Early-Life Disease Exposure and Its Heterogeneous Effects on Mortality Throughout Life: Sweden, 1905-2016.

Exposure to infectious diseases in early life has been linked to increased mortality risk in later life in high-disease settings, such as eighteenth- and nineteenth-century Europe. Less is known about the long-term effects of early-life disease exposure in milder disease environments. This study estimates heterogeneous effects from disease exposure in infancy on later-life mortality in twentieth-century Sweden, by socioeconomic status at birth and sex. Using historical population data for southern Sweden, we study 11,515 individuals who were born in 1905-1929 from age 1 until age 85. We measure exposure to disease using the local post-early neonatal mortality rate in the first 12 months after birth and apply flexible parametric survival models. For females, we find a negative effect on life expectancy (scarring) at ages 1-85 following high disease exposure in infancy, particularly for those born to unskilled workers. For males, we find no negative effect on later-life survival, likely because stronger mortality selection in infancy outweighs scarring. Thus, even as the incidence of infectious diseases declined at the start of the twentieth century, early-life disease exposure generated long-lasting negative but heterogeneous population health effects.

Adding Epidemiologically Important Meteorological Data to Peanut Rx, the Risk Assessment Framework for Spotted Wilt of Peanut.

Management of disease affecting peanut in the southeastern United States has benefited from extensive field research identifying disease-associated risk factors since the 1990s. An assessment of risk factors associated with tomato spotted wilt (TSW), caused by tomato spotted wilt virus and spread exclusively by thrips, is available to growers through Peanut Rx, a tool developed to inform peanut management decisions. Peanut Rx provides an assessment of relative TSW risk as an index. The assessment provides information about the relative degree to which a field characterized by a specified suite of practices is at risk of crop loss caused by TSW. Loss results when infection occurs, and infection rates are determined, in part, by factors outside a grower's control, primarily the abundance of dispersing, viruliferous thrips. In this study, we incorporated meteorological variables useful for predicting thrips dispersal, increasing the robustness of the Peanut Rx framework in relation to variation in the weather. We used data from field experiments and a large grower survey to estimate the relationships between weather and TSW risk mediated by thrips vectors, and developed an addition to Peanut Rx that proved informative and easy to implement. The expected temporal occurrence of major thrips flights, as a function of heat and precipitation, was translated into the existing risk-point system of Peanut Rx. Results from the grower survey further demonstrated the validity of Peanut Rx for guiding growers' decisions to minimize risk of TSW.

Trends in African Americans' Attitudes and Behaviors About Living Donor Kidney Transplantation.

BACKGROUND: Due to marginal efforts to increase living donor kidney transplantation, it is unclear whether interventions to improve African Americans' interest and pursuit of living donation should be tailored to address patients' exposure to or familiarity with dialysis or transplant settings. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional secondary analysis of baseline data from 3 separate randomized clinical trials among African Americans with varying degrees of experience with dialysis or transplantation (predialysis, on dialysis but not on transplant list, and on transplant wait-list) settings. METHODS: Interest in living donation was described using a 0 to 10 scale and pursuit of living donor kidney transplantation by achievement of at least 1 pursuant behavior. In multivariable logistic regression analyses, we assessed the association of knowledge, health literacy, and trust in health care with interest in or pursuit of living donation. RESULTS: Interest among the 3 study cohorts was high (predialysis, 62.9%; dialysis, 67.4%; and transplant wait-list, 74.2%). The dialysis and transplant wait-list study cohorts pursued living donation more readily than those not on dialysis (73%, 92%, and 45%, respectively). Interest and pursuit were not statistically significantly associated with knowledge, health literacy, or the 3 factors reflecting medical mistrust. CONCLUSION: Interest and pursuit of living donation were greater among study participants with greater exposure to dialysis or transplant settings. Efforts to promote patients' early interest and pursuit of living donor transplants may consider novel strategies to educate patients with less experience about the benefits of living donor kidney transplantation.

Immuno-spin trapping from biochemistry to medicine: advances, challenges, and pitfalls. Focus on protein-centered radicals.

BACKGROUND: Immuno-spin trapping (IST) is based on the reaction of a spin trap with a free radical to form a stable nitrone adduct, followed by the use of antibodies, rather than traditional electron paramagnetic resonance spectroscopy, to detect the nitrone adduct. IST has been successfully applied to mechanistic in vitro studies, and recently, macromolecule-centered radicals have been detected in models of drug-induced agranulocytosis, hepatotoxicity, cardiotoxicity, and ischemia/reperfusion, as well as in models of neurological, metabolic and immunological diseases. SCOPE OF THE REVIEW: To critically evaluate advances, challenges, and pitfalls as well as the scientific opportunities of IST as applied to the study of protein-centered free radicals generated in stressed organelles, cells, tissues and animal models of disease and exposure. MAJOR CONCLUSIONS: Because the spin trap has to be present at high enough concentrations in the microenvironment where the radical is formed, the possible effects of the spin trap on gene expression, metabolism and cell physiology have to be considered in the use of IST and in the interpretation of results. These factors have not yet been thoroughly dealt with in the literature. GENERAL SIGNIFICANCE: The identification of radicalized proteins during cell/tissue response to stressors will help define their role in the complex cellular response to stressors and pathogenesis; however, the fidelity of spin trapping/immuno-detection and the effects of the spin trap on the biological system should be considered. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.

Genetic Analyses of Response of Local Ghanaian Tanzanian Chicken Ecotypes to a Natural Challenge with Velogenic Newcastle Disease Virus.

Newcastle disease is a devastating poultry disease that often causes significant economic losses in poultry in the developing countries of Africa, Asia, as well as South and Central America. Velogenic Newcastle disease virus (NDV) outbreaks are associated with high mortalities, which can threaten household livelihoods, especially in the rural areas, and lead to loss of high-quality proteins in the form of meat and eggs, as well as household purchasing power. In this study, we exposed unvaccinated Ghanaian and Tanzanian chickens of six local ecotypes to velogenic NDV strains, measured NDV response traits, sequenced their DNA on a genotyping-by-sequencing platform, and performed variance component analyses. The collected phenotypes included: growth rates (pre- and post-exposure); lesion scores (gross lesion severity) in the trachea, proventriculus, intestine, and cecal tonsils; natural antibody levels; anti-NDV antibody levels at 7 days post exposure (dpe); tear and cloacal viral load at 2, 4, and 6 dpe; and survival time. Heritability estimates were low to moderate, ranging from 0.11 for average lesion scores to 0.36 for pre-exposure growth rate. Heritability estimates for survival time were 0.23 and 0.27 for the Tanzanian and Ghanaian ecotypes, respectively. Similar heritability estimates were observed when data were analyzed either separately or combined for the two countries. Survival time was genetically negatively correlated with lesion scores and with viral load. Results suggested that response to mesogenic or velogenic NDV of these local chicken ecotypes could be improved by selective breeding. Chickens that are more resilient to velogenic NDV can improve household livelihoods in developing countries.

Can disease resistance evolve independently at different ages? Genetic variation in age-dependent resistance to disease in three wild plant species.

Juveniles are typically less resistant (more susceptible) to infectious disease than adults, and this difference in susceptibility can help fuel the spread of pathogens in age-structured populations. However, evolutionary explanations for this variation in resistance across age remain to be tested.One hypothesis is that natural selection has optimized resistance to peak at ages where disease exposure is greatest. A central assumption of this hypothesis is that hosts have the capacity to evolve resistance independently at different ages. This would mean that host populations have (a) standing genetic variation in resistance at both juvenile and adult stages, and (b) that this variation is not strongly correlated between age classes so that selection acting at one age does not produce a correlated response at the other age.Here we evaluated the capacity of three wild plant species (Silene latifolia, S. vulgaris and Dianthus pavonius) to evolve resistance to their anther-smut pathogens (Microbotryum fungi), independently at different ages. The pathogen is pollinator transmitted, and thus exposure risk is considered to be highest at the adult flowering stage.Within each species we grew families to different ages, inoculated individuals with anther smut, and evaluated the effects of age, family and their interaction on infection.In two of the plant species, S. latifolia and D. pavonius, resistance to smut at the juvenile stage was not correlated with resistance to smut at the adult stage. In all three species, we show there are significant age × family interaction effects, indicating that age specificity of resistance varies among the plant families. Synthesis. These results indicate that different mechanisms likely underlie resistance at juvenile and adult stages and support the hypothesis that resistance can evolve independently in response to differing selection pressures as hosts age. Taken together our results provide new insight into the structure of genetic variation in age-dependent resistance in three well-studied wild host-pathogen systems.

How Does the Social Grouping of Animals in Nature Protect Against Sickness? A Perspective.

Sickness behavior is broadly represented in vertebrates, usually in association with the fever response in response to acute infections. The reactions to sickness behavior in a group member or potential group member in humans is quite variable, depending upon circumstances. In animals, the reactions to sickness behavior in a group member or potential group member evoke a specific response that reflects the species-specific lifestyle. Groups of animals can employ varied strategies to reduce or address exposure to sickness. Most of these have scarcely been studied in nature from a disease perspective: (1) adjusting exposure to sick conspecifics or contaminated areas; (2) caring for a sick group member; (3) peripheralization and agonistic behaviors to strange non-group conspecifics; and (4) using special strategies at parturition when newborn are healthy but vulnerable. Unexplored in this regard is infanticide, where newborn that are born with very little immunity until they receive antibody-rich colostrum, could be a target of maternal infanticide if they manifest signs of sickness and could be infectious to littermates. The strategies used by different species are highly specific and dependent upon the particular circumstances. What is needed is a more general awareness and consideration of the possibilities that avoiding or adapting to sickness behavior may be driving some social behaviors of animals in nature.

Early life effects across the life course: the impact of individually defined exogenous measures of disease exposure on mortality by sex in 19th- and 20th-century Southern Sweden.

Using micro-level longitudinal data from Southern Sweden for 1813 to 1968, this work evaluates the effect of exposure to disease in early life on mortality over the entire life course and separately by sex. The local rates of post-early neonatal mortality are considered indicators of early life disease exposure, and these rates are calculated specifically for each person based on birth date. The loss in median remaining life among exposed individuals who survived to age 1 is 1.1 years for females and 2.1 years for males. Exposed individuals show a cross-over from lower to higher relative mortality as they age. This change occurs in adulthood for males and in old age for females. During adulthood, exposed males present higher rates of death than exposed females. These results are new to the literature and shed light on the importance of adopting a full life course approach and capturing sex differences when evaluating the long-term impacts of early life exposures.