Preclinical evaluation of fenretinide against primary and metastatic intestinal type­gastric cancer.

In recent years there has been a decline in the incidence of gastric cancer, however the high mortality rate has remained constant. The present study evaluated the potential effects of the retinoid fenretinide on the viability and migration of two cell lines, AGS and NCI-N87, that represented primary and metastatic intestinal gastric cancer subtypes, respectively. It was determined that a similar2 dose of fenretinide reduced the viability of both the primary and metastatic cell lines. In addition, it was demonstrated that combined treatment with fenretinide and cisplatin may affect the viability of both primary and metastatic gastric cancer cells. Furthermore, a wound healing assay demonstrated an inhibitory effect for fenretinide on cell migration. As part of the characterization of the mechanism of action, the effect of fenretinide on reactive oxygen species production and lipid droplet content was evaluated, with the latter as an indirect means of assessing autophagy. These results support the hypothesis of combining using fenretinide with conventional therapies to improve survival rates in advanced or metastatic gastric cancer.

Exploring dietary differences among developmental stages of triatomines infected with Trypanosoma cruzi in different habitats.

Chagas disease affects millions of people in Colombia and worldwide, with its transmission influenced by ecological, environmental, and anthropogenic factors. There is a notable correlation between vector transmission cycles and the habitats of insect vectors of the parasite. However, the scale at which these cycles operate remains uncertain. While individual triatomine ecotopes such as palms provide conditions for isolated transmission cycles, recent studies examining triatomine blood sources in various habitats suggest a more intricate network of transmission cycles, linking wild ecotopes with human dwellings. This study aims to provide further evidence on the complexity of the scale of Trypanosoma cruzi transmission cycles, by exploring the different blood sources among developmental stages of infected triatomines in different habitats. We evaluated infection rates, parasite loads, feeding sources, and the distribution of Rhodnius prolixus insects in Attalea butyracea palms across three distinct habitats in Casanare, Colombia: peridomestics, pastures, and woodlands. Our results show that there is no clear independence in transmission cycles in each environment. Analyses of feeding sources suggest the movement of insects and mammals (primarily bats and didelphids) among habitats. A significant association was found between habitat and instar stages in collected R. prolixus. The N1 stage was correlated with pasture and woodland, while the N4 stage was related to pasture. Additionally, adult insects exhibited higher T. cruzi loads than N1, N2, and N3. We observed higher T. cruzi loads in insects captured in dwelling and pasture habitats, compared with those captured in woodland areas. Effective Chagas disease control strategies must consider the complexity of transmission cycles and the interplay between domestic and sylvatic populations of mammals and vectors.

Experience with the use of the DIALOG+ intervention in patients with severe mental illness in outpatient services in Colombia.

INTRODUCTION: Severe mental disorders can cause significant and lasting distress for patients and their families and generate high costs through the need for care and loss of productivity. This study tests DIALOG+, an app-based intervention to make routine patient-clinician meetings therapeutically effective. It combines a structured evaluation of patient satisfaction with a solution-focused approach. METHODS: We conducted a qualitative study, based on a controlled clinical trial, in which 9 psychiatrists and 18 patients used DIALOG+ monthly over a six-month period. Semi-structured interviews were used to explore the experiences of participants and analysed in an inductive thematic analysis focusing on the feasibility and effects of the intervention in the Colombian context. RESULTS: Experiences were grouped into five overall themes: a) impact of the intervention on the consultation and the doctor-patient relationship; b) impact on patients and in promoting change; c) use of the supporting app, and d) adaptability of the intervention to the Colombian healthcare system. CONCLUSIONS: DIALOG+ was positively valued by most of the participants. Participants felt that it was beneficial to the routine consultation, improved communication and empowered patients to take a leading role in their care. More work is required to identify the patient groups that most benefit from DIALOG+, and to adjust it, particularly to fit brief consultation times, so that it can be rolled out successfully in the Colombian healthcare system.

Experiencia con la intervención DIALOG+ en pacientes con enfermedad mental grave en servicios de consulta externa de Colombia / Experience with the use of the DIALOG+ Intervention in Patients with Severe Mental Illness in Outpatient Services in Colombia

RESUMEN Introducción: Las enfermedades mentales graves producen un impacto significativo en términos de sufrimiento de los pacientes y sus familias, costos de atención y arios de vida perdidos por discapacidad. Este estudio pone a prueba la herramienta DIALOG+, una intervención basada en una App que combina una evaluación estructurada referente a 11 dominios, con un abordaje centrado en soluciones. Métodos: Estudio cualitativo anidado en un ensayo clínico controlado en el que 9 psiquiatras y una muestra intencional de 18 pacientes que utilizaron la aplicación DIALOG+ en controles mensuales durante 6 meses realizaron entrevistas semiestructuradas sobre su experiencia. Resultados: El análisis se enfocó en determinar la aceptabilidad, la viabilidad y la efectividad de la intervención en el contexto colombiano mediante el método de análisis temático inductivo propuesto por Braun y Clarke. Los resultados fueron: a) impactos en la consulta y la relación médico-paciente; b) impactos en los pacientes y promoción del cambio; c) uso de la aplicación, y d) adaptabilidad al sistema de salud. Conclusiones: El instrumento DIALOG+ fue valorado positivamente por la mayoría de los participantes, dado que aporta al seguimiento de los pacientes con enfermedad mental grave porque incluye un componente psicoterapéutico en las consultas habituales y mejora la comunicación y el paciente se apropia de su proceso. Sin embargo, es pertinente delimitar la población que podría percibir los mayores beneficios y ajustar su esquema, sobre todo en relación con el tiempo de consulta, para que resulte exitosa su adaptación al sistema de salud colombiano.

ABSTRACT Introduction: Severe mental disorders can cause significant and lasting distress for patients and their families and generate high costs through the need for care and loss of productivity. This study tests DIALOG+, an app-based intervention to make routine patient-clinician meetings therapeutically effective. It combines a structured evaluation of patient satisfaction with a solution-focused approach. Methods: We conducted a qualitative study, based on a controlled clinical trial, in which 9 psychiatrists and 18 patients used DIALOG+ monthly over a six-month period. Semistructured interviews were used to explore the experiences of participants and analysed in an inductive thematic analysis focusing on the feasibility and effects of the intervention in the Colombian context. Results: Experiences were grouped into five overall themes: a) impact of the intervention on the consultation and the doctor-patient relationship; b) impact on patients and in promoting change; c) use of the supporting app, and d) adaptability of the intervention to the Colombian healthcare system. Conclusions: DIALOG+ was positively valued by most of the participants. Participants felt that it was beneficial to the routine consultation, improved communication and empowered patients to take a leading role in their care. More work is required to identify the patient groups that most benefit from DIALOG+, and to adjust it, particularly to fit brief consultation times, so that it can be rolled out successfully in the Colombian healthcare system.

Transmission ecology of Trypanosoma cruzi by Rhodnius prolixus (Reduviidae: Triatominae) infesting palm-tree species in the Colombian Orinoco, indicates risks to human populations.

BACKGROUND: Chagas disease, affecting approximately eight million individuals in tropical regions, is primarily transmitted by vectors. Rhodnius prolixus, a triatomine vector, commonly inhabits in ecotopes with diverse palm tree species, creating optimal conditions for vector proliferation. This study aims to explore the transmission ecology of Trypanosoma cruzi, the causative parasite of Chagas disease, by investigating the feeding patterns and natural infection rates of R. prolixus specimens collected from various wild palm species in the Colombian Orinoco region. MATERIALS AND METHODS: To achieve this objective, we sampled 35 individuals from three palm species (Attalea butyracea, Acrocomia aculeata, and Mauritia flexuosa) in a riparian forest in the Casanare department of eastern Colombia, totaling 105 sampled palm trees. DNA was extracted and analyzed from 115 R. prolixus specimens at different developmental stages using quantitative PCR (qPCR) for T. cruzi detection and identification of discrete typing units. Feeding preferences were determined by sequencing the 12S rRNA gene amplicon through next-generation sequencing. RESULTS: A total of 676 R. prolixus specimens were collected from the sampled palms. The study revealed variation in population densities and developmental stages of R. prolixus among palm tree species, with higher densities observed in A. butyracea and lower densities in M. flexuosa. TcI was the exclusive T. cruzi discrete typing unit (DTU) found, with infection frequency positively correlated with R. prolixus abundance. Insects captured in A. butyracea exhibited higher abundance and infection rates than those from other palm species. The feeding sources comprised 13 mammal species, showing no significant differences between palm species in terms of blood sources. However, Didelphis marsupialis and Homo sapiens were present in all examined R. prolixus, and Dasypus novemcinctus was found in 89.47% of the insects. CONCLUSION: This study highlights the significance of wild palms, particularly A. butyracea, as a substantial risk factor for T. cruzi transmission to humans in these environments. High population densities and infection rates of R. prolixus were observed in each examined palm tree species.

Luto e desejo na menopausa: contribuições psicanalíticas / Grief and desire in menopause: psychoanalytic contributions / Deuil et désir à la ménopause: apports psychanalytiques / Duelo y melancolia en la menopausia: aportes psicoanalíticos

Menopausa é o termo indicado pela OMS para nomear o último ciclo biológico da mulher, em que há o encerramento da capacidade reprodutiva feminina. Notando que o tema da menopausa parece despertar pouco interesse nas esferas social e científica e foi conotado negativamente pela teoria psicanalítica por um período, o objetivo deste artigo é traçar algumas considerações da psicanálise, partindo de Freud e Lacan, acerca do fenômeno. Para tal, utiliza-se o conceito de luto como operador teórico para reflexão do tema e enlaçamento com a teoria, passando por falas de mulheres menopáusicas. Considera-se, neste artigo, que o real da menopausa pode encontrar um caminho de tratamento que passe pelo luto e pelo simbólico, chegando ao desejo — colocando, assim, outras contribuições psicanalíticas a respeito do tema.

Resumos Menopause is the term indicated by the WHO to name the last biological cycle of the woman, in which there is the end of the female reproductive capacity. Noting that the topic of menopause seems to arouse little interest in the social and scientific spheres and was negatively connoted by psychoanalytic theory for a period, the purpose of this article is to outline some considerations of psychoanalysis, starting from Freud and Lacan, about the phenomenon. To this end, the concept of mourning is used as a theoretical operator to reflect on the theme and link it with the theory, passing through the speeches of menopausal women. It is considered, in this article, that the real of menopause can find a way of treatment that passes through mourning and the symbolic, reaching desire - thus placing other psychoanalytic contributions on the subject.

La ménopause est le terme indiqué par l'OMS pour nommer le dernier cycle biologique des femmes, dans lequel il y a la fin de la capacité reproductive féminine. Constatant que le thème de la ménopause semble susciter peu d'intérêt dans les sphères sociales et scientifiques et qu'il a été connoté négativement par la théorie psychanalytique, cet article retrace quelques considérations psychanalytique, basées sur Freud et Lacan, sur le phénomène. Pour ce faire, on utilise le concept de deuil comme opérateur théorique pour réfléchir au thème et le relier à la théorie, à travers les discours des femmes ménopausées. Il considère que le réel de la ménopause peut trouver une voie de traitement qui passe par le deuil et le symbolique, pour atteindre le désir — plaçant ainsi d'autres apports psychanalytiques sur le sujet.

La menopausia es el término que utiliza la Organización Mundial de la Salud (OMS) para denominar el último ciclo biológico de la mujer, en el que se produce el final de la capacidad reproductiva femenina. A partir de las observaciones de que el tema de la menopausia parece despertar poco interés en las esferas social y científica, y que fue connotado de manera negativa por la teoría psicoanalítica durante un período, el propósito de este artículo es esbozar algunas consideraciones del psicoanálisis, a partir de Freud y Lacan, sobre el fenómeno. Para ello, se utiliza el concepto de duelo como operador teórico para reflexionar sobre el tema y vincularlo con la teoría, pasando por los discursos de las mujeres menopáusicas. Se considera, en este artículo, que lo real de la menopausia puede encontrar una vía de tratamiento que pasa por el duelo y lo simbólico, y alcanza el deseo, logrando así otros aportes psicoanalíticos al tema.

Trypanosoma cruzi Parasite Burdens of Several Triatomine Species in Colombia.

Trypanosoma cruzi, the causal agent of Chagas disease, is mainly transmitted by insects of the Triatominae subfamily. In Colombia, there are 26 triatomine species, and 16 of them are naturally infected with the parasite. The parasite loads of naturally infected vectors can be significant in targeting specific species that can affect the epidemiology of the disease. Studying their ecology and behavior is vital to understand their role in T. cruzi transmission dynamics. We evaluated the parasite loads of 182 field-collected triatomines corresponding to 10 species in 13 departments across Colombia. We standardized a methodology to quantify T. cruzi DNA in these insects. We obtained a LOD (limit of detection) of 3.05 p-eq/mL. The 82% of triatomines we evaluated were positive for T. cruzi infection, with loads ranging from hundreds to millions of equivalent parasites per milliliter. Panstrongylus geniculatus, Rhodnius prolixus, and Triatoma dimidiata were the species with the highest loads of T. cruzi; however, other species whose role as vectors is still unknown were also found with high loads of parasites. Our results suggest the relevance of secondary species for T. cruzi transmission in Colombia. We hope our data can help improve entomological surveillance and vector control programs in the country and the region.

Interrogating the transmission dynamics of Trypanosoma cruzi (Trypanosomatida, Trypanosomatidae) by Triatoma venosa (Hemiptera: Reduviidae) after the elimination of vector transmission by Rhodnius prolixus in Boyacá eastern Colombia.

Chagas disease (CD) is a parasitic zoonosis (Trypanosoma cruzi) that is endemic in Colombia. Vector control of Rhodnius prolixus, the main domestic T. cruzi vector, has been achieved in a large part of the area with historically vector transmission of CD. It is necessary to understand the ecological behavior characteristics of local native vectors to ensure sustainability of the vector control programs. To evaluate the long-term success of a recent vector control campaign in the Boyacá department (Colombia), we used a combined strategy of entomological surveillance with co-existing canine surveillance from ten rural villages within six municipalities of the Tenza valley region (Boyacá, Colombia): Chinavita, Garagoa, Guateque, Somondoco, Sutatenza and Tenza, with historical reports of R. prolixus and secondary vectors. Collected triatomines and canine whole blood were analyzed for T. cruzi infection and genotyping. Triatomine bugs specimens were evaluated for blood meal source. Canine serology was performed using two distinct antibody assays. In total, 101 Triatoma venosa were collected by active search in domestic and peridomestic habitats. A natural infection prevalence of 13.9% (14/101) and four feeding sources were identified: human, dog, rat, and hen. A frequency infection of 46.5% (40/87) was observed from two independent serological tests and T. cruzi DNA was detected in 14 dogs (16.4%). Only TcIsylvatic DTU was detected. The results suggest that T. venosa present eco-epidemiological characteristics to maintain the transmission of T. cruzi in Tenza valley. This species has reinfested the intervened households and it has an active role in domestic and peridomestic transmission of T. cruzi due to their infection rates and feeding behavior. Therefore, this species should be considered as epidemiologically relevant for vector control strategies. Moreover, there is a need for human serological studies to have a close up of risk they are exposed to.

Giant Partially Thrombosed Coronary Aneurysm in Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 in Children.

Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious condition which usually develops 4 to 6 weeks after SARS-CoV-2 infection in a genetically predisposed individual. Clinical features are heterogeneous and include fever, respiratory compromise, mucocutaneous involvement with conjunctival abnormalities and erythematous exanthem, abdominal pain, and diarrhea. Neurologic and cardiovascular symptoms can also develop, including coronary artery dilatation. Some cases involve 2 or more organs and require critical admission. Echocardiography is the mainstay of cardiac evaluation in the acute setting as well as on outpatient follow-up. We present the case of a 4-month-old female with no past medical or surgical history who presented with a prolonged febrile syndrome associated with severe respiratory illness, gastrointestinal symptoms, and mucocutaneous abnormalities. Diagnosis of MIS-C was established based on clinical findings, persistently elevated markers of systemic inflammation and positive SARS-CoV-2 molecular test and evidence of prior SARS-CoV-2 infection with SARS-CoV-2 IgG positive. Echocardiogram evidenced myopericarditis and coronary aneurysms and patient was deemed candidate for immunomodulatory therapy with intravenous immunoglobulin (IVIg), resulting in favorable clinical and paraclinical outcomes. Few cases of giant coronary aneurysms have been reported in children. There are no existing literature reports about coronary thrombosis or thrombus formation resulting from vascular aneurysmal dilations in this population. As such, the prognosis and natural history of coronary artery aneurysms in the setting of MIS-C remain largely unknown.

Tele-entomology and tele-parasitology: A citizen science-based approach for surveillance and control of Chagas disease in Venezuela.

Chagas Disease (CD), a chronic infection caused by the Trypanosoma cruzi parasite, is a Neglected Tropical Disease endemic to Latin America. With a re-emergence in Venezuela during the past two decades, the spread of CD has proved susceptible to, and inhibitable by a digital, real-time surveillance system effectuated by Citizen Scientists in communities throughout the country. The #TraeTuChipo (#BringYourKissingBug) campaign implemented in January 2020, has served as such a strategy counting on community engagement to define the current ecological distribution of CD vectors despite the absence of a functional national surveillance program. This pilot campaign collected data through online surveys, social media platforms, and/or telephone text messages. A total of 79 triatomine bugs were reported from eighteen Venezuelan states; 67 bugs were identified as Panstrongylus geniculatus, 1 as Rhodnius pictipes, 1 as Triatoma dimidiata, and 10 as Triatoma maculata. We analyzed 8 triatomine feces samples spotted from 4 Panstrongylus geniculatus which were confirmed positive by qPCR for T. cruzi . Further molecular characterization of discrete typing units (DTUs), revealed that all samples contained TcI, the most highly diverse and broadly distributed strain of T. cruzi. Moreover, analysis of the mitochondrial 12S gene revealed Myotis keaysi, Homo sapiens, and Gallus gallus as the main triatomine feeding sources. This study highlights a novel Citizen Science approach which may help improve the surveillance systems for CD in endemic countries.

Estimating the genetic structure of Triatoma dimidiata (Hemiptera: Reduviidae) and the transmission dynamics of Trypanosoma cruzi in Boyacá, eastern Colombia.

Chagas disease is considered a public health issue in Colombia, where many regions are endemic. Triatoma dimidiata is an important vector after Rhodnius prolixus, and it is gaining importance in Boyacá, eastern Colombia. Following the recent elimination of R. prolixus in the region, it is pivotal to understand the behavior of T. dimidiata and the transmission dynamics of T. cruzi. We used qPCR and Next Generation Sequencing (NGS) to evaluate T. cruzi infection, parasite load, feeding profiles, and T. cruzi genotyping for T. dimidiata specimens collected in nine municipalities in Boyacá and explored T. dimidiata population genetics. We found that T. dimidiata populations are composed by a single population with similar genetic characteristics that present infection rates up to 70%, high parasite loads up to 1.46 × 109 parasite-equivalents/mL, a feeding behavior that comprises at least 17 domestic, synanthropic and sylvatic species, and a wide diversity of TcI genotypes even within a single specimen. These results imply that T. dimidiata behavior is similar to other successful vectors, having a wide variety of blood sources and contributing to the circulation of different genotypes of the parasite, highlighting its importance for T. cruzi transmission and risk for humans. In the light of the elimination of R. prolixus in Boyacá and the results we found, we suggest that T. dimidiata should become a new target for vector control programs. We hope this study provides enough information to enhance surveillance programs and a future effective interruption of T. cruzi vector transmission in endemic regions.

Discrete typing units of Trypanosoma cruzi: Geographical and biological distribution in the Americas.

Chagas disease caused by Trypanosoma cruzi is a public health issue in Latin America. This highly diverse parasite is divided into at least seven discrete typing units (DTUs) TcI-TcVI and Tcbat. Some DTUs have been associated with geographical distribution in epidemiological scenarios and clinical manifestations, but these aspects remain poorly understood. Many studies have focused on studying the parasite and its vectors/hosts, using a wide variety of genetic markers and methods. Here, we performed a systematic review of the literature for the last 20 years to present an update of DTUs distribution in the Americas, collecting ecoepidemiological information. We found that the DTUs are widespread across the continent and that there is a whole gamma of genetic markers used for the identification and genotyping of the parasite. The data obtained in this descriptor could improve the molecular epidemiology studies of Chagas disease in endemic regions.

Percepciones de madres y padres sobre el impacto ocupacional en niñas y niños a causa del confinamiento por COVID-19 en la ciudad de Punta Arenas, Chile / Mothers' and fathers' perceptions of the occupational impact of COVID 19 confinement on children in the city of Punta Arenas, Chile

El equilibrio ocupacional de la población en general está relacionado con la buena salud, sin embargo, la población infantil fue uno de los grupos más afectados por el confinamiento y las medidas de distanciamiento social durante la pandemia de COVID-19. Esta investigación tuvo como objetivo conocer el impacto ocupacional que experimentaron niñas y niños a causa del confinamiento por COVID-19 según la percepción de sus madres y padres en la ciudad de Punta Arenas, Chile. A través de un enfoque cualitativo y alcance exploratorio descriptivo se entrevistó a 25 madres y 1 padre de niñas y niños entre 6 a 12 años, estudiantes de un establecimiento educacional subvencionado que se encontraban en confinamiento en la ciudad de Punta Arenas. Según su percepción, se establece que el confinamiento ocasionó algunos cambios positivos en las actividades de la vida diaria instrumentales y negativos en las ocupaciones de juego, participación social, educación, actividades de la vida diaria de alimentación, descanso y sueño de sus hijas e hijos. Madres y padres se enfrentaron a realizar diversas adaptaciones y modificaciones como organización del tiempo, entorno e implementación de materiales, para favorecer el desempeño ocupacional. Se concluye que debido a la incertidumbre e inestabilidad emocional con relación al ambiente y sus cambios, desde la mirada de la Terapia Ocupacional, resulta relevante el apoyo de las madres y padres para reestructurar las rutinas y adaptarlas al encierro prolongado dentro del hogar, respetando y organizando horarios. El añadir actividades recreativas y fomentar el juego en el ocio y tiempo libre favoreció el equilibrio ocupacional y la sensación de satisfacción de niñas y niños junto a sus familias.

The occupational balance of the general population is related to good health; however, the child population was one of the groups most affected by confinement and social distancing measures during the COVID-19 pandemic. The objective of this research was to determine the occupational impact experienced by children as a result of COVID-19 confinement as perceived by their mothers and fathers in the city of Punta Arenas, Chile. Through a qualitative approach and descriptive exploratory scope, 25 mothers and 1 father of children between 6 and 12 years old, students of a subsidized educational establishment who were in confinement in the city of Punta Arenas, Chile, were interviewed. According to their perception, it was established that confinement caused some positive changes in instrumental daily life activities and negative changes in their children's activities of play, social participation, education, daily life activities of eating, resting and sleeping. Mothers and fathers were faced with making various adaptations and modifications such as organization of time, environment and implementation of materials, in order to favor occupational performance. It is concluded that due to the uncertainty and emotional instability in relation to the environment and its changes, from the point of view of occupational therapy, the support of mothers and fathers is relevant to restructure routines and adapt them to the prolonged confinement at home, respecting and organizing schedules. Adding recreational activities and encouraging play in leisure and free time favored occupational balance and the feeling of satisfaction of children and their families.

Pigmentación violácea dolorosa, reto clínico y enfoque diagnóstico en un país tropical / Painful violaceous pigmentation, a clinical challenge and diagnostic approach in a tropical country

RESUMEN Contrario a lo que se cree, los milpiés no se consideran animales venenosos, su mecanismo de defensa puede resultar perjudicial para el ser humano, manifestándose como lesiones de carácter eritematoso, purpúrico y cianótico, concomitante dolor local y parestesia; Según la exposición, el cuadro clínico puede evolucionar a lesiones moderadas y severas, ampollas y úlceras. Describimos el caso de un paciente pediátrico de sexo masculino de la región andina de Colombia, con temperaturas diarias que oscilan entre 15° y 30°C y una humedad promedio de 72 %, quien accidentalmente pisó un milpiés, lo cual fue un desafío diagnóstico entre el personal de salud que generó su atención.

ABSTRACT Millipedes are not considered poisonous animals, although in some cases their chemical defense mechanisms may be deleterious for human beings, manifesting as erythematous, purpuric and/ or cyanotic lesions alongside local pain and paresthesia. According to the exposure, the clinical condition may progress to moderate and severe lesions such as ulcers and blisters. We describe a case of a male child from the Andean region in Colombia, an area with daily temperatures between 15° and 30° C and 72% average humidity. The boy accidentally stepped on a millipede, and this occurrence became a challenge for its diagnosis amongst staff who provided emergency health care.

Importance of Mevalonate Pathway Lipids on the Growth and Survival of Primary and Metastatic Gastric Carcinoma Cells.

PURPOSE: This preclinical study aims to determine the effect of drugs that alter isoprenoids and cholesterol metabolism in the homeostasis of gastric carcinoma cell lines in the search for new therapeutic targets for stomach cancer. MATERIALS AND METHODS: Primary (AGS) and metastatic (NCI-N87) gastric cancer cell lines were treated with simvastatin and terbinafine, two inhibitors of the mevalonate pathway, and avasimibe, an inhibitor of cholesterol esterification. Cell viability and growth were measured as well as cholesterol levels and the expression of the hydroxy methyl-glutaryl CoA reductase (HMGCR) and the LDL receptor (LDLR). RESULTS: Primary and metastatic gastric carcinoma cells show different sensitivity to drugs that affect isoprenoid synthesis and the metabolism and uptake of cholesterol. Isoprenoids are involved in the growth and viability of both types of cells, but the role of free and esterified cholesterol for metastatic gastric cell survival is not as evident as for primary gastric cancer cells. Differential expression of LDLR due to mevalonate pathway inhibition suggests variations in the regulation of cholesterol uptake between primary and metastatic cancer cells. CONCLUSION: These results indicate that at least for primary gastric cancer, statins and avasimibe are promising candidates as potential novel antitumor drugs that target the metabolism of isoprenoids and cholesterol of gastric tumors.

Viruses in Extreme Environments, Current Overview, and Biotechnological Potential.

Virus research has advanced significantly since the discovery of the tobacco mosaic virus (TMV), the characterization of its infection mechanisms and the factors that determine their pathogenicity. However, most viral research has focused on pathogenic viruses to humans, animals and plants, which represent only a small fraction in the virosphere. As a result, the role of most viral genes, and the mechanisms of coevolution between mutualistic viruses, their host and their environment, beyond pathogenicity, remain poorly understood. This review focuses on general aspects of viruses that interact with extremophile organisms, characteristics and examples of mechanisms of adaptation. Finally, this review provides an overview on how knowledge of extremophile viruses sheds light on the application of new tools of relevant use in modern molecular biology, discussing their value in a biotechnological context.

Species-dependent variation of the gut bacterial communities across Trypanosoma cruzi insect vectors.

Triatomines (Hemiptera: Reduviidae) are the insect vectors of Trypanosoma cruzi, the causative agent of Chagas disease. The gut bacterial communities affect the development of T. cruzi inside the vector, making the characterization of its composition important in the understanding of infection development. We collected 54 triatomine bugs corresponding to four genera in different departments of Colombia. DNA extraction and PCR were performed to evaluate T. cruzi presence and to determine the discrete typing unit (DTU) of the parasite. PCR products of the bacterial 16S rRNA gene were pooled and sequenced. Resulting reads were denoised and QIIME 2 was used for the identification of amplicon sequence variants (ASVs). Diversity (alpha and beta diversity) and richness analyses, Circos plots, and principal component analysis (PCA) were also performed. The overall T. cruzi infection frequency was 75.9%, with TcI being the predominant DTU. Approximately 500,000 sequences were analyzed and 27 bacterial phyla were identified. The most abundant phyla were Proteobacteria (33.9%), Actinobacteria (32.4%), Firmicutes (19.6%), and Bacteroidetes (7.6%), which together accounted for over 90% of the gut communities identified in this study. Genera were identified for these main bacterial phyla, revealing the presence of important bacteria such as Rhodococcus, Serratia, and Wolbachia. The composition of bacterial phyla in the gut of the insects was significantly different between triatomine species, whereas no significant difference was seen between the state of T. cruzi infection. We suggest further investigation with the evaluation of additional variables and a larger sample size. To our knowledge, this study is the first characterization of the gut bacterial structure of the main triatomine genera in Colombia.

Mevalonate pathway as a novel target for the treatment of metastatic gastric cancer.

Gastric mucosa tumors may present as two distinct major entities: Diffuse and intestinal subtypes. There is no standard treatment for advanced or metastatic gastric cancer. The mevalonate pathway and cholesterol homeostasis are important processes in cancer cells that may be highly relevant in terms of cell growth, survival and metastatic potential. Two model cell lines representing intestinal (NCI-N87) and diffuse (Hs746T) metastatic gastric tumor histological subtypes were treated with different drugs that alter membrane lipid metabolism to determine whether cell proliferation, viability and migration were affected. The results indicated that the cells exhibited significant differences in proliferation when treated with the cholesterol-lowering drug simvastatin, but not with terbinafine, another compound that affects cholesterol synthesis. Only simvastatin affected migration in both cell lines. Reposition studies with mevalonolactone, farnesyl pyrophosphate and geranylgeranyl pyrophosphate in the presence of high and low FBS concentrations indicated that both isoprenoids and cholesterol reversed the antiproliferative effects of simvastatin in gastric cancer cells. The cell lines used in the present study had different sensitivities to several potential anti-neoplastic agents that affect the synthesis of membrane lipids. The diffuse gastric cancer cells were particularly sensitive to simvastatin, suggesting it as an option for combination treatment.

Polyamidoamine-based nanovector for the efficient delivery of methotrexate to U87 glioma cells.

The purpose of this study was to design a polyamidoamine (PAMAM)-based nanovector for the efficient delivery of methotrexate to U87 glioma cells. To this end, 0-100% acetylated PAMAM dendrimers of the fourth generation were synthesized and evaluated using drug encapsulation measurements, molecular dynamics simulations, neurotoxicity assays and neuronal internalization experiments. The best system was tested as a nanovector for methotrexate delivery to U87 glioma cells. The authors found that 25% acetylated PAMAM dendrimers of the fourth-generation combine low intrinsic toxicity, large drug complexation capacity and efficient internalization into hippocampal neurons. Nanovector complexation enhances the cytotoxic response of methotrexate against U87 glioma cells compared with free drug solutions. In conclusion, 25% acetylated PAMAM dendrimers of the fourth-generation increase drug uptake by glioma cells and thereby act as efficient nanovectors for methotrexate delivery.

Identification of blood-feeding sources in Panstrongylus, Psammolestes, Rhodnius and Triatoma using amplicon-based next-generation sequencing.

BACKGROUND: Triatomines are hematophagous insects that play an important role as vectors of Trypanosoma cruzi, the causative agent of Chagas disease. These insects have adapted to multiple blood-feeding sources that can affect relevant aspects of their life-cycle and interactions, thereby influencing parasitic transmission dynamics. We conducted a characterization of the feeding sources of individuals from the primary circulating triatomine genera in Colombia using amplicon-based next-generation sequencing (NGS). METHODS: We used 42 triatomines collected in different departments of Colombia. DNA was extracted from the gut. The presence of T. cruzi was identified using real-time PCR, and discrete typing units (DTUs) were determined by conventional PCR. For blood-feeding source identification, PCR products of the vertebrate 12S rRNA gene were obtained and sequenced by next-generation sequencing (NGS). Blood-meal sources were inferred using blastn against a curated reference dataset containing the 12S rRNA sequences belonging to vertebrates with a distribution in South America that represent a potential feeding source for triatomine bugs. Mean and median comparison tests were performed to evaluate differences in triatomine blood-feeding sources, infection state, and geographical regions. Lastly, the inverse Simpson's diversity index was calculated. RESULTS: The overall frequency of T. cruzi infection was 83.3%. TcI was found as the most predominant DTU (65.7%). A total of 67 feeding sources were detected from the analyses of approximately 7 million reads. The predominant feeding source found was Homo sapiens (76.8%), followed by birds (10.5%), artiodactyls (4.4%), and non-human primates (3.9%). There were differences among numerous feeding sources of triatomines of different species. The diversity of feeding sources also differed depending on the presence of T. cruzi. CONCLUSIONS: To the best of our knowledge, this is the first study to employ amplicon-based NGS of the 12S rRNA gene to depict blood-feeding sources of multiple triatomine species collected in different regions of Colombia. Our findings report a striking read diversity that has not been reported previously. This is a powerful approach to unravel transmission dynamics at microgeographical levels.