NOD2 gene variants are a risk factor for culture-positive spontaneous bacterial peritonitis and monomicrobial bacterascites in cirrhosis

Spontaneous bacterial peritonitis (SBP) is considered as result of bacterial translocation from the gastrointestinal lumen to the mesenteric lymph nodes and subsequent circulation. Variants of the NOD2 gene contribute to bacterial translocation and were associated with SBP in a recent study.

[Spontaneous bacterial peritonitis]

Spontaneous bacterial peritonitis (SBP) is the most frequent infection in patients with cirrhosis during hospitalization and is associated with high acute and long-term mortality. Diagnosis is made by paracentesis with determination of neutrophil count in ascitic fluid. Empirical antibiotic therapy must be initiated immediately. The choice of drug is dependent on prior therapies. Liver transplantation has to be considered in the absence of contra-indications. Prophylaxis of SBP is indicated in patients with ascites and gastrointestinal hemorrhage, and in patients after SBP. Primary prophylaxis should be considered in high-risk patients with cirrhosis and ascites. The development of resistance to antibiotic drugs is a relevant side-effect.

Is detection of bacterial DNA in ascitic fluid of clinical relevance?

In patients with cirrhosis, bacterial DNA has been found in ascites reflecting bacterial translocation. However, the clinical relevance of this finding is ill-defined especially compared with the standard diagnostics for detection of spontaneous bacterial peritonitis (SBP). Furthermore, other DNA tests have not been sufficiently evaluated.

Connective tissue growth factor level is increased in patients with liver cirrhosis but is not associated with complications or extent of liver injury

Connective tissue growth factor (CTGF) is a profibrotic protein whose systemic levels are increased in liver cirrhosis. Here, association of CTGF with stages of liver injury and complications of cirrhotic liver disease has been analyzed in patients with different aetiologies of hepatic injury. CTGF is significantly increased in portal venous serum (PVS), hepatic venous serum (HVS) and systemic venous serum (SVS) of 46 patients with liver cirrhosis compared to eight liver-healthy controls. In patients´ blood samples CTGF in HVS is about 6% higher than PVS levels indicating that CTGF produced in the liver is released to the circulation. CTGF is not associated with stages of liver cirrhosis defined by CHILD-PUGH or MELD score nor with secondary complications of portal hypertension (varices, ascites, spontaneous bacterial peritonitis). Transforming growth factor β (TGFβ) induces CTGF synthesis in hepatocytes and a positive association of systemic TGFβ1 and SVS and HVS CTGF is found. Three months after placing transjugular intrahepatic portosystemic shunt (TIPS) hepatic venous pressure gradient is reduced whereas CHILD-PUGH score, TGFβ1 and CTGF are not altered in serum of 15 patients. Current data show that the cirrhotic liver releases little CTGF but SVS, HVS and PVS CTGF levels are not associated with residual liver function and complications of cirrhosis.

The role of the interplay between polymer architecture and bacterial surface properties on the microbial adhesion to polyoxazoline-based ultrathin films

Surface platforms were engineered from poly(L-lysine)-graft-poly(2-methyl-2-oxazoline) (PLL-g-PMOXA) copolymers to study the mechanisms involved in the non-specific adhesion of Escherichia coli (E. coli) bacteria. Copolymers with three different grafting densities (PMOXA chains/Lysine residue of 0.09, 0.33 and 0.56) were synthesized and assembled on niobia (Nb O ) surfaces. PLL-modified and bare niobia surfaces served as controls. To evaluate the impact of fimbriae expression on the bacterial adhesion, the surfaces were exposed to genetically engineered E. coli strains either lacking, or constitutively expressing type 1 fimbriae. The bacterial adhesion was strongly influenced by the presence of bacterial fimbriae. Non-fimbriated bacteria behaved like hard, charged particles whose adhesion was dependent on surface charge and ionic strength of the media. In contrast, bacteria expressing type 1 fimbriae adhered to the substrates independent of surface charge and ionic strength, and adhesion was mediated by non-specific van der Waals and hydrophobic interactions of the proteins at the fimbrial tip. Adsorbed polymer mass, average surface density of the PMOXA chains, and thickness of the copolymer films were quantified by optical waveguide lightmode spectroscopy (OWLS) and variable-angle spectroscopic ellipsometry (VASE), whereas the lateral homogeneity was probed by time-of-flight secondary ion mass spectrometry (ToF-SIMS). Streaming current measurements provided information on the charge formation of the polymer-coated and the bare niobia surfaces. The adhesion of both bacterial strains could be efficiently inhibited by the copolymer film only with a grafting density of 0.33 characterized by the highest PMOXA chain surface density and a surface potential close to zero.

Air suctioning during colon biopsy forceps removal reduces bacterial air contamination in the endoscopy suite

Bacterial contamination of endoscopy suites is of concern; however studies evaluating bacterial aerosols are lacking. We aimed to determine the effectiveness of air suctioning during removal of biopsy forceps in reducing bacterial air contamination.

Bacterial colonization and infection of electrophysiological cardiac devices detected with sonication and swab culture

Electrophysiological cardiac devices are increasingly used. The frequency of subclinical infection is unknown. We investigated all explanted devices using sonication, a method for detection of microbial biofilms on foreign bodies.

Effects of catecholamines on hepatic and skeletal muscle mitochondrial respiration after prolonged exposure to faecal peritonitis in pigs

Use of norepinephrine to increase blood pressure in septic animals has been associated with increased efficiency of hepatic mitochondrial respiration. The aim of this study was to evaluate whether the same effect could be reproduced in isolated hepatic mitochondria after prolonged in vivo exposure to faecal peritonitis. Eighteen pigs were randomized to 27 h of faecal peritonitis and to a control condition (n = 9 each group). At the end, hepatic mitochondria were isolated and incubated for one hour with either norepinephrine or placebo, with and without pretreatment with the specific receptor antagonists prazosin and yohimbine. Mitochondrial state 3 and state 4 respiration were measured for respiratory chain complexes I and II, and state 3 for complex IV using high-resolution respirometry, and respiratory control ratios were calculated. Additionally, skeletal muscle mitochondrial respiration was evaluated after incubation with norepinephrine and dobutamine with and without the respective antagonists (atenolol, propranolol and phentolamine for dobutamine). Faecal peritonitis was characterized by decreasing blood pressure and stroke volume, and maintained systemic oxygen consumption. Neither faecal peritonitis nor any of the drugs or drug combinations had measurable effects on hepatic or skeletal muscle mitochondrial respiration. Norepinephrine did not improve the efficiency of complex I- and complex II-dependent isolated hepatic mitochondrial respiration [respiratory control ratio (RCR) complex I: 5.6 ± 5.3 (placebo) vs. 5.4 ± 4.6 (norepinephrine) in controls and 2.7 ± 2.1 (placebo) vs. 2.9 ± 1.5 (norepinephrine) in septic animals; RCR complex II: 3.5 ± 2.0 (placebo) vs. 3.5 ± 1.8 (norepinephrine) in controls; 2.3 ± 1.6 (placebo) vs. 2.2 ± 1.1 (norepinephrine) in septic animals]. Prolonged faecal peritonitis did not affect either hepatic or skeletal muscle mitochondrial respiration. Subsequent incubation of isolated mitochondria with norepinephrine and dobutamine did not significantly influence their respiration.

Intravaginal practices, bacterial vaginosis, and HIV infection in women: individual participant data meta-analysis

Background Identifying modifiable factors that increase women's vulnerability to HIV is a critical step in developing effective female-initiated prevention interventions. The primary objective of this study was to pool individual participant data from prospective longitudinal studies to investigate the association between intravaginal practices and acquisition of HIV infection among women in sub-Saharan Africa. Secondary objectives were to investigate associations between intravaginal practices and disrupted vaginal flora; and between disrupted vaginal flora and HIV acquisition. Methods and Findings We conducted a meta-analysis of individual participant data from 13 prospective cohort studies involving 14,874 women, of whom 791 acquired HIV infection during 21,218 woman years of follow-up. Data were pooled using random-effects meta-analysis. The level of between-study heterogeneity was low in all analyses (I2 values 0.0%–16.1%). Intravaginal use of cloth or paper (pooled adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.18–1.83), insertion of products to dry or tighten the vagina (aHR 1.31, 95% CI 1.00–1.71), and intravaginal cleaning with soap (aHR 1.24, 95% CI 1.01–1.53) remained associated with HIV acquisition after controlling for age, marital status, and number of sex partners in the past 3 months. Intravaginal cleaning with soap was also associated with the development of intermediate vaginal flora and bacterial vaginosis in women with normal vaginal flora at baseline (pooled adjusted odds ratio [OR] 1.24, 95% CI 1.04–1.47). Use of cloth or paper was not associated with the development of disrupted vaginal flora. Intermediate vaginal flora and bacterial vaginosis were each associated with HIV acquisition in multivariable models when measured at baseline (aHR 1.54 and 1.69, p<0.001) or at the visit before the estimated date of HIV infection (aHR 1.41 and 1.53, p<0.001), respectively. Conclusions This study provides evidence to suggest that some intravaginal practices increase the risk of HIV acquisition but a direct causal pathway linking intravaginal cleaning with soap, disruption of vaginal flora, and HIV acquisition has not yet been demonstrated. More consistency in the definition and measurement of specific intravaginal practices is warranted so that the effects of specific intravaginal practices and products can be further elucidated.

Inhibition of bacterial degradation of EtG by collection as dried urine spots (DUS)

Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are direct alcohol consumption markers widely used nowadays for clinical and forensic applications. They are detectable in blood and urine even after consumption of trace amounts of ethanol and for a longer time frame, being detectable even when no more ethanol is present. The instability of EtG against bacterial degradation in contaminated urine samples and/or the possible postcollection synthesis of this metabolite in samples containing, e.g., Escherichia coli and ethanol, may cause false identification of alcohol uptake. Therefore, it is of paramount importance to constrict these error sources by inhibition of any bacterial growth causing hydrolization or synthesis of EtG. This study evaluates a new method of collecting urine samples on filter paper, dried urine spots (DUS), for simultaneous detection of EtG, EtS and creatinine, having the great advantage of inhibiting bacterial activity. In addition, a method validation for the determination of EtG and EtS in DUS was performed according to the FDA guidelines. Sterile-filtered urine was spiked with EtG and EtS, inoculated with E. coli and incubated. Liquid and dried urine samples were collected after various time intervals up to 96 h. Liquid samples were frozen immediately after collection, whereas aliquots for DUS were pipetted onto filter paper, allowed to dry and stored at RT until analysis 1 week after. The specimens were analyzed by LC-ESI-MS/MS. As expected, degradation of EtG, but not of EtS, was observed in contaminated liquid urine samples. However, the specimens collected on filter paper and stored at RT showed no degradation during storage. Therefore, collecting urine samples on filter paper for EtG and EtS analysis turns out to be a reliable method to avoid bacterial degradation of EtG and EtS, and consequently, stabilization of these ethanol metabolites is achieved. In addition, simultaneous measurement of creatinine content as an indicator of urine dilution helps to interpret the results. Method validation for EtG and EtS in DUS was satisfactory, showing the linearity of the calibration curves in the studied concentration range, good precision, accuracy and selectivity.

Clinical settings and specialties notifying cases of bacterial sexually transmitted infections in Switzerland: A cross-sectional study

In the next Swiss National HIV and Sexually Transmitted Infection (STI) Strategy 2011-2017, STI control will be integrated with HIV prevention. Information is needed which will improve the targeting of professional education. The objective of this study was to describe the clinical specialities and settings to which patients with bacterial STI present in Switzerland.

Bacterial expression of mutant argininosuccinate lyase reveals imperfect correlation of in-vitro enzyme activity with clinical phenotype in argininosuccinic aciduria

The urea cycle defect argininosuccinate lyase (ASL) deficiency has a large spectrum of presentations from highly severe to asymptomatic. Enzyme activity assays in red blood cells or fibroblasts, although diagnostic of the deficiency, fail to discriminate between severe, mild or asymptomatic cases. Mutation/phenotype correlation studies are needed to characterize the effects of individual mutations on the activity of the enzyme.