Despite major improvements in its treatment and diagnosis, sepsis is still a leading cause of death and admittance to the intensive care unit (ICU). Failure to identify patients at high risk of developing septic shock contributes to an increase in the sepsis burden and rapid molecular tests are currently the most promising avenue to aid in patient risk determination and therapeutic anticipation. The primary goal of this study was to evaluate the genetic susceptibility that affects sepsis outcome in 72 sepsis patients admitted to the ICU. Seven polymorphisms were genotyped in key inflammatory response genes in sepsis, including tumour necrosis factor-α, interlelukin (IL)-1β, IL-10, IL-8, Toll-like receptor 4, CXCR1 and CXCR2. The primary finding showed that patients who were homozygous for the major A allele in IL-10 rs1800896 had almost five times higher chance to develop septic shock compared to heterozygotes. Similarly, selected clinical features and CXCR2 rs1126579 single nucleotide polymorphisms modulated septic shock susceptibility without affecting survival. These data support the hypothesis that molecular testing has clinical usefulness to improve sepsis prognostic models. Therefore, enrichment of the ICU portfolio by including these biomarkers will aid in the early identification of sepsis patients who may develop septic shock.

Background: Although the pancreatic ductal adenocarcinoma (PDAC) presents high mortality and metastatic potential, there is a lack of effective therapies and a low survival rate for this disease. This PDAC scenario urges new strategies for diagnosis, drug targets, and treatment. Methods: We performed a gene expression microarray meta-analysis of the tumor against normal tissues in order to identify differentially expressed genes (DEG) shared among all datasets, named core-genes (CG). We confirmed the CG protein expression in pancreatic tissue through The Human Protein Atlas. It was selected five genes with the highest area under the curve (AUC) among these proteins with expression confirmed in the tumor group to train an artificial neural network (ANN) to classify samples. Results: This microarray included 461 tumor and 187 normal samples. We identified a CG composed of 40 genes, 39 upregulated, and one downregulated. The upregulated CG included proteins and extracellular matrix receptors linked to actin cytoskeleton reorganization. With the Human Protein Atlas, we verified that fourteen genes of the CG are translated, with high or medium expression in most of the pancreatic tumor samples. To train our ANN, we selected the best genes (AHNAK2, KRT19, LAMB3, LAMC2, and S100P) to classify the samples based on AUC using mRNA expression. The network classified tumor samples with an f1-score of 0.83 for the normal samples and 0.88 for the PDAC samples, with an average of 0.86. The PDAC-ANN could classify the test samples with a sensitivity of 87.6 and specificity of 83.1. Conclusion: The gene expression meta-analysis and confirmation of the protein expression allow us to select five genes highly expressed PDAC samples. We could build a python script to classify the samples based on RNA expression. This software can be useful in the PDAC diagnosis.

Background: Although the pancreatic ductal adenocarcinoma (PDAC) presents high mortality and metastatic potential, there is a lack of effective therapies and a low survival rate for this disease. This PDAC scenario urges new strategies for diagnosis, drug targets, and treatment. Methods:We performed a gene expression microarray meta-analysis of the tumor against healthy tissues in order to identify differentially expressed genes shared among all datasets, named core-genes (CG). We confirmed the pancreatic expressed proteins of the CG through The Human Protein Atlas. The five most expressed proteins in the tumor group were selected to train an artificial neural network to classify samples. 2 Results: This microarray included 110 tumor and 77 healthy samples. We identified a CG composed of 60 genes, 58 upregulated and two downregulated. The upregulated CG included proteins and extracellular matrix receptors linked to actin cytoskeleton reorganization. With the Human Protein Atlas, we verified that thirteen genes of the CG are translated, with high or medium expression in most of the pancreatic tumor samples. To train our artificial neural network, we used the five most expressed genes (KRT19, LAMC2, MELK, MET, TOP2A). The artificial neural network model (PDAC-ANN) classified the train samples with sensitivity of 0.95, specificity of 0.9, and f1-score of 0.93. The PDAC-ANN could classify the test samples with a sensitivity of 0.97, specificity of 0.88, and f1-score 0.94. Conclusion:The gene expression meta-analysis and confirmation of the protein expression allow us to select five genes highly expressed PDAC samples. We could build a python script to classify the samples based on mRNA expression. This software can be useful in the PDAC diagnosis.1 5 migration, and metastasis. The PDAC-ANN trained using gene expression information could classify the samples in normal and PDAC with an f1-score of 0.94 and sensitivity = 0.97. The PDAC-ANN tool can only be used when the gene expression information from KRT19, LAMC2, MELK, MET, and TOP2A are available, in addition to min-max gene expression values rescaling. The PDAC-ANN is a free tool (Additional file 4) that can support in the pancreatic ductal adenocarcinoma diagnosis.

Background: We hypothesized that one single episode of acute kidney injury (AKI) reduces long-term survival compared with no acute kidney injury (No AKI) following recovery from critical illness. Materials and methods: A prospective cohort of 2,010 patients admitted to the ICU between 2000 and 2009 at a provincial referral hospital was followed to determine whether AKI influences long-term survival. Results: Of the 1,844 eligible patients, 18.4% had AKI stage 1, 12.1% had stage 2, 26.5% had stage 3, and 43.0% had No AKI, using the KDIGO classification. The mean and median follow-up time was 8.1 and 8.7 years. The 28-day, 1-year, 5-year and 10-year survival rates were 59.6%, 44.9%, 37.4%, and 33.4%, in patients with any AKI (stage 1, stage 2, stage 3), which was significantly worse compared with the critically ill patients with no AKI at any time (P < 0.01). The adjusted 10-year mortality risk associated with AKI was 1.44 (95% CI = 1.2 to 1.7) among 28-day survivors. Patients who had mild AKI (stage 1) had significantly worse survival at 28 days, 1 year, 3 years, 5 years and 10 years compared with No AKI (P < 0.01) (Figure 1A). Patients with sepsis and AKI who survived 28 days had significantly poorer 5-year and 10-year survival compared with nonseptic AKI (P < 0.01) (Figure 1B). Conclusions: Patients with one episode of mild (stage 1) AKI have significantly lower survival rates over 10 years than critically ill patients without AKI. The causes and mechanisms of this association warrant further careful study. Close medical follow-up of these patients may be warranted and mechanistic research required understanding how AKI influences distant events.

A influência do álcool na manifestação clínica da enxaqueca tem sido assunto de extensivos debates ao longo das últimas décadas. Este estudo tem como objetivo observar a relação entre o consumo de bebidas alcoólicas e ataques de enxaqueca. Do ponto de vista fisiopatológico, os relatos dos pacientes sugerem que as bebidas podem ter efeito no cérebro susceptível e levar a uma série de alterações celulares e moleculares que resultam em um ataque agudo de enxaqueca. Estudos retrospectivos mostraram que ao menos um terço dos pacientes terão o álcool como fator desencadeante para enxaqueca. O mecanismo pelo qual o álcool provoca a cefaleia é debatido e é compatível com as principais teorias fisiopatogênicas das cefaleias primárias.

ABSTRACT. Paracoccidioidomycosis (PCM) is an important systemic mycosis in LatinAmerica that occurs as active disease in 1-2% of Paracoccidioides brasiliensis infected people. Like PCM, tuberculosis (TB) affects mainly the lungs and the clinical and radiological aspects do not always allow differentiation between them. The aim of this study was to carry out serological investigation for detecting anti-P. brasiliensis antibodies, by three serological methods, in patients with symptoms suggestive of pulmonary TB. From August 2005 to September 2006, 76 patients with pulmonary symptoms suspected for TB were attended at the Regional Specialties Center Laboratory in the city of Paranavaí, Paraná, Brazil and submitted to microbiological TB research, ELISA, immunodiffusion and immunoblotting for PCM. Of all the individuals, 21 (27.63%) were reactive to P. brasiliensis by ELISA and 11 (14.47%) showed a laboratory diagnosis of pulmonary TB. Of all the individuals serologically reactive to P. brasiliensis, by ELISA, none had positive results by immunodiffusion and one reacted with antigen 43 kDa when Immunobloting was carried out. Our results lead us to reflect a necessity to obtain a more specific serologic test for diagnosis of PCM disease in patients with respiratory symptoms considering the high number of individuals reactive to P. brasiliensis especially in endemic areas.Key words: paracoccidioidomycosis, tuberculosis, serology, ELISA, immunobloting.RESUMO. Detecção de anticorpos anti-Paracoccidioides brasiliensis em pacientes suspeitos de tuberculose. Paracoccidioidomicose (PCM) é importante micose sistêmica na América Latina, que ocorre como doença ativa em 1-2% dos indivíduos infectados com Paracoccidioides brasiliensis. Assim como a PCM, a tuberculose (TB) afeta principalmente os pulmões, porém os aspectos clínicos e radiológicos nem sempre permitem a diferenciação entre essas doenças. O objetivo deste estudo foi realizar um inquérito sorológico para a detecção de anticorpos anti-P. brasiliensis, utilizando três métodos sorológicos, em pacientes com sintomas sugestivos de tuberculose pulmonar. De agosto de 2005 a setembro de 2006, 76 pacientes sintomáticos foram atendidos no Laboratório do Centro Regional de Especialidades de Paranavaí, Paraná, Brasil e submetidos à investigação microbiológica para TB e de anticorpos por ELISA, imunodifusão e immunobloting para PCM. Destes, 21 (27,63%) foram reativos para P. brasiliensis por ELISA e 11 (14,47%) apresentaram diagnóstico laboratorial de tuberculose pulmonar. Dos indivíduos sorologicamente reativos para P. brasiliensis, por ELISA, nenhum apresentou resultado positivo pela técnica de imunodifusão e um reagiu com antígeno de 43 kDa quando do uso de immunobloting. Os resultados obtidos nos levam a refletir da necessidade de se obter um teste sorológico mais específico para o diagnóstico de PCM doença em pacientes com sintomas respiratórios, considerando o elevado número de indivíduos reativos para P. brasiliensis principalmente em áreas endêmicas.