Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses

Mesenchymal stem cells (MSCs) suppress alloantigen-induced T-cell functions in vitro and infusion of third-party MSCs seems to be a promising therapy for graft-versus-host disease (GVHD). Little is known about the specificity of immunosuppression by MSCs, in particular the effect on immunity to pathogens. We have studied how MSCs affect T-cell responses specific to Epstein-Barr virus (EBV) and cytomegalovirus (CMV). We found that EBV- and CMV-induced proliferation and interferon- (IFN-) production from peripheral blood mononuclear cells (PBMCs) was less affected by third-party MSCs than the response to alloantigen and that MSCs had no effect on expansion of EBV and CMV pentamer-specific T cells. Established EBV-specific cytotoxic T cells (CTL) or CMV-CTL cultured with MSCs retained the ability to proliferate and produce IFN- in response to their cognate antigen and to kill virally infected targets. Finally, PBMCs from 2 patients who received MSCs for acute GVHD showed persistence of CMV-specific T cells and retained IFN- response to CMV after MSC infusion. In summary, MSCs have little effect on T-cell responses to EBV and CMV, which contrasts to their strong immunosuppressive effects on alloreactive T cells. These data have major implications for immunotherapy of GVHD with MSCs and suggest that the effector functions of virus-specific T cells may be retained after MSC infusion.     

Relationships of diabetes-specific emotional distress,depression, anxiety,and overall well-being with HbA1c in adult persons with type 1 diabetes

Objective

Emotional problems are common in adults with diabetes, and knowledge about how different indicators of emotional problems are related with glycemic control is required. The aim was to examine the relationships of diabetes-specific emotional distress, depression, anxiety, and overall well-being with glycosylated hemoglobin (HbA_1c).

Methods

Of the 319 adults with type 1 diabetes attending the endocrinology outpatient clinic at a university hospital in Norway, 235 (74%) completed the Diabetes Distress Scale, the Problem Areas in Diabetes Survey, the Hospital Anxiety and Depression Scale, and the World Health Organization-Five Well-Being Index. Blood samples were taken at the time of data collection to determine HbA_1c. Regression analyses examined associations of diabetes-specific emotional distress, anxiety, depression, and overall well-being with HbA_1c. The relationship between diabetes-specific emotional distress and HbA_1c was tested for nonlinearity.

Results

Diabetes-specific emotional distress was related to glycemic control (DDS total: unstandardized coefficient = 0.038, P < .001; PAID total: coefficient = 0.021, P = .007), but depression, anxiety, and overall well-being were not. On the DDS, only regimen-related distress was independently related to HbA_1c (coefficient = 0.056, P < .001). A difference of 0.5 standard deviation of baseline regimen distress is associated with a difference of 0.6 in HbA_1c. No significant nonlinearity was detected in the relationship between diabetes-specific distress and HbA_1c.

Conclusions

To stimulate adequate care strategies, health personnel should acknowledge depression and diabetes-specific emotional distress as different conditions in clinical consultations. Addressing diabetes-specific emotional distress, in particular regimen distress, in clinical consultation might improve glycemic control.     

Von Willebrand factor as new noninvasive predictor of portal hypertension, decompensation and mortality in patients with liver cirrhosis

von Willebrand factor antigen (vWF-Ag) is elevated in patients with liver cirrhosis, but the clinical significance is unclear. We hypothesized that vWF-Ag levels may correlate with portal pressure, measured by hepatic venous pressure gradient (HVPG), and predict clinically significant portal hypertension (CSPH; HVPG ≥10 mmHg), decompensation and mortality. Portal hemodynamics were assessed by HVPG measurement, whereas vWF-Ag levels were measured by enzyme-linked immunosorbent assay. During follow-up, complications of liver cirrhosis, death or transplantation were recorded. Two hundred and eighty-six patients (205 male and 81 female; mean age, 56 years) with liver cirrhosis were included. vWF-Ag correlated with HVPG (r = 0.69; P < 0.0001) and predicted CSPH independently of Child Pugh score. Higher vWF-Ag levels were associated with varices (odds ratio [OR] = 3.27; P < 0.001), ascites (OR = 3.93; P < 0.001) and mortality (hazard ratio: 4.41; P < 0.001). Using a vWF-Ag cut-off value of ≥241%, the AUC for detection of CSPH in compensated patients was 0.85, with a positive predictive value and negative predictive value of 87% and 80%, respectively. Compensated patients had 25% mortality after 53 months if the vWF-Ag was <315% compared to 15 months in patients with vWF-Ag >315% (P < 0.001). Decompensated patients had a mortality of 25% after 37 and 7 months if their vWF-Ag was <315% and >315%, respectively (P = 0.002). In compensated patients with a vWF-Ag >315% median time to decompensation or death was 32 months compared with 59 months in patients with vWF-Ag <315%. vWF-Ag equals Model for End-Stage Liver Disease (MELD) in mortality prediction (area under the curve [AUC] = 0.71 for vWF-Ag versus AUC = 0.65 for MELD; P = 0.2). Conclusion: vWF-Ag is a new, simple and noninvasive predictor of CSPH. A vWF-Ag cut-off value at 315% can clearly stratify patients with compensated and decompensated liver cirrhosis in two groups with completely different survival. vWF-Ag may become a valuable marker for the prediction of mortality in patients with liver cirrhosis in clinical practice. (HEPATOLOGY 2012).     

Inner strength in relation to age,gender and culture among old people – a cross-sectional population study in two Nordic countries

Objectives: The theoretical framework for the study was the Model of Inner Strength, and the Inner Strength Scale (ISS)developed based on the Model was used. The aim was to examine inner strength in relation to age, gender and culture among old people in Sweden and Finland.

Method: This study forms part of the GErontological Regional DAtabase (GERDA)-Botnia project that investigates healthy ageing with focus on the dignity, social participation and health of old people. The participants (N = 6119) were 65-, 70-, 75- and 80-year old and living in two counties in Sweden or Finland. The ISS consists of 20 items relating to four interrelated dimensions of inner strength, according to the Model of Inner Strength. The range of possible ISS scores is 20–120, a higher score denoting higher inner strength.

Result: The result showed that the 65-year-old participants had the highest mean ISS score, with a decrease in score for every subsequent age. The lowest score was achieved by the 80-year-old participants. Women had slightly but significantly higher mean ISS scores than men. Only small differences were found between the counties.

Conclusion: The study population came from Sweden and Finland; still, despite the different backgrounds, patterns in the distribution of inner strength were largely similar. The present study provides basic and essential information about inner strength in a population of old people.     

Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy

Purpose

Modic type 1 changes/bone edema in the vertebrae are present in 6 % of the general population and 35–40 % of the low back pain population. It is strongly associated with low back pain. The aim was to test the efficacy of antibiotic treatment in patients with chronic low back pain (>6 months) and Modic type 1 changes (bone edema).

Methods

The study was a double-blind RCT with 162 patients whose only known illness was chronic LBP of greater than 6 months duration occurring after a previous disc herniation and who also had bone edema demonstrated as Modic type 1 changes in the vertebrae adjacent to the previous herniation. Patients were randomized to either 100 days of antibiotic treatment (Bioclavid) or placebo and were blindly evaluated at baseline, end of treatment and at 1-year follow-up.

Outcome measures

Primary outcome, disease-specific disability, lumbar pain. Secondary outcome leg pain, number of hours with pain last 4 weeks, global perceived health, EQ-5D thermometer, days with sick leave, bothersomeness, constant pain, magnetic resonance image (MRI).

Results

144 of the 162 original patients were evaluated at 1-year follow-up. The two groups were similar at baseline. The antibiotic group improved highly statistically significantly on all outcome measures and improvement continued from 100 days follow-up until 1-year follow-up. At baseline, 100 days follow-up, 1-year follow-up the disease-specific disability-RMDQ changed: antibiotic 15, 11, 5.7; placebo 15, 14, 14. Leg pain: antibiotics 5.3, 3.0, 1.4; placebo 4.0, 4.3, 4.3. Lumbar pain: antibiotics 6.7, 5.0, 3.7; placebo 6.3, 6.3, 6.3. For the outcome measures, where a clinically important effect size was defined, improvements exceeded the thresholds, and a trend towards a dose–response relationship with double dose antibiotics being more efficacious.

Conclusions

The antibiotic protocol in this study was significantly more effective for this group of patients (CLBP associated with Modic I) than placebo in all the primary and secondary outcomes.     

Psychometric properties of the Norwegian Impact of Event Scale-Revised in a non-clinical sample

Background: Despite the widespread use of the Impact of Event Scale to measure post-traumatic stress symptoms, psychometric evaluations of the scale have revealed mixed findings. Aim: The aim of the present study is to provide new empirical evidence and examine the factor structure, reliability, and predictive validity of the Norwegian version of the IES-R. Methods: Posttraumatic stress symptoms were recorded in a student sample (n=312) 3 weeks after the Southeast Asian tsunami disaster in December 2004. Confirmatory factor analyses of the IES-R behavior items using structural equation modeling (SEM) were performed on four models from existing research. Results: The original three-factor model of intrusion, avoidance and hyperarousal symptoms exhibited the best goodness-of-fit indices when defined as oblique. The IES-R also revealed satisfactory reliability. Symptom levels of intrusion and avoidance were moderate, while hyperarousal scores were low, with a significant gender difference. Conclusion: Taken together, the IES-R revealed good psychometric properties in this nonclinical student sample and could be a useful instrument to assess and follow-up on PTSD symptoms after a certain identified trauma.     

Personality, physical activity, and symptoms of anxiety and depression: the HUNT study

Purpose

To analyze the association between physical activity (PA), symptoms of depression and anxiety, and personality traits.

Methods

Cross-sectional study from a Norwegian population-based survey conducted in the period 2006–2008. The sample consisted of a total of 38,743 subjects aged ≥19 years, 56.1 % women and 43.9 % men. Demographic variables, PA, depression and anxiety (The Hospital Anxiety and Depression Scale), and personality (Eysenck Personality Questionnaire) were assessed by self-reporting measurements.

Results

Individuals who reported moderate and high PA had significantly lower scores on depression and anxiety compared with less physically active individuals (p < 0.05). Significantly lower risk of HADS-defined depression and anxiety was associated with frequency, duration, and intensity of activity among women (p < 0.05), and significantly lower risk of HADS-defined depression was associated with frequency, duration, and intensity of activity among men (p < 0.05). There was a significant linear trend between extroversion and levels of PA (p < 0.01) and between neuroticism and PA (p < 0.01).

Conclusions

Subjects reporting regular leisure-time PA were less likely to report symptoms of HADS-defined depression and anxiety. Personality may be an underlying factor in explaining this association.     

Empowering senior citizens for healthy nutrition in Germany: A pilot study

Main goal of this study was to analyse how empowerment processes and bottom‐up activities aimed at healthier food choices and food environment could be initiated among a group of senior citizens (between 60 and 75 years old). The intervention was set up as a pilot study in a rural community (15,000 inhabitants) in the federal state of Bavaria, South Eastern Germany. A process evaluation documented how group formation and empowerment processes developed during the course of the intervention. Extensive field notes were taken in 27 meetings, interviews (n = 13) and focus groups (n = 4) were conducted with participants and key persons at different points of the intervention. Data were analysed using content analysis. The intervention succeeded in motivating senior citizens to participate in regular meetings over 11 months. During the intervention, the group members’ awareness of factors influencing their eating behaviour increased. Furthermore, they developed ideas to improve the community's food environment and accomplished duties needed to implement these ideas. However, initiating empowerment processes, especially in terms of fostering leadership and transferring responsibility, took longer than expected and could be realised only partially. The findings support a further use and evaluation of the empowerment approach for addressing nutritional aspects among senior citizens.