Abstract MP43: Paradoxical Response to Antibodies in Periodontal Microbes in Subjects With Intracranial Atherosclerotic Stenosis

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Nishanth Kodumuri ◽  
Souvik Sen ◽  
Elizabeth A La Valley ◽  
Fareed Suri ◽  
Bruce A Wasserman ◽  
...  

Introduction: Previously we have shown that periodontal disease and systemic inflammation are related to intracranial atherosclerosis (ICAS) in Atherosclerosis Risk In Communities study (ARIC). In this study we evaluated the relationship between serum antibodies against periodontal pathogens and ICAS. Methods: In this ongoing, prospective, longitudinal community-based cohort study, participants were assessed for antibodies to periodontal organisms including Porphyrmonas gingivalis (PG), Prevotella intermedia (PI), Prevotella nigrescens (PN), Bacteriodes forsythensis (BF), Treponema denticola (TD), Actinobacillus actinomycetemcomitans (AA), Campylobacter rectus (CR), Eikenella corrodens (EC), Fusobacterium nucleatum (FN), Peptostreptococcus micros (PM), Selenomonas noxia (SN), Capnocytophaga ochracea (CO), Veillonella parvula (VP), Streptococcus sanguinis (SS), Streptococcus intermedius (SI), Streptococcus oralis (SO), Actinomycosis viscosis (AV) and Helicobacter pylori (HP). These participants underwent 3D time-of-flight magnetic resonance angiography (MRA) to evaluate ICAS. Log mean antibody (IgG), CRP and IL-6 levels were compared using t-test between groups with and without ≥50% ICAS. Results: In this ARIC cohort, 1066 participants were assessed by MRA for ICAS. Serum CRP and IL-6 data were available for all and IgG levels were available for 772 participants. The log mean IgG level was significantly lower for patients with ≥50% ICAS versus patients with <50% ICAS in four organisms: PN (1.69 vs 1.80, p= 0.03 ), BF (1.30 vs 1.38, p=0.05 ), CO (1.23 vs 1.33, p= 0.04 ), FN (0.87 vs 1.01, p=0.02 ). The log mean IgG was also lower for CR, EC, SN, VP, SI, SO and AV though not significant. Log mean CRP was higher in the ≥50% ICAS group versus the <50% ICAS group (0.58 vs. 0.47, p < 0.001 ). Log mean IL-6 levels were also higher but not significant (0. 17 vs. 0.11, p= 0.07 ). Conclusion: Higher levels of systemic inflammatory markers (CRP, IL-6) are associated with significant ICAS, but we report a significantly lower level of IgG antibodies to specific periodontal pathogens (PN, BF, CO and FN) in patients with ≥50% ICAS. This paradoxical finding may represent the effect of systemic inflammation and oxidative stress on IgG levels to periodontal bacteria.

SLEEP ◽  
2020 ◽  
Author(s):  
Andrée-Ann Baril ◽  
Alexa S Beiser ◽  
Susan Redline ◽  
Emer R McGrath ◽  
Hugo J Aparicio ◽  
...  

Abstract Study Objectives To determine whether C-reactive protein (CRP), a marker of systemic inflammation, moderates the association between sleep and incident dementia. Methods We studied Framingham Heart Study participants who completed at baseline a serum CRP assessment and in-home polysomnography to measure sleep duration, sleep efficiency, sleep latency, wake after sleep onset (WASO), number of awakenings, arousal index, and apnea–hypopnea index. Participants were divided into groups according to their CRP level: low (&lt;1 mg/L), average (1–3 mg/L), and high inflammation (&gt;3 mg/L). Surveillance for outcomes (incident all-cause and Alzheimer’s disease [AD] dementia) commenced at baseline and continued up to 22.5 years. Results In 291 participants (mean age 67.5 ± 4.9 years, 51.6% men) followed for 13.4 ± 5.4 years, we observed 43 cases of all-cause dementia, 33 of which were clinically consistent with AD. Whereas no direct association between CRP or sleep exposures was observed with incident dementia, CRP levels interacted with nighttime wakefulness when predicting both incident all-cause and AD dementia. In the high CRP group, longer WASO (hazard ratio [HR], 2.89; 95% CI, 1.31–6.34) and more nighttime awakenings (HR, 4.55; 95% CI, 1.19–17.38) were associated with higher risk of incident dementia. In the low CRP group, fewer nighttime awakenings were associated with a higher risk of incident dementia (HR, 0.07; 95% CI, 0.01–0.68). Conclusions Our findings suggest that inflammation moderates the association between sleep, particularly nighttime wakefulness, and dementia risk. The presence of inflammation may be an important determinant in evaluating how sleep disturbances relate to neurodegeneration.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
N Balachandren ◽  
M Davies ◽  
J Hall ◽  
D Mavrelos ◽  
E Yasmin

Abstract Study question Are pregnant women in the community with confirmed diagnosis of SARS-CoV–2 infection, at increased risk of an early miscarriage? Summary answer Women diagnosed with COVID–19 in their first trimester were not at increased risk of an early miscarriage. What is known already: In the earliest stages of the pandemic, the Human Fertilisation and Embryology Authority and the European Society of Human Reproduction and Embryology, independently advised against starting assisted reproductive treatments. At the time of this recommendation, among other reasons, there were concerns about the complications of SARS-CoV–2 during pregnancy and the potential for vertical transmission. We now having growing evidence that pregnant women are at an increased risk of severe illness along with higher rates of preterm births in those with severe acute respiratory syndrome. However, data on the impact of community infections of SARS-CoV–2 in early pregnancy has been sparse. Study design, size, duration This is an online survey study undertaken in the UK between May and November 2020. Pregnant women at any stage in their pregnancy were invited to participate in the study. Study participants were asked to complete online surveys at the end of each trimester. 10, 430 women were recruited to take part in the study. Participants/materials, setting, methods: We analysed pregnancy outcomes from women who were under 13 weeks gestation at the time of registration. We compared miscarriage rates among women with a confirmed diagnosis of SARS-CoV–2 infection to healthy controls. Those in the control group had not been diagnosed with or had symptoms of SARS-CoV–2 infection nor did they have any household contacts that were diagnosed with or had symptoms of SARS-CoV–2 infection. Main results and the role of chance 10, 430 pregnant women were recruited to participate in the study. 2934 were under 13 weeks gestation at the time of registration. The median age was 32.6 [IQR 29.8–35.6]. The median gestational age at registration was 8 weeks [IQR [6–10]. 246 women reported a miscarriage before 13 weeks of gestation. The overall miscarriage rate before 13 weeks of gestation was 8.4% (95% CI 7.3%–9.4%). 68 women reported a confirmed diagnosis of SARS-CoV–2 infection in their first trimester. The overall rate of confirmed SARS-CoV–2 infections in the first trimester was 2.3% (95% CI 1.8–2.9%). 3/68 (4.4%) were asymptomatic. Among those reporting symptoms, the commonest symptoms were fatigue (82%), headache (69%) and loss of smell/taste (69%). Only 38% of those with a confirmed diagnosis reported a fever. None of the 68 women with confirmed diagnosis of SARS-CoV–2 infection were hospitalised. The rate of miscarriage before 13 weeks of gestation in women who were diagnosed with SARS-CoV–2 infections was not significantly higher compared to healthy controls (11.8% versus 9.3%, p = 0.35). A further 35 women had household contacts with confirmed SARS-CoV–2 infection although they themselves had not been diagnosed. No miscarriages were reported in this group. Limitations, reasons for caution None of the 68 patients diagnosed with SARS-CoV–2 were hospitalised. We do not know whether the rate of miscarriage among hospitalised women with SARS-CoV–2 infection is the same as those with community infections. Wider implications of the findings: The overall rate of miscarriage during the pandemic was not higher than rates occurring outside of the pandemic. The rate of miscarriage among women diagnosed with SARS-CoV–2 infection was not significantly higher compared to healthy controls. This data can be used to counsel women planning a pregnancy during this pandemic Trial registration number Not applicable


Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Akira Fujiyoshi ◽  
M.Fareed K Suri ◽  
Alvaro Alonso ◽  
Elizabeth Selvin ◽  
Haitao Chu ◽  
...  

Introduction: Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke. Determinants of ICAS include conventional cardiovascular (CV) risk factors such as hypertension and dyslipidemia. The association of diabetes mellitus (DM) and/or hyperglycemia with ICAS, however, is less well documented. Hypothesis: In a community-based population, biomarkers of hyperglycemia will be cross-sectionally associated with prevalent ICAS independent of CV risk factors. Methods: Our analyses were conducted in a subsample of participants of the Atherosclerosis Risk in Communities (ARIC) Study who participated in the ARIC-Neurocognitive Study in 2011-13 with cerebrovascular magnetic resonance angiography and no history of stroke. For the present analyses, we grouped the participants into 3 categories based on the highest ICAS category among any of the intracranial arteries we assessed: “no stenosis”, “<50%”, or “≥50% (including occlusion)”. Diagnosed diabetes was defined as self-reported physician diagnosis or use of antidiabetic medication. Ordinal logistic regression provided odds ratios of prevalent ICAS according to quintile of glucose or glycated hemoglobin (HbA1c) adjusted for CV risk factors. Results (Table): There were 1,658 individuals included in our study (age 67-90 years, women 58%, Black 29%), 31% (514/1658) had diagnosed diabetes, 10% (165/1658) had ≥50 % stenosis at any of the intracerebral arteries. In crude analyses, those with higher glucose and HbA1c were more likely to have ICAS among the non-diabetes and the diabetes. In logistic regression, highest quintile of glucose, relative to the lowest, had odds ratio of 2.26 (95% confidence interval 1.48, 3.45) for being in each successive ICAS category after adjustment for CV risk factors. Conclusion: Higher glucose and HbA1c were associated with higher odds of ICAS independent of CV risk factors. The finding suggests that hyperglycemia plays a role in pathogenesis of ICAS.


2002 ◽  
Vol 2 ◽  
pp. 1070-1078 ◽  
Author(s):  
Nicolas Padilla ◽  
Rosalinda Diaz ◽  
Alfonso Alarcon ◽  
Roberto Barreda

This study sought to examine whether the administration of quinfamide at 3- or 6-month intervals diminished the frequency ofEntamoeba histolyticacysts in stool samples compared to controls. The prospective, longitudinal, randomized, single-blind study examined children from six primary schools in Celaya and Neutla, Guanajuato. Of the 1,524 students in these schools, we selected participants for the study as follows: Children were included in the study if their parents agreed in writing to the study and if the children demonstrated evidence ofE. histolyticacysts after a parasitoscopic analysis by concentration (PSC) in three samples over consecutive days using Faust’s method. Those included in the study received a single 4.3-g/kg dose of quinfamide, and we performed PSC on days 5, 6, and 7 following dose administration to examine whether quinfamide had affected the presence of the cysts. The study participants who tested negative for cysts were divided into three groups: Group 1 had 102 patients who underwent quinfamide treatment and three CPS analyses after the 12 months of the study; Group 2 had 98 subjects who underwent the quinfamide treatment and three CPS analyses at months 3, 6, 9, and 12 after their entrance into the study; and Group 3 had 102 patients, who underwent the quinfamide treatment and series of three CPS analyses at months 6 and 12 of the study. All participants received the dose of quinfamide after providing stool samples and after a clinical gastrointestinal history was obtained. Further clinical gastrointestinal data were collected 5 days after the quintamide dose was administered. We used EpiInfo 6.0 for statistical analysis, calculatingX2andpvalues for the clinical data and the CPS data after the 12 months concluded. Of the initial samples of 1,524 subjects, 308 (20.2%) had Entamoebic cysts. Of these, six were further eliminated because they did not meet the inclusion requirements. At the conclusion of the study, Group 1 presented with 37.6% of subjects still testing positive for cysts; of Group 2, 12.5% tested positive; and in Group 3, 23.5% of participants tested positive for cysts (X2= 16.8; df = 2;p= 0.0002). For comparisons of groups 1 and 2 and 1 and 3,p> 0.05. We conclude that antiamoebic chemoprophylaxis can be a choice for control of amoebic infection where personal hygiene and food consumption habits are not improving.


2019 ◽  
Author(s):  
Anne E Justice ◽  
Geetha Chittoor ◽  
Rahul Gondalia ◽  
Phillip E Melton ◽  
Elise Lim ◽  
...  

ABSTRACTWe conducted a methylome-wide association study to examine associations between DNA methylation in whole blood and central adiposity and body fat distribution, measured as waist circumference, waist- to-hip ratio, and waist-to-height ratio adjusted for body mass index, in 2684 African American adults in the Atherosclerosis Risk in Communities study. We validated significantly associated Cytosine-phosphate-Guanine methylation sites (CpGs) among adults using the Women’s Health Initiative and Framingham Heart Study participants (combined N=5743) and generalized associations in adolescents from The Raine Study (N=820). We identified 11 CpGs that were robustly associated with one or more central adiposity trait in adults and 2 in adolescents, including CpG site associations near TXNIP, ADCY7, SREBF1, and RAP1GAP2 that had not previously been associated with obesity-related traits.


2020 ◽  
Author(s):  
Marta González-Sánchez ◽  
Fernando Bartolome ◽  
Desiree Antequera ◽  
Veronica Puertas-Martín ◽  
Pilar González ◽  
...  

Abstract Background Efforts focused on developing new less invasive biomarkers for early Alzheimer’s disease (AD) diagnosis are substantial. Evidences of infectious pathogens in AD brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary levels of Lf in AD patients, one of the major antimicrobial peptides. Methods To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-β (Aβ) load in two different cross-sectional cohorts including patients with different neurodegenerative disorders. Study participants for cohort 1 (n = 116) were enrolled from the 12 de Octubre University Hospital Neurology Service in Madrid (Spain) and Pablo de Olavide University in Sevilla (Spain). Study participants for cohort 2 (n = 142) were enrolled as part of the Atherobrain - Heart to Head (H2H) project. Participants underwent neurological and neuropsychological examination, saliva sampling, and amyloid-Positron-Emission Tomography (PET) neuroimaging. Results The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0.95 (0.911-0.992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET + ) versus healthy group, and 0.97 (0.924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0.93 (95% CI 0.876-0.989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from other dementias as FTD with over 87% sensitivity and 91% specificity. Conclusion Therefore, salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5782
Author(s):  
Fiamma Burgassi ◽  
Elena Paillaud ◽  
Johanne Poisson ◽  
Guilhem Bousquet ◽  
Frédéric Pamoukdjian

The prognostic value of the CRP to albumin ratio (CAR) among older adults with cancer is not known. Six hundred and three older outpatients with cancer and undergoing geriatric assessment before therapeutic decisions were prospectively recruited from the PF-EC cohort study. Serum albumin levels, serum CRP levels and the CAR were prospectively recorded at baseline, and at each consultation thereafter, as follows: 1, 3, 6, 9, 12, 18, 24 and 36 months. Frailty was defined as a G8-index ≤ 14. The primary endpoint was longitudinal variation in the CAR during the study follow-up. Two clusters in the longitudinal trajectories of the CAR were identified, one favourable, with lower values and better overall survival (cluster A), and the second with higher values and less favourable overall survival (cluster B). The median CAR [95% CI] for clusters A and B were respectively: 0.17 [0.04–0.48] and 0.26 [0.04–0.79] at baseline (p = 0.01), and 0.18 [0.02–3.17] and 0.76 [0.03–6.87] during the study follow-up (p < 0.0001). Cluster B was associated with the frailest patients with metastatic disease, mainly driven by a high CRP level at baseline, and low albumin during the study follow-up. Our study results suggest that the most risk-prone patients have a cancer-cachexia trajectory.


2019 ◽  
Author(s):  
L.C. Pessoa ◽  
G. Aleti ◽  
S. Choudhury ◽  
D. Nguyen ◽  
T. Yaskell ◽  
...  

AbstractSystemic lupus erythematosus (SLE) is a potentially fatal complex autoimmune disease, that is characterized by widespread inflammation manifesting tissue damage and comorbidities across the human body including heart, blood vessels, joints, skin, liver, kidneys, and periodontal tissues. The etiology of SLE is partially attributed to a deregulated inflammatory response to microbial dysbiosis and environmental changes. In the mouth, periodontal environment provides an optimal niche to assay local dynamic microbial ecological changes in health and disease important to systemic inflammation in SLE subjects. Our aim was to evaluate the reciprocal impact of periodontal subgingival microbiota on SLE systemic inflammation. Ninety-one female subjects were recruited, including healthy (n=31), SLE-inactive (n=29), and SLE-active (n=31). Patients were screened for probing depth (PD), bleeding on probing (BOP), clinical attachment level (CAL), and classified with or without periodontal dysbiosis, periodontitis. Serum inflammatory cytokines were measured by human cytokine panel and subgingival biofilm was examined by DNA-DNA checkerboard. The results showed significant upregulation of proinflammatory cytokines in individuals with SLE when compared to controls. Stratification of subject’s into SLE-inactive (I) and SLE-active (A) phenotypes or periodontitis and non-periodontitis groups provided new insights into SLE pathophysiology. While low-grade inflammation was found in SLE-I subjects, a potent anti-inflammatory cytokine, IL-10 was found to control clinical phenotypes. Out of twenty-four significant differential oral microbial abundances found in SLE, fourteen unique subgingival bacteria profiles were found to be elevated in SLE. Pathogens from periodontal disease sites (Treponema denticola and Tannerella forsythia) showed increase abundance in SLE-A subjects when compared to controls. Cytokine-microbial correlations showed that periodontal pathogens dominating the environment increased proinflammatory cytokines systemically. Deeper clinical attachment loss and periodontal pathogens were found in SLE subjects, especially on SLE-I, likely due to long-term chronic and low-grade inflammation. Altogether, local periodontal pathogen enrichment was positively associated with high systemic inflammatory profiles, relevant to the overall health and SLE disease pathogenesis.


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