Historic Redlining and Impact of Structural Racism on Diabetes Prevalence in a Nationally Representative Sample of U.S. Adults.

OBJECTIVE: We investigated direct and indirect relationships between historic redlining and prevalence of diabetes in a U.S. national sample. RESEARCH DESIGN AND METHODS: Using a previously validated conceptual model, we hypothesized pathways between structural racism and prevalence of diabetes via discrimination, incarceration, poverty, substance use, housing, education, unemployment, and food access. We combined census tract-level data, including diabetes prevalence from the Centers for Disease Control and Prevention PLACES 2019 database, redlining using historic Home Owners' Loan Corporation (HOLC) maps from the Mapping Inequality project, and census data from the Opportunity Insights database. HOLC grade (a score between 1 [best] and 4 [redlined]) for each census tract was based on overlap with historically HOLC-graded areas. The final analytic sample consisted of 11,375 U.S. census tracts. Structural equation modeling was used to investigate direct and indirect relationships adjusting for the 2010 population. RESULTS: Redlining was directly associated with higher crude prevalence of diabetes within a census tract (r = 0.01; P = 0.008) after adjusting for the 2010 population (χ2(54) = 69,900.95; P < 0.001; root mean square error of approximation = 0; comparative fit index = 1). Redlining was indirectly associated with diabetes prevalence via incarceration (r = 0.06; P < 0.001), poverty (r = -0.10; P < 0.001), discrimination (r = 0.14; P < 0.001); substance use (measured by binge drinking: r = -0.65, P < 0.001; and smoking: r = 0.35, P < 0.001), housing (r = 0.06; P < 0.001), education (r = -0.17; P < 0.001), unemployment (r = -0.17; P < 0.001), and food access (r = 0.14; P < 0.001) after adjusting for the 2010 population. CONCLUSIONS: Redlining has significant direct and indirect relationships with diabetes prevalence. Incarceration, poverty, discrimination, substance use, housing, education, unemployment, and food access may be possible targets for interventions aiming to mitigate the impact of structural racism on diabetes.

Racial/ethnic differences in social determinants of health and health outcomes among adolescents and youth ages 10-24 years old: a scoping review.

INTRODUCTION: With the recent emergence of the Healthy People 2030 goals there is a need to understand the role of SDOH on health inequalities from an upstream perspective. This review summarizes the recent body of evidence on the impact of SDOH across adolescence and youth health outcomes by race/ethnicity using the Health People 2030 Framework. METHODS: A systematic, reproducible search was performed using PubMed, Academic Search Premier, PsychInfo, and ERIC. A total of 2078 articles were screened for inclusion. A total of 263 articles met inclusion criteria, resulting in 29 articles included for final synthesis. RESULTS: Across the 29 articles, 11 were cross-sectional, 16 were cohort, and 2 were experimental. Across SDOH categories (economic stability, education access and quality, health care access and quality, neighborhood and built environment, and social and community context), 1 study examined self-efficacy, 6 educational attainment, 10 behavior, 5 smoking, 11 alcohol use, 10 substance use, and 1 quality of life. The majority of outcomes represented in this search included health behaviors such as health risk behavior, smoking, alcohol use, and substance use. Across the 29 articles identified, significant differences existed across outcomes by race/ethnicity across SDOH factors, however magnitude of differences varied by SDOH category. DISCUSSION: SDOH differentially affect adolescents and youth across race/ethnicity. The lived adverse experiences, along with structural racism, increase the likelihood of adolescents and youth engaging in risky health behaviors and negatively influencing health outcomes during adolescence and youth. Research, public health initiatives, and policies integrating SDOH into interventions at early stage of life are needed to effectively reduce social and health inequalities at a population level.

Relationship between mental health diagnoses and COVID-19 test positivity, hospitalization, and mortality in Southeast Wisconsin.

BACKGROUND: There is a paucity of literature on the relationship between pre-existing mental health conditions and coronavirus disease-2019 (COVID-19) outcomes. The aim was to examine the association between pre-existing mental health diagnosis and COVID-19 outcomes (positive screen, hospitalization, mortality). METHODS: Electronic medical record data for 30 976 adults tested for COVID-19 between March 2020 and 10th July 2020 was analyzed. COVID-19 outcomes included positive screen, hospitalization among screened positive, and mortality among screened positive and hospitalized. Primary independent variable, mental health disorders, was based on ICD-10 codes categorized as bipolar, internalizing, externalizing, and psychoses. Descriptive statistics were calculated, unadjusted and adjusted logistic regression and Cox proportional hazard models were used to investigate the relationship between each mental health disorder and COVID-19 outcomes. RESULTS: Adults with externalizing (odds ratio (OR) 0.67, 95%CI 0.57-0.79) and internalizing disorders (OR 0.78, 95% CI 0.70-0.88) had lower odds of having a positive COVID-19 test in fully adjusted models. Adults with bipolar disorder had significantly higher odds of hospitalization in fully adjusted models (OR 4.27, 95% CI 2.06-8.86), and odds of hospitalization were significantly higher among those with externalizing disorders after adjusting for demographics (OR 1.71, 95% CI 1.23-2.38). Mortality was significantly higher in the fully adjusted model for patients with bipolar disorder (hazard ratio 2.67, 95% CI 1.07-6.67). CONCLUSIONS: Adults with mental health disorders, while less likely to test positive for COVID-19, were more likely to be hospitalized and to die in the hospital. Study results suggest the importance of developing interventions that incorporate elements designed to address smoking cessation, nutrition and physical activity counseling and other needs specific to this population to improve COVID-19 outcomes.

Explanatory role of sociodemographic, clinical, behavioral, and social factors on cognitive decline in older adults with diabetes.

BACKGROUND: The aim of the study was to examine the explanatory role of sociodemographic, clinical, behavioral, and social factors on racial/ethnic differences in cognitive decline among adults with diabetes. METHODS: Adults aged 50+ years with diabetes from the Health and Retirement Survey were assessed for cognitive function (normal, mild cognitive impairment [MCI], and dementia). Generalized estimating equation (GEE) logistic regression models were used to account for repeating measures over time. Models were adjusted for sociodemographic (gender, age, education, household income and assets), behavioral (smoking), clinical (ie. comorbidities, body mass index), and social (social support, loneliness, social participation, perceived constraints and perceived mastery on personal control) factors. RESULTS: Unadjusted models showed non-Hispanic Blacks (NHB) and Hispanics were significantly more likely to progress from normal cognition to dementia (NHB OR: 2.99, 95%CI 2.35-3.81; Hispanic OR: 3.55, 95%CI 2.77-4.56), and normal cognition to MCI (NHB OR = 2.45, 95%CI 2.14-2.82; Hispanic OR = 2.49, 95%CI 2.13-2.90) compared to non-Hispanic Whites (NHW). Unadjusted models for the transition from mild cognitive decline to dementia showed Hispanics were more likely than NHW to progress (OR = 1.43, 95%CI 1.11-1.84). After adjusting for sociodemographic, clinical/behavioral, and social measures, NHB were 3.75 times more likely (95%CI 2.52-5.56) than NHW to reach dementia from normal cognition. NHB were 2.87 times more likely (95%CI 2.37-3.48) than NHW to reach MCI from normal. Hispanics were 1.72 times more likely (95%CI 1.17-2.52) than NHW to reach dementia from MCI. CONCLUSION: Clinical/behavioral and social factors did not explain racial/ethnic disparities. Racial/ethnic disparities are less evident from MCI to dementia, emphasizing preventative measures/interventions before cognitive impairment onset are important.

Identification of "Digital Sarcopenia" Can Aid the Detection of Pancreatic Exocrine Insufficiency and Malnutrition Assessment in Patients with Suspected Pancreatic Pathology.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) and subsequent malnutrition can be difficult to diagnose but lead to sarcopenia and increased mortality and morbidity even in benign disease. Digital skeletal muscle analysis has been increasingly recognised as a tool to diagnose sarcopenia. OBJECTIVE: The aim of the study was to assess the prevalence of sarcopenia in patients with PEI secondary to benign disease using novel skeletal muscle recognition software. METHODS: Prospective recruitment of patients referred for endoscopic ultrasound (EUS) with suspected pancreatic pathology. Patients with suspected pancreatic cancer on initial computed tomography (CT) were excluded. The diagnosis of chronic pancreatitis (CP) was based on CT and EUS findings. PEI was assessed with faecal elastase-1. Digital measurement of skeletal muscle mass identified sarcopenia, with demographic and comorbidity data also collected. RESULTS: PEI was identified in 45.1% (46/102) of patients recruited, and 29.4% (30/102) had changes of CP. Sarcopenia was significantly more prevalent in PEI 67.4% (31/46) than no-PEI 37.5% (21/56) (37.5%), regardless of CP changes (p < 0.003). The prevalence of sarcopenia (67% vs. 35%; p = 0.02) and sarcopenic obesity (68.4% vs. 25%; p = 0.003) was significantly higher when PEI was present without a radiological diagnosis of CP. Multivariate analysis identified sarcopenia and diabetes to be independently associated with PEI (odds ratio 4.8 and 13.8, respectively, p < 0.05). CONCLUSION: Sarcopenia was strongly associated with PEI in patients undergoing assessment for suspected benign pancreatic pathology. Digital skeletal muscle assessment can be used as a tool to aid identification of sarcopenia in patients undergoing CT scan for pancreatic symptoms.

Computed Tomographic Sarcopenia in Pancreatic Cancer: Further Utilization to Plan Patient Management.

PURPOSE: The presence of a sarcopenia adversely affects the prognosis of patients with pancreatic cancer. There is an emerging role for using computed tomography (CT) to calculate skeletal muscle index (SMI) and the presence of sarcopenia. The aim of this study was to assess if detecting 'computed tomographic sarcopenia' is feasible and can contribute to the management of patients with locally advanced pancreatic cancer (LAPC). METHODS: Patients diagnosed with LAPC referred for endoscopic ultrasound-guided biopsy (EUS-B) by our regional cancer network were identified. Age, body mass index (BMI), and Eastern Cooperative Oncology Group performance status (ECOG-PS) were noted. CT images were analysed for SMI and the presence of sarcopenia. Decision outcomes on receiving chemotherapy or not were collected from the regional oncology database. RESULTS: In total, 51/204 (25%) patients with LAPC who underwent EUS-B were not given chemotherapy and received best supportive care (BSC) only. The prevalence of sarcopenia (p = 0.0003), age ≥ 75 years old (p = 0.03), and ECOG-PS 2-3 (p = 0.01) were significantly higher in the patients receiving BSC only. Logistic regression analysis demonstrated that SMI was the only independent associated factor identifying patients with LAPC who were treated with BSC only and not chemotherapy after adjusting for age and ECOG-PS. CONCLUSION: Our study has shown that computed tomographic skeletal muscle analysis at the time of a diagnostic CT for patients with pancreatic cancer is feasible and can detect sarcopenia and malnourished patients who are much less likely to take up chemotherapy. These patients could be triaged to oncology assessment prior to EUS-B to avoid unnecessary investigations.

Seronegative Coeliac Disease Masquerading as Irritable Bowel Syndrome type Symptoms.

Coeliac disease affects 1% of the population but internationally delays in diagnosis are frequent. A relationship between irritable bowel syndrome type symptoms and coeliac disease is well established and most IBS guidelines recommend that patients presenting with IBS type symptoms should be tested serologically for coeliac disease. Seronegative coeliac disease accounts for 3-5% of all cases of coeliac disease and it is a diagnostic challenge which requires a high level of clinical suspicion and consideration of duodenal biopsies prior to confidently excluding this diagnosis. We report the first case of seronegative coeliac disease masquerading as IBS type symptoms. We suggest that if patients have evidence of haematinic deficiency, subsequent weight loss, features of malabsorption or a family history of coeliac disease, then a duodenal biopsy should be considered irrespective of negative serology.

Diagnostic yield of magnetically assisted capsule endoscopy versus gastroscopy in recurrent and refractory iron deficiency anemia.

BACKGROUND: Small-bowel capsule endoscopy is advocated and repeat upper gastrointestinal (GI) endoscopy should be considered for evaluation of recurrent or refractory iron deficiency anemia (IDA). A new device that allows magnetic steering of the capsule around the stomach (magnetically assisted capsule endoscopy [MACE]), followed by passive small-bowel examination might satisfy both requirements in a single procedure. METHODS: In this prospective cohort study, MACE and esophagogastroduodenoscopy (EGD) were performed in patients with recurrent or refractory IDA. Comparisons of total (upper GI and small bowel) and upper GI diagnostic yields, gastric mucosal visibility, and patient comfort scores were the primary end points. RESULTS: 49 patients were recruited (median age 64 years; 39 % male). Combined upper and small-bowel examination using the new capsule yielded more pathology than EGD alone (113 vs. 52; P < 0.001). In upper GI examination (proximal to the second part of the duodenum, D2), MACE identified more total lesions than EGD (88 vs. 52; P < 0.001). There was also a difference if only IDA-associated lesions (esophagitis, altered/fresh blood, angioectasia, ulcers, and villous atrophy) were included (20 vs. 10; P = 0.04). Pathology distal to D2 was identified in 17 patients (34.7 %). Median scores (0 - 10 for none - extreme) for pain (0 vs. 2), discomfort (0 vs. 3), and distress (0 vs. 4) were lower for MACE than for EGD (P < 0.001). CONCLUSION: Combined examination of the upper GI tract and small bowel using the MACE capsule detected more pathology than EGD alone in patients with recurrent or refractory IDA. MACE also had a higher diagnostic yield than EGD in the upper GI tract and was better tolerated by patients.

Should we Investigate Gastroenterology Patients for Pancreatic Exocrine Insufficiency? A Dual Centre UK Study.

BACKGROUND AND AIMS: Pancreatic exocrine insufficiency may be under recognised in gastroenterological practice. We aimed to identify the prevalence of pancreatic insufficiency in secondary care gastroenterology clinics and determine if co-morbidity or presenting symptoms could predict diagnosis. A secondary aim was to assess response to treatment. METHODS: A dual centre retrospective analysis was conducted in secondary care gastroenterology clinics. Patients tested for pancreatic exocrine insufficiency with faecal elastase-1 (FEL-1) between 2009 and 2013 were identified in two centres. Demographics, indication and co-morbidities were recorded in addition to dose and response to pancreatic enzyme replacement therapy. Binary logistic regression was used to assess if symptoms or co-morbidities could predict pancreatic insufficiency. RESULTS: 1821 patients were tested, 13.1% had low FEL-1 (<200µg/g). This prevalence was sub-analysed with 5.4% having FEL-1 100-200µg/g (mild insufficiency) and 7.6% having faecal elastase readings <100µg/g. Low FEL-1 was most significantly associated with weight loss or steatorrhoea. Co-morbidity analysis showed that low levels were significantly associated with excess alcohol intake, diabetes mellitus or human immunodeficiency virus; 80.0% treated with enzyme supplements reported symptomatic benefit with no difference in response between high and low dose supplementation (p=0.761). CONCLUSION: Targeting the use of FEL-1 in individuals with specific symptoms and associated conditions can lead to improved recognition of pancreatic exocrine insufficiency in a significant proportion of secondary care patients. Intervening with lifestyle advice such as smoking cessation and minimising alcohol intake could improve outcomes. In addition, up to 80% of patients with low faecal elastase respond to supplementation.

Early diagnosis of oesophageal cancer improves outcomes.

There are two main types of oesophageal cancer, oesophageal squamous cell carcinoma (OSCC) and oesophageal adenocarcinoma (OAC). They present in the same manner and both carry a five-year survival of only 16%. In the UK there is a 2:1 male to female ratio for oesophageal cancer. Peak incidence at presentation is in the 65-75 age group, with 95% of cases presenting in those over 50. Smoking is a major risk factor for both types and is linked to an estimated 66% of cases in the UK. OSCC is linked to alcohol, smoking, and chewing betel quid. OAC is associated with the presence of GORD, and its duration, and obesity (especially increased waist circumference). Oesophageal cancer commonly presents with dysphagia or odynophagia. This can be associated with weight loss and vomiting. All patients with recent onset dysphagia should be referred for rapid access endoscopy. Referral for urgent endoscopy should still be considered in the presence of dysphagia regardless of previous history or medication. Dysphagia is not always present so all patients with alarm symptoms should be considered for endoscopy. NICE recommends referral for urgent direct access upper GI endoscopy to assess for oesophageal cancer for patients with dysphagia or aged 55 and over with weight loss and any of the following: upper abdominal pain; reflux; dyspepsia.

Associations Between Adverse Childhood Experiences, High-Risk Behaviors, and Morbidity in Adulthood.

INTRODUCTION: Adverse childhood experiences (ACEs) are associated with early mortality and morbidity. This study evaluated the association among ACEs, high-risk health behaviors, and comorbid conditions, as well as the independent effect of ACE components. METHODS: Data were analyzed on 48,526 U.S. adults from five states in the 2011 Behavioral Risk Factor Surveillance System survey. Exposures included psychological, physical, and sexual forms of abuse as well as household dysfunction such as substance abuse, mental illness, violence, and incarceration. Main outcome measures included risky behaviors and morbidity measures, including binge drinking, heavy drinking, current smoking, high-risk HIV behavior, obesity, diabetes, myocardial infarction, coronary heart disease, stroke, depression, disability caused by poor health, and use of special equipment because of disability. Multiple logistic regression assessed the independent relationship between ACE score categories and risky behaviors/comorbidities in adulthood, and assessed the independent relationship between individual ACE components and risky behaviors/comorbid conditions in adulthood controlling for covariates. RESULTS: A total of 55.4% of respondents reported at least one ACE and 13.7% reported four or more ACEs. An ACE score ≥4 was associated with increased odds for binge drinking, heavy drinking, smoking, risky HIV behavior, diabetes, myocardial infarction, coronary heart disease, stroke, depression, disability caused by health, and use of special equipment because of disability. In addition, the individual components had different effects on risky behavior and comorbidities. CONCLUSIONS: In addition to having a cumulative effect, individual ACE components have differential relationships with risky behaviors, morbidity, and disability in adulthood after controlling for important confounders.

Effect of perceived racial discrimination on self-care behaviors, glycemic control, and quality of life in adults with type 2 diabetes.

OBJECTIVE: This study used a large sample size of black and white patients with type 2 diabetes to investigate the influence of perceived racial discrimination on biologic measures (glycemic control, blood pressure, and LDL cholesterol), the mental component of quality of life (MCS), and health behaviors known to improve diabetes outcomes. METHODS: 602 patients were recruited from two adult primary care clinics in the southeastern United States. Linear regression models were used to assess the associations between perceived racial discrimination, self-care, clinical outcomes, MCS, adjusting for relevant covariates. Race-stratified models were conducted to examine differential associations by race. RESULTS: The mean age was 61 years, with 64.9 % non-Hispanic black, and 41.6 % earning less than $20,000 annually. Perceived discrimination was significantly negatively associated with MCS (ß = -0.56, 95 % CI -0.90, 0.23), general diet (ß = -0.37, CI -0.65, -0.08), and specific diet (ß = -0.25, CI -0.47, -0.03). In African Americans, perceived discrimination was significantly associated with higher systolic blood pressure (ß = 10.17, CI 1.13, -19.22). In Whites, perceived discrimination was significantly associated with lower MCS (ß = -0.51, CI -0.89, -0.14), general diet (ß = -0.40, CI -0.69, -0.99), specific diet (ß = -0.25, CI -0.47, -0.03), and blood glucose testing (ß = -0.43, CI -0.80, -0.06). CONCLUSIONS: While no association was found with biologic measures, perceived discrimination was associated with health behaviors and the MCS. In addition, results showed a difference in influence of perceived discrimination by race.

Nitrous oxide use during colonoscopy: a national survey of English screening colonoscopists.

INTRODUCTION: Nitrous oxide can improve patient experience during colonoscopy, and its rapid elimination minimises after effects and inconvenience. Despite its advantages, nitrous oxide is used infrequently in the UK. We sought to understand the reasons for its low use. METHODS: Colonoscopists within the English Bowel Cancer Screening Programme (BCSP) were invited to participate in a web-based survey assessing the availability, current practices and perceptions towards nitrous oxide. Respondents were able to select predefined answers or offer written responses. Free text responses were assessed using thematic analysis. RESULTS: The survey was completed by 68% of the English BCSP colonoscopists. Nitrous oxide was available to 73% of respondents but with considerable regional variation. Most colonoscopists rated the properties of nitrous oxide favourably and would use it if they had a colonoscopy themselves. Despite this, nearly half used it in less than 20% of examinations. 80% instruct patients to use nitrous oxide as required, and differences in how it was used in combination with intravenous sedation and analgesia were reported. Written responses suggest nitrous oxide is often used in the patients who are expected to have the least discomfort. CONCLUSIONS: Most colonoscopists perceive that nitrous oxide is effective and reduces inconvenience and would use it themselves if they required a colonoscopy. Studies to improve patient selection and optimise the use of nitrous oxide would be of value.

Diabetes empowerment, medication adherence and self-care behaviors in adults with type 2 diabetes.

BACKGROUND: Evidence suggests that empowerment is an important factor to address everyday aspects of dealing with a chronic disease. This study evaluated the effect of diabetes empowerment on medication adherence and self-care behaviors in adults with type 2 diabetes. SUBJECTS AND METHODS: Data on 378 subjects with type 2 diabetes recruited from two primary care clinics in the southeastern United States were examined. Previously validated scales were used to measure diabetes empowerment, medication adherence, diabetes knowledge, and diabetes self-care behaviors (including diet, physical activity, blood sugar testing, and foot care). Multiple linear regression was used to assess the independent effect of diabetes empowerment on medication adherence and self-care behaviors controlling for relevant covariates. RESULTS: Eighty-three percent were non-Hispanic blacks, 69% were women, 22% were 65 years or older, 68% were not married, 26% had less than high school education, 60% were unemployed, 39% were uninsured, and 47% had a yearly income <$10,000. Empowerment had significant correlations with medication adherence (r=0.17, P<0.003), diabetes knowledge (r=0.16, P=0.007), diet (r=0.24, P<0.001), exercise (r=0.25, P<0.001), blood sugar testing (r=0.12, P=0.043), and foot care (r=0.18, P=0.002). In the regression model, diabetes empowerment was significantly associated with medication adherence (ß=-0.04, P=0.001), diabetes knowledge (ß=0.09, P=0.012), diet (ß=0.09, P<0.001), exercise (ß=0.10, P<0.001), blood sugar testing (ß=0.07, P=0.016), and foot care (ß=0.08, P=0.001). CONCLUSIONS: In this sample, diabetes empowerment was related to better diabetes knowledge, medication adherence and improved self-care behaviors. Emphasis on empowerment and self-efficacy is relevant to improve outcomes in the management of diabetes.

Emerging antiplatelet therapy for coronary artery disease and acute coronary syndrome.

Antiplatelet therapy is used widely with proven benefit for the prevention of further ischemic cardiac complications in patients with known coronary artery disease (CAD) and a history of acute coronary syndrome (ACS). The limitations of conventional antiplatelet therapy with aspirin, clopidogrel, or prasugrel, as well as the fact that rates of recurrent ischemic events still remain high with use of these agents, underscore the need to investigate alternate agents that may further reduce event rates while limiting bleeding risk. The selection of antiplatelet therapy is further influenced by the following: ticagrelor was approved in July 2011 by the United States Food and Drug Administration (FDA), and clopidogrel is slated to become available as a generic productin 2012. We provide an overview of emerging agents for the treatment of CAD and ACS, including the reversible P2Y(12) antagonists ticagrelor, cangrelor, and elinogrel, and a new class of oral protease-activated receptor-1 (PAR-1) inhibitors, vorapaxar and atopaxar.The recently approved P2Y(12) antagonists prasugrel and ticagrelor demonstrate enhanced ability to prevent adverse cardiac outcomes. However, this comes at a cost of a potential increased risk of bleeding. New adverse effects have also emerged, including dyspnea for all of the reversible P2Y(12) antagonists (ticagrelor, cangrelor, and elinogrel) and ventricular pauses for ticagrelor. In addition, the newer P2Y(12) antagonists have a faster onset and offset. Two of these agents, cangrelor and elinogrel, are available as intravenous formulations, which may provide additional benefits in patients who undergo coronary artery bypass graft (CABG) surgery. Trials with the PAR-1 inhibitors have also shown trends toward reductions in cardiac events, but not without the possibility of increased bleeding. More than ever, as the arsenal of antiplatelet therapy expands, health care providers need to understand the pharmacologic and pharmacodynamic differences between conventional and emerging antiplatelet therapies for patients with ACS and CAD. Health care providers must also carefully assess patient-specific factors such as risk of thrombosis, concomitant disease states, age, drug adherence, and aspirin dose, and plan for those patients who will be undergoing CABG when selecting antiplatelet therapy in order to optimally balance bleeding and thrombosis risk.

Altered bone marrow dendritic cell cytokine production to toll-like receptor and CD40 ligation during chronic feline immunodeficiency virus infection.

Impaired dendritic cell (DC) function is thought to be central to human immunodeficiency virus-associated immunodeficiency. In this study, we examined the effect of chronic feline immunodeficiency virus (FIV) infection on DC cytokine production in response to microbial and T-cell stimulation. Cytokine production after either Toll-like receptor (TLR) or CD40 ligation in bone marrow-derived DCs (BM-DCs) was measured in naïve and chronically FIV-infected cats. The BM-DCs were stimulated with ligands to TLR-2, -3, -4, -7 and -9 or cocultured with 3T3 cells expressing feline CD40 ligand. Ligation of TLR-4 and TLR-9 in BM-DCs from infected cats resulted in a significant decrease in the ratio of interleukin-12 (IL-12) to IL-10. Conversely, TLR-7 ligation produced a significant increase in the IL-12 : IL-10 ratio in BM-DCs from infected cats. No difference was noted for TLR-3 ligation. RNA expression levels of TLR-2, -3, -4, -7 and -9 were not significantly altered by FIV infection. CD40 ligation significantly elevated both IL-10 and IL-12 messenger RNA production but did not alter the IL-12 : IL-10 ratio. Chronic FIV infection alters the ratio of immunoregulatory cytokines produced by BM-DCs in response to certain pathogen-derived signals, which is probably relevant to the increased risk of opportunistic infections seen in lentiviral infection.