First Gallium and Indium Crystal Structures of Curcuminoid Homoleptic Complexes: All-Different Ligand Stereochemistry and Cytotoxic Potential.

The crystal structure determination of metal complexes of curcuminoids is a relevant topic to assess their unequivocal molecular structure. We report herein the first two X-ray crystal structures of homoleptic metal complexes of a curcuminoid, namely Dimethoxycurcumin (DiMeOC), with gallium and indium. Such successful achievement can be attributed to the suppression of interactions from the phenolic groups, which favor an appropriate molecular setup, rendering Dimethoxycurcumin gallium ((DiMeOC)2-Ga) and Dimethoxycurcumin indium ((DiMeOC)3-In) crystals. Surprisingly, the conformation of ligands in the crystal structures shows differences in each metal complex. Thus, the ligands in the (DiMeOC)2-Ga complex show two different conformers in the two molecules of the asymmetric unit. However, the ligands in the (DiMeOC)3-In complex exhibit three different conformations within the same molecule of the asymmetric unit, constituting the first such case described for an ML3 complex. The cytotoxic activity of the (DiMeOC)2-Ga complex is 4-fold higher than cisplatin against the K562 cell line and has comparable activity towards U251 and PC-3 cell lines. Interestingly, this complex exhibit three times lesser toxicity than cisplatin and even slightly lesser cytotoxicity than curcumin itself.

Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial.

PURPOSE: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in breast cancer; high expression is associated with an adverse prognosis. Patritumab deruxtecan (HER3-DXd) is an investigational HER3-targeted antibody-drug conjugate that is being evaluated as a novel treatment in HER3-expressing advanced breast cancer in the U31402-A-J101 study. METHODS: Adults with disease progression on previous therapies were eligible. Patients in the dose-escalation, dose-finding, and dose-expansion parts received HER3-DXd 1.6-8.0 mg/kg intravenously once every 3 weeks or one of two alternative dosing regimens. In the dose-escalation part, the primary objectives were to determine the maximum tolerated dose and recommended dose for expansion (RDE). The safety and efficacy of the RDE were assessed during dose expansion. RESULTS: One hundred eighty-two enrolled patients received ≥1 dose of HER3-DXd. Patients had a median of five previous therapies for advanced disease. Efficacy results are reported across clinical subtypes: hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer (n = 113; objective response rate [ORR], 30.1%; median progression-free survival [mPFS], 7.4 months), triple-negative breast cancer (n = 53; ORR, 22.6%; mPFS, 5.5 months), and HER2-positive breast cancer (n = 14; ORR, 42.9%; mPFS, 11.0 months). Objective responses were observed in cancers with HER3-high and HER3-low membrane expression. Dose-limiting toxicities observed during dose selection were decreased platelet count and elevated aminotransferases. In dose expansion, GI and hematologic toxicities were the most common treatment-emergent adverse events (TEAEs) observed. Grade ≥3 TEAEs were observed in 71.4% of patients, and 9.9% discontinued treatment because of TEAEs. Three grade 3 and one grade 5 treatment-related interstitial lung disease events occurred. CONCLUSION: HER3-DXd demonstrated a manageable safety profile and durable efficacy in heavily pretreated patients across clinical subtypes. These data warrant further evaluation of HER3-DXd in patients with HER3-expressing metastatic breast cancer.

Homoleptic Complexes of Heterocyclic Curcuminoids with Mg(II) and Cu(II): First Conformationally Heteroleptic Case, Crystal Structures, and Biological Properties.

We report herein the synthesis and characterization of three heterocyclic curcuminoid ligands and their homoleptic metal complexes with magnesium and copper. Thus, N-methyl-2-pyrrolecarboxaldehyde, Furan-2-carboxaldehyde, and 2-Thiophenecarboxaldehyde were condensed with 2,4-pentanedione-boron trioxide complex. The first N-methyl-2-pyrrole curcuminoid and its Mg(II) complex are reported. All curcuminoid ligands and their corresponding metal complexes were characterized by infrared spectroscopy (IR), liquid state nuclear magnetic resonance (LSNMR), electron paramagnetic resonance (EPR), mass spectrometry (MS) and single crystal X-ray diffraction (SCXRD). The ThiopheneCurc-Cu (9) constitutes the first case of a "conformationally-heteroleptic" complex. The unique six-peaks star arrangement for the ThiopheneCurc ligand derived from the supramolecular description is reported. The metal complexes of FuranCurc-Mg (5) and ThiopheneCurc-Cu (9) have a good antioxidant effect (IC50 = 11.26 ± 1.73 and 10.30 ± 0.59 µM), three and two times higher than their free ligands respectively. Additionally, (5) shows remarkable cytotoxicity against colon cancer adenocarcinoma cell line HCT-15, comparable to that of cisplatin, with a negligible toxic effect in vitro towards a healthy monkey kidney cell line (COS-7).

CdsH Contributes to the Replication of Salmonella Typhimurium inside Epithelial Cells in a Cysteine-Supplemented Medium.

Salmonella Typhimurium is a facultative, intracellular pathogen whose products range from self-limited gastroenteritis to systemic diseases. Food ingestion increases biomolecules' concentration in the intestinal lumen, including amino acids such as cysteine, which is toxic in a concentration-dependent manner. When cysteine's intracellular concentration reaches toxic levels, S. Typhimurium expresses a cysteine-inducible enzyme (CdsH), which converts cysteine into pyruvate, sulfide, and ammonia. Despite this evidence, the biological context of cdsH's role is not completely clear, especially in the infective cycle. Since inside epithelial cells both cdsH and its positive regulator, ybaO, are overexpressed, we hypothesized a possible role of cdsH in the intestinal phase of the infection. To test this hypothesis, we used an in vitro model of HT-29 cell infection, adding extra cysteine to the culture medium during the infective process. We observed that, at 6 h post-invasion, the wild type S. Typhimurium proliferated 30% more than the ΔcdsH strain in the presence of extra cysteine. This result shows that cdsH contributes to the bacterial replication in the intracellular environment in increased concentrations of extracellular cysteine, strongly suggesting that cdsH participates by increasing the bacterial fitness in the intestinal phase of the S. Typhimurium infection.

Cetuximab in Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Ovarian Cancer Without KRAS, NRAS, or BRAF Mutations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

BACKGROUND: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study, a phase II basket study, evaluates anti-tumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known as drug targets. OBJECTIVE: With no known genomic targets predictive of sensitivity to cetuximab, cetuximab was evaluated in patients with breast cancer (BC), non-small cell lung cancer (NSCLC), and ovarian cancer (OC), without KRAS, NRAS, or BRAF mutations. PATIENTS AND METHODS: Eligible patients with advanced BC, NSCLC, and OC received a cetuximab loading dose, then weekly infusions (250 mg/m2 over 60 min). A Simon two-stage design, requiring ten patients in stage I, was employed per each disease-specific cohort. The primary endpoint was disease control (objective response or stable disease for at least 16 weeks). If two or more patients in stage I achieved disease control, the cohort would enroll 18 more patients in stage II. Power and alpha of the design are 85% and 10%, respectively. Secondary endpoints included progression-free survival, overall survival, and safety. RESULTS: Patients with BC (n = 10), NSCLC (n = 10), and OC (n = 29) were enrolled between June 2016 and September 2018. No objective responses or stable disease for at least 16 weeks were observed in the BC and NSCLC cohorts. No objective responses and four patients with stable disease for at least 16 weeks were observed in the OC cohort. Six of 49 patients reported grade 3 or higher adverse events or serious adverse events at least possibly related to cetuximab. CONCLUSIONS: Cetuximab does not have clinical activity in patients with advanced BC, NSCLC, and OC without KRAS, NRAS, or BRAF mutations. CLINICAL TRIAL REGISTRATION: NCT02693535 (26 February, 2016).

Non-Cytotoxic Dibenzyl and Difluoroborate Curcuminoid Fluorophores Allow Visualization of Nucleus or Cytoplasm in Bioimaging.

Curcumin, the most important secondary metabolite isolated from Curcuma longa, is known for its numerous purported therapeutic properties and as a natural dye. Herein, based on curcumin's intrinsic fluorescence, a search for improved curcumin-based fluorophores was conducted. Within the set of semi-synthetic curcumin derivatives i.e. mono (1), di (2), tri (3), tetra (4) benzylated and dibenzyl-fluoroborate (5), the fluorescence properties of 2 and 5 in solution outstood with a two-fold quantum yield compared to curcumin. Furthermore, all benzylated derivatives showed a favorable minimal cytotoxic activity upon screening at 25 µM against human cancer and non-tumoral COS-7 cell lines, with a reduction of its cytotoxic effect related to the degree of substitution. Fluorophores 2 and 5 are versatile bioimaging tools, as revealed by Confocal Fluorescence Microscopy (CFM), and showed permeation of living cell membranes of astrocytes and astrocytomas. When 2 is excited with a 405- (blue) or 543-nm (green) laser, it is possible to exclusively and intensively visualize the nucleus. However, the fluorescence emission fades as the laser wavelength moves towards the red region. In comparison, 5 allows selective visualization of cytoplasm when a 560-nm laser is used, showing emission in the NIR region, while it is possible to exclusively observe the nucleus at the blue region with a 405-nm laser.

Facial emotion recognition and its association with symptom severity, functionality, and cognitive impairment in schizophrenia: preliminary results / Reconocimiento facial de emociones y su asociación con la gravedad sintomática, funcionalidad y deterioro cognitivo en esquizofrenia: hallazgos preliminares

Abstract Introduction There is evidence to suggest that individuals with schizophrenia have greater difficulty in recognizing facial emotions, which has been related to cognitive impairment and higher symptom severity in this disease and seems to lead to a worse functional prognosis. Objective To determine the association between facial emotion recognition and symptom severity, functionality, and cognitive impairment in a sample of schizophrenic patients. Method This is an observational, cross-sectional, and correlational study conducted on 72 patients. The following scales: PANSS, MOCA, ERI, and FACT-Sz were used to assess symptom severity in schizophrenia, cognitive functioning, facial emotion recognition, and functionality, respectively. The Pearson Correlation Coefficient was used to measure the linear association between all variables. Results Overall, moderate symptom severity and mild cognitive and functional disability were found. The most frequently recognized emotion was joy (70%) and the least frequently recognized one was anger. A positive association was also found between anger recognition and severity of the PANSS cognitive subscale (r = - .24, p = .03), sadness recognition and severity of the PANSS negative subscale (r = - .24, p = .03), and the FACT-Sz score and fear recognition (r = .31, p = .008). Discussion and conclusion The present study yields preliminary results that provide a broader perspective on facial emotion recognition and, indirectly, social interaction and functionality in people with schizophrenia.

Resumen Introducción Existe evidencia de que los pacientes con esquizofrenia tienen mayor dificultad para reconocer las emociones faciales, lo cual se ha relacionado con el deterioro cognitivo que se manifiesta en esta enfermedad y con una mayor gravedad sintomática, que parece dar lugar a un peor pronóstico funcional. Objetivo Determinar la asociación del reconocimiento facial de emociones con la gravedad sintomática, funcionalidad y deterioro cognitivo en un grupo de pacientes con esquizofrenia. Método Un estudio observacional, transversal y correlacional realizado con 72 pacientes. Se utilizaron las escalas: PANSS, MOCA, ERI y FACT-Sz para evaluar la gravedad sintomática, el funcionamiento cognitivo, el reconocimiento facial de emociones y la funcionalidad, respectivamente. Se utilizó el Coeficiente de Correlación de Pearson para medir la asociación lineal entre dichas variables. Resultados Se encontró de forma global una gravedad sintomática moderada y una discapacidad cognitiva y funcional leve. La alegría fue la emoción más reconocida (70%) y la ira la menos reconocida. Se encontró una asociación positiva entre el reconocimiento de la ira y la gravedad de la subescala cognitiva de la PANSS (r = -.24, p = .03), el reconocimiento de la tristeza y la gravedad de la subescala negativa de la PANSS (r = -.24, p = .03), y la puntuación de la FACT-Sz y el reconocimiento del miedo (r = .31, p = .008). Discusión y conclusión El presente estudio muestra algunos resultados preliminares que nos permiten tener una perspectiva más amplia de lo que ocurre con el reconocimiento facial de emociones en la esquizofrenia y, de forma indirecta, en la interacción social y la disfunción que presentan quienes lo padecen.

Development of the Mexican Version of the Empathy Quotient / Desarrollo de la versión mexicana del Cuestionario de Empatía

Abstract Introduction Empathy is defined as the ability or process to identify and understand other person's situation, feelings, and motives. These responses are essential for relationships and social behavior. Baron-Cohen et al. created the Empathy Quotient (EQ), a scale explicitly designed to have a clinical application. The instrument evaluates three constructs of empathy and several studies around worldwide, but not in Mexico. Objective To examine the psychometric properties and the factor congruence of the EQ in a community sample from Mexico City. Method Cronbach´s alpha coefficient and a correspondence factorial analysis was performed to test the relation between response options and factors from the Exploratory Factor Analysis 200 adults without Axis I disorders through the MINI, filled out the Spanish version of the short version (28-items) of the EQ. An exploratory factor analysis was performed while reliability was tested with Cronbach's alpha. In addition, correspondence factorial analysis and the factor congruence coefficient were determined. Results Five items were eliminated from the original 28-item EQ. From the 23 remaining items, only 16 were grouped in the three original proposed dimensions (cognitive empathy: 8 items, emotional reactivity: 4 items and social skills: 3 items), while one item showed communality with a different domain from the one originally proposed. Reliability was adequate (.82) as well as the congruence coefficients (.76 to .99). Discussion and conclusion The EQ Mexican 16-item version is a good tool to assess empathy in a Mexican population.

Resumen Introducción La empatía es definida como la capacidad para identificar y comprender las situaciones, sentimientos y motivaciones de otra persona. Estas respuestas son esenciales para relaciones y comportamientos sociales. Baron-Cohen et al. crearon el cociente de empatía (EQ), una escala diseñada para tener aplicación clínica. El instrumento evalúa tres constructos de empatía y ha probado sus propiedades psicométricas con resultados adecuados en varios estudios mundiales, pero no en México. Objetivo El propósito de este estudio fue examinar las propiedades psicométricas y la congruencia factorial del EQ en una muestra mexicana. Método El alpha de Cronbach y el análisis factorial fueron aplicados para probar la relación entre las opciones de respuesta y los factores en 200 adultos sin diagnóstico, a través de la entrevista MINI. Se utilizó la versión corta en español del EQ y se realizó un análisis factorial exploratorio dónde se probó la confiabilidad con el alfa de Cronbach y se determinó adecuada correspondencia y congruencia factorial. Resultados Se eliminaron cinco reactivos de la escala original de 28 reactivos. De los 23 reactivos restantes, solo 16 se agruparon en las tres dimensiones originales (empatía cognitiva: 8 reactivos, reactividad emocional: 4 reactivos y habilidades sociales: 3 reactivos) mientras que un reactivo mostró una comunalidad con un dominio diferente del original. La confiabilidad fue (.82), así como los coeficientes de congruencia (.76 a .99). Discusión y conclusión La versión del EQ es una buena herramienta para evaluar la empatía en población mexicana.

Association between prolactin serum levels and cognitive function in chronic schizophrenia patients / Asociación de los niveles de prolactina con el funcionamiento cognitivo en pacientes con esquizofrenia crónic

Abstract Introduction Several studies have explored the relationship between serum prolactin levels, symptomatology, and cognitive dysfunction in individuals at high risk for psychosis and patients with a first psychotic episode. However, the relationship between such variables is poorly understood in the case of chronic patients. Objective To assess the relationship between prolactin levels, neuropsychological impairment, and symptom severity in patients with chronic schizophrenia. Method A total of 31 patients with diagnosis of schizophrenia were evaluated between May and December 2018. The age range was 18 to 60 years, with patients receiving antipsychotic treatment during a month at least. Data was obtained from clinical records, interviews, clinimetry, and with the application of the PANSS and the MCCB battery. For the prolactin measurement, the analysis was performed on a sample of 500 microliters of serum, with a chemiluminescence technique. Results The sample was comprised mostly by men (77.4%), with a mean age of 37.65 years, 13.29 years of formal education, and disease duration of 11.58 years. No correlations were observed between prolactin levels and PANSS components and subscales. Only in male patients is there a negative correlation was found between prolactin levels with the overall combined score of the MCCB battery and cognitive domains of reasoning and verbal learning. Discussion and conclusions Men diagnosed with schizophrenia may be particularly vulnerable to the negative effects of hyperprolactinemia on cognition. These preliminary data have clinical implications for close monitoring of prolactin and cognitive decline in males with schizophrenia. Theoretically, these data are suggestive of a protective effect of hormones in women with this condition.

Resumen Introducción Diversos estudios han explorado la relación entre los niveles de prolactina sérica, la sintomatología y la disfunción cognitiva en individuos con alto riesgo de psicosis y pacientes con un primer episodio psicótico. Sin embargo, la relación entre tales variables es poco comprendida en el caso de los pacientes crónicos con esquizofrenia. Objetivo Evaluar la relación entre los niveles de prolactina, el deterioro neuropsicológico y la severidad de los síntomas en pacientes crónicos. Método Se evaluó un total de 31 pacientes. El rango de edad fue de 18 a 60 años, quienes recibieron tratamiento antipsicótico durante un mes como mínimo. Los datos se obtuvieron de entrevistas y de la aplicación de la PANSS y la MCCB. La medición de la prolactina se realizó con una muestra de 500 microlitros de suero, con una técnica de quimioluminiscencia. Resultados La muestra estuvo compuesta en su mayoría por hombres (77.4%), con una edad media de 37.65 años, 13.29 años de escolaridad y una duración de la enfermedad de 11.58 años. No se observaron correlaciones entre los niveles de prolactina y los componentes y subescalas del PANSS. Sólo en los pacientes varones se da una correlación negativa entre los niveles de prolactina con la puntuación global combinada de la batería de MCCB y los dominios cognitivos de razonamiento y aprendizaje verbal. Discusión y conclusiones Los hombres diagnosticados con esquizofrenia pueden ser particularmente vulnerables a los efectos negativos de la hiperprolactinemia sobre la cognición. Teóricamente, estos datos sugieren un efecto protector de las hormonas en las mujeres con esta enfermedad.

Male patient with metastatic stage IV breast cancer achieves complete remission on second line Abemaciclib, Fulvestrant and Leuprolide: A case report.

Male breast cancer occurs rarely, comprising <1% of breast cancers. Due to the low incidence of male breast cancer, clinical trials of this disease are lacking. Therefore, therapeutic strategies utilized in the management of female breast cancer are often applied to male patients with breast cancer. Specifically, clinical outcomes using CDK 4/6 inhibitors require further investigation in male patients. To the best of our knowledge, the present report presents the first known case of a male patient treated with second line Abemaciclib, Lupron and Fulvestrant, producing complete remission. To the best of our knowledge this is also the first report of complete remission in a male breast cancer patient with a regimen utilizing a CDK 4/6 inhibitor.

Association between circulating tumor cells and peripheral blood monocytes in metastatic breast cancer.

BACKGROUND: We retrospectively evaluated the correlation between a baseline measurement of circulating tumor cells (CTCs) and inflammation-based scores in patients with metastatic breast cancer (MBC). METHODS: The optimal value of inflammation-based scores as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) to predict survival was determined and compared with CTC <5 or ⩾5 per 7.5 ml of blood. RESULTS: In the overall population of 516 women with MBC, CTCs correlated with peripheral blood monocytes (p = 0.008) and neutrophils (p = 0.038). In triple-negative tumors, CTCs correlated with monocyte count (p = 0.009); in HER2+ tumors, CTCs correlated with neutrophil count (p = 0.009), with a trend versus monocyte count (p = 0.061), whereas no correlation was found in HER2- estrogen receptor-positive (ER+) tumors. In multivariate analysis only monocytes were associated with ⩾5 CTCs (OR = 2.72, 95% CI 1.09-6.80, p = 0.033). In multivariable analysis for predictors of overall survival, CTC (⩾5 versus <5), number of metastatic sites (>1 versus 1), tumor subtypes (triple-negative versus HER2- ER+ tumors) and MLR only remained significant. CONCLUSIONS: CTC and MLR are predictors of overall survival in MBC. CTC correlates with monocytes, in particular in triple-negative tumors.

Prácticas de ocio en complejos habitacionales para adultos mayores en Montevideo / Práticas de lazer em complexos habitacionais para idosos em Montevidéu / Leisure practices in housing complexes for older adults in Montevideo / Pratiques de loisirs dans les complexes de logements pour personnes âgées à Montevideo

Las políticas dirigidas a las personas adultas mayores concentran sus esfuerzos en brindar soluciones a necesidades básicas como vivienda, salud o alimentación posponiendo muchas veces necesidades de tipo social y cultural. El presente artículo expone los principales hallazgos de una investigación realizada desde una perspectiva del desarrollo humano y de las experiencias de ocio que analiza las prácticas de ocio en personas adultas mayores, con el objetivo de conocer la experiencia de ocio a partir del sentido que le atribuyen a estas prácticas. El enfoque metodológico considerado es el cuantitativo, para lo que se aplicó un cuestionario a una muestra de 245 personas adultas mayores que residen en Complejos habitacionales de gestión pública, en la ciudad de Montevideo (Uruguay). Se apuntó a analizar las prácticas de ocio a partir de variables sociodemográficas, así como indagar en torno a la continuidad, ruptura o aumento en la realización de dichas prácticas e identificar las principales barreras de ocio que intervienen en sus prácticas. Entre los principales hallazgos del estudio se destaca el predominio en la práctica de actividades de ocio pasivo y de baja exigencia cognitiva, tales como: Ver Tv, Escuchar música y Oír radio. Si bien dentro de las actividades de ocio más mencionadas no se observaron diferencias significativas entre hombres y mujeres, sí se observó una división sexual de ocio encontrándose actividades tradicionalmente femeninas (p.e. Cantar, Hacer manualidades) y masculinas (p.e. Hacer ejercicio, Bricolaje). Por último, las principales barreras de ocio que afectan a la población comprendida en este estudio están relacionadas con la salud (intrapersonal), la falta de compañía (interpersonal) y la economía (estructural).

Políticas destinadas a idosos concentram seus esforços em fornecer soluções para necessidades básicas, como habitação, saúde ou alimentação, muitas vezes adiando as necessidades sociais e culturais. Este artigo apresenta os principais achados de uma pesquisa realizada a partir de uma perspectiva de desenvolvimento humano e experiências de lazer que analisa as práticas de lazer em idosos, com o objetivo de conhecer a experiência de lazer com base no significado atribuído a essas práticas. Sendo a abordagem metodológica considerada quantitativa, para a qual foi aplicado um questionário. uma amostra de 245 idosos residentes em conjuntos habitacionais, na cidade de Montevidéu (Uruguai). Ele se inscriveu a analisar as práticas de lazer de variáveis sociodemográficas e inquirir sobre a continuidade, ruptura ou aumento na realização de tais práticas e identificar as principais barreiras lazer envolvido em suas práticas. Entre os principais achados do estudo está o predomínio na prática de atividades de lazer passivo e baixas demandas cognitivas, como: assistir TV, ouvir música e ouvir rádio. Enquanto em atividades mais citada lazer não foram observadas diferenças significativas entre homens e mulheres, se foi observada uma divisão sexual do lazer reunião homens tradicionalmente atividades femininas (Canto ponto de ebulição, artesanato) e (ponto de ebulição Exercício, DIY). Por fim, as principais barreiras de lazer que afetam a população incluída neste estudo estão relacionadas à saúde (intrapessoal), falta de empresa (interpessoal) e economia (estrutural).

Policies on late adulthood have focus on providing solutions to basic needs such as housing, health or food, by postponing other social and cultural needs. This article considers the main results of a research carried out from a human development perspective which analyzes leisure practices in older people, with the objective of knowing the leisure experience based on the meaning attributed to these practices. The methodological approach considered is quantitative, for which a survey design was applied to a sample of 245 older in public housing complexes, in the city of Montevideo (Uruguay). He pointed to analyze leisure practices, the continuity, rupture or increase within the activities and identify the main leisure constraints that intervene. Among the main results of the study is the predominance in practice of passive leisure activities and low cognitive demands, such as: Watching TV, listening to music and listening to radio. Although within the activities mentioned above, there were no significant differences between men and women, a sexual division of leisure was found, with traditionally feminine activities (for example singing, making crafts) and masculine activities (for instance, Do exercise, DIY activities) . Finally, the main leisure constraints that affect most of the population included in this study are related to health (intrapersonal), lack of company (interpersonal) and economy (structural).

Les politiques visant à les personnes âgées concentrent leurs efforts sur la fourniture de solutions aux besoins de base tels que le logement, la santé ou mettre de la nourriture a souvent besoin social et culturel. Cet article présente les principaux résultats de la recherche menée dans une perspective de développement humain et l'expérience des practiques de loisirs analysées chez les personnes âgées, avec l'objectif de connaître l'expérience de loisir basée sur le sens attribué à ces pratiques. L'approche méthodologique est considérée comme quantitative, pour laquelle un questionnaire à un échantillon de 245 adultes personnes âgées résidant dans la gestion des ensembles de logements sociaux dans la ville de Montevideo (Uruguay) a été appliqué. Il s'est inscrit d'analyser les pratiques de loisirs à partir de variables socio-démographiques et se renseigner sur la continuité, la rupture ou une augmentation dans la conduite de telles pratiques et d'identifier les principaux obstacles loisirs impliqués dans leurs pratiques. Regarder la télévision, écouter de la musique et écouter la radio: Parmi les principales conclusions de l'étude, la prévalence dans la pratique des activités de loisirs passifs et faible exigence cognitive comme indiqué. Alors que dans les activités les plus fréquemment mentionné loisirs aucune différence significative entre les hommes et les femmes ont été observées, si une division sexuelle des hommes de réunion de loisirs des activités traditionnellement féminines (par example, Chant, artisanat) et (par example, exercice, bricolage) a été observé. Enfin, les principaux obstacles loisirs touchant la population dans cette étude sont liés à la santé (intrapersonal), le manque de compagnie (interpersonnelle) et l'économie (structurelle).

A phase Ib study of entinostat plus lapatinib with or without trastuzumab in patients with HER2-positive metastatic breast cancer that progressed during trastuzumab treatment.

BACKGROUND: Human epidermal growth factor 2 (HER2) is an effective therapeutic target in breast cancer; however, resistance to anti-HER2 agents such as trastuzumab and lapatinib develops. In a preclinical model, an HDAC inhibitor epigenetically reversed the resistance of cancer cells to trastuzumab and showed synergistic efficacy with lapatinib in inhibiting growth of trastuzumab-resistant HER2-positive (HER2+) breast cancer. METHODS: A phase 1b, dose escalation study was performed to assess maximum tolerated dose, safety/toxicity, clinical efficacy and explored pharmacodynamic biomarkers of response to entinostat combined with lapatinib with or without trastuzumab. RESULTS: The combination was safe. The MTD was lapatinib, 1000 mg daily; entinostat, 12 mg every other week; trastuzumab, 8 mg/kg followed by 6 mg/kg every 3 weeks. Adverse events included diarrhoea (89%), neutropenia (31%), and thrombocytopenia (23%). Neutropenia, thrombocytopenia and hypokalaemia were noted. Pharmacodynamic assessment did not yield conclusive results. Among 35 patients with evaluable response, PR was observed in 3 patients and CR in 3 patients, 1 maintained SD for over 6 months. DISCUSSION: This study identified the MTD of the entinostat, lapatinib, and trastuzumab combination that provided acceptable tolerability and anti-tumour activity in heavily pre-treated patients with HER2+ metastatic breast cancer, supporting a confirmatory trial.

Elevated serum levels of sialyl Lewis X (sLeX) and inflammatory mediators in patients with breast cancer.

PURPOSE: The carbohydrate sialyl LewisX (sLeX) mediates cell adhesion, is critical in the normal function of immune cells, and is frequently over-expressed on cancer cells. We assessed the association, differential levels, and prognostic value of sLeX and inflammatory cytokines/chemokines in breast cancer sera. METHODS: We retrospectively measured sLeX and a panel of cytokines/chemokines in the sera of 26 non-invasive ductal carcinoma in situ (DCIS), 154 invasive non-metastatic breast cancer (non-MBC), 63 metastatic breast cancer (MBC) patients, and 43 healthy controls. Differences in sLeX and inflammatory cytokines among and between patient groups and healthy controls were assessed with nonparametric tests and we performed survival analysis for the prognostic potential of sLeX using a cut-off of 8 U/mL as previously defined. RESULTS: Median serum sLeX was significantly higher than controls for invasive breast cancer patients (MBC and non-MBC) but not DCIS. In univariate analysis, we confirmed patients with serum sLeX > 8 U/mL have a significantly shorter progression-free survival (PFS) (P = 0.0074) and overall survival (OS (P = 0.0003). Similarly, patients with high serum MCP-1 and IP-10 had shorter OS (P = 0.001 and P < 0.001, respectively) and PFS (P = 0.010 and P < 0.001, respectively). sLeX, MCP-1 and IP-10 remained significant in multivariate survival analysis. CONCLUSION: Elevated serum sLeX was associated with invasive cancer but not DCIS. High serum sLeX levels were associated with inflammatory mediators and may play a role in facilitating local invasion of breast tumor. Furthermore, serum MCP-1, IP-10 and sLeX may have prognostic value in breast cancer.

Full Structural Characterization of Homoleptic Complexes of Diacetylcurcumin with Mg, Zn, Cu, and Mn: Cisplatin-level Cytotoxicity in Vitro with Minimal Acute Toxicity in Vivo.

At the present time, scientists place a great deal of effort worldwide trying to improve the therapeutic potential of metal complexes of curcumin and curcuminoids. Herein, the synthesis of four homoleptic metal complexes with diacetylcurcumin (DAC), using a ligand designed to prevent the interaction of phenolic groups, rendering metal complexes through the ß-diketone functionality, is reported. Due to their physiological relevance, we used bivalent magnesium, zinc, copper, and manganese for complexation with DAC. The resulting products were characterized by ultraviolet-visible (UV-Vis), fluorescence spectroscopy, infrared spectroscopy (IR), liquid and solid-state nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), magnetic moment, mass spectrometry (MS), single crystal, and powder X-ray diffraction (SCXRD and PXRD). Crystallization was achieved in dimethylsulfoxide (DMSO) or N,N-dimethylformamide (DMF) as triclinic systems with space group P-1, showing the metal bound to the ß-diketone function, while the 1H-NMR confirmed the preference of the enolic form of the ligand. Single crystal data demonstrated a 1:2 metal:ligand ratio. The inhibition of lipid peroxidation was evaluated using the thiobarbituric acid reactive substance assay (TBARS). All four metal complexes (Mg, Zn, Cu, and Mn) exhibited good antioxidant effect (IC50 = 2.03 ± 0.27, 1.58 ± 0.07, 1.58 ± 0.15 and 1.24 ± 0.10 µM respectively) compared with butylated hydroxytoluene (BHT) and α-tocopherol. The cytotoxic activity in human cancer cell lines against colon adenocarcinoma (HCT-15), mammary adenocarcinoma (MCF-7), and lung adenocarcinoma (SKLU-1) was found comparable ((DAC)2Mg), or ca. 2-fold higher ((DAC)2Zn) than cisplatin. The acute toxicity assays indicate class 5 toxicity, according to the Organization for Economic Co-operation and Development (OECD) guidelines at doses of 3 g/kg for all complexes. No mortality or changes in the behavior of animals in any of the treated groups was observed. A therapeutic potential can be envisaged from the relevant cytotoxic activity upon human cancer cell lines in vitro and the undetected in vivo acute toxicity of these compounds.

A New Family of Homoleptic Copper Complexes of Curcuminoids: Synthesis, Characterization and Biological Properties.

We report herein the synthesis and crystal structures of five new homoleptic copper complexes of curcuminoids. The scarcity of reports of homoleptic complex structures of curcuminoids is attributed to the lack of crystallinity of such derivatives, and therefore, their characterization by single crystal X-ray diffraction is rare. The ligand design suppressing the phenolic interaction by esterification or etherification has afforded a significant increase in the number of known crystal structures of homoleptic metal complexes of curcuminoids revealing more favorable crystallinity. The crystal structures of the present new copper complexes show four-fold coordination with a square planar geometry. Two polymorphs were found for DiBncOC-Cu when crystallized from DMF. The characterization of these new complexes was carried out using infrared radiation (IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and single crystal X-ray diffraction (SCXRD) and the antioxidant and cytotoxic activity of the obtained complexes was evaluated.

Palbociclib in Patients With Pancreatic and Biliary Cancer With CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study.

PURPOSE: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study identifies signals of antitumor activity of commercially available targeted agents in patients with advanced cancers that harbor genomic alterations known as drug targets. In this article, data from two cohorts of patients with pancreatic and biliary cancers with CDKN2A loss or mutation treated with palbociclib are reported. METHODS: Eligible patients age 12 years and older with advanced measurable or evaluable solid tumors are provided treatment according to protocol-specified genomic matching rules. The primary study end point is objective response or stable disease of at least 16 weeks duration. For each cohort, a Simon two-stage design was used with a futility evaluation after 10 patients. Secondary end points include safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Between July 2016 and November 2017, 12 and 10 patients with pancreatic and biliary cancer, respectively, with CDKN2A loss or mutation were treated with palbociclib. Twenty evaluable patients (10 per cohort) were included in the analysis. No patients had objective response or stable disease at 16 weeks, and both cohorts were closed. Two patients, neither with response, were determined to be ineligible. All patients were evaluated for safety, PFS, and OS. A median PFS of 7.2 weeks (90% CI, 4.0 to 8.0 weeks) and median OS of 12.4 weeks (90% CI, 4.7 to 23.1 weeks) were observed in the pancreatic cohort. A median PFS of 7.3 weeks (90% CI, 3.9 to 7.9 weeks) and median OS of 11.1 weeks (90% CI, 5.1 to 14.0 weeks) were observed in the biliary cohort. No unexpected toxicities were observed. CONCLUSION: Palbociclib monotherapy does not have clinical activity in patients with advanced pancreatic or biliary cancers with CDKN2A loss or mutation. Toxicity is similar to reported experience with palbociclib in other tumor types.

Distinct epidemiological profiles associated with inflammatory breast cancer (IBC): A comprehensive analysis of the IBC registry at The University of Texas MD Anderson Cancer Center.

BACKGROUND: To date, studies on inflammatory breast cancer (IBC) lack comprehensive epidemiological data. We analyzed detailed prospectively collected clinical and epidemiological data from the IBC Registry at The University of Texas MD Anderson Cancer Center. METHODS: Patients with IBC (n = 248) were consecutively diagnosed and prospectively enrolled between November 2006 and April 2013. All patients were newly diagnosed and at least 18 years old. Secondary IBC was excluded. Overall 160 variables were collected and evaluated including sociodemographics, anthropometrics, tobacco and alcohol consumption, reproductive variables, and family history data. RESULTS: Mean age at diagnosis was 51.6 (±11.5 SD) years, and the majority of patients were White (77.8%). A mean BMI ≥ 25 kg/m2, irrespective of menopausal status, was observed in 80.2% of all patients, with 82.6% of African Americans being obese. Approximately 42.2% of patients were ever smokers, and 91% reported ever being pregnant. A history of breastfeeding was reported in 54% of patients, with significant differences between ethnic groups in favor of White women (P<0.0001). Other reproductive factors such as use of birth control pills & hormone replacement therapy were also more frequently associated with White women compare to other ethnic groups (P < 0.05). In the multivariate Cox proportional hazard analysis, African American or Hispanic ethnicity, not having breastfed, higher clinical stage, and TNBC subtype were associated with shorter survival. CONCLUSION: Our data suggest that IBC is associated with distinct epidemiological profiles. This information could assist in targeting patients with specific preventive strategies based on their modifiable behavioral patterns.

Safety and Efficacy of Panitumumab Plus Neoadjuvant Chemotherapy in Patients With Primary HER2-Negative Inflammatory Breast Cancer.

Importance: Combining conventional chemotherapy with targeted therapy has been proposed to improve the pathologic complete response (pCR) rate in patients with inflammatory breast cancer (IBC). Epidermal growth factor receptor (EGFR) expression is an independent predictor of low overall survival in patients with IBC. Objective: To evaluate the safety and efficacy of the anti-EGFR antibody panitumumab plus neoadjuvant chemotherapy in patients with primary human epidermal growth factor receptor 2 (HER2)-negative IBC. Design, Setting, and Participants: Women with primary HER2-negative IBC were enrolled from 2010 to 2015 and received panitumumab plus neoadjuvant chemotherapy. Median follow-up time was 19.3 months. Tumor tissues collected before and after the first dose of panitumumab were subjected to immunohistochemical staining and RNA sequencing analysis to identify biomarkers predictive of pCR. Intervention: Patients received 1 dose of panitumumab (2.5 mg/kg) followed by 4 cycles of panitumumab (2.5 mg/kg), nab-paclitaxel (100 mg/m2), and carboplatin weekly and then 4 cycles of fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2) every 3 weeks. Main Outcomes and Measures: The primary end point was pCR rate; the secondary end point was safety. The exploratory objective was to identify biomarkers predictive of pCR. Results: Forty-seven patients were accrued; 7 were ineligible. The 40 enrolled women had a median age of 57 (range, 23-68) years; 29 (72%) were postmenopausal. Three patients did not complete therapy because of toxic effects (n = 2) or distant metastasis (n = 1). Nineteen patients had triple-negative and 21 had hormone receptor-positive IBC. The pCR and pCR rates were overall, 11 of 40 (28%; 95% CI, 15%-44%); triple-negative IBC, 8 of 19 (42%; 95% CI, 20%-66%); and hormone receptor-positive/HER2-negative IBC, 3 of 21 (14%; 95% CI, 3%-36%). During treatment with panitumumab, nab-paclitaxel, and carboplatin, 10 patients were hospitalized for treatment-related toxic effects, including 5 with neutropenia-related events. There were no treatment-related deaths. The most frequent nonhematologic adverse event was skin rash. Several potential predictors of pCR were identified, including pEGFR expression and COX-2 expression. Conclusions and Relevance: This combination of panitumumab and chemotherapy showed the highest pCR rate ever reported in triple-negative IBC. A randomized phase 2 study is ongoing to determine the role of panitumumab in patients with triple-negative IBC and to further validate predictive biomarkers. Trial Registration: ClinicalTrials.gov Identifier: NCT01036087.