Evolution, Medicine, and Public Health最新文献

{"title":"Autism and psychosis as diametrical disorders of embodiment.","authors":"Bernard Crespi,&nbsp;Natalie Dinsdale","doi":"10.1093/emph/eoz021","DOIUrl":"https://doi.org/10.1093/emph/eoz021","url":null,"abstract":"<p><p>Humans have evolved an elaborate system of self-consciousness, self-identity, self-agency, and self-embodiment that is grounded in specific neurological structures including an expanded insula. Instantiation of the bodily self has been most-extensively studied via the 'rubber hand illusion', whereby parallel stimulation of a hidden true hand, and a viewed false hand, leads to the felt belief that the false hand is one's own. Autism and schizophrenia have both long been regarded as conditions centrally involving altered development of the self, but they have yet to be compared directly with regard to the self and embodiment. Here, we synthesize the embodied cognition literature for these and related conditions, and describe evidence that these two sets of disorders exhibit opposite susceptibilities from typical individuals to the rubber hand illusion: reduced on the autism spectrum and increased in schizophrenia and other psychotic-affective conditions. Moreover, the opposite illusion effects are mediated by a consilient set of associated phenomena, including empathy, interoception, anorexia risk and phenotypes, and patterns of genetic correlation. Taken together, these findings: (i) support the diametric model of autism and psychotic-affective disorders, (ii) implicate the adaptive human system of self-embodiment, and its neural bases, in neurodevelopmental disorders, and suggest new therapies and (iii) experimentally ground Bayesian predictive coding models with regard to autism compared with psychosis. Lay summary: Humans have evolved a highly developed sense of self and perception of one's own body. The 'rubber hand illusion' can be used to test individual variation in sense of self, relative to connection with others. We show that this illusion is reduced in autism spectrum disorders, and increased in psychotic and mood disorders. These findings have important implications for understanding and treatment of mental disorders.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2019 1","pages":"121-138"},"PeriodicalIF":3.7,"publicationDate":"2019-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoz021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41195846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in mutational processes and intra-tumour heterogeneity between organs: The local selective filter hypothesis.","authors":"Mathieu Giraudeau, Tuul Sepp, Beata Ujvari, François Renaud, Aurélie Tasiemski, Benjamin Roche, Jean-Pascal Capp, Frédéric Thomas","doi":"10.1093/emph/eoz017","DOIUrl":"10.1093/emph/eoz017","url":null,"abstract":"<p><p>Extensive diversity (genetic, cytogenetic, epigenetic and phenotypic) exists within and between tumours, but reasons behind these variations, as well as their consistent hierarchical pattern between organs, are poorly understood at the moment. We argue that these phenomena are, at least partially, explainable by the evolutionary ecology of organs' theory, in the same way that environmental adversity shapes mutation rates and level of polymorphism in organisms. Organs in organisms can be considered as specialized ecosystems that are, for ecological and evolutionary reasons, more or less efficient at suppressing tumours. When a malignancy does arise in an organ applying strong selection pressure on tumours, its constituent cells are expected to display a large range of possible surviving strategies, from hyper mutator phenotypes relying on bet-hedging to persist (high mutation rates and high diversity), to few poorly variable variants that become invisible to natural defences. In contrast, when tumour suppression is weaker, selective pressure favouring extreme surviving strategies is relaxed, and tumours are moderately variable as a result. We provide a comprehensive overview of this hypothesis. Lay summary: Different levels of mutations and intra-tumour heterogeneity have been observed between cancer types and organs. Anti-cancer defences are unequal between our organs. We propose that mostly aggressive neoplasms (i.e. higher mutational and ITH levels), succeed in emerging and developing in organs with strong defences.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2019 1","pages":"139-146"},"PeriodicalIF":3.3,"publicationDate":"2019-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41195862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association analysis uncovers variants for reproductive variation across dog breeds and links to domestication.","authors":"Samuel P Smith, Julie B Phillips, Maddison L Johnson, Patrick Abbot, John A Capra, Antonis Rokas","doi":"10.1093/emph/eoz015","DOIUrl":"10.1093/emph/eoz015","url":null,"abstract":"<p><strong>Background and objectives: </strong>The diversity of eutherian reproductive strategies has led to variation in many traits, such as number of offspring, age of reproductive maturity and gestation length. While reproductive trait variation has been extensively investigated and is well established in mammals, the genetic loci contributing to this variation remain largely unknown. The domestic dog, <i>Canis lupus familiaris</i> is a powerful model for studies of the genetics of inherited disease due to its unique history of domestication. To gain insight into the genetic basis of reproductive traits across domestic dog breeds, we collected phenotypic data for four traits, cesarean section rate, litter size, stillbirth rate and gestation length, from primary literature and breeders' handbooks.</p><p><strong>Methodology: </strong>By matching our phenotypic data to genomic data from the Cornell Veterinary Biobank, we performed genome-wide association analyses for these four reproductive traits, using body mass and kinship among breeds as covariates.</p><p><strong>Results: </strong>We identified 12 genome-wide significant associations between these traits and genetic loci, including variants near <i>CACNA2D3</i> with gestation length, <i>MSRB3</i> and <i>MSANTD1</i> with litter size, <i>SMOC2</i> with cesarean section rate and <i>UFM1</i> with stillbirth rate. A few of these loci, such as <i>CACNA2D3</i> and <i>MSRB3</i>, have been previously implicated in human reproductive pathologies, whereas others have been associated with domestication-related traits, including brachycephaly (<i>SMOC2</i>) and coat curl (<i>KRT71</i>).</p><p><strong>Conclusions and implications: </strong>We hypothesize that the artificial selection that gave rise to dog breeds also influenced the observed variation in their reproductive traits. Overall, our work establishes the domestic dog as a system for studying the genetics of reproductive biology and disease.</p><p><strong>Lay summary: </strong>The genetic contributors to variation in mammalian reproductive traits remain largely unknown. We took advantage of the domestic dog, a powerful model system, to test for associations between genome-wide variants and four reproductive traits (cesarean section rate, litter size, stillbirth rate and gestation length) that vary extensively across breeds. We identified associations at a dozen loci, including ones previously associated with domestication-related traits, suggesting that selection on dog breeds also influenced their reproductive traits.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2019 1","pages":"93-103"},"PeriodicalIF":3.3,"publicationDate":"2019-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10407873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionary origins of polycystic ovary syndrome: An environmental mismatch disorder.","authors":"Mia A Charifson, Benjamin C Trumble","doi":"10.1093/emph/eoz011","DOIUrl":"10.1093/emph/eoz011","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder and has important evolutionary implications for female reproduction and health. PCOS presents an interesting paradox, as it results in significant anovulation and potential sub-fecundity in industrialized populations, yet it has a surprisingly high prevalence and has a high heritability. In this review, we discuss an overview of PCOS, current diagnostic criteria, associated hormonal pathways and a review of proposed evolutionary hypotheses for the disorder. With a multifactorial etiology that includes ovarian function, metabolism, insulin signaling and multiple genetic risk alleles, PCOS is a complex disorder. We propose that PCOS is a mismatch between previously neutral genetic variants that evolved in physically active subsistence settings that have the potential to become harmful in sedentary industrialized environments. Sedentary obesogenic environments did not exist in ancestral times and exacerbate many of these pathways, resulting in the high prevalence and severity of PCOS today. Overall, the negative impacts of PCOS on reproductive success would likely have been minimal during most of human evolution and unlikely to generate strong selection. Future research and preventative measures should focus on these gene-environment interactions as a form of evolutionary mismatch, particularly in populations that are disproportionately affected by obesity and metabolic disorders.</p><p><strong>Lay summary: </strong>The most severe form of polycystic ovary syndrome (PCOS) is likely a result of interactions between genetic predispositions for PCOS and modern obesogenic environments. PCOS would likely have been less severe ancestrally and the fitness reducing effects of PCOS seen today are likely a novel product of sedentary, urban environments.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2019 1","pages":"50-63"},"PeriodicalIF":3.3,"publicationDate":"2019-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41195863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to genes that improved fitness also cost modern humans: evidence for genes with antagonistic effects on longevity and disease.","authors":"Steven N Austad,&nbsp;Jessica M Hoffman","doi":"10.1093/emph/eoz003","DOIUrl":"https://doi.org/10.1093/emph/eoz003","url":null,"abstract":"Byars and Voskarides, responding to our review of empirical support for George Williams’ antagonistic pleiotropy (AP) theory of the evolution of aging [1], feel that we have ‘failed to acknowledge’ recent human studies supporting the theory. Indeed, we mentioned no human studies because we had intended our review to present only the strongest evidence supporting the theory which has been done almost entirely in laboratory model organisms. For this reason, while we mentioned a few studies from natural populations, we emphasized how such nonexperimental studies could be consistent with the AP mechanisms, but could not be cleanly attributed to it. Thus, we focused on experimental studies—those in which experimental manipulation of a single gene had clear antagonistic effects on fitness components in early versus late life as Williams predicted. Experimental studies establish cause-and-effect in a way that correlational studies such as those cited by Byars and Voskarides cannot. It is an unfortunate truth about research on humans that because experimental studies are often impossible, results are almost inevitably correlational, which in our view makes virtually any single study highly suggestive at best, but never compelling. To illustrate why, we consider one of the studies adduced by Byars and Voskarides, although we could have chosen any of the others. That study identifies numerous human alleles (or Single nucleotide Polymorphisms) pre-disposing individuals to coronary artery disease (CAD) but also conferring reproductive advantages early in life [2]. As to the nature of the evidence they presented, they identified a correlation, e.g. signs of positive correspondence 7","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2019 1","pages":"7-8"},"PeriodicalIF":3.7,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoz003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9289676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial comment: Pre-eclampsia.","authors":"Gillian R Bentley","doi":"10.1093/emph/eoy030","DOIUrl":"https://doi.org/10.1093/emph/eoy030","url":null,"abstract":"P re-eclampsia (PE), marked symptomatically by increased blood pressure, renal or liver insufficiency, cerebral disturbances, excessive protein in urine (proteinuria) or low platelet levels and edema is a potentially fatal condition that affects a small proportion (estimated at 4.6%) of women around the globe [1]. Risk for women is increased by twin or higher gestations, age, primipaternity, an elevated body mass index, metabolic disorders and smoking among other factors [1]. The pathophysiology of this disease is otherwise not well understood; treatment is limited to alleviating symptoms and, in more severe cases, inducing labour or performing pre-term C-sections [2]. Maternal mortality associated with the condition is low relative to deaths experienced during labour and delivery, but presumably higher in regions where good medical facilities are absent. Due to the relatively small numbers of women who experience PE, it would be rarely documented among populations such as hunter-gatherers where lifestyles are presumably closer to those in which our species evolved. Apes (with among the most highly invasive trophoblasts) are the only species thought to experience this condition [3]. Evolutionary perspectives on this condition emerged with David Haig’s publication on parental genetic conflicts [4]. He argued that paternally derived genes will attempt to mediate additional resources to aid foetal growth, while maternally derived genes will attempt to control these resources in the interest of future reproductive effort. It is this conflict that, allegedly, leads to PE in mid-to-late pregnancy. Clinical studies of PE generally do not contextualize its potential evolutionary origin, but focus instead on potential proximate causes for the condition such as twin or higher gestations, age, smoking and metabolic disorders, although some sources acknowledge risk factors such as primipaternity which may also have an adaptive function. Clinical Briefs in EMPH provide short reviews of evolutionary approaches to pathologies or conditions in order to broaden the scope of thinking in medicine and public health, and that could help in finding novel treatments. Serendipitiously, two complementary Clinical Briefs on the topic of PE were simultaneously submitted to EMPH by separate sets of authors [5, 6]; we are publishing them together and briefly highlight specific contrasts. Although both focus on the genetic conflict model described above as well as immunological dysfunctions known to increase risk for PE, Varas Enriquez et al. (2018) also discuss how the nutritional requirements of large-brained infants may have exacerbated genetic conflicts during gestation. They draw attention to the suggestion that low rates of human fecundability function to increase sexual exposure to partners prior to conception, thereby lowering PE risk. editorial 295","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"295-296"},"PeriodicalIF":3.7,"publicationDate":"2018-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoy030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36812539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variation among populations in the immune protein composition of mother's milk reflects subsistence pattern.","authors":"Laura D Klein, Jincui Huang, Elizabeth A Quinn, Melanie A Martin, Alicia A Breakey, Michael Gurven, Hillard Kaplan, Claudia Valeggia, Grazyna Jasienska, Brooke Scelza, Carlito B Lebrilla, Katie Hinde","doi":"10.1093/emph/eoy031","DOIUrl":"10.1093/emph/eoy031","url":null,"abstract":"<p><strong>Lay summary: </strong>Adaptive immune proteins in mothers' milk are more variable than innate immune proteins across populations and subsistence strategies. These results suggest that the immune defenses in milk are shaped by a mother's environment throughout her life.</p><p><strong>Background and objectives: </strong>Mother's milk contains immune proteins that play critical roles in protecting the infant from infection and priming the infant's developing immune system during early life. The composition of these molecules in milk, particularly the acquired immune proteins, is thought to reflect a mother's immunological exposures throughout her life. In this study, we examine the composition of innate and acquired immune proteins in milk across seven populations with diverse disease and cultural ecologies.</p><p><strong>Methodology: </strong>Milk samples (<i>n</i> = 164) were collected in Argentina, Bolivia, Nepal, Namibia, Philippines, Poland and the USA. Populations were classified as having one of four subsistence patterns: urban-industrialism, rural-shop, horticulturalist-forager or agro-pastoralism. Milk innate (lactalbumin, lactoferrin and lysozyme) and acquired (Secretory IgA, IgG and IgM) protein concentrations were determined using triple-quadrupole mass spectrometry.</p><p><strong>Results: </strong>Both innate and acquired immune protein composition in milk varied among populations, though the acquired immune protein composition of milk differed more among populations. Populations living in closer geographic proximity or having similar subsistence strategies (e.g. agro-pastoralists from Nepal and Namibia) had more similar milk immune protein compositions. Agro-pastoralists had different milk innate immune protein composition from horticulturalist-foragers and urban-industrialists. Acquired immune protein composition differed among all subsistence strategies except horticulturist-foragers and rural-shop.</p><p><strong>Conclusions and implications: </strong>Our results reveal fundamental variation in milk composition that has not been previously explored in human milk research. Further study is needed to understand what specific aspects of the local environment influence milk composition and the effects this variation may have on infant health outcomes.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"230-245"},"PeriodicalIF":3.7,"publicationDate":"2018-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36725470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is antagonistic pleiotropy ubiquitous in aging biology?","authors":"Steven N Austad,&nbsp;Jessica M Hoffman","doi":"10.1093/emph/eoy033","DOIUrl":"10.1093/emph/eoy033","url":null,"abstract":"<p><p>Lay Summary: An evolutionary mechanism of aging was hypothesized 60 years ago to be the genetic trade-off between early life fitness and late life mortality. Genetic evidence supporting this hypothesis was unavailable then, but has accumulated recently. These tradeoffs, known as antagonistic pleiotropy, are common, perhaps ubiquitous. George Williams' 1957 paper developed the antagonistic pleiotropy hypothesis of aging, which had previously been hinted at by Peter Medawar. Antagonistic pleiotropy, as it applies to aging, hypothesizes that animals possess genes that enhance fitness early in life but diminish it in later life and that such genes can be favored by natural selection because selection is stronger early in life even as they cause the aging phenotype to emerge. No genes of the sort hypothesized by Williams were known 60 years ago, but modern molecular biology has now discovered hundreds of genes that, when their activity is enhanced, suppressed, or turned off, lengthen life and enhance health under laboratory conditions. Does this provide strong support for Williams' hypothesis? What are the implications of Williams' hypothesis for the modern goal of medically intervening to enhance and prolong human health? Here we briefly review the current state of knowledge on antagonistic pleiotropy both under wild and laboratory conditions. Overall, whenever antagonistic pleiotropy effects have been seriously investigated, they have been found. However, not all trade-offs are directly between reproduction and longevity as is often assumed. The discovery that antagonistic pleiotropy is common if not ubiquitous implies that a number of molecular mechanisms of aging may be widely shared among organisms and that these mechanisms of aging can be potentially alleviated by targeted interventions.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"287-294"},"PeriodicalIF":3.7,"publicationDate":"2018-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoy033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36760304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An ecosystem framework for understanding and treating disease.","authors":"Michael E Hochberg","doi":"10.1093/emph/eoy032","DOIUrl":"https://doi.org/10.1093/emph/eoy032","url":null,"abstract":"<p><p>Pathogens and cancers are pervasive health risks in the human population. I argue that if we are to better understand disease and its treatment, then we need to take an ecological perspective of disease <i>itself</i>. I generalize and extend an emerging framework that views disease as an ecosystem and many of its components as interacting in a community. I develop the framework for biological etiological agents (BEAs) that multiply within humans-focusing on bacterial pathogens and cancers-but the framework could be extended to include other host and parasite species. I begin by describing why we need an ecosystem framework to understand disease, and the main components and interactions in bacterial and cancer disease ecosystems. Focus is then given to the BEA and how it may proceed through characteristic states, including emergence, growth, spread and regression. The framework is then applied to therapeutic interventions. Central to success is preventing BEA evasion, the best known being antibiotic resistance and chemotherapeutic resistance in cancers. With risks of evasion in mind, I propose six measures that either introduce new components into the disease ecosystem or manipulate existing ones. An ecosystem framework promises to enhance our understanding of disease, BEA and host (co)evolution, and how we can improve therapeutic outcomes.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"270-286"},"PeriodicalIF":3.7,"publicationDate":"2018-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoy032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36776466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influenza, evolution, and the next pandemic.","authors":"David S Fedson","doi":"10.1093/emph/eoy027","DOIUrl":"https://doi.org/10.1093/emph/eoy027","url":null,"abstract":"<p><p>Mortality rates in influenza appear to have been shaped by evolution. During the 1918 pandemic, mortality rates were lower in children compared with adults. This mortality difference occurs in a wide variety of infectious diseases. It has been replicated in mice and might be due to greater tolerance of infection, not greater resistance. Importantly, combination treatment with inexpensive and widely available generic drugs (e.g. statins and angiotensin receptor blockers) might change the damaging host response in adults to a more tolerant response in children. These drugs might work by modifying endothelial dysfunction, mitochondrial biogenesis and immunometabolism. Treating the host response might be the only practical way to reduce global mortality during the next influenza pandemic. It might also help reduce mortality due to seasonal influenza and other forms of acute critical illness. To realize these benefits, we need laboratory and clinical studies of host response treatment before and after puberty.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"260-269"},"PeriodicalIF":3.7,"publicationDate":"2018-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoy027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36748365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}