Efficacy and delivery strategies of the dual Rac/Cdc42 inhibitor MBQ-167 in HER2 overexpressing breast cancer.

Trastuzumab and trastuzumab-based treatments are the standard of care for breast cancer patients who overexpress the human epidermal growth factor receptor 2 (HER2). However, patients often develop resistance to trastuzumab via signaling from alternative growth factor receptors that converge to activate guanine nucleotide exchange factors (GEFs) that in turn activate the Rho GTPases Rac and Cdc42. Since Rac and Cdc42 have been implicated in high tumor grade and therapy resistance, inhibiting the activity of Rac and Cdc42 is a rational strategy to overcome HER2-targeted therapy resistance. Therefore, our group developed MBQ-167, a dual Rac/Cdc42 inhibitor with IC50s of 103 nM and 78 nM for Rac and Cdc42, respectively, which is highly effective in reducing cell and tumor growth and metastasis in breast cancer cell and mouse models. Herein, we created a trastuzumab resistant variant of the SKBR3 HER2 positive breast cancer cell line and show that Rac activation is a central mechanism in trastuzumab resistance. Next, we tested the potential of targeting MBQ-167 to HER2 overexpressing trastuzumab-resistant cell lines in vitro, and show that MBQ-167, but not trastuzumab, reduces cell viability and induces apoptosis. When MBQ-167 was targeted to mammary fatpad tumors established from HER2 overexpressing cells via immunoliposomes functionalized with trastuzumab, MBQ-167 and MBQ-167-loaded liposomes show equal efficacy in reducing the viability of trastuzumab-resistant cells, inhibiting tumor growth in mouse xenografts, and reducing metastasis to lungs and liver. This study demonstrates the efficacy of MBQ-167 as an alternative therapeutic in HER2 overexpressing cancers, delivered either in free form or in liposomes.

Estado inicial de la virtualización del proceso de formación en una Universidad

El desarrollo de las Tecnologías de la Información y las Comunicaciones (TIC) genera nuevas demandas sociales a la educación. En los últimos años, la utilización de elementos tecnológicos en los contextos educativos ha conllevado a la realización de profundas transformaciones en las instituciones y en la forma de organizar y trabajar el proceso docente educativo. El objetivo de este artículo fue analizar el estado inicial de la virtualización del proceso de formación en la Universidad de Ciencias de la Cultura Física y Deporte Manuel Fajardo. Para lograr este propósito se aplicó un conjunto de instrumentos (encuestas a estudiantes y profesores, entrevistas a directivos y guía de observación a los cursos implementados en la plataforma virtual Moodle). Se asumió un enfoque mixto que posibilitó buscar información sobre la virtualización del proceso de formación de la Universidad de Ciencias de la Cultura Física y el Deporte (UCCFD) Manuel Fajardo desde las miradas de los distintos actores del proceso, lo que permitió lograr una mayor fidelidad de los resultados obtenidos en los instrumentos aplicados. Los resultados de las encuestas a estudiantes y profesores fueron divididos en positivos y negativos (Carencias y Fortalezas), para destacar la necesidad de elaborar un modelo de virtualización del proceso de formación de la UCCFD "Manuel Fajardo".

O desenvolvimento das Tecnologias de Informação e Comunicação (TIC) gera novas demandas sociais para a educação. Nos últimos anos, o uso de elementos tecnológicos em contextos educacionais levou a profundas transformações nas instituições e na forma de organizar e trabalhar o processo de ensino e educação. O objetivo deste artigo foi analisar o estado inicial da virtualização do processo de treinamento na Universidade Manuel Fajardo de Cultura Física e Ciências do Esporte. Para atingir esse objetivo, foi aplicado um conjunto de instrumentos (pesquisas com alunos e professores, entrevistas com diretores e um guia de observação dos cursos implementados na plataforma virtual Moodle). Foi adotada uma abordagem mista, que possibilitou a busca de informações sobre a virtualização do processo de treinamento na Universidade de Ciências da Cultura Física e do Esporte Manuel Fajardo (UCCFD) a partir dos pontos de vista dos diferentes atores do processo, o que permitiu obter maior precisão nos resultados obtidos nos instrumentos aplicados. Os resultados das pesquisas com alunos e professores foram divididos em positivos e negativos (deficiências e pontos fortes), a fim de destacar a necessidade de desenvolver um modelo de virtualização para o processo de formação na UCCFD "Manuel Fajardo".

The development of Information and Communication Technologies (ICT) generates new social demands on education. In recent years, the use of technological elements in educational contexts has led to profound transformations in institutions and in the way of organizing and working the educational teaching process. The objective of this article was to analyze the initial state of the virtualization of the training process at the Manuel Fajardo University of Physical Culture and Sports Sciences. To achieve this purpose, a set of instruments was applied (surveys to students and teachers, interviews with managers and an observation guide to the courses implemented on the Moodle virtual platform). A mixed approach was assumed that made it possible to search for information on the virtualization of the training process of the "Manuel Fajardo" University of Physical Culture and Sports Sciences (UCCFD in Spanish) from the perspectives of the different actors in the process, which allowed achieving greater fidelity of the results obtained in the applied instruments. The results of the surveys to students and teachers were divided into positive and negative (Shortcomings and Strengths), to highlight the need to develop a virtualization model of the training process of the UCCFD "Manuel Fajardo".

How the COVID-19 pandemic affects the moral reasoning of pediatric residents and the general population.

BACKGROUND: Kohlberg's theory of moral development asserts that people progress through different stages of moral reasoning as their cognitive abilities and social interactions mature. Individuals at the lowest stage of moral reasoning (preconventional stage) judge moral issues based on self-interest, those with a medium stage (conventional stage) judge them based on compliance with rules and norms, and those at the highest stage (postconventional stage) judge moral issues based on universal principles and shared ideals. Upon attaining adulthood, it can be considered that there is stability in the stage of individuals' moral development; however, the effect of a global population crisis such as the one experienced in March 2020, when the World Health Organization (WHO) declared the COVID-19 pandemic, is unknown. The purpose of this study was to evaluate the changes in the moral reasoning of pediatric residents before and after one year of the COVID-19 pandemic and compare them with a general population group. METHODS: This is a naturalistic quasi-experimental study conducted with two groups, one comprised 47 pediatric residents of a tertiary hospital converted into a COVID hospital during the pandemic and another group comprised 47 beneficiaries of a family clinic who were not health workers. The defining issues test (DIT) was applied to the 94 participants during March 2020, before the pandemic initiated in Mexico, and later during March 2021. To assess intragroup changes, the McNemar-Bowker and Wilcoxon tests were used. RESULTS: Pediatric residents showed higher baseline stages of moral reasoning: 53% in the postconventional group compared to the general population group (7%). In the preconventional group, 23% were residents and 64% belonged to the general population. In the second measurement, one year after the start of the pandemic, the group of residents had a significant decrease of 13 points in the P index, unlike the general population group in which a decrease of 3 points was observed. This decrease however, did not equalize baseline stages. Pediatric residents remained 10 points higher than the general population group. Moral reasoning stages were associated with age and educational stage. CONCLUSIONS: After a year of the COVID-19 pandemic, we found a decrease in the stage of moral reasoning development in pediatric residents of a hospital converted for the care of patients with COVID-19, while it remained stable in the general population group. Physicians showed higher stages of moral reasoning at baseline than the general population.

Efficacy of Rac and Cdc42 Inhibitor MBQ-167 in Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer, with a high predisposition for locally invasive and metastatic cancer. With the objective to reduce cancer metastasis, we developed small molecule inhibitors to target the drivers of metastasis, the Rho GTPases Rac and Cdc42. Of these, MBQ-167 inhibits both Rac and Cdc42 with IC50s of 103 and 78 nmol/L, respectively; and consequently, inhibits p21-activated kinase (PAK) signaling, metastatic cancer cell proliferation, migration, and mammosphere growth; induces cell-cycle arrest and apoptosis; and decreases HER2-type mammary fatpad tumor growth and metastasis (Humphries-Bickley and colleagues, 2017). Herein, we used nuclear magnetic resonance to show that MBQ-167 directly interacts with Rac1 to displace specific amino acids, and consequently inhibits Rac.GTP loading and viability in TNBC cell lines. Phosphokinome arrays in the MDA-MB-231 human TNBC cells show that phosphorylation status of kinases independent of the Rac/Cdc42/PAK pathway are not significantly changed following 200 nmol/L MBQ-167 treatment. Western blotting shows that initial increases in phospho-c-Jun and phospho-CREB in response to MBQ-167 are not sustained with prolonged exposure, as also confirmed by a decrease in their transcriptional targets. MBQ-167 inhibits tumor growth, and spontaneous and experimental metastasis in immunocompromised (human TNBC) and immunocompetent (mouse TNBC) models. Moreover, per oral administration of MBQ-167 at 100 mg/kg body weight is not toxic to immunocompetent BALB/c mice and has a half-life of 4.6 hours in plasma. These results highlight the specificity, potency, and bioavailability of MBQ-167, and support its clinical potential as a TNBC therapeutic.

Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors.

Inflammatory Breast Cancer (IBC) is an aggressive form of invasive breast cancer, highly metastatic, representing 2-4% of all breast cancer cases in the United States. Despite its rare nature, IBC is responsible for 7-10% of all breast cancer deaths, with a 5-year survival rate of 40%. Thus, targeted and effective therapies against IBC are needed. Here, we proposed Lipocalin-2 (LCN2)-a secreted glycoprotein aberrantly abundant in different cancers-as a plausible target for IBC. In immunoblotting, we observed higher LCN2 protein levels in IBC cells than non-IBC cells, where the LCN2 levels were almost undetectable. We assessed the biological effects of targeting LCN2 in IBC cells with small interference RNAs (siRNAs) and small molecule inhibitors. siRNA-mediated LCN2 silencing in IBC cells significantly reduced cell proliferation, viability, migration, and invasion. Furthermore, LCN2 silencing promoted apoptosis and arrested the cell cycle progression in the G0/G1 to S phase transition. We used in silico analysis with a library of 25,000 compounds to identify potential LCN2 inhibitors, and four out of sixteen selected compounds significantly decreased cell proliferation, cell viability, and the AKT phosphorylation levels in SUM149 cells. Moreover, ectopically expressing LCN2 MCF7 cells, treated with two potential LCN2 inhibitors (ZINC00784494 and ZINC00640089) showed a significant decrease in cell proliferation. Our findings suggest LCN2 as a promising target for IBC treatment using siRNA and small molecule inhibitors.

Efficacy of Virtual Reality in Neurorehabilitation of Spinal Cord Injury Patients: A Systematic Review / Eficacia de la Realidad Virtual en la Neurorrehabilitación de Pacientes con Lesión de Médula Espinal: una Revisión Sistemática

ABSTRACT This systematic review (SR) analyzed the effectiveness of interventions using virtual reality (VR) technology as a neurorehabilitation therapy in people with spinal cord injury (SCI). The SR was developed under the guidelines of the PRISMA statement and the recommendations of the Cochrane Collaboration, along with the PEDro and National Institute of Health scales to assess the risk of bias and methodological quality. The Cochrane, IEEE, BVS/LILACS, MEDLINE/PubMed, and Web of Science databases were browsed to identify studies that, between 2010 and 2020, evaluated the efficacy of these therapies. Out of 353 retrieved studies, 11 were finally selected after the application of the defined inclusion and exclusion criteria. These articles presented good methodological quality as they were mostly controlled clinical trials that analyzed mixed therapies with conventional therapies. Interventions based on non-immersive or immersive VR technology that achieved functional motor, balance, and psycho-emotional health improvement with positive effects on motivation, self-confidence, commitment, and active participation were identified in a total sample of 155 SCI patients. It was concluded that such VR technology is an effective tool of neurorehabilitation complementary to conventional therapies, which promotes functional improvement in SCI patients both in the clinic and at home.

RESUMEN Esta revisión sistemática (RS) analizó la eficacia de las intervenciones que utilizan la tecnología de realidad virtual (RV) como terapia de neurorrehabilitación en personas con lesión de médula espinal (LME). La RS fue desarrollada bajo los lineamientos de la declaración PRISMA y las recomendaciones de la Colaboración Cochrane, junto con las escalas de PEDro y del National Institute of Health para evaluar el riego de sesgo y la calidad metodológica. Se revisaron las bases de Cochrane, IEEE, BVS/LILACS, MEDLINE/PubMed y Web of Science para identificar estudios que, entre 2010 y 2020, evaluaron la eficacia de dichas terapias. De 353 estudios recuperados, 11 fueron finalmente seleccionados tras la aplicación de los criterios de inclusión y exclusión definidos. Dichos artículos presentaron una buena calidad metodológica, al ser mayormente ensayos clínicos controlados que analizaron terapias mixtas con terapias convencionales. Se identificaron intervenciones basadas en tecnología de RV no inmersiva o inmersiva que lograron una mejora funcional motora, de equilibrio y de salud psico-emocional con efectos positivos de motivación, seguridad, compromiso y activa participación en una muestra total de 155 pacientes con LME. Se concluyó que dicha tecnología de RV es una herramienta eficaz de neurorrehabilitación complementaria a las terapias convencionales, al promover una mejora funcional en pacientes con LME tanto en la clínica como en casa.

Effects of substrate temperature on patterns produced by dried droplets of proteins.

Rapid diagnosis provides better clinical management of patients, helps control possible outbreaks, and increases survival. The study of deposits produced by the evaporation of droplets is a useful tool in the diagnosis of some health problems. With the aim to improve diagnostic time in clinical practice where we use the evaporation of droplets, we explored the effects of substrate temperature on pattern formation of dried droplets in globular protein solutions. Three deposit groups were observed: "functional" patterns (from 25 to 37 ∘C), "transition" patterns (from 44 to 50 ∘C), and "eye" patterns (from 58 to 63 ∘C). The dried droplets of the first two groups show a ring structure ("coffee-ring") that confines a great diversity of aggregates such as needle-like structures, tiny blade-shape crystals, highly symmetrical crystallization patterns, and amorphous salt aggregates. In contrast, the "eye" patterns are deposits with a large inner aggregate surrounded by a coffee ring, and they can appear from the evaporation of droplets in protein binary mixtures and blood serum. Interestingly, the unfolding proteins correlates with the formation of "eye" patterns. We measured stain diameter, "coffee-ring" thickness, radial density profile, and entropy computed by GLCM-statistics to quantify the structural differences among deposit groups. We found that "functional" patterns are structurally indistinguishable among them, but they are clearly different from elements of the other deposit groups. An exponential decay function describes pattern formation time as a function of substrate temperature, which is independent from protein concentration. Patterns formation at 32 ∘C takes place up to 63% less time and preserves the structural characteristics of dried droplets in proteins formed at room temperature. Therefore, we argue that droplet evaporation at this substrate temperature could be an excellent candidate to make a more efficient diagnosis based on droplet evaporation of biofluids.

Epidemiological behavior and current forecast of syphilis in Mexico: increase in male population.

OBJECTIVES: Even when new cases of syphilis are notifiable since 1944, the Mexican National Epidemiological Surveillance System lacks information on the changes of the rate of case reports considering the geographic and demographic variables. Therefore, it is necessary to have evidence, with particular attention to the study of the epidemiological behavior by the identification of risk factors and groups. The objective of this study was to analyze the epidemiology, geographical distribution, and forecast of syphilis in Mexico. STUDY DESIGN: The design of the study was a secondary research of epidemiological databases. METHODS: A retrospective analysis of the national surveillance data (2007-2017) of acquired and congenital syphilis (CS) issued by the General Directorate of Epidemiology was performed. RESULTS: Of all cases, 34,998 and 1030 cases were reported for acquired syphilis (AS) and CS , respectively, reflecting an increasing trend in the whole country for both diseases. Cases and incidence of AS per year showed that, male gender presented an increase in reproductive age. Distribution of the rate of case reports is mostly commanded by the states in the extreme north (Gulf of California and northern Gulf of Mexico) and south (Gulf of southern Mexico and the Caribbean Sea). Likewise, the Seasonal Autoregressive Integrated Moving Average model was selected as the best-fit model for the forecast analysis. This model was used to forecast AS cases during 2018-2019. AS may have a slight fluctuation (on the rise) during the following 24 months. CONCLUSIONS: These findings underscore the importance of intensifying, as well as expanding screening and treatment in adult population, including men, who are not routinely benefiting from maternal and reproductive service-based syphilis screening and treatment.

Management of 3 Proliferating Pilar Tumors: Definition, Differential Diagnosis, and Treatment Options. / Experiencia en el manejo de 3 tumores pilares proliferantes: definición, diagnósticos diferenciales y alternativas terapéuticas.

A proliferating pilar tumor is a rare skin neoplasm that arises from the outer root sheath of a hair follicle. Presentation varies widely, as the tumor can be benign or malignant and has a high probability of recurring after excision. We report our experience managing 3 proliferating pilar tumors with different clinical presentations and pathology findings at Hospital de San José, Bogota, Colombia.

Evolution of incidence and geographical distribution of Chagas disease in Mexico during a decade (2007-2016).

Chagas disease, whose aetiological agent is the protozoan Trypanosoma cruzi, mainly occurs in Latin America. In order to know the epidemiology and the geographical distribution of this disease in Mexico, the present work analyses the national surveillance data (10 years) for Chagas disease issued by the General Directorate of Epidemiology (GDE). An ecological analysis of Chagas disease (2007-2016) was performed in the annual reports issued by the GDE in Mexico. The cases and incidence were classified by year, state, age group, gender and seasons. A national distribution map showing Chagas disease incidence was generated. An increase of new cases was identified throughout the country (rates from 0.37 to 0.81 per 100 000 inhabitants). Of the total cases accumulated (7388), the major cases were attributed to the states of Veracruz, Chiapas, Quintana Roo, Oaxaca, Morelos and Yucatán. The analysis per age groups and gender revealed that, in most age groups, the incidence was higher in the male population. The most number of cases was identified in spring and summer; a direct relationship between the environmental temperature increase and the number of new cases was identified. The analysis showed that the rate of Chagas disease increased presumably due to state programmes; the search for new cases has expanded and we speculate that the disease is associated with occupational activities. These results summarise and recall how important it is to implement the monitoring of Chagas disease mainly in south states of the Mexican Republic in order to implement strategies to control this disease.

Anogenital distance and reproductive outcomes in 9- to 11-year-old boys: the INMA-Granada cohort study.

BACKGROUND: Studies examining the association of anogenital distance (AGD), a biomarker of prenatal androgen exposure, with sexual development in children are lacking. OBJECTIVE: To assess the association between AGD measures and reproductive outcomes, including puberty onset, testicular volume, reproductive hormone levels, and urogenital malformations in boys aged 9-11 years. MATERIALS AND METHODS: A cross-sectional study was conducted among children belonging to the Spanish Environment and Childhood (INMA) Project, a population-based birth cohort study. The present sample included 279 boys for whom data were available on AGD, pubertal stage, testicular volume, and relevant covariates. Out of the boys with AGD data, 187 provided a blood sample for hormone analysis. AGD was measured from the center of the anus to the base of the scrotum. Pubertal development was assessed according to Tanner stage of genital development (G1-G5), and testicular volume was measured with an orchidometer. RESULTS: After adjusting for potential confounders, logistic regression analysis showed that AGD was positively associated with testicular volume but not with Tanner stage (>G1 vs. G1), serum hormone levels, or undescended testis. Regardless of their age, body mass index, and Tanner stage (G1 or >G1), boys with longer AGD showed increased odds of a testicular volume >3 mL (OR = 1.06, 95%CI = 1.00-1.19 per 10% increment in AGD; and OR = 3.14, 95%CI = 0.99-9.94 for AGD >42 mm vs. <33 mm). DISCUSSION: Longer AGD was associated with testicular growth, an indicator of gonadarche, but not with other reproductive outcomes. CONCLUSIONS: Although AGD was positively associated with testicular volume, it remains unclear whether AGD predicts testis size at puberty or is related to puberty onset.

Origin of the myotonic dystrophy type 1 mutation in Mexican population and influence of Amerindian ancestry on CTG repeat allelic distribution.

Myotonic dystrophy type 1 is caused by expansion of a CTG trinucleotide repeat situated in the DMPK gene. Worldwide genetic studies suggest a single or limited number of mutational events cause the disease. However, distribution of CTG alleles and disease incidence varies among ethnicities. Due to the great ethnic diversity of the Mexican population, the present study was aimed at analyzing the impact of different lineages in shaping the CTG-repeat allelic distribution in the contemporary Mexican-Mestizo population as well as to shed light on the DM1 ancestral origin. Distribution of CTG-repeat alleles was similar among Mestizo and Amerindian subpopulations with (CTG)11-13 being the most frequent alleles in both groups, which implies that Mexican-Mestizo allelic distribution has been modeled by Amerindian ancestry. We diagnosed a relatively high number of cases, consistent with the high frequency of large-normal alleles found in Mexican subpopulations. Haplotype analysis using various polymorphic-markers in proximity to DMPK gene indicates that a single founder mutation originates myotonic dystrophy type 1 in Mexico; however, Y-STR haplogroups data and the presence of pre-mutated and large normal alleles in Amerindians support the hypothesis that both European and Amerindian ancestral chromosomes might have introduced the disease to the Mexican population, which was further disseminated through mestizaje.

Cardiovascular Risk Factors and Carotid Intima-Media Thickness in a Colombian Population With Psoriasis. / Factores de riesgo cardiovascular y grosor de la íntima media carotídea en una población colombiana con psoriasis.

BACKGROUND AND OBJECTIVES: Psoriasis is now known to have a clear association with metabolic syndrome and its components. The aim of our study was to determine the prevalence of cardiovascular risk factors (CVRFs) and increased carotid intima-media thickness in psoriasis patients seen in the dermatology department of a quaternary hospital. MATERIAL AND METHODS: This was a descriptive cross-sectional study of psoriasis patients aged over 18 years seen in the dermatology department of Hospital de San José in Bogota, Colombia, between March and August, 2015. Directed medical history and physical examination were performed to detect CVRFs, laboratory studies to exclude metabolic syndrome, and ultrasound examination to measure carotid intima-media thickness. RESULTS: Forty patients with psoriasis were included in the study. The prevalence of the distinct CVRFs was 35% for systemic hypertension, 17.5% for dyslipidemia, 17.5% for smoking, and 10% for type 2 diabetes mellitus. A history of acute myocardial infarction was detected in 12.5% of patients. Metabolic syndrome was found in 20 patients (50%), and blood biochemistry revealed dyslipidemia in 32 patients (80%). Based on the Framingham score, the cardiovascular risk was low in 11 patients (31.4%), intermediate in 22 (62.8%), and high in 2 (5.7%). Mean (SD) carotid intima-media thickness was 0.7 (0.12) mm, with thickening observed in 6 patients (15%). CONCLUSIONS: This study provides evidence of the high prevalence of CVRFs in psoriasis patients and indicates the need for strict clinical control to monitor cardiovascular risk in this population.

Cervical cancer screening in rural mountainous Honduras: knowledge, attitudes and barriers.

INTRODUCTION: Because cervical cancer is the leading cause of cancer mortality in Honduras, this study assessed knowledge, attitudes and barriers to cervical cancer screening services by Papanicolaou smear (pap smear) for women in rural, remote Honduras served by Virginia Commonwealth University's Global Health and Health Disparities Program (GH2DP). METHODS: Two interviewers administered an institutional review board approved, 20 question survey by convenience sample methodology to adult female patients visiting GH2DP clinics in June 2014. A total of 146 surveys were completed. Of the respondents, 30 were living in La Hicaca, the largest and wealthiest village in the region, and 116 were living in surrounding, less affluent, villages. RESULTS: On average, women from La Hicaca had 2.9 children whereas women from surrounding villages had 4.3 children (p=0.0095). There were no significant differences between La Hicaca and surrounding villages in average respondent age, age of first intercourse and number of sexual partners. Seventy three percent (22/30) of women from La Hicaca and 60% (70/116) from surrounding villages reported undergoing cervical cancer screening by pap smear (p=0.1890). Eighty-two percent (18/22) of the respondents from La Hicaca and 84% (59/70) from surrounding villages were screened in the past two years (p=0.7846). The majority of the women from surrounding villages (81%, 57/70) and 23% (5/22) from La Hicaca traveled >1 h to receive a pap smear (p≤0.0001). Women from La Hicaca (86%, 19/22) were more likely to receive their pap smear results than women from surrounding villages (60%, 42/70) (p=0.0225). Although 17% (5/30) of respondents from La Hicaca and 11% (13/116) (p=0.4175) from surrounding villages were aware of the cause of cervical cancer, 60% (18/30) of women in La Hicaca and 82% (95/116) in surrounding villages (p=0.0106) believed it is preventable. Of the 106 women (73%) who had heard of cervical cancer screening, only 92 women (63%) had been screened (p<0.0001). Women undergoing cervical cancer screening were more likely to believe that cervical cancer is preventable (n=78, p=0.0054). The most common screening barriers were lack of awareness and fear (19/54, 35%; 15/54, 28%). CONCLUSIONS: Although yearly screening services are available in this community, knowledge and access barriers exist for increased implementation. Notification of pap smear results is suboptimal. These findings will guide regional and collaborative effort to improve cervical cancer screening services.

Characterization of a Dual Rac/Cdc42 Inhibitor MBQ-167 in Metastatic Cancer.

The Rho GTPases Rac (Ras-related C3 botulinum toxin substrate) and Cdc42 (cell division control protein 42 homolog) regulate cell functions governing cancer malignancy, including cell polarity, migration, and cell-cycle progression. Accordingly, our recently developed Rac inhibitor EHop-016 (IC50, 1,100 nmol/L) inhibits cancer cell migration and viability and reduces tumor growth, metastasis, and angiogenesis in vivo Herein, we describe MBQ-167, which inhibits Rac and Cdc42 with IC50 values of 103 and 78 nmol/L, respectively, in metastatic breast cancer cells. Consequently, MBQ-167 significantly decreases Rac and Cdc42 downstream effector p21-activated kinase (PAK) signaling and the activity of STAT3, without affecting Rho, MAPK, or Akt activities. MBQ-167 also inhibits breast cancer cell migration, viability, and mammosphere formation. Moreover, MBQ-167 affects cancer cells that have undergone epithelial-to-mesenchymal transition by a loss of cell polarity and inhibition of cell surface actin-based extensions to ultimately result in detachment from the substratum. Prolonged incubation (120 hours) in MBQ-167 decreases metastatic cancer cell viability with a GI50 of approximately 130 nmol/L, without affecting noncancer mammary epithelial cells. The loss in cancer cell viability is due to MBQ-167-mediated G2-M cell-cycle arrest and subsequent apoptosis, especially of the detached cells. In vivo, MBQ-167 inhibits mammary tumor growth and metastasis in immunocompromised mice by approximately 90%. In conclusion, MBQ-167 is 10× more potent than other currently available Rac/Cdc42 inhibitors and has the potential to be developed as an anticancer drug, as well as a dual inhibitory probe for the study of Rac and Cdc42. Mol Cancer Ther; 16(5); 805-18. ©2017 AACR.

Bioguided fractionation from Solanum elaeagnifolium to evaluate toxicity on cellular lines and breast tumor explants / Fraccionamiento biodirigido de Solanum elaeagnifolium para evaluar la toxicidad en líneas celulares y explantes de tumor de mama

Background: Bioactive compounds from the fruit of S. elaeagnifolium were isolated since could be highly potential source to develop functional foods or pharmaceutical products. Objectives: In this study a bioguided fractionation of the methanolic extract from S. elaeagnifolium fruit was carried out to evaluate their cytotoxicity and antitumoral potential on several cell lines and breast tumor explants, respectively. Methods: Microdilution method with A. salina was used to isolate bioactive compounds. Fractionation was performed by vacuum liquid chromatography, and the monitoring from fractions was done by thin layer chromatography. The effect of the fractions on viability in Vero, HeLa, and MCF-7 cells was assessed using WST-1 assay, whereas in breast tumor explants was evaluated by Alamar blue assay. A qualitative phytochemical analysis was performed to partially identify the compounds contained in the fractions and a spectroscopic characterization by RP-HPLC-MS was done to identify the group of compounds responsible for the effect on the cell lines and the mammary explants. Results: Several fractions were isolated from the fruit of S. elaeagnifolim. Notwithstanding, the FVLC7 showed a higher activity in A. salina assay. This fraction reduced the viability at 39 ± 1.67, 15.05 ± 0.09 and 66.10 ± 4 % in Vero, HeLa and MCF-7 cells, at 100 mg/mL, respectively. On the other hand, showed an effect in breast tumor explants obtained from a patient in remission. Qualitative phytochemical analysis showed that FVLC7 contains alkaloids, coumarins, and sesquiterpene lactones. Characterization by RP-HPLC-MS detected quinic acid, chlorogenic acid, dicaffeoylquinic acid as well as presence of an alkaloid. Conclusion: On this basis, our results suggest that cytotoxic effect of FVLC7 isolated from the fruit of S. elaeagnifolium could be mediated by quinic, chlorogenic, and dicaffeoylquinic acids

Antecedentes: Los compuestos bioactivos del fruto de S. elaeagnifolium fueron aislados ya que representan compuestos con un alto potencial para el desarrollo de alimentos funcionales o productos farmacéuticos. Objetivos: En este estudio se realizó un fraccionamiento biodirigido de un extracto metanólico de frutos de S. elaeagnifolium para evaluar la citotoxicidad y el potencial antitumoral en los explantes de tumor de mama. Métodos: Se utilizó el método de microdilución con A. salina para aislar los compuestos bioactivos. El fraccionamiento se realizó mediante cromatografía de líquido a vacío, y la monitorización de las fracciones se realizó por cromatografía en capa fina. La viabilidad de las fracciones en las líneas de células Vero, HeLa y MCF-7 se evaluó usando el ensayo WST-1, mientras que en los explantes tumorales de mama se evaluaron mediante el ensayo azul de Alamar. Así mismo, se realizó un análisis fitoquímico cualitativo para identificar parcialmente los compuestos que contenían las fracciones y una caracterización espectroscópica por RPHPLC-MS de los compuestos responsables del efecto sobre las líneas celulares y los explantes mamarios. Resultados: De todas las fracciones aisladas de S. elaeagnifolium, la fracción FVLC7 (100 µg/mL) tuvo la actividad más alta en el ensayo de A. salina. Por otra parte, redujo la viabilidad un 39 ± 1,67, 15,05 ± 0,09 y 66,10 ± 4,44% en las células Vero, HeLa y MCF-7, respectivamente. Esta fracción mostró un efecto en los explantes de tumor de mama obtenidos de un paciente en remisión. El análisis fitoquímico cualitativo reveló que la FVLC7 contiene alcaloides, cumarinas y lactonas sesquiterpénicas. La caracterización por RP-HPLC-MS detectó ácido quínico, ácido clorogénico, ácido dicafeoilquínico así como presencia de un alcaloide. Conclusión: Nuestros resultados sugieren que el efecto tóxico de la fracción FVLC7 aislada del fruto de S. elaeagnifolium podría deberse a los ácidos quínico, clorogénico y dicafeoilquínico.

Evaluación de una intervención educativa de enfermería dirigida a cuidadores principales de pacientes crónicos / Evaluation of an educational program for caregivers of patients with chronic diseases / Avaliação de uma intervenção educativa de enfermaria para cuidadores primários de pacientes crônicos

Es frecuente que los cuidadores principales de enfermos crónicos se conviertan en el "enfermo invisible", en la medida en que la atención y el \r\ncuidado están mayormente enfocados en el paciente, lo cual vulnera aspectos físicos, emocionales, espirituales y económicos de la persona que \r\ncuida. El objetivo de este estudio descriptivo con enfoque cualitativo es evaluar los resultados de implementar un programa educativo de inter\r\n-\r\nvención dirigido a 19 cuidadores principales de personas con enfermedad crónica, en seis delegaciones de la ciudad de Toluca, Estado de México. El estudio se desarrolló en tres etapas: diagnóstico, intervención y evaluación. Para impartir el programa educativo se realizaron visitas domiciliarias \r\nque se registraron en la bitácora de campo. \r\nEl programa denominado Cuidando a Cuidadores, se basa en los tres indicadores propuestos por \r\nNkongho: conocimiento, valor y paciencia. Consta de tres módulos, y en cada uno se realizaron tres tallerescon los 19 cuidadores,previo consen\r\n-\r\ntimiento informado. Los participantes expresaron haber adquirido conocimientos necesarios para el cuidado de su familiar; las dinámicas les \r\npermitieron reconocer fortalezas, debilidades, miedos, inseguridades y frustraciones; además, manifestaron sentirse satisfechos con el acom\r\n-\r\npañamiento y guía del equipo de salud que participó. Se puede afirmar que ser cuidador principal de un enfermo crónico es una experiencia \r\nque transforma la vida y requiere conocimiento, valor y paciencia para ejercer su tarea de manera hábil; esto puede incrementarse si se recibe \r\norientación por parte de los profesionales de enfermería

Regularly, the primary caregivers of chronically ill patients \r\nbecome the "invisible ill", to the extent that the attention and \r\ncare are mostly focused on the sick patiente, violating physical, \r\nemotional, spiritual and economic aspects of the caregiver. This \r\nproject analizes the results obtained from the implementation \r\nof an educational intervention program aimed at 19 primary \r\ncaregivers of people with chronic disease, in six delegations \r\nfrom the city of Toluca, State of Mexico. It was a descriptive \r\nstudy with a qualitative methodological approach. It was \r\ncarried out in three stages: diagnosis, intervention and evalua\r\n-\r\ntion. In order to provide the educational program, home visits \r\nwere performed using the log field. The program consisted \r\nof three modules, being imparted in workshops to the 19 \r\ncaregivers, with informed consent prior to the program. The \r\nresults were the following: Caregivers expressed that they had \r\nacquired knowledge required for the care of their family, the \r\ndynamics allowed them to recognize strengths, weaknesses, \r\nfears, insecurities and frustrations; they said they were satis\r\n-\r\nfied with the support and guidance of the health team that \r\nparticipated. It can be said that to be a primary caregiver for a \r\nchronically ill person is an experience that transforms life and \r\nrequires knowledge, courage and patience to perform their \r\nduties skillfully; these gratification may also be increased if you \r\nreceive guidance from nurses.

Muitas vezes, os cuidadores primários de pacientes crônicos se \r\ntornam o "paciente invisível", na medida em que a atenção e \r\nos cuidados são principalmente focados no doente, violando \r\naspectos físicos, emocionais, espirituais e econômicos do \r\ncuidador. Este projeto aborda os resultados obtidos na imple\r\n-\r\nmentação de um programa de intervenção educacional \r\nvoltado para 19 cuidadores primários de pessoas com doença \r\ncrónica, em seis delegações da cidade de Toluca, Estado do \r\nMéxico. O estudo era realizado em três etapas: diagnóstico, \r\nintervenção e avaliação. A fim de orientar sobre o programa \r\neducativo, foram realizadas visitas domiciliares, utilizando \r\no diário de campo. O programa consistiu de três módulos, \r\nconferindo-se oficinas aos 19 cuidadores, com prévio consen\r\n-\r\ntimento informado. Os cuidadores expressaram ter adquirido \r\nconhecimentos necessários para o cuidado de seu familiar \r\ne as dinâmica lhes permitiram reconhecer forças, fraquezas, \r\nmedos, inseguranças e frustrações. Eles disseram que estavam \r\nsatisfeitos com o apoio e orientação da equipe de saúde que \r\nparticipou. Pode-se dizer que ser o cuidador primário de um \r\npaciente crónico é uma experiência que transforma a vida e \r\nexige conhecimento, coragem e paciência para exercer as suas \r\nfunções com habilidade, podendo se aperfeiçoar se receber a \r\norientação de profissionais de enfermagem.

Prosexual Effect of Chrysactinia mexicana A. Gray (Asteraceae), False Damiana, in a Model of Male Sexual Behavior.

Chrysactinia mexicana A. Gray (Asteraceae) and Turnera diffusa Willd (Turneraceae) are employed in traditional medicine as aphrodisiacs; however, there is no scientific evidence supporting the prosexual properties of C. mexicana. The aim of this study was to determine whether an aqueous extract of C. mexicana (Cm) stimulates rat male sexual behavior in the sexual exhaustion paradigm. Sexually exhausted (SExh) male rats were treated with Cm (80, 160, and 320 mg/kg), an aqueous extract of T. diffusa (Td), or yohimbine. The sexual exhaustion state in the control group was characterized by a low percentage of males exhibiting mounts, intromissions, and ejaculations and no males demonstrating mating behavior after ejaculation. Cm (320 mg/kg), Td, or yohimbine significantly increased the proportion of SExh rats that ejaculated and resumed copulation after ejaculation. In males that exhibited reversal of sexual exhaustion, Cm (320 mg/kg) improved sexual performance by reducing the number of intromissions and shrinking ejaculation latency. The effects of treatments on sexual behavior were not related with alterations in general locomotion. In conclusion, the prosexual effects of Cm, as well as those of Td, are established at a central level, which supports the traditional use of C. mexicana for stimulating sexual activity.

Experience with Guillain-Barré syndrome in a neurological Intensive Care Unit. / Experiencia del síndrome de Guillain-Barré en una Unidad de Cuidados Intensivos neurológicos.

INTRODUCTION: Guillain-Barré syndrome, an acute polyradiculoneuropathy that presents with weakness and areflexia, is the most common cause of acute flaccid paralysis. In certain patients, respiratory failure is secondary to this disorder, eventually causing patients to require mechanical ventilation and experience additional complications due to diminished respiratory support and related mobility limitations. Prognoses for most of these cases are positive; treatment consists of basic support combined with plasmapheresis or administration of immunoglobulins. OBJECTIVE: This study sought to describe the socio-demographic, clinical, laboratory and neurophysiological characteristics of patients with Guillain-Barré syndrome who were hospitalised in the Intensive Care Unit of the Neurological Institute of Colombia between 2006 and 2012. METHODOLOGY: This study presents a case series. RESULTS: We surveyed 25 patients (32% female and 68% male) with Guillain-Barré syndrome and an average age of 54 years. Sixty per cent of these patients were admitted between days 3 and 7 after symptom onset; 64% had a history of respiratory infection and 20% had a history of intestinal infection. In addition, 84% of the patients presented with albuminocytological dissociation. We observed the following clinical subtypes of Guillain-Barré syndrome: inflammatory demyelinating polyneuropathy in 32%, acute motor-sensory axonal neuropathy in 28%, acute motor axonal neuropathy in 28%, and Miller Fisher syndrome in 12%. CONCLUSIONS: In this descriptive study of a group of critical care patients with GBS, results depended on patients' clinical severity at time of admission. Our findings are similar to results published in the international literature.

Opinión de egresados en enfermería sobre la congruencia de los contenidos curriculares con los requerimientos laborales / Nursing graduates opinion on the congruency of curricular contents and working requirements / Opinião de egressos em enfermagem sobre a congruência dos conteúdos curriculares com os requerimentos de trabalho

Los perfiles profesionales de los egresados en área de la salud, y en particular de enfermería, requieren ajustarse a la compleja interacción que demandan las necesidades sociales y las exigencias del mercado laboral. Esto crea la necesidad de identificar fortalezas y debilidades durante su formación profesional a través de la sistematización de estudios de egresados, los cuales orientan a la mejora continua de los programas educativos, para facilitar la incorporación y desarrollo de los(as) egresados(as) en el ámbito laboral. Objetivo Describir la opinión de los egresados de enfermería de la Universidad Autónoma de Tlaxcala sobre la congruencia de los contenidos curriculares y requerimientos laborales al ofrecer el cuidado profesional. Material y métodos Estudio descriptivo, transversal. Incluyó 84 egresados de 3 generaciones, seleccionados por muestreo simple aleatorio. Se empleó un cuestionario adecuado y estructurado con base en la propuesta de la Asociación Nacional de Universidades e Instituciones de Educación Superior de 1998, organizado en 6 apartados. Resultados El 87% opinan que los contenidos curriculares son congruentes con las actividades que realizan al ofrecer el cuidado, el 86% perciben satisfacción de sus conocimientos, el 85% se consideran bien aceptados laboralmente, el 95% aprecian relevante su desempeño laboral, el 66% son contratados en 2.° y 3.er nivel de atención en el sector salud. Conclusiones Los egresados consideran que existe congruencia entre los contenidos curriculares con el desempeño profesional; se ubican mayormente en áreas asistenciales del 2.° y 3.er nivel de atención, y perciben satisfacción de los conocimientos adquiridos y aceptación laboral.

Professional profiles of graduates from the health areas, and particularly those from nursing, require adjustments in order to meet the complex interactions which social needs and labor market characteristics demand. This situation creates the need to identify strengths and weaknesses in the formation of these graduates. By systematizing and continuously improving their studies, a successful incorporation and development into the complex labor markets is more likely to be achieved. Objective To describe the opinion which the nursing graduates from the Tlaxcala Autonomous University have on the congruency of the curricular contents and the working requirements while providing professional care. Materials and methods Descriptive and transversal study which included 84 graduates from 3 generations who were selected by random simple sampling, and which used a structured and convenient questionnaire following the 1998 ANUIES proposal organized in 6 dominions. Results 87% of the participants opined the curricular contents are congruent with the activities they do while providing care; 86% perceive satisfaction with their knowledge; 85% consider they are well fit regarding labor; 95% consider their working performance relevant; 66% are hired into the Health Sector's 2nd and 3rd levels of attention. Conclusions There is congruency between the curricular contents and their professional performance; the graduates are mainly located within the assisting areas of the 2nd and 3rd levels of attention; they feel satisfied with their knowledge and perceive labor acceptance.

Os perfis profissionais dos egressos da área de saúde, e no particular da enfermagem, requerem se ajustar à complexa interação que demandam as necessidades sociais e as exigências do mercado de trabalho, isto cria a necessidade de identificar fortalezas e as fraquezas durante sua formação profissional, a través da sistematização de estudos de egressos, os quais dirigem a melhora contínua dos programas educativos, para facilitar a incorporação e desenvolvimento dos egressos no contexto de trabalho. Objetivo Descrever a opinião dos egressos de Enfermagem da Universidade Autônoma de Tlaxcala sobre a congruência dos conteúdos curriculares e requerimentos de trabalho ao oferecer o cuidado profissional. Material e métodos Estudo descritivo, transversal, incluiu 84 egressos de 3 gerações, escolhidos pela amostra simples aleatória, empregando um questionário adequado e estruturado com base na proposta da ANUIES de 1998 em 6 secções. Resultados 87% acharam que os conteúdos curriculares são congruentes com as atividades que realizam ao oferecer o cuidado, 86% percebe satisfação de seus conhecimentos, 85% se considera bem aceito no trabalho, 95% percebe relevante seu desempenho no trabalho, 66% são contratados em segundo e terceiro nível de atenção no setor de saúde. Conclusões Existe congruência entre os conteúdos curriculares com o desempenho profissional; os egressos situam-se principalmente nas áreas assistenciais do segundo e terceiro nível de atenção, percebem satisfação dos conhecimentos adquiridos e aceitação no trabalho.