human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Antibodies to citrullinated proteins ( ACPA ) occur years before RA diagnosis . Porphyromonas gingivalis expresses its own peptidylarginine deiminase ( PPAD ) , and is a proposed aetiological factor for the ACPA response . Smoking is a risk factor for both ACPA-positive RA and periodontitis . We aim ed to study the relation of these factors to the risk of RA in a prospect i ve cohort . Methods We performed a nested case – control study by identifying pre-RA cases in four population s from the European Prospect i ve Investigation into Cancer and nutrition , matched with three controls . Data on smoking and other covariates were obtained from baseline question naires . Antibodies to CCP2 and citrullinated peptides from α-enolase , fibrinogen , vimentin and PPAD were measured . Antibodies to arginine gingipain ( RgpB ) were used as a marker for P.gingivalis infection and vali date d in a separate cohort of healthy controls and subjects with periodontitis . Results We studied 103 pre-RA cases . RA development was associated with several ACPA specificities , but not with antibodies to citrullinated PPAD peptides . Antibody levels to RgpB and PPAD peptides were higher in smokers but were not associated with risk of RA or with pre-RA autoimmunity . Former but not current smoking was associated with antibodies to α-enolase ( OR 4.06 ; 95 % CI 1.02 , 16.2 versus 0.54 ; 0.09 - 3.73 ) and fibrinogen peptides ( OR 4.24 ; 95 % CI 1.2 - 14.96 versus 0.58 ; 0.13 - 2.70 ) , and later development of RA ( OR 2.48 ; 95 % CI 1.27 - 4.84 versus 1.57 ; 0.85 - 2.93 ) , independent of smoking intensity . Conclusions Smoking remains a risk factor for RA well before the clinical onset of disease . In this cohort , P.gingivalis is not associated with pre-RA autoimmunity or risk of RA in an early phase before disease-onset . Antibodies to PPAD peptides are not an early feature of ACPA ontogeny OBJECTIVE To study the association of cigarette smoking with risk of  rheumatoid arthritis ( RA ) , among 377,481 female health professionals in the Women 's Health Cohort Study . METHODS Subjects completed mailed question naires regarding demographics , health habits , including cigarette smoking history , and medical history , including RA diagnosis made by a physician and date of diagnosis . Of 7,697 women who self-reported RA , 3,416 reported seropositive RA . Cox proportional hazards regression models were used to retrospectively assess the associations of smoking intensity and duration with the risk of developing RA or seropositive RA . Cigarette smoking status was treated as a time-varying exposure in these regression models . RESULTS In multivariate analyses controlling for age , race , education , age at menarche , pregnancy history , menopausal status , and postmenopausal hormone use , duration of smoking was associated with a significantly increased risk of both RA and seropositive RA ( both P < 0.01 for trend ) , after adjusting for smoking intensity . Women who smoked > or = 25 cigarettes/day for more than 20 years experienced a 39 % increased risk of RA and 49 % increased risk of seropositive RA . However , smoking intensity ( number of cigarettes/day ) was unrelated to risk of RA or seropositive RA ( both P = 0.3 for trend ) , after adjusting for duration of smoking . CONCLUSION Duration , but not intensity , of cigarette smoking is associated with a modest increased risk of RA in women OBJECTIVE This observational prospect i ve cohort study aim ed to evaluate the effects of non-surgical periodontal treatment on clinical periodontal measurements and systemic inflammatory mediator levels in low or moderate to highly active rheumatoid arthritis ( RA ) patients with chronic periodontitis . SUBJECTS AND METHODS Rheumatoid arthritis activity was assessed with disease activity score test ( DAS28 ) . Thirty patients with RA with moderate to high disease activity ( DAS28 ≥ 3.2 ) and chronic periodontitis ( MHDA group ) and thirty patients with RA with low disease activity ( DAS28 < 3.2 ) and chronic periodontitis ( LDA group ) were enrolled in the study . The patients were monitored at the beginning and 3 months after undergoing periodontal therapy . Erythrocyte sedimentation rate ( ESR ) , C-reactive protein ( CRP ) , tumour necrosis factor-alpha ( TNF-α ) levels in serum , DAS28 and periodontal parameters were evaluated . RESULTS Erythrocyte sedimentation rate , CRP , TNF-α levels in serum , DAS28 and periodontal parameters exhibited similar and significant reduction 3 months after the non-surgical periodontal treatment . CONCLUSION Non-surgical periodontal treatment may prove beneficial in reducing RA severity as measured by ESR , CRP , TNF-α levels in serum and DAS28 in low or moderate to highly active RA patients with chronic periodontitis This clinical study evaluated the survival rates of Actinobacillus actinomycetemcomitans , Porphyromonas gingivalis , and Prevotella intermedia in periodontal pockets following scaling and root planing and intra-pocket irrigation with antimicrobial agents in patients with moderate and severe periodontitis . The number of target organisms was determined utilizing DNA probes . Adult periodontitis patients were selected on the basis that the subgingival flora contained at least one of the target organisms . Forty-eight ( 48 ) inflamed pockets > or = 5 mm in depth with probing attachment loss and containing at least one of the target species were then selected in 7 adult patients who harbored these bacteria . Following baseline clinical and bacterial examination , all patients received thorough scaling and root planing . In addition , 1 or 2 teeth in each patient which harbored the target flora at baseline were r and omly assigned to each of the following 4 treatment modalities : 1 ) control group , no irrigation ; 2 ) saline group , irrigation with 2 cc of physiologic saline ; 3 ) tetracycline group , irrigation with 2 cc of aqueous tetracycline hydrochloride , 50 mg/ml ( 5 % ) ; and 4 ) chlorhexidine group , irrigation with 2 cc 0.12 % chlorhexidine . All selected sites ( 5 to 8 per patient ) were nonadjacent teeth . Clinical parameters and microbial analysis were recorded again at one week , and one month post-irrigation . The survival rate of the target microorganisms was determined and the effect of irrigation with antimicrobial agents on this microflora was compared with the control groups ( 1 and 2 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Chronic periodontitis is a silent infectious disease prevalent worldwide and affects lifestyle-related diseases . Therefore , efficient screening of patients is essential for general health . This study was performed to evaluate prospect ively the diagnostic utility of a blood IgG antibody titer test against periodontal pathogens . Oral examination was performed , and IgG titers  against periodontal pathogens were measured by ELISA in 1,387 individuals . The cut-off value of the IgG titer was determined in receiver operating characteristic curve analysis , and changes in periodontal clinical parameters and IgG titers by periodontal treatment were evaluated . The relationships between IgG titers and severity of periodontitis were analyzed . The best cut-off value of IgG titer against Porphyromonas gingivalis for screening periodontitis was 1.682 . Both clinical parameters and IgG titers decreased significantly under periodontal treatment . IgG titers of periodontitis patients were significantly higher than those of healthy controls , especially in those with sites of probing pocket depth over 4 mm . Multiplied cut-off values were useful to select patients with severe periodontitis . A blood IgG antibody titer test for Porphyromonas gingivalis is useful to screen hitherto chronic periodontitis patients ( Clinical Trials.gov number NCT01658475 ) BACKGROUND This study was conducted to determine the component that causes the disease in rheumatoid arthritis ( RA ) , which shows great resemblance to periodontitis in a pathologic context . MATERIAL S AND METHODS Within this study , the pathogen-specific IgG levels formed against Porphyromonas gingivalis FDC 381 , Prevotella melaninogenica ATCC 25845 , Actinobacillus actinomycetemcomitans Y4 , Bacteroides forsythus ATCC 43047 , and Prevotella intermedia 25611 oral bacteria were research ed from the blood serum sample s of 30 RA patients and 20 healthy controls with the enzyme-linked immunosorbent assay ( ELISA ) method . RESULTS The IgG levels of P gingivalis , P intermedia , P melaninogenica , and B forsythus were found to be significantly higher in RA patients when compared with those of the controls . Of the other bacteria antibodies , A actinomycetemcomitans was not found at greater levels in RA serum sample s in comparison with the healthy sample s. CONCLUSION The antibodies formed against P gingivalis , P intermedia , P melaninogenica , and B forsythus could be important to the etiopathogenesis of RA Objective This study aim ed to evaluate prospect ively the influence and the evolution of periodontal disease ( PD ) in rheumatoid arthritis ( RA ) patients su bmi tted to anti – tumor necrosis factor ( TNF ) therapy .  Methods Eighteen patients with RA ( according to the American College of Rheumatology criteria ) were assessed for PD before ( BL ) and after 6 months ( 6 M ) of anti-TNF treatment : 15 infliximab , 2 adalimumab , and 1 etanercept .  Periodontal assessment included plaque and gingival bleeding indices , probing pocket depth , cementoenamel junction , and clinical attachment level . Rheumatologic evaluation was performed blinded to the dentist ’s assessment : demographic data , clinical manifestations , and disease activity ( Disease Activity Score using 28 joints [ DAS28 ] , erythrocyte sedimentation rate [ ESR ] , and C-reactive protein [ CRP ] ) . Results The median age and disease duration of patients with RA were 50 years ( 25–71 y ) and 94 % were female .  Periodontal disease was diagnosed in 8 patients ( 44.4 % ) . Comparing BL to 6 M , periodontal parameters in the entire group remained stable ( P > 0.05 ) throughout the study ( plaque and gingival bleeding indices , probing pocket depth , cementoenamel junction , and clinical attachment level ) , whereas an improvement in most analyzed RA parameters was observed in the same period : DAS28 ( 5.5 vs. 3.9 , P = 0.02 ) , ESR ( 21 vs. 12.5 mm/first hour , P = 0.07 ) , and CRP ( 7.8 vs. 2.8 mg/dL , P = 0.25 ) . Further analysis revealed that this improvement was restricted to the group of patients without PD ( DAS28 [ 5.5 vs. 3.6 , P = 0.04 ] , ESR [ 23.0 vs. 11.5 mm/first hour , P = 0.008 ] , and CRP [ 7.4 vs. 2.1 , P = 0.01 ] ) . In contrast , patients with PD had lack of response , with no significant differences in disease activity parameters between BL and 6 M : DAS28 ( 5.2 vs. 4.4 , P = 0.11 ) , ESR ( 17.0 vs. 21.0 , P = 0.56 ) , and CRP ( 9.0 vs. 8.8 , P = 0.55 ) . Conclusions This study supports the notion that PD may affect TNF blocker efficacy in patients with RA . The possibility that a sustained gingival inflammatory state may hamper treatment response in this disease has high clinical interest because this is a treatable condition BACKGROUND Porphyromonas gingivalis has been implicated as an etiologic agent of rheumatoid arthritis ( RA ) because of the expression of peptidylarginine deiminase . The present study evaluates whether periodontal treatment may affect serum antibodies to P. gingivalis and citrulline levels in relation to disease activity of RA . METHODS Fifty-five patients with RA were r and omly assigned to receive oral hygiene instruction and supragingival scaling ( treatment group , n = 26 ) or no periodontal treatment ( control group , n = 29 ) . Periodontal and rheumatologic parameters and serum levels of cytokine and inflammatory markers citrulline and immunoglobulin (Ig)G to P. gingivalis were examined at baseline and 8 weeks later . RESULTS Both groups did not differ statistically in any parameters except percentage of sites with probing depth and clinical attachment level ≥ 4 mm at baseline . The treatment group exhibited a significantly greater decrease in disease activity score including 28 joints using C-reactive protein ( DAS28-CRP ) ( P = 0.02 ) , serum levels of IgG to P. 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Antibodies to citrullinated proteins ( ACPA ) occur years before RA diagnosis . Porphyromonas gingivalis expresses its own peptidylarginine deiminase ( PPAD ) , and is a proposed aetiological factor for the ACPA response . Smoking is a risk factor for both ACPA-positive RA and periodontitis . We aim ed to study the relation of these factors to the risk of RA in a prospect i ve cohort . Methods We performed a nested case – control study by identifying pre-RA cases in four population s from the European Prospect i ve Investigation into Cancer and nutrition , matched with three controls . Data on smoking and other covariates were obtained from baseline question naires . Antibodies to CCP2 and citrullinated peptides from α-enolase , fibrinogen , vimentin and PPAD were measured . Antibodies to arginine gingipain ( RgpB ) were used as a marker for P.gingivalis infection and vali date d in a separate cohort of healthy controls and subjects with periodontitis . Results We studied 103 pre-RA cases . RA development was associated with several ACPA specificities , but not with antibodies to citrullinated PPAD peptides . Antibody levels to RgpB and PPAD peptides were higher in smokers but were not associated with risk of RA or with pre-RA autoimmunity . Former but not current smoking was associated with antibodies to α-enolase ( OR 4.06 ; 95 % CI 1.02 , 16.2 versus 0.54 ; 0.09 - 3.73 ) and fibrinogen peptides ( OR 4.24 ; 95 % CI 1.2 - 14.96 versus 0.58 ; 0.13 - 2.70 ) , and later development of RA ( OR 2.48 ; 95 % CI 1.27 - 4.84 versus 1.57 ; 0.85 - 2.93 ) , independent of smoking intensity . Conclusions Smoking remains a risk factor for RA well before the clinical onset of disease . In this cohort , P.gingivalis is not associated with pre-RA autoimmunity or risk of RA in an early phase before disease-onset . Antibodies to PPAD peptides are not an early feature of ACPA ontogeny OBJECTIVE To study the association of cigarette smoking with risk of  rheumatoid arthritis ( RA ) , among 377,481 female health professionals in the Women 's Health Cohort Study . METHODS Subjects completed mailed question naires regarding demographics , health habits , including cigarette smoking history , and medical history , including RA diagnosis made by a physician and date of diagnosis . Of 7,697 women who self-reported RA , 3,416 reported seropositive RA . Cox proportional hazards regression models were used to retrospectively assess the associations of smoking intensity and duration with the risk of developing RA or seropositive RA . Cigarette smoking status was treated as a time-varying exposure in these regression models . RESULTS In multivariate analyses controlling for age , race , education , age at menarche , pregnancy history , menopausal status , and postmenopausal hormone use , duration of smoking was associated with a significantly increased risk of both RA and seropositive RA ( both P < 0.01 for trend ) , after adjusting for smoking intensity . Women who smoked > or = 25 cigarettes/day for more than 20 years experienced a 39 % increased risk of RA and 49 % increased risk of seropositive RA . However , smoking intensity ( number of cigarettes/day ) was unrelated to risk of RA or seropositive RA ( both P = 0.3 for trend ) , after adjusting for duration of smoking . CONCLUSION Duration , but not intensity , of cigarette smoking is associated with a modest increased risk of RA in women OBJECTIVE This observational prospect i ve cohort study aim ed to evaluate the effects of non-surgical periodontal treatment on clinical periodontal measurements and systemic inflammatory mediator levels in low or moderate to highly active rheumatoid arthritis ( RA ) patients with chronic periodontitis . SUBJECTS AND METHODS Rheumatoid arthritis activity was assessed with disease activity score test ( DAS28 ) . Thirty patients with RA with moderate to high disease activity ( DAS28 ≥ 3.2 ) and chronic periodontitis ( MHDA group ) and thirty patients with RA with low disease activity ( DAS28 < 3.2 ) and chronic periodontitis ( LDA group ) were enrolled in the study . The patients were monitored at the beginning and 3 months after undergoing periodontal therapy . Erythrocyte sedimentation rate ( ESR ) , C-reactive protein ( CRP ) , tumour necrosis factor-alpha ( TNF-α ) levels in serum , DAS28 and periodontal parameters were evaluated . RESULTS Erythrocyte sedimentation rate , CRP , TNF-α levels in serum , DAS28 and periodontal parameters exhibited similar and significant reduction 3 months after the non-surgical periodontal treatment . CONCLUSION Non-surgical periodontal treatment may prove beneficial in reducing RA severity as measured by ESR , CRP , TNF-α levels in serum and DAS28 in low or moderate to highly active RA patients with chronic periodontitis This clinical study evaluated the survival rates of Actinobacillus actinomycetemcomitans , Porphyromonas gingivalis , and Prevotella intermedia in periodontal pockets following scaling and root planing and intra-pocket irrigation with antimicrobial agents in patients with moderate and severe periodontitis . The number of target organisms was determined utilizing DNA probes . Adult periodontitis patients were selected on the basis that the subgingival flora contained at least one of the target organisms . Forty-eight ( 48 ) inflamed pockets > or = 5 mm in depth with probing attachment loss and containing at least one of the target species were then selected in 7 adult patients who harbored these bacteria . Following baseline clinical and bacterial examination , all patients received thorough scaling and root planing . In addition , 1 or 2 teeth in each patient which harbored the target flora at baseline were r and omly assigned to each of the following 4 treatment modalities : 1 ) control group , no irrigation ; 2 ) saline group , irrigation with 2 cc of physiologic saline ; 3 ) tetracycline group , irrigation with 2 cc of aqueous tetracycline hydrochloride , 50 mg/ml ( 5 % ) ; and 4 ) chlorhexidine group , irrigation with 2 cc 0.12 % chlorhexidine . All selected sites ( 5 to 8 per patient ) were nonadjacent teeth . Clinical parameters and microbial analysis were recorded again at one week , and one month post-irrigation . The survival rate of the target microorganisms was determined and the effect of irrigation with antimicrobial agents on this microflora was compared with the control groups ( 1 and 2 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Chronic periodontitis is a silent infectious disease prevalent worldwide and affects lifestyle-related diseases . Therefore , efficient screening of patients is essential for general health . This study was performed to evaluate prospect ively the diagnostic utility of a blood IgG antibody titer test against periodontal pathogens . Oral examination was performed , and IgG titers  against periodontal pathogens were measured by ELISA in 1,387 individuals . The cut-off value of the IgG titer was determined in receiver operating characteristic curve analysis , and changes in periodontal clinical parameters and IgG titers by periodontal treatment were evaluated . The relationships between IgG titers and severity of periodontitis were analyzed . The best cut-off value of IgG titer against Porphyromonas gingivalis for screening periodontitis was 1.682 . Both clinical parameters and IgG titers decreased significantly under periodontal treatment . IgG titers of periodontitis patients were significantly higher than those of healthy controls , especially in those with sites of probing pocket depth over 4 mm . Multiplied cut-off values were useful to select patients with severe periodontitis . A blood IgG antibody titer test for Porphyromonas gingivalis is useful to screen hitherto chronic periodontitis patients ( Clinical Trials.gov number NCT01658475 ) BACKGROUND This study was conducted to determine the component that causes the disease in rheumatoid arthritis ( RA ) , which shows great resemblance to periodontitis in a pathologic context . MATERIAL S AND METHODS Within this study , the pathogen-specific IgG levels formed against Porphyromonas gingivalis FDC 381 , Prevotella melaninogenica ATCC 25845 , Actinobacillus actinomycetemcomitans Y4 , Bacteroides forsythus ATCC 43047 , and Prevotella intermedia 25611 oral bacteria were research ed from the blood serum sample s of 30 RA patients and 20 healthy controls with the enzyme-linked immunosorbent assay ( ELISA ) method . RESULTS The IgG levels of P gingivalis , P intermedia , P melaninogenica , and B forsythus were found to be significantly higher in RA patients when compared with those of the controls . Of the other bacteria antibodies , A actinomycetemcomitans was not found at greater levels in RA serum sample s in comparison with the healthy sample s. CONCLUSION The antibodies formed against P gingivalis , P intermedia , P melaninogenica , and B forsythus could be important to the etiopathogenesis of RA Objective This study aim ed to evaluate prospect ively the influence and the evolution of periodontal disease ( PD ) in rheumatoid arthritis ( RA ) patients su bmi tted to anti – tumor necrosis factor ( TNF ) therapy .  Methods Eighteen patients with RA ( according to the American College of Rheumatology criteria ) were assessed for PD before ( BL ) and after 6 months ( 6 M ) of anti-TNF treatment : 15 infliximab , 2 adalimumab , and 1 etanercept .  Periodontal assessment included plaque and gingival bleeding indices , probing pocket depth , cementoenamel junction , and clinical attachment level . Rheumatologic evaluation was performed blinded to the dentist ’s assessment : demographic data , clinical manifestations , and disease activity ( Disease Activity Score using 28 joints [ DAS28 ] , erythrocyte sedimentation rate [ ESR ] , and C-reactive protein [ CRP ] ) . Results The median age and disease duration of patients with RA were 50 years ( 25–71 y ) and 94 % were female .  Periodontal disease was diagnosed in 8 patients ( 44.4 % ) . Comparing BL to 6 M , periodontal parameters in the entire group remained stable ( P > 0.05 ) throughout the study ( plaque and gingival bleeding indices , probing pocket depth , cementoenamel junction , and clinical attachment level ) , whereas an improvement in most analyzed RA parameters was observed in the same period : DAS28 ( 5.5 vs. 3.9 , P = 0.02 ) , ESR ( 21 vs. 12.5 mm/first hour , P = 0.07 ) , and CRP ( 7.8 vs. 2.8 mg/dL , P = 0.25 ) . Further analysis revealed that this improvement was restricted to the group of patients without PD ( DAS28 [ 5.5 vs. 3.6 , P = 0.04 ] , ESR [ 23.0 vs. 11.5 mm/first hour , P = 0.008 ] , and CRP [ 7.4 vs. 2.1 , P = 0.01 ] ) . In contrast , patients with PD had lack of response , with no significant differences in disease activity parameters between BL and 6 M : DAS28 ( 5.2 vs. 4.4 , P = 0.11 ) , ESR ( 17.0 vs. 21.0 , P = 0.56 ) , and CRP ( 9.0 vs. 8.8 , P = 0.55 ) . Conclusions This study supports the notion that PD may affect TNF blocker efficacy in patients with RA . The possibility that a sustained gingival inflammatory state may hamper treatment response in this disease has high clinical interest because this is a treatable condition BACKGROUND Porphyromonas gingivalis has been implicated as an etiologic agent of rheumatoid arthritis ( RA ) because of the expression of peptidylarginine deiminase . The present study evaluates whether periodontal treatment may affect serum antibodies to P. gingivalis and citrulline levels in relation to disease activity of RA . METHODS Fifty-five patients with RA were r and omly assigned to receive oral hygiene instruction and supragingival scaling ( treatment group , n = 26 ) or no periodontal treatment ( control group , n = 29 ) . Periodontal and rheumatologic parameters and serum levels of cytokine and inflammatory markers citrulline and immunoglobulin (Ig)G to P. gingivalis were examined at baseline and 8 weeks later . RESULTS Both groups did not differ statistically in any parameters except percentage of sites with probing depth and clinical attachment level ≥ 4 mm at baseline . The treatment group exhibited a significantly greater decrease in disease activity score including 28 joints using C-reactive protein ( DAS28-CRP ) ( P = 0.02 ) , serum levels of IgG to P. 
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