The burden of clostridium difficile infection in patients with liver cirrhosis

Clostridium Difficile Infection (CDI) has registered a dramatically increasing incidence in the general population over the past decades. Nowadays, Clostridium Difficile is the leading cause of hospital-acquired diarrhea in Europe and North America. Liver cirrhosis is the final stage of any chronic liver disease (CLD). The most common causes are chronic hepatitis C or B and viral co-infections, alcohol misuse, and nonalcoholic fatty liver disease (NAFLD). CLD and cirrhosis are listed among the ten leading causes of death in the US. Cirrhosis due to any etiology disrupts the homeostatic role of the liver in the body. Cirrhosis-associated immune dysfunction (CAID) leads to alterations in both inherited and acquired systemic and local liver immunity. CAID is caused by increased systemic inflammation and immunodeficiency and it is responsible for 30% of mortality rates all over the world. Clostridium Difficile infection frequently affects patients suffering from liver cirrhosis because of the high number of prolonged hospitalizations, regular use of antibiotics for the prevention or treatment of SBP, proton pump inhibitor (PPI) use, and an overall immunocompromised state. Clostridium Difficile is a Gram-positive bacterium responsible for the high morbidity and mortality rates in patients with cirrhosis, with an essential increase in a 30-day mortality

Alcoholic liver cirrhosis, more than a simple hepatic disease – A brief review of the risk factors associated with alcohol abuse

Liver cirrhosis is a significant public health problem, being an important cause of mortality and morbidity, responsible for approximately 1.8% of the total number of deaths in Europe. Chronic alcohol consumption is the most common cause of liver cirrhosis in developed countries. Europe has the highest level of alcohol consumption among all the global World Health Organisation (WHO) regions. In this paper, we briefly review major factors leading to excessive alcohol consumption in order to draw attention to the fact that alcoholic liver cirrhosis is more than a simple liver disease, and if those risk/causal factors can be prevented, the incidence of this disease could be reduced greatly. Although excessive alcohol consumption is regarded as the cause of alcoholic liver cirrhosis, the etiology is complex, involving multiple factors that act in synchrony, and which, if prevented, could greatly reduce the incidence of this disease. Children of addicts are likely to develop an alcohol-related mental disorder; however, there is no “gene for alcoholism”

Infrastructure for Detector Research and Development towards the International Linear Collider

The EUDET-project was launched to create an infrastructure for developing and testing new and advanced detector technologies to be used at a future linear collider. The aim was to make possible experimentation and analysis of data for institutes, which otherwise could not be realized due to lack of resources. The infrastructure comprised an analysis and software network, and instrumentation infrastructures for tracking detectors as well as for calorimetry.Comment: 54 pages, 48 picture

Pion and proton showers in the CALICE scintillator-steel analogue hadron calorimeter

Showers produced by positive hadrons in the highly granular CALICE scintillator-steel analogue hadron calorimeter were studied. The experimental data were collected at CERN and FNAL for single particles with initial momenta from 10 to 80 GeV/c. The calorimeter response and resolution and spatial characteristics of shower development for proton- and pion-induced showers for test beam data and simulations using Geant4 version 9.6 are compared.Comment: 26 pages, 16 figures, JINST style, changes in the author list, typos corrected, new section added, figures regrouped. Accepted for publication in JINS

Development of a chemically defined medium and discovery of new mitogenic growth factors for mouse hepatocytes: Mitogenic effects of FGF1/2 and PDGF

Chemically defined serum-free media for rat hepatocytes have been useful in identifying EGFR ligands and HGF/MET signaling as direct mitogenic factors for rat hepatocytes. The absence of such media for mouse hepatocytes has prevented screening for discovery of such mitogens for mouse hepatocytes. We present results obtained by designing such a chemically defined medium for mouse hepatocytes and demonstrate that in addition to EGFR ligands and HGF, the growth factors FGF1 and FGF2 are also important mitogenic factors for mouse hepatocytes. Smaller mitogenic response was also noticed for PDGF AB. Mouse hepatocytes are more likely to enter into spontaneous proliferation in primary culture due to activation of cell cycle pathways resulting from collagenase perfusion. These results demonstrate unanticipated fundamental differences in growth biology of hepatocytes between the two rodent species. Copyright: © 2014 Reekie et al

The burden of clostridium difficile infection in patients with liver cirrhosis

Clostridium Difficile Infection (CDI) has registered a dramatically increasing incidence in the general population over the past decades. Nowadays, Clostridium Difficile is the leading cause of hospital-acquired diarrhea in Europe and North America. Liver cirrhosis is the final stage of any chronic liver disease (CLD). The most common causes are chronic hepatitis C or B and viral co-infections, alcohol misuse, and nonalcoholic fatty liver disease (NAFLD). CLD and cirrhosis are listed among the ten leading causes of death in the US. Cirrhosis due to any etiology disrupts the homeostatic role of the liver in the body. Cirrhosis-associated immune dysfunction (CAID) leads to alterations in both inherited and acquired systemic and local liver immunity. CAID is caused by increased systemic inflammation and immunodeficiency and it is responsible for 30% of mortality rates all over the world. Clostridium Difficile infection frequently affects patients suffering from liver cirrhosis because of the high number of prolonged hospitalizations, regular use of antibiotics for the prevention or treatment of SBP, proton pump inhibitor (PPI) use, and an overall immunocompromised state. Clostridium Difficile is a Gram-positive bacterium responsible for the high morbidity and mortality rates in patients with cirrhosis, with an essential increase in a 30-day mortality

Dissimilar responses of fungal and bacterial communities to soil transplantation simulating abrupt climate changes.

Both fungi and bacteria play essential roles in regulating soil carbon cycling. To predict future carbon stability, it is imperative to understand their responses to environmental changes, which is subject to large uncertainty. As current global warming is causing range shifts toward higher latitudes, we conducted three reciprocal soil transplantation experiments over large transects in 2005 to simulate abrupt climate changes. Six years after soil transplantation, fungal biomass of transplanted soils showed a general pattern of changes from donor sites to destination, which were more obvious in bare fallow soils than in maize cropped soils. Strikingly, fungal community compositions were clustered by sites, demonstrating that fungi of transplanted soils acclimatized to the destination environment. Several fungal taxa displayed sharp changes in relative abundance, including Podospora, Chaetomium, Mortierella and Phialemonium. In contrast, bacterial communities remained largely unchanged. Consistent with the important role of fungi in affecting soil carbon cycling, 8.1%-10.0% of fungal genes encoding carbon-decomposing enzymes were significantly (p < 0.01) increased as compared with those from bacteria (5.7%-8.4%). To explain these observations, we found that fungal occupancy across samples was mainly determined by annual average air temperature and rainfall, whereas bacterial occupancy was more closely related to soil conditions, which remained stable 6 years after soil transplantation. Together, these results demonstrate dissimilar response patterns and resource partitioning between fungi and bacteria, which may have considerable consequences for ecosystem-scale carbon cycling

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland