Intervenção sobre o precesso de trabalho para o controle da hipertensão arterial na equipe Sol Nascente em Cataguases/MG

A Equipe de Saúde da Família da Sol Nascente em Cataguases /MG é responsável por 3.559 usuários, sendo que boa parte procura os serviços da equipe com níveis pressóricos alterados. Com a vivencia no trabalho da equipe, percebeu-se o processo de trabalho insuficiente para atender esta demanda. Para reduzir o elevado índice de hipertensos, elaborou-se uma proposta de intervenção para instrumentalizar os profissionais da equipe de saúde para a promoção do autocuidado e conhecimentos sobre a hipertensão entre usuários adscritos. Este trabalho foi proposto após a realização da análise situacional e pelo levantamento dos principais problemas de saúde existentes no território. Assim, foram planejadas ações em saúde, utilizando o método de Planejamento Estratégico Situacional (PES) e com as informações coletadas nos registros da equipe, consulta médica e contato com pacientes durante as visitas domiciliares. O método da Estimativa Rápida Participativa proporcionou conhecer as condições de vida da população do território da equipe Sol nascente, suas características e ambiente onde vivem e da maneira como se distribui no território. Os nós críticos identificados foram: Falta de acompanhamento pela equipe de saúde; Falta do acolhimento; Falta de comunicação entre a equipe e os usuários; Falta de adesão aos medicamentos anti-hipertensivos e demais medicamentos auxiliares. A realização desta intervenção necessita da participação de toda a equipe e aumento da oferta de consultas médica e de enfermagem e assistência farmacêutica que irão contribuir com a melhoria do processo de trabalho e consequentemente dos níveis pressóricos dos acometidos melhorando a qualidade de vida dos hipertensos

Gestión óptima de citas médicas mediante la aplicación de un modelo de optimización multicriterio

The Cuban health system is known worldwide for its good results in the prevention of diseases and for its continuous improvements in health standards. However, we want to go a step further and put the patient at the center of the system. To this task, we propose a methodology that allows a complete automatization of the medical appointment system so that patients will know in advance the average time they will spend in the hospital the day of the appointment, as well as the sequence of medical tests that will have to undertake. We develop a non linear integer multi-goal model (NLIMGM) model to perform an optimal distribution of patients. Our model assign appointments to patients according to two different goals: to give the appointments as soon as possible and to minimize the time that a patient would spend in the hospital to complete a protocol.The performance of the resulting NLIMGM policies was compared with traditional practices decision rules for the diagnosis and treatment of ophthalmology diseases in a Cuba hospital. The results show that this method outperforms traditional methods by far. Specifically, this approach will increase the efficiency of appointments scheduling and reduces the total diagnosis time for cataract, cornea, glaucoma by 46% on average or, in other words, by roughly one hour, relative to the standard approach. Arguably, this translates into improved patient satisfaction and efficiency in the use of resources in health services. <br /

Deep Proteomic Analysis on Biobanked Paraffine-Archived Melanoma with Prognostic/Predictive Biomarker Read-Out

SIMPLE SUMMARY: Malignant melanoma is one of the most aggressive cancer types among the solid tumors; therefore, more clinically applicable protein biomarkers predicting survival and therapy response have mandatory importance, impacting patient treatment. The aim of the study was to discover new proteins in biobanked FFPE samples that relate to progression-free survival and response to targeted- and immuno-therapies in patients with melanoma. Protein expressions were detected and quantified by high-resolution mass spectrometry and were integrated with the clinical data and in-depth histopathology characterization. Sample groups with distinct protein expression profiles were connected to longer and shorter survival as well as other clinicopathologic features. In addition, key regulating proteins were assigned, as predictive of progression-free survival in immuno- and/or targeted therapy. Some of the proteins exhibited functionally important correlations to progression and therapy response, which ultimately contributes to a better understanding of melanoma pathology. ABSTRACT: The discovery of novel protein biomarkers in melanoma is crucial. Our introduction of formalin-fixed paraffin-embedded (FFPE) tumor protocol provides new opportunities to understand the progression of melanoma and open the possibility to screen thousands of FFPE samples deposited in tumor biobanks and available at hospital pathology departments. In our retrospective biobank pilot study, 90 FFPE samples from 77 patients were processed. Protein quantitation was performed by high-resolution mass spectrometry and validated by histopathologic analysis. The global protein expression formed six sample clusters. Proteins such as TRAF6 and ARMC10 were upregulated in clusters with enrichment for shorter survival, and proteins such as AIFI1 were upregulated in clusters with enrichment for longer survival. The cohort’s heterogeneity was addressed by comparing primary and metastasis samples, as well comparing clinical stages. Within immunotherapy and targeted therapy subgroups, the upregulation of the VEGFA-VEGFR2 pathway, RNA splicing, increased activity of immune cells, extracellular matrix, and metabolic pathways were positively associated with patient outcome. To summarize, we were able to (i) link global protein expression profiles to survival, and they proved to be an independent prognostic indicator, as well as (ii) identify proteins that are potential predictors of a patient’s response to immunotherapy and targeted therapy, suggesting new opportunities for precision medicine developments

The Hidden Story of Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma-Association with Clinical Outcome and Tumor Phenotypes

In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter-and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma

CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research

CK2 represents an oncology target scientifically validated. However, clinical research with inhibitors of the CK2-mediated phosphorylation event is still insufficient to recognize it as a clinically validated target. CIGB-300, an investigational peptide-based drug that targets the phosphoaceptor site, binds to a CK2 substrate array in vitro but mainly to B23/nucleophosmin in vivo. The CIGB-300 proapoptotic effect is preceded by its nucleolar localization, inhibition of the CK2-mediated phosphorylation on B23/nucleophosmin and nucleolar disassembly. Importantly, CIGB-300 shifted a protein array linked to apoptosis, ribosome biogenesis, cell proliferation, glycolisis, and cell motility in proteomic studies which helped to understand its mechanism of action. In the clinical ground, CIGB-300 has proved to be safe and well tolerated in a First-in-Human trial in women with cervical malignancies who also experienced signs of clinical benefit. In a second Phase 1 clinical trial in women with cervical cancer stage IB2/II, the MTD and DLT have been also identified in the clinical setting. Interestingly, in cervical tumors the B23/nucleophosmin protein levels were significantly reduced after CIGB-300 treatment at the nucleus compartment. In addition, expanded use of CIGB-300 in case studies has evidenced antitumor activity when administered as compassional option. Collectively, our data outline important clues on translational and clinical research from this novel peptide-based drug reinforcing its perspectives to treat cancer and paving the way to validate CK2 as a promising target in oncology.Fil: Perea, Silvio E.. Center for Genetic Engineering and Biotechnology; CubaFil: Baladron, Idania. Center for Genetic Engineering and Biotechnology; CubaFil: Garcia, Yanelda. Center for Genetic Engineering and Biotechnology; CubaFil: Perera, Yasser. Center for Genetic Engineering and Biotechnology; CubaFil: Lopez, Adlin. Center for Genetic Engineering and Biotechnology; CubaFil: Soriano, Jorge L.. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Batista, Noyde. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Palau, Aley. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Hernández, Ignacio. Center for Genetic Engineering and Biotechnology; CubaFil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Idrian. Center for Genetic Engineering and Biotechnology; CubaFil: Gonzalez, Lidia. Center for Genetic Engineering and Biotechnology; CubaFil: Gil, Jeovanis. Center for Genetic Engineering and Biotechnology; CubaFil: Rodriguez, Arielis. Center for Genetic Engineering and Biotechnology; CubaFil: Solares, Margarita. Center for Genetic Engineering and Biotechnology; CubaFil: Santana, Agueda. Center for Genetic Engineering and Biotechnology; CubaFil: Cruz, Marisol. Center for Genetic Engineering and Biotechnology; CubaFil: Lopez, Matilde. Center for Genetic Engineering and Biotechnology; CubaFil: Valenzuela, Carmen. Center for Genetic Engineering and Biotechnology; CubaFil: Reyes, Osvaldo. Center for Genetic Engineering and Biotechnology; CubaFil: López Saura, Pedro A.. Center for Genetic Engineering and Biotechnology; CubaFil: González, Carlos A.. Center for Genetic Engineering and Biotechnology; CubaFil: Diaz, Alina. Center for Genetic Engineering and Biotechnology; CubaFil: Castellanos, Lila. Center for Genetic Engineering and Biotechnology; CubaFil: Sanchez, Aniel. Center for Genetic Engineering and Biotechnology; CubaFil: Betancourt, Lazaro. Center for Genetic Engineering and Biotechnology; CubaFil: Besada, Vladimir. Center for Genetic Engineering and Biotechnology; CubaFil: González, Luis J.. Center for Genetic Engineering and Biotechnology; CubaFil: Garay, Hilda. Center for Genetic Engineering and Biotechnology; CubaFil: Gómez, Roberto. Center for Genetic Engineering and Biotechnology; CubaFil: Gomez, Daniel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perrin, Phillipe. No especifíca;Fil: Renualt, Jean Yves. No especifíca;Fil: Sigman, Hugo. No especifíca;Fil: Herrera, Luis. Center for Genetic Engineering and Biotechnology; CubaFil: Acevedo, Boris. Center for Genetic Engineering and Biotechnology; Cub

Challenging the heterogeneity of disease presentation in malignant melanoma-impact on patient treatment

There is an increasing global interest to support research areas that can assist in understanding disease and improving patient care. The National Cancer Institute (NIH) has identified precision medicine-based approaches as key research strategies to expedite advances in cancer research. The Cancer Moonshot program ( https://www.cancer.gov/research/key-initiatives/moonshot-cancer-initiative ) is the largest cancer program of all time, and has been launched to accelerate cancer research that aims to increase the availability of therapies to more patients and, ultimately, to eradicate cancer. Mass spectrometry-based proteomics has been extensively used to study the molecular mechanisms of cancer, to define molecular subtypes of tumors, to map cancer-associated protein interaction networks and post-translational modifications, and to aid in the development of new therapeutics and new diagnostic and prognostic tests. To establish the basis for our melanoma studies, we have established the Southern Sweden Malignant Melanoma Biobank. Tissues collected over many years have been accurately characterized with respect to the tumor and patient information. The extreme variability displayed in the protein profiles and the detection of missense mutations has confirmed the complexity and heterogeneity of the disease. It is envisaged that the combined analysis of clinical, histological, and proteomic data will provide patients with a more personalized medical treatment. With respect to disease presentation, targeted treatment and medical mass spectrometry analysis and imaging, this overview report will outline and summarize the current achievements and status within malignant melanoma. We present data generated by our cancer research center in Lund, Sweden, where we have built extensive capabilities in biobanking, proteogenomics, and patient treatments over an extensive time period

The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome

The MM500 meta‐study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass‐spectrometry‐based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well‐annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of driver genes. More than 50 million MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum matches (PSMs). Altogether 13 176 protein‐coding genes, represented by 366 172 peptides, in addition to 52 000 phosphorylation sites, and 4 400 acetylation sites were successfully annotated. This data covers 65% and 74% of the predicted and identified human proteome, respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma transcriptome of the TCGA repository, with an overlap of 12 751 gene products, was found. Mapping of the expressed proteins with quantitation, spatiotemporal localization, mutations, splice isoforms, and PTM variants was proven not to be predicted by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis of blood protein expression, including data on proteins regulated after immunotherapy. By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma disease