The predictive value of laboratory parameters for no-reflow phenomenon in patients with ST-elevation myocardial infarction following primary percutaneous coronary intervention: A meta-analysis.

To date, the predictive role of laboratory indicators for the phenomenon of no flow is unclear. Hence, our objective was to conduct a meta-analysis to investigate the association between laboratory parameters and the risk of the no-reflow phenomenon in patients with ST-elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI). This, in turn, aims to offer valuable insights for early clinical prediction of no-reflow. We searched Pubmed, Embase, and Cochrane Library from the establishment of the database to October 2023. We included case-control or cohort study that patients with STEMI following primary PCI. We excluded repeated publication, research without full text, incomplete information or inability to conduct data extraction and animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. The pooled results indicated that elevated white blood cell (WBC) count (odds ratio [OR] = 1.061, 95% confidence interval [CI]: 1.013-1.112), neutrophil count (OR = 1.324, 95% CI: 1.128-1.553), platelet (PLT) (OR = 1.002, 95% CI: 1.000-1.005), blood glucose (OR = 1.005, 95% CI: 1.002-1.009), creatinine (OR = 1.290, 95% CI: 1.070-1.555), total cholesterol (TC) (OR = 1.022, 95% CI: 1.012-1.032), d-dimer (OR = 1.002, 95% CI: 1.001-1.004), and fibrinogen (OR = 1.010, 95% CI: 1.005-1.015) were significantly associated with increased risk of no-reflow. However, elevated hemoglobin was significantly associated with decreased risk of no-reflow. In conclusion, our comprehensive analysis highlights the predictive potential of various parameters in assessing the risk of no-reflow among STEMI patients undergoing PCI. Specifically, WBC count, neutrophil count, PLT, blood glucose, hemoglobin, creatinine, TC,  d-dimer, and fibrinogen emerged as significant predictors. This refined risk prediction may guide clinical decision-making, allowing for more targeted and effective preventive measures to mitigate the occurrence of no-reflow in this patient population.

Energy acquisition strategy for reproduction in a semelparous squid.

BACKGROUND: Energy demand for reproduction leads to a wide diversity of foraging and life-history strategy among wild animals, linking to a common objective to maximize reproductive success. Semelparous squid species in particular can use up to 50% of the total energy intake for reproduction. However, the energy acquisition strategy for reproduction is still a controversial issue regarding whether the squid shift in diet ontogenetically. Here we used Argentinean shortfin squid (Illex argentinus) as a case study to investigate the strategy of energy acquisition for reproduction, by analyzing energy density of the squid's reproductive tissues including ovary, nidamental glands and oviduct eggs, and stable isotopes and fatty acids of the squid's ovary. RESULTS: The reproductive energy (the sum of the energy accumulated in ovary, nidamental glands and oviduct eggs) increased significantly with maturation. The ovary nitrogen stable isotopes (δ15N) showed a significant increase with maturation, but the increase by maturity stage was not equal to the typical enrichment of about 3‰ per trophic level. Isotopic niche width showed an increasing trend with maturation, and isotopic niche space exhibited greater overlap at advanced maturity stages. The relative amounts of 16:0, 20:5n3 and 20:4n6 in the ovary, tracing for carnivores and top predators, increased after the onset of maturation. The overall fatty acid profiles of the ovary showed significant differences among maturity stages, but obvious overlaps were found for mature squids. Mixed-effects model results revealed that reproductive energy was positively correlated with δ15N values. The reproductive energy was also positively related to the relative amounts of 18:0 and 20:4n6, respectively tracing for herbivores and top predators. CONCLUSIONS: Our results validate that the squid shifts to feed on higher trophic prey for reproduction as energy demand increases once maturation commences. However, the squid does not shift feeding habits at a trophic level but instead broadens prey spectrum, coupled with increasing intake of higher trophic prey items, to meet the energy demand for reproduction. Such energy acquisition strategy may be selected by the squid to maximize reproductive success by balancing energy intake and expenditure from foraging, warranting future studies that aim to clarify such strategy for reproduction among semelparous species.

Fatty acid comparison of four sympatric loliginid squids in the northern South China Sea: Indication for their similar feeding strategy.

Feeding strategies of sympatric squid species help to understand their role in marine ecosystems. Four loliginid squids, Uroteuthis duvaucelii, Uroteuthis edulis, Uroteuthis chinensis, and Loliolus uyii are the major cephalopod species in the coastal waters of the northern South China Sea, where they occur together. We investigated their feeding strategies in terms of foraging behavior and habitat use by comparing fatty acid profiles and spatial distributions. There were no significant differences in the proportions of saturated or polyunsaturated fatty acids among species. Similar findings were obtained for most individual fatty acids that made up of an average of more than 84% of total fatty acid content for each species. Substantial overlap and high similarity in the fatty acid composition were observed. However, there were no significant effects of individual size or sampling station on the fatty acid compositions. The spatial overlap analysis demonstrated that there was clear spatial segregation and habitat use among the species. Cumulatively, our results suggest that the four squids are opportunistic carnivores, unselectively foraging on similar prey items, while spatial segregation is likely a major mechanism leading to their coexistence in the northern South China Sea.

Top predator reveals the stability of prey community in the western subarctic Pacific.

The stability of the ecosystems depends on the dynamics of the prey community, but changes in the composition and abundance of prey species are poorly understood, especially in open ocean ecosystems. We used neon flying squid Ommastrephes bartramii, an active top predator, as a biological sampler to investigate the dynamics of the prey community in the southwestern part of the Western Subarctic Gyre in the northwestern Pacific Ocean. Squid were collected monthly from July to November 2016. There were no significant differences among months in stable isotopes (δ13C and δ15N) in the digestive gland, a fast turnover organ reflecting recent dietary information. Similar findings were obtained from analyses of isotopic niche width and fatty acid profiles. The potential influence of the environment (monthly mean sea surface temperature, SST, and chlorophyll-a, Chl-a) on the prey community was examined with SST and Chl-a both varying significantly among sampling months. We found little evidence for significant effects of SST and Chl-a on the isotopic values, nor on the fatty acid profiles except for 20:4n6 and 24:1n9. These lines of evidence indicate that the prey community in the southwestern part of the gyre remains stable, with little evidence for systematic changes at the community level. This study provides a novel understanding of the dynamics of the prey community and highlights the use of top predators to study the trophic dynamics of an oceanic system where a long-term scientific survey is unavailable.

The breeding strategy of female jumbo squid Dosidicus gigas: energy acquisition and allocation.

Reproductive investment generally involves a trade-off between somatic growth and energy allocation for reproduction. Previous studies have inferred that jumbo squid Dosidicus gigas support growth during maturation through continuous feeding (an "income" source). However, our recent work suggests possible remobilization of soma during maturation (a "capital" source). We used fatty acids as biochemical indicators to investigate energy acquisition and allocation to reproduction for female D. gigas. We compared the fatty acid profiles of the ovary to those of the mantle muscle (slow turnover rate tissue, representing an energy reserve) and the digestive gland (fast turnover rate organ, reflecting recent consumption). For each tissue, the overall fatty acids among maturity stages overlapped and were similar. The changes with maturation in fatty acid composition in the ovary consistently resembled those of the digestive gland, with the similarity of fatty acids in the mantle muscle and the ovary increasing during maturation, indicating some energy reserves were utilized. Additionally, squid maintained body condition during maturation regardless of increasing investment in reproduction and a decline in feeding intensity. Cumulatively, D. gigas adopt a mixed income-capital breeding strategy in that energy for reproduction is mainly derived from direct food intake, but there is limited somatic reserve remobilization.

miR-410-5p promotes the development of diabetic cardiomyopathy by suppressing PIM1-induced anti-apoptosis.

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus that can cause many severe symptoms, such as heart failure, arrhythmia, and sudden death. However, the molecular mechanisms underlying cardiac dysfunction in DCM remain elusive. In this study, we found that miR-410-5p was increased in the myocardial tissue of a diabetes mellitus (DM) rat model. Further studies confirmed that inhibition of miR-410-5p reduced cell apoptosis by regulating the Bcl-2/Bax axis. Through bioinformatics analysis and luciferase reporter assays, we observed that miR-410-5p directly targets PIM1. Moreover, knockdown of miR-410-5p by antagomir-410-5p improved diabetes-induced cardiac function and myocardial tissue structure. In conclusion, our study demonstrated that miR-410-5p might be involved in the progression of DCM by targeting PIM1 and might be a promising therapeutic target for DCM in the future.

Isofraxidin Alleviates Myocardial Infarction Through NLRP3 Inflammasome Inhibition.

Isofraxidin is a well-known coumarin compound refined from traditional Chinese medicines. It has been previously demonstrated to play an anti-inflammatory role in various inflammatory conditions. However, the effect of isofraxidin on myocardial infarction (MI) remains uncovered. In this study, we aimed to investigate the effect of isofraxidin on MI. MI mice was created and triphenyltetrazolium chloride (TTC) staining as well as echocardiographic evaluation were conducted to analyze the severity of MI. Oxygen-glucose deprivation (OGD) was used for the mimics of ischemic stress in murine cardiomyocytes, and Cell Counting Kit-8 (CCK-8), Annexin V, and lactate dehydrogenase (LDH) release assays were conducted for cell viability. Western blot was used for the detection of NOD-like receptor family, pyrin domain containing 3 (NLRP3), and adapter protein apoptosis-associated speck-like protein (ASC) in heart tissues and cardiomyocytes. Real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) were applied for the detection of proinflammatory cytokines. We found that isofraxidin alleviated the severity of MI and produced a cardio-protective effect against OGD damage. Isofraxidin also decreased the overall and local inflammatory reaction in MI. Those effects were through the inhibition of the NLRP3 inflammasome. Taken together, we initially reported the cardio-protective and alleviative effect of isofraxidin on MI and uncovered its underlying mechanism related to the NLRP3 inflammasome inhibition.

The effect of esomeprazole vs famotidine on aspirin/clopidogrel dual therapy after percutaneous coronary intervention.

BACKGROUND: Regarding drug interactions between proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT), controversies have arisen over the possibility that PPIs may interfere with the antiplatelet effect of DAPT. However, whether this interaction is drug-specific or a class effect needs to be determined. It is not clear whether famotidine, an H2-receptor antagonist (H2RA), interacts with DAPT. OBJECTIVES: The aim of this study was to assess the impact of esomeprazole and famotidine on the efficacy of DAPT. MATERIAL AND METHODS: The study involved 160 patients undergoing elective percutaneous coronary interventions and treated with DAPT and concomitant use of esomeprazole (40 mg/d) or famotidine (40 mg/d). Platelet reactivity was measured with adenosine diphosphate (ADP)-induced light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) at baseline, 14 and 30 days after applying randomized acid-suppressing agents. RESULTS: No significance differences were observed in treatment-by-period interactions with LTA values (p = 0.298) and VASP-PRI values (p = 0.867), which suggested no carryover effect in either regimen over the 30-day treatment period. Intergroup comparisons were done between the 2 groups at 3 times, and similar findings were observed at each time (all p > 0.05). As for intragroup measurements among the separate times, significantly lower LTA and VASP-PRI values existed on day 14 for both agents (both p < 0.05). CONCLUSIONS: The antiplatelet effect of DAPT was not affected by concomitant use of esomeprazole or famotidine. These 2 agents were much less likely than CYP2C19 polymorphisms to influence aspirin/clopidogrel therapy, supporting the assertion that the pharmacodynamic interaction between aspirin/clopidogrel and acid-suppressing agents is a drug-specific rather than a class effect.

Association of the gene polymorphisms of BMPR2, ACVRL1, SMAD9 and their interactions with the risk of essential hypertension in the Chinese Han population.

Objective: Genetic factors are involved in the occurrence, development, and progression of essential hypertension (EH). To study the association between single nucleotide polymorphisms (SNPs) of the rs6435156 and rs1048829 loci of the bone morphogenetic protein receptor type 2 (BMPR2) gene, the rs121909287 and rs121909284 loci of the activin receptor-like kinase 1 (ACVRL1) gene, and the rs397514716 and rs121918359 loci of the mothers against decapentaplegic homolog 9 (SMAD9) gene with the risk of EH in the Chinese Han population. Materials and methods: A total of 460 EH patients and 460 healthy controls were recruited for the study. Genomic DNA of white blood cells was extracted, and the genotypes were analyzed by Sanger sequencing after polymerase chain reaction amplification. Multi-factor dimensionality reduction (MDR) was used to analyze the effect of gene-environment interactions on EH risk. Results: The risk of EH increased in the BMPR2 gene rs6435156 locus dominant model (adjusted odds ratio [OR] = 1.572, 95% confidence interval [CI]: 1.385-1.765, P<0.001) and recessive model (adjusted OR = 1.926, 95% CI: 1.693-2.067, P<0.001). The risk of EH increased in the rs1048829 recessive model (adjusted OR = 1.444, 95% CI: 1.142-1.696, P=0.003). The risk of EH increased in the recessive model of the ACVRL1 gene rs121909287 locus (adjusted OR = 1.403, 95% CI: 1.101-1.660, P=0.008). The risk of EH increased in the SMAD9 gene rs397514716 locus dominant model (adjusted OR = 1.370, 95% CI: 1.183-1.559, P<0.001) and recessive model (adjusted OR = 1.803, 95% CI: 1.470-1.983, P<0.001). The CG haplotype of the rs6435156 and rs1048829 loci of the BMPR2 gene, the CC haplotype of the ACVRL1 gene rs121909287 and rs121909284 loci, and the CC haplotype of the rs397514716 and rs121918359 loci of the SMAD9 gene were factors that protect against EH, whereas the TT haplotype of the rs6435156 and rs1048829 loci in the BMPR2 gene was a risk factor for EH. MDR analysis showed that the BMPR2 gene rs6435156 locus TT genotype carriers, the SMAD9 gene rs397514716 locus TT genotype carriers, and alcohol drinkers had the highest EH risk (OR = 4.523, 95% CI: 2.235-6.871, P<0.001). Conclusion: The SNPs of the rs6435156 and rs1048829 locus in the BMPR2 gene, the rs121909287 loci in the ACVRL1 gene, and the rs397514716 locus in the SMAD9 gene were associated with a risk of EH in Han Chinese.

[An epidemiological investigation on a food-born outbreak of noroviru caused by Sydney 2012 G II.4 strain].

OBJECTIVE: To identify the source of infection, route of transmission and risk factors related to a cluster of acute gastroenteritis cases in a university of Guangzhou. METHODS: Cases were identified according to the definition. Descriptive epidemiological approaches and case-control study designs were employed in the analysis. All the samples were tested for norovirus by RT-PCR. Positive samples were subjected to both nucleotide sequence and homology analysis. RESULTS: A total of 141 cases related to norovirus gastroenteritis were identified in January 8 to 21, 2013, with the attack rate as 8.5 per thousand (141/16,600). The peak in morbidity was seen on January 8 to 9. No clustering was found in different classes or dormitories. Results from the case-control study revealed that early cases were infected in Restaurant A (OR = 3.46, 95% CI: 1.07-11.16) and the cold shredded chicken set meal (OR = 17.82, 95% CI: 4.46-78.17) served at lunch (OR = 4.34, 95% CI: 1.18 -17.37) on January 7 was under suspicion. A total of 266 samples, including rectal swabs from the patients and kitchen wokers, leftover food and environmental swabs, were collected. Twenty-one samples (collected from 17 persons) were positive for norovirus by RT-PCR. About 29.6% (8/27) of the kitchen workers in the Restaurant A were tested positive for the virus. The pathogen was identified as the new norovirus genotype II.4 variant, termed Sydney 2012. The virus strains isolated from the patients among student and staff and the kitchen workers were 100% identical in their nucleotide sequence. CONCLUSION: This was the first reported acute gastroenteritis outbreak caused by the new norovirus genotype II.4 variant, Sydney 2012, which showed that the food was contaminated by the asymptomatic kitchen workers who carried the virus.

Retrospective analysis of porcelain failures of metal ceramic crowns and fixed partial dentures supported by 729 implants in 152 patients: patient-specific and implant-specific predictors of ceramic failure.

STATEMENT OF PROBLEM: Porcelain fracture associated with an implant-supported, metal ceramic crown or fixed partial denture occurs at a higher rate than in tooth-supported restorations, according to the literature. Implant-specific and patient-specific causes of ceramic failure have not been fully evaluated. PURPOSE: The purpose of this retrospective study was to evaluate the potential statistical predictors for porcelain fracture of implant-supported, metal ceramic restorations. MATERIAL AND METHODS: Over a 6-month period, a consecutive series of patients having previously received implant-supported, metal ceramic fixed restorations were examined during periodic recall appointments. The number of supporting implants, number of dental units, type of restoration, date of prosthesis insertion, location in the dental arch, opposing dentition, type of occlusion, presence of parafunctional habits, use of an occlusal protective device, presence or absence of ceramic fractures, gender, and age were recorded for each patient. The generalized estimating equation (GEE) approach was used for the intrasubject correlated measurements analysis of categorical outcomes (presence or absence of ceramic fractures) to determine which patient- and implant-specific factors would predict porcelain fracture (alpha=.05). RESULTS: Data were collected from 152 patients representing 998 dental units (390 single crowns and 94 fixed partial dentures) supported by 729 implants. Porcelain fractures of 94 dental units occurred in 35 patients. The fractures were significantly (P<.05) associated with opposing implant-supported metal ceramic restorations, bruxism, and not wearing a protective occlusal device. Metal ceramic prostheses (single crown or fixed partial dentures) had approximately 7 times higher odds of porcelain fracture (odds ratio (OR)=7.06; 95% confidence interval (CI): 2.57 to 19.37) and 13 times greater odds of a fracture requiring either repair or replacement (OR=13.95; 95% CI: 2.25 to 86.41) when in occlusion with another implant-supported restoration, as compared to opposing a natural tooth. In addition, patients exhibiting bruxism or not wearing an occlusal device had approximately 7 times higher odds (OR=7.23; 95% CI: 3.86 to 13.54), and 2 times higher odds (OR=1.92; 95% CI: 1.01 to 3.67) of porcelain fracture when compared to patients without bruxism and patients not wearing an occlusal device. CONCLUSIONS: Implant-supported metal ceramic single crowns and fixed partial dentures were found to have a significantly higher risk of porcelain fracture in patients with bruxism habits, when a protective occlusal device was not used, and when the restoration opposed another implant-supported metal ceramic restoration.

Persistently high levels of periodontal pathogens associated with preterm pregnancy outcome.

BACKGROUND: Few studies examining the association between periodontal diseases and preterm birth have explored the underlying microbial and antibody responses associated with oral infection. METHODS: A nested case-control study was performed using data from a recent interventional trial following the delayed-treatment control group of 31 subjects with periodontal diseases. The levels of eight oral bacteria and the maternal immunoglobulin G (IgG) responses in serum to these bacteria were measured at antepartum and postpartum visits to determine the relationship to cases (preterm delivery <37 weeks' gestation) and controls (term delivery). RESULTS: Antepartum, the levels of periodontal pathogens tended to be higher in the preterm (case group) deliveries compared to the term deliveries (control group). Maternal anti-Porphyromonas gingivalis IgG was significantly lower in the preterm group compared to the term group (P = 0.028). Postpartum, levels of P. gingivalis, Tannerella forsythia, Prevotella intermedia, and Prevotella nigrescens were statistically significantly higher in preterm births compared to term deliveries, adjusting for baseline levels. The joint effects of red and orange microbial clusters were significantly higher in the preterm group compared to the term group. CONCLUSIONS: High levels of periodontal pathogens and low maternal IgG antibody response to periodontal bacteria during pregnancy are associated with an increased risk for preterm delivery. Further studies elucidating the role of the microbial load and maternal immune response as related to pregnancy outcome seem merited.

Sensory retraining after orthognathic surgery: effect on patients' perception of altered sensation.

PURPOSE: The primary research hypothesis was that the magnitude and duration of the perceived burden from altered sensation reported by patients after bilateral sagittal split osteotomy and trauma to the third division of the trigeminal nerve are decreased when facial sensory retraining exercises are performed in conjunction with standard opening exercises as compared with standard opening exercises alone. SUBJECTS AND METHODS: A total of 186 subjects were enrolled in a multicenter, double-blind, 2 parallel group-stratified block randomized clinical trial. Oral and facial pain, unusual sensations, numbness, and loss of sensitivity were scored from "no problem" to "serious problem" before surgery and 1 month, 3 months, and 6 months after surgery. A proportional odds model for the ordered multinomial response was used to compare the responses of the 2 exercise groups. RESULTS: The 2 exercise groups did not differ significantly at any postsurgical time in terms of perceived problem level from intraoral of facial pain. The difference between the 2 groups at each visit was not statistically significant for unusual sensations, although the trend was for the sensory retraining group to have a higher likelihood of reporting fewer problems. By 6 months, the likelihood of a subject reporting lower problem or interference level related to numbness or decreased lip sensitivity was significantly higher in the sensory-retraining group, approximately twice that of the opening exercise-only group. CONCLUSIONS: Our results support the premise that a simple noninvasive exercise program initiated shortly after orthognathic surgery can lessen the objectionable impression of negative altered sensations.

Effects of periodontal therapy during pregnancy on periodontal status, biologic parameters, and pregnancy outcomes: a pilot study.

BACKGROUND: Few studies have examined the potential effects of periodontal treatment during pregnancy on pregnancy outcomes, periodontal status, and inflammatory biomarkers. METHODS: A randomized, delayed-treatment, controlled pilot trial was conducted to evaluate the effects of second-trimester scaling and root planing and the use of a sonic toothbrush on the rate of preterm delivery (<37 weeks gestation). Secondary outcome measures included changes in periodontal status, levels of eight oral pathogens, levels of gingival crevicular fluid (GCF) interleukin-1beta (IL-1beta), prostaglandin E(2) (PGE(2)), 8-isoprostane (8-iso), and IL-6, and serum levels of IL-6, soluble intercellular adhesion molecule 1 (sICAM1), 8-isoprostane, soluble glycoprotein 130 (sGP130), IL-6 soluble receptor (IL-6sr), and C-reactive protein (CRP). Logistic regression models were used to test for effects of treatment on preterm delivery. Secondary outcomes were analyzed by analysis of covariance adjusting for subject baseline values. RESULTS: Periodontal intervention resulted in a significantly decreased incidence odds ratio (OR) for preterm delivery (OR = 0.26; 95% confidence interval = 0.08 to 0.85), adjusting for baseline periodontal status which was unbalanced after randomization. Pregnancy without periodontal treatment was associated with significant increases in probing depths, plaque scores, GCF IL-1beta, and GCF IL-6 levels. Intervention resulted in significant improvements in clinical status (attachment level, probing depth, plaque, gingivitis, and bleeding on probing scores) and significant decreases in levels of Prevotella nigrescens and Prevotella intermedia, serum IL-6sr, and GCF IL-1beta. CONCLUSIONS: Results from this pilot study (67 subjects) provide further evidence supporting the potential benefits of periodontal treatment on pregnancy outcomes. Treatment was safe, improved periodontal health, and prevented periodontal disease progression. Preliminary data show a 3.8-fold reduction in the rate of preterm delivery, a decrease in periodontal pathogen load, and a decrease in both GCF IL-1beta and serum markers of IL-6 response. However, further studies will be needed to substantiate these early findings.

Periodontal disease and coronary heart disease: a reappraisal of the exposure.

BACKGROUND: Results from studies relating periodontal disease to cardiovascular disease have been mixed. Residual confounding by smoking and use of clinical measures of periodontal disease rather than measures of infection have been 2 major criticisms. The aims of this study were to investigate relationships between prevalent coronary heart disease (CHD) and 2 exposures, (1) clinical periodontal disease and (2) IgG antibodies to 17 oral organisms, and to evaluate the role of smoking in these relationships. METHODS AND RESULTS: Our study is based on a subset of participants in the Atherosclerosis Risk in Communities (ARIC) Study, who received a complete periodontal examination during visit 4 (1996-1998). The exposures were periodontal status and serum IgG antibody levels against 17 periodontal organisms, and the outcome was prevalent CHD at visit 4. Multivariable analyses indicate that periodontal status is not significantly associated with CHD in either ever smokers or never smokers. Similar analyses evaluating antibodies indicate that high antibodies (above the median) to Treponema denticola (odds ratio [OR]=1.7; 95% CI, 1.2 to 2.3), Prevotella intermedia (OR=1.5; 95% CI, 1.1 to 2.0), Capnocytophaga ochracea (OR=1.5; 95% CI, 1.1 to 2.1), and Veillonella parvula (OR=1.7; 95% CI, 1.2 to 2.3) are significantly associated with CHD among ever smokers, whereas Prevotella nigrescens (OR=1.7; 95% CI, 1.1 to 2.6), Actinobacillus actinomycetemcomitans (OR=1.7; 95% CI, 1.2 to 2.7), and Capnocytophaga ochracea (OR=2.0; 95% CI, 1.3 to 3.0) were associated with CHD among never smokers. CONCLUSIONS: Clinical signs of periodontal disease were not associated with CHD, whereas systemic antibody response was associated with CHD in ever smokers and never smokers. These findings indicate that the quality and quantity of the host response to oral bacteria may be an exposure more relevant to systemic atherothrombotic coronary events than clinical measures.

Associations between IgG antibody to oral organisms and carotid intima-medial thickness in community-dwelling adults.

AIMS: The aims of this study are to describe the relationships between IgG antibodies to 17 oral organisms and atherosclerosis as indexed by carotid intima-medial wall thickness (IMT) and to evaluate the role of smoking. METHODS AND RESULTS: Our study is based on a subset of participants in the Atherosclerosis Risk in Communities (ARIC) Study, who received a complete periodontal examination during visit 4 (1996-1998). The outcome was mean carotid IMT>/=1mm assessed by B-mode ultrasound. The exposures were serum IgG antibody levels against 17 periodontal organisms using a whole bacterial checkerboard immunoblotting technique. Evaluation of all 17 antibodies indicated that antibody to Campylobacter rectus resulted in the best-fitting model (OR=2.3, 95% CI=1.83-2.84) and individuals with both high C. rectus and Peptostreptococcus micros titers had almost twice the prevalence of IMT>/=1mm than those with only a high C. rectus antibody (8.3% versus 16.3%). Stratification by smoking indicated that all microbial models significant for smokers were also significant for never smokers except for Porphyromonas gingivalis (p=0.08). CONCLUSIONS: This is the first study to report a relationship between IgG antibody reactive to oral organisms and subclinical atherosclerosis with significant relationships evident in both ever and never smokers.

Evidence for periodontitis as a tertiary vascular infection.

Periodontal infections create an oral wound that serves as a portal for the systemic dissemination of oral pathogens. Clinical assessments of periodontal disease that account for the number and severity of diseased periodontal sites and teeth; including measurements of pocketing, the degree of redness, inflammation and bleeding on probing, can all provide an estimate of the severity of the clinical condition. However, these clinical signs appear inadequate to completely characterize the size, patency and integrity of the periodontal lesion which serves as a portal for systemic exposure. Increasingly, measures of infectious exposure including systemic antibodies, inflammatory mediators and acute phase reactants serve as surrogates or biomarkers for periodontal disease that provide further insight into the linkages between periodontitis and atherogenesis. This review discusses the evidence for systemic inflammatory responses to oral organisms and the potential role of chronic vessel pathology as a manifestation of tertiary periodontal infections.

Campylobacter rectus mediates growth restriction in pregnant mice.

BACKGROUND: Recent studies have suggested that subclinical infection may be an important cause of low birth weight. Campylobacters are important human pathogens, causing septicemia and occasionally abortion, premature labor, or severe perinatal infection. The potential role of oral species of Campylobacter in mediating adverse pregnancy outcomes in animal models has not yet been determined. Our objective was to determine the effects of Campylobacter rectus (C. rectus) infection on pregnancy outcomes in a mouse model. METHODS: On embryonic day (E) 7.5, pregnant mice received a subcutaneous, intra-chamber challenge with live C. rectus at concentrations of 0, 10(7) or 10(9) colony forming units (CFU)/ml. They were sacrificed on E 16.5 and fetuses were evaluated for stage of development, weight, and crown-rump length. RESULTS: Dams receiving C. rectus had more fetal resorptions after challenge with 10(7) or 10(9) CFU/ml (24.1% and 30.1%, respectively) than controls (9%). Higher numbers of growth-restricted fetuses were also observed in the C. rectus challenged groups (21%) as compared to controls (2.3%). Fetuses from dams challenged with 10(9) CFU/ml weighed less (0.49 +/- 0.05 g) and had shorter crown-rump lengths (14.69 +/- 0.56 mm) than controls (0.53 +/- 0.04 g; 15.54 +/- 0.63 mm). C. rectus was detected by polymerase chain reaction (PCR) in the placentas from both treated groups and in maternal liver tissues from the 10(9) CFU/ml challenged group. CONCLUSIONS: Remote subcutaneous maternal C. rectus infection increases fetal resorptions and fetal growth restriction in a mouse model. The effects of an oral C. rectus infection on pregnancy remain to be determined.

Porphyromonas gingivalis infection during pregnancy increases maternal tumor necrosis factor alpha, suppresses maternal interleukin-10, and enhances fetal growth restriction and resorption in mice.

Epidemiological studies have shown a potential association between maternal periodontitis and pregnancy complications. We used a pregnant murine model to study the effect of infection with the periodontal pathogen Porphyromonas gingivalis on pregnancy outcomes. Female BALB/c mice were inoculated with heat-killed P. gingivalis (10(9) CFU) in a subcutaneous chamber and mated 2 weeks later. At gestation day (GD) 7.5, mice were challenged with live P. gingivalis (10(7) CFU) (n = 20) or broth (control; n = 8) and sacrificed at GD 16.5. Fetal growth restriction (FGR, <0.46 g) was defined as fetuses with weights 2 standard deviations (SD) smaller than controls (0.56 +/- 0.05 g [mean +/- SD]). Among the 20 challenged mice, 8 had both normal-weight (0.51 +/- 0.11 g) and FGR (0.34 +/- 0.1 g) fetuses within the same litter. All other challenged dams had normal-weight fetuses (0.57 +/- 0.04 g). Maternal liver, uterus, and spleen samples were examined for P. gingivalis DNA using a PCR technique. Of the eight challenged mice with FGR fetuses, three had PCR signals for P. gingivalis in liver and uterus, but not in the spleen. Liver, uterus, and spleen were negative for P. gingivalis DNA among all other challenged and control mice. In serum of dams with FGR fetuses, tumor necrosis factor alpha levels were elevated significantly, while interleukin-10 levels were significantly reduced compared to levels in dams with normal fetuses. P. gingivalis-specific serum immunoglobulin G levels were significantly elevated in dams with FGR fetuses compared to dams without any FGR fetuses. These data demonstrate that P. gingivalis-induced murine FGR is associated with systemic dissemination of the organism and activated maternal immune and inflammatory responses.

Porphyromonas gingivalis infection in pregnant mice is associated with placental dissemination, an increase in the placental Th1/Th2 cytokine ratio, and fetal growth restriction.

Our previous animal studies showed that maternal Porphyromonas gingivalis infection in a subcutaneous chamber is associated with hepatic and uterine translocation, as well as systemic induction of maternal inflammatory responses, both of which were associated with fetal growth restriction (FGR). However, P. gingivalis-challenged dams had fetuses with either FGR (2 standard deviations below mean weight of nonchallenged dams) or normal weight. Therefore, the objective of this study was to determine whether maternal infection with P. gingivalis compromises normal fetal development via direct placental invasion and induction of fetus-specific placental immune responses characterized by a proinflammatory Th1-type cytokine profile. P. gingivalis-specific DNA was detected in placentas and fetuses of FGR and normal littermates from P. gingivalis-infected dams. Th1- and Th2-type cytokine mRNA as well as tumor necrosis factor alpha and transforming growth factor beta 2 mRNA were examined in placental tissue by using reverse transcription-PCR to determine Th1/Th2 ratios. For eight litters containing both normal-weight and FGR fetuses, P. gingivalis DNA was detected only in the placentas of FGR fetuses. All fetuses and all amniotic fluid samples from infected and control dams were negative for P. gingivalis DNA. mRNA levels of gamma interferon and interleukin-2 (IL-2) were significantly increased in placentas of FGR fetuses, while expression of IL-10 was significantly decreased in the same group. These data indicate that, in P. gingivalis-challenged dams, within each litter there is placenta-specific translocation of P. gingivalis that results in growth restriction of the targeted fetus, which is associated with a shift in the placental Th1/Th2 cytokine balance.