Ultraflexible electrodes for recording neural activity in the mouse spinal cord during motor behavior.

Implantable electrode arrays are powerful tools for directly interrogating neural circuitry in the brain, but implementing this technology in the spinal cord in behaving animals has been challenging due to the spinal cord's significant motion with respect to the vertebral column during behavior. Consequently, the individual and ensemble activity of spinal neurons processing motor commands remains poorly understood. Here, we demonstrate that custom ultraflexible 1-µm-thick polyimide nanoelectronic threads can conduct laminar recordings of many neuronal units within the lumbar spinal cord of unrestrained, freely moving mice. The extracellular action potentials have high signal-to-noise ratio, exhibit well-isolated feature clusters, and reveal diverse patterns of activity during locomotion. Furthermore, chronic recordings demonstrate the stable tracking of single units and their functional tuning over multiple days. This technology provides a path for elucidating how spinal circuits compute motor actions.

Trans-segmental imaging in the spinal cord of behaving mice.

Spinal cord circuits play crucial roles in transmitting pain, but the underlying activity patterns within and across spinal segments in behaving mice have remained elusive. We developed a wearable widefield macroscope with a 7.9-mm2 field of view, ~3- to 4-µm lateral resolution, 2.7-mm working distance and <10-g overall weight and show that highly localized painful mechanical stimuli evoke widespread, coordinated astrocyte excitation across multiple spinal segments.

Multiplex translaminar imaging in the spinal cord of behaving mice.

While the spinal cord is known to play critical roles in sensorimotor processing, including pain-related signaling, corresponding activity patterns in genetically defined cell types across spinal laminae have remained challenging to investigate. Calcium imaging has enabled cellular activity measurements in behaving rodents but is currently limited to superficial regions. Here, using chronically implanted microprisms, we imaged sensory and motor-evoked activity in regions and at speeds inaccessible by other high-resolution imaging techniques. To enable translaminar imaging in freely behaving animals through implanted microprisms, we additionally developed wearable microscopes with custom-compound microlenses. This system addresses multiple challenges of previous wearable microscopes, including their limited working distance, resolution, contrast, and achromatic range. Using this system, we show that dorsal horn astrocytes in behaving mice show sensorimotor program-dependent and lamina-specific calcium excitation. Additionally, we show that tachykinin precursor 1 (Tac1)-expressing neurons exhibit translaminar activity to acute mechanical pain but not locomotion.

Glycemic Control in Type 1 Diabetes Mellitus and COVID-19: What We Learned From the Lockdown Experience.

INTRODUCTION: Confinement measures that were imposed during the COVID-19 pandemic drastically changed the routines of the population. Some studies on the impact of confinement on glycemic control suggest a reduction of 0.1 to 0.5% in glycated hemoglobin. The objective of this study was to evaluate the impact of the COVID-19 pandemic lockdown on glycemic control in adult patients with type 1 diabetes mellitus. METHODS: An observational retrospective cohort study of patients with type 1 diabetes mellitus followed in a Diabetes Unit was performed. The study compared the metabolic control of these patients before (between January 1st and March 18th, 2020) and after (between May 3rd and July 31st, 2020) the lockdown. RESULTS: The study included 102 patients with type 1 diabetes mellitus (51% females), with a median age of 36 years (interquartile range 18.75, (24.25-43)) and a median duration of diabetes of 15 years (interquartile range 13, (8-21)). After lockdown, a significant decrease of 0.28±0.71% in glycated hemoglobin was observed (7.88±1.33% vs 7.59±1.23%, p=<0.001). In patients using continuous glucose monitoring a significant improvement in time in range was also noted (47.25±17.33% vs 49.97±18.61%, p=0.008). CONCLUSIONS: This study demonstrated an improvement in glycemic control after the lockdown. This might be explained by the positive impact of stable schedules, healthy meals and greater availability to make therapeutic adjustments to glycemic control. The fact that diabetes was considered a risk factor for the development of severe COVID-19 disease might also influence patients to increase their efforts to optimize their glycemic control.

Psychiatric disorders in post-traumatic brain injury patients: A scoping review.

Background: Traumatic Brain Injury (TBI) is an important antecedent in the evaluation of patients with psychiatric disorders. The association between TBI and the subsequent appearance of psychiatric disorders has been documented, however, the findings found in the literature are diverse and controversial. Objective: To identify the most prevalent psychiatric disorders after head trauma. Design: An exploratory review (SCOPING) was carried out using the PRISMA extension protocol. Articles published between the years 2010-2022 were used to identify and describe the most prevalent psychiatric disorders after a TBI. Psychiatric disorders were classified according to clinical characteristics in neurotic syndromes, psychotic syndromes, cognitive disorders, among others. Results: A total of 32 articles were included. In the framework of neurotic syndromes, depression is the most prevalent psychiatric alteration after a TBI, becoming a sequel that shows a higher incidence in the first year after the traumatic event. The findings found in relation to post-traumatic stress disorder are controversial, showing great variability regarding the degree of severity of the injury. The prevalence of psychotic syndromes is relatively low because it is difficult to determine if the psychosis is a direct consequence of a TBI. In the cognitive sphere, it was found that people with TBI presented alterations in cognitive functions. Conclusions: The findings found in the review respond to the hypothesis initially raised, which assumes that head trauma is an important etiological factor in the appearance of psychiatric disorders.

Type 1 Diabetes Mellitus and Multiple Sclerosis: An Association to Consider.

Type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) have been described as chronic organ-specific diseases, approached by different medical specialties. However, they share more etiologic and pathologic features than expected between two autoimmune diseases. The authors present the case of a 40-year-old Caucasian male, diagnosed with type 1 diabetes mellitus at age 18, with poor metabolic control in the early years after the diagnosis. Fourteen years after the diagnosis of diabetes, he started complaining of paresthesias in both feet and sexual dysfunction. Months later, he began to have episodes of muscle weakness and decreased strength in the right lower limb, with a relapsing-remitting pattern and diplopia. This typical course of the symptoms associated with characteristic findings in brain magnetic resonance imaging, with multiple lesions, with evidence of space and time dissemination, established the diagnosis of multiple sclerosis. The presence of oligoclonal bands in the cerebrospinal fluid analysis sustained this diagnosis. Other alternative etiologies were excluded. People with type 1 diabetes mellitus are at an increased risk for other autoimmune diseases, with autoimmune thyroiditis (AIT), celiac disease, and pernicious anemia being the most common. Other less recognized associations, such as the co-occurrence of type 1 diabetes mellitus and multiple sclerosis, are also more frequent than might be thought, with studies reporting a threefold to fivefold higher prevalence of T1D in patients with MS. The exact mechanism behind this co-occurrence is not fully understood, but environmental factors (viral infections and vitamin D deficiency) and variations in non-human leucocyte antigen (HLA) class II alleles may be implicated. Understanding the similarities in the etiology and pathophysiology of these diseases may help clarify causality and create new strategies for the management of these conditions.

Cost-optimal nZEB reform strategies and the influence of building orientation for Mediterranean university buildings: case study of the University of Málaga.

The Energy Performance of Buildings Directive (EPBD) requires the transformation of European buildings into nearly zero-energy buildings (nZEBs) before 2050 as a mitigation strategy against the imminent climate emergency. This paper aims to determine the cost-optimal nZEB reform strategy for Spanish university buildings located in the Mediterranean climate, evaluating the influence of the building's orientation on nZEB cost optimality. The present work carries out a case study on three similar buildings at the University of Málaga. The optimal cost-efficiency nZEB reform strategy is determined, rigorously maintaining the formal design of the building through energy simulations with Sefaira Systems software under the EPBD framework. Six reform options were proposed to determine the cost-optimal strategy meeting nZEB requirements for each building. The results show that the most profitable strategy is to improve the efficiency of the thermal envelope and the HVAC system, reducing the energy consumption of the studied buildings by 85-93%. Although a general strategy for nZEB renovations was identified, building orientation proved to be a governing factor in energy performance. As such, the cost-optimal reform strategy was found to be specific to each particular building.

Evaluation of Saliva Stability for NMR Metabolomics: Collection and Handling Protocols.

Maintaining a salivary metabolic profile upon sample collection and preparation is determinant in metabolomics. Nuclear magnetic resonance (NMR) spectroscopy was used to identify metabolite changes during short-term storage, at room temperature (RT)/4 °C/-20 °C, and after sample preparation, at RT/4 °C (mimicking typical clinical/laboratory settings). Interestingly, significant metabolic inter-individual and inter-day variability were noted, probably determining sample stability to some extent. After collection, no changes were noted at -20 °C (at least for 4 weeks). RT storage induced decreases in methylated macromolecules (6 h); lactate (8 h); alanine (12 h); galactose, hypoxanthine, pyruvate (24 h); sarcosine, betaine, choline, N-acetyl-glycoproteins (48 h), while acetate increased (48 h). Less, but different, changes were observed at 4 °C, suggesting different oral and microbial status at different temperatures (with a possible contribution from inter-individual and inter-day variability), and identifying galactose, hypoxanthine, and possibly, choline esters, as potential general stability indicators. After preparation, addition of NaN3 did not impact significantly on saliva stabilization, neither at RT nor at 4 °C, although its absence was accompanied by slight increases in fucose (6.5 h) and proline (8 h) at RT, and in xylose (24 h) at 4 °C. The putative metabolic origins of the above variations are discussed, with basis on the salivary microbiome. In summary, after collection, saliva can be stored at RT/4 °C for up to 6 h and at -20 °C for at least 4 weeks. Upon preparation for NMR analysis, samples are highly stable at 25 °C up to 8 h and at 4 °C up to 48 h, with NaN3 addition preventing possible early changes in fucose, proline (6-8 h), and xylose (24 h) levels.

Unraveling the Lipidome and Antioxidant Activity of Native Bifurcaria bifurcata and Invasive Sargassum muticum Seaweeds: A Lipid Perspective on How Systemic Intrusion May Present an Opportunity.

Brown seaweeds are known to present components with appealing bioactive properties eliciting great interest for industrial applications. However, their lipid content is generally disregarded beyond their fatty acid (FA) composition. This study thoroughly characterized the lipid profile of two brown seaweeds collected from Portuguese coast, the native Bifurcaria bifurcata and the invasive Sargassum muticum species, and bioprospecting for antioxidant activity. An integrated state-of-the-art approach including gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (HILIC-ESI-MS/MS), allowed a comprehensive picture of FA and polar lipid content. Polar lipid profile of B. bifurcata and S. muticum included 143 and 217 lipid species respectively, distributed between glycolipids, phospholipids, and betaine lipids. Some of the lipid species found have been assigned biological activity and contain of n-3 and n-6 FA. Sargassum muticum presented the highest n-3 FA content. Low concentrations of extracts of both seaweeds displayed antioxidant activity, with S. muticum presenting more promising results. These findings contribute to the nutritional and industrial exploitation of both seaweeds, highlighting their relevance as viable sources of bioactive and added-value compounds. Sargassum muticum presented interesting lipid composition and bioactivity, which may represent an accessible opportunity for the exploitation of this invasive seaweed, especially taking advantage of Sargassum blooms.

[Assessment of a method for automatic match classification in probabilistic data linkage]. / Avaliação de método para classificação automatizada de pares em relacionamentos probabilísticos de bancos de dados.

The objective was to test and assess the accuracy of a scoring method in probabilistic data linkage in order to enable automatic identification of true matches, dispensing with the manual inspection stage. Accuracy study using data from the Breast Cancer Information System (SISMAMA) base in Minas Gerais State, Brazil, from 2009 and 2010. After cleaning and standardization, a 16-step probabilistic linkage of the 2009 and 2010 databases was performed, where each step was inspected manually to obtain a gold standard. Samples were then selected, inspected, and assessed to calculate the method's accuracy in selecting true matches. All the steps and samples with 200 and 300 matches showed high sensitivity (recall) > 0.97, high positive predictive value (precision) > 0.95, high accuracy (> 0.97) and F measure (> 0.96), and high area under the curve precision-recall (> 0.98). The sample with 100 matches showed high values for these measures, but with low scores. Of the 16 steps assessed, the combined use of only three was sufficient to identify 99.24% of the true matches in the total database. The proposed method allows automatically linking databases, maintaining the method's accuracy. It facilitates the use of probabilistic linkage in health services, especially for health surveillance and management.

O objetivo foi testar e avaliar a acurácia de um método para a seleção de escore em relacionamento probabilístico de banco de dados, de forma a viabilizar a automatização da identificação de pares verdadeiros dispensando a etapa de inspeção manual. Estudo de acurácia utilizando dados do Sistema de Informação do Câncer de Mama (SISMAMA) de Minas Gerais, Brasil, de 2009 e 2010. Após o processo de limpeza e padronização, foi realizado o relacionamento probabilístico dos bancos 2009 e 2010 utilizando 16 passos, sendo que cada passo foi inspecionado manualmente para se obter um padrão-ouro. Posteriormente, selecionaram-se amostras que foram inspecionadas e avaliadas para calcular a acurácia do método de seleção dos pares verdadeiros. Todos os passos e amostras com 200 e 300 pares apresentaram alta sensibilidade (recall) > 0,97, alto valor preditivo positivo (precision) > 0,95 e altas acurácia (> 0,97), medida F (> 0,96) e área sob a curva precision-recall (> 0,98). A amostra com 100 pares evidenciou altos valores para essas medidas, porém com escores mais baixos. Dos 16 passos avaliados, o uso de apenas três de forma combinada foi suficiente para identificar 99,24% dos pares verdadeiros no banco total. O método proposto permite automatizar o relacionamento das bases de dados, mantendo a acurácia do método. Facilita a utilização de relacionamento probabilístico no âmbito dos serviços de saúde, especialmente para a vigilância e gestão em saúde.

El objectivo fue robar y evaluar la exactitud de un método para la selección de una puntuación, en la relación probabilística de bancos de datos, de forma que sea viable la automatización de la identificación de pares verdaderos, eximiendo la etapa de revisión manual. Estudio de precisión, utilizando datos del Sistema de Información del Cáncer de Mama (SISMAMA) de Minas Gerais, Brasil, de 2009 y 2010. Tras el proceso de limpieza y estandarización, se realizó la relación probabilística de los bancos 2009 y 2010, utilizando 16 pasos, donde cada paso se revisó manualmente para obtener un patrón-oro. Posteriormente, se seleccionaron muestras que fueron revisadas y evaluadas para calcular la precisión del método de selección de los pares verdaderos. Todos los pasos y muestras con 200 y 300 pares presentaron una alta sensibilidad (recall) > 0,97, un alto valor predictivo positivo (precision) > 0,95 y exactitud alta (> 0,97), medida F (> 0,96) y el área bajo la curva precision-recall (> 0,98). La muestra con 100 pares evidenció altos valores para estas medidas, aunque con puntuaciones más bajas. De los 16 pasos evaluados, el uso de solo tres de forma combinada fueron suficientes para identificar 99,24% de los pares verdaderos en el banco total. El método propuesto permite automatizar la relación de las bases de datos, manteniendo la precisión del método. Facilita la utilización de la relación probabilística en el ámbito de los servicios de salud, especialmente para vigilancia y gestión en salud.

Saliva NMR metabolomics: Analytical issues in pediatric oral health research.

OBJECTIVES: Saliva metabolome is a promising diagnostic tool concerning oral and systemic diseases. We aimed at establishing a suitable protocol for saliva collection and gauging the relative impacts of gender, dentition stage, and caries on the saliva metabolome of a small children cohort. SUBJECTS AND METHODS: A nuclear magnetic resonance-based metabolomics cross-sectional study of children saliva (n = 38) compared the effects of: (a) stimulation and unstimulation conditions, and (b) collection through passive drool and using an absorbing device. Multivariate and univariate statistical analyses were applied to evaluate such effects and those related to gender, dentition stage and caries. RESULTS: No significant differences were found between unstimulated and stimulated saliva, and the former was used for subsequent studies. Swab collection induced significant changes in sample composition, indicating passive drool as preferential. The impacts of gender and dentition stage were not significant compared to that of caries, which induced variations in the levels of 21 metabolites. These comprised amino acids and monosaccharides observed for the first time to our knowledge regarding children caries, suggesting protein hydrolysis and deglycosylation. CONCLUSIONS: Unstimulated passive drool saliva metabolome may carry a caries signature.

Urine Nuclear Magnetic Resonance (NMR) Metabolomics in Age-Related Macular Degeneration.

Biofluid biomarkers of age-related macular degeneration (AMD) are still lacking, and their identification is challenging. Metabolomics is well-suited to address this need, and urine is a valuable accessible biofluid. This study aimed to characterize the urinary metabolomic signatures of patients with different stages of AMD and a control group (>50 years). It was a prospective, cross-sectional study, where subjects from two cohorts were included: 305 from Coimbra, Portugal (AMD patients n = 252; controls n = 53) and 194 from Boston, United States (AMD patients n = 147; controls n = 47). For all participants, we obtained color fundus photographs (for AMD staging) and fasting urine samples, which were analyzed using 1H nuclear magnetic resonance (NMR) spectroscopy. Our results revealed that in both cohorts, urinary metabolomic profiles differed mostly between controls and late AMD patients, but important differences were also found between controls and subjects with early AMD. Analysis of the metabolites responsible for these separations revealed that, even though distinct features were observed for each cohort, AMD was in general associated with depletion of excreted citrate and selected amino acids at some stage of the disease, suggesting enhanced energy requirements. In conclusion, NMR metabolomics enabled the identification of urinary signals of AMD and its severity stages, which might represent potential metabolomic biomarkers of the disease.

Avaliação de método para classificação automatizada de pares em relacionamentos probabilísticos de bancos de dados / Assessment of a method for automatic match classification in probabilistic data linkage / Evaluación del método para la clasificación automatizada de pares en relaciones probabilísticas de bancos de datos

Resumo: O objetivo foi testar e avaliar a acurácia de um método para a seleção de escore em relacionamento probabilístico de banco de dados, de forma a viabilizar a automatização da identificação de pares verdadeiros dispensando a etapa de inspeção manual. Estudo de acurácia utilizando dados do Sistema de Informação do Câncer de Mama (SISMAMA) de Minas Gerais, Brasil, de 2009 e 2010. Após o processo de limpeza e padronização, foi realizado o relacionamento probabilístico dos bancos 2009 e 2010 utilizando 16 passos, sendo que cada passo foi inspecionado manualmente para se obter um padrão-ouro. Posteriormente, selecionaram-se amostras que foram inspecionadas e avaliadas para calcular a acurácia do método de seleção dos pares verdadeiros. Todos os passos e amostras com 200 e 300 pares apresentaram alta sensibilidade (recall) > 0,97, alto valor preditivo positivo (precision) > 0,95 e altas acurácia (> 0,97), medida F (> 0,96) e área sob a curva precision-recall (> 0,98). A amostra com 100 pares evidenciou altos valores para essas medidas, porém com escores mais baixos. Dos 16 passos avaliados, o uso de apenas três de forma combinada foi suficiente para identificar 99,24% dos pares verdadeiros no banco total. O método proposto permite automatizar o relacionamento das bases de dados, mantendo a acurácia do método. Facilita a utilização de relacionamento probabilístico no âmbito dos serviços de saúde, especialmente para a vigilância e gestão em saúde.

Abstract: The objective was to test and assess the accuracy of a scoring method in probabilistic data linkage in order to enable automatic identification of true matches, dispensing with the manual inspection stage. Accuracy study using data from the Breast Cancer Information System (SISMAMA) base in Minas Gerais State, Brazil, from 2009 and 2010. After cleaning and standardization, a 16-step probabilistic linkage of the 2009 and 2010 databases was performed, where each step was inspected manually to obtain a gold standard. Samples were then selected, inspected, and assessed to calculate the method's accuracy in selecting true matches. All the steps and samples with 200 and 300 matches showed high sensitivity (recall) > 0.97, high positive predictive value (precision) > 0.95, high accuracy (> 0.97) and F measure (> 0.96), and high area under the curve precision-recall (> 0.98). The sample with 100 matches showed high values for these measures, but with low scores. Of the 16 steps assessed, the combined use of only three was sufficient to identify 99.24% of the true matches in the total database. The proposed method allows automatically linking databases, maintaining the method's accuracy. It facilitates the use of probabilistic linkage in health services, especially for health surveillance and management.

Resumen: El objectivo fue robar y evaluar la exactitud de un método para la selección de una puntuación, en la relación probabilística de bancos de datos, de forma que sea viable la automatización de la identificación de pares verdaderos, eximiendo la etapa de revisión manual. Estudio de precisión, utilizando datos del Sistema de Información del Cáncer de Mama (SISMAMA) de Minas Gerais, Brasil, de 2009 y 2010. Tras el proceso de limpieza y estandarización, se realizó la relación probabilística de los bancos 2009 y 2010, utilizando 16 pasos, donde cada paso se revisó manualmente para obtener un patrón-oro. Posteriormente, se seleccionaron muestras que fueron revisadas y evaluadas para calcular la precisión del método de selección de los pares verdaderos. Todos los pasos y muestras con 200 y 300 pares presentaron una alta sensibilidad (recall) > 0,97, un alto valor predictivo positivo (precision) > 0,95 y exactitud alta (> 0,97), medida F (> 0,96) y el área bajo la curva precision-recall (> 0,98). La muestra con 100 pares evidenció altos valores para estas medidas, aunque con puntuaciones más bajas. De los 16 pasos evaluados, el uso de solo tres de forma combinada fueron suficientes para identificar 99,24% de los pares verdaderos en el banco total. El método propuesto permite automatizar la relación de las bases de datos, manteniendo la precisión del método. Facilita la utilización de la relación probabilística en el ámbito de los servicios de salud, especialmente para vigilancia y gestión en salud.

Creating and validating a warfarin pharmacogenetic dosing algorithm for Colombian patients.

PURPOSE: Warfarin is an oral anticoagulant associated with adverse reaction to drugs due to wide inter- and intra-individual dosage variability. Warfarin dosage has been related to non-genetic and genetic factors. CYP2C9 and VKORC1 gene polymorphisms affect warfarin metabolism and dosage. Due to the central role of populations' ethnical and genetic origin on warfarin dosage variability, novel algorithms for Latin American subgroups are necessary to establish safe anticoagulation therapy. PATIENTS AND METHODS: We genotyped CYP2C9*2 (c.430C > T), CYP2C9*3 (c.1075A > C), CYP4F2 (c.1297G > A), and VKORC1 (-1639 G > A) polymorphisms in 152 Colombian patients who received warfarin. We evaluated the impact on the variability of patients' warfarin dose requirements. Multiple linear regression analysis, using genetic and non-genetic variables, was used for creating an algorithm for optimal warfarin maintenance dose. RESULTS: Median weekly prescribed warfarin dosage was significantly lower in patients having the VKORC1-1639 AA genotype and poor CYP2C9*2/*2,*2/*3 metabolizers than their wild-type counterparts. We found a 2.3-fold increase in mean dose for normal sensitivity patients (wild-type VKORC1/CYP2C9 genotypes) compared to the other groups (moderate and high sensitivity); 31.5% of the patients in our study group had warfarin sensitivity-related genotypes. The estimated regression equation accounted for 44.4% of overall variability in regard to warfarin maintenance dose. The algorithm was validated, giving 45.9% correlation (R 2=0.459). CONCLUSION: Our results describe and validate the first algorithm for predicting warfarin maintenance in a Colombian mestizo population and have contributed toward the understanding of pharmacogenetics in a Latin American population subgroup.

Iniquidade social e mortalidade por câncer de mama e colo do útero: uma revisão integrativa social / Iniquity and mortality related to breast and cervical cancers: an integrative review / La desigualdad social y la mortalidad por cáncer de mama y cáncer de cuello uterino: una revisión integradora

Objective: The leading purpose has been to identify the main publications related to social iniquity and mortality related to breast cancer (BC) and/or cervical cancer (CC), while investigating the type of association between the triggering factor and the case outcome. Methods: It is an Integrative Literature Review from the articles searching in the Medline, Lilacs, PubMed and Scielo databases. A total of 3,439 studies were obtained, from which only 85 have met the inclusion criteria. Results: The vast majority of the studies have found an association between high socioeconomic status and mortality by BC and also between low socioeconomic status and mortality by CC. The principal indicators used to evaluate these associations were as follows: education, income/poverty and labor market. Conclusion: Areas with high social iniquity have higher mortality rates related to CC, while those with higher socioeconomic status exhibit high mortality rates related to BC. These phenomena have several explanations: personal lifestyle, offer and accessibility to screening services and/or treatment, social stratification based on the economic model adopted in the country

Objetivo: Identificar as principais publicações relacionadas à iniquidade social e mortalidade por câncer de mama (CAM) e/ou colo do útero (CCU) e investigar o tipo de associação existente entre fator e desfecho. Método: Revisão Integrativa de Literatura a partir da busca de artigos nas bases Medline, Lilacs, PubMed e Scielo. Obteve-se 3.439 estudos, destes apenas 85 atendiam aos critérios de inclusão. Resultados: A maioria dos estudos encontrou associação entre alto nível socioeconômico e mortalidade CAM e entre baixo nível socioeconômico e mortalidade por CCU. Educação, renda/pobreza e mercado de trabalho foram os principais indicadores utilizados para avaliação dessas associações. Conclusão: Áreas com grande desigualdade social apresentam maior mortalidade por CCU enquanto aquelas com melhor nível socioeconômico exibem altas taxas de mortalidade por CAM. Estes fenômenos possuem várias explicações: estilo de vida dos indivíduos, oferta e acessibilidade aos serviços de rastreamento e/ou tratamento, estratificação social baseada no modelo econômico do país

Objetivo: Identificar las principales publicaciones relacionadas con la desigualdad social y la mortalidad por cáncer de mama (CAM) y/o el cuello uterino (CCU) e investigan el tipo de asociación entre el factor y el resultado. Método: una revisión integradora de la literatura de la búsqueda de artículos en el Medline, Lilacs, PubMed y Scielo. Obtenido 3.439 estudios, de éstos sólo 85 cumplieron con los criterios de inclusión. Resultados: La mayoría de los estudios encontraron una asociación entre el nivel socioeconómico alto y el CAM y la mortalidad entre el bajo nivel socioeconómico y la mortalidad por cáncer de cuello uterino. Educación, ingresos/pobreza y el mercado de trabajo fueron los principales indicadores utilizados para evaluar estas asociaciones. Conclusión: Las áreas con gran desigualdad social tienen mayores tasas de mortalidad por cáncer de cuello de útero, mientras que aquellos con mayor nivel socioeconómico presentan altas tasas de mortalidad por CAM. Estos fenómenos tienen varias explicaciones: el estilo de vida de los individuos, la oferta y la accesibilidad de los servicios de seguimiento y / o tratamiento, la estratificación social basada en el modelo económico del país

Intestinal Microbial and Metabolic Profiling of Mice Fed with High-Glucose and High-Fructose Diets.

Increased sugar intake is implicated in Type-2 diabetes and fatty liver disease; however, the mechanisms through which glucose and fructose promote these conditions are unclear. We hypothesize that alterations in intestinal metabolite and microbiota profiles specific to each monosaccharide are involved. Two groups of six adult C57BL/6 mice were fed for 10-weeks with diets with glucose (G) or fructose (F) as sole carbohydrates, and a third group was fed with a normal chow carbohydrate mixture (N). Fecal metabolites were profiled by nuclear magnetic resonance (NMR) and microbial composition by real-time polymerase chain reaction (qPCR). Although N, G and F mice exhibited similar weight gains (with slight slower gains for F) and glucose tolerance, multivariate analysis of NMR data indicated that F mice were separated from N and G, with decreased butyrate and glutamate and increased fructose, succinate, taurine, tyrosine, and xylose. The different sugar diets also resulted in distinct intestinal microbiota profiles. That associated with fructose seemed to hold more potential to induce host metabolic disturbances compared to glucose, mainly by promoting bile acid deconjugation and taurine release and compromising intestinal barrier integrity. This may reflect the noted nonquantitative intestinal fructose absorption hence increasing its availability for microbial metabolism, a subject for further investigation.

Assessing Exposome Effects on Pregnancy through Urine Metabolomics of a Portuguese (Estarreja) Cohort.

This nuclear magnetic resonance metabolomics study compared the influence of two different central Portugal exposomes, one of which comprised an important source of pollutants (the Estarreja Chemical Complex, ECC), on the urinary metabolic trajectory of a cohort of healthy pregnant women (total n = 107). An exposome-independent description of pregnancy metabolism was found to comprise a set of 18 metabolites reflecting expected changes in branched-chain amino acid catabolism and hormone and lipid metabolisms. In addition, a set of small changes in some metabolites was suggested to be exposome-dependent and characteristic of pregnant subjects from the Estarreja region. These results suggested that the Estarreja exposome may impact to a very low extent pregnancy metabolism, inducing slight changes in amino acid metabolism (alanine, glycine, and 3-hydroxyisobutyrate, possibly involved in valine metabolism), tricarboxylic acid (TCA) cycle (cis-aconitate), diet, or gut microflora (furoylglycine) as well as allantoin, 2-hydroxyisobutyrate, and an unassigned resonance at δ 8.45. Furthermore, the urine of Estarreja subjects was found to generally contain higher levels of 4-hydroxyphenylacetate and lower levels of citrate. However, out of the above metabolites, only glycine and citrate seemed to correlate with the proximity to the ECC, with slightly relative higher levels of these compounds found for subjects living closer to the ECC. This suggested possible small effects of local pollutants on energy metabolism, with the remaining exposome-dependent metabolite changes most probably originating from other aspects of the local exposome such as diet and lifestyle. Despite the limitation of this study regarding the unavailability of objective environmental parameters for the period under study, our results confirm the usefulness of metabolomics of human urine to gauge exposome effects on human health and, particularly, during pregnancy.

Biofluid Metabolomics in Preterm Birth Research.

This article presents an account of the research carried out so far in the use of metabolomics to find biomarkers of preterm birth (PTB) in fetal, maternal, and newborn biofluids. Metabolomic studies have employed mainly nuclear magnetic resonance spectroscopy or mass spectrometry-based methodologies to analyze, on one hand, prenatal biofluids (amniotic fluid, maternal urine/maternal blood, cervicovaginal fluid) to identify predictive biomarkers of PTB, and on the other hand, biofluids collected at or after birth (amniotic fluid, umbilical cord blood, newborn urine, and newborn blood, maternal blood, or breast milk) to assess and follow up the health status of PTB babies. Besides advancing on the biochemical knowledge of PTB metabolism mainly during the in utero period and at birth, the work carried out has also helped to identify important requirements related to experimental design and analytical protocol that need to be addressed, if translation of these biomarkers to the clinic is to be envisaged. An outlook of possible future developments for the translation of laboratory results to the clinic is presented.

Rastreamento do câncer do colo do útero em Minas Gerais: avaliação a partir de dados do Sistema de Informação do Câncer do Colo do Útero (SISCOLO) / Cervical cancer tracking in Minas Gerais: assessment of data from Cervical Cancer Information System (SISCOLO)

Resumo Objetivo Avaliar os indicadores relacionados à oferta de exames citopatológicos do colo do útero, sua qualidade, frequência de alterações celulares e seguimento informado de lesões de alto grau, em Minas Gerais e suas macrorregiões de saúde. Métodos Estudo descritivo com base em dados do Sistema de Informação do Câncer do Colo do Útero (SISCOLO), de 2006 a 2011. Resultados A razão de exames citopatológicos do colo do útero em mulheres de 25 a 59 anos manteve-se estável, porém sem alcançar a meta estadual pactuada. Aproximadamente 75% dos exames foram realizados na população-alvo e houve progressiva redução na proporção de citopatológicos do colo do útero sem citologia anterior. Em média, 51,2% dos exames foram realizados no período de até um ano. Quanto à qualidade do exame, destaca-se o índice de positividade, categorizado como baixo durante todo o período analisado. Observou-se baixo percentual de seguimento informado no estado. Conclusão Os resultados evidenciam a necessidade de aprimoramento do programa de rastreamento em relação à oferta e qualidade do exame, bem como ao direcionamento correto quanto à faixa etária e à periodicidade, visando garantir o acesso da população-alvo e o encaminhamento para a investigação diagnóstica e tratamento das lesões precursoras, quando indicado.

Abstract Objective To evaluate the indicators related to cervical cytology, quality, frequency of cellular changes and informed follow-up of high-grade lesions in Minas Gerais and its macro-regions of health. Methods a descriptive study based on data from the Cervical Cancer Information System (SISCOLO) from 2006 to 2011. Results The ratio of cervical cytopathologic exams in women aged 25 to 59 years remained stable, but did not reach the goal set by the state. Approximately 75% of the exams were performed in the target population and there was a progressive reduction in the proportion of cervical cytopathologists without previous cytology. On average, 51.2% of the exams were performed within a year. Regarding the quality of the exam, the positivity index was categorized as low throughout the analyzed period. We observed a low percentage of follow-up reported in the state. Conclusion The results evidenced the need to improve the tracking program regarding the quality of the exam, as well as the correct orientation regarding the age group and the periodicity, aiming to guarantee the target population's access and referral for diagnostic investigation and treatment of precursor lesions, when indicated.

Human plasma metabolomics in age-related macular degeneration (AMD) using nuclear magnetic resonance spectroscopy.

PURPOSE: To differentiate the plasma metabolomic profile of patients with age related macular degeneration (AMD) from that of controls, by Nuclear Magnetic Resonance (NMR) spectroscopy. METHODS: Two cohorts (total of 396 subjects) representative of central Portugal and Boston, USA phenotypes were studied. For each cohort, subjects were grouped according to AMD stage (early, intermediate and late). Multivariate analysis of plasma NMR spectra was performed, followed by signal integration and univariate analysis. RESULTS: Small changes were detected in the levels of some amino acids, organic acids, dimethyl sulfone and specific lipid moieties, thus providing some biochemical information on the disease. The possible confounding effects of gender, smoking history and age were assessed in each cohort and found to be minimal when compared to that of the disease. A similar observation was noted in relation to age-related comorbidities. Furthermore, partially distinct putative AMD metabolite fingerprints were noted for the two cohorts studied, reflecting the importance of nutritional and other lifestyle habits in determining AMD metabolic response and potential biomarker fingerprints. Notably, some of the metabolite changes detected were noted as potentially differentiating controls from patients diagnosed with early AMD. CONCLUSION: For the first time, this study showed metabolite changes in the plasma of patients with AMD as compared to controls, using NMR. Geographical origins were seen to affect AMD patients´ metabolic profile and some metabolites were found to be valuable in potentially differentiating controls from early stage AMD patients. Metabolomics has the potential of identifying biomarkers for AMD, and further work in this area is warranted.