Conocimiento y uso de las distintas herramientas de tamizaje del cáncer de mama entre médicos del primer nivel de atención: un estudio transversal / Knowledge and use of different breast cancer screening tools among primary care physicians: a cross-sectional study / Conhecimento e uso de diferentes ferramentas de rastreamento do câncer de mama entre médicos da atenção primária: um estudo transversal

Resumen: Introducción: en Uruguay el cáncer de mama (CM) ocupa el primer lugar en incidencia y mortalidad por cáncer en la mujer. Objetivo: conocer la implementación del tamizaje del CM en la práctica clínica habitual y el grado de adhesión a las recomendaciones planteadas en el año 2015 por el Ministerio de Salud Pública (MSP) para la detección temprana del CM entre los médicos del primer nivel de atención. Material y métodos: se trata de un estudio observacional descriptivo y transversal. Se aplicó una encuesta dirigida a médicos del primer nivel de atención, de carácter anónimo. Resultados: se incluyeron 169 médicos, 89,4% (151) considera que el uso de la mamografía de tamizaje disminuye la mortalidad por CM, 54,4% (92) indica la mamografía a partir de los 40 años de edad y 38,5% (65) a partir de los 50 años. El 56,8% (96) indica la mamografía cada 2 años en la población de mujeres que se encuentran entre 50 y 69 años. El 65,7% de los encuestados (111) conoce la guía nacional y 47,9% (81) la utiliza, mientras que el 18,9% (32) utiliza recomendaciones de otras sociedades científicas. Conclusión: el presente estudio evidenció que los médicos del primer nivel de atención hacen un uso correcto de las distintas herramientas de tamizaje del CM. Se necesitan medidas activas para desarrollar programas educativos para el personal de salud, que podrían permitirles difundir conocimientos e influir positivamente en las actitudes de los pacientes.

Summary: Introduction: in Uruguay, breast cancer (BC) is the leading cause of cancer incidence and mortality in women. Objective: to understand the implementation of BC screening among primary care physicians in routine clinical practice and the degree of adherence to the recommendations put forward in 2015 by the Ministry of Public Health (MPH) for the early detection of BC. Materials and methods: this was a descriptive, cross-sectional, observational study. An anonymous survey was administered to physicians working in primary care. Results: 169 physicians were included, 89.4% (151) consider the use of screening mammography decreases mortality from BC, 54.4% (92) indicate mammography from 40 years of age and 38.5% (65) from 50 years of age. The majority (56.8%, 96) indicate mammography every 2 years in the population of women aged 50-69 years. Of the respondents, 65.7% (111) were aware of the national guidelines and 47.9% (81) followed them, while 18.9% (32) followed recommendations from other scientific bodies. Conclusion: this study showed that primary care physicians make correct use of the different BC screening tools. Active measures are needed to develop educational programs for healthcare personnel, which may enable them to disseminate knowledge and positively influence patients' attitudes.

Resumo: Introdução: o câncer de mama (CM) ocupa o primeiro lugar em incidência e mortalidade por câncer em mulheres no Uruguai. Objetivo: conhecer a implementação do rastreamento do CM na prática clínica de rotina e o grau de adesão às recomendações de 2015 do Ministério da Saúde Pública para detecção precoce do CM entre os médicos do primeiro nível de atenção. Material e métodos: trata-se de um estudo observacional descritivo e transversal. Foi aplicada uma pesquisa anônima destinada aos médicos do primeiro nível de atenção. Resultados: foram incluídos 169 médicos; 89,4% (151) consideram que o uso da mamografia de rastreamento diminui a mortalidade por CM, 54,4% (92) indicam mamografia a partir dos 40 anos e 38,5% (65) a partir dos 50 anos; 56,8% (96) indicam mamografia a cada 2 anos na população de mulheres entre 50 e 69 anos. 65,7% dos respondentes (111) conhecem o guia nacional e 47,9% (81) o utilizam, enquanto 18,9% (32) utilizam recomendações de outras sociedades científicas. Conclusão: este estudo mostrou que os médicos do primeiro nível de atenção fazem uso correto das diferentes ferramentas de rastreamento do CM. São necessárias medidas ativas para desenvolver programas educacionais para os profissionais de saúde, que possam permitir que eles disseminem o conhecimento e influenciem positivamente as atitudes dos pacientes.

Activity-based protein profiling identifies alternating activation of enzymes involved in the bifidobacterium shunt pathway or mucin degradation in the gut microbiome response to soluble dietary fiber.

While deprivation of dietary fiber has been associated with adverse health outcomes, investigations concerning the effect of dietary fiber on the gut microbiome have been largely limited to compositional sequence-based analyses or utilize a defined microbiota not native to the host. To extend understanding of the microbiome's functional response to dietary fiber deprivation beyond correlative evidence from sequence-based analyses, approaches capable of measuring functional enzymatic activity are needed. In this study, we use an activity-based protein profiling (ABPP) approach to identify sugar metabolizing and transport proteins in native mouse gut microbiomes that respond with differential activity to the deprivation or supplementation of the soluble dietary fibers inulin and pectin. We found that the microbiome of mice subjected to a high fiber diet high in soluble fiber had increased functional activity of multiple proteins, including glycoside hydrolases, polysaccharide lyases, and sugar transport proteins from diverse taxa. The results point to an increase in activity of the Bifidobacterium shunt metabolic pathway in the microbiome of mice fed high fiber diets. In those subjected to a low fiber diet, we identified a shift from the degradation of dietary fibers to that of gut mucins, in particular by the recently isolated taxon "Musculibacterium intestinale", which experienced dramatic growth in response to fiber deprivation. When combined with metabolomics and shotgun metagenomics analyses, our findings provide a functional investigation of dietary fiber metabolism in the gut microbiome and demonstrates the power of a combined ABPP-multiomics approach for characterizing the response of the gut microbiome to perturbations.

Functional morphogenesis from embryos to adults: Late development shapes trophic niche in coral reef damselfishes.

The damselfishes are one of the dominant coral reef fish lineages. Their ecological diversification has involved repeated transitions between pelagic feeding using fast bites and benthic feeding using forceful bites. A highly-integrative approach that combined gene expression assays, shape analyses, and high-speed video analyses was used to examine the development of trophic morphology in embryonic, larval, juvenile, and adult damselfishes. The anatomical characters that distinguish pelagic-feeding and benthic-feeding species do not appear until after larval development. Neither patterns of embryonic jaw morphogenesis, larval skull shapes nor larval bite mechanics significantly distinguished damselfishes from different adult trophic guilds. Analyses of skull shape and feeding performance identified two important transitions in the trophic development of a single species (the orange clownfish; Amphiprion percula): (a) a pronounced transformation in feeding mechanics during metamorphosis; and (b) more protracted cranial remodeling over the course of juvenile development. The results of this study indicate that changes in postlarval morphogenesis have played an important role in damselfish evolution. This is likely to be true for other fish lineages, particularly if they consist of marine species, the majority of which have planktonic larvae with different functional requirements for feeding in comparison to their adult forms.

Structure Dependent Determination of Organophosphate Targets in Mammalian Tissues Using Activity-Based Protein Profiling.

Acute and chronic exposures to organophosphates (OPs), including agricultural pesticides, industrial chemicals, and chemical warfare agents, remain a significant worldwide health risk. The mechanisms by which OPs alter development and cognition in exposed individuals remain poorly understood, in part due to the large number of structurally diverse OPs and the wide range of affected proteins and signaling pathways. To investigate the influence of structure on OP targets in mammalian systems, we have developed a series of probes for activity-based protein profiling (ABPP) featuring two distinct reactive groups that mimic OP chemical reactivity. FOP features a fluorophosphonate moiety, and PODA and CODA utilize a dialkynyl phosphate ester; both reactive group types target serine hydrolase activity. As the oxon represents the highly reactive and toxic functional group of many OPs, the new probes described herein enhance our understanding of tissue-specific reactivity of OPs. Chemoproteomic analysis of mouse tissues treated with the probes revealed divergent protein profiles, demonstrating the influence of probe structure on protein targeting. These targets also vary in sensitivity toward different OPs. The simultaneous use of multiple probes in ABPP experiments may therefore offer more comprehensive coverage of OP targets; FOP consistently labeled more targets in both brain and liver than PODA or CODA, suggesting the dialkyne warhead is more selective for enzymes in major signaling pathways than the more reactive fluorophosphonate warhead. Additionally, the probes can be used to assess reactivation of OP-inhibited enzymes by N-oximes and may serve as diagnostic tools for screening of therapeutic candidates in a panel of protein targets. These applications will help clarify the short- and long-term effects of OP toxicity beyond acetylcholinesterase inhibition, investigate potential points of convergence for broad spectrum therapeutic development, and support future efforts to screen candidate molecules for efficacy in various model systems.

Thyroid hormone modulation during zebrafish development recapitulates evolved diversity in danionin jaw protrusion mechanics.

Protrusile jaws are a highly useful innovation that has been linked to extensive diversification in fish feeding ecology. Jaw protrusion can enhance the performance of multiple functions, such as suction production and capturing elusive prey. Identifying the developmental factors that alter protrusion ability will improve our understanding of fish diversification. In the zebrafish protrusion arises postmetamorphosis. Fish metamorphosis typically includes significant changes in trophic morphology, accompanies a shift in feeding niche and coincides with increased thyroid hormone production. We tested whether thyroid hormone affects the development of zebrafish feeding mechanics. We found that it affected all developmental stages examined, but that effects were most pronounced after metamorphosis. Thyroid hormone levels affected the development of jaw morphology, feeding mechanics, shape variation, and cranial ossification. Adult zebrafish utilize protrusile jaws, but an absence of thyroid hormone impaired development of the premaxillary bone, which is critical to jaw protrusion. Premaxillae from early juvenile zebrafish and hypothyroid adult zebrafish resemble those from adults in the genera Danionella, Devario, and Microdevario that show little to no jaw protrusion. Our findings suggest that evolutionary changes in how the developing skulls of danionin minnows respond to thyroid hormone may have promoted diversification into different feeding niches.

A Probe-Enabled Approach for the Selective Isolation and Characterization of Functionally Active Subpopulations in the Gut Microbiome.

Commensal microorganisms in the mammalian gut play important roles in host health and physiology, but a central challenge remains in achieving a detailed mechanistic understanding of specific microbial contributions to host biochemistry. New function-based approaches are needed that analyze gut microbial function at the molecular level by coupling detection and measurements of in situ biochemical activity with identification of the responsible microbes and enzymes. We developed a platform employing ß-glucuronidase selective activity-based probes to detect, isolate, and identify microbial subpopulations in the gut responsible for this xenobiotic metabolism. We find that metabolic activity of gut microbiota can be plastic and that between individuals and during perturbation, phylogenetically disparate populations can provide ß-glucuronidase activity. Our work links biochemical activity with molecular-scale resolution without relying on genomic inference.