CXCR5 is critically involved in progression of lupus through regulation of B cell and double-negative T cell trafficking.

The recruitment of immune cells to sites of tissue inflammation is orchestrated by chemokine/chemokine receptor networks. Among these, the CXCL13/CXCR5 axis is thought to be involved critically in systemic lupus erythematosus (SLE) and lupus nephritis pathogenesis. Beyond B cell abnormalities, another hallmark of SLE disease is the occurrence of aberrant T cell responses. In particular, double-negative (DN) T cells are expanded in the peripheral blood of patients with SLE and in lupus-prone mice. DN T cells induce immunoglobulin production, secrete proinflammatory cytokines and infiltrate inflamed tissue, including kidneys. We aimed to investigate how CXCR5 deficiency changes immune cell trafficking in murine lupus. We therefore crossed CXCR5(-/-) mice with B6/lpr mice, a well-established murine lupus model. B cell numbers and B cellular immune responses were diminished in CXCR5-deficient B6/lpr mice. In addition, we observed reduced accumulation of DN T cells in spleen and lymph nodes, paralleled by reduced splenomegaly and lymphadenopathy. In-vivo migration assays revealed reduced migration of CXCR5-deficient DN T cells into lymph nodes, and ex-vivo-activated CXCR5-deficient DN T cells failed to infiltrate kidneys of recipients. Moreover, DN T cells and B cells of CXCR5-deficient B6/lpr mice failed to migrate towards CXCL13 in vitro. We propose that CXCR5 is involved critically in B cell trafficking and germinal cell (GC) formation in murine lupus and in guiding pathogenic DN T cells into lymphoid organs and kidneys, and we therefore describe new pathomechanisms for the CXCL13/CXCR5 axis in SLE.

[Parental Distress Caused by Child's Cancer Diagnosis]. / Belastungserleben von Eltern krebskranker Kinder.

INTRODUCTION: Considering that parental well-being influences the healing process of a child significantly, the relevance of psychosocial care of parents with children with cancer is obvious. Since the parental distress has hardly been studied in Germany, this study examines the burdens of parents of children with cancer. In addition, it provides a diagnostic tool that is used to standardize and facilitate the whole patient management. METHODS: n=213 parents have participated in the survey scheduled from September 2013 to September 2014 in pediatric oncology centers. The examination of parental distress was based on five burdens (namely "depression", "anxiety", "somatization", "posttraumatic stress disorder (PTSD)" and "obsessive-compulsive"). Moreover, confirmatory factor analyzes were calculated which form the basis of the tools. RESULTS: 42% of parents show above-average depression scores (z>1), 56,7% above-average anxiety scores, 30,6% above-average obsessive-compulsive scores, 17,4% above-average PTSD scores and 25,9% above-average somatization scores. The confirmatory factor analyzes provide evidence for a dimensional factor model and a second-order factor model. DISCUSSION: The results show that parents of children with cancer in Germany represent a risk group in terms of developing their own mental health problems.

Interleukin-2 treatment reverses effects of cAMP-responsive element modulator α-over-expressing T cells in autoimmune-prone mice.

Systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), are often characterized by a failure of self-tolerance and result in an uncontrolled activation of B cells and effector T cells. Interleukin (IL)-2 critically maintains homeostasis of regulatory T cells (T(reg)) and effector T cells in the periphery. Previously, we identified the cAMP-responsive element modulator α (CREMα) as a major factor responsible for decreased IL-2 production in T cells from SLE patients. Additionally, using a transgenic mouse that specifically over-expresses CREMα in T cells (CD2CREMαtg), we provided in-vivo evidence that CREMα indeed suppresses IL-2 production. To analyse the effects of CREMα in an autoimmune prone mouse model we introduced a Fas mutation in the CD2CREMαtg mice (FVB/Fas(-/-) CD2CREMαtg). Overexpression of CREMα strongly accelerated the lymphadenopathy and splenomegaly in the FVB/Fas(-/-) mice. This was accompanied by a massive expansion of double-negative (DN) T cells, enhanced numbers of interferon (IFN)-γ-producing T cells and reduced percentages of T(regs). Treatment of FVB/Fas(-/-) CD2CREMαtg mice with IL-2 restored the percentage of T(regs) and reversed increased IFN-γ production, but did not affect the number of DNTs. Our data indicate that CREMα contributes to the failure of tolerance in SLE by favouring effector T cells and decreasing regulatory T cells, partially mediated by repression of IL-2 in vivo.

Predicting risk of peripartum blood transfusion during vaginal and cesarean delivery: A risk prediction model.

OBJECTIVE: The objective of this study is to develop a model that will help predict the risk of blood transfusion using information available prior to delivery. STUDY DESIGN: The study is a secondary analysis of the Consortium on Safe Labor registry. Women who had a delivery from 2002 to 2008 were included. Pre-delivery variables that had significant associations with transfusion were included in a multivariable logistic regression model predicting transfusion. The prediction model was internally validated using randomly selected samples from the same population of women. RESULTS: Of 156,572 deliveries, 5,463 deliveries (3.5%) required transfusion. Women who had deliveries requiring transfusion were more likely to have a number of comorbidities such as preeclampsia (6.3% versus 4.1%, OR 1.21, 95% CI 1.08-1.36), placenta previa (1.8% versus 0.4%, OR 4.11, 95% CI 3.25-5.21) and anemia (10.6% versus 5.4%, OR 1.30, 95% CI 1.21-1.41). Transfusion was least likely to occur in university teaching hospitals compared to community hospitals. The c statistic was 0.71 (95% CI 0.70-0.72) in the derivation sample. The most salient predictors of transfusion included type of hospital, placenta previa, multiple gestations, diabetes mellitus, anemia, asthma, previous births, preeclampsia, type of insurance, age, gestational age, and vertex presentation. The model was well-calibrated and showed strong internal validation. CONCLUSION: The model identified independent risk factors that can help predict the risk of transfusion prior to delivery. If externally validated in another dataset, this model can assist health care professionals counsel patients and prepare facilities/resources to reduce maternal morbidity.

Transformation-optics description of nonlocal effects in plasmonic nanostructures.

We develop an insightful transformation-optics approach to investigate the impact that nonlocality has on the optical properties of plasmonic nanostructures. The light-harvesting performance of a dimer of touching nanowires is studied by using the hydrodynamical Drude model, which reveals nonlocal resonances not predicted by previous local calculations. Our method clarifies the interplay between radiative and nonlocal effects in this nanoparticle configuration, which enables us to elucidate the optimum size that maximizes its absorption and field enhancement capabilities.

Seroprimatology of chimpanzees: blood-group distribution as a "racial" characteristic.

Significant differences in the distribution of human-type and simian-type blood groups have been demonstrated in chimpanzees classified into subspecies or "races" on the basis of morphological traits. The differences in chimpanzees are analogous to racial differences in the distribution of blood groups in man.

Health-related quality of life (HRQL) in all-patients treated with chemotherapy only: a report from the late effects surveillance system in Germany.

BACKGROUND: The study examines the HRQL in children suffering from ALL over time. PATIENTS: 96 patients (average age 7.1 years) were included, treated with chemotherapy in 15 German study centres between 1997 and 2003. METHODS: The HRQL was assessed based on both the parent report (POQOLS) and the patient self-report (KINDL) at 3 intervals: up to 2 weeks after diagnosis (T1), upon completion of the re-induction therapy (T2) and at the end of the maintenance therapy (T3). To analyse the changes of HRQL over time, the differences between the individual scores (T2-T1 and T3-T1) were calculated and statistically tested. The HRQL results from KINDL were also compared to a sample from the German general population. RESULTS: POQOLS (scale 0 (optimum) to 6): A decrease of HRQL was found in the domain "activity" at T1 (mean score=3.1) and T2 (mean score=2.6). Over time, HRQL improved significantly with a mean score-difference T3-T1=-0.7 (p=0.001). KINDL (scale 0 to 100 (optimum)): The individual HRQL-scores improved over time with the major increases occurring in the domains "physical" with a mean score-difference T2-T1=21.7 (p<0.0001) and a mean score-difference T3-T1=20.6 (p=0.0002) and "mental" with a mean score-difference T2-T1=7.1 (p=0.02) and T3-T1=8.1 (p=0.02). However, the mean overall HRQL-score was significantly lower compared to the general population. CONCLUSIONS: Children with ALL show lower HRQL compared to the general population. Over time, HRQL improved significantly from both the patient and the parent perspective.

Defect in the excretion of a vasoactive polypeptide fraction A possible genetic marker of primary hypertension.

A polypeptide fraction isolated from the urine of normotensive subjects lowers the blood pressure (BP) in a rabbit bioassay (mean BP decrease 33.8% +/- 0.6%, SEM). Patients with primary hypertension exhibit reduced or no activity (mean BP decrease 8.8% +/- 1.2%). In contrast, patients with secondary forms of hypertension show activity like normotensives (mean BP decrease 33.4% +/- 1.0%). The results of the bioassay in the two patient groups correlate well with the family incidence of hypertension (68% and 37% for primary and secondary hypertension respectively). Cases with borderline hypertension fall into two groups; a larger one with vasoactivity inthe bioassay and lower family incidence of hypertension; and a smaller group reacting like patients with primary hypertension. Only the latter group may represent an initial stage of primary hypertension. In normotensive children and young men, an inactive fraction was found in 31% and 28% respectively. These inactive groups had twice the family incidence of hypertension compared to the groups with vasoactivity. These results suggest the existence of a possible genetic marker of primary hypertension and may offer the possibility to detect the disease before its manifestation.

Silica-related rheumatoid arthritis without lung involvement.

We report a young male with recent onset of rheumatoid arthritis (RA) in whom the remarkable severity of the disease led to additional investigations. The only significant finding was mediastinal lymphadenopathy, without lung involvement. Biopsy of the mediastinal lymph node revealed pathological findings typical of silicosis. To our knowledge, this is the first report of silicosis apparent solely in the mediastinal lymph node of an RA patient. This suggests that lung involvement is not crucial for the development of silica-related arthritis.

Familial homozygous hypercholesterolemia: clinical and cardiovascular features in 18 patients.

Homozygous familial hypercholesterolemia (HFH) is a very rare autosomal dominant disease characterized by accelerated severe atherosclerosis. We examined 18 patients from 9 families with HFH. The age range was 6-30 years (mean = 16 years). Male to female ratio was equal. All patients had huge, multiple tuberous xanthomas on the skin and tendons. Mean +/- standard deviation of plasma cholesterol, triglycerides, low-density lipoproteins (LDL), and high-density lipoproteins (HDL) cholesterol levels were 608 +/- 89, 122 +/- 39, 550 +/- 88, and 26 +/- 8 mg/dl, respectively. Five patients (28%) had angina pectoris, two sustained a myocardial infarction, and one died at the age of 15 years. Two-dimensional echocardiography demonstrated supravalvular aortic stenosis in 3 of the 13 patients (23%). Coronary arteriography performed in 11 patients demonstrated significant obstruction in 6 patients, 2 each with single-, double-, and triple-vessel disease. Left main stenosis was present in 3 patients (27%). Supravalvular aortic narrowing was demonstrated in 6 patients (54%) and was associated with a gradient in 2 (25 and 35 mmHg, respectively). Segmental contraction abnormalities were detected in 2 of the 11 patients (18%). It is concluded that coronary artery disease is prevalent in patients with HFH and, based on the data presented, we recommend the performance of noninvasive technique, coronary arteriography and supravalvular aortography at an early age to detect and to follow the progression of the disease.

Psychiatric guidelines for licensing drivers.

The role of personality, psychopathology, suicidality and stress in the proneness of some individuals to traffic accidents is presented. Although several studies described risk factors towards traffic accidents, it is not clear how driving fitness should be determined on an individual basis. This assessment should include a combination of psychiatric diagnosis, personality questionnaire, possible stressful events, and most important, the individual's driving record. We endorse the importance of research in this area with more carefully planned studies and a greater involvement of physicians and psychologists in this field.