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Entrainment emerges when oscillatory movements synchronize with environmental stimuli processing. The purpose of this experiment was to assess how cognitive-motor entrainment during a dual-task would influence the quality of gait and affect episodic long-term memory. Twenty-one participants (22.56 y/o; 64 % F) walked at preferred paces while listening to 40-item word lists. In separate sessions, unique word lists were presented predictably on every fourth stride, unpredictably related to stepping, or predictably while standing. Memory tests administered 24-hr after encoding revealed that predictable word presentation led to better free-recall performance than unpredicted (p = .044); recognition memory was not impacted. Gait phase parameters during the predicted condition were more stable than the unpredicted condition or baseline assessments. Cognitive-motor entrainment may alleviate dual-task costs and enhance memory retention., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Nathan Scott reports financial support was provided by Life University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The role of two types of acute physical activity (PA) bouts were assessed on young adults' free-recall and recognition memory in two experiments, which differed in the temporal relation of PA and word encoding. Before or following training on the Rey Auditory Verbal Learning Task, participants performed a simple two-step dance, a complex four-step dance, or remained seated. Hypotheses proposed that PA prior to encoding and complex PA would enhance PA's mnemonic benefits. Memory assessed post-PA, 24 h, and 7 days after training indicated that timing and complexity of PA did not impact free-recall or recognition memory. Findings differ from a previous study showing complex PA benefited motor learning more than simple PA (Tomporowski & Pendleton, 2018). The inconsistency may be due to different working memory processes underlying consolidation and retrieval of procedural or episodic information. Theory-based explanations regarding memory storage and retrieval are proposed to elucidate this selective process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The unprecedented success of mRNA vaccines in managing the COVID-19 pandemic raises the prospect of applying the mRNA platform to other viral diseases of humans and domesticated animals, which may lead to more efficacious vaccines for some agents. We briefly discuss reasons why mRNA vaccines achieved such success against COVID-19 and indicate what other virus infections and disease conditions might also be ripe for control using mRNA vaccines. We also evaluate situations where mRNA could prove valuable to rebalance the status of immune responsiveness and achieve success as a therapeutic vaccine approach against infections that induce immunoinflammatory lesions., Competing Interests: Declaration of competing interest The authors declare no conflict of financial interest., (Copyright © 2022 Institut Pasteur. All rights reserved.)

Aims: This study aims at understanding left ventricular (LV) mechanics of non-compaction (LVNC) phenotype using echocardiographic strain analysis and at assessing the association of functional parameters with cardiovascular (CV) outcomes., Methods and Results: Longitudinal (GLS) and circumferential strain (GCS) as well as rotation of the LV were analyzed in 55 LVNC patients and 55 matched controls. Cardiovascular outcomes were documented for a median follow-up duration of 6 years. GLS and GCS were impaired in LVNC. Similary, regional longitudinal and circumferential strain as well as twist were reduced. CV events occurred in 28 LVNC patients. Apical peak circumferential strain (APCS), peak systolic rotation of apical segments (APSR), and twist were strongly associated with events. This was independent of and incremental to LVEF and non-compacted to compacted myocardial thickness ratio (NC:C ratio). The association of twist with events was also independent of and slightly superior to GLS., Conclusions: GLS, GCS, regional strain, and twist were impaired in LVNC. APCS, APSR, and twist exhibited strong association with CV events independent of and incremental to LVEF and NC:C ratio, and in case of twist even GLS. Thus, STE-derived parameters may complement the echocardiographic assessment of LVNC patients in clinical routine., Competing Interests: Declaration of Competing Interest Nothing to disclose., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti-glycoprotein E (gE) antibody levels (n = 43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17-2.89) after the first (median OD 3.41, IQR 2.54-3.81, p < .0001) and second vaccine dose (median OD 3.63, IQR 3.39-3.86, p < .0001). gE-specific polyfunctional CD4+ T cell frequencies (n = 38) also increased from baseline (median 85 per 10 6 CD4+ T cells; IQR: 46-180) to the first (median 128 per 10 6 CD4+ T cells; IQR: 82-353; p = .023) and after the second dose (median 361 per 10 6 CD4+ T cells; IQR: 146-848; p < .0001). Tenderness (83.0%; 95%CI: 69.2-92.4%) and redness (31.9%; 95%CI: 19.1-47.1%) at injection site were common. One rejection episode within 3 weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell-mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Although a link between regular yogurt consumption and mortality appears plausible, data are sparse and have yielded inconsistent results., Objectives: We examined the association between regular yogurt consumption and risk of all-cause and cause-specific mortality among US women and men., Methods: A total of 82,348 women in the Nurses' Health Study and 40,278 men in the Health Professionals Follow-Up Study without a history of cardiovascular disease (CVD) and cancer in 1980 (women) or 1986 (men) were followed up until 2012. Yogurt consumption was assessed by updated validated FFQs., Results: During 3,354,957 person-years of follow-up, 20,831 women and 12,397 men died. Compared with no yogurt consumption, the multivariable-adjusted HRs (95% CIs) of mortality were 0.89 (0.86, 0.93), 0.85 (0.81, 0.89), 0.88 (0.84, 0.91), and 0.91 (0.85, 0.98) for ≤1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and >4 servings/wk in women (P-trend = 0.34), respectively. For men, the corresponding HRs (95% CIs) were 0.99 (0.94, 1.03), 0.98 (0.91, 1.05), 1.04 (0.98, 1.10), and 1.05 (0.95, 1.16), respectively. We further noted inverse associations for cancer mortality (multivariable-adjusted HR comparing extreme categories: 0.87; 95% CI: 0.78, 0.98; P-trend = 0.04) and CVD mortality (HR: 0.92; 95% CI: 0.79, 1.08; P-trend = 0.41) in women, although the latter was attenuated in the multivariable-adjusted model. Replacement of 1 serving/d of yogurt with 1 serving/d of nuts (women and men) or whole grains (women) was associated with a lower risk of all-cause mortality, whereas replacement of yogurt with red meat, processed meat (women and men), and milk or other dairy foods (women) was associated with a greater mortality., Conclusions: In our study, regular yogurt consumption was related to lower mortality risk among women. Given that no clear dose-response relation was apparent, this result must be interpreted with caution., (Copyright © The Author(s) 2020.)

Objectives: Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe., Methods: Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures., Results: Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths., Conclusions: The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Prostate cancer (PCa) is one of the most common cancers among men, yet little is known about its modifiable risk and protective factors. This study aims to quantitatively summarize observational studies relating physical activity (PA) to PCa incidence and mortality., Materials and Methods: Published articles pertaining to PA and PCa incidence and mortality were retrieved in July 2017 using the Medline and EMBASE databases. The literature review yielded 48 cohort studies and 24 case-control studies with a total of 151 748 PCa cases. The mean age of the study participants at baseline was 61 years., Results: In random-effects models, comparing the highest versus the lowest level of overall PA showed a summary relative risk (RR) estimate for total PCa incidence close to the null [RR = 0.99, 95% confidence interval (CI) = 0.94-1.04]. The corresponding RRs for advanced and non-advanced PCa were 0.92 (95% CI = 0.80-1.06) and 0.95 (95% CI = 0.85-1.07), respectively. We noted a statistically significant inverse association between long-term occupational activity and total PCa (RR = 0.83, 95% CI = 0.71-0.98, n studies = 13), although that finding became statistically non-significant when individual studies were removed from the analysis. When evaluated by cancer subtype, an inverse association with long-term occupational activity was noted for non-advanced/non-aggressive PCa (RR = 0.51, 95% CI = 0.37-0.71, n studies = 2) and regular recreational activity was inversely related to advanced/aggressive PCa (RR = 0.75, 95% CI = 0.60-0.95, n studies = 2), although these observations are based on a low number of studies. Moreover, PA after diagnosis was related to reduced risk of PCa mortality among survivors of PCa (summary RR based on four studies = 0.69, 95% CI = 0.55-0.85)., Conclusions: Whether PA protects against PCa remains elusive. Further investigation taking into account the complex clinical and pathologic nature of PCa is needed to clarify the PA and PCa incidence relation. Moreover, future studies are needed to confirm whether PA after diagnosis reduces risk of PCa mortality.

Milled zerovalent iron (milled ZVI) particles have been recognized as a promising agent for groundwater remediation because of (1) their high reactivity with chlorinated aliphatic hydrocarbons, organochlorine pesticides, organic dyes, and a number of inorganic contaminants, and (2) a possible greater persistance than the more extensively investigated nanoscale zerovalent iron. We have used laboratory-scale batch degradation experiments to investigate the effect that hydrogeochemical conditions have on the corrosion of milled ZVI and on its ability to degrade trichloroethene (TCE). The observed pseudo first-order degradation rate constants indicated that the degradation of TCE by milled ZVI is affected by groundwater chemistry. The apparent corrosion rates of milled ZVI particles were of the same order of magnitude for hydrogeochemical conditions representative for two contaminated field sites (133-140mmolkg -1 day -1 , indicating a milled ZVI life-time of 128-135days). Sulfate enhances milled ZVI reactivity by removing passivating iron oxides and hydroxides from the Fe 0 surface, thus increasing the number of reactive sites available. The organic matter content of 1.69% in the aquifer material tends to suppress the formation of iron corrosion precipitates. Results from scanning electron microscopy, X-ray diffraction, and iron K-edge X-ray adsorption spectroscopy suggest that the corrosion mechanisms involve the partial dissolution of particles followed by the formation and surface precipitation of magnetite and/or maghemite. Numerical corrosion modeling revealed that fitting iron corrosion rates and hydrogen inhibitory terms to hydrogen and pH measurements in batch reactors can reduce the life-time of milled ZVI particles by a factor of 1.2 to 1.7., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Studies have investigated a possible association between family history of HZ and the occurrence of HZ. However, the results were inconclusive and susceptible to bias. We evaluated this association in an elderly population., Methods: The matched case-control study conducted at Kaiser Permanente Southern California in 2012-2015 included 656 incident HZ patients ≥60 whose skin lesion tested positive for varicella zoster virus by polymerase chain reaction. Half of the HZ patients were vaccinated with zoster vaccine as achieved by stratified sampling. The controls were randomly selected and 1:1 matched to the cases on sex, age (±1year), and zoster vaccination (±3 months of the case's vaccination date). Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI)., Results: Having any blood relative with a history of HZ was associated with a slightly increased risk of HZ (adjusted OR=1.37, 95% CI 1.05-1.79). The adjusted OR associated with having one and two categories of first-degree blood relatives with a history of HZ was 1.30 (95% CI: 0.97-1.73) and 2.53 (95% CI: 1.17-5.44), respectively., Conclusions: Our results suggested a weak association between the development of HZ and a positive family history of HZ among the elderly population., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Submicron-scale milled zerovalent iron (milled ZVI) particles produced by grinding macroscopic raw materials could provide a cost-effective alternative to nanoscale zerovalent iron (nZVI) particles for in situ degradation of chlorinated aliphatic hydrocarbons in groundwater. However, the aggregation and settling of bare milled ZVI particles from suspension presents a significant obstacle to their in situ application for groundwater remediation. In our investigations we reduced the rapid aggregation and settling rate of bare milled ZVI particles from suspension by stabilization with a "green" agar agar polymer. The transport potential of stabilized milled ZVI particle suspensions in a diverse array of natural heterogeneous porous media was evaluated in a series of well-controlled laboratory column experiments. The impact of agar agar on trichloroethene (TCE) removal by milled ZVI particles was assessed in laboratory-scale batch reactors. The use of agar agar significantly enhanced the transport of milled ZVI particles in all of the investigated porous media. Reactivity tests showed that the agar agar-stabilized milled ZVI particles were reactive towards TCE, but that their reactivity was an order of magnitude less than that of bare, non-stabilized milled ZVI particles. Our results suggest that milled ZVI particles could be used as an alternative to nZVI particles as their potential for emplacement into contaminated zone, their reactivity, and expected longevity are beneficial for in situ groundwater remediation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The high specific surface area and high reactivity of nanoscale zero-valent iron (nZVI) particles have led to much research on their application to environmental remediation. The reactivity of nZVI is affected by both the water chemistry and the properties of the particular type of nZVI particle used. We have investigated the reactivity of three types of commercially available Nanofer particles (from Nanoiron, s.r.o., Czech Republic) that are currently either used in, or proposed for use in full scale environmental remediation projects. The performance of one of these, the air-stable and thus easy-to-handle Nanofer Star particle, has not previously been reported. Experiments were carried out first in batch shaking reactors in order to derive maximum reactivity rates and provide a rapid estimate of the Nanofer particle's reactivity. The experiments were performed under near-natural environmental conditions with respect to the pH value of water and solute concentrations, and results were compared with those obtained using synthetic water. Thereafter, the polyelectrolyte-coated Nanofer 25S particles (having the highest potential for transport within porous media) were chosen for the experiments in column reactors, in order to elucidate nanoparticle reactivity under a more field-site realistic setting. Iopromide was rapidly dehalogenated by the investigated nZVI particles, following pseudo-first-order reaction kinetics that was independent of the experimental conditions. The specific surface area normalized reaction rate constant (kSA) value in the batch reactors ranged between 0.12 and 0.53Lm(-2)h(-1); it was highest for the uncoated Nanofer 25 particles, followed by the polyacrylic acid-coated Nanofer 25S and air-stable Nanofer Star particles. In the batch reactors all particles were less reactive in natural water than in synthetic water. The kSA values derived from the column reactor experiments were about 1000 times lower than those from the batch reactors, ranging between 2.6×10(-4) and 5.7×10(-4)Lm(-2)h(-1). Our results revealed that the easy-to-handle and air-stable Nanofer Star particles are the least reactive of all the Nanofer products tested. The reaction kinetics predicted by column experiments were more realistic than those predicted by batch experiments and these should therefore be used when designing a full-scale field application of nanomaterials for environmental remediation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: An Austrian boarding school reported a cluster of gastroenteritis on January 10, 2014. Environmental swabs from the school cafeteria and a nearby kebab restaurant tested positive for norovirus. The outbreak was investigated to identify its source(s)., Methods: An outbreak case was defined as a student or staff member with diarrhoea or vomiting that developed between January 7 and 13. Details on food exposure were collected via a self-administered questionnaire; risk ratios (RR) and 95% confidence intervals (CI) were calculated. Norovirus from the stool specimens of cases and asymptomatic kebab restaurant workers were genotyped., Results: Twenty-eight cases were identified among 144 persons (attack rate 19%). The outbreak emerged and peaked on January 9, and ended on January 12. Compared to those who did not eat kebab, those who ate kebab on 7, 8, and 9 January were respectively 11 (95% CI 4.2-28), 6.7 (95% CI 3.4-13), and 9.3 (95% CI 4.0-22) times more likely to develop disease within the following 2 days. Stool specimens from three cases and three restaurant workers were positive for norovirus GII.P21., Conclusions: The kebab prepared by norovirus-positive restaurant workers was the most likely source of the outbreak. It is recommended that food handlers comply strictly with hand hygiene and avoid bare-handed contact with ready-to-eat food to minimize the risk of food-borne infection., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Epidemiologic studies have reported that cardiorespiratory fitness is inversely associated with mortality from cancer. However, the evidence relating cardiorespiratory fitness to cancer mortality has not yet been quantitatively summarized., Methods: Following the preferred reporting items for sytematic reviews and meta-analyses (PRISMA) checklist, we conducted a systematic review and meta-analysis of the association between cardiorespiratory fitness and total cancer mortality. Relevant studies were identified through a literature search in PubMed up to August 2013 and by screening reference lists of qualifying articles. Data extraction was carried out independently by both authors and summary risk estimates were obtained using random-effects models., Results: Six prospective studies with an overall number of 71 654 individuals and 2002 cases of total cancer mortality were included. The median follow-up time in the studies was 16.4 years. Cardiorespiratory fitness showed a strong, graded, inverse association with total cancer mortality. Using low cardiorespiratory fitness as the reference group, intermediate and high levels of cardiorespiratory fitness were related to statistically significant decreased summary relative risks (RRs) of total cancer mortality of 0.80 [95% confidence interval (CI) 0.67-0.97] and 0.55 (95% CI 0.47-0.65), respectively. Studies that adjusted for adiposity yielded similar results to those that did not adjust for adiposity., Conclusion: Increased cardiorespiratory fitness represents a strong predictor of decreased total cancer mortality risk, independent of adiposity., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Physical activity improves physical function during and after cancer treatment, but whether physical activity imparts survival benefit remains uncertain., Design: Using prospective studies published through June 2013, we conducted a systematic review and random-effects meta-analysis of pre- and post-diagnosis physical activity in relation to total and cancer mortality among breast or colorectal cancer survivors., Results: Sixteen studies of breast cancer survivors and seven studies of colorectal cancer survivors yielded 49095 total cancer survivors, including 8129 total mortality cases and 4826 cancer mortality cases. Comparing the highest versus lowest levels of pre-diagnosis physical activity among breast cancer survivors, the summary relative risks (RRs) of total and breast cancer mortality were 0.77 [95% confidence interval (CI) = 0.69-0.88] and 0.77 (95% CI = 0.66-0.90, respectively. For post-diagnosis physical activity, the summary RRs of total and breast cancer mortality were 0.52 (95% CI = 0.42-0.64) and 0.72 (95% CI = 0.60-0.85), respectively. For pre-diagnosis physical activity among colorectal cancer survivors, the summary RRs of total and colorectal cancer mortality were 0.74 (95% CI = 0.63-0.86) and 0.75 (95% CI = 0.62-0.91), respectively. For post-diagnosis physical activity, the summary RRs of total and colorectal cancer mortality were 0.58 (95% CI = 0.48-0.70) and 0.61 (95% CI = 0.40-0.92), respectively. Each 10 metabolic equivalent task-hour/week increase in post-diagnosis physical activity (equivalent to current recommendations of 150 min/week of at least moderate intensity activity) was associated with 24% (95% CI = 11-36%) decreased total mortality risk among breast cancer survivors and 28% (95% CI = 20-35%) decreased total mortality risk among colorectal cancer survivors. Breast or colorectal cancer survivors who increased their physical activity by any level from pre- to post-diagnosis showed decreased total mortality risk (RR = 0.61; 95% CI = 0.46-0.80) compared with those who did not change their physical activity level or were inactive/insufficiently active before diagnosis., Conclusion: Physical activity performed before or after cancer diagnosis is related to reduced mortality risk among breast and colorectal cancer survivors., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A cluster of seven human cases of listeriosis occurred in Austria and in Germany between April 2011 and July 2013. The Listeria monocytogenes serovar (SV) 1/2b isolates shared pulsed-field gel electrophoresis (PFGE) and fluorescent amplified fragment length polymorphism (fAFLP) patterns indistinguishable from those from five food producers. The seven human isolates, a control strain with a different PFGE/fAFLP profile and ten food isolates were subjected to whole genome sequencing (WGS) in a blinded fashion. A gene-by-gene comparison (multilocus sequence typing (MLST)+) was performed, and the resulting whole genome allelic profiles were compared using SeqSphere(+) software version 1.0. On analysis of 2298 genes, the four human outbreak isolates from 2012 to 2013 had different alleles at ≤6 genes, i.e. differed by ≤6 genes from each other; the dendrogram placed these isolates in between five Austrian unaged soft cheese isolates from producer A (≤19-gene difference from the human cluster) and two Austrian ready-to-eat meat isolates from producer B (≤8-gene difference from the human cluster). Both food products appeared on grocery bills prospectively collected by these outbreak cases after hospital discharge. Epidemiological results on food consumption and MLST+ clearly separated the three cases in 2011 from the four 2012-2013 outbreak cases (≥48 different genes). We showed that WGS is capable of discriminating L. monocytogenes SV1/2b clones not distinguishable by PFGE and fAFLP. The listeriosis outbreak described clearly underlines the potential of sequence-based typing methods to offer enhanced resolution and comparability of typing systems for public health applications., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Background: Clostridium difficile infection is the leading cause of gastroenteritis-associated deaths in the industrialized world, followed by infection with norovirus., Methods: Using a cohort study design, we compared 90 inpatients with diarrhea due to C. difficile infection (CDI) with 180 inpatients with diarrhea due to other infectious agents (including 55% with norovirus infection) with respect to complications and all-cause mortality. The effects of age, severity of underlying diseases and additional infections were assessed by stratified analyses., Results: Diarrhea recurrence occurred 8.9 (95%CI: 2.9-27.3) times more often in CDI independent of age and severity of comorbidities. The all-cause mortality in CDI patients pre-discharge and at 30 and 180 days, respectively, was 20.0%, 17.0% and 42.3% versus 7.2%, 6.7% and 22.5% in non-CDI diarrhea patients. Among those patients with low comorbidities, who were younger than 65 years and without additional infections, the all-cause pre-discharge, 30-day and 180-day mortality risks were significantly higher for the CDI diarrhea patients than the non-CDI diarrhea patients. This association was not observed among patients with an older age, more severe comorbidities or additional infections., Conclusion: CDI results in higher all-cause mortality than diarrhea due to other infectious agents in younger patients with low comorbidities., (Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

In 2010 a case of a dual infection with Legionella pneumophila serogroup (sg) 1 and sg 3 was identified by culture of a blood sample collected from a female Austrian patient with septic pneumonia. Subsequently all 35 European National Legionella Reference Laboratories were interviewed regarding the frequency of dual infections in legionellosis. The Reference Laboratories in Denmark, the UK and Germany reported the detection of another 14 cases of dual infections with different Legionella strains between 2002 and 2012. Among the 15 cases, there were four cases with different Legionella species, six cases with different L. pneumophila serogroups, and five cases of dual infections with L. pneumophila sg 1 with different MAb-types. The median age of the 15 cases was 56 years and the male to female ratio 1:1.14. Six of the 15 patients were receiving immunosuppressive treatment following organ transplantation (n = 3) or for underlying haematological and solid malignancies (n = 3). Five of the 15 cases died within 30 days following diagnosis. Efforts to detect dual infections with different Legionella strains will improve our ability to correctly elucidate the causative sources of infection and enhance our understanding of the epidemiology of Legionella infections., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

In forensic genetics mitochondrial DNA (mtDNA) is usually analyzed by direct Sanger-type sequencing (STS). This method is known to be laborious and sometimes prone to human error. Alternative methods have been proposed that lead to faster results. Among these are methods that involve mass-spectrometry resulting in base composition profiles that are, by definition, less informative than the full nucleotide sequence. Here, we applied a highly automated electrospray ionization mass spectrometry (ESI-MS) system (PLEX-ID) to an mtDNA population study to compare its performance with respect to throughput and concordance to STS. We found that the loss of information power was relatively low compared to the gain in speed and analytical standardization. The detection of point and length heteroplasmy turned out to be roughly comparable between the technologies with some individual differences related to the processes. We confirm that ESI-MS provides a valuable platform for analyzing mtDNA variation that can also be applied in the forensic context., (Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

We describe an extraordinarily protracted case of varicella zoster virus (VZV) multifocal vasculopathy in a man who presented initially with ischemic optic neuropathy and then suffered 4 episodes of stroke manifesting as multi-infarct dementia over a 2-year period. Brain magnetic resonance imaging (MRI) and angiography (MRA) revealed cortical and subcortical infarctions as well as vasculitic occlusion and stenosis. The patient was treated with corticosteroids and later with cyclophosphamide. More than 2 years after the onset of neurological disease, two cerebrospinal fluid (CSF) examinations revealed the presence of anti-VZV IgG antibody with reduced serum-to-CSF ratios of anti-VZV IgG compared with ratios for total IgG and albumin, indicative of intrathecal synthesis of anti-VZV IgG. After definitive diagnosis, immunosuppressive drugs were discontinued and he was treated with intravenous acyclovir; both mental status and gait improved and no further episodes of neurological dysfunction ensued. The favorable outcome in this patient indicates that VZV vasculopathy can be treated successfully even after 26 months. VZV must be considered as a possible cause of neurological disease in any patient with idiopathic multifocal vasculopathy., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Introduction: Bone strength determines fracture risk and fixation strength of osteosynthesis implants. In vivo, bone strength is currently measured indirectly by quantifying bone mineral density (BMD) which is however only one determinant of the bone's biomechanical competence besides the bone's macro- and micro-architecture and tissue related parameters. We have developed a measurement principle (DensiProbe™ Hip) for direct, mechanical quantification of bone strength within the proximal femur upon hip fracture fixation. Previous cadaver tests indicated a close correlation between DensiProbe™ Hip measurements, 3D micro-CT analysis and biomechanical indicators of bone strength. The goal of this study was to correlate DensiProbe™ Hip measurements with areal bone mineral density (BMD)., Methods: Forty-three hip fracture patients were included in this study. Intraoperatively, DensiProbe™ Hip was inserted to the subsequent hip screw tip position within the femoral head. Peak torque to breakaway of local cancellous bone was registered. Thirty-seven patients underwent areal BMD measurements of the contralateral proximal femur. Failure of fixation was assessed radio graphically 6 and 12 weeks postoperatively., Results: Peak torque and femoral neck BMD showed significant correlations (R=0.60, P=0.0001). In regression analysis, areal BMD explained 46% of femoral neck BMD variance in a quadratic relationship. Throughout the 12-week follow-up period, no failure of fixation was observed., Conclusions: DensiProbe™ Hip may capture variations of bone strength beyond areal BMD which are currently difficult to measure in vivo. A multicenter study will clarify if peak torque predicts fixation failure., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We report on an outbreak caused by Salmonella enteritidis phage type 4 (PT4) among 143 participants at a soccer camp in Austria in August 2010. The outbreak affected 34 persons, including 24 epidemiologically related cases and 10 laboratory-confirmed cases. Food-specific cohort analyses revealed spaetzle (homemade noodles) (relative risks (RR): 2.68; 95% CI: 1.13-6.45), hamburger (RR: 2.70; 95% CI: 1.13-6.45) and potato salad (RR: 2.91; 95% CI: 1.69-5.02) as the most biologically plausible infection sources. Eggs used as ingredients were considered to be the vehicle of infection for the outbreak strain. The sole egg producer supplying the hotel that housed the soccer camp participants with table eggs operated two flocks. One flock had been epidemiologically and microbiologically related to a previous S. enteritidis PT4 outbreak affecting the same Austrian province in the four months preceding the August outbreak. We hypothesize that eggs from this flock, already condemned for industrial use only, were falsely declared table eggs and sold among eggs from the non-banned flock causing the subsequent outbreak. In Austria, the illegal distribution of eggs designated for industrial use (i.e., false declaration of these eggs as table eggs) has been previously documented. Our findings underscore the potential of proper epidemiological outbreak investigation to identify the pitfalls of regulatory responses in risk management., (Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

Immune recognition and rejection of tissues expressing transfected genes is a major complication of gene replacement therapy for inherited genetic disorders. Owing to the high immunogenicity of human bullous pemphigoid antigen 2 (hBPAG2), the induction and maintenance of tolerance to this neo-antigen is essential to deliver the gene product to patients with epidermolysis bullosa junctionalis. In a skin grafting mouse model, we used gene gun transfection with a construct encoding hNC16A, the immunodominant domain of hBPAG2, to induce antigen-specific immune tolerance. Eighty percent of wild-type mice transfected with hNC16A showed long-term survival of skin grafts expressing hBPAG2. Tolerance was stable and transferable by T cells but not by B cells of tolerant mice to naive hosts. A dense Foxp3(+) regulatory T-cell (T(reg)) infiltrate was noticed in grafts of tolerant mice and depletion of these cells resulted in a loss of tolerance. Taken together, we show that long-lasting hBPAG2-specific tolerance was induced with gene gun delivery of hNC16A through a T(reg)-dependent mechanism. This is of relevance to patients undergoing gene therapy and has broader implications for the treatment of antigen-specific autoimmune diseases.

We describe a 26-year-old man treated with azathioprine for myasthenia gravis who developed acute left-sided peripheral facial weakness. Brain magnetic resonance imaging (MRI) revealed enhancement in the left geniculate ganglion and in the intracanalicular and tympanic segments of the facial nerve. Analysis of cerebrospinal fluid (CSF) and serum revealed intrathecal synthesis of anti-varicella zoster virus (VZV) IgG antibody. Although previous analyses of saliva, blood mononuclear cells, serum antibodies, middle ear fluid, and auricular and geniculate zone skin scrapings have shown that a small but definite proportion of patients with idiopathic peripheral facial palsy ("Bell's palsy") have the Ramsay Hunt syndrome zoster sine herpete (RHS ZSH), this is the first confirmation of RHS ZSH by intrathecal synthesis of anti-VZV IgG antibody. In addition, herpes simplex virus (HSV)-1 DNA was found in saliva of the patient on 3 consecutive days. Simultaneous reactivation of two alphaherpesviruses (HSV-1 and VZV) in our immunosuppressed patient underscores the need to consider opportunistic infection as a cause of facial weakness., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: The composition of long-chain PUFAs (LCPUFAs) in the maternal diet may affect obesity risk in the mother's offspring., Objective: We hypothesized that a reduction in the n-6 (omega-6):n-3 (omega-3) LCPUFA ratio in the diet of pregnant women and breastfeeding mothers may prevent expansive adipose tissue growth in their infants during the first year of life., Design: In a randomized controlled trial, 208 healthy pregnant women were randomly assigned to an intervention (1200 mg n-3 LCPUFAs as a supplement per day and a concomitant reduction in arachidonic acid intake) or a control diet from the 15th wk of pregnancy to 4 mo of lactation. The primary outcome was infant fat mass estimated by skinfold thickness (SFT) measurements at 4 body sites at 3-5 d, 6 wk, and 4 and 12 mo postpartum. Secondary endpoints included sonographic assessment of abdominal subcutaneous and preperitoneal fat, fat distribution, and child growth., Results: Infants did not differ in the sum of their 4 SFTs at ≤1 y of life [intervention: 24.1 ± 4.4 mm (n = 85); control: 24.1 ± 4.1 mm (n = 80); mean difference: -0.0 mm (95% CI: -1.3, 1.3 mm)] or in growth. Likewise, longitudinal ultrasonography showed no significant differences in abdominal fat mass or fat distribution., Conclusions: We showed no evidence that supplementation with n-3 fatty acids and instructions to reduce arachidonic acid intake during pregnancy and lactation relevantly affects fat mass in offspring during the first year of life. Prospective long-term studies are needed to explore the efficacy of this dietary approach for primary prevention. This trial was registered at clinicaltrials.gov as NCT00362089.

Aims: In vivo application of the K(ATP)-channel blocker glibenclamide can reverse endotoxin-induced hypotension, vascular hyporeactivity and shock in experimental animals. The hypothesis of the present study is, that the drug effects might not only be based on direct inhibition of K(ATP)-channels of vascular smooth muscle cells, but might also reflect reduction of shock-induced excess proinflammatory cytokines and procoagulatory molecules produced in the blood monocytes., Main Methods: Human whole blood (normoxaemic or hypoxaemic) supplemented ex vivo with 100 ng/ml LPS was used to assess glibenclamide (3-100 μM) effects on IL-1 beta, IL-6, TNF-alpha, tissue factor, and plasminogen-activator-inhibitor-2 (PAI-2). Co-incubations with monocytes and erythrocytes and cytosolic calcium measurements were performed to reveal their purinergic intercellular interaction., Key Findings: In heparinized blood, glibenclamide reduced LPS-induced release of IL-1 beta and TNF-alpha, tissue factor and PAI-2 mRNA in a concentration-dependent manner. When samples were subjected to strong hypoxemia using 95% N(2)/5% CO(2), these parameters became even more sensitive to the drug. No drug effect was observable in citrated blood or in isolated monocytes. IL-1 beta mRNA inhibition by glibenclamide appeared to be dependent on P2X7-receptor activation of monocytes by ATP-releasing erythrocytes during hypoxia. Cytosolic calcium values as well as the duration of calcium transients elicited by P2X7-receptor stimulation in isolated monocytes were strongly increased during hypoxia, both of which could be abolished by glibenclamide., Significance: We conclude that the anti-inflammatory effect of glibenclamide is mainly based on the reduction of calcium entry by drug-induced depolarization of hypoxic monocytes. Thus, glibenclamide possesses a potentially beneficial shock-specific anti-inflammatory action., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The aims of this study were to assess a cohort of patients with head and neck squamous cell carcinoma (HNSCC) for: (1) the prevalence of synchronous distant metastases (DM) as detected by the initial staging by using (18)F-FDG PET/CT, (2) the prevalence of metachronous DM, and (3) the validity of published risk factors with special emphasis on the maximum standardized uptake value (SUV max) for the prediction of DM. Two hundred and ninety nine patients with advanced HNSCC were included. Following risk factors at the time of diagnosis and during follow-up were analyzed: advanced T/N stage, poor histological differentiation, level IV/Vb lymph nodes, primary site in the larynx/hypopharynx, and SUV max. The prevalence of DM at initial staging and during follow-up was 10% and 11%, respectively. At initial staging, primary site in the larynx/hypopharynx and neck nodes in level IV/Vb, and during follow-up only level IV/Vb nodes achieved statistical significance. The sensitivity for (18)F-FDG PET/CT with regard to the detection of DM was 96.8%, the specificity 95.4%, the positive predictive value (PV) 69.8%, and the negative PV 99.6%. Patients without DM showed a significantly better overall survival (OS) than patients developing DM (p<0.001). There was no significant difference in OS with regard to the time of diagnosis of DM. The prevalence for synchronous and metachronous DM in advanced HNSCC is considerable. (18)F-FDG PET/CT is highly accurate for initial staging and follow-up. DM carries a bad prognosis regardless of the time of diagnosis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Analysis of 200 paired serum and cerebrospinal fluid (CSF) samples from 180 HIV-positive individuals, 136 of whom had AIDS, revealed intrathecal synthesis of antibodies specific for varicella zoster virus (VZV) in 28 (16%) individuals, measles virus in 15 (8%), herpes simplex virus-1 (HSV-1) in 1 (0.6%), and HSV-2 in none. Of the 28 subjects with a positive VZV antibody specificity index, only 1 had zoster rash at the time of serum and CSF sampling; of the total 180 HIV-positive subjects, 146 (81%) had no history of zoster. Based on an estimated 33.4 million HIV-positive individuals worldwide, subclinical reactivation of VZV in even less than 16% of HIV-positive people suggests the possibility that millions of people have active VZV infection of the central nervous system. In cases of VZV vasculopathy, myelopathy and even zoster sine herpete, the CSF is often positive for anti-VZV antibody, but negative for VZV DNA. To rule out VZV infection of the nervous system, CSF must be tested for VZV DNA and anti-VZV IgG and IgM antibody., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Failure to adjust hypertension therapy despite elevated blood pressure (BP) levels is an important contributor to lack of BP control. One possible explanation is that small elevations above goal BP are not concerning to clinicians. BP levels farther above goal, however, should be more likely to prompt clinical action. We reviewed 1 year's worth of primary care records of 3742 North Carolina Medicaid recipients 21 years and older with hypertension (a total of 15,516 office visits) to examine variations in hypertension management stratified by level of BP above goal and the association of BP level above goal with documented antihypertensive medication change. Among the 53% of patients not at goal BP, 42% were within 10/5 mm Hg of goal; 11% had a BP 40/20 mm Hg or higher above goal. Higher level of BP above goal was independently associated with antihypertensive medication change. Compared with visits at which BP was less than 10/5 mm Hg above goal, the adjusted odds of medication change were 7.9 (95% Confidence Interval 6.2-10.2) times greater at visits when patients' BP was 40/20 mm Hg or higher above goal. However, even when BP was above goal at this level, treatment change occurred only 46% (95% Confidence Interval 40.2-51.8) of the time., (Copyright © 2010 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

We describe an immunocompetent 45-year-old woman who had four episodes of neurological disease (meningoencephalitis, multifocal vasculopathy, myelitis and inflammatory brain stem disease) produced by varicella zoster virus (VZV) over an 11-month period, all in the absence of rash. The cerebrospinal fluid (CSF) contained anti-VZV IgG antibody, but not VZV DNA throughout her illness, reaffirming the superiority of detection of anti-VZV IgG in CSF compared to VZV DNA in diagnosing VZV infection of the nervous system. Moreover, 3 of 7 CSF samples examined during the 11 months showed a VZV-induced pleocytosis consisting predominantly of polymorphonuclear cells (PMNs), and 4 of 7 samples also contained increased numbers of red blood cells (RBCs). Because increased PMNs and RBCs in CSF can also occur in patients with central and peripheral nervous system disease produced by cytomegalovirus (CMV), the differential diagnosis of chronic nervous system infection with increased PMNs and RBCs in CSF should include analyses for both VZV and CMV., (Copyright 2010 Elsevier B.V. All rights reserved.)

A foodborne norovirus outbreak occurred after a pre-Christmas celebration among a group of local foresters in Austria in December 2007. A total of 66 persons, 60 participants of the Christmas party and 6 kitchen staff members of the restaurant where the party took place, were identified as the at-risk cohort. Questioning of this cohort was performed by self-report questionnaires or telephone interviews (response rate of 95%). The outbreak attack rate was 33.3% (21 of 63 persons), including two of the kitchen staff. Three stool specimens yielded norovirus genogroup II. Univariate analysis revealed that exposure to a ham roll and pastry was possibly associated with risk of gastroenteritis (risk ratio [RR] of 4.45, 95% CI of 1.91 to 10. RR of 2.44, 95% CI of 0.93 to 6.39). After controlling for the effects of sex, age, and other food items with a log-linear model, ham roll remained significantly associated with disease risk (RR of 3.91, 95% CI of 1.57 to 9.76). Ham roll was most likely contaminated with norovirus during preparation by a disease-free kitchen assistant, whose infant became sick with laboratory-confirmed norovirus gastroenteritis 2 days before the party. Informing food handlers about the possible risk of food contamination with norovirus and training them in the appropriate measures of hand hygiene and environmental disinfection at the working place and at home are essential for preventing food-related norovirus outbreaks. Norovirus-infected household members of healthy food handlers must be considered a possible reservoir for foodborne norovirus outbreaks.

STR investigations of telogen hair are invariably difficult due to the small amounts of nuclear DNA and its degradation products. However, in recent years there has been a considerable improvement. This study examined the suitability of a new STR kit with shortened amplicons for the investigation of hair in routine casework. This kit allows the simultaneous amplification of the eight STR-loci D3S1358, VWA, FGA, TH01, SE33, D8S1179, D18S51, and D21S11, and the sex-determining amelogenin system. It was tested against the genRES MPX-SP1 and genRES MPX-SP2 kits. The sensitivity of the new genRES MPX-2SP kit was demonstrated to be inferior to that of the genRES MPX-SP1, but almost equal to that of the genRES MPX-SP2 kit.

The detection of low levels of pharmaceuticals in aquatic environments has lately raised concerns regarding possible adverse effects of these highly active substances on aquatic organisms. The non-steroidal anti-inflammatory drug diclofenac (DCF) is one of the pharmaceutical substances regularly detected in surface waters and has lately been demonstrated to elicit adverse effects in salmonid species at environmentally relevant concentrations. The aim of the present study was to investigate the distribution of DCF in indigenous brown trout (Salmo trutta f. fario) following intraperitoneal (i.p.) injection of a single dose of (14)C-labelled DCF. A distribution kinetic over 36 h provides information on possible accumulation of DCF in different organs as well as on DCF detoxification in trout, possibly enabling identification of sites of preferential toxicity. Approximately 57% of the total single DCF dose appeared in the bile 6 h after i.p. application. Subsequently, DCF was observed to undergo enterohepatic cycling with an amount of (14)C-activity comparable to the 6 h bile values reappearing in bile 36 h after application. Results for (14)C-activity in intestine and pylori support the observation of enterohepatic cycling with a small peak in intestine at 3 h post i.p. injection and a low peak in intestine and pylori at 6 h post i.p. injection, reflecting presence of the drug substance in bile. The highest activity in intestine was found 24 h post-injection coinciding with low levels in bile, followed by a gradual decrease of activity in intestine mirroring the re-uptake of DCF into bile. The finding of enterohepatic cycling of DCF in brown trout is suggestive of a prolonged retention of DCF in brown trout.

Since 2005, increasing numbers of seizures of the designer drug of abuse 1-(3-chlorophenyl)piperazine (mCPP) have been reported. This paper describes the unequivocal proof of a mCPP intake. Differentiation from the intake of its precursor drugs trazodone and nefazodone was performed by a systematic toxicological analysis (STA) procedure using full-scan GC-MS after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation. The found mCPP/hydroxy-mCPP ratio indicated altered metabolism of this cytochrome (CYP) 2D6 catalyzed reaction compared to published studies using the same procedure. Although this might be ascribed to a poor metabolizer (PM) phenotype, genotyping revealed no PM genotype but indications for an intermediate metabolizer genotype. However, a PM phenotype could also be caused by drug-drug interactions with CYP2D6 inhibitors or substrates such as the co-consumed cocaine and diltiazem and/or diltiazem metabolites, respectively. In conclusion, the presented data indicate a possible relevance of CYP2D6 polymorphism and/or drug interactions to mCPP toxicokinetics, which is important for risk assessment of this new designer drug of abuse, in particular if it is used as adulterant of CYP2D6 substrates such as cocaine.

There has been an intensive debate whether dietary exposure to acrylamide could increase the risk of human cancer since the first description of the presence of acrylamide in food in 2002. As the intestinal mechanisms of acrylamide absorption are poorly investigated we studied the transport of acrylamide in differentiated Caco-2 cells and its effects on biotransformation enzymes (CYP2E1 and glutathione S-transferase) and glutathione levels. We found that the apparent permeability of [1-(14)C] acrylamide from the basal to the apical compartment was approximately 20% higher compared to that in the opposite direction. No differences were detected for apical-basal transport against a basal gradient. Transport rates from the apical to the basal chamber at 4 degrees C were about 50% lower than at 37 degrees C. Concentration dependent transport from apical to basal was linear. Predominantly, basal to apical transport was decreased when energy metabolism of the cells was inhibited by application of sodium azide and 2-deoxy-d-glucose. Finally, more acrylamide was transported at luminal pH 6 compared to pH 7.4 from basal to the apical direction. Increasing levels of acrylamide showed no effects on the activity of glutathione S-transferase but resulted in a depletion of total glutathione concentrations. In conclusion transport of acrylamide in the intestine is mediated primarily by passive processes possibly combined with a modest energy- and pH-dependent active secretory component. Depletion of cellular glutathione levels may be one potential mechanism for acrylamide (geno)toxicity.

Blood stasis is one of the key risk factors in deep vein thrombosis. Localized blood oxygen and glucose depletion are main characteristics observed during stasis. However, the causal chain leading to clot formation is still obscure. According to our hypothesis, energy depletion causes opening of K(ATP) channels present on monocytes, facilitating influx of calcium and triggering tissue factor-(TF)-dependent procoagulatory activity and eventually clot formation. Using Reverse-Transcript-PCR (RT-PCR) in magnetically enriched human monocytes, mRNA transcription of the K(ATP)-channel subunits Kir6.1 and Kir6.2 could be confirmed. Membrane potential and cytosolic calcium were recorded by time-resolved flow cytometry. The specific K(ATP)-channel opener pinacidil caused a glibenclamide-sensitive hyperpolarization of monocytes and a prolongation of cytosolic calcium transients triggered by purinergic stimulation. TF-initiated whole blood clotting time (TiFaCT) was accelerated comparing 2 and 8 h of simulated in vitro blood stasis using blood of male healthy volunteers. Both with and without activation of the monocytes with 100 ng/ml LPS, the K(ATP)-channel blocker glibenclamide resulted in a significantly (p<0.001) prolonged clotting time after 8 h of stasis compared to vehicle control and LPS, respectively. In the course of stasis, flow cytometry showed an increase in monocytes expressing TF (0.1% and 1.3% after 2 and 8 h, respectively). LPS (100 ng/ml) increased the amount of TF expression significantly to 36%, whereas 30 microM glibenclamide partly reversed this increase down to 24%. Phosphatidylserine-exposure (PSE) on monocytes increased strongly during stasis by 11.2 times, a process which glibenclamide attenuated by 23%. LPS increased PSE further by 65%, which glibenclamide reduced by 50%. In conclusion, presence of integral subunits of K(ATP)-channels is demonstrated in human monocytes. These channels are able to enhance Ca(2+)-dependent intracellular signalling and can increase TF-activity and phosphatidylserine exposure thereby accelerating clot formation during stasis by monocytes.

An outbreak of gastroenteritis due to Salmonella Enteritidis phage type 4 occurred in people who attended a traditional hunting festivity in a small village in western Austria 6 through 11 November 2005. Of approximately 250 attendees, 227 had consumed dishes offered at the festival, and of these consumers 35 persons fulfilled the outbreak case definition (attack rate of 15.4%). Spätzle (traditional pastalike side dish) was most likely the contaminated part of the incriminated main course (relative risk of 18.9, 95% confidence interval of 4.6 to 76.7; P < 0.001). Thirteen eggs that remained from the preparation of the spätzle were negative for Salmonella when tested individually without shell disinfection, as were 1200 eggs collected at the egg production plant and examined with shell disinfection. The back-traced egg production farm had been initially certified as Salmonella free by a voluntary quality control program. However, an intensified environmental investigation of the incriminated egg production farm performed in the first quarter of 2006 and based on an appropriate method of sampling revealed Salmonella Enteritidis phage type 4 in 4 of 13 flocks. Although a combination of epidemiological and microbiological investigations allowed elucidation of the mode of spread, no restrictions were placed on the incriminated flocks of laying hens. These flocks were kept in production until they were stalled out due to age in August 2006. In June 2006, a cluster of 23 cases of Salmonella Enteritidis phage type 6 infection was again associated with this egg production farm. Evidence provided by epidemiological analyses is often disregarded by decision makers. However, negative results from microbiological testing of food involved in an outbreak are often weighted as strong evidence against a causal association between that food and the outbreak.

Drug-induced hypersensitivity reactions have been explained by the hapten concept, according to which a small chemical compound is too small to be recognized by the immune system. Only after covalently binding to an endogenous protein the immune system reacts to this so called hapten-carrier complex, as the larger molecule (protein) is modified, and thus immunogenic for B and T cells. Consequently, a B and T cell immune response might develop to the drug with very heterogeneous clinical manifestations. In recent years, however, evidence has become stronger that not all drugs need to bind covalently to the MHC-peptide complex in order to trigger an immune response. Rather, some drugs may bind directly and reversibly to immune receptors like the major histocompatibility complex (MHC) or the T cell receptor (TCR), thereby stimulating the cells similar to a pharmacological activation of other receptors. This concept has been termed pharmacological interaction with immune receptors the (p-i) concept. While the exact mechanism is still a matter of debate, non-covalent drug presentation clearly leads to the activation of drug-specific T cells as documented for various drugs (lidocaine, sulfamethoxazole (SMX), lamotrigine, carbamazepine, p-phenylendiamine, etc.). In some patients with drug hypersensitivity, such a response may occur within hours even upon the first exposure to the drug. Thus, the reaction to the drug may not be due to a classical, primary response, but rather be mediated by stimulating existing, pre-activated, peptide-specific T cells that are cross specific for the drug. In this way, certain drugs may circumvent the checkpoints for immune activation imposed by the classical antigen processing and presentation mechanisms, which may help to explain the peculiar nature of many drug hypersensitivity reactions.