The protective role of commensal gut microbes and their metabolites against bacterial pathogens.

Multidrug-resistant microorganisms have become a major public health concern around the world. The gut microbiome is a gold mine for bioactive compounds that protect the human body from pathogens. We used a multi-omics approach that integrated whole-genome sequencing (WGS) of 74 commensal gut microbiome isolates with metabolome analysis to discover their metabolic interaction with Salmonella and other antibiotic-resistant pathogens. We evaluated differences in the functional potential of these selected isolates based on WGS annotation profiles. Furthermore, the top altered metabolites in co-culture supernatants of selected commensal gut microbiome isolates were identified including a series of dipeptides and examined for their ability to prevent the growth of various antibiotic-resistant bacteria. Our results provide compelling evidence that the gut microbiome produces metabolites, including the compound class of dipeptides that can potentially be applied for anti-infection medication, especially against antibiotic-resistant pathogens. Our established pipeline for the discovery and validation of bioactive metabolites from the gut microbiome as novel candidates for multidrug-resistant infections represents a new avenue for the discovery of antimicrobial lead structures.

Compositional and functional differences of the vaginal microbiota of women with and without cervical dysplasia.

Alterations in the vaginal microbiota, including both species composition and functional pathways, have been associated with HPV infection and progression of dysplasia to cervical cancer. To further explore this, shotgun metagenomic sequencing was used to taxonomically and functionally characterize the vaginal microbiota of women with and without cervical dysplasia. Women with histologically verified dysplasia (n = 177; low grade dysplasia (LSIL) n = 81, high-grade dysplasia (HSIL) n = 94, cancer n = 2) were compared with healthy controls recruited from the cervical screening programme (n = 177). Women with dysplasia had a higher vaginal microbial diversity, and higher abundances of Gardnerella vaginalis, Aerococcus christensenii, Peptoniphilus lacrimalis and Fannyhessea vaginae, while healthy controls had higher relative abundance of Lactobacillus crispatus. Genes involved in e.g. nucleotide biosynthesis and peptidoglycan biosynthesis were more abundant in women with dysplasia. Healthy controls showed higher abundance of genes important for e.g. amino acid biosynthesis, (especially L-lysine) and sugar degradation. These findings suggest that the microbiota may have a role in creating a pro-oncogenic environment in women with dysplasia. Its role and potential interactions with other components in the microenvironment deserve further exploration.

Sensitive quantification of short-chain fatty acids combined with global metabolomics in microbiome cultures.

The microbiome has been identified to have a key role for the physiology of their human host. One of the major impacts is the clearance of bacterial pathogens. We have now developed a chemoselective probe methodology for the absolute quantification of short-chain fatty acids at low nM concentrations, with high reproducibility and spiked isotope labelled internal standards. Immobilization to magnetic beads allows for separation from the matrix and the tagged metabolites upon bioorthogonal cleavage can be analyzed via UHPLC-MS. The major advantage of our sensitive method is the simple combination with global metabolomics analysis as only a small sample volume is required. We have applied this chemical metabolomics strategy for targeted SCFA analysis combined with global metabolomics on gut microbiome co-cultures with Salmonella and investigated the effect of antibiotic treatment.

A 3D Bioprinted Gut Anaerobic Model for Studying Bacteria-Host Interactions.

The role of the human intestinal tract in host-microbe interactions has been highlighted in recent years. Several 3-dimensional (3D) models have been developed to reproduce the physiological characteristics of the human gut and to investigate the function of the gut microbiota. One challenge for 3D models is to recapitulate the low oxygen concentrations in the intestinal lumen. Moreover, most earlier 3D culture systems used a membrane to physically separate bacteria from the intestinal epithelium, which has sometimes made the studies of bacteria adhering to or invading cells less feasible. We report the establishment of a 3D gut epithelium model and cultured it at high cell viability under an anaerobic condition. We further cocultured intestinal bacteria including both commensal and pathogen directly with epithelial cells in the established 3D model under the anaerobic condition. We subsequently compared the gene expression differences of aerobic and anaerobic conditions for cell and bacterial growth via dual RNA sequencing. Our study provides a physiologically relevant 3D gut epithelium model that mimics the anaerobic condition in the intestinal lumen and supplies a powerful system for future in-depth gut-microbe interactional investigations.

Lipase-Catalyzed Synthesis and Biological Evaluation of N-Picolineamides as Trypanosoma cruzi Antiproliferative Agents.

In our search for new safe antiparasitic agents, an enzymatic pathway was applied to synthesize a series of N-pyridinylmethyl amides derived from structurally different carboxylic acids. Thirty derivatives, including 11 new compounds, were prepared through lipase-catalyzed acylation in excellent yields. In order to optimize the synthetic methodology, the impact of different reaction parameters was analyzed. Some compounds were evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible for American trypanosomiasis (Chagas' disease). Some of them showed significant activity as parasite proliferation inhibitors. Amides derived from 2-aminopicoline and stearic and elaidic acids were as potent as nifurtimox against the amastigote form of T. cruzi, the clinically relevant form of the parasite. Even more, a powerful synergism between nifurtimox and N-(pyridin-2-ylmethyl)stereamide was observed, almost completely inhibiting the proliferation of the parasite. Besides, the obtained compounds showed no toxicity in Vero cells, making them excellent potential candidates as lead drugs.

Impacts of the 2017 Brazilian National Primary Care Policy on public primary health care in Rio de Janeiro, Brazil.

In 2017, in a scenario of financial restrictions caused by an economic crisis in Brazil, a new primary health care policy promoted changes in the way different primary health care models were prioritized and implemented, with possible negative effects on the access to primary health care. This study aims to investigate if the 2017 Brazilian National Primary Care Policy (PNAB) negatively affected the primary care organization based on the Family Health Strategy (FHS) model and on the access to public primary care services in the city of Rio de Janeiro. The annual averages and the pre- and post-2017 averages of 15 variables were analyzed to identify possible trend breaks in 2017. A Bayesian structural time series model was used to determine the differences between actual and predicted post-2017 averages of each variable. The data were obtained via the Brazilian Health Informatics Department (DATASUS), the Department of Informatics of the Brazilian Unified National Health System. The annual average of family health teams was 1,179.9 teams, in 2017, and 788.8 teams in 2020, while the annual average of equivalent family health teams was 163.6, in 2017, and 125.4, in 2020. The actual post-2017 average of 989.3 family health teams (p = 0.004) was 16.7% lower than the predicted post-2017 average of 1,187.4 teams. In total, 62.6% and 40.5% of the population in Rio de Janeiro were covered by the FHS in 2017, and 2020, respectively. The provision of public primary care services decreased after 2017. Results show a deterioration of the FHS in Rio de Janeiro after 2017 and no increase in the traditional primary care model. Access to public primary care services reduced in the same period.

Impacts of the 2017 Brazilian National Primary Care Policy on public primary health care in Rio de Janeiro, Brazil / Os impactos da Política Nacional de Atenção Básica de 2017 sobre a atenção primária pública no Rio de Janeiro, Brasil / Impactos de la Política Nacional de Atención Primaria 2017 en la atención primaria pública en Río de Janeiro, Brasil

In 2017, in a scenario of financial restrictions caused by an economic crisis in Brazil, a new primary health care policy promoted changes in the way different primary health care models were prioritized and implemented, with possible negative effects on the access to primary health care. This study aims to investigate if the 2017 Brazilian National Primary Care Policy (PNAB) negatively affected the primary care organization based on the Family Health Strategy (FHS) model and on the access to public primary care services in the city of Rio de Janeiro. The annual averages and the pre- and post-2017 averages of 15 variables were analyzed to identify possible trend breaks in 2017. A Bayesian structural time series model was used to determine the differences between actual and predicted post-2017 averages of each variable. The data were obtained via the Brazilian Health Informatics Department (DATASUS), the Department of Informatics of the Brazilian Unified National Health System. The annual average of family health teams was 1,179.9 teams, in 2017, and 788.8 teams in 2020, while the annual average of equivalent family health teams was 163.6, in 2017, and 125.4, in 2020. The actual post-2017 average of 989.3 family health teams (p = 0.004) was 16.7% lower than the predicted post-2017 average of 1,187.4 teams. In total, 62.6% and 40.5% of the population in Rio de Janeiro were covered by the FHS in 2017, and 2020, respectively. The provision of public primary care services decreased after 2017. Results show a deterioration of the FHS in Rio de Janeiro after 2017 and no increase in the traditional primary care model. Access to public primary care services reduced in the same period.

Em 2017, dentro de um cenário de restrições financeiras provocadas por uma crise econômica no Brasil, uma nova política de atenção primária em saúde introduziu mudanças na maneira que diferentes modelos de atenção primária eram priorizados e implementados, com possíveis efeitos negativos no acesso à atenção primária. O estudo teve como objetivo investigar se a Política Nacional de Atenção Básica de 2017 teve impacto negativo sobre a organização da atenção primária baseada no modelo da Estratégia Saúde da Família (ESF) e no acesso aos serviços de atenção primária no Município do Rio de Janeiro. Foram analisadas as médias anuais e as médias pré- e pós-2017 de 15 variáveis para identificar possíveis quebras de tendência em 2017. Foi usado um modelo bayesiano de séries temporais estruturais para determinar as diferenças entre as médias pós-2017 reais e previstas para cada variável. Os dados foram obtidos do Departamento de Informática do SUS (DATASUS). O número anual médio de equipes de saúde da família foi 1.179,9 em 2017 e 788,8 em 2020, enquanto a média anual de equivalentes de equipes de saúde da família foi 163,6 em 2017 e 125,4 em 2020. A média pós-2017 real de 989,3 equipes de saúde da família (p = 0,004) foi 16,7% mais baixa que a média pós-2017 prevista, de 1.187,4 equipes. A cobertura da população do Rio de Janeiro pela ESF era 62,6% em 2017, caindo para 40,5% em 2020. A prestação de serviços públicos de atenção primária caiu depois de 2017. Os resultados demonstram a deterioração da ESF no Rio de Janeiro depois de 2017, sem nenhum aumento no modelo tradicional de atenção primária. O acesso aos serviços públicos de atenção primário diminuiu durante o mesmo período.

En 2017, en un escenario de restricciones financieras causadas por una crisis económica en Brasil, la nueva política nacional de atención primaria promovió cambios, con el fin de que se priorizaran e implementaran diferentes modelos de atención primaria, con posibles efectos negativos en el acceso a la atención primaria en salud. El objetivo de este estudio fue investigar si la Política Nacional de Atención Primária de 2017 tuvo un impacto negativo en la organización de la atención primaria, basada en el modelo de Estrategia de Salud Familiar (ESF), y en el acceso a los servicios públicos de atención primaria en la ciudad de Río de Janeiro. Se analizaron los promedios anuales y los pre- y post-2017 promedios de 15 variables para identificar posibles rupturas de tendencia en 2017. Se usó uno modelo Bayesiano estructural de series temporales para determinar las diferencias entre los promedios actuales y previstos post-2017 de cada variable. Los datos se obtuvieron mediante el Departamento de Informática del Sistema Único de Salud (DATASUS). El promedio anual de equipos de salud familiar fue 1.179,9 equipos en 2017 y 788,8 equipos en 2020, mientras que el promedio anual de los equipos equivalentes familiares fue 163,6 en 2017 y 125,4 en 2020. El promedio actual post-2017 de 989,3 equipos de salud familiares (p = 0,004) fue un 16,7% más bajo que el promedio previsto post-2017 de 1.187,4 equipos. El porcentaje de población en Río de Janeiro cubierto por la ESF fue 62,6% en 2017 y 40,5% en 2020. La provisión de servicios públicos de atención primaria se redujo después de 2017. Los resultados demostraron el deterioro de la ESF en Río de Janeiro después 2017 y no hubo incrementos en el modelo de atención primaria tradicional. El acceso a los servicios de atención primaria pública decayó en el mismo periodo.

Nanomedicine and therapy of lung diseases / Nanomedicina e terapia de doenças pulmonares

The use of nanotechnology has significantly increased in different fields of science, including the development of drug delivery systems. Currently, the most modern pharmaceutical nanocarriers, such as liposomes, micelles, nanoemulsions and polymeric nanoparticles, demonstrate extremely useful properties from the point of view of drug therapy. In this context, the development of nanocarriers for pulmonary application has been much debated by the scientific community in recent decades. Although research on the use of nanoparticles for pulmonary application are still in the initial phase, the studies conducted to date suggest that the development of drug delivery systems for systemic or local treatment of diseases that affect the respiratory system may be promising.

O uso da nanotecnologia tem aumentado significativamente em diversas áreas da ciência. Entre elas, está o desenvolvimento de sistemas de liberação de medicamentos. Atualmente, os nanocarreadores farmacêuticos mais modernos, como os lipossomas, as micelas, as nanoemulsões e as nanopartículas poliméricas, demonstram propriedades extremamente úteis do ponto de vista farmacoterápico. Nesse contexto, o desenvolvimento de nanocarreadores para aplicação pulmonar tem sido um tema amplamente debatido pela comunidade científica nas últimas décadas. Embora as pesquisas sobre o uso de nanopartículas para aplicação pulmonar ainda estejam em fase inicial, estudos realizados até hoje sugerem que o delineamento de sistemas de liberação de medicamentos para o tratamento sistêmico ou local de doenças que afetam o sistema respiratório, pode ser promissor no desenvolvimento de novas terapias de doenças pulmonares.

Nanomedicine and therapy of lung diseases.

The use of nanotechnology has significantly increased in different fields of science, including the development of drug delivery systems. Currently, the most modern pharmaceutical nanocarriers, such as liposomes, micelles, nanoemulsions and polymeric nanoparticles, demonstrate extremely useful properties from the point of view of drug therapy. In this context, the development of nanocarriers for pulmonary application has been much debated by the scientific community in recent decades. Although research on the use of nanoparticles for pulmonary application are still in the initial phase, the studies conducted to date suggest that the development of drug delivery systems for systemic or local treatment of diseases that affect the respiratory system may be promising.

Cistadenocarcinoma mucinso gigante de ovario en el embarazo. Presentación de un caso y revisión de la literatura / Giant mucinous cystadenocarcinoma of the ovary during pregancy. A case report and literature of review

El tumor maligno de ovario en el embarazo se encuentra en un 2 a 5 por ciento de todas las masas anexiales que ocurren en el embarazo. El embarazo no tiene un efecto adverso directo en el pronóstico de las pacientes con un tumor de ovario maligno; se requiere de una buena clasificación por estadios durante el procedimiento quirúrgico para establecer un adecuado tratamiento. Presentamos el caso de una mujer de 35 años diagnosticado y manejado en el Hospital San Rafael de Tunja. Colombia, con 20 semanas de embarazo y un tumor de ovario gigante que fue clasificado por el estudio histopatológico como cistadenocarcinoma mucinoso; se hace una revisión detallada de la literatura de tumor de ovario y embarazo