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A nationwide outbreak of human listeriosis in Switzerland was traced to persisting environmental contamination of a cheese dairy with Listeria monocytogenes serotype 4b, sequence type 6, cluster type 7488. Whole-genome sequencing was used to match clinical isolates to a cheese sample and to samples from numerous sites within the production environment.

Background: Juglone is a naphthoquinone currently obtained by chemical synthesis with biological activities including antitumor activity. Additionally, juglone is present in the green husk of walnut, which suggests evaluating the effect of GH extracts on carcinogenic cell lines. Results: Walnut green husk ethanolic extract was obtained as 169.1 mg juglone/100 g Green Husk and antioxidant activity (ORAC) of 44,920 μmol Trolox Equivalent/100 g DW Green Husk. At 1 μM juglone in HL-60 cell culture, green husk extract showed an antiproliferative effect, but pure juglone did not; under these conditions, normal fibroblast cells were not affected. A dose-dependent effect on mitochondrial membrane potential loss was observed. Apoptosis of HL-60 was detected at 10 μM juglone. Despite high ORAC values, neither purified juglone nor the extract showed protective effects on HL-60 cells under oxidative conditions. Conclusions: Green husk extract generates an antiproliferative effect in HL-60 cells, which is related to an induction of the early stages of apoptosis and a loss of mitochondrial membrane potential. The normal cells were not affected when juglone is present at concentrations of 1 μM, while at higher concentrations, there is loss of viability of both cancerous and healthy cells.How to cite: Soto-Maldonado C, Vergara-Castro M, Jara-Quezada J, et al. Polyphenolic extracts of walnut (Juglans regia) green husk containing juglone inhibit the growth of HL-60 cells and induce apoptosis. Electron J Biotechnol 2019;39. https://doi.org/10.1016/j.ejbt.2019.02.001. Keywords: walnut husk discards, solvent extraction, antioxidant activity, mammalian cells, leukemia cells line inhibition, Polyphenolic extracts, Juglans regia, green husk, juglone, HL-60 cells, apoptosis

Shiga toxin-producing Escherichia coli (STEC) O80:H2 is an uncommon hybrid pathotype that has emerged in Switzerland and France. Here, we report the draft genome sequences of 19 stx-harboring Escherichia coli O80:H2 strains isolated between 2003 and 2019 from patients in Switzerland.

Shiga toxin-producing Escherichia coli (STEC) belonging to the serogroup O91 are among the most common non-O157 STEC serogroups associated with human illness in Europe. This study aimed to analyse the virulence factors, antimicrobial resistance genes and phylogenetic relatedness among 48 clinical STEC O91 isolates collected during 2003-2019 in Switzerland. The isolates were subjected to whole genome sequencing using short-read sequencing technologies and a subset of isolates additionally to long-read sequencing. They belonged to O91:H10 (n=6), O91:H14 (n=40), and O91:H21 (n=2). Multilocus sequence typing showed that the O91:H10 isolates all belonged to sequence type (ST)641, while the O91:H14 isolates were assigned to ST33, ST9700, or were non-typeable. Both O91:H21 isolates belonged to ST442. Shiga toxin gene stx1a was the most common Shiga toxin gene subtype among the isolates, followed by stx2b, stx2d and stx2a. All isolates were LEE-negative and carried one or two copies of the IrgA adhesin gene iha. In a subset of long-read sequenced isolates, modules of the Locus of Adhesion and Autoaggregation pathogenicity island (LAA-PAI) carrying iha and other genes such as hes, lesP or agn43 were identified. A large proportion of STEC O91:H14 carried the subtilase cytotoxin gene subA, colicin genes (cba, cea, cib and cma) or microcin genes (mcmA, mchB, mchC and mchF). STEC O91:H14 were further distinguished from STEC O91:H10/H21 by one or more virulence factors found in extraintestinal pathogenic E. coli (ExPEC), including hlyF, iucC/iutA, kpsE and traT. The hlyF gene was identified on a novel mosaic plasmid that was unrelated to hlyF+ plasmids described previously in STEC. Core genome phylogenetic analysis revealed that STEC O91:H10 and STEC O91:H21 were clonally conserved, whereas STEC O91:H14 were clonally diverse. Among three STEC O91:H14 isolates, a number of resistance genes were identified, including genes that mediate resistance to aminoglycosides (aadA, aadA2, aadA9, aadA23, aph(3'')-Ib and aph(6)-Id), chloramphenicol (cmlA), sulphonamides (sul2 and sul3), and trimethoprim (drfA12). Our data contribute to understanding the genetic diversity and differing levels of virulence potential within the STEC O91 serogroup.

Objective The study aimed to determine the influence of head neck position on imaging measurements used to assess the craniovertebral junction (CVJ) and to recommend the most appropriate position for the evaluation of the CVJ. Study Design A cross-sectional sample of adult dogs' cadavers was subjected to a computed tomography scan of the cranium and the cranial cervical region in three standardized head positions. Imaging measurements often used to assess the CVJ were measured. The influence of the head neck position, breed, weight and gender on imaging measurements was tested using repeated measures analysis of variance. Results Twenty-eight cadavers of small breed dogs were enrolled in the study. All cadavers examined had occipital dysplasia. All transarticular imaging measurements were dependent on the head neck position. In addition, the breed, weight and gender had an influence on several measurements. Conclusion We recommend a standardized head neck position of 50 degrees flexion if quantitative imaging measurements of the CVJ are used to diagnose pathologies in this region. Future studies should focus on the definition of cut-off values for quantitative imaging measurements of the CVJ to differentiate between healthy and diseased small breed dogs. Regarding atlantoaxial instability, a combination of six parameters (C1-C2 angle, C1-C2 overlap, atlantoaxial distance, dens-to-axis length ratio, ventral compression index and clivus canal angle) is promising for its diagnosis.

Health risk associated with air pollution and its exposure has gained much importance in the recent years. The potential toxicity of air pollutants especially particulate matter (PM) is attributed to its chemical composition and size. Hence, it is imperative to understand the morphology, size, and chemical composition of PM for health risk assessment. Polyaromatic hydrocarbons (PAHs) present in PM have high toxicity and mutagenic potential. Recent advancement in technology such as bioassays for cytotoxicity, oxidative stress, and apoptosis studies using human cell lines has allowed us to comprehend the underlying mechanism of particle toxicity and its impact on human health. This chapter deals with the health risks associated with air pollution and exposure assessment with a focus on chemical toxicity associated with air pollutants, especially PM. Health risks associated with particle-bound chemical compounds in school children are also explained in this chapter.

Caligidosis and Piscirickettsiosis are currently the most important sanitary challenges for the Chilean salmon industry. Caligidosis is caused by the ectoparasite, Caligus rogercresseyi and Piscirickettsiosis is caused by the intracellular bacterium, Piscirickettsia salmonis. Both diseases are highly prevalent and widely distributed in farming areas in Chile. The co-occurrence of the two diseases is frequently reported on salmon farms. However, there is little epidemiological evidence as to whether these two diseases are associated and generate interactive effects. This study was undertaken to evaluate the potential effects of C. rogercresseyi infestation on P. salmonis-attributed mortalities in farmed salmonids in Chile. Using a linear regression model, the potential association between the mean abundance of adult C. rogercresseyi in a period of 10 weeks and Piscirickettsiosis cumulative mortalities observed in the following 10 weeks was evaluated, while controlling for important confounders. These two 10-week windows were set around the time-point at which Piscirickettsiosis weekly mortality exceeded 0.1% for the first time in a production cycle. We found that the mean abundance of adult C. rogercresseyi was significantly associated with the Piscirickettsiosis cumulative mortality, suggesting the two diseases have a synergistic relationship. This relationship was of the same intensity in Atlantic salmon and rainbow trout. Our findings highlight the importance of taking effective control measures for C. rogercresseyi as a part of the strategies in place to reduce P. salmonis-attributed mortalities on salmon farms in Chile.

The genome of Salmonella bongori N19-781, a strain isolated from a patient with diarrhea, was sequenced. It consists of a 4.5-Mbp chromosome.

Matthias Peter Hilty, Andrea Mueller, Daniela Flück, Christoph Siebenmann, Peter Rasmussen, Stefanie Keiser, Katja Auinger, Carsten Lundby, and Marco Maggiorini. Effect of increased blood flow on the pulmonary circulation before and during high altitude acclimatization. High Alt Med Biol. 17:305-314, 2016.-Introduction and Methods: Acute exposure to high altitude increases pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR). The evolution of Ppa and PVR with continuous hypoxic exposure remains, however, elusive. To test the hypothesis that altitude exposure leads to a persistent elevation in Ppa and PVR throughout acclimatization in seven healthy male subjects, echocardiography was performed at sea level (SL; 488 m) weekly during a 4-week sojourn at 3454 m (HA1-HA4) and upon return (SL2). Pulmonary artery catheterization and bilateral thigh cuff release maneuver were performed at SL and HA3 to study the properties of pulmonary circulation after 3 weeks of acclimatization.Pulmonary artery catheter determined that systolic Ppa (mean ± SEM) was increased from 20 ± 1 at SL to 27 ± 2 mmHg at HA3 (p 0.01). Echocardiography assessed that systolic Ppa remained equally increased throughout acclimatization (26 ± 2, 25 ± 2, 25 ± 2, and 24 ± 2 mmHg at HA1-HA4; p = 0.93) and returned to baseline upon return (17 ± 2, 18 ± 1 mmHg at SL, SL2; p = 0.3). The same was shown for PVR. Right heart function remained unaffected. Thigh cuff release maneuvers at SL and HA3 resulted in similar increase in cardiac output (2.5 ± 0.5 and 2.2 ± 0.4 L/min; p = 0.61) without affecting mean Ppa.Prolonged altitude exposure leads to a persistent increase in Ppa and PVR without affecting right heart function and is fully reversible within 1 week after return to SL. The thigh cuff release maneuver-induced increase in cardiac output suggests a preserved ability of pulmonary circulation to cope with sudden remarkable increase in pulmonary blood flow throughout acclimatization.

Few studies describe recent changes in the incidence, treatment and outcome of successfully resuscitated STEMI patients after out-of-hospital cardiac arrest (OHCA) compared with non-OHCA STEMI patients.To examine temporal trends in the incidence, therapeutic management, most serious complications, mortality rate and outcome of OHCA patients fulfilling criteria of STEMI compared with a reference group of STEMI patients without OHCA.Analysis of registry data (AMIS Plus Registry) among STEMI patients both with and without OHCA between 1997 and 2017.Among 31,650 patients with STEMI, 6.8% were successfully resuscitated prior to hospital admission. Increasing incidences of hospital-admitted patients following successful out-of-hospital CPR were observed (4.5% in 1999 vs. 8.6% in 2017). OHCA STEMI patients were at higher clinical risk at presentation (36.1% vs. 2.7%; p 0.001 with cardiogenic shock) despite a shorter time span from the onset of symptoms to hospitalization (195 min vs. 107 min; p 0.001) and a lower prevalence of cardiovascular risk factors except smoking. More PCIs were performed in STEMI patients with OHCA (78.9% vs. 74.5% for non-OHCA patients; p 0.001). However, over time PCI became the preferred primary intervention irrespective of the OHCA status of STEMI patients. For STEMI patients without OHCA, there was a significant correlation between PCI and time periods on in-hospital mortality (p 0.001), which was p = 0.002 when adjusted for age and gender. For STEMI patients with OHCA, the interaction between PCI and time was unadjusted p = 0.395 and p = 0.438 when adjusted for age and gender.

Laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are common and effective methods to treat severe obesity, but these procedures can adversely influence bone metabolism and areal bone mineral density (aBMD). This was a prospective 24-month single-center interventional two-arm study in 220 women and similarly aged men (median age 40.7 years) with a body mass index (BMI) >38 kg/m(2) after RYGB and SG procedures. Patients were randomized into: 1) an intervention group receiving: 28,000 IU cholecalciferol/wk for 8 weeks before bariatric surgery, 16,000 IU/wk and 1000 mg calciummonocitrate/d after surgery, daily BMI-adjusted protein supplementation and physical exercise (Nordic walking, strength perseverance, and equipment training); 2) a non-intervention group: no preoperative loading, nutritional supplementation, or obligatory physical exercise. At study endpoint, when comparing the intervention group to the non-intervention group, the relative percentage changes of serum levels of sclerostin (12.1% versus 63.8%), cross-linked C-telopeptide (CTX, 82.6% versus 158.3%), 25-OH vitamin D (13.4% versus 18.2%), phosphate (23.7% versus 32%, p < 0.001 for all), procollagen type 1 amino-terminal propeptide (P1NP, 12% versus 41.2%), intact parathyroid hormone (iPTH, -17.3% versus -7.6%), and Dickkopf-1 (-3.9% versus -8.9%, p < 0.05 for all) differed. The decline in lumbar spine, total hip and total body aBMD, changes in BMI, lean body mass (LBM), as well as changes in trabecular bone score (TBS) values (p < 0.005 for all) were less, but significantly, pronounced in the intervention group. We conclude that vitamin D loading and ongoing vitamin D, calcium, and BMI-adjusted protein supplementation in combination with physical exercise decelerates the loss of aBMD and LBM after bariatric surgery. Moreover, the well-known increases of bone turnover markers are less pronounced.

Contains fulltext : 196138.pdf (Publisher’s version ) (Open Access) This case report discusses continuous epidural administration of ropivacaine 0.56 mg kg(-1) h (-1) for 8 days in a 7-year-old trauma patient to prevent pain, after performing a lower right and upper left leg guillotine amputation. Venous sampling after 8 days revealed bound and unbound ropivacaine concentrations of 1.1 mg/l and 0.06 mg/l in plasma, respectively. Arterial sampling for bound and unbound ropivacaine was 1.2 mg/l and 0.05 mg/l in plasma, respectively. In this case report, long-term high dose epidural infiltration of ropivacaine did not result in severe side effects or complications. Further studies are needed to explore safety of these concentrations in larger populations of children.

Plant health is strongly connected with plants´ microbiome. In case of raw-eaten plants, the microbiome can also affect human health. To study potential impacts on health issues of both hosts, the microbiome composition of seven different Brassica vegetables, originating from different food processing pathways, was analyzed by a combined approach of amplicon sequencing, metagenomic mining and cultivation. All Brassica vegetables harbored a highly diverse microbiota as identified by 16S rRNA gene amplicon sequencing. The composition of the microbiota was found to be rather driven by the plant genotype than by the processing pathway. We characterized isolates with potential cancer-preventing properties by tracing myrosinase activity as well as isolates with biological control activity towards plant pathogens. We identified a novel strain with myrosinase activity and we found bacterial myrosinase genes to be enriched in rhizosphere and phyllosphere metagenomes of Brassica napus and Eruca sativa in comparison to the surrounding soil. Strains which were able to suppress plant pathogens were isolated from naturally processed vegetables and represent a substantial part (4.1%) of all vegetable microbiomes. Our results shed first light on the microbiome of edible plants and open the door to harnessing the Brassica microbiome for plant disease resistance and human health.

As treatment results for high-risk soft tissue sarcoma are still disappointing, treatment intensification is warranted. We performed a retrospective analysis of multimodal preoperative treatment to evaluate the additional effect of concurrent chemotherapy and/or locoregional hyperthermia in comparison to radiotherapy alone. Between 1999 and 2011, 28 patients were treated with neoadjuvant radiotherapy to a median 45 Gy for high-risk soft tissue sarcoma. All tumors were deep-seated and grade 2 or 3, 86% (n = 24) larger than 5 cm. Multimodal treatment (n = 12) consisted of ifosfamide (n = 7), locoregional hyperthermia (n = 3), or both modalities (n = 2) concurrent to radiotherapy. Prognostic factors (grade, size, histology, location) were balanced in the groups with and without concurrent multimodal treatment. There was a significant improvement of disease-specific survival (100% vs. 70% at 3 years, p = 0.03) with multimodal treatment. Distant metastases-free survival was influenced, but was not statistically significant. Local control and disease-free survival did not differ in the two groups. Our data suggest that multimodal treatment with ifosfamide and/or locoregional hyperthermia in combination with neoadjuvant radiotherapy might improve outcome in high-risk soft tissue sarcomas.

Most research approaches the genesis of risk prone behaviour in juvenile delinquents from a single point of view, psychological or sociological. In our research, we have attempted to eliminate this unilateralism. To this end, we have tested an integrative model composed of the psychological and sociological factors of juvenile delinquency. The empirical research was performed on a sample of 420 randomly selected juvenile delinquents and a control group of 420 individuals selected by stratified random sampling. The research methodology consisted of analysing documents (family situation, age, etc.) and applying psychological tests (Nowicki & Strickland's Internal-External Control Scale for Children, McGuire & Priestley's Testing Your Reaction, Zuckerman-Kuhlman's Personality Questionnaire and A.W. Tucker's Inmate Dilemma Test). Data confirmed that young delinquents are more impulsive and have a higher sensation seeking tendency, but their decision-making capacity in risk situations is not significantly different compared to the control group. Looking at the data of the psychological tests and the descriptors of the social situation of juvenile delinquents, it looks like personality factors are associated with social factors (family shortcomings, low level of schooling, substance abuse, entourage, friends) as important determinants of delinquency.

The objective of this study was i) to quantify the risk of hepatitis E for Swiss consumers by specified pork products and ii) to estimate the total burden of human food-borne hepatitis E in Switzerland. A quantitative risk assessment from slaughter to consumption was carried out according to the Codex Alimentarius framework. In the hazard characterization, assumptions were made due to the lack of a dose-response relationship for oral exposure to hepatitis E virus (HEV). The prevalence of HEV in 160 pig livers of 40 different Swiss fattening farms was examined and determined to be 1.3% (CI 0.3%; 4.4%). This result was used as input in the risk assessment model, together with data from other published studies. The annual burden of hepatitis E was estimated in terms of Disability Adjusted Life Years (DALY), using data about hepatitis E cases diagnosed between 2010 and 2015 at two major hospitals located in the canton Ticino. Only the risk of foodborne hepatitis E from products containing pork liver was evaluated, as those containing only pork meat could not be evaluated because of lack of data on HEV load in pork. Assuming that successful oral infection occurs in 1% of servings contaminated with high HEV loads (>105 genome copies), and that acute illness develops in 5% of susceptible consumers, the most likely annual number of foodborne hepatitis E cases in Switzerland was estimated to be 1481 (95% CI 552; 4488) if all products containing pork liver were considered. If only high-risk products, such as plain pork liver and liver sausages (e.g. Saucisse au Foie), were considered, the annual number of cases was estimated to be 176 (95% CI 64; 498). We were unable to calculate the total burden of hepatitis E in Switzerland due to lack of data. Yet, for the canton Ticino, it was shown that a significant increase had occurred from 50 DALY per 100,000 inhabitants in 2015. This change could partly be due to an increased reporting and higher awareness among medical practitioners. Extrapolation to other regions could be accomplished if detailed information on food consumption patterns were available. Notification of HEV cases and attempts of cases source attribution would improve the basis for risk assessments.

Customizable endonucleases are providing an effective tool for genome engineering. The resulting primary transgenic individuals (T0) are typically heterozygous and/or chimeric with respect to any mutations induced. To generate genetically fixed mutants, they are conventionally allowed to self-pollinate, a procedure which segregates individuals into mutant heterozygotes/homozygotes and wild types. The chances of recovering homozygous mutants among the progeny depend not only on meiotic segregation but also on the frequency of mutated germline cells in the chimeric mother plant. In Nicotiana species, the heritability of Cas9-induced mutations has not been demonstrated yet. RNA-guided Cas9 endonuclease-mediated mutagenesis was targeted to the green fluorescent protein (GFP) gene harbored by a transgenic tobacco line. Upon retransformation using a GFP-specific guide RNA/Cas9 construct, the T0 plants were allowed to either self-pollinate, or were propagated via regeneration from in vitro cultured embryogenic pollen which give rise to haploid/doubled haploid plants or from leaf explants that form plants vegetatively. Single or multiple mutations were detected in 80% of the T0 plants. About half of these mutations proved heritable via selfing. Regeneration from in vitro cultured embryogenic pollen allowed for homozygous mutants to be produced more efficiently than via sexual reproduction. Consequently, embryogenic pollen culture provides a convenient method to rapidly generate a variety of genetically fixed mutants following site-directed mutagenesis. The recovery of a mutation not found among sexually produced and analyzed progeny was shown to be achievable through vegetative plant propagation in vitro, which eventually resulted in heritability when the somatic clones were selfed. In addition, some in-frame mutations were associated with functional attenuation of the target gene rather than its full knock-out. The generation of mutants with compromised rather than abolished gene functionality holds promise for future approaches to the conclusive functional validation of genes which are indispensible for the plant.

Background Investigate the usefulness of echocardiography and acoustic cardiography to monitor patients exposed to anthracycline chemotherapy. Hypothesis Serial echocardiographies to monitor systolic function may not be neccessary in all patients undergoing anthracycline chemotherapy. Methods In a prospective study, consecutive patients undergoing anthracycline-containing chemotherapy were evaluated with echocardiography and acoustic cardiography at baseline, after completion of chemotherapy, and after a median follow-up of 3.8 years. Systolic dysfunction was defined as a left ventricular ejection fraction ≤50%. Results A total of 187 patients (83% female) with a mean age of 55 ± 14 years underwent chemotherapy for breast cancer (73%), malignant lymphoma (23%), and sarcoma (4%). None of the patients had systolic dysfunction at baseline. Patients were treated with doxorubicin 276 ± 74 mg/m2 or epirubicin 317 ± 55 mg/m2. After chemotherapy, 170 (91%) had normal systolic function, 8 (4%) developed systolic dysfunction, and 9 (5%) had died. Of those 8 patients with systolic dysfunction, 4 (50%) improved to normal systolic function, 1 (13%) remained unchanged, and 3 (37%) died. Patients with normal systolic function after chemotherapy had a mortality rate of 3.5%, and 1.8% developed late systolic dysfunction. Acoustic cardiography-derived percent electromechanical activation time >12.4% had a sensitivity of 88% and a specificity of 84% to identify patients with systolic dysfunction (area under the receiver operating characteristic curve 0.87). Conclusions Patients with systolic dysfunction early after anthracycline treatment had worse outcome. Acoustic cardiography was able to identify these patients with a high sensitivity and specificity. Based on the findings of this study, we propose a simple algorithm to monitor patients undergoing anthracycline-containing chemotherapy. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Eine 52-jahrige Patientin wurde wegen progredienter Thrombosen unter therapeutischer Antikoagulation sowie Leukozytose mit Eosinophilie und Thrombozytopenie stationar aufgenommen. Bei Aufnahme prasentierte sich die Patientin mit Dyspnoe und Schwellung des linken Beins und Arms. Im Labor fielen eine Leukozytose (31 000/μl) mit Eosinophilie (54%), eine Thrombozytopenie (58 000/μl) und ein erhohtes C-reaktives Protein von 247 mg/dl (Normwert < 5 mg/dl) auf. In der Bildgebung waren eine Lungenembolie beidseits sowie ein leicht vergroserter Leistenlymphknoten nachweisbar. Die Biopsie des Lymphknotens (LK) ergab histologisch eine teils epitheloide, teils spindelige tumorose Lasion mit leicht vermehrter Gewebseosinophilie, passend zu einem inflammatorischen myofibroblastaren Tumor (IMT). Nach Resektion des LK links inguinal kam es zu einer sofortigen Ruckbildung der paraneoplastischen Eosinophilie und Thrombozytopenie. Anschliesend wurde eine antiinflammatorische Therapie mit Ibuprofen eingeleitet. 3 Monate nach Entlassung war bildgebend kein Rezidiv sowie klinisch kein Anhalt fur ein erneutes paraneoplastisches Syndrom nachweisbar. Der IMT ist ein seltener Weichgewebstumor von intermediarer Dignitat mit geringer Metastasierungsneigung. Er wird immer wieder von paraneoplastischen Syndromen begleitet. Die Therapie der Wahl besteht in der kompletten Tumorentfernung, bei nicht resektablen Tumoren wurden Kortikosteroide oder nichtsteroidale Antirheumatika erfolgreich eingesetzt. Aufgrund des sehr variablen klinischen Verlaufs von spontaner Ruckbildung bis hin zu Metastasierung konnte es sich beim IMT um verschiedene Entitaten (inflammatorisch, neoplastisch, autoimmun) handeln, die histologisch noch nicht ausreichend voneinander abgegrenzt werden konnen. Wichtig ist daher eine klinische Abschatzung der Dignitat so lange, bis eine Subtypisierung dieser seltenen Erkrankung moglich ist

Background Epidemiologic studies show statistical associations between levels of air pollutants and respiratory outcomes. Objective We sought to determine the effects of exposure to petrochemical pollution on the respiratory health of children. Methods Children aged 6 to 12 years living close to the petrochemical plants in La Plata, Argentina (n = 282), were compared with those living in a region with exposure to heavy traffic (n = 270) or in 2 relatively nonpolluted areas (n = 639). Parents answered a validated questionnaire providing health and demographic data. A random sample (n = 181) had lung function measured. Particulate matter and outdoor and indoor volatile organic compound levels were measured during 4-week study periods and reported as overall means for each study area. Results Children living near the petrochemical plant had more asthma (24.8% vs 10.1% to 11.5%), more asthma exacerbations (6.7 vs 2.9-3.6 per year), more respiratory symptoms (current wheeze, dyspnea, nocturnal cough, and rhinitis), and lower lung function (>13% decrease in FEV 1 percent predicted) than those living in other regions. Length of residence in the area was a significant risk factor, but age, sex, body mass index, proximity to busy roads and other nonpetrochemical industries, length of breast-feeding, and socioeconomic and demographic characteristics of children or their families were not. Conclusion Exposure to particulate matter and volatile organic compounds arising from petrochemical plants but not from high traffic density was associated ith worse respiratory health in children.

In this study, extended-spectrum s-lactamase (ESBL)-producing Escherichia coli isolates recovered from the following sources were characterized with regard to the occurrence and distribution of uropathogenic and enteric pathogenic virulence factors: surface waters (rivers and lakes, n=60), the intestines of freshwater fish (n=33), fresh vegetables (n=26), retail poultry meat (n=13) and the fecal samples of livestock (n=28), healthy humans (n=34) and primary care patients (n=13). Among the 207 isolates, 82% tested positive by PCR for one or more of the virulence factors (VF) that predict uropathogenicity, TraT, fyuA, chuA, PAI, yfcv or vat. Uropathogenic E. coli (UPEC) were detected in each of the analyzed sources. Regarding virulence factors for intestinal pathogenic E. coli, these were found more rarely and predominantly associated with the aquatic environment, with aagR (EAEC) found in isolates from surface waters and STp (porcine heat stable enterotoxin) and LT (heat-labile enterotoxin) associated with isolates from fish. Aggregate VF scores (the number of unique virulence factors detected for each isolate) were lowest among isolates belonging to phylogenetic group B1 and highest among group B2. Clustering of the isolates by phylogenetic group, multilocus sequence type (MLST) and ESBL-types revealed clonal overlaps of A:ST10(CTX-M-1) and D:ST350(CTX-M-1) between the sources of livestock, poultry meat and healthy humans, suggesting livestock, in particular poultry, represents a potential reservoir for these particular UPEC clones. The clones A:ST10(CTX-M-55) and B2:ST131(CTX-M-27), harboring uropathogenic virulence factors were significantly associated with fresh vegetables and with fish, respectively. Further clonal complexes with source overlaps included D:ST38(CTX-M-14), D:ST69(CTX-M-15), D:ST405(CTX-M-15) and D:ST648(CTX-M-15), which were found in surface water and healthy humans. Identifying potential reservoirs of UPEC in the environment, animals, food and humans is important in order to assess routes of transmission and risk factors for acquiring UPEC.

The representatives of the Ministry of Health have stated that the causes bringing about the ranking of Romania on the “negative list” in Europe regarding the occurrence of tuberculosis are the consequences of the poor social, economic and educational level of a segment of population. Besides this fact, the other causes for the high occurrence of tuberculosis are smoking and chronic alcoholism. General purpose of research: assessment of psycho-social and economic level of tuberculosis patients in order to develop an intervention program. Specific purpose of research: assessment of alcohol consumption habits in the population subjected to research. Materials and Methods. For this purpose we relayed on a population of 205 tuberculosis patients from Cluj-Napoca and the investigation was made through the following research instruments: questionnaires, individualized semi-structured interviews and document analysis. The results have shown that social, cultural and economic factors are playing a crucial role in development of chronic tuberculosis. Conclusion. Moreover, the patients are hospitalized for a long time because of the sickness and set-backs are frequent because they are not changing their lifestyle (alcohol and drug consumption habits). Due to this fact we consider to be important the role of prevention and intervention in the framework of social work.

Summary: Purpose: Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for generalized and focal epilepsies. We provide an update on hepatotoxic side effects in Germany between 1994 and 2003. Methods: We mailed a questionnaire to all members of the German Section of the International League Against Epilepsy, asking for VPA-induced side effects, especially severe side effects such as hepatopathy. Results: As a result of our questionnaire, we found 31 cases of reversible hepatotoxicity and nine cases of lethal hepatopathies in Germany from 1994 to 2003. Conclusions: The outcome of patients with severe hepatotoxicity is better than that in the past. The risk of a VPA-induced hepatopathy is not limited to patients younger than 2 years, receiving polytherapy, or patients with congenital or acquired metabolic diseases.

Air particulate matter (PM) and bound chemicals are potential mediators for adverse health effects. The cytotoxicity and changes in energy-providing processes caused by chemical compounds bound to PM of different size fractions were investigated in Tetrahymena pyriformis. The PM samplings were carried out using a high volume cascade impactor (6 size fractions between 10 μm and less than 0.49 μm) at three points of La Plata, Argentina: in an industrial area, a traffic-influenced urban area, and a control area. Extracts from respirable particles below 1 μm initiated the highest cytotoxic effects, demonstrating their higher risk. In contrast, an increase on oxygen consumption was observed especially in tests of extracts from particles less than 1 μm from urban and industrial areas. The increase on oxygen consumption could be caused by decoupling processes in the respiratory chain. Otherwise the ATP concentration was increased too, even though to a lower extent. The observed imbalance between oxygen consumption and ATP concentration in exposed T. pyriformis cells may be due to oxidative stress, caused by chemical compounds bound to the particles. Owing to the complexity of effects related to PM and their associated chemical compounds, various physiological parameters necessarily need to be investigated to obtain more information about their possible involvement in human relevant pathogenic processes. As shown here, effects on cell proliferation and on energy-providing processes are suitable indicators for the different impact of PM and adsorbed chemicals from various sampling locations. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 457–463, 2006.

Summary The roots of Epipremnum aureum , though not synthesizing nicotine themselves, take up exogenously fed nicotine as a xenobiotic. The alkaloid is subsequently translocated to the leaves, via the xylem path, where it accumulates in the mesophyll up to levels comparable with nicotine-rich Nicotiana species. The Epipremnum plants accept nicotine only up to a distinct level; saturation is reached after about 10 days. All mature, non-senescent leaves accumulate the same amount of nicotine. By different experimental approaches, unequivocal evidence could be provided that root pressure is the ‘translocative force’ for nicotine transport in E. aureum . Xylem sap exudates, collected from shoot stumps that were connected to an intact root system immersed in nicotine solution were analyzed for nicotine content. Nicotine uptake from the medium by the root and its subsequent transfer into the xylem of the shoot persisted for more than 10 h without measurable decline of the transport rate, provided the nicotine concentrations applied were ⩽0.05%. In intact plants, where both components of water transport in the xylem — root pressure and transpirative water flow — are in operation, no surplus transport of nicotine from the roots into the leaves took place beyond the level observed in amputated plants. Under the influence of inhibitors of root respiration, nicotine uptake was halted slowly in case of oxygen deprivation and in case of cyanide, or it stopped very rapidly when CCCP, an uncoupler of mitochondrial ATP formation, was applied to the roots. This threshold of toxicity against the xenobiotic was established by dose effect curves for nicotine sensitivity of the roots for root respiration and by transpiration measurements. Leaves, bearing a heavy ‘nicotine load’, showed symptoms of senescence only after 3–6 weeks, as indicated by a decline in the chlorophyll content, the chl a / b ratio, and the maximal quantum yield efficiency ( F v / F m ), and by an increase in catalase activity. Our results provide insight into the mechanisms of uptake, transport and storage of nicotine as a xenobiotic.

Routine prophylactic antiemetic treatment of surgical patients appears justified only in case of an increased risk of postoperative nausea and vomiting (PONV.). The objective of this investigation was to assess the feasibility and efficacy of a dichotomized risk score adapted management of PONV. based on ondansetron prophylaxis and treatment with respect to the overall institutional rate of PONV. After estimating the individual PONV. risk by a simplified score, 162 adult patients scheduled for elective surgery received either 4 mg ondansetron intravenously (two to four risk factors = high-risk) or no prophylaxis (zero to one risk factor = low-risk). For antiemetic treatment ondansetron was given intravenously and orally. Incidence of PONV. was recorded during the first 24 hr after recovery. Data from 159 subjects were analyzed with 44 patients classified as low-risk and 115 patients classified as high-risk. Nine low-risk and 58 high-risk patients experienced PONV. The expected institutional PONV. incidence of 47% was reduced to 36%. Treatment with ondansetron was necessary in seven low-risk and 37 high-risk patients with a complete response rate of 71% (lowrisk) and 43% (high-risk). Providing antiemetic prophylaxis with ondansetron to high-risk patients strictly based on a simplified risk score can reduce the overall institutional rate of PONV. However, classifying patients into two groups while using ondansetron as the single antiemetic in the high-risk group appears to be of limited efficacy as the incidence of PONV in high-risk patients is still double that of low-risk patients.

A series of 138 nonchiral 3-amidinobenzyl-1H-indole-2-carboxamides and analogues as inhibitors of the blood coagulation enzyme factor Xa (fXa) were designed, synthesized, and investigated by X-ray structure analysis and 3D quantitative structure-activity relationship (QSAR) studies (CoMFA, CoMSIA) in order to identify important protein-ligand interactions responsible for biological affinity and selectivity. Several compounds from this series are highly potent and selective inhibitors of this important enzyme linking extrinsic and intrinsic coagulation pathways. To rationalize biological affinity and to provide guidelines for further design, all compounds were docked into the factor Xa binding site. Those docking studies were based on X-ray structures of factor Xa in complex with literature-known inhibitors. It was possible to validate those binding modes by four X-ray crystal structures of representative ligands in factor Xa, while one ligand was additionally crystallized in trypsin to rationalize requirements for selective factor Xa inhibition. The 3D-QSAR models based on a superposition rule derived from these docking studies were validated using conventional and cross-validated r(2) values using the leave-one-out method and repeated analyses using two randomly chosen cross-validation groups plus randomization of biological activities. This led to consistent and highly predictive 3D-QSAR models with good correlation coefficients for both CoMFA and CoMSIA, which were found to correspond to experimentally determined factor Xa binding site topology in terms of steric, electrostatic, and hydrophobic complementarity. Subsets selected as smaller training sets using 2D fingerprints and maximum dissimilarity methods resulted in 3D-QSAR models with remarkable correlation coefficients and a high predictive power. The final quantitative SAR information agrees with all experimental data for the binding topology and thus provides reasonable activity predictions for novel factor Xa inhibitors.

Airborne particulates, especially fine particles and bound chemical compounds, are a potential mediator of adverse health effects. In this study an analysis was done of the concentration and size distribution of air particulate matter, the content of bound polycyclic aromatic hydrocarbons (PAHs), and the biological effects of organic extracts from different fractions of dust that had been influenced by urban and industrial emissions from the regions of La Plata, Argentina, and Leipzig, Germany, along with samples from control areas. Air particulate matter was sampled in summer and winter in each region using a high-volume sampler with a six-stage cascade impactor, classifying dust in six size fractions from 10-μm particles to those less than 0.49 μm in size. Organic extracts of dust were tested for mutagenicity (Ames test, Salmonella typhimurium TA98 strain, S9+) and cytotoxicity (Tetrahymena pyriformis test system, growth rate, cell respiration). The content of PAHs was analyzed by high-performance liquid chromatography (HPLC) with diode array and fluorescence detection. Mutagenic and cytotoxic effects were found to be associated with very fine (

Little is known regarding alterations of the renin-angiotensin system in patients referred for cardiac catheterization. Here, we measured plasma levels of active renin and aldosterone in patients referred for cardiac catheterization in order to determine the prevalence of elevated renin, aldosterone, and the aldosterone-renin ratio. A chemiluminescence assay was used to measure plasma aldosterone concentration (PAC) and active renin levels in 833 consecutive patients, after an overnight fasting and without any medication for least 12 hours. We evaluated associations of the hormonal elevations in relation to hypertension, atrial fibrillation (AF), hypertensive cardiomyopathy, coronary artery disease (CAD), valvular disease, impaired left ventricular ejection fraction (LVEF 25 mm Hg). Hyperaldosteronism occurred in around one-third of all examined patients, without significant differences between patients with or without the named cardiac diseases. In a comparison between patients with or without any given cardiac disease condition, renin was significantly elevated in patients with either hypertension (36.4% vs 15.9%), CAD (33.9% vs 22.1%), or impaired LVEF (47.3% vs 24.8%). The angiotensin-renin ratio was elevated in AF patients and in patients with hypertensive cardiomyopathy. Patients with AF and coexisting hypertension had elevated renin more frequently than AF patients without coexisting hypertension (35.3% vs 16.5%; P = .005). Patients with persistent/permanent AF more frequently had elevated renin than patients with paroxysmal AF (34.1% vs 15.8%; P = .007). This prospective study of consecutive cardiac disease patients referred for cardiac catheterization has revealed distinct cardiac disease condition-associated differences in the frequencies of elevations in plasma renin, PAC, and the aldosterone-renin ratio.

The temperate cereal barley is grown as a source of food, feed, and malt. The development of a broad range of genetic resources and associated technologies in this species has helped to establish barley as the prime model for the other Triticeae cereals. The specific advantage of the transformation method presented here is that transgene homozygosity is attained in the same generation as the transgenic event occurred through the coupling of haploid technology with Agrobacterium-mediated transformation. Pollen is haploid and, following transformation, can be induced to regenerate into haploid plantlets, which can subsequently subjected to colchicine treatment to obtain diploid, genetically fixed plants. The routine application of the method based on the winter-type barley cultivar 'Igri' over a period of over 10 years has achieved an average yield of about two transgenic plants per donor spike. The whole procedure from pollen isolation to non-segregating transgenic, mature grain takes less than 12 months.

Endolymphatic ion composition in the adult inner ear is characterized by high K(+) and low Na(+) concentration. This unique ion composition is essential for proper functioning of sensory processing. Although a lot has been learned in recent years about molecules involved in K(+) transport in inner ear, the molecules involved in Na(+) transport are only beginning to emerge. The epithelial Na(+) channel (ENaC) is a highly selective Na(+) channel that is expressed in many Na(+)-reabsorbing tissues. The aim of our study was to investigate whether ENaC is expressed in inner ear of rats and could account for Na(+) reabsorption from endolymph. We detected mRNA for the three channel-forming subunits (alpha, beta and gamma ENaC) in cochlea, vestibular system and endolymphatic sac. mRNA abundance increased during the first 12 days of life in cochlea and vestibular system, coinciding with decreasing Na(+) concentration in endolymph. Expression was strongest in epithelial cells lining scala media, most notably Claudius' cells. As these cells are characterized by a very negative resting potential they would be ideally suited for reabsorption of Na(+). mRNA abundance in endolymphatic sac decreased during the first 6 days of life, suggesting that ENaC might be implicated in reabsorption of endolymph in the endolymphatic sac of neonatal animals. Together, our results suggest that the epithelial Na+ channel is a good candidate for a molecule involved in Na(+) homeostasis in inner ear.

We investigated the pattern of glial fibrillary acidic protein (GFAP) and Wisteria floribunda agglutinin (WFA) labeled structures in the superior colliculus and in the somatosensory cortex of humans and rats of different age groups using immunohistochemical methods, light and confocal laser-scanning microscopy. We never found a double labeling of WFA and GFAP positive structures neither in the superior colliculus nor in the cortex of both man and rat. The complementary pattern of WFA and GFAP labeling was present both at the macroscopic and microscopic level. We found a clear prevalence of either WFA or GFAP expression in the arborization of the astrocytes as well as in the pattern of lamination.

We report the case of a young patient with repaired Ebstein’s anomaly who developed severe tachycardia-induced cardiomyopathy and a large apical thrombus as a consequence of sustained atrial flutter with a 2:1 conduction. In spite of a dramatic course in hospital with prolonged mechanical resuscitation and extracorporeal membrane oxygenation, she survived and made a rapid and full recovery. This remarkable case underlines that atrial arrhythmias, the most common complication in adults with congenital heart disease, may have devastating outcomes when timely recognition is missed and treatment delayed—thus, emphasizing the importance of good patient education.

During acute altitude exposure tachycardia increases cardiac output (Q) thus preserving systemic O2 delivery. Within days of acclimatization, however, Q normalizes following an unexplained reduction in stroke volume (SV). To investigate whether the altitude-mediated reduction in plasma volume (PV) and hence central blood volume (CBV) is the underlying mechanism we increased/decreased CBV by means of passive whole body head-down (HDT) and head-up (HUT) tilting in seven lowlanders at sea level (SL) and after 25/26 days of residence at 3454 m. Prior to the experiment on day 26, PV was normalized by infusions of a PV expander. Cardiovascular responses to whole body tilting were monitored by pulse contour analysis. After 25/26 days at 3454 m PV and blood volume decreased by 9 ± 4% and 6 ± 2%, respectively (P < 0.001 for both). SV was reduced compared to SL for each HUT angle (P < 0.0005). However, the expected increase in SV from HUT to HDT persisted and ended in the same plateau as at SL, albeit this was shifted 18 ± 20° toward HDT (P = 0.019). PV expansion restored SV to SL during HUT and to an ∼8% higher level during HDT (P = 0.003). The parallel increase in SV from HUT to HDT at altitude and SL to a similar plateau demonstrates an unchanged dependence of SV on CBV, indicating that the reduced SV during HUT was related to an attenuated CBV for a given tilt angle. Restoration of SV by PV expansion rules out a significant contribution of other mechanisms, supporting that resting SV at altitude becomes reduced due to a hypovolemia.

A birth cohort study (LARS - Leipzig Allergy Risk Children Study) was used to investigate the influence of indoor mould exposure on T cell function in early childhood. T cell cytokines (IFN-γ, IL-4) were analysed in a sub-group of the LARS cohort (birth: n = 39, 6 months: n = 11, 12 months: n = 50, 36 months: n = 33). Mould burden was assessed by analysis of questionnaires completed at the birth of the child and measurement of indoor mould spores was carried out when the children were 3 years old. Children whose parents reported mould burden or dampness in their dwellings at the time of birth showed lower amounts of IFN-γ producing Th1 cells during the first year of life (significant at 12 months) in comparison to unexposed children. The capacity to produce IL-4 was not altered, however. When the children were 3 years old, an association between measured indoor mould and suppressed Th1 reactivity was observed. The data suggest that indoor mould exposure is associated with reduced Th1 reactivity in early childhood.

The complex tissue remodeling process of menstruation is experienced by humans and some primates, whereas most placental mammals, including mice, go through an estrous cycle. How menstruation and the underlying mechanisms evolved is still unknown. Here we demonstrate that the process of menstruation is not just species-specific but also depends on factors which can be induced experimentally. In intact female mice endogenous progesterone levels were raised by the induction of pseudopregnancy. Following an intrauterine oil injection, the decidualization of the endometrium was reliably induced as a prerequisite for menstruation. The natural drop of endogenous progesterone led to spontaneous breakdown of endometrial tissue within an average of 3 days post induction of decidualization. Interestingly, morphological changes such as breakdown and repair of the endometrial layer occurred in parallel in the same uterine horn. Most importantly, endometrial breakdown was accompanied by vaginally visible (overt) bleeding and flushing out of shed tissue comparable to human menstruation. Real-time PCR data clearly showed temporal changes in the expression of multiple factors participating in inflammation, angiogenesis, tissue modulation, proliferation, and apoptosis, as has been described for human menstruating endometrium. In conclusion, human menstruation can be mimicked in terms of extravaginally visible bleeding, tissue remodeling, and gene regulation in naturally non-menstruating species such as intact female mice without the need for an exogenous hormone supply.

Aims Cardiac progenitor cells (CPCs) have been shown to promote cardiac regeneration in vivo. Understanding the function of CPCs is essential for further implementation of these cells in the treatment of cardiac diseases. The present study tested the hypothesis that adult CPC exert paracrine effects that lead to an improvement in the functional characteristics of cardiomyocytes. This study also investigated whether aging (we included patients aged between 4 months and 81 years) has any effect on the paracrine mechanisms of CPC. Methods and results The supernatant of CPC generated both from human and rat hearts—so called ‘conditioned cardiosphere medium’ improved the contractile behaviour of isolated adult cardiomyocytes in a concentration-dependent manner after incubation for 24 h and increased the SERCA/NCX ratio. The observed positive effects on contractile behaviour were independent of the CPC donors' age. Conditioned cardiosphere media also normalized angiotensin II-induced contractile dysfunction. Cytokines released by CPC into the media were detected by cytokine arrays. Conclusion The observed diversity of cytokines released by CPC needs to be further elucidated in detail. Nevertheless, CPC are a promising therapeutic approach in the field of cardiac disease. The methods described allow investigation of the underlying paracrine mechanisms in a standardized in vitro situation.

The aim of this research was to analyse whether there are associations between lung function parameters and living in mould exposed conditions. Domestic exposure to mould is a common problem nowadays. It is known that mould burden can provoke allergies and unspecific disorders. The role of constituent parts of mould, and in particular of microbial volatile compounds (MVOC), on health is currently partially unclear. 124 persons from the city of Erfurt, Germany (some of whom have been exposed to mould) were investigated within a special consultation-hour with focus on environmental medicine. Simultaneously home visits were carried out. During these visits dust and air samples were collected for further analysis. Among other items, the indoor air concentrations of MVOC as metabolites of mould were determined. The medical checkup included in-depth anamnesis and clinical investigation completed by a detailed lung function test. MVOC data are based on GC-MS measurements of total amounts of 2-Methylfurane, 3-Methylfurane, 2-Methyl-1-Propanol, 2-Pentanol, 3-Methyl-1-Butanol, Dimethyldisulfide, 2-Hexanone, 1-Octene, 2-Heptanone, 2-Octanone, 3-Octanol, Fenchone, α-Terpineol and Thujopsene. It was found that the burden with mould and the burden with MVOC in accommodation is positively associated with changes in lung function parameters. Different lung function parameters were influenced depending on points of view. Generally, more parameters were influenced by looking for associations with mould and the effects found are stronger. An increase of residual volume could be obtained for mould (p=0.001, n=84) and for MVOC (p=0.04, n=76). Furthermore, an OR (95% confidence interval): 3.01 (1.03-9.05) could be found for mould and for MVOC: OR (95% confidence interval): 1.07 (1.01-1.15), both adjusted for daily smoking, general smoking in accommodation, medication against allergies and pulmonary infects during the last four weeks It can be concluded that MVOC are able to contribute to negative health effects caused by mould. Although the described effects appear to be low, it should be taken into account that ORs given for Σ MVOC are per change of 1μg/m3. Therefore an increase of 10 μg/m3 leads to an OR of 1.110 = 2.59.

Cytochrome P450 1A1 (CYP1A1) belongs to the enzymes of biotransformation of phase I. CYP1A1 performs the catalytic activation of exogenous and endogenous substrates to more carcinogenic metabolites. Overexpression of the wild-type and a recently described splice variant (CYP1A1v, ovarian cancer) are attributed to neoplastic transformation. Here we describe novel CYP1A1 splicing variants commonly and frequently transcribed in leucocytes of healthy volunteers, separated from variants exclusively expressed in tumour cell lines. Interestingly, all the novel splicing variants in leukocytes are generated by employing of two nested splice site pairs, one outer canonical and one inner non-canonical splice site pair, within the exon 2 of the human CYP1A1. In general, the frequent presence of common splicing variants in healthy volunteers has to be consider as a physiological feature of human CYP1A1 transcription process, rather than a signature of carcinogenesis.

Various studies have documented the associations between mold exposure and effects on health. Mycotoxins, which occur in spores and mold fragments, can be involved in processes that have pathological effects, such as adynamia of the immune system, recurrent infections of the respiratory tract, or asthma. Using Tetrahymena pyriformis, a single-cell organism well established as a suitable model for human respiratory epithelium-cell functionalities, we investigated dose–response relationships of the mycotoxins gliotoxin and penicillic acid. Our study focused on the viability (cell count, MTT assay), energy levels (adenosine-5′-triphosphate content), energy-providing processes (MTT reduction per cell), and cell respiration (oxygen consumption). Both mycotoxins acted as cytotoxins in a dose-dependent manner. Gliotoxin had a stronger inhibitory effect (EC50 0.38 μM) than did penicillic acid (EC50 343.19 μM). The energy-providing processes were not inhibited or were only weakly inhibited under the influence of gliotoxin, whereas penicillic acid caused stimulation of the physiological parameters. Summarizing the results, it is clear that the two investigated mycotoxins must have different modes of action. They are not only different in the strength of their toxic effects but also in a variety of physiological aspects. In addition, T. pyriformis showed differences in its ability to overcome the negative effects of particular mycotoxin exposures. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 111–117, 2006.

This study takes into consideration an analysis of the chemical polycyclic aromatic hydrocarbon (PAH) profile and its distribution in inhalable and respirable particulate matter in urban and industrial areas in La Plata, Argentina, and Leipzig, Germany. Representative samples from three locations in La Plata (industrial, traffic influenced and control area) and two locations in Leipzig (traffic influenced and control area) were obtained in summer and winter. The sampling of particulate matter was carried out with high volume collectors using cascade impactors to separate six size fractions. PAHs were extracted with hexane through a solid–liquid equilibrium extraction and analysed by HPLC/UV/fluorescence detection. The results showed a PAH seasonal behaviour in both regions, with lower contents in summer and higher ones in winter. Highest concentrations of total PAHs were found in the industrial area in La Plata. The size distribution of particles demonstrates the greater relevance of smaller particles. More than 50% of PAHs were associated with particles of less than 0.49 μm. Moreover, this particle size fraction was associated with traffic, whereas other sources of combustion were related also to particles between 0.49 and 0.95 μm. Considering the ratio of benzo(ghi)perylene (BgP)/benzo(a)pyrene (BaP) as an indicator for traffic influence, it was observed that La Plata City was more affected than Leipzig by the same proportion in summer and in winter. The BgP/InP (indeno(123-cd)pyrene) ratio was lower in winter than in summer in both places and indicates the presence of domestic combustion sources. It is important to point out the significance of using fingerprint compound ratios to identify possible sources of pollution with PAHs bound to particles.

Indoor air contamination with mould spores currently experiences an increasing interest with respect to their relevance to health. To assess adverse health effects, epidemiological studies combine the health outcome of individuals with their concomitant exposure to airborne spores, which is observed, for example, during the current month. While the latter is representative for the studied period, health effects might also be the result of long term-exposure or emerge in consequence of a peak of pollution throughout the year. To consider such questions, additional information about the spatiotemporal distribution of airborne spores is necessary. This paper aims at elucidating the spatial and temporal variation of spore concentrations in Leipzig, Germany. The analysis is based on 1165 matched pairs of indoor and outdoor measurements taken in the period 1998–2002. All data were collected in the frame of previous epidemiological studies and refer to apartments. The analysis comprised spore concentrations (as CFU m3 in air) of the most important genera, such as Penicillium, Aspergillus, Alternaria, Mucorales, Cladosporium, and also for yeasts. We found two groups of fungi differing in their spatiotemporal distribution. As this behaviour can be explained by the predominant origin and growing conditions, we call them indoor-relevant and outdoor-relevant genera. Penicillium species are a representative of the former group, while the latter is well represented by Cladosporium. In the studied period we did not observe a clear trend in the spore concentration. Outdoors there is a year-to-year variation of Cladosporium spore concentrations, which follow the prevalent climatic conditions. For the spore concentration of the outdoor-relevant group a significant annual cycle was observed. Highest concentrations occurred during the summer months and were about 100 x the winter burden. That means, for a direct comparison of measurements of spore concentrations taken during different months the season has to be considered. We summarise the findings in a seasonal model, which is fitted to our measurements. Based on the model we developed a procedure for seasonal adjustment, which enabled us to estimate the annual peak spore concentration utilising one monthly observation.

To investigate mould effects on health, the concentration of mould spores in air and dust was determined during a prospective cohort study. Clinical outcome was estimated by questionnaires and determination of specific IgE antibodies and intracellular cytokine production of T cells. A significant association was observed between the incidence of respiratory tract infections and exposure to Penicillium spores. Moreover, Aspergillus exposure was found to be associated with allergic rhinitis or related symptoms. In addition, T cells of children exposed to Aspergillus showed a significantly lower content of TH1 cytokines (IFN-γ, TNF-α, IL-2) producing cells. Our data suggest that mould exposure is associated with several effects on health, depending on the species involved.

Patient death after liver resection for hepatocellular carcinoma in cirrhosis is caused by tumor recurrence as well as by complications of cirrhosis. Liver transplantation represents the only simultaneous treatment of tumor and primary liver disease. Certain criteria regarding the number (up to three) and size (up to 5 cm) of tumor nodules have to be observed in order to ensure a low risk of extrahepatic spread or vascular infiltration. Liver transplantation, as treatment for recurrent hepatocellular carcinoma, has to observe the same rules. Only few patients have undergone liver transplantation for recurrent hepatocellular carcinoma in cirrhosis. The reason for this restraint is not fully evident. Poor survival rates after liver transplantation as therapy for advanced hepatocellular carcinoma in the 1980s and an increasing shortage of donor grafts are certainly two factors. We report on two cases from our experience and review the European literature. Outcome in a few selected patients has been rather favorable, despite varying approaches. The only conclusion that can be drawn is that tumor control by liver transplantation is possible in individual patients suffering from recurrent hepatocellular carcinoma. Adult living donor liver transplantation is one way to overcome graft shortage. Other strategies, for example, salvage transplantation, are presented.

Cisplatin is a widely used anti-cancer drug. Ototoxicity is a major dose-limiting side-effect. A reproducible mammalian in-vitro model of cisplatin ototoxicity is required to screen and validate otoprotective drug candidates. We utilized a whole organ culture system of the postnatal mouse inner ear in a rotating wall vessel bioreactor under “simulated microgravity” culture conditions. As previously described this system allows whole organ culture of the inner ear and quantitative assessment of ototoxic effects of aminoglycoside induced hair cell loss. Here we demonstrate that this model is also applicable to the assessment of cisplatin induced ototoxicity. In this model cisplatin induced hair cell loss was dose and time dependent. Increasing exposure time of cisplatin led to decreasing EC50 concentrations. Outer hair cells were more susceptible than inner hair cells, and hair cells in the cochlear base were more susceptible than hair cells in the cochlear apex. Initial cisplatin dose determined the final extent of hair cell loss irrespective if the drug was withdrawn or continued. Dose dependant otoprotection was demonstrated by co-administration of the antioxidant agent N-acetyl l -cysteine. The results support the use of this inner ear organ culture system as an in vitro assay and validation platform for inner ear toxicology and the search for otoprotective compounds.

Group B Streptococcus (GBS) cell walls potently activate phagocytes by a largely TLR2-independent mechanism. In contrast, the cell wall component lipoteichoic acid (LTA) from diverse Gram-positive bacterial species has been shown to engage TLR2. In this study we examined the role of LTA from GBS in phagocyte activation and the requirements for TLR-LTA interaction. Using cells from knockout mice and genetic complementation in epithelial cells we found that highly pure LTA from both GBS and Staphylococcus aureus interact with TLR2 and TLR6, but not TLR1, in contrast to previous reports. Furthermore, NF-κB activation by LTA required the integrity of two putative PI3K binding domains within TLR2 and was inhibited by wortmannin, indicating an essential role for PI3K in cellular activation by LTA. However, LTA from GBS proved to be a relatively weak stimulus of phagocytes containing ∼20% of the activity observed with LTA from Staphylococcus aureus. Structural analysis by nuclear magnetic resonance spectrometry revealed important differences between LTA from GBS and S. aureus, specifically differences in glycosyl linkage, in the glycolipid anchor and a lack of N-acetylglucosamine substituents of the glycerophosphate backbone. Furthermore, GBS expressing LTA devoid of d-alanine residues, that are essential within immune activation by LTA, exhibited similar inflammatory potency as GBS with alanylated LTA. In conclusion, LTA from GBS is a TLR2/TLR6 ligand that might contribute to secreted GBS activity, but does not contribute significantly to GBS cell wall mediated macrophage activation.