolayer of the RBC membrane. The assessment of the protective capacity of CRO was revealed by the carotenoid inhibition of the morphological alterations caused by hypochlorous acid (HOCl) to RBC.

Fallopian Tube-Derived Tumor Cells Induce Testosterone Secretion from the Ovary, Increasing Epithelial Proliferation and Invasion.

The fallopian tube epithelium is the site of origin for a majority of high grade serous ovarian carcinomas (HGSOC). The chemical communication between the fallopian tube and the ovary in the development of HGSOC from the fallopian tube is of interest since the fimbriated ends in proximity of the ovary harbor serous tubal intraepithelial carcinoma (STICs). Epidemiological data indicates that androgens play a role in ovarian carcinogenesis; however, the oncogenic impact of androgen exposure on the fallopian tube, or tubal neoplastic precursor lesions, has yet to be explored. In this report, imaging mass spectrometry identified that testosterone is produced by the ovary when exposed to tumorigenic fallopian tube derived PTEN deficient cells. Androgen exposure increased cellular viability, proliferation, and invasion of murine cell models of healthy fallopian tube epithelium and PAX2 deficient models of the preneoplastic secretory cell outgrowths (SCOUTs). Proliferation and invasion induced by androgen was reversed by co-treatment with androgen receptor (AR) antagonist, bicalutamide. Furthermore, ablation of phosphorylated ERK reversed proliferation, but not invasion. Investigation of two hyperandrogenic rodent models of polycystic ovarian syndrome revealed that peripheral administration of androgens does not induce fallopian proliferation in vivo. These data suggest that tumorigenic lesions in the fallopian tube may induce an androgenic microenvironment proximal to the ovary, which may in turn promote proliferation of the fallopian tube epithelium and preneoplastic lesions.

Silencing PTEN in the fallopian tube promotes enrichment of cancer stem cell-like function through loss of PAX2.

High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy that is primarily detected at the metastatic stage. Most HGSOC originates from the fallopian tube epithelium (FTE) and metastasizes to the ovary before invading the peritoneum; therefore, it is crucial to study disease initiation and progression using FTE-derived models. We previously demonstrated that loss of PTEN from the FTE leads to ovarian cancer. In the present study, loss of PTEN in FTE led to the enrichment of cancer stem cell markers such as LGR5, WNT4, ALDH1, CD44. Interestingly, loss of the transcription factor PAX2, which is a common and early alteration in HGSOC, played a pivotal role in the expression of cancer stem-like cells (CSC) markers and cell function. In addition, loss of PTEN led to the generation of two distinct subpopulations of cells with different CSC marker expression, tumorigenicity, and chemoresistance profiles. Taken together, these data suggest that loss of PTEN induces reprogramming of the FTE cells into a more stem-like phenotype due to loss of PAX2 and provides a model to study early events during the FTE-driven ovarian cancer tumor formation.

COVID-19 en Pediatría. ¿Qué se sabe? / COVID-19 in Pediatrics. What is known about it?

Introducción: La COVID-19 es una pandemia mundial que flagela la supervivencia del hombre. Este problema sanitario estremece cada jornada los servicios de salud y genera mortalidad en casi todos los grupos de edad. Objetivo: Aportar datos sobre la COVID-19 que tribute a mejoras en el proceso de atención a niños sospechosos y enfermos con SARS-CoV-2. Material y Método: Se hizo revisión sobre la COVID-19 en Pubmed/Medline, ScienceDirecty SciELO. Se utilizó el buscador Google Académico. Se usaron las palabras coronavirus, COVID-19, y SARS-CoV-2, en idioma español e inglés. La información obtenida se clasificó según tipo fuente. Después de este proceso, se inició la redacción del artículo. Desarrollo: La mayor parte de los casos pediátricos es asintomático. Las manifestaciones clínicas comunes incluyen fiebre, tos, odinofagia y dificultad respiratoria. Aunque la presentación asintomática sigue siendo preponderante, la afectación respiratoria, digestiva, neurológica y cutánea se señala en grado variable. El hábito de fumar, y otras condiciones individuales se relacionan con la evolución de la enfermedad. Las pruebas de laboratorio describen leucopenia; sobre todo, en formas graves. La elevación de la procalcitonina y la proteína C reactiva orientan a sobreinfección bacteriana, y es justificación para usar antibióticos. La radiografía de tórax habitualmente es normal, pero puede revelar infiltrados en forma de parches en pacientes con afectación parenquimatosa. La evolución es favorable, y la mortalidad baja. Conclusiones: La COVID-19 en niños tiene presentación heterogénea. Por lo general, es asintomática, aunque puede tener afectación en sistemas y aparatos. Evoluciona hacia la recuperación total en 3-4 semanas(AU)

Introduction: COVID-19 is a global pandemic that threats the survival of man. This health problem shakes health services every day and generates mortality in almost all age groups. Objective: To provide data on COVID-19 that contribute to improve quality of the care process in children with suspected SARS-CoV-2 or with the infection. Material and Methods: A review of COVID-19 was carried out in Pubmed/Medline, Science Direct and SciELO. Google Scholar search engine was used. The words coronavirus, COVID-19, and SARS-CoV-2 in Spanish and English were used. The information obtained was classified according to the type of source. After this process, the drafting of the article began. Development: Most pediatric cases are asymptomatic. Common clinical manifestations include fever, cough, odynophagia, and respiratory difficulty. Although asymptomatic presentation remains to be predominant, respiratory, digestive, neurological and cutaneous involvement is noted in varying degrees. Smoking and other individual conditions are related to the evolution of the disease. Laboratory tests describe leukopenia, above all, in serious ways. Elevation of procalcitonin and C-reactive protein suggest bacterial overinfection, justifying the prescription of antibiotics. Chest X-ray is usually normal, but it may reveal patchy infiltrates in patients with parenchymal involvement. The evolution is favorable and the mortality is low. Conclusions: COVID-19 in children has a heterogeneous presentation. It is usually asymptomatic, although it may affect systems and organs. It evolves towards recovering in 3-4 weeks(AU)

Overview of toxic cyanobacteria and cyanotoxins in Ibero-American freshwaters: Challenges for risk management and opportunities for removal by advanced technologies.

The increasing occurrence of cyanobacterial blooms worldwide represents an important threat for both the environment and public health. In this context, the development of risk analysis and management tools as well as sustainable and cost-effective treatment processes is essential. The research project TALGENTOX, funded by the Ibero-American Science and Technology Program for Development (CYTED-2019), aims to address this ambitious challenge in countries with different environmental and social conditions within the Ibero-American context. It is based on a multidisciplinary approach that combines ecology, water management and technology fields, and includes research groups from Chile, Colombia, Mexico, Peru and Spain. In this review, the occurrence of toxic cyanobacteria and cyanotoxins in freshwaters from these countries are summarized. The presence of cyanotoxins has been confirmed in all countries but the information is still scarce and further monitoring is required. In this regard, remote sensing or metagenomics are good alternatives at reasonable cost. The risk management of freshwaters from those countries considering the most frequent uses (consumption and recreation) has been also evaluated. Only Spain and Peru include cyanotoxins in its drinking water legislation (only MC-LR) and thus, there is a need for regulatory improvements. The development of preventive strategies like diminishing nutrient loads to aquatic systems is also required. In the same line, corrective measures are urgently needed especially in drinking waters. Advanced Oxidation Processes (AOPs) have the potential to play a major role in this scenario as they are effective for the elimination of most cyanotoxins classes. The research on the field of AOPs is herein summarized considering the cost-effectiveness, environmental character and technical applicability of such technologies. Fenton-based processes and photocatalysis using solar irradiation or LED light represent very promising alternatives given their high cost-efficiency. Further research should focus on developing stable long-term operation systems, addressing their scale-up.

Factores de riesgo asociados a la anemia ferropénica en niños menores de dos años / Risk factors associated to iron-deficiency anemia in children younger than two years old

Introducción: La anemia ferropénica es un problema que tiene consecuencias de gran alcance para lasalud humana, el desarrollo social y económico de los países. En la actualidad se relacionacon la desnutrición y la enfermedad, suele utilizarse como indicador para estimar la calidadde los programas sociosanitarios de las naciones.Objetivo: Identificar factores de riesgo para el desarrollo de anemia ferropénica en niños menores dedos años de edad.Método: Se realizó estudio descriptivo, transversal y retrospectivo el Policlínico Comunitario DocenteLidia y Clodomira, del municipio de Regla, provincia La Habana, desde diciembre de 2018hasta febrero de 2019. Las variables estudiadas fueron: los antecedentes prenatales (anemiamaterna) y posnatales (edad, sexo, tiempo gestacional; peso al nacer, tipo de lactanciadurante el primer semestre de vida; estado nutricional, morbilidades asociadas; uso dehierro profiláctico e intensidad de la anemia). Los datos obtenidos se depositaron en unaplanilla confeccionada al efecto, se trabajaron en Excel.Resultados: Predominó el grupo de niños entre 6 y 9 meses (49.5 por ciento), el sexo masculino (56.4 por ciento), los hijosde madres con anemia anteparto (67.3 por ciento), sin lactancia materna exclusiva en primersemestre (71.3 por ciento) y sin suplementación (68.3 por ciento). Al relacionar la anemia ferropénica con elestado nutricional, existió predominio en niños normopeso (42.6 por ciento); sobresalió la anemialigera (71.3 por ciento).Conclusiones: La presencia de anemia en niños está vinculada con factores de riesgo maternos y propiosdel infante que deben ser tratados en la puericultura, con actividades de promoción y prevención de salud.(AU)

Introduction: Anemia, iron-deficiency is a generalized problem that has great reaching consequences forhuman health, and for the social and economic development of the countries. Nowadays itis closely related to malnourishment and diseases; and it can be used as an indicator toestimate the quality of the socio-sanitary programs of the nations.Objective: To identify risk factors for the development of iron-deficiency anemia in children youngerthan 2 years old.Method: A descriptive cross sectional, and retrospective study was carried out in children youngerthan two years old diagnosed with iron-deficiency anemia, from Lidia y ClodomiraTeaching Community Policlinic in Regla, La Habana province; from December, 2018 toFebruary, 2019. The variables under study were: prenatal history (maternal anemia), andpostnatal (age, sex, gestational time and birth weight, type of milk feeding during the firstsemester of life, nutritional estate, associate morbidities, use of prophylactic iron andintensity of the anemia). The obtained data were collocated in a form made for it and theywere worked in Excel.Results. The 6 to 9 months age group prevailed (49.5 per cent), the male sex (56.4 per cent), children withmothers who suffered from anemia before delivery, without exclusive breast feeding in theirfirst semester and without supplementation; this mostly caused slight anemia.Conclusions. The presence of anemia in children is linked to maternal risk factors and to the infantsthemselves that should be treated in pediatric consultations with promotion and prevention health activities.(AU)

Phytochemical Analysis and Antioxidant and Anti-Inflammatory Capacity of the Extracts of Fruits of the Sechium Hybrid.

In addition to their own antioxidants, human cells feed on external antioxidants, such as the phenolic compounds of fruits and vegetables, which work together to keep oxidative stress in check. Sechium edule, an edible species of chayote, has phenolic compounds with antioxidant activity and antineoplastic activity. A Sechium hybrid shows one thousand times greater antineoplastic activity than edible species, but its antioxidant and anti-inflammatory activities and the content of phenolic compounds are unknown. The aim of this study was to determine the antioxidant and anti-inflammatory capacity of the extract of fruits of the Sechium hybrid in vitro and in vivo. Phytochemical analysis using HPLC showed that the extract of the Sechium hybrid has at least 16 phenolic compounds; galangin, naringenin, phloretin and chlorogenic acid are the most abundant. In an in vitro assay, this extract inhibited 2,2-diphenyl-L-picrylhydrazyl (DPPH) activity and protected the dimyristoylphosphatidylethanolamine (DMPE) phospholipid model cell membrane from oxidation mediated by hypochlorous acid (HClO). In vivo, it was identified that the most abundant metabolites in the extract enter the bloodstream of the treated mice. On the other hand, the extract reduces the levels of tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and interleukin-6 (IL-6) but increases interleukin-10 (IL-10) and glutathione peroxidase levels. Our findings indicate that intake of the fruits of the Sechium hybrid leads to antioxidant and anti-inflammatory effects in a mouse model. Therefore, these results support the possibility of exploring the clinical effect of this hybrid in humans.

Exposure of human fallopian tube epithelium to elevated testosterone results in alteration of cilia gene expression and beating.

STUDY QUESTION: How does exposure to a testosterone rich environment affect the function and gene expression of human fallopian tube epithelium (hFTE)? SUMMARY ANSWER: Elevated testosterone level alters several gene transcripts that regulate cilia expression and negatively impacts the rate of cilia beating. WHAT IS KNOWN ALREADY: The presence of estrogen in the follicular phase of the menstrual cycle increases the human fallopian tube ciliary beating frequency. The luteal phase, triggered by ovulation and increasing progesterone, is marked by a decrease in ciliary beating. Women with polycystic ovarian syndrome (PCOS) may have twice the serum level of testosterone than ovulatory women. To date, the effect of elevated androgens on the function of the human fallopian tube is not well-understood. We chose to examine the impact of elevated testosterone on hFTE. STUDY DESIGN, SIZE, DURATION: A prospective basic science study of human fallopian tube specimens from reproductive-aged women undergoing benign gynecologic surgery was performed. Fallopian tube removal at a large US academic center was collected and provided to us to continue with epithelium isolation and culturing. A total of 12 patients were analyzed in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fallopian tube epithelium was isolated and exposed to two different conditions: normal with low testosterone concentration of 0.8 nM and PCOS-like, with high testosterone concentration of 2 nM. The study was conducted in both static and dynamic conditions in microfluidic devices for a total of 14 days, after which the tissue was collected for processing including RNA extraction, quantitative PCR and immunohistochemistry. After the first 7 days of each experiment, a sample of tissue from each condition was imaged to quantify cilia beating frequency. MAIN RESULTS AND THE ROLE OF CHANCE: hFTE exposed to the 2 nM testosterone displayed slower cilia beating, inhibited estrogen signaling and decreased expression of the ciliary marker FOXJ1 when compared to stimulation with 0.8 nM testosterone. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The in vivo response to elevated testosterone may differ from in vitro studies. RNA amount was limited from tissue cultured in the microfluidic devices as compared to static culture. WIDER IMPLICATIONS OF THE FINDINGS: Understanding elevated testosterone in tubal function may explain an additional contribution to subfertility in women with PCOS and other hyper-androgen disorders, aside from oligo-ovulation. Furthermore, this adds to the body of literature of fallopian tube function using a microfluidic device. STUDY FUNDING/COMPETING INTEREST(S): NIH grants: UH3 ES029073 and R01 CA240301. There are no competing interests.

Toxic effects of the anticancer drug epirubicin in vitro assayed in human erythrocytes.

Epirubicin is a cytotoxic drug used in the treatment of different types of cancer and increasing evidence suggests that its target is cell membranes. In order to gain insight on its toxic effects, intact red blood cells (RBC), human erythrocyte membranes and molecular models were used. The latter consisted in bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipid classes found mainly in the outer and inner monolayers of the human erythrocyte membrane, respectively. The results obtained by X-ray diffraction displayed that epirubicin induced structural perturbations in multilayers of DMPC. Differential scanning calorimetry (DSC) showed that epirubicin disturbed the thermotropic behavior of both DMPC and DMPE vesicles, whereas fluorescence spectroscopy demonstrated alterations in the fluidity of DMPC vesicles and the erythrocyte membrane. Scanning electron microscopy (SEM) revealed that epirubicin changed the normal discoid form of RBC to echinocytes and stomatocytes. Electron paramagnetic resonance (EPR) disclosed that this drug induced conformational changes in the erythrocyte membrane proteins. These findings demonstrate that epirubicin interacts with lipids and proteins of the human erythrocyte membrane, effects that might compromise the integrity and function of cell membranes. This is the first time that its toxic effects on the human erythrocyte membrane have been described.

Enfrentamiento a la COVID-19. Reflexiones tras 90 días de experiencia en el Hospital Pediátrico San Miguel del Padrón / COVID-19 confrontation:reflections after 90 days of experience in San Miguel del Padrón Pediatric Hospital

En la actualidad, su editorial dedica espacio a los trabajos sobre infección por SARS-CoV-2. Recientemente se publicó del profesor Humberto Guanche, el artículo "COVID-19. La necesidad de nuevos paradigmas de cooperación y riesgo de los trabajadores de la salud"1 texto que recoge medidas a cumplir para evitar la propagación del virus en centros de atención a personas sospechosas o confirmadas de la COVID-19; pero siguen siendo escasos los trabajos que reportan el alcance de su cumplimiento. El Hospital Pediátrico San Miguel del Padrón, desde el pasado 22 de abril, por indicaciones de la dirección del país, comenzó a recibir casos pediátricos sospechosos y confirmados de la COVID-19 de la capital. Esta alta responsabilidad fue asumida por la dirección administrativa y los trabajadores con altruismo y responsabilidad.....

Reduced PAX2 expression in murine fallopian tube cells enhances estrogen receptor signaling.

High-grade serous ovarian cancer (HGSOC) is thought to progress from a series of precursor lesions in the fallopian tube epithelium (FTE). One of the preneoplastic lesions found in the FTE is called a secretory cell outgrowth (SCOUT), which is partially defined by a loss of paired box 2 (PAX2). In the present study, we developed PAX2-deficient murine cell lines in order to model a SCOUT and to explore the role of PAX2 loss in the etiology of HGSOC. Loss of PAX2 alone in the murine oviductal epithelium (MOE) did not induce changes in proliferation, migration and survival in hypoxia or contribute to resistance to first line therapies, such as cisplatin or paclitaxel. RNA sequencing of MOE PAX2shRNA cells revealed significant alterations in the transcriptome. Silencing of PAX2 in MOE cells produced a messenger RNA expression pattern that recapitulated several aspects of the transcriptome of previously characterized human SCOUTs. RNA-seq analysis and subsequent qPCR validation of this SCOUT model revealed an enrichment of genes involved in estrogen signaling and an increase in expression of estrogen receptor α. MOE PAX2shRNA cells had higher estrogen signaling activity and higher expression of putative estrogen responsive genes both in the presence and absence of exogenous estrogen. In summary, loss of PAX2 in MOE cells is sufficient to transcriptionally recapitulate a human SCOUT, and this model revealed an enrichment of estrogen signaling as a possible route for tumor progression of precursor lesions in the fallopian tube.

Aspectos clínico-epidemiológicos en 36 niños cubanos con COVID-19

Introducción: La COVID-19 es una enfermedad infecciosa de alta transmisibilidad. Objetivo: Caracterizar la casuística pediátrica que posibilite disponer de conocimientos para el enfrentamiento a la pandemia en Cuba. Métodos: Estudio descriptivo, observacional y transversal en pacientes con COVID-19, ingresados en el Hospital Pediátrico San Miguel del Padrón: abril-junio de 2020. Se analizó: edad, sexo, estado nutricional, enfermedad previa, área de residencia, sintomatología al ingreso, resultados de complementarios, y condición al egreso. Resultados: Se identificaron 36 niños con COVID-19. La proporción según sexo no mostró diferencias. Hubo predominio del grupo de edad entre 10-14 años, piel mestiza y presentación asintomática en 72,2 %. Las comorbilidades más observadas fueron el asma bronquial leve y la anemia ligera. Prevalecieron los residentes del Este de la capital, sobre todo, en la semana estadística 21 y 25. En el grupo de enfermos sintomáticos predominaron las manifestaciones respiratorias y la fiebre. Los complementarios revelaron linfocitosis (63,9 %), anemia (13,9 %) e infiltrados pulmonares (8,3 %). El 100 % de los pacientes tuvo evolución favorable y PCR negativo tras concluir tratamiento. Conclusiones: La COVID-19 tuvo mayor incidencia en niños de 10 años o más. No hubo variaciones en cuanto al sexo. Predominó el color de piel mestizo. Los pacientes tuvieron espectro clínico variable, y evolución de PCR condicionada por la presencia de factores de riesgo individual y social. La recuperación clínica y la regresión de alteraciones hematológicas y radiológicas se logró en todos los pacientes entre 2-3 semanas.

Introduction: COVID-19 is an infectious disease with high transmissibility. Objective: To characterize the pediatrics casuistry that allows having the relevant knowledge to fight COVID-19 pandemic in Cuba. Methods: Descriptive, observational and cross-sectional study in patients with COVID-19 admitted in San Miguel del Padrón municipality's Pediatric Hospital from April to June, 2020. There were analyzed as variables: age, sex, nutritional state, previous diseases, living area, sintomatology in the moment of admission, results of complementary tests, and state in the moment of discharge. Results: 36 children were identified with COVID-19. Proportion according to sex had no differences. There was a predominance of the group age among 10 to 14 years, mixed race patients and the asymptomatic forms in 72,2% of them. The most frequent comorbidities were slight bronchial asthma and slight anemia. There was predominance of patients living in the Eastern area of the capital, mainly in the statistic weeks #21 and #25. In the group of symptomatic patients prevailed the respiratory manifestations and the fever. The complementary tests showed lymphocytes (63,9%), anemia (13,9) and pulmonary infiltrates (8,3%). 100% of the patients had favorable evolution and negative PCR after finishing the treatment. Conclusions: COVID-19 had a higher incidence in 10 or more year's children. There were not variations regarding sex. Mixed race patients predominated. Patients had a variable clinical spectrum, and an evolution of the PCR conditioned by the presence of individual and social risk factors. Clinical recovery and regression of hematologic and radiologic alterations was achieved in all the patients among 2 to 3 weeks.

In vitro effects of the antitumor drug miltefosine on human erythrocytes and molecular models of its membrane.

This study was aimed at elucidating the molecular mechanisms of the interaction of the antitumor alkylphospholipid drug miltefosine with human erythrocytes (RBC) and molecular models of its membrane. The latter consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. X-ray results showed that the drug interacted with DMPC multilayers; however, no effects on DMPE were detected. The experimental findings obtained by differential scanning calorimetry (DSC) indicated that miltefosine altered the thermotropic behavior of both DMPC and DMPE vesicles. Fluorescence spectroscopy evidenced an increase in the fluidity of DMPC vesicles and human erythrocyte membranes. Scanning electron microscopy (SEM) observations on human erythrocytes showed that miltefosine induced morphological alterations to RBC from its normal biconcave to an echinocyte type of shape. These results confirm that miltefosine interacts with the outer moiety of the human erythrocyte membrane affecting the cell morphology.