Outbreaks of virulent diarrheagenic Escherichia coli - are we in control?

Shiga toxin-producing Escherichia coli (STEC) are the most virulent diarrheagenic E. coli known to date. They can be spread with alarming ease via food as exemplified by a large sprout-borne outbreak of STEC O104:H4 in 2011 that was centered in northern Germany and affected several countries. Effective control of such outbreaks is an important public health task and necessitates early outbreak detection, fast identification of the outbreak vehicle and immediate removal of the suspected food from the market, flanked by consumer advice and measures to prevent secondary spread

Nerve tolerance to high-dose-rate brachytherapy in patients with soft tissue sarcoma: a retrospective study

BACKGROUND: Brachytherapy, interstitial tumor bed irradiation, following conservative surgery has been shown to provide excellent local control and limb preservation in patients with soft tissue sarcomas (STS), whereas little is known about the tolerance of peripheral nerves to brachytherapy. In particular, nerve tolerance to high-dose-rate (HDR) brachytherapy has never been properly evaluated. In this study, we examined the efficacy and radiation neurotoxicity of HDR brachytherapy in patients with STS in contact with neurovascular structures. METHODS: Between 1995 and 2000, seven patients with STS involving the neurovascular bundle were treated in our institute with limb-preserving surgery, followed by fractionated HDR brachytherapy. Pathological examination demonstrated that 6 patients had high-grade lesions with five cases of negative margins and one case with positive margins, and one patient had a low-grade lesion with a negative margin. Afterloading catheters placed within the tumor bed directly upon the preserved neurovascular structures were postoperatively loaded with Iridium-192 with a total dose of 50 Gy in 6 patients. One patient received 30 Gy of HDR brachytherapy combined with 20 Gy of adjuvant external beam radiation. RESULTS: With a median follow-up of 4 years, the 5-year actuarial overall survival, disease-free survival, and local control rates were 83.3, 68.6, and 83.3%, respectively. None of the 7 patients developed HDR brachytherapy-induced peripheral neuropathy. Of 5 survivors, 3 evaluable patients had values of motor nerve conduction velocity of the preserved peripheral nerve in the normal range. CONCLUSION: In this study, there were no practical and electrophysiological findings of neurotoxicity of HDR brachytherapy. Despite the small number of patients, our encouraging results are valuable for limb-preserving surgery of unmanageable STS involving critical neurovascular structures

Epidemiology of reported Yersinia enterocolitica infections in Germany, 2001-2008

<p>Abstract</p> <p>Background</p> <p>Yersiniosis is the third most common zoonotic bacterial disease in Germany and the European Union. Sequelae of <it>Yersinia enterocolitica </it>infections, such as reactive arthritis, have been reported. Consumption of pork and its products, especially eaten raw or undercooked, is an important risk factor of yersiniosis. Infection with <it>Y. enterocolitica </it>is notifiable through the national surveillance system for infectious diseases in Germany and several thousands of cases are being reported each year. We present recent data on the epidemiology of reported yersiniosis in Germany.</p> <p>Methods</p> <p>Surveillance data on yersiniosis, accessed through the national level database (SurvNet), were analyzed with regard to time trends, demographical and geographical distribution, serotypes, and hospitalization, for the time period 2001-2008.</p> <p>Results</p> <p>A total of 47,627 cases of yersiniosis were reported. The mean annual incidence of yersiniosis was 7.2/100,000 population. A downward trend in the number of reportable cases has occurred since 2002. Almost all <it>Y. enterocolitica </it>infections were reported as single cases, i.e., with no apparent links to other cases. The number of reported infections showed substantially less seasonal variation than in other zoonotic enteric diseases. The incidence was highest in children under five years (58/100,000 population), in particular in one-year-old children (108/100,000 population). Almost 97% of infections were acquired domestically. High incidences occurred in the eastern German federal states Thuringia, Saxony, and Saxony-Anhalt. Differences in incidences across federal states were driven primarily by incidence differences in children under five years. Hospitalization was reported for 17% of cases, the proportion being highest among teenagers. Almost 90% of <it>Y. enterocolitica </it>strains were diagnosed as serotype O:3, which is the serotype most frequently isolated from pigs.</p> <p>Conclusions</p> <p>Yersiniosis is a zoonotic foodborne disease of relevance to public health in Germany because of its high incidence and risk for sequelae. The incidence of reported yersiniosis in Germany varies markedly from state to state, mainly due to incidence difference among young children. More research efforts should be directed towards the elucidation of risk factors of yersiniosis in this age group.</p

The first case report of dental floss pick-related injury presenting with massive hemoptysis: A case report

<p>Abstract</p> <p>Introduction</p> <p>A tracheobronchial foreign body is a rarely mentioned cause of massive hemoptysis. Although an aspirated toothpick is a well-known cause of traumatic injury to the respiratory tract, a similar device called a dental floss pick, which is much larger than a toothpick, has never been described as a tracheobronchial foreign body.</p> <p>Case presentation</p> <p>We report a case of massive hemoptysis in a 32-year-old man due to a dental floss pick in the left main bronchus. Flexible fiberoptic bronchoscopy was successful in removing the foreign body.</p> <p>Conclusion</p> <p>Tracheobronchial foreign body can be a medical emergency requiring immediate intervention and massive hemoptysis may be the presenting symptom. Flexible fiberoptic bronchoscopy is recommended as the first-line treatment modality for tracheobronchial foreign body removal. A dental floss pick may present as a tracheobronchial foreign body and can reside in the airway asymptomatically for many years.</p

Functionalized boron nitride membranes with ultrafast solvent transport performance for molecular separation

Pressure-driven, superfast organic solvent filtration membranes have significant practical applications. An excellent filtration membrane should exhibit high selectivity and permeation in aqueous and organic solvents to meet increasing industrial demand. Here, we report an amino functionalized boron nitride (FBN) based filtration membrane with a nanochannel network for molecular separation and permeation. This membrane is highly stable in water and in several organic solvents and shows high transport performance for solvents depending on the membranes&apos; thickness. In addition, the FBN membrane is applicable for solute screening in water as well as in organic solvents. More importantly, the FBN membranes are very stable in acidic, alkaline and oxidative media for up to one month. The fast-flow rate and good separation performance of the FBN membranes can be attributed to their stable networks of nanochannels and thin laminar structure, which provide the membranes with beneficial properties for practical separation and purification processes

Antibody Response to Shiga Toxins in Argentinean Children with Enteropathic Hemolytic Uremic Syndrome at Acute and Long-Term Follow-Up Periods

Shiga toxin (Stx)-producing Escherichia coli (STEC) infection is associated with a broad spectrum of clinical manifestations that include diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Systemic Stx toxemia is considered to be central to the genesis of HUS. Distinct methods have been used to evaluate anti-Stx response for immunodiagnostic or epidemiological analysis of HUS cases. The development of enzyme-linked immunosorbent assay (ELISA) and western blot (WB) assay to detect the presence of specific antibodies to Stx has introduced important advantages for serodiagnosis of HUS. However, application of these methods for seroepidemiological studies in Argentina has been limited. The aim of this work was to develop an ELISA to detect antibodies against the B subunit of Stx2, and a WB to evaluate antibodies against both subunits of Stx2 and Stx1, in order to analyze the pertinence and effectiveness of these techniques in the Argentinean population. We studied 72 normal healthy children (NHC) and 105 HUS patients of the urban pediatric population from the surrounding area of Buenos Aires city. Using the WB method we detected 67% of plasma from NHC reactive for Stx2, but only 8% for Stx1. These results are in agreement with the broad circulation of Stx2-expressing STEC in Argentina and the endemic behavior of HUS in this country. Moreover, the simultaneous evaluation by the two methods allowed us to differentiate acute HUS patients from NHC with a great specificity and accuracy, in order to confirm the HUS etiology when pathogenic bacteria were not isolated from stools

Enterohaemorrhagic Escherichia coli and Shigella dysenteriae type 1-induced haemolytic uraemic syndrome

Haemolytic uraemic syndrome (HUS) can be classified according to the aetiology of the different disorders from which it is composed. The most prevalent form is that induced by shigatoxin producing Escherichia coli (STEC) and, in some tropical regions, by Shigella dysenteriae type 1. STEC cause a zoonosis, are widely distributed in nature, enter the food chain in different ways, and show regional differences. Not all STEC are human pathogens. Enterohaemorrhagic E. coli usually cause attachment and effacing lesions in the intestine. This is not essential, but production of a shigatoxin (Stx) is. Because Stx are encoded by a bacteriophage, this property is transferable to naïve strains. Laboratory methods have improved by identifying STEC either via the toxin or its bacteriophage. Shigella dysenteriae type 1 produces shigatoxin, identical to Stx-1, but also has entero-invasive properties that enterohaemorrhagic Escherichia coli (EHEC) do not. Shigella patients risk bacteremia and benefit from early antibiotic treatment, unlike those with EHEC

Moxifloxacin enhances antiproliferative and apoptotic effects of etoposide but inhibits its proinflammatory effects in THP-1 and Jurkat cells

Etoposide (VP-16) is a topoisomerase II (topo II) inhibitor chemotherapeutic agent. Studies indicate that VP-16 enhances proinflammatory cytokines secretion from tumour cells, including IL-8, a chemokine associated with proangiogenic effects. Fluoroquinolones inhibit topo II activity in eukaryotic cells by a mechanism different from that of VP-16. The fluoroquinolone moxifloxacin (MXF) has pronounced anti-inflammatory effects in vitro and in vivo. We studied the effects of MXF and VP-16 on purified human topo II activity and further analysed their combined activity on proliferation, apoptosis and caspase-3 activity in THP-1 and Jurkat cells. Moxifloxacin alone slightly inhibited the activity of human topo II; however, in combination with VP-16 it led to a 73% reduction in enzyme activity. VP-16 inhibited cell proliferation in a time and dose-dependent manner. The addition of moxifloxacin for 72 h to low-dose VP-16 doubled its cytotoxic effect in THP-1 and Jurkat cells (1.8- and 2.6-fold decrease in cell proliferation, respectively) (P<0.004). Moxifloxacin given alone did not induce apoptosis but enhanced VP-16-induced apoptosis in THP-1 and Jurkat cells (1.8- and two-fold increase in annexin V positive cells and caspase-3 activity, respectively) (P<0.04). VP-16 induced the release of IL-8 in a time and dose-dependent manner from THP-1 cells. Moxifloxacin completely blocked the enhanced release of IL-8 induced by 0.5 and 1 μg ml−1 VP-16, and decreased IL-8 release from cells incubated for 72 h with 3 μg ml−1 VP-16 (P<0.001). VP-16 enhanced the release of IL-1β and TNF-α from THP-1 cells, whereas the addition of MXF prevented the enhanced cytokine secretion (P<0.001). We conclude that MXF significantly enhances VP-16 cytotoxicity in tumour-derived cells while preventing VP-16-induced proinflammatory cytokine release. This unique combination may have clinical benefits and cytotoxic drug ‘sparing effect' and should be further studied in vivo

Somatic Mutation Profiles of MSI and MSS Colorectal Cancer Identified by Whole Exome Next Generation Sequencing and Bioinformatics Analysis

BACKGROUND: Colorectal cancer (CRC) is with approximately 1 million cases the third most common cancer worldwide. Extensive research is ongoing to decipher the underlying genetic patterns with the hope to improve early cancer diagnosis and treatment. In this direction, the recent progress in next generation sequencing technologies has revolutionized the field of cancer genomics. However, one caveat of these studies remains the large amount of genetic variations identified and their interpretation. METHODOLOGY/PRINCIPAL FINDINGS: Here we present the first work on whole exome NGS of primary colon cancers. We performed 454 whole exome pyrosequencing of tumor as well as adjacent not affected normal colonic tissue from microsatellite stable (MSS) and microsatellite instable (MSI) colon cancer patients and identified more than 50,000 small nucleotide variations for each tissue. According to predictions based on MSS and MSI pathomechanisms we identified eight times more somatic non-synonymous variations in MSI cancers than in MSS and we were able to reproduce the result in four additional CRCs. Our bioinformatics filtering approach narrowed down the rate of most significant mutations to 359 for MSI and 45 for MSS CRCs with predicted altered protein functions. In both CRCs, MSI and MSS, we found somatic mutations in the intracellular kinase domain of bone morphogenetic protein receptor 1A, BMPR1A, a gene where so far germline mutations are associated with juvenile polyposis syndrome, and show that the mutations functionally impair the protein function. CONCLUSIONS/SIGNIFICANCE: We conclude that with deep sequencing of tumor exomes one may be able to predict the microsatellite status of CRC and in addition identify potentially clinically relevant mutations