Annals of periodontology最新文献

{"title":"Periodontitis and Diabetes Interrelationships: Role of Inflammation","authors":"Anthony M. Iacopino Dr.","doi":"10.1902/annals.2001.6.1.125","DOIUrl":"10.1902/annals.2001.6.1.125","url":null,"abstract":"<p>Diabetes mellitus is a systemic disease with several major complications affecting both the quality and length of life. One of these complications is periodontal disease (periodontitis). Periodontitis is much more than a localized oral infection. Recent data indicate that periodontitis may cause changes in systemic physiology. The interrelationships between periodontitis and diabetes provide an example of systemic disease predisposing to oral infection, and once that infection is established, the oral infection exacerbates systemic disease. In this case, it may also be possible for the oral infection to predispose to systemic disease. In order to understand the cellular/molecular mechanisms responsible for such a cyclical association, one must identify common physiological changes associated with diabetes and periodontitis that produce a synergy when the conditions coexist. A potential mechanistic link involves the broad axis of inflammation, specifi-cally immune cell phenotype, serum lipid levels, and tissue homeostasis. Diabetes-induced changes in immune cell function produce an inflammatory immune cell phenotype (upregulation of proinflammatory cytokines from monocytes/polymorphonuclear leukocytes and downregulation of growth factors from macrophages). This predisposes to chronic inflammation, progressive tissue breakdown, and diminished tissue repair capacity. Periodontal tissues frequently manifest these changes because they are constantly wounded by substances emanating from bacterial biofilms. Diabetic patients are prone to elevated low density lipoprotein cholesterol and triglycerides (LDL/TRG) even when blood glucose levels are well controlled. This is significant, as recent studies demonstrate that hyperlipidemia may be one of the factors associated with diabetes-induced immune cell alterations. Recent human studies have established a relationship between high serum lipid levels and periodontitis. Some evidence now suggests that periodontitis itself may lead to elevated LDL/TRG. Periodontitis-induced bacteremia/endotoxemia has been shown to cause elevations of serum proinflammatory cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), which have been demonstrated to produce alterations in lipid metabolism leading to hyperlipidemia. Within this context, periodontitis may contribute to elevated proinflammatory cytokines/serum lipids and potentially to systemic disease arising from chronic hyperlipidemia and/or increased inflammatory mediators. These cytokines can produce an insulin resistance syndrome similar to that observed in diabetes and initiate destruction of pancreatic β cells leading to development of diabetes. Thus, there is potential for periodontitis to exacerbate diabetes-induced hyperlipidemia, immune cell alterations, and diminished tissue repair capacity. It may also be possible for chronic periodontitis to induce diabetes. <i>Ann Periodontol 2001;6:125-137.</i></p>","PeriodicalId":79473,"journal":{"name":"Annals of periodontology","volume":"6 1","pages":"125-137"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1902/annals.2001.6.1.125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68174869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periodontal Disease and Pregnancy: Discussion, Conclusions, and Recommendations","authors":"Gary C. Armitage Dr.","doi":"10.1902/annals.2001.6.1.189","DOIUrl":"10.1902/annals.2001.6.1.189","url":null,"abstract":"","PeriodicalId":79473,"journal":{"name":"Annals of periodontology","volume":"6 1","pages":"189-192"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1902/annals.2001.6.1.189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68174973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Candidate Genes as Potential Links Between Periodontal and Cardiovascular Diseases","authors":"Kenneth S. Kornman Dr.,&nbsp;Gordon W. Duff","doi":"10.1902/annals.2001.6.1.48","DOIUrl":"10.1902/annals.2001.6.1.48","url":null,"abstract":"<p>Recent epidemiological associations between periodontal disease and cardiovascular disease have led to a search for biological mechanisms that explain the associations. Genetic factors that influence biological processes involved in both diseases represent one of the potential mechanisms that may link periodontitis and cardiovascular disease. At present, several candidate genes have been investigated in one of the diseases but not the other. Although there are limited data to support a specific candidate gene as the explanation for observed associations between the 2 diseases, a few candidates look promising. One candidate that influences inflammation, interleukin-1 gene polymorphisms, has been associated with periodontal disease and cardiovascular disease. This review will consider biological mechanisms and genes that may be reasonable candidates for an etiological mechanism that influences the clinical characteristics of both periodontal disease and cardiovascular disease. <i>Ann Periodontol 2001;6:48-57.</i></p>","PeriodicalId":79473,"journal":{"name":"Annals of periodontology","volume":"6 1","pages":"48-57"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1902/annals.2001.6.1.48","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68178721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional Interrelationships Between Diabetes and Periodontal Diseases: An Epidemiologic Perspective","authors":"George W. Taylor Dr.","doi":"10.1902/annals.2001.6.1.99","DOIUrl":"10.1902/annals.2001.6.1.99","url":null,"abstract":"<p>This review evaluates evidence for a bidirectional relationship between diabetes and periodontal diseases. A comprehensive Medline search of the post-1960 English language literature was employed to identify primary research reports of relationships between diabetes and periodontal diseases. Reports included in the review on the adverse effects of diabetes on periodontal health (DM→PD) were restricted to those comparing periodontal health in subjects with and without diabetes. Review of adverse affects of periodontal infection on glycemic control included reports of periodontal treatment studies and follow-up observational studies in which changes in glycemic control could be assessed. Observational studies reporting DM→PD provided consistent evidence of greater prevalence, severity, extent, or progression of at least one manifestation of periodontal diseases in the large majority of reports (supportive evidence in 44/48 total reviewed; 37/41 cross-sectional and 7/7 cohort). Additionally, there were no studies reviewed with superior design features to refute this association. Treatment studies provided direct evidence to support periodontal infection having an adverse, yet modifiable, effect on glycemic control. However, not all investigations reported an improvement in glycemic control after periodontal treatment. Additional evidence to support the effect of severe periodontitis on increased risk for poorer glycemic control comes from 2 follow-up observational studies. The evidence reviewed supports viewing the relationship between diabetes and periodontal diseases as bidirectional. Further rigorous, systematic study is warranted to establish that treating periodontal infections can be influential in contributing to glycemic control management and possibly to the reduction of the burden of complications of diabetes mellitus. <i>Ann Periodontol 2001;6:99-112.</i></p>","PeriodicalId":79473,"journal":{"name":"Annals of periodontology","volume":"6 1","pages":"99-112"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1902/annals.2001.6.1.99","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68179699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relationship Between Infections and Adverse Pregnancy Outcomes: An Overview","authors":"Ronald S. Gibbs Dr.","doi":"10.1902/annals.2001.6.1.153","DOIUrl":"10.1902/annals.2001.6.1.153","url":null,"abstract":"<p>Preterm birth with its subsequent morbidity and mortality is the leading perinatal problem in the United States. Infants born before the thirty-seventh week of gestation account for approximately 6% to 9% of all births, but 70% of all perinatal deaths and half of all long-term neurologic morbidity. Current approaches focus on symptomatic treatment. Despite widespread use of drugs to arrest preterm labor (tocolytics), there has been no decrease in low birth weight or preterm infants in the last 20 years. It is likely that therapy directed at preventing or treating underlying causes would be more successful. Evidence from many sources links preterm birth to symptomatic infections, for example, of the urinary or respiratory tracts. In the last decade, great interest has been generated to support the hypothesis that subclinical infection is an important cause of preterm labor. Evidence to support this may be categorized as follows: histological chorioamnionitis is increased in preterm births; clinical infection is increased after preterm birth; there is significant association of some lower genital tract organisms and infections with preterm birth or preterm premature rupture of the membranes; there are positive cultures of amniotic fluid or membranes from some patients with preterm labor and preterm birth; there are markers of infections in preterm birth; bacteria or their products induce preterm birth in animal models; and some antibiotic trials have shown a lower rate of preterm birth or have deferred preterm birth. In the last 5 years, additional exciting information has suggested that not only is subclinical infection responsible for preterm birth but also many serious neonatal sequelae including periventricular leukomalacia, cerebral palsy, respiratory distress, and even bronchopulmonary dysplasia and necrotizing enterocolitis. In sum, a large body of clinical and laboratory information suggests that subclinical infection is a major cause of preterm birth, especially those occurring before 30 weeks. This concept holds promise that new approaches can be developed to prevent prematurity. <i>Ann Periodontol 2001;6:153-163.</i></p>","PeriodicalId":79473,"journal":{"name":"Annals of periodontology","volume":"6 1","pages":"153-163"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1902/annals.2001.6.1.153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68175278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relationship Between Skeletal and Oral Bone Mineral Density: An Overview","authors":"Charles H. Chesnut III Dr.","doi":"10.1902/annals.2001.6.1.193","DOIUrl":"10.1902/annals.2001.6.1.193","url":null,"abstract":"<p>Is oral osteopenia (bone loss of the jaws) a component of systemic osteopenia/osteoporosis (systemic bone loss, with or without fracture) or only an accompanying manifestation of periodontal disease? Put other ways: 1) is systemic osteopenia a risk factor for periodontitis; 2) is systemic osteopenia a risk factor for oral osteopenia independent of periodontal disease; or 3) is periodontal disease the primary (exclusive) risk factor for oral osteopenia? Despite 2 decades of scientific inquiry into these questions, the answers remain elusive. <i>Ann Periodontol 2001;6: 193-196.</i></p>","PeriodicalId":79473,"journal":{"name":"Annals of periodontology","volume":"6 1","pages":"193-196"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1902/annals.2001.6.1.193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68176860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Bacteria and Respiratory Infection: Effects on Respiratory Pathogen Adhesion and Epithelial Cell Proinflammatory Cytokine Production","authors":"Frank A. Scannapieco Dr.,&nbsp;Bingyan Wang,&nbsp;Harlan J. Shiau","doi":"10.1902/annals.2001.6.1.78","DOIUrl":"10.1902/annals.2001.6.1.78","url":null,"abstract":"<p>Several microbiologic and epidemiologic studies have suggested an association between dental plaque, poor oral health, and respiratory diseases such as nosocomial pneumonia and chronic obstructive pulmonary disease (COPD). A number of hypotheses are suggested to help explain how oral bacteria may participate in the pathogenesis of respiratory infection. Resident bacteria in oral secretions are likely aspirated along with respiratory pathogens and may affect the adhesion of the later organisms to the respiratory epithelium. Preliminary studies performed in our laboratory suggest that oral bacteria may modulate the adhesion of respiratory pathogens to epithelial cell lines. In addition, oral bacterial products or cytokines in oral/pharyngeal aspirates may stimulate cytokine production from respiratory epithelial cells, resulting in recruitment of inflammatory cells. The resulting inflamed epithelium may be more susceptible to respiratory infection. Further preliminary data are presented that some species of oral bacteria may induce the release of proinflammatory cytokines from epithelial cell lines to an extent similar to that seen for respiratory pathogens. <i>Ann Periodontol 2001;6:78-86.</i></p>","PeriodicalId":79473,"journal":{"name":"Annals of periodontology","volume":"6 1","pages":"78-86"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1902/annals.2001.6.1.78","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68178785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Periodontal Disease and Control of Diabetes: An Assessment of the Evidence and Need for Future Research","authors":"Sara G. Grossi Dr.","doi":"10.1902/annals.2001.6.1.138","DOIUrl":"10.1902/annals.2001.6.1.138","url":null,"abstract":"<p>Evidence points to an increased cytokine response in type 2 diabetes, especially the proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Genetics, age, and, nutrition are important signals for this increased response and as reported more recently, infections and inflammation. Persistent elevation of IL-1β, IL-6, and TNF-α in the diabetic state have an effect on the liver, stimulate the release of acute-phase proteins, produce the characteristic dysregulation of lipid metabolism associated with type 2 diabetes, and have effects on pancreatic beta cells as well. In addition, TNF-α, a potent inhibitor of the tyrosine kinase activity of the insulin receptor, has been implicated as an etiologic factor for insulin resistance. Collectively, the evidence supports a role for cytokine elevation in the pathophysiology and metabolic abnormalities associated with diabetes. Periodontitis is an infection that is twice as prevalent in diabetic individuals compared to non-diabetics. <i>Porphyromonas gingivalis</i>, one of the microorganisms responsible for this infection, is able to invade endothelial cells and is a potent signal for monocyte and macrophage activation. Thus, once established in the diabetic host, this chronic infection complicates diabetes control and increases the occurrence and severity of microvascular and macrovascular complications. Unlike treatment of acute infections, modalities of treatment for chronic infections are a matter of debate. Evidence indicates that mechanical removal of subgingival infection does not result in complete elimination of periodontal infection and consequently there is no effect on diabetes control measured as reduction in glycated hemoglobin. On the other hand, studies incorporating systemic antibiotics as adjuncts to mechanical debridement result in a reduction of <i>P. gingivalis</i> to nondetectable levels and a concomitant reduction in glycated hemoglobin, independent of the hypoglycemic effects of diabetes drugs or insulin. The evidence supports the notion that treatment of chronic periodontal infection is essential in the diabetic patient. Assessment of infection status in diabetic patients is fundamental for appropriate treatment decisions. <i>Ann Periodontol 2001;6:138-145.</i></p>","PeriodicalId":79473,"journal":{"name":"Annals of periodontology","volume":"6 1","pages":"138-145"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1902/annals.2001.6.1.138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68175002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Periodontal Diseases and Cardiovascular Diseases: A State-of-the-Science Review","authors":"James D. Beck Dr.,&nbsp;Steven Offenbacher","doi":"10.1902/annals.2001.6.1.9","DOIUrl":"10.1902/annals.2001.6.1.9","url":null,"abstract":"<p>Early case-control and cross-sectional studies demonstrating associations between chronic periodontitis and cardiovascular disease (CVD) were quickly followed by secondary analyses of data available from existing longitudinal studies, which indicated that individuals with periodontitis, as determined by clinical measures, were at greater risk for CVD events. Many of these studies contained large numbers of subjects and were adjusted for traditional risk factors. Within the last 18 months, one case-control study and one longitudinal study have reported finding positive associations that were not statistically significant. The earlier studies stimulated a number of studies focused on identifying potential biological mechanisms that might underlie this association. While still early in that process, such studies have implicated a systemic role for oral microorganisms and for the quality and quantity of the host inflammatory response as key biologic processes that may underlie the association of CVD with the clinical manifestation of periodontitis. It is a positive development when changes in our knowledge regarding biologic mechanisms result in reevaluation of past studies, and this reevaluation leads to new studies that incorporate the design elements demanded by this new knowledge. In that spirit, we conclude that all longitudinal studies reported to date can be characterized as follows: none were initially designed to actually test the association of interest; almost all were restricted to clinical measures of periodontitis to index the exposure and lacked measures of infectious burden and host response; and they used a variety of cardiovascular clinical events to index the outcome and did not include subclinical measures of atherosclerosis. In addition, the longitudinal studies that failed to show a significant association between periodontitis and CVD used the least sensitive and crudest clinical measures of periodontal disease. Based upon the current state-of-the-science, all previous studies should be viewed as lacking sufficiently sensitive and comprehensive measures of periodontal disease as a systemic exposure. Since the potential health care impact of this relationship might be extensive, it is time to enter the next phase of research by conducting molecular epidemiology studies that are appropriately designed to test our current understanding of the molecular and cellular mechanisms involved. <i>Ann Periodontol 2001;6:9-15.</i></p>","PeriodicalId":79473,"journal":{"name":"Annals of periodontology","volume":"6 1","pages":"9-15"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1902/annals.2001.6.1.9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68178923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal periodontitis and prematurity. Part II: Maternal infection and fetal exposure.","authors":"Robert P. N. Madianos, S. Lieff, A. Murtha, K. Boggess, R. Auten, J. Beck, S. Offenbacher","doi":"10.1097/01.OGX.0000074320.16796.CE","DOIUrl":"https://doi.org/10.1097/01.OGX.0000074320.16796.CE","url":null,"abstract":"Clinical data from the first 812 deliveries from a cohort study of pregnant mothers entitled Oral Conditions and Pregnancy (OCAP) demonstrate that both antepartum maternal periodontal disease and incidence/progression of periodontal disease are associated with preterm birth and growth restriction after adjusting for traditional obstetric risk factors. In the current study we present measures of maternal periodontal infection using whole chromosomal DNA probes to identify 15 periodontal organisms within maternal periodontal plaque sampled at delivery. In addition, maternal postpartum IgG antibody and fetal exposure, as indexed by fetal cord blood IgM level to these 15 maternal oral pathogens, was measured by whole bacterial immunoblots. The potential role of maternal infection with specific organisms within 2 bacterial complexes most often associated with periodontitis, conventionally termed \"Orange\" (Campylobacter rectus, Fusobacterium nucleatum, Peptostreptococcus micros, Prevotella nigrescens, and Prevotella intermedia) and \"Red\" (Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola) complexes, respectively, to prematurity was investigated by relating the presence of oral infection, maternal IgG, and fetal cord IgM, comparing full-term to preterm (gestational age < 37 weeks). The prevalence of 8 periodontal pathogens was similar among term and preterm mothers at postpartum. There was a 2.9-fold higher prevalence of IgM seropositivity for one or more organisms of the Orange or Red complex among preterm babies, as compared to term babies (19.9% versus 6.9%, respectively, P = 0.0015, chi square). Specifically, the prevalence of positive fetal IgM to C. rectus was significantly higher for preterm as compared to full-term neonates (20.0% versus 6.3%, P = 0.0002, as well as P. intermedia (8.8% versus 1.1%, P = 0.0003). A lack of maternal IgG antibody to organisms of the Red complex was associated with an increased rate of prematurity with an odds ratio (OR) = 2.2; confidence interval (CI) 1.48 to 3.79), consistent with the concept that maternal antibody protects the fetus from exposure and resultant prematurity. The highest rate of prematurity (66.7%) was observed among those mothers without a protective Red complex IgG response coupled with a fetal IgM response to Orange complex microbes (combined OR 10.3; P < 0.0001). These data support the concept that maternal periodontal infection in the absence of a protective maternal antibody response is associated with systemic dissemination of oral organisms that translocate to the fetus resulting in prematurity. The high prevalence of elevated fetal IgM to C. rectus among premature infants raises the possibility that this specific maternal oral pathogen may serve as a primary fetal infectious agent eliciting prematurity.","PeriodicalId":79473,"journal":{"name":"Annals of periodontology","volume":"6 1 1","pages":"175-82"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/01.OGX.0000074320.16796.CE","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61584852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}