Impact of thoracic injury on traumatic brain injury outcome.

BACKGROUND: To assessed the significance of thoracic injury on the 30-day mortality and outcome of traumatic brain injury (TBI). METHODS: TBI patients admitted to our department were retrospectively evaluated. We developed two prognostic models based on admission predictors with logistic regression analysis to assess the significance of thoracic injuries in determining the 30-day mortality and outcome. The internal validity of the models was evaluated with the bootstrap re-sampling technique. We also validated the models in an external series of 165 patients that collected from our center. Discriminative ability was evaluated with C statistic. Calibrative ability was assessed with the Hosmer-Lemeshow test (H-L test). RESULTS: Among 505 TBI patients admitted, 102 (20.2%) had thoracic injuries. Patients with a PCS ≥ 6 had a 3.142 and 8.065 times higher odds of mortality and poor outcome compared with patients with a PCS <6, respectively. Any one-score increase of the TTS had a 1.193 times higher odds of a poor outcome (p = 0.017). The predictive model for mortality and 30-day functional outcome both had good accuracy (AUC: 0.875; 95% confidence interval [CI], 0.841-0.910 and AUC: 0.888; 95%CI, 0.860-0.916, respectively). Internal validation showed no over optimism in any of the two models' predictive C statistics (C statistic 0.872 for 30-day mortality and C statistic 0.884 for the 30-day neurological outcome). The external validation confirmed the discriminatory ability of these models (C statistic 0.949 (95%CI: 0.919-0.980) for 30-day mortality and C statistic 0.915 (95%CI: 0.868-0.963) for the 30-day neurological outcome). The calibration was also good for patients from the validation population (H-L test p>0.05). CONCLUSION: Thoracic injury diagnosed by CT has a negative impact on the 30-day mortality and functional outcome of TBI patients. The extent of PC and the TTS are the predictors for TBI outcome

The Zfx gene is expressed in human gliomas and is important in the proliferation and apoptosis of the human malignant glioma cell line U251

Abstract Background Zfx is a zinc finger protein of the Zfy family, whose members are highly conserved in vertebrates. Zfx is a shared transcriptional regulator of both embryonic stem cells (ESC) and hematopoietic stem cells (HSC), which suggests a common genetic basis of self-renewal in embryonic and adult stem cells. The level of Zfx expression correlates with aggressiveness and severity in many cancer types, including prostate cancer, breast cancer, and leukemia. However, the importance of Zfx in human glioma is largely unknown. In the present study, we examined the role of Zfx in human glioma. Methods We detected expression levels of Zfx mRNA in U251 cells, U87 cells, U373 cells, and A172 cells by semi-quantitative RT-PCR. To analyze the expression of Zfx mRNA in glioma tissues, we performed real-time quantitative PCR on 35 pathologically confirmed glioma samples (Grade I-4cases, Grade II-13cases, Grade III-11cases, and Grade IV-7cases) and on 5 noncancerous brain tissue samples. We used lentivirus-mediated small interfering RNAs (siRNAs) to knock down Zfx expression in the human malignant glioma cell line U251. Changes in Zfx target gene expression were determined by real-time RT-PCR. Cell proliferation was examined by a High Content Screening assay. DNA synthesis in proliferating cells was determined by BrdU incorporation. Cell cycle distribution and apoptosis were detected by flowcytometric analysis. Results We discovered that Zfx mRNA was expressed in U251 cells, U87 cells, U373 cells, and A172 cells. The expression level of Zfx is significantly higher in gliomas compared to noncancerous brain tissue. Using a lentivirus-based RNAi approach, Zfx expression was significantly inhibited in human glioblastoma U251 cells. The effects of Zfx knockdown on cell proliferation, cell cycle distribution, and apoptosis were assessed. Inhibition of Zfx expression in U251 cells by RNAi significantly impaired cell proliferation, increased apoptosis, and arrested cells in S phase. Conclusions The results of our study demonstrate that the Zfx gene is highly expressed in glioma tissue and in glioma cell lines. Furthermore, Zfx may play a critical role in cell proliferation, cell cycle distribution, and apoptosis of human malignant glioma cells.</p

ROC curve for prediction of poor outcome estimated using multiple logistic regression.

<p>Predictive variables for this equation are age, head AIS >3, PCS ≥6, GCS group, and TTS score with an AUC of 0.888, indicating good accuracy.</p

Validation of the prognostic models for 30-day mortality in validation patients (n = 165).

<p>The smooth dash curves reflect the relation between observed probability of mortality and predicted probability of mortality. The triangles indicate the observed frequencies by deciles of predicted probability.</p

Validation of the prognostic models for 30-day outcome in validation patients (n = 165).

<p>The smooth dash curves reflect the relation between observed probability of outcome and predicted probability of outcome. The triangles indicate the observed frequencies by deciles of predicted probability.</p

Memory T cell RNA rearrangement programmed by heterogeneous nuclear ribonucleoprotein hnRNPLL

Differentiation of memory cells involves DNA-sequence changes in B lymphocytes but is less clearly defined in T\ua0cells. RNA rearrangement is identified here as a key event in memory T\ua0cell differentiation by analysis of a mouse mutation that altered the proportions of naive and memory T\ua0cells and crippled the process of Ptprc exon silencing needed to generate CD45RO in memory T\ua0cells. A single substitution in\ua0a memory-induced RNA-binding protein, hnRNPLL, destabilized an RNA-recognition domain that bound with micromolar affinity to RNA containing the Ptprc exon-silencing sequence. Hnrpll mutation selectively diminished T\ua0cell accumulation in peripheral lymphoid tissues but not proliferation. Exon-array analysis of Hnrpll mutant naive and memory T\ua0cells revealed an extensive program of alternative mRNA splicing in memory T\ua0cells, coordinated by hnRNPLL. A remarkable overlap with alternative splicing in neural tissues may reflect a co-opted strategy for diversifying memory T\ua0cells

Memory T cell RNA rearrangement programmed by heterogeneous nuclear ribonucleoprotein hnRNPLL

Differentiation of memory cells involves DNA-sequence changes in B lymphocytes but is less clearly defined in T cells. RNA rearrangement is identified here as a key event in memory T cell differentiation by analysis of a mouse mutation that altered th