Many bacteria can infect and persist inside their hosts for long periods of time. This can be due to immunosuppression of the host, immune evasion by the pathogen and/or ineffective killing by antibiotics. Bacteria can survive antibiotic treatment if they are resistant or tolerant to a drug. Persisters are a subpopulation of transiently antibiotic-tolerant bacterial cells that are often slow-growing or growth-arrested, and are able to resume growth after a lethal stress. The formation of persister cells establishes phenotypic heterogeneity within a bacterial population and has been hypothesized to be important for increasing the chances of successfully adapting to environmental change. The presence of persister cells can result in the recalcitrance and relapse of persistent bacterial infections, and it has been linked to an increase in the risk of the emergence of antibiotic resistance during treatment. If the mechanisms of the formation and regrowth of these antibiotic-tolerant cells were better understood, it could lead to the development of new approaches for the eradication of persistent bacterial infections. In this Review, we discuss recent developments in our understanding of bacterial persisters and their potential implications for the treatment of persistent infections.

Hepatocellular carcinoma (HCC) is a highly aggressive vascular cancer characterized by diverse etiology, activation of multiple signal transduction pathways, and various gene mutations. Here, we have determined a specific role for astrocyte elevated gene-1 (AEG1) in HCC pathogenesis. Expression of AEG1 was extremely low in human hepatocytes, but its levels were significantly increased in human HCC. Stable overexpression of AEG1 converted nontumorigenic human HCC cells into highly aggressive vascular tumors, and inhibition of AEG1 abrogated tumorigenesis by aggressive HCC cells in a xenograft model of nude mice. In human HCC, AEG1 overexpression was associated with elevated copy numbers. Microarray analysis revealed that AEG1 modulated the expression of genes associated with invasion, metastasis, chemoresistance, angiogenesis, and senescence. AEG1 also was found to activate Wnt/β-catenin signaling via ERK42/44 activation and upregulated lymphoidenhancing factor 1/T cell factor 1 (LEF1/TCF1), the ultimate executor of the Wnt pathway, important for HCC progression. Inhibition studies further demonstrated that activation of Wnt signaling played a key role in mediating AEG1 function. AEG1 also activated the NF-κB pathway, which may play a role in the chronic inflammatory changes preceding HCC development. These data indicate that AEG1 plays a central role in regulating diverse aspects of HCC pathogenesis. Targeted inhibition of AEG1 might lead to the shutdown of key elemental characteristics of HCC and could lead to an effective therapeutic strategy for HCC.

Measurements of the specific heat of Mg11B2 from 1 to 50 K, in magnetic fields to 9 T, give the Debye temperature, Theta = 1050 K, the coefficient of the normal-state electron contribution, gamma(n) = 2.6 mJ mol(-1) K-2, and a discontinuity in the zero-field specific heat of 133 mJ mol(-1) K-1 at T(c) = 38.7 K. The estimated value of the electron-phonon coupling parameter, lambda = 0.62, could account for the observed T(c) only if the important phonon frequencies are unusually high relative to Theta. At low T, there is a strongly field-dependent feature that suggests the existence of a second energy gap, about 4 times smaller than the major gap.

The objective of this study was to prospectively define outcomes of cirrhosis due to nonalcoholic steatohepatitis (NASH) and compare them with those associated with hepatitis C virus (HCV) infection. We compared 152 patients with cirrhosis due to NASH with 150 matched patients with cirrhosis due to HCV. Over 10 years, 29/152 patients with cirrhosis due to NASH died compared with 44/150 patients with HCV (P < .04). This was mainly due to the lower mortality rate in patients with Child class A cirrhosis due to NASH versus HCV (3/74 vs. 15/75; P < .004). There were no significant across-group differences in mortality in patients with Child class B or C cirrhosis. Sepsis was the most common cause of death in both groups; patients with NASH had a higher cardiac mortality (8/152 vs. 1/150; P < .03). Patients with Child class A cirrhosis due to NASH also had a significantly lower risk of decompensation, defined by a 2-point increase in Child-Turcotte-Pugh score (P < .007). Cirrhosis due to NASH was associated with a lower rate of development of ascites (14/101 vs. 40/97 patients at risk; P < .006). NASH also had a significantly lower risk of development of hepatocellular carcinoma (10/149 vs. 25/147 patients at risk; P < .01). In conclusion, compensated cirrhosis due to NASH is associated with a lower mortality rate compared with that due to HCV. It is also associated with a lower rate of development of ascites, hyperbilirubinemia, and hepatocellular carcinoma. However, cardiovascular mortality is greater in patients with NASH. (HEPATOLOGY 2006;43:682-689.)

Abstract. -We show that the specific heat of the superconductor MgB2 in zero field, for which significant non-BCS features have been reported, can be fitted, essentially within experimental error, over the entire range of temperature to Tc by a phenomenological two-gap model. The resulting gap parameters agree with previous determinations from band-structure calculations, and from various spectroscopic experiments. The determination from specific heat, a bulk property, shows that the presence of two superconducting gaps in MgB2 is a volume effect.The discovery of superconductivity in MgB 2 [1] raised the questions of its nature and the origin of its relatively high transition temperature T c ∼ 40 K. Specific heat (C) is a powerful tool to aid in answering these questions and, more generally, to provide information on the thermodynamics of the transition. Several groups have reported such measurements on MgB 2 [2-10]. It is now established that C significantly deviates from the standard BCS behaviour. First, a large excess in C is observed in the vicinity of T c /4 [2-6]. Second, an exponential fit of C(T ) in the region T ≪ T c indicates a gap ratio 2∆ 0 /k B T c only onequarter to one-third of the isotropic BCS value [3,4,6]. This excess was interpreted as a possible sign of a second superconducting gap, whose existence is predicted by band-structure calculations [11][12][13]. The specific heat near T c is puzzling also with the jump ∆C at T c consistently smaller than the BCS weak-coupling lower bound. In this Letter, we present an empirical two-gap model that fits the experimental data over the whole range of temperature to T c . This model resolves the apparent contradiction between different analyses of the specific heat, and relevant parameters show good agreement with determinations based on independent experiments.We focus on two sets of specific-heat data obtained independently in two different laboratories. Experimental methods and results have been described elsewhere [2,3,5,6]. The unusual excess specific heat at ∼ T c /4, which denotes the presence of excitations within the c EDP Sciences

Background & Aims-Reports of complications among adult right hepatic lobe donors have been limited to single centers. The rate and severity of complications in living donors were investigated in the 9-center Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL).

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A wider application of living donor liver transplantation is limited by donor morbidity concerns. An observational cohort of 760 living donors accepted for surgery and enrolled in the Adult-to-Adult Living Donor Liver Transplantation cohort study provides a comprehensive assessment of incidence, severity and natural history of living liver donation (LLD) complications. Donor morbidity (assessed by 29 specific complications), predictors, time from donation to complications and time from complication onset to resolution were measured outcomes over a 12-year period. Out of the 760 donor procedures, 20 were aborted and 740 were completed. Forty percent of donors had complications (557 complications among 296 donors), mostly Clavien grades 1 and 2. Most severe counted by complication category; grade 1 (minor, n = 232); grade 2 (possibly life-threatening, n = 269); grade 3 (residual disability, n = 5) and grade 4 (leading to death, n = 3). Hernias (7%) and psychological complications (3%) occurred >1 year postdonation. Complications risk increased with transfusion requirement, intraoperative hypotension and predonation serum bilirubin, but did not decline with the increased center experience with LLD. The probability of complication resolution within 1 year was overall 95%, but only 75% for hernias and 42% for psychological complications. This report comprehensively quantifies LLD complication risk and should inform decision making by potential donors and their caregivers.