Effects of Exercise Training and L-Arginine Loaded Chitosan Nanoparticles on Hippocampus Histopathology, ß-Secretase Enzyme Function, APP, Tau, Iba1and APOE-4 mRNA in Aging Rats.

The objective of this study was to evaluate the combined and independent effects of exercise training and L-Arginine loaded chitosan nanoparticles (LA CNPs) supplementation on hippocampal Tau, App, Iba1, and ApoE gene expression, oxidative stress, ß-secretase enzyme activity, and hippocampus histopathology in aging rats. Thirty-five male Wistar rats were randomly assigned to five groups (n = 7 in each): Young (8 weeks old), Old (20 months old), old + L-arginine supplementation (Old Sup), old + exercise (Old Exe) and old + L-arginine supplementation + exercise (Old Sup + Exe). LA CNPs were administered to the supplement groups through gavage at a dosage of 500 mg/kg/day for 6-weeks. Exercise groups were subjected to a swimming exercise program five days/week for the same duration. Upon the completion of their interventions, the animals underwent behavioral and open-field task tests and were subsequently sacrificed for hippocampus genetic and histopathological evaluation. For histopathological analysis of brain, Cresyl violet staining was used. Congo Red staining was employed to confirm amyloid plaques in the hippocampus. Expressions of Tau, App, Iba1, and ApoE genes were determined by real-time PCR. In contrast to the Old group, Old Exe and Old Sup + Exe groups spent more time in the central space in the open field task (p < 0.05) and have more live cells in the hippocampus. Old rats (Old, Old Sup and Old Exe groups) exhibited a significant Aß peptide accumulation and increases in APP, Tau, Iba1, APOE-4 mRNA and MDA, along with decreases in SOD compared to the young group (p < 0.05). However, LA CNPs supplementation, exercise, and their combination (Old Sup, Old Exe and Old Sup + Exe) significantly reduced MDA, Aß plaque as well as APP, Tau, Iba1, and APOE-4 mRNA compared to the Old group (p < 0.05). Consequently, the administration of LA CNPs supplements and exercise might regulate the risk factors of hippocampus cell and tissue.

UTexas Aptamer Database: the collection and long-term preservation of aptamer sequence information.

A growing interest in aptamer research, as evidenced by the increase in aptamer publications over the years, has led to calls for a go-to site for aptamer information. A comprehensive, publicly available aptamer dataset, which may be a repository for aptamer data, standardize aptamer reporting, and generate opportunities to expand current research in the field, could meet such a demand. There have been several attempts to create aptamer databases; however, most have been abandoned or removed entirely from public view. Inspired by previous efforts, we have published the UTexas Aptamer Database, https://sites.utexas.edu/aptamerdatabase, which includes a publicly available aptamer dataset and a searchable database containing a subset of all aptamer data collected to date (1990-2022). The dataset contains aptamer sequences, binding and selection information. The information is regularly reviewed internally to ensure accuracy and consistency across all entries. To support the continued curation and review of aptamer sequence information, we have implemented sustaining mechanisms, including researcher training protocols, an aptamer submission form, data stored separately from the database platform, and a growing team of researchers committed to updating the database. Currently, the UTexas Aptamer Database is the largest in terms of the number of aptamer sequences with 1,443 internally reviewed aptamer records.

Medication Adherence With Polypill in Cardiovascular Disease and High-Risk Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Involving 7364 Participants.

Considering the worldwide mortality and morbidity of cardiovascular diseases (CVDs), the necessity of using multiple pills due to the chronicity of this condition, and the importance of medication adherence in these patients, we conducted this systematic review and meta-analysis to assess the polypill effect on adherence in patients with established CVD and at high risk. To accomplish this review, we searched various databases to access grey literature and several electronic databases to find randomized controlled trials (RCTs) assessing polypills compared to individual pills from January 2000 to October 2022. The outcomes were primarily medication adherence, secondarily systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C) serum level, and serious adverse events (SAEs). Ultimately, 2820 studies were detected and narrowed to 8 RCTs based on the eligibility criteria. In this study, involving 7364 patients, there was a significant improvement in medication adherence in the polypill group compared to the individual pills group (Risk Ratio [RR] = 1.29; [95%CI: 1.10; 1.50]). Out of secondary outcomes, SBP was significantly decreased (Mean Difference [MD] = -1.72 mmHg; [95%CI: -2.40; 1.03]), but LDL-C serum level (MD = -0.65 mg/dl; [95%CI: -4.47; 3.16]) and SAE (RR = 1.08; [95%CI: f0.98; 1.20]) did not have a notable difference in polypill compared to individual pills.

Workplace Risk Factors Assessment in North-Azadegan Oil Field Based on Harmful Agents Risk Priority Index (HARPI).

Background: Considering the necessity of health risk management, the present study conducted to provide a comprehensive model for identifying, evaluating, and prioritizing occupational health risks in an oilfield. Methods: We conducted this descriptive-analytical cross-sectional study in 2022 at the North-Azadegan oil field in Iran. The occupational health risk was assessed using the "Harmful Agents Risk Priority Index" (HARPI) method. Results: Among the employees for the office section in all job groups, ergonomic risks due to people's posture while working has the highest risk score and is the most critical risk for implementing corrective actions. In the operational section, for the HSE group, benzene, the production group, Electromagnetic Fields (EMFs), and other groups, undesirable lighting has the highest risk score, and exposure to Toluene, Ethylbenzene, Xylenes (TEX) has the lowest risk score. In this oil field, controlling exposure to benzene, correcting ergonomic conditions, and controlling noise exposure, with scores of 81.3,74.85 and 71.36, have the highest priority, respectively. Sequentially, Toluene, Xylene, and ethylbenzene, with scores of 10.25,11.61, and 11.61, have the lowest control priority. Conclusion: The proposed model can prioritize the workplaces' harmful agents based on the HARPI score due to exposure to chemicals, physical factors, and analysis posture.

Semi-quantitative risk assessment for workers exposed to occupational harmful agents in an oilfield in Iran.

BACKGROUND: Workers are exposed to occupational health hazards from physical, chemical, biological, ergonomic, and psychological agents. Assessing occupational health risks is vital for executing control measures to protect employees' health against harmful occupational agents. OBJECTIVE: The present study aimed to identify, evaluate, and prioritize occupational health risks to assist senior management in determining where to allocate the budget to carry out the required corrective actions in the oilfields project. METHODS: This descriptive-analytical cross-sectional study was performed in 2021 among Iran's Sarvak Azar oil field job groups. The occupational health risk was assessed using the Harmful Agents Risk Priority Index (HARPI) as a semi-quantitative method. Then, to simplify decision-making and budget allocation, we reported HARPI final score in the Pareto principle format. RESULTS: The results show that in this oil field, controlling exposure to adverse lighting, improving the thermal conditions and ergonomics, and preventing noise exposure has the highest priority, with scores of 6342, 5269, 5629, and 5050, respectively. Production, HSE, laboratory, and commissioning need the most health care measures with scores of 8683, 5815, 5394, and 4060, respectively. CONCLUSION: HARPI could be used to prioritize occupational health hazards, and this method can simplify managers' decisions to allocate resources to implement control measures.

The effect of treatment with fexofenadine and fluticasone propionate on the gene expression levels of Th9 transcription factors in patients with allergic rhinitis.

T helper-9 (Th9) is a new T cell subset involved in allergic rhinitis (AR) pathogenesis. Fexofenadine and fluticasone propionate are the first effective line of AR treatment. This study aimed to evaluate the effect of fexofenadine and fluticasone propionate on the gene expression levels of Interferon regulatory factor 4 (IRF4), B cell-activating transcription factor-like (BATF), and SPI1 gene-encoded protein (PU.1), essential transcription factors for Th9 cell differentiation, in AR patients. Twenty-six AR patients (aged 32.8 ± 9.1 years, 13 men and 13 women) were treated with fexofenadine and fluticasone propionate for one month. Expression levels of PU.1, IRF4, and BATF genes were measured using Real-Time PCR. Our results showed that after one month of treatment, the expression level of IRF4 and BATF genes decreased significantly (P < 0.001, P < 0.01, respectively), while PU.1 gene expression was not remarkably different. Overall, our results showed that after one month of treatment with fexofenadine and fluticasone propionate, the expression levels of IRF4 and BATF genes in AR patients decreased, which may be due to this treatment regimen. However, the exact mechanism of action of fexofenadine and fluticasone propionate needs further study.

Cancer Risk Assessment for Workers Exposed to Pollution Source, a Petrochemical Company, Iran.

BACKGROUND: Air pollution have led to severe problem of adverse health effect in the world. This study aimed to conduct the health risk assessment, cancer risk analysis, and non-cancer risk for exposure to volatile organic compounds (VOCs) and hydrogen sulfide (H 2 S) in petrochemical industry. METHODS: In this cross-sectional research, 123 samples were collected in the ambient air in Iran during winter 2016. For sampling and analysis of VOCs and H 2 S, 3 methods (numbers 1500, 1501, and 6013) presented by the National Institute of Occupational Safety and Health (NIOSH) were used. For determination of risk assessment of chemical pollutants, semi-quantitative method presented by the Occupational Safety and Health Division, Singapore was used. Finally, for calculation of cancer risk analysis, Chronic Daily Intake (CDI) and calculation of non-cancer risk, Exposure Concentration (EC) were used. RESULTS: Average concentration of benzene (2.12±0.95) in breathing zone of workers were higher than the Threshold Limit Values-Time Weighted Average (TLV-TWA) (P<0.05). Among chemical substance, benzene had very high rank of risk in petrochemical industry. Rank of risk for H 2 S, toluene, and xylene present in the breathing zone of workers was low. The mean cancer risk for workers exposed to benzene was estimated 8.78×10-3, in other words, 8.7 cancer per 1000 i.e. higher than the acceptable standard of 10-6. In our study, non-cancer risk for BTX was higher than the acceptable standard of 1. CONCLUSION: In particular, overall cancer and toxic risk can be associated with long term exposure to benzene.

Red Cell Distribution Width Is Positively Correlated with Atherosclerotic Cardiovascular Disease 10-Year Risk Score, Age, and CRP in Spondyloarthritis with Axial or Peripheral Disease.

BACKGROUND: Red blood cell distribution width (RDW) is a routine hematologic parameter that is a predictor of cardiovascular disease (CVD) events and is independent of combined traditional risk factor scoring systems. The RDW has also been associated with rheumatic disease activity. Whether RDW is associated with traditional CVD risk factors or Atherosclerotic Cardiovascular Disease (ASCVD) 10-year CVD risk score in patients with seronegative spondyloarthritis with axial or peripheral disease has not been previously determined. METHODS: We performed a retrospective, chart review study evaluating the relationship between RDW, albumin, hemoglobin, C-reactive protein (CRP), absolute lymphocyte count (ALC), and ASCVD scoring parameters [age, hypertension status, diabetes mellitus (DM) status, lipid profile, and smoking status] in a cohort of spondyloarthritis patients, taking into consideration their HLA-B27 status, race, and treatment status. RESULTS: RDW was found to positively correlate with ASCVD 10-year score and age, and ASCVD score did not change over time after patients were treated for spondyloarthritis. Albumin was found to negatively correlate with ASCVD 10-year risk score. Both RDW and albumin correlated with CRP. ALC failed to correlate with ASCVD 10-year score but did show a tendency to be associated with CVD, CVD events, and cardiac conduction abnormalities. CONCLUSIONS: These data indicate that further study is warranted to evaluate RDW, albumin level, and ALC as potential predictors of CVD in the spondyloarthritis patient population.

Achieving Sustained Viral Remission in Patients with Chronic HCV Infection and Cryoglobulinemic Vasculitis Does Not Always Correlate with Normalization of the Serologic Markers.

OBJECTIVE: We aim to describe the persistence of symptoms associated with HCV-associated cryoglobulinemic vasculitis following achievement of (SVR) with IFN- free direct acting antiviral (DAA) therapy. In particular, we describe the persistence of C4 hypocomplementemia and positive Rheumatoid Factor (RF). METHODS: We analyzed a case series of four patients enrolled from the Cleveland VA and known to have chronic HCV infection complicated by mixed cryoglobulinemia. The study included patients treated with interferon (IFN) based treatment and IFN free direct acting antiviral (DAA) therapy. RESULTS: Of the four patients, patients 1 and 2 experienced decline of RF without resolution following DAA therapy. Patient 1 continues to have evidence of disease following treatment. Patient 3 did not have resolution of RF during IFN-based treatment and experienced stabilization of kidney function while on treatment. Patient 4, previously a non-responder to IFN based treatment, experienced significant decline in RF titers along with resolution of cryoglobulin-associated rash with DAA therapy. C4 remained low following treatment in patients 1 and 3. Of the four patients, only patient 1 had prolonged persistence of cryoglobulinemia, measured at 3%, 17 months following achievement of SVR. CONCLUSIONS: We highlight the complexity of the viral-mediated immunologic mechanism that causes cryoglobulinemic vasculitis. Our cases also emphasize the need to consider cryoglobulinemic vasculitis as part of the differential diagnosis even with treated HCV infection. Recognizing these findings are important in our understanding of the pathophysiology of the disease and management in the era of IFN-free DAA therapy.

Idiopathic Inflammatory Myopathies: A Review of the Classification and Impact of Pathogenesis.

Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune muscle diseases with significant morbidity and mortality. This review details and updates the pathogenesis and emerging importance of myositis-specific antibodies in the development of IIMs. An increase in the understanding of how these myositis-specific antibodies play a role in IIMs has led to the further categorization of IIMs from the traditional polymyositis versus dermatomyositis, to additional subcategories of IIMs such as necrotizing autoimmune myositis (NAM). The diagnosis of IIMs, including manual muscle testing, laboratory studies, and non-invasive imaging have become important in classifying IIM subtypes and for identifying disease severity. Treatment has evolved from an era where glucocorticoid therapy was the only option to a time now that includes traditional steroid-sparing agents along with immunoglobulin therapy and biologics, such as rituximab.

Incidence and risk of heart failure in systemic lupus erythematosus.

BACKGROUND: Although case series suggest a higher burden of cardiovascular risk factors in patients with systemic lupus erythematosus (SLE) compared with the general population, the association between SLE and heart failure (HF) remains undefined. We sought to investigate the incidence and risk of HF in patients with SLE. METHODS: In April 2016, we performed a retrospective cohort analysis using the Explorys platform, which provides aggregated electronic medical record data from 26 major integrated healthcare systems across the USA from 1999 to present. Demographic and regression analyses were performed to assess the impact of SLE on HF incidence. RESULTS: Among 45 284 540 individuals in the database, we identified 95 400 (0.21%) with SLE and 98 900 (0.22%) with a new diagnosis of HF between May 2015 and April 2016. HF incidence was markedly higher in the SLE group compared with controls (0.97% vs 0.22%, relative risk (RR): 4.6 (95% CI 4.3 to 4.9)), as were other cardiovascular risk factors. In regression analysis, SLE was an independent predictor of HF (adjusted OR: 3.17 (2.63 to 3.83), p<0.0001). RR of HF was highest in young males with SLE (65.2 (35.3 to 120.5) for age 20-24), with an overall trend of increasing absolute risk but decreasing RR with advancing age in both sexes. Renal involvement in SLE correlated with earlier and higher incidence of HF. CONCLUSIONS: The findings of this study suggest that patients with SLE have significantly higher risk of developing HF and a worse cardiovascular risk profile compared with the general population. These results need to be confirmed by prospective studies.

Esophageal Perforation in a Patient With Kidney Transplantation.

Esophageal perforation is a rupture of the esophageal wall, caused by iatrogenesis in 56% of cases. Perforation of the esophagus remains a challenge, and its incidence has increased as the use of endoscopic procedures has become more frequent. We report a 54-year-old woman with esophageal perforation 8 days after kidney transplantation. She had received a gastrointestinal consultation prior to her transplantation. This report highlights the fact that perforation may occur after any organ transplantation, especially during the initial 2 weeks after transplantation, when mycophenolate mofetil and cyclosporine as well as and high doses of corticosteroid are administered. If there is a delay in passage and a swallowing difficulty, high doses of immunosuppressive drugs are likely to cause ulceration and perforation. Preventive strategies including intravenous steroids for the first 2 to 3 weeks and divided doses of pills should be considered for such patients.

The Relationship between NALP3 and Autoinflammatory Syndromes.

The nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing-3 (NALP3) inflammasome, which is required for synthesis of interleukin-1ß, has been implicated in the pathogenesis of several autoinflammatory syndromes. This review of the literature summarizes the interconnectedness of NALP3 inflammasome with some of these disorders. Familial Mediterranean fever results from a mutation in the Mediterranean fever (MEFV) gene, which encodes the pyrin protein. Previous study results suggest that pyrin suppresses caspase-1 activation, perhaps by competing for the adaptor protein, termed, pyrin domain of apoptosis/speck-like protein containing a caspase-recruitment domain (ACS) which therefore interferes with NALP3 inflammasome activation. The nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing-3 (NALP3) inflammasome is constitutively activated in cryopyrin-associated periodic syndromes due to gain-of-function mutations resulting from point mutations within the neuronal apoptosis inhibitor protein/class 2 transcription factor/heterokaryon incompatibility/telomerase-associated protein-1 (NACHT) domain of the NALP3 protein. Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is caused by mutations in the genes encoding proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1). These PSTPIP1 mutants are thought to bind to pyrin causing an increase in the pyrin domain of apoptosis/speck-like protein containing a caspase-recruitment domain (ASC) pyroptosome assembly leading to procaspase-1 recruitment and therefore its activation. Hyperimmunoglublinemia D syndrome is caused by mevalonate kinase (MVK) deficiency, which may be affected by protein accumulation that leads to NALP3 inflammasome activation. Tumor necrosis factor receptor-associated periodic syndrome is associated with mutations in the tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A) gene which decreases the level of soluble tumor necrosis factor receptor-1 (TNFR1) leading to neutralization of tumor necrosis factor (TNF)-α. In general, these autoinflammatory disorders have shown a clinical response to interleukin-1 (IL-1) antagonists, suggesting that the NALP3 inflammasome serves a critical role in their pathogenesis.

The biological and clinical activity of anti-malarial drugs in autoimmune disorders.

Chloroquine and hydroxychloroquine are 4-aminoquinoline compounds commonly employed as anti-malarial drugs. Chloroquine and its synthetic analogue, hydroxychloroquine also belong to the disease-modifying anti-rheumatic drug class because these drugs are immunosuppressive. The immunosuppressive activity of chloroquine and hydroxychloroquine is likely to account for their capacity to reduce T-cell and B-cell hyperactivity as well as pro-inflammatory cytokine gene expression. This review evaluated experimental and clinical trials results as well as clinical response data relative to the use of chloroquine and/or hydroxychloroquine as first-line medical therapies in systemic lupus erythematosus, rheumatoid arthritis, primary Sjogren's syndrome, the anti-phospholipid syndrome and in the treatment of sarcoidosis. A primary outcomes measure in these clinical trials was the extent to which chloroquine and/or hydroxychloroquine reduced disease progression or exacerbations and/or the use and dosage of corticosteroids. The relative efficacy of chloroquine and hydroxychloroquine in modifying the clinical course of these autoimmune disorders is balanced against evidence that these drugs induce adverse effects which may reduce their use and effectiveness in the therapy of autoimmune disorders.

Identification of oral bacterial DNA in synovial fluid of patients with arthritis with native and failed prosthetic joints.

OBJECTIVE: We examined the presence of bacterial DNA in synovial fluids of native or clinically aseptically failed prosthetic joints from patients having periodontal disease and arthritis to determine whether there is bacterial spread from the oral cavity to the joints. METHODS: A total of 36 subjects were enrolled in the study. Among these, 11 were diagnosed with rheumatoid arthritis (RA) and 25 were diagnosed with osteoarthritis (OA). Eight patients with OA and 1 patient with RA had failed prostheses. Synovial fluid was aspirated from the affected hip or knee joint. Pooled subgingival plaque samples were collected, followed by clinical periodontal examination. Bacterial DNA was extracted from the collected synovial fluid and dental plaque samples were followed by polymerase chain reactions and DNA sequence analysis of the 16S-23S rRNA genes. RESULTS: Of the 36 patients, bacterial DNA was detected in the synovial fluid samples from 5 patients (13.9%): 2 with RA (1 native and 1 failed prosthetic joints) and 3 with OA (1 native and 2 failed prosthetic joints). Of these 5 patients, 2 were diagnosed with periodontitis and had identical bacterial clones (Fusobacterium nucleatum and Serratia proteamaculans, respectively) detected in both the synovial fluid and the dental plaque samples. Fusobacterium nucleatum was the most prevalent, detected in 4 of the 5 positive samples. No cultures were done and no patients were treated with antibiotics or developed clinical infection. CONCLUSIONS: The present findings of bacterial DNA in the synovial fluid suggest the possibility of organisms translocating from the periodontal tissue to the synovium. We suggest that patients with arthritis or failed prosthetic joints be examined for the presence of periodontal diseases and be treated accordingly.

Comparison of dysfunctional attitudes and social adjustment among infertile employed and unemployed women in Iran.

This study aims to compare dysfunctional attitudes and social adjustment in infertile employed and unemployed females. Due to the stresses of infertility, infertile females are faced with a variety of sexual and psychological problems, as well as dysfunctional attitudes that can lead to depression. Moreover, infertility problems provoke women into maladjustment and inadvertent corruption of relationships. In this regard, our goal is to consider the effects of employment in conjunction with education on dysfunctional attitudes and social adjustment among infertile women in Iran. In this work, we employed the survey method. We recruited 240 infertile women, utilizing the cluster random sampling method. These women filled out the Dysfunctional Attitudes Scale and the social adjustment part of the California Test of Personality. Next, multivariate analysis of variance was performed to test the relationship of employment status and education with dysfunctional attitudes and social adjustment. Our results indicated that dysfunctional attitudes were far more prevalent in infertile unemployed women than in infertile employed women. Also, social adjustment was better in infertile employed women than in infertile unemployed women. It was shown that education level alone does not have significant effect on dysfunctional attitudes and social adjustment. However, we demonstrated that the employment status of infertile women in conjunction with their education level significantly affects the two dimensions of dysfunctional attitudes (relationships, entitlements) and has insignificant effects on social adjustment. It was revealed that in employed infertile women in Iran, the higher education level, the less dysfunctional were attitudes in relationships and entitlements, whereas in unemployed infertile women, those with a college degree had the least and those with master's or higher degrees had the most dysfunctional attitudes in terms of relationships and entitlements.

Cardiovascular disease complications in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a highly variable autoimmune disease characterized by aberrant host-immune responses and chronic inflammation. Recently, a strong association between cardiovascular (CV) disease and SLE has emerged. Thus, low serum, high-density lipoprotein strongly correlated with elevated erythrocyte sedimentation rate, IL-6, TNF-alpha and the SLE disease activity index after adjusting for age, gender, race, BMI, insulin sensitivity and any concurrent drug use. In SLE, CV disease is characterized by increased VEGF, which may alter vascular hemostasis and promote neoangiogenesis. Increased low-density lipoprotein-cholesterol and proinflammatory high-density lipoprotein-cholesterol uptake by monocytes together with enhanced low-density lipoprotein-cholesterol oxidation results in the deposition of altered cholesterol forms into the vascular wall. This contributes to precocious and accelerated development of coronary artery plaques. Cholesterol-reducing drugs should be considered in the standard of care of SLE patients, especially in those with an unfavorable CV disease risk profile, which could reduce the probability of atherosclerosis progressing to CV disease or stroke in these patients.

Control of periodontal infection reduces the severity of active rheumatoid arthritis.

OBJECTIVE: To determine if eliminating periodontal infection and gingival inflammation affects the severity of active rheumatoid arthritis (RA) in patients with chronic inflammatory periodontal disease. METHODS: Twenty-nine subjects with confirmed diagnosis of RA and mild-to-moderate chronic periodontitis of at least 3 years' duration were enrolled in the study. The activity of RA was assessed using the disease activity score test (DAS28). Seventeen subjects completing the study received periodontal treatment consisting of scaling/root planing and oral hygiene instruction; 12 subjects completing the study received no treatment. Participants continued their usual disease-modifying medications for RA without any changes in DMARD therapy during the study period. RA measurements, and periodontal indices were recorded at baseline and at 8 weeks for each participant. Mann-Whitney U and chi tests were used to test for significant differences in the severity of RA in the periodontally treated group compared with the untreated groups. RESULTS: Ten of 17 subjects (58.8%) in the treated group and 2 of 12 subjects (16.7%) in the untreated group showed improvement in RA scores. There was a statistically significant difference in DAS28 (4.3 +/- 1.6 vs. 5.1 +/- 1.2) and erythrocyte sedimentation rate (31.4 +/- 24.3 vs. 42.7 +/- 22) between the treatment and the control groups. CONCLUSION: Control of periodontal infection and gingival inflammation by scaling/root planing and plaque control in subjects with periodontal disease may reduce the severity of RA. This notion is supported by reported subjective improvement in treated patients.

Phenotypic and functional analysis of EBV-specific memory CD8 cells in SLE.

T cell dysfunction has been described in systemic lupus erythematosus (SLE). However, the specific phenotype and function of antigen-specific CD8 cells is less clear. Here we determined phenotype and function of Epstein-Barr virus (EBV)-specific CD8 cells at the single-cell level in SLE. HLA-A2-restricted EBV-BMLF-1-specific CD8 cells were enumerated by flow cytometry using tetramers in SLE and healthy control subjects. Antigen-specific CD8 cells were analyzed for expression of differentiation, activation, proliferation, and anti-apoptotic markers. EBV-specific, other virus-specific (specific against a viral peptide pool consisting of cytomegalovirus, EBV and influenza virus peptides), and mitogen-induced CD8 cell function was assessed by INF-gamma ELISPOT assay. Frequencies of EBV-specific CD8 cells tended to be greater in SLE subjects than in healthy control subjects (p=0.07). While over 10% of EBV-specific CD8 cells were capable of producing IFN-gamma in four out of five healthy control subjects, such proportions of EBV-specific CD8 cells capable of IFN-gamma production were observed in only one out of six SLE subjects (p=0.04). In contrast, viral peptide pool-specific and mitogen-induced IFN-gamma-producing T cell function was intact in SLE subjects. Phenotypic analysis revealed EBV-specific CD8 cells to be in an early to intermediate differentiation and resting memory state in both groups. While EBV-specific CD8 cells are similar in phenotype, their frequency tends to be increased, and function appears to be decreased in SLE. Therefore, an impaired EBV-specific CD8 immune response may exist in SLE, potentially contributing to disease pathogenesis.