The prognostic association of SPAG5 gene expression in breast cancer patients with systematic therapy

Background: Despite much effort on the treatment of breast cancer over the decades, a great uncertainty regarding the appropriate molecular biomarkers and optimal therapeutic strategy still exists. This research was performed to analyze the association of SPAG5 gene expression with clinicopathological factors and survival outcomes. Methods: We used a breast cancer database including 5667 patients with a mean follow-up of 69 months. Kaplan-Meier survival analyses for relapse free survival (RFS), overall survival (OS), and distant metastasis-free survival (DMFS) were performed. In addition, ROC analysis was performed to validate SPAG5 as a prognostic candidate gene. Results: Mean SPAG5 expression value was significantly higher with some clinicopathological factors that resulted in tumor promotion and progression, including poor differentiated type, HER2 positive or TP53 mutated breast cancer. Based on ROC-analysis SPAG 5 is a suitable prognostic marker of poor survival. In patients who received chemotherapy alone, SPAG5 had only a moderate and not significant predictive impact on survival outcomes. However, in hormonal therapy, high SPAG5 expression could strongly predict prognosis with detrimental RFS (HR = 1.57, 95% CI 1.2-2.06, p = 0.001), OS (HR = 2, 95% CI 1.05-3.8, p = 0.03) and DMFS (HR = 2.36, 95% CI 1.57-3.54, p < 0.001), respectively. In addition, SPAG5 could only serve as a survival predictor in ER+, but not ER- breast cancer patients. Patients might also be at an increased risk of relapse despite being diagnosed with a lower grade cancer (well differentiated type). Conclusions: SPAG5 could be used as an independent prognostic and predictive biomarker that might have clinical utility, especially in ER+ breast cancer patients who received hormonal therapy. © 2019 The Author(s)

Understanding Streptococcus suis serotype 2 infection in pigs through a transcriptional approach

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus suis </it>serotype 2 (<it>S. suis </it>2) is an important pathogen of pigs. <it>S suis 2 </it>infections have high mortality rates and are characterized by meningitis, septicemia and pneumonia. <it>S. suis </it>2 is also an emerging zoonotic agent and can infect humans that are exposed to pigs or their by-products. To increase our knowledge of the pathogenesis of meningitis, septicemia and pneumonia in pigs caused by <it>S. suis </it>2, we profiled the response of peripheral blood mononuclear cells <b>(</b>PBMC), brain and lung tissues to infection with <it>S. suis </it>2 strain SC19 using the Affymetrix Porcine Genome Array.</p> <p>Results</p> <p>A total of 3,002 differentially expressed transcripts were identified in the three tissues, including 417 unique genes in brain, 210 in lung and 213 in PBMC. These genes showed differential expression (DE) patterns on analysis by visualization and integrated discovery (DAVID). The DE genes involved in the immune response included genes related to the inflammatory response (CD163), the innate immune response (TLR2, TLR4, MYD88, TIRAP), cell adhesion (CD34, SELE, SELL, SELP, ICAM-1, ICAM-2, VCAM-1), antigen processing and presentation (MHC protein complex) and angiogenesis (VEGF), together with genes encoding cytokines (interleukins). Five selected genes were validated by qRT-PCR analysis.</p> <p>Conclusions</p> <p>We studied the response to infection with <it>S. suis </it>2 strain SC19 by microarray analysis. Our findings confirmed some genes identified in previous studies and discovered numerous additional genes that potentially function in <it>S. suis </it>2 infections in vivo. This new information will form the foundation of future investigations into the pathogenesis of <it>S. suis</it>.</p

East Coast Fever Caused by Theileria parva Is Characterized by Macrophage Activation Associated with Vasculitis and Respiratory Failure

Respiratory failure and death in East Coast Fever (ECF), a clinical syndrome of African cattle caused by the apicomplexan parasite Theileria parva, has historically been attributed to pulmonary infiltration by infected lymphocytes. However, immunohistochemical staining of tissue from T. parva infected cattle revealed large numbers of CD3- and CD20-negative intralesional mononuclear cells. Due to this finding, we hypothesized that macrophages play an important role in Theileria parva disease pathogenesis. Data presented here demonstrates that terminal ECF in both Holstein and Boran cattle is largely due to multisystemic histiocytic responses and resultant tissue damage. Furthermore, the combination of these histologic changes with the clinical findings, including lymphadenopathy, prolonged pyrexia, multi-lineage leukopenia, and thrombocytopenia is consistent with macrophage activation syndrome. All animals that succumbed to infection exhibited lymphohistiocytic vasculitis of small to medium caliber blood and lymphatic vessels. In pulmonary, lymphoid, splenic and hepatic tissues from Holstein cattle, the majority of intralesional macrophages were positive for CD163, and often expressed large amounts of IL-17. These data define a terminal ECF pathogenesis in which parasite-driven lymphoproliferation leads to secondary systemic macrophage activation syndrome, mononuclear vasculitis, pulmonary edema, respiratory failure and death. The accompanying macrophage phenotype defined by CD163 and IL-17 is presented in the context of this pathogenesis

Escala de Coma de Glasgow: subestimação em pacientes com respostas verbais impedidas Escala de Coma de Glasgow: subestimación en pacientes con respuestas verbales impedidas Glasgow Coma Scale: underestimation in patients with verbal responses impeded

Questão freqüente no uso da Escala de Coma de Glasgow (ECGl), na fase aguda, em pacientes internados devido ao trauma crânio-encefálico (TCE) é a subestimação decorrente de situações impeditivas como intubação endotraqueal/traqueostomia, sedação e edema palpebral. O objetivo deste estudo foi identificar e determinar a subestimação na pontuação total da ECGl quando se utiliza a pontuação 1 nas situações de impedimento para a sua avaliação. A amostra estudada foi de 76 pacientes internados com TCE no Hospital das Clínicas da FMUSP. Em 42 (55,3%) pacientes, não havia impedimentos e foram realizadas 136 avaliações. Em 34 (44,7%), havia impedimentos caracterizados por intubação ou traqueostomia, podendo estar ou não associados com edema palpebral e sedação, e o total de avaliações foi de 310. A pontuação nesses pacientes total variou de 3 a 11, com os escores mais freqüentes de 3 e 6. Pelos valores estimados pela regressão linear, a partir das pontuações obtidas em AO e MRM foram obtidas as seguintes subestimações: média=1,03 ±1,36, mediana=0,54 (intubação ou traqueostomia); média=0,40 ±0,79, mediana=0,00 (intubação ou traqueostomia + sedação); média=0,57 ±0,96, mediana=0,27 (intubação ou traqueostomia + sedação + edema palpebral). Conclui-se que, no TCE grave, a pontuação total da ECGl fixando a MRV em 1, embora subestimada, encontra-se próxima da real.<br>Cuestionamiento frecuente en el uso de la Escala de Coma de Glasgow (ECG), en la fase aguda, en pacientes internados debido al trauma craneoencefalico es la subestimación decorrient de situaciones impeditivas como intubación endotraqueal/traqueostomía, sedación y edema palpebral. El objetivo de ese estudio fue identificar y determinar la subestimación en la puntuación total de la ECG cuando es utilizada la puntuación 1 en las situaciones de impedimiento para su avaliación. La muestra estudiada fue de 76 pacientes internados por TEC en el Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. En 42 (55.3%) pacientes, no habia impedimientos y fueron realizadas 136 avaliaciones. Em 34 (44,7%), habia impedimientos caracterizados por intubación o traqueostomía, estando o no asociados con edema palpebral y sedación y el total de avaliaciones fue de 310. En eses, la puntuación total varió de 3 para 11 con los escores más frecuentes en 3 y 6. Por los valores estimados por la regresión linear a partir de las puntuaciones obtenidas en AO y MRM, fueron obtenidas las seguintes subestimaciones: media=1.03±1.36, mediana=0.54 (intubatión o traqueostomía), media=0,40±0.79, mediana=0,00 (intubatión o traqueostomía + sedatión), media=0.57± 0.96, mediana=0.27 (intubatión o traqueostomía + sedatión + edema palpebral). Fue concluído que, en el TEC grave, la puntuación total de la ECG1 mantenendo la MRV en 1, mismo subestimada, se encuentra prójima de la real.<br>Frequent question in the use of Glasgow Coma Scale (GCS), on the acute phase, on inpatients due to encephalic cranial trauma (TBI) is the subestima because of the impeditive situations such as tracheostomy/endotracheal intubation, sedation and palpebral edema. The aim of this study was identify and determining the subestima on the total score of GCS when the score 1 is used on the impediment situations for your assessment. The sample studied had 76 inpatients for TBI at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Within 42 (55,3%) inpatients, there are not impediments and were carried out 136 assessments. In 34 (44,7%), there are impediments characterized by intubation or tracheostomy, being or not related to palpebral edema and sedation and the total evaluation was 310. Within them, the total score varied of 3 to 11 with the more frequent scores in 3 and 6. Through estimated values by linear regression since the scores obtained in EO and VRM, the following subestimas were obtained: mean=1.03±1.36, median=0.54 (intubation or tracheostomy), mean=0,40±0.79, median=0,00 (intubation or tracheostomy + sedation), mean=0.57±0.96, median=0.27 (intubation or tracheostomy + sedation + palpebral edema). It was concluded that, in the serious ECT, the total score of GCS maintained a VRM in 1, although underestimated, it is near the real one