Liposarcomas paratesticulares simultáneos con diferencias histopatológicas. Reporte de un caso

El liposarcoma es un tumor de origen mesenquimal que se presenta comúnmente en el retroperitoneo; es de crecimiento lento y su capacidad de producir metástasis depende de su tipo histológico. Este trabajo tiene como propósito presentar un caso de liposarcomas paratesticulares simultáneos con diferentes tipos histológicos, en un paciente masculino, de 80 años con antecedentes de salud y nivel socioeconómico bajo que venía presentando desde hacía dos años aumento de volumen en la región inguinal izquierda y testículo ipsilateral, al inicio fue indoloro; luego, a medida que aumentó de tamaño se tornó doloroso, abarcando la región inguinoescrotal derecha en su totalidad. El examen físico, incluido el signo de la transiluminación fue negativo. El estudio analítico mostró solamente velocidad de sedimentación globular en 95 mm/h y la LDH en 650 U/l; la ecografía testicular mostró una masa heterogénea, solida e hiperecoica, de aspecto graso inguinoescrotal y de más de 30 cm, sin llegarse a observar el testículo. Se realizó exéresis tumoral encontrándose tres tumores liposarcomatosos, dos de ellos con características histopatológicas similares y el otro con patrón histológico diferente. Luego del tratamiento quirúrgico el paciente se recuperó satisfactoriamente y no ha presentado recidiva según los controles periódicos realizados. Se consideró la publicación del caso pues los liposarcomas pueden llegar a confundirse a la exploración clínica con la presencia de una hernia inguinal de contenido graso con sintomatología similar a estas; por lo que debe hacerse una exploración clínica exhaustiva para realizar un correcto diagnóstico. El estudio histopatológico confirmó el diagnóstico de la enfermedad que, además, reveló la presencia de tres tumores liposarcomatosos y dos variantes histopatológicas del mismo, de lo cual no se encontraron reportes en la literatura revisada.

Liposarcoma is a mesenchymal origin tumor that commonly occurs in the retroperitoneum; It is slow growing and its ability to produce metastasis depends on its histological type. The purpose of this work is to present a case of simultaneous paratesticular liposarcomas with different histological types, in an 80-years-old male patient with a health history and low socioeconomic level; For two years he had been experiencing an increase in volume in the left inguinal region and ipsilateral testicle, which at first was painless; Then, as it increased in size, it became painful, covering the entire right inguinoscrotal region. Physical examination, including transillumination sign, was negative. The analytical study only showed erythrocyte sedimentation rate at 95 mm/h and LDH at 650 U/l; The testicular ultrasound showed heterogeneous, solid and hyperechoic mass, with a fatty inguinoscrotal appearance and measuring more tan 30 cm, without the testicle being observed. Tumor excision was performed and three liposarcomatous tumors were found, two of them with similar histopathological characteristics and the other with a different histological pattern. After the surgical treatment, the patient recovered satisfactorily and has not had a recurrence according to the periodic controls carried out. The publication of the case was considered because liposarcomas can be confused on clinical examination with the presence of an inguinal hernia with fatty content with symptoms similar to these; Therefore, a thorough clinical examination must be performed to make a correct diagnosis. The histopathological study confirmed the diagnosis of the disease; which, in addition, revealed the presence of three liposarcomatous tumors and two histopathological variants of the same, from which no reports were found in the reviewed literature.

Synthesis of Quinoline and Dihydroquinoline Embelin Derivatives as Cardioprotective Agents.

A set of new dihydroquinoline embelin derivatives was obtained from the reaction of the natural benzoquinone embelin (1) with anilines and aromatic aldehydes in the presence of AgOTf. The synthesis of these compounds involves the formation of a Knoevenagel adduct, followed by nucleophilic addition of aniline and subsequent electrocyclic ring closure. The scope of the reaction regarding the aldehydes and anilines was determined. Quinoline derivatives were also obtained from the corresponding dihydroquinolines under oxidation with DDQ. The cardioprotective activity of the synthesized compounds was screened using a doxorubicin-induced cardiotoxicity model in H9c2 cardiomyocytes. Some structure-activity relationships were outlined, and the best activities were achieved with quinoline-embelin derivatives having a 4-nitrophenyl group attached at the pyridine ring. The obtained results indicated that embelin derivatives 4i, 6a, 6d, 6k, and 6m could have potential as cardioprotective agents, as they attenuated a DOX-induced cardiotoxicity effect acting on oxidative stress and apoptosis.

Mesenquimoma pélvico maligno. Informe de caso

Se presentó un enfermo de 73 años en el Hospital Clínico Quirúrgico Docente "Amalia Simoni" de la ciudad de Camagüey, Cuba, que fue intervenido quirúrgicamente hace cinco años y cuyo resultado fue desconocido. En aquel entonces presentó dolor y limitación funcional del miembro inferior derecho, lo que motivó la resección de un tumor en el fémur ipsilateral; cinco años después recidiva, esta vez con invasión de la pelvis ósea y del recto, evidenciándose trastornos miccionales y constipación. La radiografía de pelvis ósea, tomografía computarizada y resonancia magnética de dicha región evidenciaron una imagen tumoral mixta con lesiones líticas que invadió y desplazó los órganos de la cavidad pélvica. El paciente fue sometido a exéresis del tumor, el cual fue de 173×156 mm, con un peso de aproximadamente 1 380 g. El análisis histopatológico de la pieza quirúrgica evidenció un mesenquimoma pélvico maligno.

It was reported a case of a 73 years old patient with a history of an unknown outcomes surgical procedure 5 years ago at the Hospital Clínico Quirúrgico Docente "Amalia Simoni" in Camaguey, Cuba. He presented pain and functional limitation of the right lower limb, which led to the resection of a tumor in the ipsilateral femur; five years later the tumor present signs of recurrence, this time with invasion of the bony pelvis and rectum and resulting in urinary disorders and constipation. Pelvis bone radiology, computed tomography scan and magnetic resonance imaging of the pelvis showed a mixed tumor with lytic lesions that invaded and displaced the organs in the pelvic cavity. The patient underwent excision of the tumor, which was 173×156 mm, weighing approximately 1.380 g. Histopathological analysis of the surgical resection specimen revealed a pelvic malignant mesenchymoma.

Apresentou-se um paciente de 73 anos, operado há 5 anos no Hospital Provincial Amalia Simoni, na cidade de Camagüey, Cuba, cujo resultado era desconhecido. Na época, apresentava dor e limitação funcional do membro inferior direito, o que levou à ressecção de tumoração no fêmur ipsilateral; cinco anos depois, recidiva, desta vez com invasão de pelve óssea e reto, evidenciando distúrbios miccionais e constipação. A radiografia óssea da pelve, a tomografia computadorizada e a ressonância magnética da referida região revelaram uma imagem tumoral mista com lesões líticas que invadiam e deslocavam os órgãos da cavidade pélvica. A paciente foi submetida à exérese do tumor, que media 173×156 mm, com peso aproximado de 1380 g. A análise histopatológica da peça cirúrgica revelou um mesenquimoma pélvico maligno.

Competencias en salud ambiental y cambio climático en estudiantes universitarios / Competences in environmental health and climate change in university students

El deterioro del medio ambiente ha acelerado el cambio climático (CC) afectando mútiples escenarios, el aumento de la temperatura ha conllevado a la proliferación de diversas enfermedades trasmitidas por vectores de importancia a nivel de salud pública. Como objetivo, se propuso determinar la cultura ecosaludable ante el cambio climático en estudiantes del Área Ciencias de la Educación, Universidad Nacional Experimental Rómulo Gallegos (UNERG), Calabozo, Venezuela 2022. El estudio fue cuantitativo exploratorio no experimental de corte transversal con una muestra de 180 estudiantes. Para la recolección de datos se aplicó el Cuestionario de Dimensiones Ambientales (CDA) compuesto de 75 ítems distribuidos en tres dimensiones; conocimientos, actitudes, emociones y comportamientos. El análisis de los datos fue por estadística descriptiva con porcentajes a través del programa Epidat 3.0. Como resultado, 63% indicó la importancia atribuida de los elementos de ecosalud afectados sobre el agua y 55% al calentamiento global. No obstante, solo 12% indicó la educación como un elemento de ecosalud afectado por el cambio climático, así mismo, en la dimensión de conocimientos se encontró 54,50% a CSN, 6,50% a CPR y 39,50% a CEA, en la dimensión de actitudes y emociones se encontró 55,50% a la subcategoria TD, 44,00% a CVA y 36,50% a E, finalmente, en la dimensión de comportamiento, se evidenció 36,50% a la subategoria de PC, 29,00% a IC y 20,00% a PI. Se debe evitar el daño ambiental a través del cambio de comportamiento individual que debe ser enseñado desde los recintos universitarios(AU)

The deterioration of the environment has accelerated climate change (CC) affecting multiple scenarios, the increase in temperature has led to the proliferation of various diseases transmitted by vectors of importance at the public health level. As an objective, it was proposed to determine the eco-healthy culture in the face of climate change in students of the Educational Sciences Area, Rómulo Gallegos National Experimental University (UNERG), Calabozo, Venezuela 2022. The study was quantitative, exploratory, non-experimental, cross-sectional with a sample of 180 students. For data collection, the Environmental Dimensions Questionnaire (CDA) was applied, consisting of 75 items distributed in three dimensions; knowledge, attitudes and emotions and behaviors. Data analysis was by descriptive statistics with percentages through the Epidat 3.0 program. As a result, 63% indicated the importance attributed to the affected ecohealth elements on water and 55% on global warming. However, only 12% indicated education as an element of ecohealth affected by climate change, likewise, in the knowledge dimension, 54.50% were found to CSN, 6.50% to CPR and 39.50% to CEA, in the dimension of attitudes and emotions, 55.50% were found in the TD subcategory, 44.00% in CVA and 36.50% in E, finally, in the behavior dimension, 36.50% were found in the subcategory of PC, 29.00% to IC and 20.00% to PI. Environmental damage must be avoided through individual behavior change that must be taught from university campuses(AU)

Test para evaluar la rapidez específica en porteras de balonmano de la preselección nacional cubana / Teste para avaliar a velocidade específica dos goleiros nacionais cubanos de pré-seleção de handebol / Test to evaluate the specific speed in female handball goalkeepers of the Cuban national preselection

RESUMEN Introducción: El portero de balonmano debe poseer una excelente condición física para superar las múltiples exigencias actuales del juego. En el juego ofensivo, se constata un aumento en la velocidad de las acciones, fuerza y la resistencia de los jugadores y un elevado bagaje técnico-táctico, entre otros, por lo que los porteros necesitan destacar la rapidez específica en su posición en los que se encuentran los desplazamientos defensivos ante los lanzamientos a portería. Objetivo: El estudio que se presenta tuvo por objetivo diseñar un test para la evaluación y control de la rapidez específica de las porteras de la preselección nacional cubana de balonmano. En la investigación, participaron las tres porteras de la selección nacional cubana de balonmano que se preparaban para el ciclo olímpico 2012-2016, y que posteriormente asistieron al Campeonato Panamericano La Habana, 2015. Materiales y métodos: Se utilizaron métodos teóricos y empíricos como el sistémico estructural funcional, la observación directa y la medición. Resultados: Se presentaron los resultados de los análisis llevados a cabo en el estudio. De acuerdo con las observaciones realizadas a los entrenamientos de la preparación, se constató que no se contaba con un instrumento para evaluar y controlar la rapidez específica de la posición de las porteras, se incluían en el control y evaluación de las jugadoras de campo; por lo que no se tenía una valoración del estado de esta capacidad esencial en esta posición en el balonmano. Conclusiones: Tras la aplicación del test y la valoración de los especialistas y los miembros de la comisión nacional de balonmano, se incorporó el Test en el Programa de Preparación Integral del Deportista de la disciplina por los resultados alcanzados de manera ascendente por las porteras durante la preparación y la competencia.

SÍNTESE Introdução: O goleiro de handebol deve possuir uma excelente condição física para superar as múltiplas exigências atuais do jogo. No jogo ofensivo, há um aumento na velocidade das ações, força e resistência dos jogadores e um alto background técnico-táctico, entre outros, portanto os goleiros precisam destacar a velocidade específica em sua posição na qual os deslocamentos defensivos antes dos chutes a gol são encontrados. Objetivo: O objetivo deste estudo foi elaborar um teste para a avaliação e controle da velocidade específica dos goleiros da equipe nacional cubana de pré-seleção de handebol. A pesquisa envolveu os três goleiros da seleção nacional cubana de handebol que se preparavam para o ciclo olímpico 2012-2016, e que posteriormente participaram do Campeonato Pan-Americano de 2015 em Havana. Materiais e métodos: Foram utilizados métodos teóricos e empíricos, tais como sistêmico estrutural funcional, observação direta e medição. Resultados: Foram apresentados os resultados das análises realizadas no estudo. De acordo com as observações feitas nas sessões de treinamento da preparação, verificou-se que não havia nenhum instrumento para avaliar e controlar a velocidade específica da posição dos goleiros, eles foram incluídos no controle e avaliação dos jogadores de campo; portanto, não houve avaliação do estado desta capacidade essencial nesta posição no handebol. Conclusões: Após a aplicação do teste e a avaliação dos especialistas e dos membros da comissão nacional de handebol, o teste foi incorporado ao Programa de Preparação Integral do Desportista da disciplina devido aos resultados alcançados de forma ascendente pelos goleiros durante a preparação e a competição.

ABSTRACT Introduction: The handball goalkeeper must have an excellent physical condition to overcome the multiple current demands of the game. In the offensive game, there is an increase in the speed of the actions, strength and endurance of the players and a high technical-tactical background, among others, so the goalkeepers need to highlight the specific speed in their position in which are the defensive movements before the shots on goal. Objective: The present study aimed to design a test for the evaluation and control of the specific speed of the goalkeepers of the Cuban national handball team. The three goalkeepers of the Cuban national handball team who were preparing for the 2012-2016 Olympic cycle, and who later attended the Pan American Championship in Havana, 2015, participated in the research. Materials and methods: Theoretical and empirical methods were used, such as functional structural systemic, direct observation and measurement. Results: The results of the analyses carried out in the study were presented. According to the observations made during the training sessions, it was found that there was no instrument to evaluate and control the specific speed of the goalkeepers' position, they were included in the control and evaluation of the field players; therefore, there was no assessment of the state of this essential capacity in this position in handball. Conclusions: After the application of the test and the evaluation of the specialists and the members of the national handball commission, the Test was incorporated into the Comprehensive Preparation Program for the Athlete of the discipline due to the results achieved in an ascending manner by the goalkeepers during the preparation and competition.

A Qualitative Exploration of Maternal Anxiety: Implications for Helping Professionals.

OBJECTIVES: To gain insight into the nature of maternal anxiety among mothers from diverse cultures through exploring the components of maternal anxiety and ways mothers cope with it in order to assist helping professionals in providing psychoeducation and counseling to mothers who experience intense anxiety regarding their children. METHODS: In this qualitative study, 17 mothers participated in cognitive interviews conducted as a part of the maternal anxiety scale development. Data from semi-structured interviews was explored using thematic analysis. RESULTS: Four themes related to mothers' experiences of anxiety emerged from the data: (1) maternal insecurities and social comparison, (2) coping with anxiety, (3) dependence versus autonomy, (4) cultural considerations. CONCLUSIONS FOR PRACTICE: The results of this study can be used by helping professionals working with mothers by implementing emotion regulation skills for maternal anxiety that are described in the implications section of the paper.

Prevalence of Chronic Infection by Hepatitis C Virus in Asymptomatic Population With Risk Factors in Cartagena, Colombia.

Introduction: Infection by the hepatitis C virus (HCV) is an important cause of chronic liver disease, considered a public health problem worldwide with high morbidity and mortality due to limited access to diagnostic tests in developing countries. Only a small percentage know their infection status and receive timely treatment. It is critical to make diagnostic tests for HCV infection accessible and to provide timely treatment, which not only reduces the spread of infection but also stops the progression of HCV disease without symptoms. Objective: To determine the prevalence of chronic infection by HCV in patients with risk factors by using rapid tests in Cartagena, Colombia, and describe their epidemiological characteristics. Methodology: A cross-sectional descriptive observational study was carried out on asymptomatic adults with risk factors for HCV infection in the city of Cartagena between December 2017 and November 2019. A rapid immunochromatographic test was performed to detect antibodies, characterizing the population. Results: In total, 1,023 patients were identified who met the inclusion criteria, 58.5% women and 41.4% men, obtaining nine positive results, confirming chronic infection with viral load for HCV, finding seven cases of genotype 1b and two genotype 1a. Conclusion: In our study, a prevalence of hepatitis C infection of 0.9% was found in asymptomatic individuals with risk factors, which allows us to deduce that the active search for cases in risk groups constitutes a pillar for the identification of the disease, the initiation of antiviral therapy, and decreased morbidity and mortality.

A clickable photoaffinity probe of betulinic acid identifies tropomyosin as a target.

Target identification of bioactive compounds is important for understanding their mechanisms of action and provides critical insights into their therapeutic utility. While it remains a challenge, unbiased chemoproteomics strategy using clickable photoaffinity probes is a useful and validated approach for target identification. One major limitation of this approach is the efficient synthesis of appropriately substituted clickable photoaffinity probes. Herein, we describe an efficient and consistent method to prepare such probes. We further employed this method to prepare a highly stereo-congested probe based on naturally occurring triterpenoid betulinic acid. With this photoaffinity probe, we identified tropomyosin as a novel target for betulinic acid that can account for the unique biological phenotype on cellular cytoskeleton induced by betulinic acid.

Prediction of ACE-I Inhibitory Peptides Derived from Chickpea (Cicer arietinum L.): In Silico Assessments Using Simulated Enzymatic Hydrolysis, Molecular Docking and ADMET Evaluation.

Chickpea (Cicer arietinum L.) peptides have shown in vitro potential to inhibit the angiotensin I-converting enzyme (ACE-I). However, the potential molecular interactions between chickpea peptides (CP) and ACE-I as well as their ADMET (absorption/distribution/metabolism/excretion/toxicity) characteristics remain unknown. Thus, our aim was to study the in silico interactions of CP with ACE-I and the CP ADMET characteristics. Legumin and provicilin sequences were submitted to in silico analysis to search for ACE-I inhibitory peptides. Simulated enzymatic hydrolysis was performed using the BIOPEP-UWM database, and the ACE-I inhibitory peptides generated (EC50 ≤ 200 µM) were selected to perform molecular docking and ADMET analysis. After hydrolysis, 59 out of 381 peptides with ACE-I inhibitory potential were released. Based on A and B parameters, the legumin peptides showed better ACE-I inhibitory potential than the provicilin ones. CP mainly interact with residues from pocket S1 (Ala354/Glu384) and S2 (His353/His513) through hydrogen bonds (distances < 3.0 Å) and hydrophobic interactions (binding energy from −5.7 to −9.2 kcal/mol). Through ADMET analysis, CP showed optimal values for inhibiting ACE-I in vivo. ACE-I inhibitory peptides from legumin and provicilin can bind strongly and tightly to the active site of ACE-I. Further studies to evaluate in vivo the antihypertensive effects of CP are warranted.

Insuficiencia renal en cirrosis: revisión de la literatura

Contexto: en el curso de la enfermedad del paciente cirrótico, la insuficiencia renal es un evento de mal pronóstico. Objetivo: identificar en estos pacientes los factores de riesgo de IRA, tales como: presencia de procesos infecciosos, hipovolemia inducida por hemorragia, pérdidas gastrointestinales o renales y agentes nefrotóxicos, ya que conocer de su aparición es primordial para dar comienzo a las medidas terapéuticas y las acciones profilácticas. Metodología: se realizó una búsqueda bibliográfica en las bases de datos PubMed, EMBASE, Scopus y Google académico, usando los términos MeSH como insuficiencia renal aguda, creatinina, cirrosis hepática, síndrome hepatorenal. Se obtuvieron resultados entre artículos originales, metaanálisis, reportes de casos, series de casos y revisiones de la literatura, y se escogieron 16 documentos para la elaboración de esta revisión. Resultados: los nuevos criterios definidos por el Club Internacional de Ascitis (AKI-IAC), los cuales eliminan el gasto urinario, se determinan por un aumento de la creatinina sérica ≥ 0,3 mg/dL en menos de 48 horas y, mejoran el pronóstico, permitiendo realizar intervenciones oportunas. Conclusiones: la creatinina sigue siendo el biomarcador más utilizado en insuficiencia renal aguda (IRA), incluso en pacientes cirróticos, a pesar de sus múltiples limitaciones. Un criterio dinámico modificado a partir de los criterios de AKIN, se convierte en el patrón de oro para el diagnóstico de IRA en cirrosis.

Introduction: During the cirrhotic patient's disease, renal failure is a poor prognostic event. Purpose: Knowing the risk factors for AKI in these patients given by the presence of infectious processes, loss of fluids due to hemorrhage, gastrointestinal or kidney, and nephrotoxic agents are essential for initiating therapeutic measures and prophylactic actions. Methodology: A bibliographic search was carried out in the PubMed, EMBASE, Scopus and academic Google databases, using the terms MeSH acute renal failure, creatinine, liver cirrhosis, hepatorenal syndrome. Original articles, meta-analyzes, case reports, case series and literature reviews were obtained, choosing 16 documents for the preparation of this review. Results: The new criteria defined by the International Ascites Club (AKI-IAC), which eliminate urinary output, are determined by an increase in serum creatinine ≥ 0.3 mg / dL in less than 48 hours and improve the prognosis, allowing timely interventions. Conclusions: Creatinine continues to be the most widely used biomarker in AKI, even in cirrhotic patients, despite its multiple limitations. A dynamic criterion modified from the AKIN criteria becomes the gold standard for the diagnosis of AKI in cirrhosis.

Colon injury and gastrocolocutaneous fistula complication of percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) insertion is an effective endoscopic procedure for enteral feeding in patients with difficulty swallowing. Many postprocedural complications have been reported after the PEG procedure. The displacement of the transverse colon over the anterior gastric wall can predispose the patient to colonic injury and fistulae during PEG placement. Gastrocolonic fistulas represent a serious but rare complication post PEG placement. We report a 90 year old man with a background of multiple comorbidities and high preoperative risk who developed a gastrocolocutaneous fistula post PEG placement due to a colonic injury. He was successfully treated with nonoperative management.

Toxic Hepatitis Associated With the Use of Contraceptives: A Diagnosis to Bear in Mind.

Drug-induced liver injury (DILI) is a rare condition with a high burden of morbidity and risk of severe complications that may even require liver transplantation to survive. There are no pathognomonic diagnostic tests for this condition, thus being a challenge it is considered a diagnosis of exclusion. We present the case of a patient who, after starting intramuscular contraceptives, presented with acute alteration of liver function that requires the ruling out of multiple pathologies that could be the cause of the biochemical findings. With the pharmacological suspension and initiation of support measures, full recovery was achieved.

Tunable Redox Mediators for Li-O2 Batteries Based on Interhalide Complexes.

Li-O2 batteries can provide significantly higher gravimetric energy density than Li-ion batteries, but their practical use is limited by a number of fundamental issues associated with oxidizing discharge products such as Li2O2 and LiOH during charging. Soluble inorganic redox mediators (RMs) like LiI and LiBr have been shown to enhance round-trip efficiency where different solvents can greatly shift the redox potential of the RMs, significantly altering the overpotential during charging, as well as their oxidizing power against the discharge product. Unfortunately, other design requirements like (electro)chemical stability with the electrode as well as reactive discharge products greatly constrain the selection of solvent, making it impractical to additionally design the solvent to provide optimal RM performance. In this work, we demonstrate that interhalide RMs based on LiI/LiBr and LiI/LiCl mixtures can enable tuning of the oxidizing power of the RM in a given solvent. I-Br interhalides I2Br- to IBr2- showed increasing chemical oxidizing power toward Li2O2 and LiOH with increasing Br, and DEMS measurements during charging of Li-O2 cells demonstrated that these I-Br interhalide RMs led to increased O2 evolution with respect to LiI and reduced charging potential and CO2 evolution with respect to LiBr.

Modular Synthesis and Antiproliferative Activity of New Dihydro-1H-pyrazolo[1,3-b]pyridine Embelin Derivatives.

A set of new dihydro-1H-pyrazolo[1,3-b]pyridine and pyrazolo[1,3-b]pyridine embelin derivatives was synthesized through a multicomponent reaction from natural embelin, 3-substituted-5-aminopyrazoles and aldehydes. The synthesized compounds were evaluated against three hematologic tumor cell lines, HEL (acute erythroid leukemia), K-562 (chronic myeloid leukemia) and HL-60 (acute myeloid leukemia), and five breast cancer cell lines (SKBR3, MCF-7, MDA-MB-231, BT-549, HS-578T). The primate non-malignant kidney Vero cell line was used as the control of cytotoxicity. From the obtained results, some structure-activity relationships were outlined. Furthermore, in silico prediction of physicochemical properties and ADME parameters were determined for the derivatives with the best antiproliferative values.

JKST6, a novel multikinase modulator of the BCR-ABL1/STAT5 signaling pathway that potentiates direct BCR-ABL1 inhibition and overcomes imatinib resistance in chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is a hematological malignancy that highly depends on the BCR-ABL1/STAT5 signaling pathway for cell survival. First-line treatments for CML consist of tyrosine kinase inhibitors that efficiently target BCR-ABL1 activity. However, drug resistance and intolerance are still therapeutic limitations in Ph+ cells. Therefore, the development of new anti-CML drugs that exhibit alternative mechanisms to overcome these limitations is a desirable goal. In this work, the antitumoral activity of JKST6, a naphthoquinone-pyrone hybrid, was assessed in imatinib-sensitive and imatinib-resistant human CML cells. Live-cell imaging analysis revealed JKST6 potent antiproliferative activity in 2D and 3D CML cultures. JKST6 provoked cell increase in the subG1 phase along with a reduction in the G0/G1 phase and altered the expression of key proteins involved in the control of mitosis and DNA damage. Rapid increases in Annexin V staining and activation/cleavage of caspases 8, 9 and 3 were observed after JKST6 treatment in CML cells. Of interest, JKST6 inhibited BCR-ABL1/STAT5 signaling through oncokinase downregulation that was preceded by rapid polyubiquitination. In addition, JKST6 caused a transient increase in JNK and AKT phosphorylation, whereas the phosphorylation of P38-MAPK and Src was reduced. Combinatory treatment unveiled synergistic effects between imatinib and JKST6. Notably, JKST6 maintained its antitumor efficacy in BCR-ABL1-T315I-positive cells and CML cells that overexpress BCR-ABL and even restored imatinib efficacy after a short exposure time. These findings, together with the observed low toxicity of JKST6, reveal a novel multikinase modulator that might overcome the limitations of BCR-ABL1 inhibitors in CML therapy.

Influence of the degree of adherence to the mediterranean diet and its components on cardiometabolic risk during pregnancy. The GESTAFIT project.

BACKGROUND AND AIMS: Studies regarding dietary patterns and cardiometabolic risk markers during pregnancy are scarce. The aim of the present study was to analyse whether different degrees of adherence to the Mediterranean diet (MD) and the MD components were associated with cardiometabolic markers and a clustered cardiometabolic risk during pregnancy. METHODS AND RESULTS: This study comprised 119 pregnant women from the GEStation and FITness (GESTAFIT) project. Dietary habits were assessed with a food frequency questionnaire at the 16th and 34th gestational weeks (g.w.). The Mediterranean Diet Score was employed to assess MD adherence. The following cardiometabolic markers were assessed: pre-pregnancy body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, triglycerides and high-density lipoprotein cholesterol (HDL-C). A greater MD adherence was associated with a better cardiometabolic status in cross-sectional (16th g.w. and 34th g.w.) and prospective analyses (MD adherence at the 16th g.w. and cardiometabolic markers at the 34th g.w.; SBP, DBP and HDL-C; all, p < 0.05). Participants with the highest MD adherence (Tertile 3) had a lower clustered cardiometabolic risk than those with the lowest MD adherence (Tertile 1) at the 16th and 34th g.w. (both, p < 0.05). A higher intake of fruits, vegetables and fish and a lower intake of refined cereals and red meat and subproducts were associated with a lower cardiometabolic risk during pregnancy (all, p < 0.05). CONCLUSION: A higher MD adherence, a greater intake of fruits, vegetables and fish and a lower intake of refined cereals and red meat and subproducts showed a cardioprotective effect throughout gestation.

Tumor de células gigantes del fémur / Tumor of giant cells of the femur

El tumor de células gigantes de hueso es un tumor raro de características benignas con un comportamiento agresivo localmente. Predomina en mujeres y por lo general se presenta en la epífisis y metáfisis de los huesos largos. El propósito de este estudio es presentar el caso de un paciente con una lesión tumoral de rodilla y muslo izquierdos de 2 años de evolución y señalar las características diagnósticas de este tumor al mismo tiempo que se revisan los métodos imagenológicos recientes para su confirmación. Se presenta a un paciente masculino de 19 años de edad, que comenzó con dolor, aumento de volumen de la rodilla y muslo izquierdos, acompañado de impotencia funcional. Se reportaron los hallazgos clínicos, radiográficos e histológicos. Debido a la demora entre el inicio de los síntomas y el diagnóstico se practicó el tratamiento quirúrgico del miembro afectado (amputación). Tras 10 meses de observación no se han presentado recidivas o metástasis. Se envió al Servicio de Oncología para valorar e tratamiento con radioterapia. El tumor de células gigantes del hueso es un tumor raro, de buen pronóstico, pero que puede recidivar y causar metástasis cuando se maligniza. Por la posibilidad de transformación en sarcoma requiere estudio y observación periódica. El tiempo para realizar el diagnóstico es fundamental y debe pensarse en este tumor en caso de lesiones líticas de hueso reportadas por imagenología(AU)

The giant cell tumor of bone is a rare benign tumor with a locally aggressive behavior. It predominates in women and usually occurs in the epiphysis and metaphysis of long bones. To present a patient with a tumor lesion left knee and thigh two years of evolution, also noted the diagnostic characteristics of this tumor while recent imaging methods are reviewed for confirmation. 19-year-old male who began with pain, increased volume of the knee and left thigh, accompanied by functional impotensia. clinical, radiological and histological findings were reported. Because of the delay between the onset of symptoms and diagnosis surgical treatment of the affected limb (amputation) was performed. After ten months of observation there have been no recurrences or metastases. The giant cell tumor of bone is a rare tumor with good prognosis but can recur and metastasize when it becomes malignant. The possibility of transformation in sarcoma requires periodic study and observation. The time for diagnosis is essential and should think of this tumor in case of lytic bone lesions reported by imaging(AU)

PROTACs to address the challenges facing small molecule inhibitors.

Small molecule inhibitors of proteins represent important medicines and critical chemical tools to investigate the biology of the target proteins. Advances in various -omics technologies have fueled the pace of discovery of disease-relevant proteins. Translating these discoveries into human benefits requires us to develop specific chemicals to inhibit the proteins. However, traditional small molecule inhibitors binding to orthosteric or allosteric sites face significant challenges. These challenges include drug selectivity, therapy resistance as well as drugging undruggable proteins and multi-domain proteins. To address these challenges, PROteolysis TArgeting Chimera (PROTAC) has been proposed. PROTACs are heterobifunctional molecules containing a binding ligand for a protein of interest and E3 ligase-recruiting ligand that are connected through a chemical linker. Binding of a PROTAC to its target protein will bring a E3 ligase in close proximity to initiate polyubiquitination of the target protein ensuing its proteasome-mediated degradation. Unlike small molecule inhibitors, PROTACs achieve target protein degradation in its entirety in a catalytical fashion. In this review, we analyze recent advances in PROTAC design to discuss how PROTACs can address the challenges facing small molecule inhibitors to potentially deliver next-generation medicines and chemical tools with high selectivity and efficacy. We also offer our perspectives on the future promise and potential limitations facing PROTACs. Investigations to overcome these limitations of PROTACs will further help realize the promise of PROTACs for human benefits.

Colangitis esclerosante primaria / Primary sclerosing cholangitis

La colangitis esclerosante primaria (CEP) se define por la inflamación, fibrosis y estenosis de los conductos biliares intra o extrahepáticos que no pueden ser explicadas por otras causas. La prevalencia de CEP está estimada entre 0 a 16,2 por 100.000 habitantes, mientras que la incidencia está entre 0 y 1,3 casos por cada 100.000 personas por año. Las causas siguen siendo difíciles de dilucidar y en muchos casos se establece como de origen idiopático. Sin embargo, se han propuesto factores genéticos, ambientales e isquémicos asociados, además de un componente autoinmune. Existe además una fuerte asociación entre la enfermedad inflamatoria intestinal y la CEP. Los síntomas suelen ser inespecíficos, 50% de los pacientes son asintomáticos, presentando únicamente alteración en el perfil hepático de patrón colestásico, con predominio de elevación de la fosfatasa alcalina. La ictericia es un signo de mal pronóstico que con frecuencia se asocia a colangiocarcinoma. La confirmación diagnóstica se hace por colangiopancreatografía retrógrada endoscópica (CPRE) e imágenes por resonancia magnética. Aún no existe un tratamiento establecido, y en la mayoría de los casos coexiste con otras patologías. El tratamiento es multimodal con fármacos, terapia endoscópica y trasplante hepático.

Primary sclerosing cholangitis (PSC) is defined by inflammation, fibrosis, and stenosis of the intra or extrahepatic bile ducts that cannot be explained by other causes. The prevalence of PSC is estimated between 0 to 16.2 per 100,000 inhabitants, while the incidence is between 0 and 1.3 cases per 100,000 persons-year. The causes remain elusive and, in many cases, it is established as idiopathic in origin. However, genetic, environmental and ischemic factors have been proposed in addition to an autoimmune component. There is also a strong association between inflammatory bowel disease and PSC. Symptoms are usually nonspecific, 50% of the patients are asymptomatic, presenting only an alteration in the liver profile with a cholestatic pattern, and predominance of elevated alkaline phosphatase. Jaundice is a poor prognostic sign and is frequently associated with cholangiocarcinoma. Diagnostic confirmation is made by endoscopic retrograde cholangiopancreatography and magnetic resonance imaging. There is still no established treatment, and in most cases, the disease coexists with other pathologies. Treatment is multimodal with drugs, endoscopic therapy and liver transplantation.

Gastrostomía endoscópica percutánea en paciente con catéter de diálisis peritoneal. Reporte de caso / Percutaneous endoscopic gastrostomy in a patient with a peritoneal dialysis catheter. Case report

Resumen La gastrostomía endoscópica percutánea (GEP), descrita por primera vez en la década de 1980, es un procedimiento universalmente utilizado para asegurar la alimentación enteral en pacientes que conservan la función del tracto digestivo, pero que por alguna condición médica o quirúrgica no pueden ingerir alimentos sólidos o líquidos. La realización de una GEP en pacientes con diálisis peritoneal (DP) sigue siendo controvertida, ya que muchos autores la consideran una contraindicación absoluta debido al alto riesgo de morbimortalidad asociada a infección intraperitoneal. Se presenta el caso de un paciente de 70 años, con antecedente de enfermedad renal crónica en estadio terminal y portador de catéter de DP, quien requirió GEP. Se socializa la estrategia utilizada en este caso particular.

Abstract Percutaneous endoscopic gastrostomy (PEG), described in the 1980s, is a procedure universally used to ensure enteral feeding in patients who retain digestive tract function, but who cannot eat solid or liquid foods due to any medical or surgical condition. The performance of PEG in patients with peritoneal dialysis (PD) remains controversial, being considered an absolute contraindication for many authors, taking into account the high risk of morbidity and mortality associated with intraperitoneal infection. We present the case of a 70-year-old patient, with a history of chronic end-stage renal disease with a peritoneal dialysis catheter, who required PEG; and we propose a management protocol for this type of patient.