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Background. Neonatal invasive candidiasis (IC) presenting in the first week of life is less common and less well described than later-onset IC. Risk factors, clinical features, and disease outcomes have not been studied in early-onset disease (EOD, ⩽7 days) or compared to late-onset disease (LOD, >7 days). Methods. All extremely low birth weight (ELBW, <1000 g) cases with IC and controls from a multicenter study of neonatal candidiasis enrolled from 2001 to 2003 were included in this study. Factors associated with occurrence and outcome of EOD in ELBW infants were determined. Results. Forty-five ELBW infants and their 84 matched controls were included. Fourteen (31%) ELBW infants had EOD. Birth weight <750 g, gestation <25 weeks, chorioamnionitis, and vaginal delivery were all strongly associated with EOD. Infection with Candida albicans, disseminated disease, pneumonia, and cardiovascular disease were significantly more common in EOD than in LOD. The EOD case fatality rate (71%) was higher than in LOD (32%) or controls (15%) (P = .0001). The rate of neurodevelopmental impairment and mortality combined was similar in EOD (86%) and LOD (72%), but higher than in controls (32%; P = .007). Conclusions. ELBW infants with EOD have a very poor prognosis compared to those with LOD. The role of perinatal transmission in EOD is supported by its association with chorioamnionitis, vaginal delivery, and pneumonia. Dissemination and cardiovascular involvement are common, and affected infants often die. Empiric treatment should be considered for ELBW infants delivered vaginally who have pneumonia and whose mothers have chorioamnionitis or an intrauterine foreign body. [ABSTRACT FROM AUTHOR]

Aggressive metastasis is the chief cause of the high morbidity and mortality associated with pancreatic cancer, yet the basis for its aggressive behavior remains elusive. Extracellular DNA (exDNA) is a recently discovered component of inflammatory tissue states. Here, we report that exDNA is present on the surface of pancreatic cancer cells where it is critical for driving metastatic behavior. exDNA was abundant on the surface and vicinity of cultured pancreatic cancer cells but absent from normal pancreas cells. Strikingly, treatment of cancer cell cultures with DNase I to degrade DNA nonspecifically reduced metastatic characters associated with matrix attachment, migration, and invasion. We further assessed the role of exDNA in pancreatic cancer metastasis in vivo using an orthotopic xenograft model established by implantation of pancreatic cancer cells expressing firefly luciferase. Noninvasive bioluminescent imaging confirmed that DNase I treatment was sufficient to suppress tumor metastasis. Mechanistic investigations suggested the existence of a positive feedback loop in which exDNA promotes expression of the inflammatory chemokine CXCL8, which leads to higher production of exDNA by pancreatic cancer cells, with a significant reduction in CXCL8 levels achieved by DNase I treatment. Taken together, our results strongly suggest that exDNA contributes to the highly invasive and metastatic character of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Deregulated translation plays an important role in human cancer. We previously reported decreased eukaryotic initiation factor 3 subunit f (eIF3f) expression in pancreatic cancer. Whether decreased eIF3f expression can transform normal epithelial cells is not known. In our current study, we found evidence that stable knockdown of eIF3f in normal human pancreatic ductal epithelial cells increased cell size, nuclear pleomorphism, cytokinesis defects, cell proliferation, clonogenicity, apoptotic resistance, migration, and formation of 3-dimensional irregular masses. Our findings support the tumor suppressive role of eIF3f in pancreatic cancer. Mechanistically, we found that eIF3f inhibited both cap-dependent and cap-independent translation. An increase in the ribosomal RNA (rRNA) level was suggested to promote the generation of cancer. The regulatory mechanism of rRNA degradation in mammals is not well understood. We demonstrated here that eIF3f promotes rRNA degradation through direct interaction with heterogeneous nuclear ribonucleoprotein (hnRNP) K. We showed that hnRNP K is required for maintaining rRNA stability: under stress conditions, eIF3f dissociates hnRNP K from rRNA, thereby preventing it from protecting rRNA from degradation. We also demonstrated that rRNA degradation occurred in non-P body, non-stress granule cytoplasmic foci that contain eIF3f. Our findings established a new mechanism of rRNA decay regulation mediated by hnRNP K/eIF3f and suggest that the tumor suppressive function of eIF3f may link to impaired rRNA degradation and translation. [ABSTRACT FROM AUTHOR]

It is extremely challenging to imitate neural networks with their high-speed parallel signal processing, low power consumption, and intelligent learning capability. In this work, we report a spike neuromorphic module composed of “synapstors” made from carbon nanotube/C60/polyimide composite and “CMOS Somas” made from complementary metal-oxide semiconductor electronic circuits. The “synapstor” emulates a biological synapse with spike signal processing, plasticity, and memory; the “CMOS Soma” emulates a Soma in a biological neuron with analog parallel signal processing and spike generation. Spikes, short potential pulses, and input to the synapstors trigger postsynaptic currents and generate output spikes from the CMOS Somas in a parallel manner with low power consumption. The module can be modified dynamically on the basis of the synapstor plasticity. Spike neuromorphic modules could potentially be scaled up to emulate biologic neural networks and their functions. [ABSTRACT FROM AUTHOR]

Fucosylation regulates various pathological events in cells. We reported that different levels of CRT (calreticulin) affect the cell adhesion and metastasis of bladder cancer. However, the precise mechanism of tumour metastasis regulated by CRT remains unclear. Using a DNA array, we identified FUT1 (fucosyltransferase 1) as a gene regulated by CRT expression levels. CRT regulated cell adhesion through α1,2- linked fucosylation of β1 integrin and this modification was catalysed by FUT1. To clarify the roles for FUT1 in bladder cancer, we transfected the human FUT1 gene into CRT-RNAi stable cell lines. FUT1 overexpression in CRT-RNAi cells resulted in increased levels of β1 integrin fucosylation and rescued cell adhesion to type-I collagen. Treatment with UEA-1 (Ulex europaeus agglutinin-1), a lectin that recognizes FUT1-modified glycosylation structures, did not affect cell adhesion. In contrast, a FUT1-specific fucosidase diminished the activation of β1 integrin. These results indicated that α1,2-fucosylation of β1 integrin was not involved in integrin-collagen interaction, but promoted β1 integrin activation. Moreover, we demonstrated that CRT regulated FUT1 mRNA degradation at the 3'-UTR. In conclusion, the results of the present study suggest that CRT stabilized FUT1 mRNA, thereby leading to an increase in fucosylation of β1 integrin. Furthermore, increased fucosylation levels activate β1 integrin, rather than directly modifying the integrin-binding sites. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The pulmonary embolism severity index (PESI) and the recently derived simplified PESI prognostic model have been developed to estimate the risk of 30-day mortality in patients with acute PE. We sought to assess if the PESI and simplified PESI prognostic models can accurately identify adverse events and to determine the rates of events in patients treated as outpatients. Methods: A retrospective cohort study of patients with acute pulmonary embolism (PE) presenting at the Ottawa Hospital (Canada) was conducted between 1 January 2007 and 31 December 2008. Results: Two hundred and forty three patients were included. A total of 118 (48.6%) and 81 (33.3%) were classified as low risk patients using the original and simplified PESI prognostic models respectively. None of the low risk patients died within the 3months of follow-up. One hundred and fifteen (47.3%) patients were safely treated as outpatients with no deaths or bleeding episodes and only 1 recurrent event within the first 14days or after 30days of follow-up. Thirty four (29.6%) of these outpatients were classified as high risk patients according to the original PESI and 54 (47.0%) to the simplified PESI prognostic model. Conclusion: Both PESI strategies accurately identify patients with acute PE who are at low risk and high risk for short-term adverse events. However, 30 to 47% of patients with acute PE and a high risk PESI score were safely managed as outpatients. Future research should be directed at developing tools that predict which patients would benefit from inpatient management. [Copyright &y& Elsevier]