Sexual dimorphism in colorectal cancer: molecular mechanisms and treatment strategies.

INTRODUCTION: Sexual dimorphism significantly influences cancer incidence and prognosis. Notably, females exhibit a lower risk and favorable prognosis for non-reproductive cancers compared to males, a pattern observable beyond the scope of risk behaviors such as alcohol consumption and smoking. Colorectal cancer, ranking third in global prevalence and second in mortality, disproportionately affects men. Sex steroid hormones, particularly estrogens and androgens, play crucial roles in cancer progression, considering epidemiological in vivo and in vitro, in general estrogens imparting a protective effect in females and androgens correlating with an increasing risk of colorectal cancer development. MAIN BODY: The hormonal impact on immune response is mediated by receptor interactions, resulting in heightened inflammation, modulation of NF-kB, and fostering an environment conducive to cancer progression and metastasis. These molecules also influence the enteric nervous system, that is a pivotal in neuromodulator release and intestinal neuron stimulation, also contributes to cancer development, as evidenced by nerve infiltration into tumors. Microbiota diversity further intersects with immune, hormonal, and neural mechanisms, influencing colorectal cancer dynamics. A comprehensive understanding of hormonal influences on colorectal cancer progression, coupled with the complex interplay between immune responses, microbiota diversity and neurotransmitter imbalances, underpins the development of more targeted and effective therapies. CONCLUSIONS: Estrogens mitigate colorectal cancer risk by modulating anti-tumor immune responses, enhancing microbial diversity, and curbing the pro-tumor actions of the sympathetic and enteric nervous systems. Conversely, androgens escalate tumor growth by dampening anti-tumor immune activity, reducing microbial diversity, and facilitating the release of tumor-promoting factors by the nervous system. These findings hold significant potential for the strategic purposing of drugs to fine-tune the extensive impacts of sex hormones within the tumor microenvironment, promising advancements in colorectal cancer therapies.

Convergence between helminths and breast cancer: intratumoral injection of the excretory/secretory antigens of the human parasite Toxocara canis (EST) increase lung macro and micro metastasis.

Introduction: Worldwide, breast cancer is the most important cancer in incidence and prevalence in women. Different risk factors interact to increase the probability of developing it. Biological agents such as helminth parasites, particularly their excretory/secretory antigens, may play a significant role in tumor development. Helminths and their antigens have been recognized as inducers or promoters of cancer due to their ability to regulate the host's immune response. Previously in our laboratory, we demonstrated that chronic infection by Toxocara canis increases the size of mammary tumors, affecting the systemic response to the parasite. However, the parasite does not invade the tumor, and we decided to study if the excretion/secretion of antigens from Toxocara canis (EST) can affect the progression of mammary tumors or the pathophysiology of cancer which is metastasis. Thus, this study aimed to determine whether excretion/secretion T. canis antigens, injected directly into the tumor, affect tumor growth and metastasis. Methods: We evaluated these parameters through the monitoring of the intra-tumoral immune response. Results: Mice injected intratumorally with EST did not show changes in the size and weight of the tumors; although the tumors showed an increased microvasculature, they did develop increased micro and macro-metastasis in the lung. The analysis of the immune tumor microenvironment revealed that EST antigens did not modulate the proportion of immune cells in the tumor, spleen, or peripheral lymph nodes. Macroscopic and microscopic analyses of the lungs showed increased metastasis in the EST-treated animals compared to controls, accompanied by an increase in VEGF systemic levels. Discussion: Thus, these findings showed that intra-tumoral injection of T. canis EST antigens promote lung metastasis through modulation of the tumor immune microenvironment.

Sexual Dimorphism in the Physiopathology and Immune Response during Acute Toxocara canis Infection.

BACKGROUND: Toxocara canis (T. canis) is a helminth parasite of zoonotic and veterinary health significance that causes the disease known as Toxocariasis. This disease has been associated with conditions of poverty, especially in tropical climate zones throughout the world. Although it rarely causes important clinical manifestations, T. canis can lead to blindness, meningoencephalitis, or other nervous manifestations in humans. Moreover, some studies show its importance in the development of tumor growth, which have been associated with the parasite's ability to modulate the host's immune response. While different studies have evaluated the immune response during this disease, currently, there are no studies where the infection is analyzed from the perspective of sexual dimorphism. METHODS: To evaluate sex differences in susceptibility, we analyzed lesions and parasite loads in lung and liver at 7 days post-infection. In addition, immune cell subpopulations were analyzed in spleen, mesenteric and peripheral lymph nodes. Finally, the production of cytokines and specific antibodies were determined in the serum. Statical analyses were performed using a Two-way ANOVA and a post-hoc Bonferroni multiple comparison test. RESULTS: Female rats had a higher number of larvae in the liver, while male rats had them in the lungs. The percentages of immune cells were evaluated, and in most cases, no significant differences were observed. Regarding the cytokines production, infection can generate a decrease in Th1 such as IL-1ß in both sexes and IL-6 only in females. In the case of Th2, IL-4 increases only in infected males and IL-5 increases in males while decreasing in females due to the effect of infection. IL-10 also decreases in both sexes as a consequence of the infection, and TGF-ß only in females. Finally, the infection generates the production of antibodies against the parasite, however, their quantity is lower in females. CONCLUSIONS: This study demonstrates that T. canis infection is dimorphic and affects females more than males. This is due to a polarization of the inadequate immune response, which is reflected as a higher parasite load in this sex.

Impact of Chronic Moderate Exercise on Immune Cells and Cytokine Levels in Rats: Focus on the Endocannabinergic Pathway.

Although the modulation of immunity by exercise has been a long-studied paradigm, the molecular pathways connecting the two are still not fully understood. Regular moderate aerobic exercise is associated with improved health and directly impacts the immune system by changing the proportion of cell subpopulations, their function, and interleukin production. The endocannabinoid system has gained importance as an immune modulator, affected by moderate aerobic promoting the production of endocannabinoids, which are ligands of the cannabinoid receptors (CBRs) expressed on the surface of all immune cells. Our group previously reported a reduction of lymphocytic populations in the spleen of chronically exercised rats, accompanied by an increase in CBR expression. Given the complex and compartmentalized nature of the immune system, we decided to study the effects of chronic exercise on the proportion of peripheral blood mononuclear cells, serum interleukins, and the expression of CBRs on these cells. Overall, our results indicate that chronic exercise decreases the proportion of T helper and Tγδ cells but increases the expression of cannabinoids (CBR1) on T helper and natural killer cells, and the production of interleukins, including IL-1ß, interferon-gamma, tumor necrosis factor-alpha, IL-10, and IL-4, suggesting higher reactivity and efficiency from the immune system conferred by exercise.

Mature cystic teratoma overlapping with giant serous cystadenoma of the ovary: A case report.

Ovarian lesions represent a diagnostic challenge for the radiologist and should be approached according to the patient's age, menstrual cycle, and imaging characteristics. These lesions can be cystic, mixed, or solid-predominant structures. Generally, the occurrence of benign lesions surpasses that of malignant ones at a ratio of 3:1. However, within infantile and juvenile age groups, this becomes an infrequent occurrence, making up only about 5% of ovarian tumor cases. This case report sheds light on a unique scenario involving a pediatric patient who harbored 2 benign tumors simultaneously: a mature cystic teratoma and a serous cystadenoma.

Comparing iDNA from mosquitoes and flies to survey mammals in a semi-controlled Neotropical area.

Ingested-derived DNA (iDNA) from insects represents a powerful tool for assessing vertebrate diversity because insects are easy to sample, have a diverse diet and are widely distributed. Because of these advantages, the use of iDNA for detecting mammals has gained increasing attention. Here we aimed to compare the effectiveness of mosquitoes and flies to detect mammals with a small sampling effort in a semi-controlled area, a zoo that houses native and non-native species. We compared mosquitoes and flies regarding the number of mammal species detected, the amount of mammal sequence reads recovered, and the flight distance range for detecting mammals. We also verified if the combination of two mini-barcodes (12SrRNA and 16SrRNA) would perform better than either mini-barcode alone to inform local mammal biodiversity from iDNA. To capture mosquitoes and flies, we distributed insect traps in eight sampling points during 5 days. We identified 43 Operational Taxonomic Units from 10 orders, from the iDNA of 17 mosquitoes and 46 flies. There was no difference in the number of species recovered per individual insect between mosquitoes and flies, but the number of flies captured was higher, resulting in more mammal species recovered by flies. Eight species were recorded exclusively by mosquitoes and 20 by flies, suggesting that using both samplers would allow a more comprehensive screening of the biodiversity. The maximum distance recorded was 337 m for flies and 289 m for mosquitoes, but the average range distance did not differ between insect groups. Our assay proved to be efficient for mammal detection, considering the high number of species detected with a reduced sampling effort.

Validação de conteúdo de uma tecnologia sobre cateter de inserção periférica em unidades neonatais / Content validation of a technology on peripherally inserted central catheter in neonatal units / Validación de contenido de una tecnología sobre catéter de inserción periférica en unidades neonatales

Objetivo: Buscou-se validar uma tecnologia do tipo e-book sobre cateter de inserção periférica para unidades neonatais. Método: Trata-se de uma pesquisa do tipo metodológico, que inferiu como critérios de inclusão enfermeiros neonatologista total de 15 juízes com comprovada experiência prática e científica na área do estudo, com pelo menos 2 anos de atuação profissional e no mínimo de 2 anos em habilitação comprovada por certificado de inserção de catete de inserção periférica, sendo identificados pelo currículo lattes. Os critérios de informações do instrumento foram avaliados por enfermeiros, obtendo um Índice de Validade de Conteúdo mínimo de 90,5% dos conteúdos na primeira rodada de validação. Resultado: Demonstraram que a estratégia metodológica permitiu a construção de conteúdos que representam a necessidade do enfermeiro e demais profissionais na manipulação do cateter. Conclusão: A utilização de tecnologias educacionais facilita o processo de aquisição de conhecimento técnico científica para melhoria assistencial na segurança ao recém-nascido.(AU)

Objective: To validate an e-book technology on peripherally inserted central catheter in neonatal units. Methods: This is a methodological research, thus, a total of 15 expert judges participated in the study. The inclusion criteria were defined as being a nurse, having a specialization in neonatology, 2 years of professional experience in a neonatal intensive care unit and at least 2 years of training in a peripherally inserted central catheter. Results: The instrument's criteria were evaluated by nurses, obtaining approval of 90.5% and Cronbach's alpha 0.915, high reliability among all contents in the first round of validation. The results showed that the methodological strategy allowed the construction of contents that represent the needs of nurses and other professionals in handling the catheter. Conclusion: The use of educational technologies facilitates the process of acquiring scientific technical knowledge to improve care in the safety of newborns.(AU)

Objetivo: validar una tecnología de libro electrónico sobre catéter central de inserción periférica en unidades neonatales. Esta es una investigación metodológica. Un total de 15 jueces expertos participaron en el estudio. Como criterios de inclusión: ser enfermero, tener especialidad en neonatología, 2 años de experiencia profesional en unidad de cuidados intensivos neonatales y al menos 2 años de calificación en catéter central de inserción periférica. Los criterios del instrumento fueron evaluados por enfermeros, obteniendo aprobación del 90,5% y alfa de Cronbach de 0,915, alta confiabilidad entre todos los contenidos en la primera ronda de validación. Los resultados mostraron que la estrategia metodológica permitió la construcción de contenidos que representan las necesidades de los enfermeros y otros profesionales en el manejo del catéter. El uso de tecnologías educativas facilita el proceso de adquisición de conocimientos técnicos y científicos para mejorar la atención en términos de seguridad para los recién nacidos.(AU)

Toxic and antigenic characterization of Peruvian Micrurus surinamensis coral snake venom.

Micrurus surinamensis is a semi-aquatic coral snake found in primary forest region and can cause relevant human accidents. In this work we investigated the toxic and antigenic activities of the Peruvian Micrurus surinamensis venom (MsV). We found that MsV show hyaluronidase activity but lack LAAO and PLA2 enzymatic activities. Interestingly, MsV induce edematogenic responses but cannot cause nociceptive effects. Furthermore, MsV can reduce in vitro cell viability in MGSO-3 cell line derived from human breast cancer tissue. To evaluate its antigenic potential, rabbits were immunized with MsV, which proved to be immunogenic. ELISA, immunobloting and in vivo neutralization assays demonstrated that the specific rabbit anti-MsV antivenom is more efficient than the therapeutic Brazilian antivenom in recognizing and neutralizing the lethal activity of MsV. MsV differs in protein profile and biological activities from M. frontalis venom (MfV), used as control, which impairs its recognition and neutralization by Brazilian therapeutic anti-elapidic antivenom. We performed a SPOT immunoassay for the identification of B-cell linear epitopes in the main toxins described for MsV targeted by the elicited neutralizing antibodies previously produced. A membrane containing 15-mer peptides representing the sequences of five 3TFxs and five PLA2s was produced and probed with anti- MsV antibodies. Results revealed important regions in 3FTx toxins for venom neutralization. Identifying the main MsV components and its biological activities can be helpful in guiding the production of antivenoms and in the optimization of treatment for coral snake envenomation in Brazil.

Acute appendicitis after closed abdominal trauma: A case report.

We present the case of a 14-year-old female patient with no clinical history who was admitted due to an impact on the abdomen and pelvis with a soccer ball during a match and who developed acute post-traumatic appendicitis. Acute appendicitis is one of the most common causes of acute abdomen. The diagnosis is mainly clinical and based on definitive history; however, the images can be decisive for the diagnosis. The etiology of acute appendicitis is well-reported in the literature, with the traumatic mechanism being one of the etiologies described. Acute post-traumatic appendicitis is rare; a timely diagnosis requires a high index of suspicion, a careful history, and a physical examination. Imaging with ultrasound or computed tomography is recommended if there is a discrepancy between the medical history and physical examination.

Prevalencia de alteraciones musculoesqueléticas en pacientes que asisten al Centro de Salud de la provincia del Guayas / Prevalence of musculoskeletal disorders in patients attending the Health Center of the province of Guayas / Prevalência de perturbações músculo-esqueléticas em doentes que frequentam o Centro de Saúde da província de Guayas

Los Trastornos musculoesqueléticos (TME) abarcan más de 150 patologías que pueden afectar al sistema locomotor, siendo considerado por la Organización Mundial de la Salud (OMS) en el año 2021 como el principal factor para la incapacidad laboral y de requerir rehabilitación. Estas lesiones se presentan de forma repentina y pueden llegar a ser enfermedades crónicas, las cuales pueden afectar de una manera social, económica y laboral. Objetivo. Establecer la prevalencia de las alteraciones musculoesqueléticas más frecuentes, asociadas a incapacidad laboral en pacientes que asisten al Centro de Salud en la provincia del Guayas. Materiales y métodos. Este trabajo de investigación tiene un alcance descriptivo observacional, de enfoque cuantitativo con un diseño no experimental de corte transversal, el mismo que se apoyó en una base de datos de tipo numérico. Resultados. Obteniendo como resultado una mayor prevalencia en el dolor articular con un 32,49%, seguido de lumbalgia 14,13%, patologías artrósicas 13.73% y dorsalgia 2,62%. Conclusiones. Al realizar la comparación entre varios estudios se pudo determinar que la edad más frecuente para presentar alteraciones musculoesqueléticas es de los 30 a 70 años de edad dentro de la población laboral, siendo a mayor edad, mayor prevalencia a incapacidad laboral.

Musculoskeletal disorders (MSDs) encompass more than 150 pathologies that can affect the locomotor system, being considered by the World Health Organization (WHO) in the year 2021 as the main factor for work incapacity and requiring rehabilitation. These injuries occur suddenly and can become chronic diseases, which can affect socially, economically and occupationally. Objective. To establish the prevalence of the most frequent musculoskeletal alterations associated with incapacity for work in patients attending the Health Center in the province of Guayas. Materials and methods. This research work has a descriptive observational scope, with a quantitative approach and a non-experimental cross-sectional design, which was supported by a numerical database. Results. Obtaining as a result a higher prevalence of joint pain with 32.49%, followed by low back pain 14.13%, osteoarthritic pathologies 13.73% and dorsalgia 2.62%. Conclusions. When comparing several studies, it was possible to determine that the most frequent age for presenting musculoskeletal alterations is between 30 and 70 years of age within the working population, the older the age, the higher the prevalence of incapacity for work.

As doenças musculoesqueléticas (MSDs) abrangem mais de 150 patologias que podem afetar o sistema locomotor, sendo consideradas pela Organização Mundial da Saúde (OMS) no ano 2021 como o principal fator de incapacidade de trabalho e que necessitam de reabilitação. Essas lesões ocorrem repentinamente e podem se tornar doenças crônicas, que podem afetar social, econômica e profissionalmente. Objetivo. Estabelecer a prevalência dos distúrbios musculoesqueléticos mais frequentes associados à incapacidade de trabalho em pacientes que frequentam o Centro de Saúde na província de Guayas. Materiais e métodos. Este trabalho de pesquisa tem um escopo observacional descritivo, com uma abordagem quantitativa e um projeto transversal não-experimental, que foi apoiado por um banco de dados numérico. Resultados. Obtendo como resultado uma maior prevalência de dores articulares com 32,49%, seguida de dores lombares baixas 14,13%, patologias artríticas 13,73% e dores nas costas 2,62%. Conclusões. Uma comparação entre vários estudos mostrou que a idade mais frequente para apresentar distúrbios musculoesqueléticos é entre 30 e 70 anos de idade na população trabalhadora, sendo que quanto maior a idade, maior a prevalência de incapacidade para o trabalho.

Intratumoral Treatment with 5-Androstene-3ß, 17α-Diol Reduces Tumor Size and Lung Metastasis in a Triple-Negative Experimental Model of Breast Cancer.

Breast cancer treatment failure is related to low response rates, high costs, and long-term toxicities. Thus, it is necessary to find less toxic, cheaper, and more effective treatments. In situ administration ensures drug delivery to tumor cells and decreases systemic toxic effects. The androstene-3ß, 17α-diol (α-AED) reduces breast tumor cell proliferation and is an ideal candidate to treat mammary tumors. This study aims to identify the in vitro and in vivo effects of α-AED on a triple-negative mammary tumor model. An in vitro biphasic steroid effect was observed in mouse and human mammary tumor cells treated with α-AED. In this sense, cells treated with higher doses (100 and 200 µM) showed an antiproliferative effect. The α-AED administrated intratumorally reduced average tumor weight and increased the percentage of natural killer cells (NK), plasmatic, and plasmablast cells in mice tumors. Of note, VEGF levels in all α-AED-treated tumors was lower than in the control and vehicle groups. The tumor in situ increased response was reflected systemically by higher anti-4T1 IgG concentration in serum from α-AED-treated mice, but no other associated systemic changes were detected. The reduction in tumor size for the local injection of α-AED is associated with the anti-proliferative effect of this steroid, and the lower local levels of VEGF may be related to the imperceptible macroscopic metastasis in α-AED-treated mice. The above suggests that α-AED may be used in clinical studies to prove its efficacy as an alternative breast tumor treatment or in conjunction with already established therapies.

Association of Serum Levels of Plasticizers Compounds, Phthalates and Bisphenols, in Patients and Survivors of Breast Cancer: A Real Connection?

Phthalates and bisphenols are ubiquitous environmental pollutants with the ability to perturb different systems. Specifically, they can alter the endocrine system, and this is why they are also known as endocrine-disrupting compounds (EDCs). Interestingly, they are related to the development and progression of breast cancer (BC), but the threshold concentrations at which they trigger that are not well established. OBJECTIVES: The aim of this study was to compare the concentration measures of parent EDCs in three groups of women (without BC, with BC, and BC survivors) from two urban populations in Mexico, to establish a possible association between EDCs and this disease. We consider the measure of the parent compounds would reflect the individual's exposure. METHODS: The levels of di-ethyl-hexyl-phthalate (DEHP), butyl-benzyl-phthalate (BBP), di-n-butyl phthalate (DBP) and di-ethyl-phthalate (DEP), bisphenol A (BPA) and bisphenol S (BPS) were determined by gas chromatograph-mass spectrometry in 102 subjects, including 37 women without any pathological disease, 46 patients with BC and 19 women survivals of BC of Mexico and Toluca City. RESULTS: All phthalates were detected in 100% of women, two of them were significantly higher in patients with different BC subtypes in Mexico City. Differential increases were observed mainly in the serum concentration of phthalates in women with BC compared to women without disease between Mexico and Toluca City. In addition, when performing an analysis of the concentrations of phthalates by molecular type of BC, DEP and BBP were found mainly in aggressive and poorly differentiated types of BC. It should be noted that female BC survivors treated with anti-hormonal therapy showed lower levels of BBP than patients with BC. BPA and BPS were found in most samples from Mexico City. However, BPS was undetectable in women from Toluca City. DISCUSSION: The results of our study support the hypothesis of a positive association between exposure to phthalates and BC incidence.

Definition of germ layer cell lineage alternative splicing programs reveals a critical role for Quaking in specifying cardiac cell fate.

Alternative splicing is critical for development; however, its role in the specification of the three embryonic germ layers is poorly understood. By performing RNA-Seq on human embryonic stem cells (hESCs) and derived definitive endoderm, cardiac mesoderm, and ectoderm cell lineages, we detect distinct alternative splicing programs associated with each lineage. The most prominent splicing program differences are observed between definitive endoderm and cardiac mesoderm. Integrative multi-omics analyses link each program with lineage-enriched RNA binding protein regulators, and further suggest a widespread role for Quaking (QKI) in the specification of cardiac mesoderm. Remarkably, knockout of QKI disrupts the cardiac mesoderm-associated alternative splicing program and formation of myocytes. These changes arise in part through reduced expression of BIN1 splice variants linked to cardiac development. Mechanistically, we find that QKI represses inclusion of exon 7 in BIN1 pre-mRNA via an exonic ACUAA motif, and this is concomitant with intron removal and cleavage from chromatin. Collectively, our results uncover alternative splicing programs associated with the three germ lineages and demonstrate an important role for QKI in the formation of cardiac mesoderm.

Neuropatías periféricas, un enfoque multidimensional y práctico de una compleja condición / Peripheral neuropathies, a multidimensional and practical approach to a complex condition

Resumen Introducción: las neuropatías periféricas comprenden una amplia gama de entidades que afectan uno o múltiples nervios periféricos en cualquiera de sus categorías funcionales. Métodos: revisión de la literatura sobre la temática, mediante la búsqueda de artículos en las bases de datos Pubmed y Google Scholar publicadas en los últimos 21 años, sin restricción idiomática, excluyendo estudios descriptivos y reportes de caso. Resultados: las neuropatías periféricas tienen una prevalencia del 2 % al 3 %, pueden ser causadas por etiologías infecciosas, enfermedades inflamatorias, inmunológicas, trastornos neoplásicos, exposición a tóxicos, fármacos y deficiencias nutricionales. El diagnóstico depende del juicio clínico. La aplicación de estudios de laboratorios y electrodiagnóstico pueden clasificar adecuadamente estas entidades. El tratamiento depende de la entidad subyacente y debe incluir un enfoque multimodal. Conclusiones: establecer estrategias de prevención, detección y tratamiento temprano permite una potencial recuperación y disminuye los costos para el sistema de salud.

Abstract Introduction: peripheral neuropathies comprise a wide range of entities affecting one or multiple peripheral nerves in any of their functional categories. Methods: review of the literature on the subject, by searching for articles in Pubmed and Google Scholar databases published in the last 21 years, without language restriction, excluding descriptive studies and case reports. Results: peripheral neuropathies have a prevalence of 2 % to 3 %, and can be caused by infectious etiologies, inflammatory diseases, immunological, neoplastic disorders, exposure to toxins, drugs and nutritional deficiencies. Their diagnosis depends on clinical judgment. The application of laboratory and electrodiagnostic studies can adequately classify these entities. Treatment depends on the underlying entity and should include a multimodal approach. Conclusions: establishing strategies for prevention, early detection and treatment allows for potential recovery and decreases costs for the health system.

The Endocrine Disruptor Compound Bisphenol-A (BPA) Regulates the Intra-Tumoral Immune Microenvironment and Increases Lung Metastasis in an Experimental Model of Breast Cancer.

Breast cancer (BC) metastasis represents the main physiopathology leading to poor prognosis and death. Bisphenol A (BPA) is a pollutant, classified as an endocrine-disrupting chemical compound with estrogenic properties, their exposure in the early stages of neonatal life leads to an increase in the size and weight of breast tumors and induces cellular changes in the tumoral immune microenvironment where cytokines play a key role. Thus, we used female BALB/c mice exposed neonatally to a single dose of BPA. Once mice reached sexual maturity, a mammary tumor was induced, injecting 4T1 cells in situ. After 25 days of injection, we evaluated endocrine alterations, cytokine expression, tissue alterations denoted by macro or micro-metastasis in the lung, and cell infiltration induced by metastasis. We found that BPA neonatal treatment did not show significant endocrine alterations. Noteworthy, BPA led to an augmented rate of metastasis to the lung associated with higher intratumoral expression of IL-1ß, IL-6, IFN-γ, TNF-α, and VEGF. Our data suggest that cytokines are key players in the induction of BC metastasis and that BPA (an environmental pollutant) should be considered as a risk factor in the clinical history of patients as a possible inductor of BC metastasis.

Sexual Dimorphism of the Neuroimmunoendocrine Response in the Spleen during a Helminth Infection: A New Role for an Old Player?

The interaction of the nervous, immune, and endocrine systems is crucial in maintaining homeostasis in vertebrates, and vital in mammals. The spleen is a key organ that regulates the neuroimmunoendocrine system. The Taenia crassiceps mouse system is an excellent experimental model to study the complex host-parasite relationship, particularly sex-associated susceptibility to infection. The present study aimed to determine the changes in neurotransmitters, cytokines, sex steroids, and sex-steroid receptors in the spleen of cysticercus-infected male and female mice and whole parasite counts. We found that parasite load was higher in females in comparison to male mice. The levels of the neurotransmitter epinephrine were significantly decreased in infected male animals. The expression of IL-2 and IL-4 in the spleen was markedly increased in infected mice; however, the expression of Interleukin (IL)-10 and interferon (IFN)-γ decreased. We also observed sex-associated differences between non-infected and infected mice. Interestingly, the data show that estradiol levels increased in infected males but decreased in females. Our studies provide evidence that infection leads to changes in neuroimmunoendocrine molecules in the spleen, and these changes are dimorphic and impact the establishment, growth, and reproduction of T. crassiceps. Our findings support the critical role of the neuroimmunoendocrine network in determining sex-associated susceptibility to the helminth parasite.

Knowledge, Attitudes, Behavior, and Practices of Self Breast Examination in Nicaragua.

Self breast examination (SBE) has been recommended as an important preventative practice for the early identification of breast cancer in women. However, our understanding of women's knowledge, attitudes, and practices of self breast examination in Nicaragua is limited. In the present study, we conducted a cross-sectional study of women aged 18 years and over (n=500) living in selected urban and rural areas of Nicaragua. Measures included the survey reflected knowledge, attitudes, behaviors, and practices related to self breast examination. We compared these measures between women living in urban and rural areas and women aged 18-39 years and 40+ years. Using a t-test, we tested the significance of these differentials. Results indicate widespread and significant differentials in basic knowledge and behaviors on self-breast examination practices among women living in rural and urban locations in Nicaragua. Further, while younger women reported significant and lower overall knowledge about breast cancer (BC), purpose and reasons for SBE, characteristics of women who tend to be at higher risk for BC, and strategies and steps women take performing SBE compared to women who were in the 40+ age group. Study results call for location and population-specific programs and policies addressing disparities in breast cancer prevention efforts in the country.

Molecular identification of a PGRMC-2 receptor in maturing oocytes of the zoonotic nematode parasite Trichinella spiralis.

We previously reported that the Trichinella nematode showed higher parasite loads in one gender than another, but also the parasite molting rate decreased when it was cultivated in the presence of progesterone. In this study we explored the hypothesis that the direct effect of progesterone on Trichinella spiralis could be mediated by a steroid-binding parasite protein. We sequenced, cloned and amplified the Cyt-domain of the progesterone receptor membrane component-2 of Trichinella spiralis (PGRMC2-Ts). Furthermore, we expressed the protein and developed an antibody to perform confocal microscopy and flow cytometry. The expression of the PGRMC2-Ts protein was exclusively detected at the oocyte and the parasite's cuticle in cross-sections of the parasite, and this expression was confirmed by western blot and flow cytometry. Molecular modeling studies and computer docking for the PGRMC2-Ts protein showed that it is potentially able to bind to progesterone, estradiol, testosterone, and dihydrotestosterone with different affinities. Furthermore, phylogenetic analysis demonstrated that T. spiralis PGRMC2 is related to a steroid-binding protein of another platyhelminth. Progesterone probably acts upon Trichinella spiralis oocytes by binding to PGRMC2-Ts. Our data showed that the PGRMC2-Ts protein is present in the parasite's oocytes, a development step that is crucial for the life cycle of the parasite. Indeed, this research might have implications in the field of host-parasite co-evolution and the sex-associated susceptibility to this infection. In a more practical matter, these results may contribute to the design of new drugs with anti-parasite effects.

Environmental Pollution to Blame for Depressive Disorder?

Public concern has emerged about the effects of endocrine-disrupting compounds (EDCs) on neuropsychiatric disorders. Preclinical evidence suggests that exposure to EDCs is associated with the development of major depressive disorder (MDD) and could result in neural degeneration. The interaction of EDCs with hormonal receptors is the best-described mechanism of their biological activity. However, the dysregulation of the hypothalamic-pituitary-gonadal adrenal axis has been reported and linked to neurological disorders. At a worldwide level and in Mexico, the incidence of MDD has recently been increasing. Of note, in Mexico, there are no clinical associations on blood levels of EDCs and the incidence of the MDD. Methodology: Thus, we quantified for the first time the serum levels of parent compounds of two bisphenols and four phthalates in patients with MDD. The levels of di-ethyl-hexyl-phthalate (DEHP), butyl-benzyl-phthalate (BBP), di-n-butyl phthalate (DBP), and di-ethyl-phthalate (DEP), bisphenol A (BPA), and bisphenol S (BPS) in men and women with or without MDD were determined with a gas chromatograph-mass spectrometer. Results/conclusion: We found significant differences between concentrations of BBP between controls and patients with MDD. Interestingly, the serum levels of this compound have a dysmorphic behavior, being much higher in women (~500 ng/mL) than in men (≤10 ng/mL). We did not observe significant changes in the serum concentrations of the other phthalates or bisphenols tested, neither when comparing healthy and sick subjects nor when they were compared by gender. The results point out that BBP has a critical impact on the etiology of MDD disorder in Mexican patients, specifically in women.