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AbstractHost organisms can harbor microbial symbionts that defend them from pathogen infection in addition to the resistance encoded by the host genome. Here, we investigated how variation in defenses, generated from host genetic background and symbiont presence, affects the emergence of pathogen genetic diversity across evolutionary time. We passaged the opportunistic pathogen Pseudomonas aeruginosa through populations of the nematode Caenorhabditis elegans varying in genetic-based defenses and prevalence of a protective symbiont. After 14 passages, we assessed the amount of genetic variation accumulated in evolved pathogen lineages. We found that diversity begets diversity. An overall greater level of pathogen whole-genome and per-gene genetic diversity was measured in pathogens evolved in mixed host populations compared with those evolved in host populations composed of one type of defense. Our findings directly demonstrate that symbiont-generated heterogeneity in host defense can be a significant contributor to pathogen genetic variation.

Widespread antibiotic usage has resulted in the rapid evolution of drug-resistant bacterial pathogens and poses significant threats to public health. Resolving how pathogens respond to antibiotics under different contexts is critical for understanding disease emergence and evolution going forward. The impact of antibiotics has been demonstrated most directly through in vitro pathogen passaging experiments. Independent from antibiotic selection, interactions with hosts have also altered the evolutionary trajectories and fitness landscapes of pathogens, shaping infectious disease outcomes. However, it is unclear how interactions between hosts and antibiotics impact the evolution of pathogen virulence. Here, we evolved and re-sequenced Staphylococcus aureus, a major bacterial pathogen, varying exposure to host and antibiotics to tease apart the contributions of these selective pressures on pathogen adaptation. After 12 passages, S. aureus evolving in Caenorhabditis elegans nematodes exposed to a sub-minimum inhibitory concentration of antibiotic (oxacillin) became highly virulent, regardless of whether the ancestral pathogen was methicillin-resistant (MRSA) or methicillin-sensitive (MSSA). Host and antibiotic exposure selected for reduced drug susceptibility in MSSA lineages while increasing MRSA total growth outside hosts. We identified mutations in genes involved in complex regulatory networks linking virulence and metabolism, including codY , agr , and gdpP , suggesting that rapid adaptation to infect hosts may have pleiotropic effects. In particular, MSSA populations under selection from host and antibiotic accumulated mutations in the global regulator gene codY , which controls biofilm formation in S. aureus. These populations had indeed evolved more robust biofilms-a trait linked to both virulence and antibiotic resistance-suggesting evolution of one trait can confer multiple adaptive benefits. Despite evolving in similar environments, MRSA and MSSA populations proceeded on divergent evolutionary paths, with MSSA populations exhibiting more similarities across replicate populations. Our results underscore the importance of considering multiple and concurrent selective pressures as drivers of pervasive pathogen traits.

Introduction: Oral hygiene is a crucial factor in oral health, especially in children. To increase the awareness of oral care behaviour among children, oral care motivation plays a critical role in daily dental practices. Therefore, this cross-sectional study was conducted to investigate the current oral hygiene status and evaluate the association between oral care motivation and oral hygiene index in 7-9-year-old children at Primary School in Hanoi, Vietnam., Methods: Clinical examinations were performed on 200 randomly selected children to assess the Simplified Oral Hygiene Index (OHI-S). Face-to-face interviews were applied to record students' intrinsic and extrinsic motivation for oral care through a questionnaire, which consisted of questions regarding demographic characteristics and oral care motivation. Data were analyzed using STATA 15.0 software and a p-value < 0.05 was statistically significant., Results: The mean OHI-S score was 2.48 ± 0.72. Good and fair oral hygiene were observed in 7.5 % and 66 % of participants, respectively. Students' motivation for dental care was predominantly extrinsic, with a mean score of 15.87 ± 1.322. Higher motivation in dental care is statistically significantly associated with oral hygiene index score (Coef=-0.27)., Conclusion: These results indicate that students with intrinsic motivation exhibit better oral hygiene practices. Consequently, strengthening oral health educational programs in primary schools based on intrinsic motivation could be helped improve the oral hygiene status and oral care behaviours of children., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Incomplete immunity in recovered hosts is predicted to favor more virulent pathogens upon re-infection in the population. 1 The microbiota colonizing animals can generate a similarly long-lasting, partial immune response, allowing for infection but dampened disease severity. 2 We tracked the evolutionary trajectories of a widespread pathogen (Pseudomonas aeruginosa), experimentally passaged through populations of nematodes immune-primed by a natural microbiota member (P. berkeleyensis). This bacterium can induce genes regulated by a mitogen-activated protein kinase (MAPK) signaling pathway effective at conferring protection against pathogen-induced death despite infection. 3 Across host populations, this incomplete immunity selected for pathogens more than twice as likely to kill as those evolved in non-primed (i.e., naive) or immune-compromised (mutants with a knockout of the MAPK ortholog) control populations. Despite the higher virulence, pathogen molecular evolution in immune-primed hosts was slow and constrained. In comparison, evolving pathogens in immune-compromised hosts were characterized by substantial genomic differentiation and attenuated virulence. These findings directly attribute the incomplete host immunity induced from microbiota as a significant force shaping the virulence and evolutionary dynamics of novel infectious diseases., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Symbiosis can benefit hosts in numerous ways, but less is known about whether interactions with hosts benefit symbionts-the smaller species in the relationship. To determine the fitness impact of host association on symbionts in likely mutualisms, we conducted a meta-analysis across 91 unique host-symbiont pairings under a range of spatial and temporal contexts. Specifically, we assess the consequences to symbiont fitness when in and out of symbiosis, as well as when the symbiosis is under suboptimal or varying environments and biological conditions (e.g., host age). We find that some intracellular symbionts associated with protists tend to have greater fitness when the symbiosis is under stressful conditions. Symbionts of plants and animals did not exhibit this trend, suggesting that symbionts of multicellular hosts are more robust to perturbations. Symbiont fitness also generally increased with host age. Lastly, we show that symbionts able to proliferate in- and outside host cells exhibit greater fitness than those found exclusively inside or outside cells. The ability to grow in multiple locations may thus help symbionts thrive. We discuss these fitness patterns in light of host-driven factors, whereby hosts exert influence over symbionts to suit their own needs., Supplementary Information: The online version contains supplementary material available at 10.1007/s13199-024-00984-6., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2024.)

Global climate change has led to more extreme thermal events. Plants and animals harbour diverse microbial communities, which may be vital for their physiological performance and help them survive stressful climatic conditions. The extent to which microbiome communities change in response to warming or cooling may be important for predicting host performance under global change. Using a meta-analysis of 1377 microbiomes from 43 terrestrial and aquatic species, we found a decrease in the amplicon sequence variant-level microbiome phylogenetic diversity and alteration of microbiome composition under both experimental warming and cooling. Microbiome beta dispersion was not affected by temperature changes. We showed that the host habitat and experimental factors affected microbiome diversity and composition more than host biological traits. In particular, aquatic organisms-especially in marine habitats-experienced a greater depletion in microbiome diversity under cold conditions, compared to terrestrial hosts. Exposure involving a sudden long and static temperature shift was associated with microbiome diversity loss, but this reduction was attenuated by prior-experimental lab acclimation or when a ramped regime (i.e., warming) was used. Microbial differential abundance and co-occurrence network analyses revealed several potential indicator bacterial classes for hosts in heated environments and on different biome levels. Overall, our findings improve our understanding on the impact of global temperature changes on animal and plant microbiome structures across a diverse range of habitats. The next step is to link these changes to measures of host fitness, as well as microbial community functions, to determine whether microbiomes can buffer some species against a more thermally variable and extreme world., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Defensive symbionts protect their hosts against imminent threats. A new study uncovers a symbiosis whereby a fungus safeguards its beetle host from predation, but also exploits the beetle as a vector to help it attack plants and cause disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Virtually all organisms are colonized by microbes. Average temperatures are rising because of global climate change - accompanied by increases in extreme climatic events and heat shock - and symbioses with microbes may determine species persistence in the 21st century. Although parasite infection typically reduces host upper thermal limits, interactions with beneficial microbes can facilitate host adaptation to warming. The effects of warming on the ecology and evolution of the microbial symbionts remain understudied but are important for understanding how climate change might affect host health and disease. We present a framework for untangling the contributions of symbiosis to predictions of host persistence in the face of global change., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Many host organisms live in polymicrobial environments and must respond to a diversity of pathogens. The degree to which host defences towards one pathogen species affect susceptibility to others is unclear. We used a panel of Caenorhabditis elegans nematode isolates to test for natural genetic variation in fitness costs of immune upregulation and pathogen damage, as well as for trade-offs in defence against two pathogen species, Staphylococcus aureus and Pseudomonas aeruginosa. We examined the fitness impacts of transient pathogen exposure (pathogen damage and immune upregulation) or exposure to heat-killed culture (immune upregulation only) by measuring host population sizes, which allowed us to simultaneously capture changes in reproductive output, developmental time and survival. We found significant decreases in population sizes for hosts exposed to live versus heat-killed S. aureus and found increased reproductive output after live P. aeruginosa exposure, compared with the corresponding heat-killed challenge. Nematode isolates with relatively higher population sizes after live P. aeruginosa infection produced fewer offspring after live S. aureus challenge. These findings reveal that wild C. elegans genotypes display a trade-off in defences against two distinct pathogen species that are evident in subsequent generations., (© 2022 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.)

Reciprocal adaptation between hosts and symbionts can drive the maintenance of symbioses, resulting in coevolution and beneficial genotypic interactions. Consequently, hosts may experience decreased fitness when paired with nonsympatric partners compared to sympatric symbionts. However, coevolution does not preclude conflict-host and symbiont can act to advance their own fitness interests, which do not necessarily align with those of their partner. Despite coevolution's importance in extant symbioses, we know little about its role in shaping the origin of symbioses. Here, we tested the role of coevolution in establishing a novel association by experimentally (co)evolving a host with a protective bacterium under environmental stress. Although evolution in the presence of nonevolving bacteria facilitated host adaptation, co-passaged hosts did not exhibit greater adaptation rates than hosts paired with nonevolving bacteria. Furthermore, co-passaged hosts exhibited greater fecundity when paired with sympatric, co-passaged bacteria compared to co-passaged bacteria with which they did not share an evolutionary history. Thus, shared evolutionary history between the hosts and microbes actually reduced host fitness and has the potential to impede evolution of new beneficial associations., (© 2022 The Authors. Evolution published by Wiley Periodicals LLC on behalf of The Society for the Study of Evolution.)

Protective symbionts can defend hosts from parasites through several mechanisms, from direct interference to modulating host immunity, with subsequent effects on host and parasite fitness. While research on symbiont-mediated immune priming (SMIP) has focused on ecological impacts and agriculturally important organisms, the evolutionary implications of SMIP are less clear. Here, we review recent advances made in elucidating the ecological and molecular mechanisms by which SMIP occurs. We draw on current works to discuss the potential for this phenomenon to drive host, parasite, and symbiont evolution. We also suggest approaches that can be used to address questions regarding the impact of immune priming on host-microbe dynamics and population structures. Finally, due to the transient nature of some symbionts involved in SMIP, we discuss what it means to be a protective symbiont from ecological and evolutionary perspectives and how such interactions can affect long-term persistence of the symbiosis.

Background: There is still limited data on severe recurrent pneumonia in children, especially in developing countries as Vietnam. This study was conducted to identify the underlying causes and clinical profile of children with severe recurrent pneumonia admitted to the Pediatric Intensive Care Unit (PICU), National Children's Hospital., Methods: This was a prospective and descriptive study on 110 children with severe pneumonia admitted to the PICU from November 2019 to August 2020. Data were collected to investigate the clinical profile and underlying diseases., Results: Severe recurrent pneumonia accounted for 29.4%. Underlying causes were diagnosed in 91.8% of sRP children, in which the most common causes were abnormalities in respiratory, cardiovascular system and immune disorders. 74.5% of sRP children admitted to ICU had been previously intubated or ventilated, 34.5% had shock, 7.3% had multiple organ failure. Recurrent lesions on chest x-ray in the same lobe accounted for 18.2%., Conclusions: The majority of patients with severe recurrent pneumonia had an underlying disease. Comprehensive management is necessary for severe recurrent pneumonia., (© 2021 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

Protective symbionts can allow hosts to occupy otherwise uninhabitable niches. Despite the importance of symbionts in host evolution, we know little about how these associations arise. Encountering a microbe that can improve host fitness in a stressful environment may favor persistent interactions with that microbe, potentially facilitating a long-term association. The bacterium Bacillus subtilis protects Caenorhabditis elegans nematodes from heat shock by increasing host fecundity compared to the nonprotective Escherichia coli . In this study, we ask how the protection provided by the bacterium affects the host's evolutionary trajectory. Because of the stark fitness contrast between hosts heat shocked on B. subtilis versus E. coli , we tested whether the protection conferred by the bacteria could increase the rate of host adaptation to a stressful environment. We passaged nematodes on B. subtilis or E. coli , under heat stress or standard conditions for 20 host generations of selection. When assayed under heat stress, we found that hosts exhibited the greatest fitness increase when evolved with B. subtilis under stress compared to when evolved with E. coli or under standard (nonstressful) conditions. Furthermore, despite not directly selecting for increased B. subtilis fitness, we found that hosts evolved to harbor more B. subtilis as they adapted to heat stress. Our findings demonstrate that the context under which hosts evolve is important for the evolution of beneficial associations and that protective microbes can facilitate host adaptation to stress. In turn, such host adaptation can benefit the microbe., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Evolution Letters published by Wiley Periodicals LLC on behalf of Society for the Study of Evolution (SSE) and European Society for Evolutionary Biology (ESEB).)

Immune system processes serve as the backbone of animal defences against pathogens and thus have evolved under strong selection and coevolutionary dynamics. Most microorganisms that animals encounter, however, are not harmful, and many are actually beneficial. Selection should act on hosts to maintain these associations while preventing exploitation of within-host resources. Here, we consider how several key aspects of beneficial symbiotic associations may shape host immune system evolution. When host immunity is used to regulate symbiont populations, there should be selection to evolve and maintain targeted immune responses that recognize symbionts and suppress but not eliminate symbiont populations. Associating with protective symbionts could relax selection on the maintenance of redundant host-derived immune responses. Alternatively, symbionts could facilitate the evolution of host immune responses if symbiont-conferred protection allows for persistence of host populations that can then adapt. The trajectory of immune system evolution will likely differ based on the type of immunity involved, the symbiont transmission mode and the costs and benefits of immune system function. Overall, the expected influence of beneficial symbiosis on immunity evolution depends on how the host immune system interacts with symbionts, with some interactions leading to constraints while others possibly relax selection on immune system maintenance. This article is part of the theme issue 'The role of the microbiome in host evolution'.

Microbes can provide their hosts with protection from biotic and abiotic factors. While many studies have examined how certain bacteria can increase host lifespan, fewer studies have examined how host reproduction can be altered. The nematode Caenorhabditis elegans has been a particularly useful model system to examine how bacteria affect the fitness of their hosts under different contexts. Here, we examine how the bacterium Bacillus subtilis , compared to the standard C. elegans lab diet, Escherichia coli , affects C. elegans survival and reproduction after experiencing a period of intense heat stress. We find that under standard conditions, nematodes reared on B .  subtilis produce fewer offspring than when reared on E .  coli .However, despite greater mortality rates on B .  subtilis after heat shock, young adult nematodes produced more offspring after heat shock when fed B .  subtilis compared to E. coli . Because offspring production is necessary for host population growth and evolution, the reproductive advantage conferred by B .  subtilis supersedes the survival advantage of E. coli . Furthermore, we found that nematodes must be reared on B .  subtilis (particularly at the early stages of development) and not merely be exposed to the bacterium during heat shock, to obtain the reproductive benefits provided by B .  subtilis . Taken together, our findings lend insight into the importance of environmental context and interaction timing in shaping the protective benefits conferred by a microbe toward its host., Competing Interests: The authors declare no competing interests.

Aphids, like most animals, mount a diverse set of defenses against pathogens. For aphids, two of the best studied defenses are symbiont-conferred protection and transgenerational wing induction. Aphids can harbor bacterial symbionts that provide protection against pathogens, parasitoids and predators, as well as against other environmental stressors. In response to signals of danger, aphids also protect not themselves but their offspring by producing more winged than unwinged offspring as a way to ensure that their progeny may be able to escape deteriorating conditions. Such transgenerational wing induction has been studied most commonly as a response to overcrowding of host plants and presence of predators, but recent evidence suggests that pea aphids (Acyrthosiphon pisum) may also begin to produce a greater proportion of winged offspring when infected with fungal pathogens. Here, we explore this phenomenon further by asking how protective symbionts, pathogen dosage and environmental conditions influence this response. Overall, while we find some evidence that protective symbionts can modulate transgenerational wing induction in response to fungal pathogens, we observe that transgenerational wing induction in response to fungal infection is highly variable. That variability cannot be explained entirely by symbiont association, by pathogen load or by environmental stress, leaving the possibility that a complex interplay of genotypic and environmental factors may together influence this trait., Competing Interests: Nicole Gerardo, one of the authors of this manuscript, was a PLOS ONE editor until 2014. This does not alter the authors’adherence to all the PLOS ONE policies on sharing data and materials.

The principles underlying smooth and effortless human walking while maintaining stability as well as the ability to quickly respond to unexpected perturbations result from a plethora of well-balanced parameters, most of them yet to be determined. In this paper, we investigate criteria that may be useful for benchmarking stability properties of human walking. We perform dynamic reconstructions of human walking motions of unimpaired subjects and subjects walking with transfemoral prostheses from motion capture recordings using optimal control. We aim at revealing subject-specific strategies in applying dynamics in order to maintain steady gait considering irregularities such as deviating gait patterns or asymmetric body segment properties. We identify foot placement with respect to the Instantaneous Capture Point as the strategy globally applied by the subjects to obtain steady gait and propose the Residual Orbital Energy as a measure allowing for benchmarking human-like gait toward confident vs. cautious gait., (Copyright © 2018 Ho Hoang, Wolf and Mombaur.)

Sit to stand (STS) transfers form a challenging type of motion, in particular for geriatric patients. Physical assistive devices that are built to enhance the mobility of this class of patients therefore must especially be able to support STS transfers. This paper presents a method to predict geriatric STS movements and compute the best possible actions by external devices to support these movements. We treat three types of active devices that act on different parts of the patient's body and provide different levels of support. Our approach is based on the solution of optimal control problems for a whole-body multi-phase model of humans standing up from sitting to upright position. Computations are performed for percentiles 20/50/80 of male and female geriatric population. The actions of the external devices are simulated by external forces at moving contact points, which are all determined by the optimization, simultaneously with the expected movements and joint torques of the patients. The results serve as inputs for design optimizations of the different device types., (Copyright © 2017. Published by Elsevier Ltd.)

Soybean C 3 photosynthesis can suffer a severe loss in efficiency due to photorespiration and the lack of a carbon concentrating mechanism (CCM) such as those present in other plant species or cyanobacteria. Transgenic soybean (Glycine max cv. Thorne) plants constitutively expressing cyanobacterial ictB (inorganic carbon transporter B) gene were generated using Agrobacterium-mediated transformation. Although more recent data suggest that ictB does not actively transport HCO3-/CO 2 , there is nevertheless mounting evidence that transformation with this gene can increase higher plant photosynthesis. The hypothesis that expression of the ictB gene would improve photosynthesis, biomass production and seed yield in soybean was tested, in two independent replicated greenhouse and field trials. Results showed significant increases in photosynthetic CO 2 uptake (A net ) and dry mass in transgenic relative to wild type (WT) control plants in both the greenhouse and field trials. Transgenic plants also showed increased photosynthetic rates and biomass production during a drought mimic study. The findings presented herein demonstrate that ictB, as a single-gene, contributes to enhancement in various yield parameters in a major commodity crop and point to the significant role that biotechnological approaches to increasing photosynthetic efficiency can play in helping to meet increased global demands for food., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Microorganisms play a significant role in the evolution and functioning of the eukaryotes with which they interact. Much of our understanding of beneficial host-microbe interactions stems from studying already established associations; we often infer the genotypic and environmental conditions that led to the existing host-microbe relationships. However, several outstanding questions remain, including understanding how host and microbial (internal) traits, and ecological and evolutionary (external) processes, influence the origin of beneficial host-microbe associations. Experimental evolution has helped address a range of evolutionary and ecological questions across different model systems; however, it has been greatly underutilized as a tool to study beneficial host-microbe associations. In this review, we suggest ways in which experimental evolution can further our understanding of the proximate and ultimate mechanisms shaping mutualistic interactions between eukaryotic hosts and microbes. By tracking beneficial interactions under defined conditions or evolving novel associations among hosts and microbes with little prior evolutionary interaction, we can link specific genotypes to phenotypes that can be directly measured. Moreover, this approach will help address existing puzzles in beneficial symbiosis research: how symbioses evolve, how symbioses are maintained, and how both host and microbe influence their partner's evolutionary trajectories. By bridging theoretical predictions and empirical tests, experimental evolution provides us with another approach to test hypotheses regarding the evolution of beneficial host-microbe associations.

Dynamic modeling of the human body is an important tool to investigate the fundamentals of the biomechanics of human movement. To model the human body in terms of a multi-body system, it is necessary to know the anthropometric parameters of the body segments. For young healthy subjects, several data sets exist that are widely used in the research community, e.g. the tables provided by de Leva. None such comprehensive anthropometric parameter sets exist for elderly people. It is, however, well known that body proportions change significantly during aging, e.g. due to degenerative effects in the spine, such that parameters for young people cannot be used for realistically simulating the dynamics of elderly people. In this study, regression equations are derived from the inertial parameters, center of mass positions, and body segment lengths provided by de Leva to be adjustable to the changes in proportion of the body parts of male and female humans due to aging. Additional adjustments are made to the reference points of the parameters for the upper body segments as they are chosen in a more practicable way in the context of creating a multi-body model in a chain structure with the pelvis representing the most proximal segment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Polysubstituted indolizine derivatives are constructed via intramolecular CN bond formation/CH bond cleavage under metal-free conditions. These methods offer straightforward pathways to transform pyridyl chalcones into a variety of indolizines., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Sudden cardiac death (SCD) has been shown to be a significant cause of death after heart transplantation. QT dispersion (QTd) is associated with SCD in several high-risk populations. We hypothesized that QTd would predict mortality and SCD in heart transplantation patients., Methods: We examined the clinical charts and most recent electrocardiograms (ECGs) for patients who received heart transplants at Stanford University Medical Center during the period 1981-1995. QTd was measured with all 12 leads and the precordial leads. Analysis was performed by a single reader blinded to patient outcomes., Results: A total of 346 patients who had undergone transplantation had available ECGs and known outcomes; 155 of these patients died, and 42 of these deaths were attributed to SCD. The 12-lead mean QTd was not significantly different between outcome groups: patients who survived had a 12-lead mean QTd of 58 +/- 29 milliseconds and those who died had a 12-lead mean QTd of 61 +/- 32 milliseconds (P = .57). Patients who died from SCD had a 12-lead mean QTd of 57 +/- 31 milliseconds (P = .40), and those who died of other causes had a 12-lead mean QTd of 59 +/- 34 milliseconds (P = .36 vs those who died of SCD). Similarly, the precordial-lead mean QTd did not differ significantly between the different outcome groups., Conclusions: We found no correlation between QTd and SCD or mortality in heart transplant recipients. Until additional studies prove a positive association, QTd should not be used as a prognostic marker in these patients.

Right bundle branch block (RBBB) is the most common electrocardiographic abnormality in heart transplant recipients, but the cause remains unknown, data regarding the prognosis are conflicting, and all previous studies have been limited to <100 patients. This was a study of patients who underwent heart transplantation at Stanford University Medical Center from 1981 to 1995 with known outcomes and >or=2 available electrocardiograms (ECGs). Outcomes were assessed in those with and without conduction disturbances recorded from the ECGs closest to the time of transplantation and the most recent ECGs. Of the 322 heart transplant recipients studied, 141 (44%) died over a mean follow-up of 9 +/- 3.5 years, and 40 (13%) died of sudden cardiac death. In the first ECG obtained, a mean of 1.8 +/- 2.4 years after transplantation, 44 patients (14%) had incomplete RBBB and 26 (8%) had RBBB; in the second ECG, obtained a mean of 5.6 +/- 3.7 years after transplantation, 59 patients (18%) had incomplete RBBB and 63 (20%) had RBBB. Increasing time from transplantation was associated with a greater likelihood for RBBB on the first and second ECGs (p = 0.001 and p <0.0001, respectively). QRS duration, incomplete RBBB, RBBB, or the development of RBBB was not associated with mortality or sudden cardiac death. In conclusion, although RBBB was the most common electrocardiographic abnormality in our study, the prevalence was lower than previously reported. The cause of RBBB appears to be largely related to events that occur well after transplantation, and the prognosis is benign.

The importance of leptospirosis in Southeast Asia was assessed in conjunction with other studies supported by the U.S. Naval Medical Research Unit No. 2 (US NAMRU-2), Jakarta, Republic of Indonesia. These included studies of hospital-based, acute clinical jaundice in Indonesia, Lao PDR, and Socialist Republic of Vietnam; nonmalarial fever in Indonesia; and hemorrhagic fever in Cambodia. Background prevalence estimates of leptospiral infection were obtained by a cross-sectional, community-based study in Lao PDR. Laboratory testing methods involved serology, microscopic agglutination test, and reverse-transcriptase polymerase chain reaction. Suggestive evidence of recent leptospiral infections was detected in 17%, 13%, and 3% of patients selected on the basis of non-hepatitis A through E jaundice, nonmalarial fever, and hemorrhagic fever (in the absence of acute, dengue viral infections). Leptospiral IgG antibody, reflective of prior infections, was detected in 37% of human sera, collected in Lao PDR. The predominant leptospiral serogroups identified from cases with clinical jaundice were Hurstbridge, Bataviae, and Icterohaemorrhagiae tonkini LT 96 69. Among the nonmalarial febrile cases, Bataviae was the most frequently recognized serogroup. Pyrogenes and Hurstbridge were the principal serogroups among the hemorrhagic fever case subjects. These findings further attest to the relative importance of clinical leptospirosis in Southeast Asia. The wide spectrum of clinical signs and symptoms associated with probable, acute, leptospiral infections contributes to the potential of significant underreporting.