Barriers and Facilitators of Colonoscopy Screening Among Latino Men in a Colorectal Cancer Screening Promotion Program.

Colorectal cancer (CRC) is the second leading cause of cancer death among Latino men in the United States, yet they have low screening rates. This study explored barriers and facilitators of colonoscopy screening among Latino participants in a CRC screening promotion program. Six focus groups were conducted, in Spanish, with 45 Latino men, of which 28 had received and 17 had not received a colonoscopy. Analysis of the discussion transcripts identified barriers to CRC screening, facilitators to CRC screening, and recommendations for health information dissemination. There was consensus among all participants that they had not received adequate information on colonoscopy screening from their health care providers. Unscreened participants wanted more details about the colonoscopy procedure and bowel preparation. Screened men were more knowledgeable than unscreened men about CRC, the colonoscopy procedure, and the benefits of early detection. Participants also expressed their fears, concerns, and perceptions of stigma in relation to colonoscopy screening. They described family and personal testimonials as facilitators to engaging in colorectal cancer screening. Findings underscore the need for ongoing research and educational efforts to address personal and cultural stigma surrounding colonoscopy and CRC, particularly in underserved communities. Study findings also highlight the danger of missing out on opportunities to increase CRC screening when colonoscopy is the primary screening option offered. Additional research is needed to ensure trust in the health care system and to examine the effectiveness of testimonials on CRC screening among Latino men.

Critical Consciousness for Connectivity: Decoding Social Isolation Experienced by Latinx and LGBTQ+ Youth Using a Multi-Stakeholder Approach to Health Equity.

Systemic oppression creates a context in which Latinx LGBTQ+ youth experience social isolation. Social isolation has been associated with mental and physical health disparities, including disproportionate levels of depression, substance use, self-harm, and attempted suicide. These disparities are often magnified in rural and suburban areas with fewer identity-affirming spaces. This community-engaged study reports on the formative process of developing a Latinx LGBTQ+ telenovela (soap opera) allyship intervention based on critical consciousness theory. We conducted eight focus groups with community advisory boards, which included Latinx LGBTQ+ youth (n = 12), health and social service providers serving LGBTQ+ youth (n = 10), 4-H Latinx alumni youth (n = 12), and 4-H Latinx parents (n = 8). We interviewed nine Latinx LGBTQ+ youth enrolled in a film-making workshop. As a result of our multi-stakeholder approach, we: (1) described how stakeholders reflected on and decoded intersectional isolation on the individual, community, and structural levels; and (2) identified ways that stakeholders suggested taking action by improving access to resources to address social isolation, provide culturally competent healthcare, and co-create an enabling social environment. Our study indicated the importance of tapping into core values and intersectional identities to build solidarity among and within marginalized groups to dismantle oppressive systems.

Sub-classification of borderline changes into diffuse or focal and its impact on long-term renal transplant outcomes.

BACKGROUND: Borderline changes (BL) with stable renal function is a controversial category in renal transplantation, given its contradictory outcomes. The aim of this study was to compare the clinical outcomes of BL in patients with stable renal function classified as focal and diffuse according to the extent of tubulitis. METHODS: Patients with no history of rejection with a surveillance graft biopsy at 3 or 12 months showing BL (n = 40), acute cellular rejection (n = 20) or normal biopsies (n = 20), were included in this study. Biopsies with BL were divided into diffuse BL (BLD) and focal BL (BLF) according to the extent of tubulitis. Because of the low frequency of subclinical ACR (ACRND) (n = 12), biopsies with ACR and graft dysfunction (ACRD) (n = 8) were also included. A composite outcome that included the presence of rejection in subsequent biopsies, graft loss, patient death, decrease in GFR ≥30% or presence of de novo DSA (dnDSA) during the first year of follow-up was evaluated. RESULTS: The primary composite outcome occurred in five patients of each of the Normal, BLF and ACRND, eight patients with BLD and six patients with ACRD (p = 0.105). A trend towards more rejection episodes was observed in the ACRND and ACRD. Also, a shorter time to rejection in the BLD, ACRND and ACRD groups compared to BLF and Normal groups (p = 0.039) was observed. During the first year of follow-up, no patient in the ACRND group developed dnDSA, compared to 15-25% in the other groups. The median time of dnDSA development in the BLF group was 45 months, and in the BLD group was 10 months (p = 0.020). CONCLUSION: Classifying BL biopsies with stable renal function into focal and diffuse categories, is a simple and feasible strategy that helps to differentiate between BLD with a phenotype that shows a trend towards worse outcomes, and BLF that behaves more similar to normal biopsies.

Regulation of the double-stranded RNA response through ADAR1 licenses metaplastic reprogramming in gastric epithelium.

Cells recognize both foreign and host-derived double-stranded RNA (dsRNA) via a signaling pathway that is usually studied in the context of viral infection. It has become increasingly clear that the sensing and handling of endogenous dsRNA is also critical for cellular differentiation and development. The adenosine RNA deaminase, ADAR1, has been implicated as a central regulator of the dsRNA response, but how regulation of the dsRNA response might mediate cell fate during injury and whether such signaling is cell intrinsic remain unclear. Here, we show that the ADAR1-mediated response to dsRNA was dramatically induced in 2 distinct injury models of gastric metaplasia. Mouse organoid and in vivo genetic models showed that ADAR1 coordinated a cell-intrinsic, epithelium-autonomous, and interferon signaling-independent dsRNA response. In addition, dsRNA accumulated within a differentiated epithelial population (chief cells) in mouse and human stomachs as these cells reprogrammed to a proliferative, reparative (metaplastic) state. Finally, chief cells required ADAR1 to reenter the cell cycle during metaplasia. Thus, cell-intrinsic ADAR1 signaling is critical for the induction of metaplasia. Because metaplasia increases cancer risk, these findings support roles for ADAR1 and the response to dsRNA in oncogenesis.

Hiperbilirrubinemia: visión del patólogo / Hyperbilirubinemia: pathologist's view

Los niveles de bilirrubina sérica normal en el adulto varían entre 0,3 mg/dL y 1,2 mg/dL, y su valor está determinado por la tasa de captación hepática, conjugación y excreción. La ictericia se hace evidente cuando los niveles de bilirrubina sérica se elevan por encima de 2,5 mg/dL a 3 mg/dL, siendo un indicador de enfermedad subyacente. La bilis es producida por los hepatocitos y fluye desde los canalículos, canales de Hering, conductos biliares intrahepáticos, conductos hepáticos derechos e izquierdos hasta llegar al duodeno. A nivel histopatológico, cualquier entidad que lleve a la acumulación intrahepática de bilis por disfunción hepatocelular u obstrucción biliar genera colestasis, que se observa en la biopsia hepática como la acumulación de tapones de color marrón verdoso de pigmento biliar en los hepatocitos, y secundariamente se observan los canalículos dilatados. Las causas de colestasis intrahepática son diversas e incluyen enfermedades como colangitis biliar primaria, colangitis esclerosante primaria, hepatitis autoinmune, hepatitis virales y toxicidad medicamentosa. Esta revisión tiene como objetivo analizar algunos tipos de hiperbilirrubinemia, resaltando sus características histopatológicas.

Normal serum bilirubin levels in adults range from 0.3 mg/dL to 1.2 mg/dL, and its value is determined by the rate of hepatic uptake, conjugation, and excretion. Jaundice becomes apparent when serum bilirubin levels rise above 2.5 mg/dL to 3.5 mg/dL and is an indicator of underlying disease. Bile is produced by hepatocytes and flows from the canaliculi, Hering's canals, intrahepatic bile ducts, and right and left hepatic ducts to the duodenum. Pathologically, any condition that leadsto intrahepatic accumulation of bile due to hepatocellular dysfunction or biliary obstruction, generates cholestasis, which is observed in liver biopsy as the accumulation of greenish-brown deposits of bile pigment in hepatocytes, with dilated canaliculi. The causes of intrahepatic cholestasis are diverse and include diseases such as primary biliary cholangitis and primary sclerosing cholangitis, autoimmune hepatitis, viral hepatitis, and drug toxicity. This review aims to analyze some types of hyperbilirubinemia, highlighting their histopathological characteristics.

Engaging Latino Families About COVID-19 Vaccines: A Qualitative Study Conducted in Oregon, USA.

OBJECTIVES: Latinos are disproportionately vulnerable to severe COVID-19 due to workplace exposure, multigenerational households, and existing health disparities. Rolling out COVID-19 vaccines among vulnerable Latinos is critical to address disparities. This study explores vaccine perceptions of Latino families to inform culturally centered strategies for vaccine dissemination. METHOD: Semistructured telephone interviews with Latino families (22 mothers and 24 youth, 13-18 years old) explored COVID-19 vaccine perceptions including (1) sources of information, (2) trust of vaccine effectiveness and willingness to get vaccinated, and (3) access to the vaccine distribution. We identified thematic patterns using immersion-crystallization. RESULTS: We found that (1) 41% expressed optimism and willingness to receive the vaccine coupled with concerns about side effects; (2) 45% expressed hesitancy or would refuse vaccination based on mistrust, myths, fear of being used as "guinea pigs," and the perceived role of politics in vaccine development; (3) families "digested" information gathered from social media, the news, and radio through intergenerational communication; and (4) participants called for community-led advocacy and "leading by example" to dispel fear and misinformation. Optimistic participants saw the vaccine as a way to protect their families, allowing youth to return to schools and providing safer conditions for frontline essential workers. CONCLUSIONS: Culturally centered vaccine promotion campaigns may consider the Latino family unit as their target audience by providing information that can be discussed among parents and youth, engaging a range of health providers and advocates that includes traditional practitioners and community health workers, and disseminating information at key venues, such as schools, churches, and supermarkets.

Perceived barriers to and suggested interventions for physical activity during pregnancy among participants of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in Southern California.

BACKGROUND: The American College of Obstetricians and Gynecologists (ACOG) recommends that pregnant women engage in at least 20 to 30 min of moderate-intensity physical activity on most days of the week. Regular exercise during pregnancy is associated with many benefits for the mother and the developing fetus; yet, a large number of pregnant women do not engage in the recommended amounts. This study aimed to investigate barriers to and interventions for physical activity among pregnant WIC participants in Southern California. METHODS: We conducted four focus groups (FGs) with pregnant low-income women aged 18 years or older in either their second or third trimester. FGs were conducted at a WIC center in Southern California. The FGs were held according to language (English vs. Spanish-speaking) and BMI category (normal weight vs. overweight and obese). A total of 28 women participated. We used ATLAS. ti. to analyze the focus group transcripts. The study adhered to the Consolidated Criteria for Reporting Qualitative Research. RESULTS: The mean age of focus group participants was 28.9 years (SD = 6.6), and the majority were Latina. Intrapersonal barriers to physical activity were fatigue and lack of energy, pain and swelling, lack of childcare, medical restrictions and safety concerns, lack of knowledge about exercise safety, and lack of time. Interpersonal barriers included concerns and lack of support from partners and families, conflicting advice from friends and neighbors, and lack of advice on safe exercise from physicians. Women in all four groups suggested a community-based intervention where they can mingle with each other and share their challenges and concerns. Other suggestions to interventions differed among groups and reflected the women's experiences and backgrounds. Specifically, to promote education, English-speaking women preferred a brochure while Spanish-speaking women preferred a video. Overweight women emphasized including children in their exercise activities to promote healthy behavior in youth. CONCLUSIONS: Interventions should be tailored to pregnant women's needs. Primary care providers should provide reassurance and information to pregnant women and their partners on the type and frequency of safe exercise.

Social isolation and connectedness as determinants of well-being: Global evidence mapping focused on LGBTQ youth.

Social isolation describes a lack of a sense of belonging, the inability to engage and connect with others, and the neglect or deterioration of social relationships. This conceptual review describes how social isolation and connectedness affect the well-being of LGBTQ youth. Most studies focused on the psychosocial experience of social isolation, which led to suicide attempt, self-harm, sexual risk, and substance use. Scholarly work has drawn from a variety of frameworks, ranging from minority stress theory to positive youth development, to devise interventions that target isolation and connectedness in schools, community-based organisations, and in online environments. Finally, we discuss the importance of addressing social, cultural, and structural dimensions of social isolation in order to foster enabling environments that allow LGBTQ youth to thrive. This conceptual review suggests that individual and social transformations are the result of young people's meaningful participation in shaping their environment, which is made possible when their capabilities are fostered through social well-being. Our findings suggest the need for measures of social isolation among youth in databanks produced by global institutions, such as the World Health Organization.

Riesgos psicosociales intralaborales y de estrés en trabajadores del sector secundario / Psychosocial labor risk and stress from a secondary sector workers

INTRODUCCIÓN. La presencia de factores de riesgo psicosociales y de estrés en trabajadores de los países en desarrollo puede generar trastornos diversos, como alteración en el sueño, alimentación, entre otros. OBJETIVO. Establecer los riesgos psicosociales intralaborales y de estrés en los trabajadores de una empresa del sector secundario en Querétaro, México. MATERIAL Y MÉTODOS. Investigación transversal, descriptiva realizada en 96 trabajadores. Se aplicó cuestionario COPSOQ-ISTAS21, documento para la evaluación del estrés y la batería para la Evaluación de factores de riesgo psicosocial intralaboral. Se obtuvieron frecuencias y desviación estándar. Se consideraron los aspectos éticos de la investigación en humanos. RESULTADOS.63% son mujeres. Sobre los riesgos psicosociales en el trabajo se encontró que el66%de los participantes nunca influye en la cantidad de trabajo que se le asigna. En relación al estrés,el20% casi siempre presenta dolores en el cuello y espalda. CONCLUSIONES. Múltiples factores generadores de estrés son reversibles, donde la empresa puede generar estrategias no costosas y sencillas para modificarlos.

INTRODUCTION.The presence of psychosocial risk factors can lead to disorders on workers mainly in the developing economies. OBJECTIVE.To establish the psychosocial and stress risk factors and stress in a secondary sector employees in Queretaro, Mexico. MATERIAL AND METHODS. A descriptive cross-sectional study was done to 96 workers. It was apply the Copenhagen Psychosocial Questionnaire its Spanish version (COPSOQ-ISTAS21), stress questionnaire and a battery to assess psychosocial risk factors at the workplace. We obtained frequency and standard deviation. We considered ethical standards and procedures for research with human beings. RESULTS.63% of the workers were female. About the psychosocial risk, the results show that 66% not influence on the labors demands. Concerning to the stress 20% of workers often tend to upper back and neck pain. CONCLUSION.Multiple sources of stress are reversible; employers can be managed stress at work by seeking support from easy strategies to reduce it.

Mapa de riesgos en salud y seguridad en el trabajo en una empresa de manufactura de la ciudad de Querétaro, México / Risk map on health and safety in a manufacturing organization in Queretaro city, Mexico

INTRODUCCIÓN. Salud ocupacional y seguridad industrial conforman un binomio involucrado en la minimización de riesgos laborales, prevención de accidentes y enfermedades de trabajo. El análisis, detección y eliminación de riesgos en los trabajadores ayudan a proteger la salud e incentivar los procesos productivos. OBJETIVO. Construir el mapa de riesgos en salud y seguridad en el trabajo de una empresa de manufactura en la Ciudad de Querétaro que permita fomentar el trabajo seguro y garantice la salud de los trabajadores. MÉTODOS. Investigación descriptiva basada en las etapas de la metodología SafeWork-OIT. Se aplicó a 15 trabajadores de una microempresa que firmaron el consentimiento informado. RESULTADOS. El 100% de los trabajadores fue del sexo masculino, promedio de edad de 26,5 años D.E. de 6,17. Antigüedad laboral de 6 meses a 4 años. La microempresa de manufactura enfrenta cuatro tipos de riesgo laboral: físico (ruido y vibraciones), químico, ergonómico y psicosocial, mismos que se asocian a precariedad laboral, factores psicosociales y de diseño, sumado a estilos de vida que exacerban la presencia de riesgos al interior del centro de trabajo. CONCLUSIONES. El mapa de riesgos resulta una herramienta útil en las empresas y para la enfermera del trabajo. Brinda la posibilidad de desarrollar un proceso de mejora continua, a la vez que evidencia la importancia de continuar la investigación de situaciones que enfrentan las organizaciones micro y medianas, posibilitando implementar acciones educativas para la prevención de riesgos laborales.

INTRODUCTION. Occupational health and industrial safety are both involved in the prevention of risk, occupational accidents and work-related illnesses. It is necessary to analysis, identify and remove risk from workers in order to protect their health and to contribute to the production process. OBJECTIVE. To create a health and safety risk map of the manufacturing company in Queretaro City that promotes safe working conditions that guarantee the workers' health. MATERIAL AND METHODS. A descriptive study design based onthe Safework-ILO methodology. It was apply to 15 workers from a small company by consent. RESULTS. 100% of the workers were male with an average age of 26.5 years old S.D. of 6.17, who were employed for 6 months to 4 years in the company. The small manufacturing company faces 4 risk types: physical (noise and vibrations), chemical, ergonomic and psychosocial, which are associated with informal work, psychological factors and workplace design, adding to the workers lifestyles which may increase the risk hazards. CONCLUSION. The risk map is a useful tool for companies and the occupational health nursing because it allows to develop a continuous improvement as it reflects the importance ongoing research of companies mainly small companies in order to prevent hazards.

Tropism for Spasmolytic Polypeptide-Expressing Metaplasia Allows Helicobacter pylori to Expand Its Intragastric Niche.

BACKGROUND & AIMS: In patients with chronic Helicobacter pylori (H pylori) infection, parietal and chief cell atrophy in the gastric corpus, a process known as spasmolytic polypeptide-expressing metaplasia (SPEM), increases the risk for progression to cancer. The relation between H pylori and these metaplastic changes is unclear. We investigated whether H pylori localizes to regions of SPEM. METHODS: We developed an in situ adherence assay in which we incubated H pylori with free-floating tissue sections from the gastric corpora of mice; we assessed H pylori distribution along the gastric unit by immunofluorescence. We analyzed the interactions of H pylori with tissue collected from mice with acute SPEM, induced by high-dose tamoxifen. We also evaluated how adhesin-deficient H pylori strains, chemical competition assays, and epithelial glycosylation affected H pylori adhesion to SPEM glands. Mice colonized with the mouse-adapted PMSS1 strain were analyzed for H pylori colonization in vivo during tamoxifen-induced SPEM or after decrease of stomach acid with omeprazole. RESULTS: Compared with uninjured glands, H pylori penetrated deep within SPEM glands, in situ, through interaction of its adhesin, SabA, with sialyl-Lewis X, which expanded in SPEM. H pylori markedly increased gastric corpus colonization when SPEM was induced, but this proximal spread reversed in mice allowed to recover from SPEM. Decreasing corpus acidity also promoted proximal spread. However, H pylori penetrated deep within corpus glands in vivo only when sialyl-Lewis X expanded during SPEM. CONCLUSIONS: Helicobacter pylori differentially binds SPEM glands in situ and in mice, in large part by interacting with sialyl-Lewis X. Our findings indicate that H pylori expands its niche into the gastric corpus by promoting and exploiting epithelial metaplastic changes that can lead to tumorigenesis.

Calidad de vida emocional en estudiantes foráneos de tres licenciaturas de una universidad pública del estado de Querétaro, México / Emotional life quality in foreign students from three programs of a public university of Querétaro, Mexico

INTRODUCCIÓN: La calidad de vida (CV) engloba aspectos que son comunes en todos los individuos. Ser estudiante foráneo implica que la persona tenga cambios significativos en su vida. OBJETIVO: Evaluar la calidad de vida emocional de los estudiantes foráneos de las Licenciaturas de Enfermería, Fisioterapia, Educación Física y Ciencias del Deporte (LEF). MATERIAL Y MÉTODOS: Estudio descriptivo, transversal. Se administró el instrumento "Calidad de vida emocional del estudiante foráneo" de 55 preguntas. Alfa de Cronbach de 0,9, validado y piloteado. Se seleccionaron para participar en el estudio alumnos que no viven en Querétaro, que tienen que trasladarse de un municipio lejano a la ciudad u otro estado para estudiar; mayores de edad, hombres y mujeres. RESULTADOS: se aplicaron 147 instrumentos a estudiantes de todos los semestres de cada licenciatura, 35 de la Lic. en Enf, 55 de LEF y 57 de Fisioterapia. CONCLUSIONES: la calidad de vida de los estudiantes foráneos que estudian en la UAQ están sustancialmente en niveles bajos. Lo anterior puede implicar diversas fuentes de estrés, lo que puede repercutir en la salud y el desempeño académico, por lo que se considera importante tomar en cuenta reforzar el aspecto tutorial en estos alumnos.

INTRODUCTION: Life Quality (LQ) covers aspects that are common in all person. To be a foreign student implies that the person had significant changes in his life. OBJECTIVE: To evaluate the emotional life quality of foreign students from Nursing, Physical Education and Sports Science (LEF) and Physiotherapy programs. MATERIAL AND METHODS: Descriptive and cross sectional study. It was applied the instrument "emotional quality life of the foreign student" with 55 questions. Cronbach's alpha of 0.9, validated and piloted. Students who don ́t are from Queretaro city were selected to participate in the study, that have to move of a distant municipality to the city or another condition to study; age more than 18th, men and women. RESULTS: 147 instruments were applied to students from all the semesters of each degree, 35 from nursing, 55 from LEF and 57 from Physiotherapy. CONCLUSIONS: life quality of the foreign students who study at UAQ are substantially in low levels. This can imply diverse sources of stress, what can reverberate in the health and the academic performance. It is important to have in mind to reinforce the tutorial aspect in these students.

Factores asociados a la ocurrencia de accidentes de trabajo en la industria manufacturera / Risk factors associated with occupational accidents in manufacturing industry

La alta prevalencia de accidentes de trabajo está directamente relacionada con el estrés laboral, el turno nocturno, el uso inadecuado o insuficiente de equipos de protección personal, el nivel educativo, manejo de sustancias químicas y el consumo de alcohol, sumado a factores de riesgo ergonómico tales como el ruido, movimientos repetitivos y temperaturas elevadas, que traen consigo una mayor incidencia de accidentes, destacando las caídas de personas al mismo o distinto nivel, caída de objetos, aplastamiento y atrapamiento de miembros. Con todo lo anterior, el presente trabajo pretende mostrar un panorama actualizado de los factores que intervienen en la ocurrencia de accidentes de trabajo en el ramo de manufactura, siendo este, un sector con alta incidencia de accidentes registrados en el mundo. Se revisaron manuscritos publicados en Cochrane Library, Tripdatabase, Embase, Medlinevía PubMedy Cuiden. La búsqueda arrojó 10 textos, 5 de ellos corresponden a revisiones sistemáticas, dos a su vez emplean el meta-análisis, tres estudios de tipo transversal, uno observacional y un análisis de cohorte. Los factores psicosociales y ergonómicos son las exposiciones perjudiciales para la salud más frecuentes en la población trabajadora de la industria de manufactura, lo anterior a consecuencia de la demanda de actividades como el manejo de cargas, operar máquinas, herramientas y ensamble. Riesgos emergentes son descritos en relación con la creación de nuevos empleos, la globalización de mercados y la inclusión de tecnología en los centros de trabajo.

The high prevalence of occupational accidents is directly associated to work stress, night shifts, inadequate or insufficient personal protection equipment, educational level and alcohol consumption. In addition, to the risk factors which are present at work centers, such as: ergonomic, noise and handling of chemicals. All of the latter, generate a high incidence of accidents, like prevailing falls, flattening and entrapment of limbs. With all of this, the following document reflects the current factors which influence occupational accidents in the manufacturing area. Systematic review studies which were published in English and Spanish that evaluate the association of risk factors in manual labors were reviewed. As well as, published texts from the databases of the Cochrane Library, Tripdatabase, Embase, PubMed and Cuiden. Ten studies were found. Ten documents, five of which were a systematic review, two were meta-analysis, three were transsectional studies, one observational and another, a cohort analysis. The most frequent and harmful factors that injure workers are the psychosocial and ergonomic factors. The creation of new jobs, global marketing and the inclusion of new technology in the work centers are related to new emerging risk factors.

Venoms of Micrurus coral snakes: Evolutionary trends in compositional patterns emerging from proteomic analyses.

The application of proteomic tools to the study of snake venoms has led to an impressive growth in the knowledge about their composition (venomics), immunogenicity (antivenomics), and toxicity (toxicovenomics). About one-third of all venomic studies have focused on elapid species, especially those of the Old World. The New World elapids, represented by coral snakes, have been less studied. In recent years, however, a number of venomic studies on Micrurus species from North, Central, and South America have been conducted. An overview of these studies is presented, highlighting the emergence of some patterns and trends concerning their compositional, functional, and immunological characteristics. Results gathered to date, encompassing 18 out of the approximately 85 species of Micrurus, reveal a dichotomy of venom phenotypes regarding the relative abundance of the omnipresent phospholipases A2 (PLA2) and 'three-finger' toxins (3FTx): a group of species express a PLA2-predominant venom composition, while others display a 3FTx-predominant compositional pattern. These two divergent toxin expression phenotypes appear to be related to phylogenetic positions and geographical distributions along a North-South axis in the Americas, but further studies encompassing a higher number of species are needed to assess these hypotheses. The two contrasting phenotypes also show correlations with some toxic functionalities, complexity in the diversity of proteoforms, and immunological cross-recognition patterns. The biological significance for the emergence of a dichotomy of venom compositions within Micrurus, in some cases observed even among sympatric species that inhabit relatively small geographic areas, represents a puzzling and challenging area of research which warrants further studies.

Snake venomics of Micrurus alleni and Micrurus mosquitensis from the Caribbean region of Costa Rica reveals two divergent compositional patterns in New World elapids.

Protein composition, toxicity, and neutralization of the venoms of Micrurus alleni and Micrurus mosquitensis, two sympatric monadal coral snakes found in humid environments of the Caribbean region of Costa Rica, were studied. Proteomic profiling revealed that these venoms display highly divergent compositions: the former dominated by three-finger toxins (3FTx) and the latter by phospholipases A2 (PLA2). Protein family abundances correlated with enzymatic and toxic characteristics of the venoms. Selective inhibition experiments showed that PLA2s play only a marginal role in the lethal effect of M. alleni venom, but have a major role in M. mosquitensis venom. Proteomic data gathered from other Micrurus species evidenced that the two divergent venom phenotypes are recurrent, and may constitute a general trend across New World elapids. Further, M. mosquitensis, but not M. alleni, venom contains PLA2-like/Kunitz-type inhibitor complex(es) that resemble the ASIC1a/2-activating MitTx heterodimeric toxin isolated from Micrurus tener venom. The evolutionary origin and adaptive relevance of the puzzling phenotypic variability of Micrurus venoms remain to be understood. An antivenom against the PLA2-predominant Micrurus nigrocinctus venom strongly cross-recognized and neutralized M. mosquitensis venom, but only weakly M. alleni venom.

BMP-7 Induces Adult Human Pancreatic Exocrine-to-Endocrine Conversion.

The exocrine pancreas can give rise to endocrine insulin-producing cells upon ectopic expression of key transcription factors. However, the need for genetic manipulation remains a translational hurdle for diabetes therapy. Here we report the conversion of adult human nonendocrine pancreatic tissue into endocrine cell types by exposure to bone morphogenetic protein 7. The use of this U.S. Food and Drug Administration-approved agent, without any genetic manipulation, results in the neogenesis of clusters that exhibit high insulin content and glucose responsiveness both in vitro and in vivo. In vitro lineage tracing confirmed that BMP-7-induced insulin-expressing cells arise mainly from extrainsular PDX-1(+), carbonic anhydrase II(-) (mature ductal), elastase 3a (acinar)(-) , and insulin(-) subpopulations. The nongenetic conversion of human pancreatic exocrine cells to endocrine cells is novel and represents a safer and simpler alternative to genetic reprogramming.

MicroRNA expression in alpha and beta cells of human pancreatic islets.

microRNAs (miRNAs) play an important role in pancreatic development and adult ß-cell physiology. Our hypothesis is based on the assumption that each islet cell type has a specific pattern of miRNA expression. We sought to determine the profile of miRNA expression in α-and ß-cells, the main components of pancreatic islets, because this analysis may lead to a better understanding of islet gene regulatory pathways. Highly enriched (>98%) subsets of human α-and ß-cells were obtained by flow cytometric sorting after intracellular staining with c-peptide and glucagon antibody. The method of sorting based on intracellular staining is possible because miRNAs are stable after fixation. MiRNA expression levels were determined by quantitative high throughput PCR-based miRNA array platform screening. Most of the miRNAs were preferentially expressed in ß-cells. From the total of 667 miRNAs screened, the Significant Analysis of Microarray identified 141 miRNAs, of which only 7 were expressed more in α-cells (α-miRNAs) and 134 were expressed more in ß-cells (ß-miRNAs). Bioinformatic analysis identified potential targets of ß-miRNAs analyzing the Beta Cell Gene Atlas, described in the T1Dbase, the web platform, supporting the type 1 diabetes (T1D) community. cMaf, a transcription factor regulating glucagon expression expressed selectively in α-cells (TFα) is targeted by ß-miRNAs; miR-200c, miR-125b and miR-182. Min6 cells treated with inhibitors of these miRNAs show an increased expression of cMaf RNA. Conversely, over expression of miR-200c, miR-125b or miR-182 in the mouse alpha cell line αTC6 decreases the level of cMAF mRNA and protein. MiR-200c also inhibits the expression of Zfpm2, a TFα that inhibits the PI3K signaling pathway, at both RNA and protein levels.In conclusion, we identified miRNAs differentially expressed in pancreatic α- and ß-cells and their potential transcription factor targets that could add new insights into different aspects of islet biology and pathophysiology.

Intracardial embryonic delivery of developmental modifiers in utero.

Our knowledge of organ ontogeny is largely based on loss-of-function (knockout) or gain-of-function (transgenesis) approaches. However, developmental modulators such as proteins, mRNAs, microRNAs(miRNAs), small interfering RNAs, and other small molecules may complement the above DNA-modifying technologies in a much more direct way. Unfortunately, their use is often limited by the ability of these compounds to cross the placenta and reach physiologically relevant concentrations when administered systemically to the mother. The design of safe and effective techniques to deliver these compounds into the embryo is therefore an area of great scientific potential. In this article we report a new method for introducing developmental modulators into murine embryos by means of direct injection into the heart. Unlike other reported methods that require surgical exposure of the uterus, our percutaneous ultrasound-guided approach allows for the intracardial injection of mouse embryos as early as embryonic day 10.5 (e10.5) and throughout gestation in a minimally invasive manner that largely preserves embryo viability. This system offers a critical advantage over in vitro settings because the effects of any given treatment can be observed without disturbing the native environment of the developing organ. Procedures are described for the delivery and detection of transducible proteins as well as morpholinos designed to block the expression of specific miRNAs within the living embryo.

Inflammation-Mediated Regulation of MicroRNA Expression in Transplanted Pancreatic Islets.

Nonspecific inflammation in the transplant microenvironment results in ß-cell dysfunction and death influencing negatively graft outcome. MicroRNA (miRNA) expression and gene target regulation in transplanted islets are not yet well characterized. We evaluated the impact of inflammation on miRNA expression in transplanted rat islets. Islets exposed in vitro to proinflammatory cytokines and explanted syngeneic islet grafts were evaluated by miRNA arrays. A subset of 26 islet miRNAs was affected by inflammation both in vivo and in vitro. Induction of miRNAs was dependent on NF-κB, a pathway linked with cytokine-mediated islet cell death. RT-PCR confirmed expression of 8 miRNAs. The association between these miRNAs and mRNA target-predicting algorithms in genome-wide RNA studies of ß-cell inflammation identified 238 potential miRNA gene targets. Several genes were ontologically associated with regulation of insulin signaling and secretion, diabetes, and islet physiology. One of the most activated miRNAs was miR-21. Overexpression of miR-21 in insulin-secreting MIN6 cells downregulated endogenous expression of the tumor suppressor Pdcd4 and of Pclo, a Ca(2+) sensor protein involved in insulin secretion. Bioinformatics identified both as potential targets. The integrated analysis of miRNA and mRNA expression profiles revealed potential targets that may identify molecular targets for therapeutic interventions.

Antisense miR-7 impairs insulin expression in developing pancreas and in cultured pancreatic buds.

MicroRNAs regulate gene expression by inhibiting translation or inducing target mRNA degradation. MicroRNAs regulate organ differentiation and embryonic development, including pancreatic specification and islet function. We showed previously that miR-7 is highly expressed in human pancreatic fetal and adult endocrine cells. Here we determined the expression profile of miR-7 in the mouse-developing pancreas by RT-PCR and in situ hybridization. MiR-7 expression was low between embryonic days e10.5 and e11.5, then began to increase at e13.5 through e14.5, and eventually decreased by e18. In situ hybridization and immunostaining analysis showed that miR-7 colocalizes with endocrine marker Isl1, suggesting that miR-7 is expressed preferentially in endocrine cells. Whole-mount in situ hybridization shows miR-7 highly expressed in the embryonic neural tube. To investigate the role of miR-7 in development of the mouse endocrine pancreas, antisense miR-7 morpholinos (MO) were delivered to the embryo at an early developmental stage (e10.5 days) via intrauterine fetal heart injection. Inhibition of miR-7 during early embryonic life results in an overall downregulation of insulin production, decreased ß-cell numbers, and glucose intolerance in the postnatal period. This phenomenon is specific for miR-7 and possibly due to a systemic effect on pancreatic development. On the other hand, the in vitro inhibition of miR-7 in explanted pancreatic buds leads to ß-cell death and generation of ß-cells expressing less insulin than those in MO control. Therefore, in addition to the potential indirect effects on pancreatic differentiation derived from its systemic downregulation, the knockdown of miR-7 appears to have a ß-cell-specific effect as well. These findings suggest that modulation of miR-7 expression could be utilized in the development of stem cell therapies to cure diabetes.