Saccadic latency in hepatic encephalopathy: a pilot study

Hepatic encephalopathy is a common complication of cirrhosis. The degree of neuro-psychiatric impairment is highly variable and its clinical staging subjective. We investigated whether eye movement response times—saccadic latencies—could serve as an indicator of encephalopathy. We studied the association between saccadic latency, liver function and paper- and pencil tests in 70 patients with cirrhosis and 31 patients after liver transplantation. The tests included the porto-systemic encephalopathy (PSE-) test, critical flicker frequency, MELD score and ammonia concentration. A normal range for saccades was established in 31 control subjects. Clinical and biochemical parameters of liver, blood, and kidney function were also determined. Median saccadic latencies were significantly longer in patients with liver cirrhosis when compared to patients after liver transplantation (244 ms vs. 278 ms p < 0.001). Both patient groups had prolonged saccadic latency when compared to an age matched control group (175 ms). The reciprocal of median saccadic latency (μ) correlated with PSE tests, MELD score and critical flicker frequency. A significant correlation between the saccadic latency parameter early slope (σE) that represents the prevalence of early saccades and partial pressure of ammonia was also noted. Psychometric test performance, but not saccadic latency, correlated with blood urea and sodium concentrations. Saccadic latency represents an objective and quantitative parameter of hepatic encephalopathy. Unlike psychometric test performance, these ocular responses were unaffected by renal function and can be obtained clinically within a matter of minutes by non-trained personnel

Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer

Pancreatic cancer (PC) mobilizes myeloid cells from the bone marrow to the tumor where they promote tumor growth and proliferation. Cancer stem cells (CSCs) are a population of tumor cells that are responsible for tumor initiation. Aldehyde dehydrogenase-1 activity in PC identifies CSCs, and its activity has been correlated with poor overall prognosis in human PC. Myeloid cells have been shown to impact tumor stemness, but the impact of immunosuppressive tumor-infiltrating granulocytic and monocytic myeloid-derived suppressor cells (Mo-MDSC) on ALDH1(Bright) CSCs and epithelial to mesenchymal transition is not well understood. In this study, we demonstrate that Mo-MDSC (CD11b(+)/Gr1(+)/Ly6G(−)/Ly6C(hi)) significantly increase the frequency of ALDH1(Bright) CSCs in a mouse model of PC. Additionally, there was significant upregulation of genes associated with epithelial to mesenchymal transition. We also found that human PC converts CD14(+) peripheral blood monocytes into Mo-MDSC (CD14(+)/HLA-DR(low/−)) in vitro, and this transformation is dependent on the activation of the STAT3 pathway. In turn, these Mo-MDSC increase the frequency of ALDH1(Bright) CSCs and promote mesenchymal features of tumor cells. Finally, blockade of STAT3 activation reversed the increase in ALDH1(Bright) CSCs. These data suggest that the PC tumor microenvironment transforms monocytes to Mo-MDSC by STAT3 activation, and these cells increase the frequency of ALDH1(Bright) CSCs. Therefore, targeting STAT3 activation may be an effective therapeutic strategy in targeting CSCs in PC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-014-1527-x) contains supplementary material, which is available to authorized users

Pediatric multiple sclerosis: update on diagnostic criteria, imaging, histopathology and treatment choices

Pediatric multiple sclerosis (MS) represents less than 5% of the MS population, but patients with pediatric-onset disease reach permanent disability at a younger age than adult onset patients. Accurate diagnosis at presentation and optimal long-term treatment is vital to mitigate ongoing neuroinflammation and irreversible neurodegeneration. However, it may be difficult to early differentiate pediatric MS from acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica spectrum disorders (NMOSD) as they often have atypical presentation that differs from that of adult-onset MS. The purpose of this review is to summarize the updated views on diagnostic criteria, imaging, histopathology and treatment choices

Soilborne Diseases and their Control

Seed and seedling diseases, root rots, and wilts are caused by a number of soilborne fungi, all of which are facultative saprophytes and can survive in soil for long periods in the absence of a susceptible host. In general, these diseases are serious yield constraints where short rotations or monoculture of legume crops are the rule. Seedling diseases and root rots are enhanced by poor seed vigor, poor seedbed preparation, and other biotic and abiotic stresses which predispose the host plant. Control of these diseases requires an integrated approach of genetic resistance/tolerance, cultural practices, appropriate seed treatments, and high seed vigor. The most economical and durable control of Fusarium wilt is to grow resistant varieties. New races of a wilt pathogen have arisen due to increased selection pressure from growing resistant varieties in short rotations but have not outpaced the development of resistant cultivars

The tides of Enceladus' porous core

The inferred density of Enceladus' core, together with evidence of hydrothermal activity within the moon, suggests that the core is porous. Tidal dissipation in an unconsolidated core has been proposed as the main source of Enceladus' geological activity. However, the tidal response of its core has generally been modeled assuming it behaves viscoelastically rather than poroviscoelastically. In this work, we analyze the poroviscoelastic response to better constrain the distribution of tidal dissipation within Enceladus. A poroviscoelastic body has a different tidal response than a viscoelastic one; pressure within the pores alters the stress field and induces a Darcian porous flow. This flow represents an additional pathway for energy dissipation. Using Biot's theory of poroviscoelasticity, we develop a new framework to obtain the tidal response of a spherically symmetric, self-gravitating moon with porous layers and apply it to Enceladus. We show that the boundary conditions at the interface of the core and overlying ocean play a key role in the tidal response. The ocean hinders the development of a large-amplitude Darcian flow, making negligible the Darcian contribution to the dissipation budget. We therefore infer that Enceladus' core can be the source of its geological activity only if it has a low rigidity and a very low viscosity. A future mission to Enceladus could test this hypothesis by measuring the phase lags of tidally induced changes of gravitational potential and surface displacements