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When making decisions about resource use, social species must integrate not only environmental factors but also the influence of opportunities and costs associated with group living. Bigger groups are expected to move further and to need access to larger areas for adequate food acquisition, but the relationships with group size can vary seasonally and with reproductive stage. Shelters are often more consistent in availability than food, but their use relates to factors such as predator defense and parasite transmission that are themselves influenced by group size and seasonality. Here, we used long-term data to investigate resource use and associated movement in a wild population of dwarf mongooses ( Helogale parvula ). We found that bigger groups occupied larger home ranges, moved larger daily distances and covered more daily area than smaller ones, while environmental greenness (measured by normalized difference vegetation index [NDVI]) influenced daily movements in the breeding season but not the non-breeding season. Both assessed axes of seasonality also had pronounced effects on shelter use: mongoose groups used more unique sleeping burrows, and switched between burrows more often, in the breeding season, but also switched more when environmental greenness was higher. By investigating specific periods within the breeding season, we revealed the constraints that vulnerable, poorly mobile offspring impose on both group movements and burrow use, highlighting a potentially overlooked cost of reproduction. Our results show how both social and environmental factors can affect key resource-use decisions, demonstrating potential costs and benefits to group living within distinctly seasonal geographic areas., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Behavioral Ecology.)

Cooperatively breeding societies show distinct interspecific variations in social and genetic organization. Long-term studies provide invaluable data to further our understanding of the evolution and maintenance of cooperative breeding but have also demonstrated how variation exists within species. Here we integrate life-history, behavioural and genetic data from a long-term study of dwarf mongooses Helogale parvula in South Africa to document mating, breeding, dispersal and relatedness patterns in this population and compare them to those found in a Tanzanian population at the other extreme of the species' range. Our genetic data reveal high levels of reproductive skew, above that expected through observational data. Dispersal was male-biased and was seen more frequently towards the onset of the breeding season, but females also regularly switched between groups. These patterns of breeding and dispersal resulted in a genetically structured population: individuals were more related to groupmates than outsiders, apart from the unrelated dominant pair, ultimately resulting in reduced inbreeding risk. Our results also demonstrate that dwarf mongooses are largely consistent in their social structure across their sub-Saharan distribution. This work demonstrates the direct and indirect pathways to reproductive success for dwarf mongooses and helps to explain the maintenance of cooperative breeding in the species., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Background: Nosocomial infections pose a serious threat. In neonatal intensive care units (NICUs) especially, there are repeated outbreaks caused by micro-organisms without the sources or dynamics being conclusively determined., Aim: To use amorphous silica nanoparticles with encapsulated DNA (SPED) to simulate outbreak events and to visualize dissemination patterns in a NICU to gain a better understanding of these dynamics., Methods: Three types of SPED were strategically placed on the ward to mimic three different dissemination dynamics among real-life conditions and employee activities. SPED DNA, resistant to disinfectants, was sampled at 22 predefined points across the ward for four days and quantitative polymerase chain reaction analysis was conducted., Findings: Starting from staff areas, a rapid ward-wide SPED dissemination including numerous patient rooms was demonstrated. In contrast, a primary deployment in a patient room only led to the spread in the staff area, with no distribution in the patient area., Conclusion: This study pioneers SPED utilization in simulating outbreak dynamics. By unmasking staff areas as potential key trigger spots for ward-wide dissemination the revealed patterns could contribute to a more comprehensive view of outbreak events leading to rethinking of hygiene measures and training to reduce the rate of nosocomial infections in hospitals., Competing Interests: Conflict of interest statement None declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Although diagnostic stewardship issues in clinical microbiology harbor an optimization potential for anti-infective consumption, they are only marginally addressed in antimicrobial stewardship (AMS) programs. As part of an AMS point prevalence (PPS) survey we therefore aimed to gain a more dynamic view on the microbiological awareness within therapeutic regimens. By examining whether initial microbiological sampling was performed and in which way microbiological results were incorporated into further treatment considerations we sought to find out to what extent these points determine the appropriateness of treatment regimens., Methods: PPS was performed at the University Hospital Salzburg (1524 beds) in May 2021. Relevant data was determined from the patient charts and the appropriateness of anti-infective use was assessed using predefined quality indicators. Six months after the PPS, a questionnaire was administered to clinicians to obtain information on the use of microbiological findings and their relevance in the clinic., Results: Lack of microbiological awareness in the clinical setting proved to be the key reason for an overall inadequate use of anti-infectives (35.4% of cases rated as inadequate), ahead of the aspects of dose (24.1%), empirical therapy (20.3%) and treatment duration (20.2%). This was particularly the case for broad-acting agents and was most evident in urinary tract infections, skin and soft tissue infections, and pneumonia. The results of the questionnaire indicate a discrepancy between the physicians surveyed and the routine clinical setting., Conclusion: A high potential in improving the use of anti-infectives in hospitals seems to lie in a strong emphasis on microbiological diagnostic stewardship measures., (© 2023. The Author(s).)

Anthropogenic (man-made) noise constitutes a novel and widespread pollutant which is increasing in prevalence in terrestrial and aquatic ecosystems, resulting in alterations of natural soundscapes. There is proliferating evidence that noise leads to maladaptive behaviour in wildlife, yet few studies have addressed the effect on mammalian parent-offspring interactions. We investigated the impact of road noise on dwarf mongoose ( Helogale parvula ) offspring nearest-neighbour decision-making while foraging, using a field-based playback experiment. We predicted that offspring would forage closer to groupmates, especially adult and dominant individuals, when experiencing road noise compared with ambient sound to reduce communication masking and alleviate stress. We also predicted that noise would have a reduced effect with increasing offspring age owing to reduced reliance on adult groupmates for provisioning and predator defence. However, we found that mean nearest-neighbour distance and nearest-neighbour intrinsic characteristics (age, sex and dominance status) did not differ significantly between sound treatments, and these responses did not vary significantly with focal individual age. Noise may not impact nearest-neighbour decision-making owing to habituation from chronic natural exposure; alternatively, noise could induce stress and distraction, resulting in maladaptive decision-making. Future work should aim to detangle the underlying mechanisms mediating parent-offspring interactions in conditions of anthropogenic noise., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

Outgroup conflict is a powerful selective force across all social taxa. While it is well documented that individual outgroup contests can have a range of direct and indirect fitness consequences, the cumulative pressure of outgroup threats could also potentially impact reproductive success. Here, we use long-term life-history data from a wild population of dwarf mongooses ( Helogale parvula ) to investigate how intergroup interaction (IGI) rate might influence breeding and offspring survival. IGI rate did not predict the number of litters produced in a season or the inter-litter interval. Unexpectedly, IGI rate was positively associated with the number of pups alive three months after emergence from the breeding burrow. This was not due to a difference in how many pups emerged but because those in groups experiencing more IGIs had a higher survival likelihood post-emergence. Detailed natural observations revealed that both IGI occurrence and the threat of intergroup conflict led to more sentinel behaviour by adults, probably reducing the predation risk to young. Our results contrast the previously documented negative effects of outgroup interactions on reproductive success and highlight the need to assess cumulative threat, rather than just the impact of physical contests, when considering outgroup conflict as a social driver of fitness.

Social instability frequently arises in group-living species, but the potential costs have rarely been investigated in free-living cooperative breeders, especially across different timeframes. Using natural observations, body mass measurements and life-history data from dwarf mongooses ( Helogale parvula ), we determined the short- and long-term consequences of a change in one of the dominant breeding pairs. We found that a new breeder led to alterations in both collective and individual behaviours (i.e. increases in communal scent-marking, engagement in intergroup interactions, sentinel activity and within-group grooming), as well as reduced body mass gain, further demographic changes and decreased reproductive success (i.e. fewer pups surviving to adulthood). The effects were particularly apparent when it was the female breeder who changed; new female breeders were younger than more experienced counterparts. Our findings support the idea that stability and cooperation are strongly linked and provide potential reasons for previously documented health and fitness benefits of social stability.

Therapeutic plasma exchange (TPE) is used for drug-resistant neuroimmunological disorders, but its mechanism of action remains poorly understood. We therefore prospectively explored changes in soluble, humoral, and cellular immune components associated with TPE. We included ten patients with neurological autoimmune disorders that underwent TPE and assessed a panel of clinically relevant pathogen-specific antibodies, total serum immunoglobulin (Ig) levels, interleukin-6 (IL-6, pg/mL), C-reactive protein (CRP, mg/dL), procalcitonin (PCT, µg/L) and major lymphocyte subpopulations (cells/µL). Blood was collected prior to TPE (pre-TPE, baseline), immediately after TPE (post-TPE), as well as five weeks (follow-up1) and 130 days (follow-up2) following TPE. Pathogen-specific antibody levels were reduced by -86% ( p < 0.05) post-TPE and recovered to 55% (follow-up1) and 101% (follow-up2). Ig subclasses were reduced by -70-89% ( p < 0.0001) post-TPE with subsequent complete (IgM/IgA) and incomplete (IgG) recovery throughout the follow-ups. Mean IL-6 and CRP concentrations increased by a factor of 3-4 at post-TPE ( p > 0.05) while PCT remained unaffected. We found no alterations in B- and T-cell populations. No adverse events related to TPE occurred. TPE induced a profound but transient reduction in circulating antibodies, while the investigated soluble immune components were not washed out. Future studies should explore the effects of TPE on particular cytokines and assess inflammatory lymphocyte lineages to illuminate the mode of action of TPE beyond autoantibody removal.

Little is known about the antimicrobial resistance (AMR) status of uropathogens in Western Africa. We performed a retrospective evaluation of urine cultures collected from the rural Margret Marquart Catholic Hospital, Kpando, Ghana during the time period from October 2019−December 2021. Urine samples from 348 patients (median age 40 years, 52.6% male) were examined. Of these, 125 (35.9%) showed either fungal or bacterial growth, including Escherichia coli in 48 (38.4%), Candida species (spp.) in 29 (23.2%), Klebsiella spp. in 27 (21.6%), Proteus spp. in 12 (9.6%), Citrobacter spp. in 10 (8.0%), Salmonella spp. in 4 (3.2%), Staphylococcus spp. in 3 (2.4%), and Pseudomonas spp. in 2 (1.6%) cases. Two bacterial spp. were detected in 7 samples (5.6%). Antibiotic susceptibility testing showed resistance to a mean 8.6 out of 11 tested antibiotics per patient. Significant predictors (p < 0.05) of bacterial growth were age (OR 1.03), female sex (OR 3.84), and the number of pus cells (OR 1.05) and epithelial cells (OR 1.07) in urine microscopy. We observed an alarmingly high AMR rate among the uropathogens detected, even to reserve antibiotics. A similar resistance profile can be expected in West African patients living in high-income countries. These observations warrant the implementation of restrictive antibiotic protocols, together with the expansion of urine culture testing capacities, improvement of documentation and reporting of AMR rates, and continued research and development of new antibiotic therapies in order to stem the progression of AMR in this West African region.

Convalescent plasma (CP) has been in use for the treatment of numerous infectious diseases for more than a century, recently also for coronavirus disease 2019 (COVID-19). A major challenge for this treatment is identifying suitable donors with sufficient levels of functional antibodies and to determine the optimal time span for CP donation. In this retrospective study, we analyzed 189 CP donations of 66 donors regarding anti-SARS-CoV-2 anti-S IgG antibody levels. We found a significant correlation between the semi-quantitative SARS-CoV-2 IgG ratio values and in vitro antibody functionality. A time-to-event analysis allowed us to predict the optimal time span of COVID-19 CP donor suitability. We found that high IgG ratio values, which significantly correlate with high in vitro antibody functionality, were suitable for CP donation for a median of 134 days after the first CP donation. Donors with lower IgG ratios were suitable for a median of 53 days. Our data support plasma collection centers to determine optimal points in time for CP donation by means of widely used semi-quantitative laboratory IgG ratio values.

Conflict between rival groups is rife in nature. While recent work has begun exploring the behavioural consequences of this intergroup conflict, studies have primarily considered just the 1-2 h immediately after single interactions with rivals or their cues. Using a habituated population of wild dwarf mongooses ( Helogale parvula ), we conducted week-long manipulations to investigate longer-term impacts of intergroup conflict. Compared to a single presentation of control herbivore faeces, one rival-group faecal presentation (simulating a territorial intrusion) resulted in more within-group grooming the following day, beyond the likely period of conflict-induced stress. Repeated presentations of outsider cues led to further changes in baseline behaviour by the end of the week: compared to control weeks, mongooses spent less time foraging and foraged closer to their groupmates, even when there had been no recent simulated intrusion. Moreover, there was more baseline territorial scent-marking and a higher likelihood of group fissioning in intrusion weeks. Consequently, individuals gained less body mass at the end of weeks with repeated simulated intrusions. Our experimental findings provide evidence for longer-term, extended and cumulative, effects of an elevated intergroup threat, which may lead to fitness consequences and underpin this powerful selective pressure.

In many species, within-group conflict leads to immediate avoidance of potential aggressors or increases in affiliation, but no studies have investigated delayed post-conflict management behaviour. Here, we experimentally test that possibility using a wild but habituated population of dwarf mongooses ( Helogale parvula ). First, we used natural and playback-simulated foraging displacements to demonstrate that bystanders take notice of the vocalisations produced during such within-group conflict events but that they do not engage in any immediate post-conflict affiliative behaviour with the protagonists or other bystanders. We then used another playback experiment to assess delayed effects of within-group conflict on grooming interactions: we examined affiliative behaviour at the evening sleeping burrow, 30-60 min after the most recent simulated foraging displacement. Overall, fewer individuals groomed on evenings following an afternoon of simulated conflict, but those that did groomed more than on control evenings. Subordinate bystanders groomed with the simulated aggressor significantly less, and groomed more with one another, on conflict compared to control evenings. Our study provides experimental evidence that dwarf mongooses acoustically obtain information about within-group contests (including protagonist identity), retain that information, and use it to inform conflict-management decisions with a temporal delay., Competing Interests: AM, JK, AR No competing interests declared, (© 2021, Morris-Drake et al.)

In cooperatively breeding animals, much of the variation in the quantity of help provided by group members remains unexplained. A new study on an Australian songbird suggests we need to look to the context-specific benefits of helping for new insights., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Etiological, microbiological and epidemiological factors changed over time, but mortality rates remain high in infective endocarditis (IE). Healthcare-associated IE is nowadays responsible for a significant proportion of cases due to increasing numbers of cardiac devices. Cardiac implantable electronic devices, transcatheter aortic valve replacement, and percutaneous valve repair are meanwhile used, especially in old and sick patients. In suspected IE modified Duke criteria, integrating clinical results, imaging, and biomarkers are traditionally applied. Newer imaging technologies such as multi-slice computed tomography, photon-emission computed tomography, and magnetic resonance imaging might add value to conventional echocardiography in diagnosis and management of IE. Treatment consists of long-term antibiotic therapy, infectiological source control and/or cardiac surgery. Recently, antibiotic parenteral outpatient regimens and partial oral treatment strategies were shown to shorten hospital stays in patients suffering from IE. However, it remains unclear how to best select patients for partial oral therapy. This review describes new trends in diagnosing, imaging, and treating IE in a changing patient collective with particular focus on patients with implantable cardiac devices., (Copyright © 2020 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

We report the case of a 56-year-old woman with microfilaremic dirofilariasis due to Dirofilaria repens , which is a very rare condition in humans. Of note, just one of six large-volume blood samples of this patient was positive for microfilariae. Polymerase chain reaction (PCR) and sequencing of the parasite gene determined the geographic origin of the causative helminth. The patient was treated successfully with doxycycline. This drug was chosen because of the patient's reluctance to the use of ivermectin and to provide an anthelmintic effect by targeting the bacterial endosymbiont Wolbachia present in most filarial species.

In social species, conspecific outsiders present various threats to groups and their members. These out-group threats are predicted to affect subsequent within-group interactions (e.g., affiliation and aggression) and individual behavior (e.g., foraging and vigilance decisions). However, experimental investigations of such consequences are rare, especially in natural conditions. We used field-based call playbacks and fecal presentations on habituated wild dwarf mongooses ( Helogale parvula )-a cooperatively breeding, territorial species-to examine postinteraction responses to the simulated threat of a rival group. Dwarf mongooses invested more in grooming of groupmates, foraged closer together, and more regularly acted as sentinels (a raised guard) after encountering indicators of rival-group presence compared to control conditions. These behavioral changes likely arise from greater anxiety and, in the case of increased vigilance, the need to seek additional information about the threat. The influence of an out-group threat lasted at least 1 h but individuals of different dominance status and sex responded similarly, potentially because all group members suffer costs if a contest with rivals is lost. Our results provide field-based experimental evidence from wild animals that out-group threats can influence within-group behavior and decision making, and suggest the need for greater consideration of the lasting impacts of social conflict., (© The Author(s) 2019. Published by Oxford University Press on behalf of the International Society for Behavioral Ecology.)

Background: At birth, the majority of neonates born at <30 weeks of gestation require respiratory support to facilitate transition and ensure adequate gas exchange. Although the optimal approach to the initial respiratory management is uncertain, the American Academy of Pediatrics endorses noninvasive respiratory support with nasal continuous positive airway pressure (nCPAP) for premature neonates with respiratory insufficiency. Despite evidence for its use, nCPAP failure, requiring intubation and mechanical ventilation, is common. Recently, investigators have described a novel method to deliver bubble nCPAP, termed Seattle-PAP. While preclinical and pilot studies are encouraging regarding the potential value of Seattle-PAP, a large trial is needed to compare Seattle-PAP directly with the current standard of care for bubble nCPAP (Fisher & Paykel CPAP or FP-CPAP)., Methods/design: We designed a multicenter, non-blinded, randomized controlled trial that will enroll 230 premature infants (22 0/7 to 29 6/7 weeks of gestation). Infants will be randomized to receive Seattle-PAP or FP-CPAP. The primary outcome is respiratory failure requiring intubation and mechanical ventilation. Secondary outcomes include measures of short- and long-term respiratory morbidity and cost-effectiveness., Discussion: This trial will assess whether Seattle-PAP is more efficacious and cost-effective than FP-CPAP in real-world practice among premature neonates., Trial Registration: ClinicalTrials.gov, NCT03085329 . Registered on 21 March 2017.

Many animals participate in biological markets, with strong evidence existing for immediate cooperative trades. In particular, grooming is often exchanged for itself or other commodities, such as coalitionary support or access to food and mates. More contentious is the possibility that nonhuman animals can rely on memories of recent events, providing contingent cooperation even when there is a temporal delay between two cooperative acts. Here we provide experimental evidence of delayed cross-commodity grooming exchange in wild dwarf mongooses ( Helogale parvula ). First, we use natural observations and social-network analyses to demonstrate a positive link between grooming and sentinel behavior (acting as a raised guard). Group members who contributed more to sentinel behavior received more grooming and had a better social-network position. We then used a field-based playback experiment to test a causal link between contributions to sentinel behavior and grooming received later in the day. During 3-h trial sessions, the perceived sentinel contributions of a focal individual were either up-regulated (playback of its surveillance calls, which are given naturally during sentinel bouts) or unmanipulated (playback of its foraging close calls as a control). On returning to the sleeping refuge at the end of the day, focal individuals received more grooming following surveillance-call playback than control-call playback and more grooming than a matched individual whose sentinel contributions were not up-regulated. We believe our study therefore provides experimental evidence of delayed contingent cooperation in a wild nonprimate species., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Linezolid is an oxazolidinone antibiotic with activity against gram-positive organisms, particularly methicillin-resistant Staphylococcus aureus (MRSA). To the best of our knowledge, there are only two case reports on rhabdomyolysis in patients treated with linezolid. Here, we describe two cases of serious rhabdomyolysis: one in a patient with septic community-acquired (CA)-MRSA pneumonia and a second case in a patient with suspected catheter-related blood stream infection.

Anthropogenic noise is an evolutionarily novel and widespread pollutant in both terrestrial and aquatic habitats. Despite increasing evidence that the additional noise generated by human activities can affect vocal communication, the majority of research has focused on the use of conspecific acoustic information, especially sexual signals. Many animals are known to eavesdrop on the alarm calls produced by other species, enhancing their likelihood of avoiding predation, but how this use of heterospecific information is affected by anthropogenic noise has received little empirical attention. Here, we use two field-based playback experiments on a habituated wild population of dwarf mongooses (Helogale parvula) to determine how anthropogenic noise influences the response of foragers to heterospecific alarm calls. We begin by demonstrating that dwarf mongooses respond appropriately to the alarm calls of sympatric chacma baboons (Papio ursinus) and tree squirrels (Paraxerus cepapi); fleeing only to the latter. We then show that mongoose foragers are less likely to exhibit this flee response to tree squirrel alarm calls during road-noise playback compared to ambient-sound playback. One explanation for the change in response is that noise-induced distraction or stress result in maladaptive behaviour. However, further analysis revealed that road-noise playback results in increased vigilance and that mongooses showing the greatest vigilance increase are those that do not subsequently exhibit a flee response to the alarm call. These individuals may therefore be acting appropriately: if the greater gathering of personal information indicates the absence of an actual predator despite an alarm call, the need to undertake costly fleeing behaviour can be avoided. Either way, our study indicates the potential for anthropogenic noise to interfere with the use of acoustic information from other species, and suggests the importance of considering how heterospecific networks are affected by this global pollutant., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Strong social bonds form between individuals in many group-living species, and these relationships can have important fitness benefits. When responding to vocalizations produced by groupmates, receivers are expected to adjust their behaviour depending on the nature of the bond they share with the signaller. Here we investigate whether the strength of the signaller-receiver social bond affects response to calls that attract others to help mob a predator. Using field-based playback experiments on a habituated population of wild dwarf mongooses (Helogale parvula), we first demonstrate that a particular vocalization given on detecting predatory snakes does act as a recruitment call; receivers were more likely to look, approach and engage in mobbing behaviour than in response to control close calls. We then show that individuals respond more strongly to these recruitment calls if they are from groupmates with whom they are more strongly bonded (those with whom they preferentially groom and forage). Our study, therefore, provides novel evidence about the anti-predator benefits of close bonds within social groups., (© 2016 The Author(s).)

Anthropogenic noise is rapidly becoming a universal environmental feature. While the impacts of such additional noise on avian sexual signals are well documented, our understanding of its effect in other terrestrial taxa, on other vocalisations, and on receivers is more limited. Little is known, for example, about the influence of anthropogenic noise on responses to vocalisations relating to predation risk, despite the potential fitness consequences. We use playback experiments to investigate the impact of traffic noise on the responses of foraging dwarf mongooses (Helogale parvula) to surveillance calls produced by sentinels, individuals scanning for danger from a raised position whose presence usually results in reduced vigilance by foragers. Foragers exhibited a lessened response to surveillance calls in traffic-noise compared to ambient-sound playback, increasing personal vigilance. A second playback experiment, using noise playbacks without surveillance calls, suggests that the increased vigilance could arise in part from the direct influence of additional noise as there was an increase in response to traffic-noise playback alone. Acoustic masking could also play a role. Foragers maintained the ability to distinguish between sentinels of different dominance class, increasing personal vigilance when presented with subordinate surveillance calls compared to calls of a dominant groupmate in both noise treatments, suggesting complete masking was not occurring. However, an acoustic-transmission experiment showed that while surveillance calls were potentially audible during approaching traffic noise, they were probably inaudible during peak traffic intensity noise. While recent work has demonstrated detrimental effects of anthropogenic noise on defensive responses to actual predatory attacks, which are relatively rare, our results provide evidence of a potentially more widespread influence since animals should constantly assess background risk to optimise the foraging-vigilance trade-off., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Cytomegalovirus reactivation can be life threatening. However, little evidence on its incidence in solid cancers is available. Therefore our single center Cytomegalovirus polymerase chain reaction database with altogether 890 CMV positive blood serum samples of mainly hematological and oncological patients was retrospectively analyzed to examine the occurrence of Cytomegalovirus reactivation in patients with solid tumors, resulting in 107 patients tested positive for Cytomegalovirus reactivation. Seventeen patients with solid cancer and a positive CMV-PCR test were identified, of which eight patients had clinically relevant CMV disease and received prompt antiviral treatment. Five patients fully recovered, but despite prompt antiviral treatment three patients died. Among these three patients two had significant co-infections (in one case EBV and in the other case Aspergillus) indicating that that CMV reactivation was at least one factor contributing to sepsis. The patient with the EBV co-infection was treated in an adjuvant therapy setting for breast cancer and died due to Cytomegalovirus and Epstein-Barr virus associated pneumonia despite intensive therapy. The other two patients had progressive disease of an underlying pancreatic cancer at the time of CMV diagnosis. One patient died due to attendant uncontrollable Aspergillus pneumonia, the other patient most likely died independent from CMV disease because of massively progressive underlying disease. Cytomegalovirus reactivation and disease might be underestimated in routine clinical practice. In our retrospective analysis we show that approximately 50 % of our patients suffering from solid cancers with a positive Cytomegalovirus polymerase chain reaction also had clinically relevant Cytomegalovirus disease requiring antiviral therapy.

Introduction: The first case of human immunodeficiency virus type 2 (HIV-2) seropositivity in Austria was confirmed in 1993 in a dually human immunodeficiency virus type 1 (HIV-1)- and HIV-2-infected patient from Ghana, who died in 2001. Before this investigation, no further HIV-2 infection was published., Methods: The aim of this study was to describe HIV-2 epidemiology in Austria, using serological and molecular techniques, and to perform a sequence analysis of the circulating viral strains., Results: Six additional cases of HIV-2 were identified from 2000 to 2009. All patients originated from high-prevalence areas. In one patient, the HIV-2 infection was revealed 11 years after initial HIV-1 diagnosis, and further analysis confirmed a dual infection., Conclusion: The HIV-2 epidemic has its epicentre in West Africa, but sociocultural issues, especially migration, are contributing to the low but continuous worldwide spread of HIV-2. Diagnosis of HIV-2 implies a different therapeutical management to avoid treatment failure and clinical progression. Differential diagnosis of HIV-1 and HIV-2 is complicated due to antibody cross-reactivity, and paradoxical findings (e.g. declining CD4 cell count despite HIV-1 suppression) may require careful reassessment, especially in patients from endemic countries.

In the past two years an enormous amount of molecular, genetic, metabolomic and mechanistic data on the host-bacterium interaction, a healthy gut microbiota and a possible role for probiotics in Clostridium difficile infection (CDI) has been accumulated. Also, new hypervirulent strains of C. difficile have emerged. Yet, clinical trials in CDI have been less promising than in antibiotic associated diarrhoea in general, with more meta-analysis than primary papers on CDI-clinical-trials. The fact that C. difficile is a spore former, producing at least three different toxins has not yet been incorporated in the rational design of probiotics for (recurrent) CDI. Here we postulate that the plethora of effects of C. difficile and the vast amount of data on the role of commensal gut residents and probiotics point towards a multistrain mixture of probiotics to reduce CDI, but also to limit (nosocomial) transmission and/or endogenous reinfection. On the basis of a retrospective chart review of a series of ten CDI patients where recurrence was expected, all patients on adjunctive probiotic therapy with multistrain cocktail (Ecologic®AAD/OMNiBiOTiC® 10) showed complete clinical resolution. This result, and recent success in faecal transplants in CDI treatment, are supportive for the rational design of multistrain probiotics for CDI.

Mycoplasma contamination is a frequent problem in chlamydial cell culture. After obtaining contradictory contamination results, we compared three commercial PCR kits for mycoplasma detection. One kit signaled contamination in mycoplasma-free Chlamydia pneumoniae cultures. Sequencing of cloned PCR products revealed primer homology with the chlamydial genome as the basis of this false-positive result.

Clostridium difficile is considered to be a leading cause of hospital-acquired diarrhea. C. difficile (CDI) infection shows a high rate of recurrence. There would have to be a predominantly monoclonal mechanism of CDI within individual patients in order for molecular epidemiologic tools such as polymerase chain reaction (PCR) ribotyping to be useful in outbreak investigation or differentiation between infection relapse versus re-infection. It was the aim of our study to determine whether CDI is of monoclonal or of polyclonal genesis. Between December 2009 and June 2010, 11 patients with nosocomial CDI were chosen arbitrarily. Five individual colonies of C. difficile were picked from each of the primary culture plates. Of 55 isolates gained, 47 were available for PCR ribotyping (eight isolates failed attempts to re-culture). Among these 47 isolates, eight different PCR ribotypes were identified. Only one of the 11 patients had a stool sample that yielded more than one ribotype (PCR ribotypes 438 and 232); this 67-year-old female cancer patient was already suffering from recurring diarrhea prior to the fatal episode of colitis which was subsequently investigated. We conclude that polyclonal infections may occasionally occur in patients with CDI. Our findings of predominantly monoclonal origin of CDI within patients suggest that molecular epidemiologic investigations can be used reliably for outbreak investigations or discrimination between relapse and re-infection.

Chlamydia pneumoniae is an intracellular bacterium that responds poorly to antibiotic treatment. Insufficient antibiotic usage leads to chronic infection, which is linked to disease processes of asthma, atherosclerosis, and Alzheimer's disease. The Chlamydia research lacks genetic tools exploited by other antimicrobial research, and thus other approaches to drug discovery must be applied. A set of 2-arylbenzimidazoles was designed based on our earlier findings, and 33 derivatives were synthesized. Derivatives were assayed against C. pneumoniae strain CWL-029 in an acute infection model using TR-FIA method at a concentration of 10 μM, and the effects of the derivatives on the host cell viability were evaluated at the same concentration. Fourteen compounds showed at least 80% inhibition, with only minor changes in host cell viability. Nine most potential compounds were evaluated using immunofluorescence microscopy on two different strains of C. pneumoniae CWL-029 and CV-6. The N-[3-(1H-benzimidazol-2-yl)phenyl]-3-methylbenzamide (42) had minimal inhibitory concentration (MIC) of 10 μM against CWL-029 and 6.3 μM against the clinical strain CV-6. This study shows the high antichlamydial potential of 2-arylbenzimidazoles, which also seem to have good characteristics for lead compounds.

Due to its dependence on intracellular development Chlamydia pneumoniae has developed numerous strategies to create an adequate environment within its host cells ensuring both chlamydial reproduction and target cell survival. The bacterium that has been related to atherogenesis due to its presence in vascular tissue is able to enter a persistent state of chronic infection in the vasculature that escapes antibiotic targeting. Ingestion of the bacterium results in severe modifications and reprogramming of signalling pathways and the metabolism of the host cell. Processes range from the prevention of direct lysosomal destruction of chlamydial inclusions to the inhibition of host cell apoptosis and an enhanced cellular glucose uptake to maintain energy-consuming mechanisms. Furthermore, infection regularly causes the development of a proinflammatory and proproliferative phenotype in the host cell in vitro, ex vivo and in vivo and own new findings suggest a detrimental proliferative loop within vascular cells upon a modified endothelin-1 axis demonstrating a potential for proatherosclerotic processes in early and progressed atherosclerosis. This review displays crucial mechanisms of Chlamydia pneumoniae-induced interactions with vascular host cell signalling cascades with an emphasis on mitogenic and inflammatory processes as well as target cell activation.

Endothelin-1 (ET-1) is a vasoactive peptide that modifies vascular function via the G-protein coupled transmembrane receptors, Endothelin-A receptor (ETAR) and Endothelin-B receptor (ETBR). Dysregulation of the ET-1 axis plays a role in atherosclerotic development as it triggers cell proliferation, inflammation, and vasoconstriction. The respiratory pathogen Chlamydia pneumoniae (Cp) has been recovered from atherosclerotic lesions, and related to atherogenesis, via activation of vascular small GTPases and leukocyte recruitment. Cp effectively reprograms host cell signalling and is able to enter an intracellular persistent state in vascular cells that is refractory to antibiotics. Upon chlamydial infection, vascular smooth muscle cells, which do not produce significant ET-1 under physiological conditions were switched into a fundamental source of ET-1 mRNA and protein in a p38-MAP-kinase-dependent pathway. Endothelial cells did not overproduce ET-1 but showed upregulation of mitogenic ETAR mRNA and protein while the counterbalancing ETBR, which regulates ET-1 clearance, remained unaffected. This disruption of the ET-1 axis was confirmed in an ex vivo mouse aortic ring model, and resulted in endothelial cell proliferation that could be abrogated by ETAR-siRNA and the selective ETAR-antagonist BQ-123. Chronic chlamydial infection of the vascular wall might represent a permanent noxious stimulus linked to the endothelial cell proliferation characteristic of early atherosclerosis. Suppression of this deleterious paracrine loop by ETAR antagonism opens up a new option of preventing possible vascular sequelae of otherwise untreatable chronic chlamydial infection. In conclusion, this is the first study to demonstrate infection to dysregulate the ET-1 axis towards inducing a proatherogenic proliferative phenotype.

Since its description in 1986, Chlamydia pneumoniae has remained one of the most enigmatic pathogens. This intracellular bacterium is highly seroprevalent, but rarely recovered from cell culture, it can genetically switch between a proliferative and a nonreplicative state and has been linked to a vast number of chronic diseases, most notably to atherosclerosis, as it can be found in the plaques. It has become quite clear that persistent bacteria in atherosclerotic lesions cannot be eradicated by currently available antibiotic treatments and that attempts to do so without a better understanding of the pathobiology of chlamydial persistence are futile. However, there is growing knowledge on how vascular chlamydial infection may lead to the pathological reprogramming of the host cell signaling pathways. Chlamydia pneumoniae is now well known to induce, at least in vitro, the two pathogenetic main events that define atherosclerosis: angiogenesis and inflammation. In vivo a contribution of chlamydial infection to the progression of atherosclerosis remains unproven. This minireview provides a brief overview on the proproliferative and proinflammatory effects of vascular C. pneumoniae infection and their potential link to atherogenesis.

Owing to its unique host cell-dependent development cycle, Chlamydia pneumoniae occupies an intracellular niche that enables the bacterium to survive and to multiply, secluded from both the extracellular and the cytoplasmic environments. Within its separate chlamydial inclusion, it is able to genetically switch between a replicative and a persisting non-replicative state, linking the pathogen to acute as well as chronic diseases. Although its role in acute respiratory infection has been established, a potential link between chronic vascular infection with C. pneumoniae and the development of atherosclerosis remains enigmatic, in particular because chronic chlamydial infection cannot be eradicated by antibiotics. C. pneumoniae has developed numerous mechanisms to establish an adequate growth milieu involving the type III secretion-mediated release of chlamydial effector proteins that interact with cellular structures and reprogram host cell regulatory pathways. This brief overview of these pathomechanisms focuses on chronic vascular infection.

A new bistable rotaxane, consisting of a 2,2'-bipyridine-containing thread and a ring incorporating both a bidentate chelate and a tridentate fragment, has been prepared; this complex undergoes an electrochemically driven pirouetting motion of the ring around the axis which takes place on the millisecond timescale, i.e. several orders of magnitude faster than the other copper-based machines previously described.

Rhodium(III) has been used as a templating metal center for building a [2]catenane. In the first stage, a Rh(phen)(2) motif has been incorporated into a large ring. Subsequently, a 2,2'-bipyridine derivative has been threaded through the ring, this process being driven by coordination of the chelate to the Rh(III) center. The formation of the second ring has been performed using the ring-closing metathesis approach. Contrary to the other catenanes synthesized around transition metals, the second ring is formed at the rear of the coordination unit which it contains, by cyclizing two flexible end-functionalized fragments attached at the 4 and 4' positions of the 2,2'-bipyridine chelate.

Two new copper [3]rotaxanes have been synthesized. The axes are identical for both compounds and incorporate two bidentate chelates joined together by a disulfide bridge. The rings contain either the single phen (phen = 1,10-phenanthroline) chelate or two different chelates (phen and terpy; terpy = 2,2',6',2' '-terpyridine, a tridentate chelate). The key intermediates for both synthetic routes are semi-rotaxanes obtained in high yields using the three-dimensional effect of copper(I). In the case where the wheels are heterobischelating macrocycles, large molecular motions, namely rotation or oscillation of the wheels around the axle, have been induced electrochemically. Anchoring of these two copper [3]rotaxanes on a gold electrode was carried out by standard procedures. Cleavage of the disulfide bridge and formation of monolayers of rotaxanes were evidenced by cyclic voltammetry. The adsorbed rotaxanes can be viewed as copper [2]rotaxanes for which the gold electrode surface acts as a stopper linked to one end of their axes.

[reaction: see text] The synthesis of a ruthenium[2]catenane is described. One ring includes two 1,10-phenanthroline moieties, the other a bipyridinic unit. The interlocking ring system was formed by using a double ring closing metathesis reaction. Under irradiation, a rapid and selective decoordination of the bipyridinic fragment was observed, leading to a new catenane in which the metal is only coordinated to the bis-phenanthroline moiety.

A nonsymmetrical [2]-catenane has been synthesized, with a 5-coordinated metal center (Zn(2+)) as template. One of the two rings contains a terdentate ligand (2,2',6',2' '-terpyridine) and the other one incorporates a bidentate chelate (1,10-phenanthroline). The first ring was prepared separately and, subsequently, Zn(2+) was used as the gathering and threading element to pass the stringlike component through the ring. This open-chain species bears two terminal olefins, which were reacted with Grubbs first-generation catalyst (ring-closing metathesis) to afford the desired catenane. Hydrogenation of the double bond and removal of the zinc(II) template afforded the final free [2]-catenane in 40% yield from the terdentate ligand-containing cycle and the diolefinic compound. Complexation studies on this new pentacoordinating catenane were carried out with Fe(II) or Cu(II). The most interesting observation is that the 5-coordinated complexes obtained are strongly stabilized. Their electrochemical reduction occurs at negative potentials.

Two new copper-complexed [2]catenanes have been prepared, both of which consist of two different interlocking rings. In both cases, one of the rings incorporates a disulfide bridge. The other ring contains either a single chelate (phen=1,10-phenanthroline, a bidentate ligand) or two different chelates (phen and terpy, 2,2',6',2"-terpyridine, a tridentate chelate). Deposition of these two complexes on a gold electrode surface was carried out by standard procedures, leading to reductive cleavage of the S-S bridge. The adsorbed species can be viewed as [2]catenanes for which the gold atoms of the electrode surface are an integral fragment of one of the two rings. They yield clear electrochemical responses, but no motion is observed for the catenane incorporating a phen unit and a terpy fragment in one of the two rings, regardless of the metal oxidation state. This is at odds with the behavior of the parent compound in solution, which undergoes ring-gliding motions upon electrochemical reduction or oxidation of the copper center. Near-field microscopy was used to study the deposited layers (STM and AFM). STM images suggest that the molecules do not tend to order at long range on the surface. Polarization modulation-infrared reflection absorption spectroscopy (PM-IRRAS) led to promising results: the two catenanes deposited are likely to be oriented perpendicular to the gold surface. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc&#95;2111/2002/f3636&#95;s.pdf or from the author. 1: Infrared spectra of [Cu.2]+ as a powder (black line, transmission IR spectroscopy) and as a SAM on gold (dotted line, PM-IRRAS). (Spectra offset and scaled for clarity; significant peaks marked with an asterisk.) 2: STM image (819x819 nm2) of a monolayer of [Cu.3]+ on Au(111) on mica.

Societal and governmental pressures to reduce diesel exhaust emissions are reflected in the existing and projected future heavy-duty certification standards of these emissions. Various factors affect the amount of emissions produced by a heterogeneous charge diesel engine in any given situation, but these are poorly quantified in the existing literature. The parameters that most heavily affect the emissions from compression ignition engine-powered vehicles include vehicle class and weight, driving cycle, vehicle vocation, fuel type, engine exhaust aftertreatment, vehicle age, and the terrain traveled. In addition, engine control effects (such as injection timing strategies) on measured emissions can be significant. Knowing the effect of each aspect of engine and vehicle operation on the emissions from diesel engines is useful in determining methods for reducing these emissions and in assessing the need for improvement in inventory models. The effects of each of these aspects have been quantified in this paper to provide an estimate of the impact each one has on the emissions of diesel engines.