Characterization of Antigen-Presenting Cell Subsets in Human Liver-Draining Lymph Nodes

T-cell immunity in the liver is tightly regulated to prevent chronic liver inflammation in response to antigens and toxins derived from food and intestinal bacterial flora. Since the main sites of T cell activation in response to foreign components entering solid tissues are the draining lymph nodes (LN), we aimed to study whether Antigen-Presenting Cell (APC) subsets in human liver lymph-draining LN show features that may contribute to the immunologically tolerant liver environment. Healthy liver LN, iliac LN, spleen and liver perfusates were obtained from multi-organ donors, while diseased liver LN were collected from explanted patient livers. Inguinal LN were obtained from kidney transplant recipients. Mononuclear cells were isolated from fresh tissues, and immunophenotypic and functional characteristics of APC subsets were studied using flowcytometry and in ex vivo cultures. Healthy liver-draining LN contained significantly lower relative numbers of CD1c+ conventional dendritic cells (cDC2), plasmacytoid DC (PDC), and CD14+CD163+DC-SIGN+ macrophages (MF) compared to inguinal LN. Compared to spleen, both types of LN contained low relative numbers of CD141hi cDC1. Both cDC subsets in liver LN showed a more activated/mature immunophenotype than those in inguinal LN, iliacal LN, spleen and liver tissue. Despite their more mature status, cDC2 isolated from hepatic LN displayed similar cytokine production capacity (IL-10, IL-12, and IL-6) and allogeneic T cell stimulatory capacity as their counterparts from spleen. Liver LN from patients with inflammatory liver diseases showed a further reduction of cDC1, but had increased relative numbers of PDC and MF. In steady state conditions human liver LN contain relatively low numbers of cDC2, PDC, and macrophages, and relative numbers of cDC1 in liver LN decline during liver inflammation. The paucity of cDC in liver LN may contribute to immune tolerance in the liver environment

Explanations of socioeconomic differences in changes in physical function in older adults: results from the Longitudinal Aging Study Amsterdam

BACKGROUND: This study examines the association between socioeconomic status and changes in physical function in younger- (aged 55–70 years) and older-old (aged 70–85 years) adults and seeks to determine the relative contribution of diseases, behavioral, and psychosocial factors in explaining this association. METHODS: Data were from 2,366 men and women, aged 55–85 years, participating in the Longitudinal Aging Study Amsterdam (LASA). Two indicators of socioeconomic status were used: education and income. Physical function was measured by self-reported physical ability over nine years of follow-up. RESULTS: In older adults, low socioeconomic status was related to a poorer level of physical function during nine years of follow-up. In subjects who were between 55 and 70 years old, there was an additional significant socioeconomic-differential decline in physical function, while socioeconomic differentials did not further widen in subjects 70 years and older. Behavioral factors, mainly BMI and physical activity, largely explained the socioeconomic differences in physical function in the youngest age group, while psychosocial factors reduced socioeconomic status differences most in the oldest age group. CONCLUSION: The findings indicate age-specificity of both the pattern of socioeconomic status differences in function in older persons and the mechanisms underlying these associations

Socioeconomic differences in incident depression in older adults: The role of psychosocial factors, physical health status, and behavioral factors

Objective: The objective of this study was to examine the association between socioeconomic status (SES) and the onset of depression in older adults and to determine the relative contribution of psychosocial factors, physical health status, and behavioral factors in explaining this link. Methods: Data were from 2593 men and women, aged 55-85 years, participating in the Longitudinal Aging Study Amsterdam. Two indicators of SES were used: education and income. The onset of depression was measured over 9 years of follow-up. Results: Adjusted hazard ratios of incident depression were significantly higher in those with low education and low income. Psychosocial factors explained on average 16% of the SES differences in incident depression, physical health status on average 7%, and behavioral factors less than 5%. Conclusion: In older adults, low SES predicted the incidence of depression. Part of this association was explained by psychosocial factors and physical health status

A Minimal Psychological Intervention in Chronically Ill Elderly Patients with Depression: A Randomized Trial

Background: Among older persons with chronic somatic diseases, depression often remains unrecognized and untreated in primary care. The Depression in Elderly with Long-Term Afflictions (DELTA) study aimed to evaluate the effectiveness of a nurse-led minimal psychological intervention (MPI) in chronically ill elderly persons with depression. Methods: A randomized controlled trial was conducted, comparing the MPI with usual care in 361 primary care patients. Four nurses had an average of 4 sessions with the intervention patients, each lasting 1 h, over a maximum period of 3 months. Patients were aged 60 years and older, had a minor depression or mild-to-moderate major depression, and either had type II diabetes or chronic obstructive pulmonary disease. Results: Nine months after the intervention, patients receiving the MPI had significantly fewer depressive symptoms; the intervention patients were also more likely than usual-care controls to show a >= 50% reduction in depressive symptoms relative to baseline values. At 9 months, diabetic MPI patients had a better quality of life than diabetic controls. Conclusions: The nurse-led MPI appears to be a feasible and moderately effective method of managing minor-to-moderate depression in chronically ill elderly persons. However, we cannot rule out attention-placebo effects, and the disappointing finding of a recent economic evaluation showing only a 63% chance of the MPI being cost-effective. From a clinical point of view, however, it is of interest to further evaluate adaptations of the MPI, with a stronger emphasis on detection, watchful waiting and mental health problems in general

A blunted diurnal cortisol response in the lower educated does not explain educational differences in coronary heart disease: findings from the AGES-Reykjavik study.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageLower educational attainment generally is a strong predictor of coronary heart disease (CHD). The underlying mechanisms of this effect are, however, less clear. One hypothesis is that stress related to limitations imposed by lower socioeconomic status elicits changes in hypothalamic-pituitary-adrenal axis functioning, which, in turn, increases risk of CHD. In a large cohort study, we examined whether educational attainment was related to risk of fatal and non-fatal CHD and the extent to which salivary cortisol mediated this relation independent of potential confounders, including lifestyles. Data came from 3723 participants aged 66 through 96 from the Age, Gene/Environment Susceptibility (AGES) - Reykjavik Study. Between 2002 and 2006, data were collected using questionnaires and examinations including morning and evening salivary samples. Hospital admission records and cause of death registries (ICD-9 and ICD-10 codes) were available until December 2009. Linear regression and Cox proportional hazards analyses were performed. Even after adjustment for potential confounders, including lifestyle, persons with lower educational attainment showed a blunted cortisol response and also greater risk of incident CHD. However, our data did not support the role of cortisol as a mediator in the association between education and CHD in an older sample (192).N01-AG-12100/AG/NIA NIH HHS/United States Intramural NIH HHS/United State

Association of inflammatory markers with socioeconomic status

Background. This study examines the association between socioeconomic status (SES) and inflammatory markers in well-functioning older adults and seeks to determine whether any association remains after adjusting for biomedical and behavioral factors typically related to elevated serum levels of inflammatory markers. Methods. Data were obtained from 3044 men and women, aged 70-79 from Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health, Aging and Body Composition study. Three indicators of SES were used: education, income, and ownership of financial assets. Serum levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α were measured. Results. Low SES was associated with significantly elevated levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α compared to high SES. Behavioral factors (including smoking, drinking, obesity) explained a substantial part of the inverse association between SES and inflammatory markers. Adjustment for prevalent diseases (including heart diseases, lung disease, and diabetes) associated with inflammation explained less of the association. Conclusions. This study suggests that interventions to improve health behaviors, even in old age and especially in low SES groups, may be useful in reducing risks associated with inflammation

Unhealthy Lifestyles Do Not Mediate the Relationship Between Socioeconomic Status and Incident Depressive Symptoms: The Health ABC study

BACKGROUND: The relationship between low socioeconomic status (SES) and depressive symptoms is well described, also in older persons. Although studies have found associations between low SES and unhealthy lifestyle factors and between unhealthy lifestyle factors and depressive symptoms, not much is known about unhealthy lifestyles as a potential explanation of socioeconomic differences in depressive symptoms in older persons. METHODS: To study the independent pathways between SES (education, income, perceived income, and financial assets), lifestyle factors (smoking, alcohol use, body mass index, and physical activity), and incident depressive symptoms (CES-D 10 and reported use of antidepressant medication), we used 9 years of follow-up data (1997–2007) from 2,694 American black and white participants aged 70–79 from the Health, Aging, and Body Composition (Health ABC) study. At baseline, 12.1% of the study population showed prevalent depressive symptoms, use of antidepressant medication, or treatment of depression in the five years prior to baseline. These persons were excluded from the analyses. RESULTS: Over a period of 9 years time, 860 participants (31.9%) developed depressive symptoms. Adjusted hazard ratios for incident depressive symptoms were higher in participants from lower SES groups compared to the highest SES group. The strongest relationships were found for black men. Although unhealthy lifestyle factors were consistently associated with low SES, they were weakly related to incident depressive symptoms. Lifestyle factors did not significantly reduce hazard ratios for depressive symptoms by SES. CONCLUSION: In generally healthy persons aged 70–79 years lifestyle factors do not explain the relationship between SES and depressive symptoms. (250

Unhealthy Lifestyles Do Not Mediate the Relationship Between Socioeconomic Status and Incident Depressive Symptoms: The Health ABC study

Background: The relationship between low socioeconomic status (SES) and depressive symptoms is well described, also in older persons. Although studies have found associations between low SES and unhealthy lifestyle factors, and between unhealthy lifestyle factors and depressive symptoms, not much is known about unhealthy lifestyles as a potential explanation of socioeconomic differences in depressive symptoms in older persons. Methods: To study the independent pathways between SES (education, income, perceived income, and financial assets), lifestyle factors (smoking, alcohol use, body mass index, and physical activity), and incident depressive symptoms (Center for Epidemiologic Studies Depression [CES-D 10] and reported use of antidepressant medication), we used 9 years of follow-up data (1997 2007) from 2,694 American black and white participants aged 70-79 years from the Health, Aging, and Body Composition (Health ABC) study. At baseline, 12.1% of the study population showed prevalent depressive symptoms, use of antidepressant medication, or treatment of depression in the 5 years prior to baseline. These persons were excluded from the analyses. Results: Over a period of 9 years time, 860 participants (31.9%) developed depressive symptoms. Adjusted hazard ratios for incident depressive symptoms were higher in participants from lower SES groups compared with the highest SES group. The strongest relationships were found for black men. Although unhealthy lifestyle factors were consistently associated with low SES, they were weakly related to incident depressive symptoms. Lifestyle factors did not significantly reduce hazard ratios for depressive symptoms by SES. Conclusion: In generally healthy persons aged 70-79 years, lifestyle factors do not explain the relationship between SES and depressive symptoms

Kumar versus Olsen cannulation technique for intraoperative cholangiography:a randomized trial

<p>There is resistance to routine intraoperative cholangiography (IOC) during cholecystectomy because it prolongs surgery and may be experienced as cumbersome. An alternative instrument may help to reduce these drawbacks and lower the threshold for IOC. This trial compared the Kumar cannulation technique to the more commonly used Olsen clamp for IOC (KOALA trial; Dutch Trial Register NTR2582).</p><p>Patients undergoing elective laparoscopic cholecystectomy were randomized between IOC using the Kumar clamp and the Olsen clamp. Primary end points were the time that the IOC procedure took and its perceived ease as measured on a visual analog scale from 0 (impossible) to 10 (effortless). To detect a difference of 33 % in IOC time, a total sample size of 40 patients was required.</p><p>Fifty-nine patients were randomized. Nine were excluded because of conversion to open cholecystectomy before the IOC procedure. Twenty-eight patients underwent IOC with the Kumar clamp and 22 with the Olsen clamp. The success rate was 23 (82.1 %) of 28 for the Kumar clamp and 19 (86.4 %) of 22 for the Olsen clamp (p > 0.999). The mean IOC time was 10 min 27 s +/- A 6 min 17 s using the Kumar clamp and 11 min 34 s +/- A 7 min 27 s using the Olsen clamp (p = 0.537). Surgeons graded the ease of the Kumar clamp as 6.8 +/- 2.7 and the Olsen clamp as 6.8 +/- A 2.1 (p = 0.977).</p><p>IOC using the Kumar clamp was neither faster nor easier than using the Olsen clamp. Both clamps facilitated IOC in just over 10 min. Individual surgeon preference should dictate which clamp is used.</p>