Risk Of Inflammatory Disease Research Articles

Development of a beverage based on citric juice with the addition of whey

Abstract Faced with new trends in healthy eating, there is a need to expand this market. The Argentine Society of Nutrition, based on local and international studies, has suggested that an adequate intake of dairy products not only provides calcium but also provides compounds associated with a decrease in the risk of chronic inflammatory diseases. The objectives of this work were to formulate and develop beverages based on orange juice with the addition of liquid and powdered whey, sweetened naturally, and study the physicochemical, nutritional and sensory characteristics. The samples were homogenized and pasteurized at 85 °C for 30 minutes and the pH value, acidity, solids content and colour were analyzed. A just-about-right (JAR) scale was used to evaluate the intensities of the acid taste, bitter taste and flavour, and also the colour attributes, and a 5-point hedonic scale was used to evaluate the global acceptability of the samples. The intensity analyses showed that the taste and colour were “ideal”. With respect to global acceptability, the pleasant categories scored more than 60% and only 10% considered it unpleasant. The beverage presented a pH value, colour and solids content similar to those of other citrus beverages, and was rated as pleasant by the consumers.

Calcium signaling and regulation of neutrophil functions: Still a long way to go

Neutrophils are the most abundant leukocytes in blood and disruption in their functions often results in an increased risk of serious infections and inflammatory autoimmune diseases. Following recent discoveries in their influence over disease progression, a resurgence of interest for neutrophil biology has taken place. The multitude of signaling pathways activated by the engagement of numerous types of receptors, with which neutrophils are endowed, reflects the functional complexity of these cells. It is therefore not surprising that there remains a huge lack in the understanding of molecular mechanisms underlining neutrophil functions. Moreover, studies on neutrophils are undoubtedly limited by the difficulty to efficiently edit the cell's genome. Over the past 30 years, compelling evidence has clearly highlighted that Ca2+ -signaling is governing the key processes associated with neutrophil functions. The confirmation of the role of an elevation of intracellular Ca2+ concentration has come from studies on NADPH oxidase activation and phagocytosis. In this review, we give an overview and update of our current knowledge on the role of Ca2+ mobilization in the regulation of pro-inflammatory functions of neutrophils. In particular, we stress the importance of Ca2+ in the formation of NETs and cytokine secretion in the light of newest findings. This will allow us to embrace how much further we have to go to understand the complex dynamics of Ca2+ -dependent mechanisms in order to gain more insights into the role of neutrophils in the pathogenesis of inflammatory diseases. The potential for therapeutics to regulate the neutrophil functions, such as Ca2+ influx inhibitors to prevent autoimmune and chronic inflammatory diseases, has been discussed in the last part of the review.

C-reactive protein is associated with cognitive performance in a large cohort of euthymic patients with bipolar disorder.

Data support the notion that 40-60% of patients with bipolar disorder (BD) have neurocognitive deficits. It is increasingly accepted that functioning in BD is negatively impacted by these deficits, yet they have not been a successful target for treatment. The biomarkers that predict cognitive deficits in BD are largely unknown, however recent evidence suggests that inflammation may be associated with poorer cognitive outcomes in BD. We measured C-reactive protein (CRP), a marker of systemic inflammation and risk of inflammatory disease, in 222 euthymic BD patients and 52 healthy controls. Within the patient sample, using multivariate analyses of covariance (MANCOVA) we compared cognitive performance of those with high CRP (≥5 mg/L) versus the remaining subjects (<5 mg/L) on a battery of cognitive tests. We evaluated relationships with several other relevant clinical features. We also examined the role of CRP in cognitive decline using a proxy cognitive decline metric, defined as the difference between premorbid and current IQ estimates, in a logistic regression analysis. Approximately 80% of our sample were BD-I, and the remainder were BD-II and 42.6% of our sample had a history of psychosis. We found a statistically significant effect of CRP on cognitive performance on a broad range of tests; participants with CRP ≥ 5 mg/L had worse performance on several measures of executive functioning, MATRICS processing speed andMATRICS reasoning and problem solving relative to those with lower CRP. We also identified CRP as a significant positive predictor of proxy cognitive decline. Our results indicate that elevated CRP is associated with a broad cognitive dysfunction in affectively remitted BD patients. These results may point to a subgroup of patients who might benefit from treatments to reduce inflammation.

Рефракционная хирургия как фактор риска возникновения воспалительных заболеваний глаз

Рефракционная хирургия как фактор риска возникновения воспалительных заболеваний глаз

The role of the miR1976/CD105/integrin \u03b1v\u03b26 axis in vaginitis induced by Escherichia coli infection in mice

Vaginitis is very common among women, especially women of childbearing age, and is associated with significantly increased risk of preterm birth and pelvic inflammatory diseases. An imbalance in the vaginal flora, the primary cause of vaginitis, promotes the initiation and progression of vaginal infections. However, the responsible mechanisms are still poorly understood. Using a murine vaginitis model of Escherichia coli infection, we demonstrated that decreased expression of microRNA1976 and increased expression of CD105 and integrin αvβ6 were closely associated with the progression of vaginal infection. Importantly, we demonstrated for the first time that the microRNA1976/CD105/integrin αvβ6 axis regulates E. coli-mediated vaginal infection in mice, as evidenced by the finding that E. coli-induced vaginal infection was reversed by microRNA1976 overexpression and exacerbated by CD105 overexpression. The regulation of CD105 and integrin αvβ6 by microRNA1976 was further confirmed in a murine model of vaginitis with adenoviral vector treatment. Taken together, our data suggested that microRNA1976 negatively regulates E. coli-induced vaginal infection in mice at least in part by suppressing CD105 and integrin αvβ6 expression. These findings may provide new insight into the mechanisms of E. coli-induced vaginitis, identify a novel diagnostic biomarker and a potential therapeutic target for flora imbalance-associated vaginitis.

Plasma Metabolic Signature and Abnormalities in HIV-Infected Individuals on Long-Term Successful Antiretroviral Therapy.

Targeted metabolomics studies reported metabolic abnormalities in both treated and untreated people living with human immunodeficiency virus (HIV) (PLHIV). The present study aimed to understand the plasma metabolomic changes and predicted the risk of accelerated aging in PLHIV on long-term suppressive antiretroviral therapy (ART) in a case-control study setting and its association with the plasma proteomics biomarkers of inflammation and neurological defects. Plasma samples were obtained from PLHIV on successful long-term ART for more than five years (n = 22) and matched HIV-negative healthy individuals (n = 22, HC herein). Untargeted metabolite profiling was carried out using ultra-high-performance liquid chromatography/mass spectrometry/mass spectrometry (UHPLC/MS/MS). Plasma proteomics profiling was performed using proximity extension assay targeting 184 plasma proteins. A total of 250 metabolites differed significantly (p < 0.05, q < 0.1) between PLHIV and HC. Plasma levels of several essential amino acids except for histidine, branched-chain amino acids, and aromatic amino acids (phenylalanine, tyrosine, tryptophan) were significantly lower in PLHIV compared to HC. Machine-learning prediction of metabolite changes indicated a higher risk of inflammatory and neurological diseases in PLHIV. Metabolic abnormalities were observed in amino-acid levels, energetics, and phospholipids and complex lipids, which may reflect known differences in lipoprotein levels in PLHIV that can resemble metabolic syndrome (MetS).

57 INVESTIGATING THE COMMON GENETIC BASIS OF ANTIDEPRESSANT RESPONSE

New research is revealing a strong association between inflammatory markers with bipolar disorder (BD), potentially due to the high prevalence of cardiovascular disease and cardiovascular risk factors in BD. We aimed to synthesize the literature examining the association between the clinically most relevant inflammatory marker, C-reactive protein (CRP) and cardiovascular disease and cardiovascular risk factors in patients with BD.MEDLINE, Embase and PsychInfo were systematically searched for all relevant English language articles published prior to April 2017. Articles were included if they examined the association between CRP and cardiovascular risk factors/disease in BD.Fifteen relevant articles were retrieved. Studies were mostly cross-sectional and heterogeneous in the cardiovascular risk factors investigated. Overall, elevated CRP was associated with increased risk of metabolic syndrome, elevated body mass index, higher waist circumference, and obesity. CRP was inconsistently associated with elevated fasting glucose, insulin levels, serum triglycerides, total cholesterol levels, and low high density lipoprotein (HDL) levels. Atypical antipsychotic use may mediate some of these effects. No study examined CRP's association with actual cardiovascular disease (e.g. coronary artery disease) in BD.In BD, CRP is associated with increases in several cardiovascular risk factors, suggesting that systemic inflammation could be a shared driving force for both outcomes of BD and cardiovascular risk. Further longitudinal research is needed in this area to verify causality, including an examination of actual cardiovascular disease. Non-pharmacological and pharmacological treatments with anti-inflammatory effects should also be investigated, particularly in patients with increased CRP, for their potential to reduce cardiovascular risk in BD.

Gut bacteria responding to dietary change encode sialidases that exhibit preference for red meat-associated carbohydrates.

Dietary habits have been associated with alterations of the human gut resident microorganisms contributing to obesity, diabetes, and cancer1. In Western diets, red meat is one of the frequently eaten foods2, but long-term consumption has been associated with increased risk of disease3,4. Red meat is enriched in N-glycolylneuraminic acid (Neu5Gc) that cannot be synthesized by humans5. However, consumption can cause Neu5Gc incorporation into cell surface glycans6, especially in carcinomas4,7. As a consequence, an inflammatory response is triggered when Neu5Gc-containing glycans encounter circulating anti-Neu5Gc antibodies8,9. Although bacteria can utilize free sialic-acids as a nutrient source10-12, it is currently unknown if gut microorganisms contribute to releasing Neu5Gc from food. We found that a Neu5Gc-rich diet induces changes in the gut microbiota, with Bacteroidales and Clostridiales responding for the most. Genome assembling of mouse and human shotgun metagenomic sequencing identified bacterial sialidases with previously unobserved substrate preference for Neu5Gc-containing glycans. X-ray crystallography revealed key amino-acids potentially contributing to substrate preference. Additionally, we verified that mouse and human sialidases were able to release Neu5Gc from red meat. The release of Neu5Gc from red meat using bacterial sialidases could reduce the risk of inflammatory diseases associated with red meat consumption, including colorectal cancer4 and atherosclerosis13.

Erratum to: Chlamydia trachomatis and the Risk of Pelvic Inflammatory Disease, Ectopic Pregnancy, and Female Infertility: A Retrospective Cohort Study Among Primary Care Patients.

BACKGROUND: We evaluated the risk of pelvic inflammatory disease (PID), ectopic pregnancy, and infertility in women with a previous Chlamydia trachomatis (CT) diagnosis compared with women who tested negative for CT and CT untested women, considering both targeted and incidental (ie, prescribed for another indication) use of CT-effective antibiotics. METHODS: This was a retrospective study of women aged 12-25 years at start of follow-up within the Clinical Practice Research Datalink GOLD database linked to index of multiple deprivation quintiles, 2000-2013. CT test status and antibiotic use were determined in a time-dependent manner. Risk of PID, ectopic pregnancy, or female infertility were evaluated using of Cox proportional hazard models. RESULTS: We studied 857 324 women, contributing 6 457 060 person-years. Compared with women who tested CT-negative, women who tested CT-positive had an increased risk of PID (adjusted hazard ratio [aHR], 2.36; 95% confidence interval [CI], 2.01-2.79), ectopic pregnancy (aHR, 1.87; 95% CI, 1.38-2.54), and infertility (aHR, 1.85; 95% CI, 1.27-2.68). The PID risk was higher for women with 2 or more positive CT tests than those with 1 positive test. PID risk increased with the number of previous antibiotic prescriptions, regardless of CT test status. CONCLUSIONS: We showed an association between CT-positive tests and 3 adverse reproductive health outcomes. Moreover, this risk increased with repeat CT infections. CT-effective antibiotic use showed no decreased risks of subsequent PID regardless of CT history. Our results confirm the reproductive health burden of CT, which requires adequate public health interventions.

Association between regular walking and periodontitis according to socioeconomic status: a cross-sectional study

Physical activity reduces the risk and mortality risk of inflammatory diseases. This study aimed to examine the relationship between regular walking and periodontitis in a Korean representative sample of adults according to socioeconomic status. Data acquired by the Sixth Korea National Health and Nutrition Examination Survey in 2014 and 2015 were used. The survey was completed by 11,921 (5,175 males; 6,746 females) participants (≥19 years). Individuals without values on periodontitis were excluded, and 9,728 participants remained. Multivariable logistic regression analysis was done using socio-demographic characteristics (age, gender, income, education), oral health-related variables (flossing, interdental brushing, community periodontal index), oral and general health status and behaviour (smoking, diabetes mellitus), and regular walking. In all models, subjects who walked regularly had significantly lower risks of periodontitis. After adjusting for age, gender, income, education, smoking, diabetes mellitus, flossing, and interdental brushing, the odds ratio for periodontitis in subjects who walked regularly was 0.793 (95% Confidence interval: 0.700–0.898). Non-regular walking groups showed similar social gradients. Risk of low socioeconomic status was not significant in the regular walking group after adjusting for age, gender, income, and education. This study found that regular walking is associated to lower prevalence of periodontitis and can attenuate the relationship between periodontitis and low socioeconomic status.

Dietary Inflammatory Index Score and Cardiovascular Disease Risk Markers in Women with Systemic Lupus Erythematosus

BackgroundPatients with systemic lupus erythematosus (SLE), a chronic inflammatory autoimmune disease, have an increased risk of developing cardiovascular diseases. Environmental factors like diet and nutrition are known to play a key role in modulating inflammation and the prognosis of cardiovascular diseases. ObjectiveTo investigate the relationship between Dietary Inflammatory Index score and cardiovascular disease risk markers in a population of women with SLE. DesignA cross-sectional study was conducted in women with SLE recruited from 2016 through 2017. Participants/settingsClinically stable women with SLE were enrolled from three public hospitals in the Andalusian region of Spain. Participants with chronic renal failure, active infections, recent trauma, pregnancy, and/or other autoimmune diseases were excluded. Main outcome measuresA 24-hour diet recall was used to estimate Dietary Inflammatory Index score and physical activity was assessed through the International Physical Activity Questionnaires. Cardiovascular disease risk markers included blood lipid profile (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels), high-sensitivity C-reactive protein levels, and homocysteine levels, along with diagnosis of obesity, diabetes mellitus, hypertension, dyslipidemia, and ankle-brachial index measurement. Statistical analysisComparisons of cardiovascular disease risk markers across Dietary Inflammatory Index score tertiles were analyzed through a one-way analysis of variance and linear regressions adjusting for age, physical activity level, and medical treatment. ResultsA total of 105 women (aged 45.4±12.8 years) were included. Linear regression analysis revealed that Dietary Inflammatory Index score was significantly associated with total cholesterol levels (β=.26, 95% CI 1.66 to 14.28; P=0.014) after adjusting for age, physical activity, and the use of medical treatment. No significant associations were observed between Dietary Inflammatory Index score and the other cardiovascular markers considered. ConclusionsHigher inflammatory potential of the diet was positively associated with higher total cholesterol levels in women with SLE. These findings suggest that the inflammatory potential of a person’s diet may play a role in lipid profiles in this population. Future intervention studies are needed to build on these results and explore the effect of anti-inflammatory diets on health outcomes in individuals with SLE.

Protective Effect of Trans-chalcone Against High-Fat Diet-Induced Pulmonary Inflammation Is Associated with Changes in miR-146a And pro-Inflammatory Cytokines Expression in Male Rats.

High-fat diet (HFD) increases the risk of non-communicable inflammatory diseases including pulmonary disorders. Trans-chalcone is a chalcone with antioxidant and anti-inflammatory effects. This study aimed to explore the effect of this natural compound and molecular mechanism of its effect on HFD-induced pulmonary inflammation. Twenty-eight male Wistar rats were randomly divided into four main groups (n = 7 per each group): control, receiving 10% tween 80; Chal, receiving trans-chalcone, HFD, receiving a high-fat emulsion and 10% tween 80; HFD + Chal, receiving a high-fat emulsion and trans-chalcone. After 6weeks, the lungs were dissected, and the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and miR-146a were determined using real-time PCR. Moreover, histological analysis was done by hematoxylin and eosin staining. Significant elevations in TNF-α, IL-1β, IL-6, and miR-146a expression levels (P < 0.001) were observed within the lungs of HFD-fed rats compared with the control. However, oral administration of trans-chalcone reduced TNF-α, IL-1β, IL-6 (P < 0.001), and miR-146a (P < 0.05) expression levels and also improved HFD-induced histological abnormalities. These findings indicate that trans-chalcone ameliorates lung inflammatory response and structural alterations. It seems that this beneficial effect is associated with the down-regulation of pro-inflammatory cytokines and miR-146a.

Risk of immune-mediated inflammatory diseases in newly diagnosed ankylosing spondylitis patients: a population-based matched cohort study

ObjectiveTo investigate the risk of immune-mediated inflammatory diseases (IMIDs) in patients with ankylosing spondylitis (AS).MethodsUsing 2003–2012 claims data from the Taiwanese National Health Insurance Research Database, we identified 30,911 newly diagnosed AS patients requiring medical therapy from 2006 to 2012. In addition, we randomly selected 309,110 non-AS individuals matching (1:10) the AS patients with regard to age, sex and the year of the index date. After excluding subjects with the corresponding prior IMIDs, we calculated the incidence rates (IRs) of various IMIDs in the AS and non-AS cohorts and estimated the hazard ratios (HRs) with 95% confidence intervals after adjusting for age, sex, the Charlson comorbidity index, the frequency of ambulatory visits during the follow-up period and medications. We conducted sensitivity analyses by excluding those who developed IMIDs within 3 months after the index date.ResultsIn the follow-up period, we found that newly diagnosed AS patients had significantly increased risks of acute anterior uveitis, psoriasis, Sjögren’s syndrome, thromboangiitis obliterans, Behcet’s disease and sarcoidosis. However, the risk of Sjögren’s syndrome did not increase in AS patients in the sensitivity analysis. In the same period, this study found no significant differences in the risks of Crohn’s disease, ulcerative colitis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, polymyositis, pemphigus and vitiligo between newly diagnosed AS patients and non-AS individuals. AS patients had a significantly reduced risk of rheumatoid arthritis.ConclusionNewly diagnosed Taiwanese AS patients had increased risks of acute anterior uveitis, psoriasis, thromboangiitis obliterans, Behcet’s disease and sarcoidosis, but a reduced risk of rheumatoid arthritis.

Chlamydia trachomatis and the Risk of Pelvic Inflammatory Disease, Ectopic Pregnancy, and Female Infertility: A Retrospective Cohort Study Among Primary Care Patients.

BackgroundWe evaluated the risk of pelvic inflammatory disease (PID), ectopic pregnancy, and infertility in women with a previous Chlamydia trachomatis (CT) diagnosis compared with women who tested negative for CT and CT untested women, considering both targeted and incidental (ie, prescribed for another indication) use of CT-effective antibiotics.MethodsThis was a retrospective study of women aged 12–25 years at start of follow-up within the Clinical Practice Research Datalink GOLD database linked to index of multiple deprivation quintiles, 2000–2013. CT test status and antibiotic use were determined in a time-dependent manner. Risk of PID, ectopic pregnancy, or female infertility were evaluated using of Cox proportional hazard models.ResultsWe studied 857 324 women, contributing 6 457 060 person-years. Compared with women who tested CT-negative, women who tested CT-positive had an increased risk of PID (adjusted hazard ratio [aHR], 2.36; 95% confidence interval [CI], 2.01–2.79), ectopic pregnancy (aHR, 1.87; 95% CI, 1.38–2.54), and infertility (aHR, 1.85; 95% CI, 1.27–2.68). The PID risk was higher for women with 2 or more positive CT tests than those with 1 positive test. PID risk increased with the number of previous antibiotic prescriptions, regardless of CT test status.ConclusionsWe showed an association between CT-positive tests and 3 adverse reproductive health outcomes. Moreover, this risk increased with repeat CT infections. CT-effective antibiotic use showed no decreased risks of subsequent PID regardless of CT history. Our results confirm the reproductive health burden of CT, which requires adequate public health interventions.

MITOL deletion in the brain impairs mitochondrial structure and ER tethering leading to oxidative stress.

Mitochondrial abnormalities are associated with developmental disorders, although a causal relationship remains largely unknown. Here, we report that increased oxidative stress in neurons by deletion of mitochondrial ubiquitin ligase MITOL causes a potential neuroinflammation including aberrant astrogliosis and microglial activation, indicating that mitochondrial abnormalities might confer a risk for inflammatory diseases in brain such as psychiatric disorders. A role of MITOL in both mitochondrial dynamics and ER-mitochondria tethering prompted us to characterize three-dimensional structures of mitochondria in vivo. In MITOL-deficient neurons, we observed a significant reduction in the ER-mitochondria contact sites, which might lead to perturbation of phospholipids transfer, consequently reduce cardiolipin biogenesis. We also found that branched large mitochondria disappeared by deletion of MITOL. These morphological abnormalities of mitochondria resulted in enhanced oxidative stress in brain, which led to astrogliosis and microglial activation partly causing abnormal behavior. In conclusion, the reduced ER-mitochondria tethering and excessive mitochondrial fission may trigger neuroinflammation through oxidative stress.

Sleep and inflammation: partners in sickness and in health.

The discovery of reciprocal connections between the central nervous system, sleep and the immune system has shown that sleep enhances immune defences and that afferent signals from immune cells promote sleep. One mechanism by which sleep is proposed to provide a survival advantage is in terms of supporting a neurally integrated immune system that might anticipate injury and infectious threats. However, in modern times, chronic social threats can drive the development of sleep disturbances in humans, which can contribute to the dysregulation of inflammatory and antiviral responses. In this Review, I describe our current understanding of the relationship between sleep dynamics and host defence mechanisms, with a focus on cytokine responses, the neuroendocrine and autonomic pathways that connect sleep with the immune system and the role of inflammatory peptides in the homeostatic regulation of sleep. Furthermore, I discuss the therapeutic potential of harnessing these reciprocal mechanisms of sleep-immune regulation to mitigate the risk of inflammatory and infectious diseases.

Adverse Childhood Experiences and Immune System Inflammation in Adults Residing on the Blackfeet Reservation: The Moderating Role of Sense of Belonging to the Community.

Previous research documents an association between adverse childhood experiences (ACEs) and immune system inflammation. High chronic inflammation is believed to be one biological pathway through which childhood adversity may affect health into adulthood. The Blackfeet tribal community has high rates of childhood trauma and community members are disproportionately affected by inflammatory diseases. To investigate whether belonging to the tribal community may moderate the relationship between childhood trauma and immune system inflammation in the Blackfeet tribal community. In a sample of 90 adults residing on the Blackfeet reservation, we measured ACEs belonging to the tribal community and two markers of immune system inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP). We found that independent of age, gender, annual income, body mass index, and depressive symptoms, belonging to the tribal community and ACEs interacted to predict levels of both IL-6 and CRP (B= -.37, t[81] = -3.82, p < .001, R2 change = .07 and B = -.29, t[81] = -2.75, p = .01, R2 change = .08, respectively). The association between ACEs and markers of immune system inflammation was statistically significant for community members who reported low levels of belonging to the community. The findings of this study have important implications for intervention research seeking to reduce risk for inflammatory diseases for at-risk populations. Fostering stronger connections to the larger tribal community may positively affect risk for inflammatory diseases. Future work should examine the behavioral and psychosocial pathways through which stronger connections to community may confer health benefits.

Can physical activity ameliorate immunosenescence and thereby reduce age-related multi-morbidity?

Remodelling of the immune system with age - immunosenescence - is a substantial contributor to poor health in older adults, with increasing risk of infections, cancer and chronic inflammatory disease contributing to age-related multi-morbidity. What is seldom considered when examining the immune response of an aged individual is that the immune system is profoundly influenced by physical activity. Habitual physical activity levels decline with age, with significant consequences for muscle mass and function. Skeletal muscle is a major immune regulatory organ and generates a range of proteins, termed myokines, which have anti-inflammatory and immunoprotective effects. Several studies indicate that maintaining physical activity has immune benefits in older adults, for example, it reduces the systemic inflammation associated with chronic age-related diseases. Here, we discuss how physical activity can prevent or ameliorate age-related multi-morbidity by boosting immune function, and we consider whether physical activity could improve immunotherapy outcomes in age-related conditions such as cancer.

Inflammaging: Age and Systemic, Cellular, and Nuclear Inflammatory Biology in Older Adults.

Systemic inflammation is associated with increasing age. Yet, there are limited data about the association between age and systemic inflammation within older adults, and whether older age is also associated with cellular and nuclear signaling markers of inflammation. In community-dwelling older adults (N = 262, 60-88 years), systemic levels of C-reactive protein, interleukin-6, and soluble tumor necrosis factor receptor II; levels of toll-like receptor-4-stimulated monocytic production of interleukin-6 and tumor necrosis factor α; and resting nuclear levels of activated nuclear factor kappa B and signal transducer and activator of transcription (STAT1, STAT3, STAT5) were evaluated. Adjusting for demographic and clinical factors, multivariate linear regression tested the association between age and each inflammatory marker. Age was positively associated with increased levels of interleukin-6 and soluble tumor necrosis factor receptor II (p's < .05) and with increases in STAT1, STAT3, and STAT5 activation (p's < .05). However, no relationship was found between age and C-reactive protein, toll-like receptor-4-stimulated interleukin-6/tumor necrosis factor alpha α production, or nuclear factor kappa B. Within a community-dwelling sample of older adults, older age is associated with increases in STAT activation, along with increases of systemic inflammatory cytokines. In older adults, heterogeneity in age-related increases in inflammatory disease risk may be related to individual variability in inflammation.

Incidence of osteoarthritis, osteoporosis and inflammatory musculoskeletal diseases in adults with cerebral palsy: A population-based cohort study.

People with cerebral palsy (CP) may be at increased risk of musculoskeletal conditions due to various factors including malnutrition and abnormal levels of skeletal loading. This study aimed to compare the incidence of osteoporosis, osteoarthritis and inflammatory musculoskeletal diseases between adults with and without CP. A population based cohort study was conducted using data from the Clinical Practice Research Datalink collected between 1987 and 2015. Adults with CP were matched to adults without CP for age, sex and general practice. Cox models, stratified by matched set and adjusted for potential confounders, were fitted to compare the risk of osteoporosis, osteoarthritis and inflammatory musculoskeletal diseases. 1705 adults with CP were matched to 5115 adults without CP. Adults with CP had an increased risk of osteoporosis in unadjusted (Hazard Ratio (HR) 3.67, 95% Confidence Interval (CI) 2.32 to 5.80, p < 0.001) and adjusted (HR 6.19, 95% CI 3.37 to 11.39, p < 0.001) analyses. No evidence of increased risk of inflammatory musculoskeletal diseases was observed in unadjusted or adjusted analyses. For osteoarthritis no evidence of increased risk was seen in the unadjusted analysis, but evidence of an increased risk was seen when the analysis was adjusted for alcohol consumption, smoking status, and mean yearly general practice (GP) visits (HR 1.54, 95% CI 1.17 to 2.02, p < 0.001). After accounting for potential confounding variables, we found that CP is associated with increased risk of osteoporosis and osteoarthritis. These findings provide the strongest epidemiological evidence to date for increased risk of osteoporosis and osteoarthritis in people with CP, and highlight need for clinical awareness of such conditions in this population.