CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice.

Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM/AF10 leukemogenesis has not yet been evaluated. We generated double mutant mice, which express the Lck-CALM/AF10 fusion gene and are haploinsufficient for the Cebpa gene. To characterize the hematopoiesis, we quantified hematopoietic stem cells, myeloid progenitor cells, megakaryocyte-erythrocyte progenitor cells, common myeloid progenitor cells, and granulocyte-macrophage progenitor cells. No significant difference was detected in any of the progenitor subsets. Finally, we tested if Cebpa haploinsufficiency would lead to the expansion of Mac-1+/B220+/c-Kit+ cells proposed as the CALM/AF10 leukemic progenitor. Less than 1% of bone marrow cells expressed Mac-1, B220, and c-Kit with no significant difference between groups. Our results showed that the reduction of Cebpa gene expression in Lck-CALM/AF10 mice did not affect their hematopoiesis or induce leukemia. Our data corroborated previous studies suggesting that the CALM/AF10 leukemia-initiating cells are early progenitors with lymphoid/myeloid differentiating potential.

The -2549 -2567 del18 Polymorphism in VEGF and Irreversible Bronchoconstriction in Asthmatics.

BACKGROUND: While the importance of vascular endothelial growth factor (VEGF) in the pathogenesis of several diseases (eg, neoplasms) has been proven, its role in asthma, especially in terms of the potential associations between genetic variants of VEGF and airway remodeling, has received relatively little attention. Objectives: This study aimed to evaluate the possible connection between a genetic factor, ie, the polymorphism del/ins in the VEGF promoter region, and airway remodeling potential in asthmatics with and without irreversible bronchoconstriction. MATERIAL AND METHODS: The study population comprised 82 patients with asthma (of whom 42 had irreversible bronchoconstriction) and a group of 40 controls. DNA was isolated from peripheral blood leukocytes. Polymerase chain reaction was used to type the VEGF (18-bp deletion/insertion) gene polymorphism at loci -2549 -2567. Other factors (ie, smoking, disease duration) were also taken into consideration. RESULTS: The del/del genotype was found in 74.39% of patients with asthma (P=.031; OR=2.38), 80.95% of patients with irreversible bronchoconstriction (P=.012; OR=3.48), and 67.5% patients with reversible bronchoconstriction (P=.251; OR=1.70). The proportion of smokers to nonsmokers was higher (P=.032) and disease duration was longer (P=.041) in patients with irreversible bronchoconstriction than in those with reversible bronchoconstriction. CONCLUSIONS: Our results showed that the risk of irreversible bronchoconstriction in asthmatics was associated with the presence of the del18 genotype at the -2549 -2567 position in the promoter region of the VEGF gene, as were disease duration and other factors such as smoking.

CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice

Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM/AF10 leukemogenesis has not yet been evaluated. We generated double mutant mice, which express the Lck-CALM/AF10 fusion gene and are haploinsufficient for the Cebpa gene. To characterize the hematopoiesis, we quantified hematopoietic stem cells, myeloid progenitor cells, megakaryocyte-erythrocyte progenitor cells, common myeloid progenitor cells, and granulocyte-macrophage progenitor cells. No significant difference was detected in any of the progenitor subsets. Finally, we tested if Cebpa haploinsufficiency would lead to the expansion of Mac-1+/B220+/c-Kit+ cells proposed as the CALM/AF10 leukemic progenitor. Less than 1% of bone marrow cells expressed Mac-1, B220, and c-Kit with no significant difference between groups. Our results showed that the reduction of Cebpa gene expression in Lck-CALM/AF10 mice did not affect their hematopoiesis or induce leukemia. Our data corroborated previous studies suggesting that the CALM/AF10 leukemia-initiating cells are early progenitors with lymphoid/myeloid differentiating potential.

[Willingness of Students of Economics to Pay for Predictive Oncological Genetic Testing - An Empirical Analysis]. / Die Zahlungsbereitschaft von Studierenden der Wirtschaftswissenschaften für prädiktive onkologische Gentests ­ eine empirische Analyse.

Objectives: The present study aims to investigate the interest of young adults in predictive oncological genetic testing and their willingness to pay for such a test. Furthermore, major determinants of the 2 variables of interest were identified. Methods: 348 students of economics from the Leibniz University of Hanover were queried in July 2013 using an extensive questionnaire. Among other things, the participants were asked if they are interested in information about the probability to develop cancer in the future and their willingness to pay for such information. Data were analysed using descriptive statistics and ordinal probit regressions. Additionally marginal effects were calculated. Results: About 50% of the students were interested in predictive oncological genetic testing and were willing to pay for the test. Moreover, the participants who were willing to pay for the test partly attach high monetary values to the information that could so be obtained. The study shows that the interest of the students and their willingness to pay were primarily influenced by individual attitudes and perceptions. Conclusions: The study proves that young adults were interested in predictive genetic testing and appreciate information about their probability of develop cancer someday.

Population-based study of the incidence of congenital hip dysplasia in preterm infants from the Survey of Neonates in Pomerania (SNiP).

BACKGROUND: Some etiological factors involved in developmental dysplasia of the hip (DDH) occur in the last trimester of pregnancy, which could result in a decreased incidence of DDH in preterm infants. The aim of this study was to compare the incidence of DDH between preterm and term infants. METHODS: Ultrasound of the hip joint was performed in 2,534 term infants and 376 preterm infants within the population-based Survey of Neonates in Pomerania (SNiP) study. RESULTS: A total of 42 (1.66%) term infants had DDH (Graf type II c, 0.8%; type D, 0.3% left and 0.4% right; type III a, 0.2% left). Eighteen infants had bilateral findings. Hip dysplasia occurred more frequently in female neonates (32/1,182 vs. 10/1,302, p < 0.023; 95% CI 0.012-0.022, χ 2 test). A familial disposition for DDH was found in 169 (6.7%) term infants and 181 (7.1%) infants in the overall population. In preterm infants, dysplasia of the hip was found in only three late preterm infants with gestational age between 36 and 37 weeks (n = 97) and not in preterm infants <36 weeks gestational age (n = 279). Regression analysis revealed a narrowly significant association between gestational week of birth and DDH (relative risk = 1.17; 95% confidence interval 0.99-1.37; p = 0.065). CONCLUSION: Our study suggests that preterm infants <36 weeks gestational age have a decreased risk of DDH.

Topography-Guided PRK and Crosslinking in Eyes with Keratoconus and Post-LASIK Ectasia.

Topography-guided photorefractive keratectomy (TG-PRK) combined with corneal collagen crosslinking (CXL) has been shown to potentially improve vision and stabilize progression in patients with keratoconus (KC). We attempted to reproduce the previously published results using a different laser platform (AMARIS 500E) in patients with KC and post-LASIK ectasia (PLE). All of the 9 included eyes showed improved topography (Kmax, Kmean, RMS HOA, vertical coma, cylinder; p < 0.05) and improved visual acuity (BCVA, UCVA; p < 0.05) after 18 months. Despite some still uncontrollable factors, the combination of TG-PRK and CXL may be a promising option to regularize and stabilize corneas with KC and PLE and improve visual acuity.

[Adjustment disorder and DSM-5: A review]. / Le trouble de l'adaptation et le DSM-5 : une revue de la littérature.

INTRODUCTION: This paper exposes the complexity and discrete characteristic of the adjustment disorder with reference to its clinical and scientific diagnosis. Even though the disorder occurs in frequent clinical circumstances after important life events, such as mobbing, burn-out, unemployment, divorce or separation, pregnancy denial, surgical operation or cancer, the adjustment disorder is often not considered in the diagnosis since better known disorders with similar symptoms prevail, such as major depression and anxiety disorder. Ten years ago, Bottéro had already noticed that the adjustment disorder diagnosis remained rather uncommon with reference to patients he was working with while Langlois assimilated this disorder with an invisible diagnosis. METHODOLOGY: In order to maximize the data collection, we used the article review below and challenged their surveys and results: National Center for Biotechnology Information (NBCI - Pubmed) for international articles and Cairn.info for French literature. Moreover, we targeted the following keywords on the search engine and used articles, which had been published from 1 February 1975 to 31 January 2015: "adjustment", "adjustment disorder" and the French translation "trouble de l'adaptation". RESULTS: One hundred and ninety-one articles matched our search criteria. However, after a closer analysis, solely 105 articles were selected as being of interest. Many articles were excluded since they were related to non-psychiatric fields induced by the term "adaptation". Indeed, the number of corresponding articles found for the adjustment disorder literally pointed-out the lack of existing literature on that topic in comparison to more known disorders such as anxiety disorder (2661 articles) or major depression (5481 articles). This represents up to 50 times more articles in comparison to the number of articles we found on adjustment disorder and up to 20 times more articles for the eating disorder (1994), although the prevalence is not significantly higher than for the adjustment disorder. According to their relevance and their content, we have split the articles into seven subcategories: 1. General description: most scientific articles generally describe the adjustment disorder as being a transition diagnosis, which is ambiguous, marginal and difficult to detect. The findings claim that only a few studies have been conducted on the adjustment disorder despite a high prevalence in the general population and in the clinical field. 2. CLASSIFICATION: the DSM-5 defined the adjustment disorder as a set of different outcomes and syndromes induced by stress after a difficult life event. While the link to other disorders has not been mentioned, the diagnosis of this disorder is no longer excluded or perceived as a secondary diagnosis. The DSM-5 faced criticism from three points of view: the operationalization of the concept of stress, the differential diagnosis and the description. 3. Prevalence: different samples have shown a significantly high prevalence of the adjustment disorder within the population. In addition to the psychiatric pain induced by difficult life events we need to emphasize the fact that 12.5 to 19.4 percent of the patients faced heavy and severe pathologies and depended on clinical care and treatment. 4. Etiology, comorbidity or associated symptomatology: the literature identified the tendency to commit suicide and stressful life events as being two fundamental characteristics of adjustment disorder. The third one is the personality profile. 5. DIFFERENTIAL DIAGNOSIS: that motivates researchers to focus on the adjustment disorder: the differentiation approach as to the major depression. Indeed, the aetiology, the symptomatology and the treatment differ from the adjustment disorder. 6. ASSESSMENT: very recently, Dutch researchers have developed and validated the Diagnostic Interview Adjustment Disorder (DIAD). 7. TREATMENT: in 2014, no data or meta-analysis recommended drug treatment in addition to therapy. In fact, several authors have demonstrated the ineffectiveness of drug therapy. The literature suggests a psychotherapeutic approach to treat adjustment disorder. CONCLUSION: Emotional reactions triggered by life events are responsible for full therapy agendas and for the rush in emergency rooms and hospitals. The reflex when faced with crying, insomnia or suicidal thoughts to give a diagnostic of major depressive disorder s is generally accepted by everyone. The elevated risk to commit suicide and the approved success of remission or healing through treatment (psychotherapy) are two major reasons why several studies promote the importance and the need to identify the adjustment disorder of our patients.

The impact of socioeconomic factors on the efficiency of voluntary toxoplasmosis screening during pregnancy: a population-based study.

BACKGROUND: Congenital toxoplasmosis is associated with severe complications. German state health insurance covers rubella, but not toxoplasmosis, immunity screening. We analysed the effect of socioeconomic factors on the efficiency of private toxoplasmosis screening during pregnancy. METHODS: Toxoplasmosis and rubella screening data (n = 5402 mothers) were collected within the population-based Survey of Neonates in Pomerania (SNiP). RESULTS: At the first-trimester screening, 34.4 % (88.1 %) of expecting mothers were immune to toxoplasmosis (rubella). Susceptibility for toxoplasmosis (rubella) was observed in 39.6 % (8.9 %) and 25.8 % (2.95 %) were not tested. Data on a 2(nd) screening were available in a subgroup of women with negative immunity showing less than 45 % participation rate. Active toxoplasmosis (no rubella) infection was observed in 0.3 % (n = 17) of pregnant women. A multiple logistic regression model (AIC = 719.67; AUC = 0.725) revealed that the likelihood of participating in a second toxoplasmosis screening increased among women with a good level of education and a steady partnership and decreased with paternal unemployment and the absence of breastfeeding. The highest probability of non-participation in toxoplasmosis screening was found among women with temporal burden and family responsibilities. A cost-benefit analysis showed that covering general screening for toxoplasmosis with health insurance saved costs. CONCLUSION: Toxoplasmosis carried a substantial risk of infection during pregnancy. Although increased socioeconomic status was positively associated with the participation in toxoplasmosis screening, this was not the case when pregnant women had strong temporal burden and family responsibilities. This data supports the need for toxoplasmosis screening among pregnant women as a general healthcare benefit covered by insurance.

Appendectomy in the pediatric population-a German nationwide cohort analysis.

BACKGROUND: Meta-analyses indicate advantages of laparoscopic compared to open appendectomy. Nationwide analyses on results of laparoscopic appendectomy are scarce and studies from Germany are not available. This observational cohort study based on a nationwide insurance database was performed to analyze results of pediatric laparoscopic versus open appendectomy in general use. METHODS: Data were extracted from the largest German statutory health insurance TK (∼9 million clients) in a 3-year period (2010-2012). All patients aged 4-17 years with International Classification of Procedures in Medicine (ICPM) code "appendectomy" were included. Logistic regression analysis for the risk of a surgical complication within 180 postoperative days was performed. RESULTS: Appendectomy was performed in 8110 patients (52.6 % male; 47.4 % female) and conducted laparoscopically in 75.0 % of the patients (conversion rate = 1.2 %). Laparoscopic compared to open surgery was associated with a shorter length of hospital stay in both uncomplicated and complicated appendicitis. Patients with complicated appendicitis had lower readmission rates for surgical complications after laparoscopic appendectomy and logistic regression analysis confirmed a significantly lower risk of readmission for surgical complications after laparoscopic compared to open operation in adolescents. Pediatric surgeons operated 23.9 % and general surgeons 76.1 % of patients. Laparoscopy was less frequently used and the conversion rate was significantly higher in pediatric surgical departments. CONCLUSION: This first nationwide German cohort study confirms that laparoscopic appendectomy is associated with a less complicated postoperative course compared to open appendectomy, particularly in patients with complicated appendicitis. Pediatric surgeons used laparoscopy less frequently compared to general surgeons. Laparoscopic appendectomy should therefore be further promoted in pediatric surgical centers in Germany.

A retrospective evaluation of doxorubicin-based chemotherapy for dogs with right atrial masses and pericardial effusion.

OBJECTIVE: To report the outcome of doxorubicin-based chemotherapy as the sole treatment for dogs with echocardiographically identified right atrial masses and pericardial effusion. METHODS: A retrospective study of case records of dogs with right atrial masses treated with doxorubicin. Dogs were excluded from the study if they had any type of surgery performed such as pericardiectomy or right atrial mass resection, or if their chemotherapy protocol did not include doxorubicin. The data collected included signalment, history, physical examination findings, diagnostic test results and long-term survival. RESULTS: Dogs with right atrial masses and pericardial effusion that received doxorubicin-based chemotherapy alone had a median survival of 139 · 5 days (range 2 to 302 days). Chemotherapy side effects were frequent but mild. CLINICAL SIGNIFICANCE: Doxorubicin-based chemotherapy alone appears to be a viable treatment option for dogs with echocardiographically identified right atrial masses and pericardial effusion.

[Incidence and duration of therapy of pathological hip findings in U2 and U3 examinations (SNiP study)]. / Inzidenz und Therapiedauer pathologischer Hüftbefunde im Rahmen der U2- und U3-Untersuchung (SNiP Studie).

INTRODUCTION AND OBJECTIVES: Determination of the efficacy of an early ultrasound examination followed by immediate treatment of hip joint dysplasia as well as measuring the therapeutic success in a population-based cohort study of neonates. MATERIAL AND METHODS: The Survey of Neonates in Pomerania (SNiP) study included 4,093 neonates which represents 95.1 % of the total neonatal population. Of these children 2,534 (61.9 %) underwent ultrasound examination of the hip joint during the U2 stage (3-10 days after birth). The mean gestational age was 38.9 weeks. The sonographic classification was performed according to Graf. RESULTS: Initially (U2 stage) 42 (1.66 %) children were reported to be in need of therapy (stage IIc or higher according to Graf). The analysis showed a significantly higher incidence in girls (32 girls vs. 10 boys, p < 0.023, χ(2) test) and in children who had a breech birth (116, 4.6 %). A genetic predisposition was ascertained in 180 (7.1 %) children. The children could be subdivided into two groups: 1) children who underwent hip joint ultrasound during both U2 and U3 and 2) children who were first screened at the U3 stage. Of the 49 out of 54 neonates where the ultrasound findings were positive at the U2 examination the hip joint was matured in 32 children at U3 (4-8 weeks), 11 children had to be treated for 8-12 weeks 5 children were treated for over 3 months and1 child needed surgical correction. CONCLUSION: The early diagnosis of hip maturation disorders and joint dysplasia facilitates early implementation of effective treatment. At our clinic over 60 % of the infants underwent the U2 check up and, given a pathological finding, could undergo early treatment. It was possible to successfully treat 78 % of these children with a Tübingen hip flexion splint in just 4-8 weeks. In contrast, infants who were first examined at the U3 stage needed treatment for 4-12 months. In our opinion, early diagnosis at the age of 3-10 days should be carried out for all newborns.

A systematic review of cost-effectiveness of monoclonal antibodies for metastatic colorectal cancer.

UNLABELLED: Metastatic colorectal cancer (mCRC) imposes a substantial health burden on patients and society. In recent years, advances in the treatment of mCRC have mainly resulted from the introduction of monoclonal antibodies (MoAbs). However, the application of these MoAbs considerably increases treatment costs. The objective of this article is to review and assess the economic evidence of MoAB treatment in mCRC. A systematic literature review was conducted and cost-effectiveness (CE) as well as cost-utility-studies were identified. For this, Medline, Embase, SciSearch, Cochrane, and nine other databases were searched from 2000 through February 2013 for full-text publications. The quality of the studies was assessed via a validated assessment tool (Quality of Health Economic Studies (QHES)). A total of 843 publications were screened. Of those, 15 studies involving the MoAbs bevacizumab, cetuximab and panitumumab met all inclusion criteria. Four studies analysed the CE of first-line treatment with bevacizumab and nine the CE of cetuximab in subsequent treatment lines. Two studies dealt with the CE of panitumumab. The analysis of sequential regimes and the direct comparison of two MoABs were analysed by only one study each. The quality of the included studies was high with the exception of one study. CONCLUSIONS: The treatment with bevacizumab, cetuximab and panitumumab is mainly considered to be not cost-effective in patients with mCRC. However, testing for Kirsten ras oncogene (KRAS) mutation prior to the treatment with cetuximab or panitumumab is found to be clearly cost-effective compared to no testing. Future research should focus on the CE of first-line treatment with cetuximab or panitumumab and studies on upcoming agents like regorafenib and aflibercept.

Chimerism in children with primary immunodeficiencies is influenced by number of activating killer cell immunoglobulin-like receptor genes in the donor and/or killer cell immunoglobulin-like receptor ligand mismatch.

BACKGROUND: Stem cell transplantation (SCT) is a curative treatment for children with primary immunodeficiencies. METHODS: The present retrospective analysis describes the long-term outcomes at a median follow-up of 9 years of 29 patients with immunodeficiency after SCT; 5 sibling and 24 alternative donor transplantations. T-cell engraftment emphazed on thymic dependent signal-joint T-cell receptor excision circles (sjTREC) generation and donor chimerism in relation to killer cell immunoglobulin-like receptor genes and their ligands. RESULTS: All children except two were reconstituted successfully from grafted material, including 9 and 18 cases of mixed chimerism (MC) and complete chimerism (CC), respectively. Univariate analyses showed that the number of activating KIR genes or HLA-C1/C2 ligand mismatches (P = .048) and possibly transplantation from an alternative donor (P = .054) facilitated CC development. Multivariate analysis showed that the presence of donor KIR haplotype B or incompatibility within C1/C2 ligands (relative risk, 6.1; 95% confidence interval, 1.08-34.69; P = .025) were significantly associated with the development of CC. CONCLUSIONS: These results suggested that the donor-activating KIR gene repertoire affected successful engraftment.

The genesis and unique properties of the lymphovascular tumor embolus are because of calpain-regulated proteolysis of E-cadherin.

The genesis and unique properties of the lymphovascular tumor embolus are poorly understood largely because of the absence of an experimental model that specifically reflects this important step of tumor progression. The lymphovascular tumor embolus is a blastocyst-like structure resistant to chemotherapy, efficient at metastasis and overexpressing E-cadherin (E-cad). Conventional dogma has regarded E-cad as a metastasis-suppressor gene involved in epithelial-mesenchymal transition. However, within the lymphovascular embolus, E-cad and its proteolytic processing by calpain and other proteases have a dominant oncogenic rather than suppressive role in metastasis formation and tumor cell survival. Studies using a human xenograft model of inflammatory breast cancer, MARY-X, demonstrated the equivalence of xenograft-generated spheroids with lymphovascular emboli in vivo with both structures demonstrating E-cad overexpression and specific proteolytic processing. Western blot revealed full-length (FL) E-cad (120 kDa) and four fragments: E-cad/NTF1 (100 kDa), E-cad/NTF2 (95 kDa), E-cad/NTF3 (85 kDa) and E-cad/NTF4 (80 kDa). Compared with MARY-X, only E-cad/NTF1 was present in the spheroids. E-cad/NTF1 was produced by calpain, E-cad/NTF2 by γ-secretase and E-cad/NTF3 by a matrix metalloproteinase (MMP). Spheroidgenesis and lymphovascular emboli formation are the direct result of calpain-mediated cleavage of E-cad and the generation of E-cad/NTF1 from membrane-associated E-cad rather than the de novo presence of either E-cad/NTF1 or E-cad/CTF1. E-cad/NTF1 retained the p120ctn-binding site but lost both the ß-catenin and α-binding sites, facilitating its disassembly from traditional cadherin-based adherens junctions and its 360° distribution around the embolus. This calpain-mediated proteolysis of E-cad generates the formation of the lymphovascular embolus and is responsible for its unique properties of increased homotypic adhesion, apoptosis resistance and budding.

IL-10 promoter polymorphisms influence susceptibility to aGvHD and are associated with proportions of CD4+FoxP3+ lymphocytes in blood after hematopoietic stem cell transplantation.

Four hundred and ninety-five patients (390 and 105 grafted from unrelated and sibling (SIB) donors, respectively) and their donors were analyzed for the impact of interleukin-10 (IL-10) promoter genotype [rs18000896 (-1082 G/A), rs18000871 (-819 C/T) and rs18000872 (-592 C/A)] on the outcome of hematopoietic stem cell transplantation (HSCT). Patients having ACC haplotype were at a lower risk of acute graft versus host disease (aGvHD, grade > I) if transplanted from human leukocyte antigen (HLA) well-matched (10/10) unrelated donors (20/135 vs 39/117, P < 0.001, Pcorr = 0.002), which was not seen if patients were transplanted from either sibling (SIB) or poorly matched (<10/10) unrelated donors (MUD). In addition, GCC haplotype positive recipients of unrelated donor transplants tended to be more susceptible to aGvHD (68/199 vs 39/169, P = 0.019, Pcorr = 0.057). Multivariate logistic regression analysis in the MUD transplanted group showed that donor-recipient human leukocyte antigen (HLA) mismatch [odds ratio (OR) = 3.937, P = 0.001] and a lack of ACC haplotype in recipients (OR = 0.417, P = 0.013) played a significant role as independent risk factors of aGvHD grade > I. ACC carriers had higher proportions of FoxP3+ lymphocytes gated in CD4+ lymphocytes as compared with patients with other IL-10 haplotypes. It was seen at the time of hematological recovery (mean ± SEM: 3.80 ± 0.91% vs 2.06 ± 0.98%, P = 0.012) and 2 weeks later (5.32 ± 0.87% vs 2.50 ± 0.83%, P = 0.013); -592 C/A polymorphism was separately analyzed and it was found that AA homozygotes tended to have a higher incidence of aGvHD (8/15 vs 116/456, P = 0.034) and low proportions of FoxP3 CD4+ lymphocytes in blood (0.43 ± 0.22% vs 4.32 ± 0.71%, P = 0.051) measured 2 weeks after hematological recovery. Functional IL-10 polymorphism associated features influenced the risk of aGvHD with a positive effect of ACC on the pool of Treg in blood.

[Economic aspects of integrated care]. / Ökonomische Aspekte der integrierten Versorgung.

For more than 10 years integrated care has been an inherent part of the German healthcare system. The aims of selective contracts are to minimize interface problems between outpatient and inpatient sectors, generalist und specialist care as well as to intensify competition. Despite repeated efforts by the legislator, comprehensive integrated healthcare is still limited to a few flagship projects. This is mainly due to low incentives on the part of both suppliers and customers. Therefore, this article focuses on the economic aspects of integrated care. From a theoretical perspective, integrated care improves efficiency in the healthcare sector by reducing interface problems and asymmetric information as well as by intensifying competition. In practice, however, there are a number of obstacles to implementation. Particularly noteworthy are the financial difficulties in addition to problems regarding sectoral budgeting and the long-term nature of investments. However, the political environment and thus the financial arrangements within the statutory health insurance seem to be more important for further development of integrated care in Germany than the financing issues.

[Implementation of the new German job role code and its application in claims data analysis. Possibilities and limitations]. / Einführung des neuen Tätigkeitsschlüssels und seine Anwendung in GKV-Routinedatenauswertungen. Möglichkeiten und Limitationen.

In recent years, claims data analyses have become of increasing importance in several scientific disciplines in Germany. In specific research projects, it can be necessary to refine and to standardize the results by socioeconomic data. Information about graduation, social status, and occupation are provided by the German job role code for all people insured by statutory health insurance. During recent years, the working scheme has changed and new professions have appeared. Therefore, there has been a discussion about actualization and modification of the job role code. Since December 2011, an actualized job role code with an extensive set of new information is available. In addition, a new classification of professions is available in Germany which was considered in the design of the new job role code. The aim of this overview is to describe the structure of the new job role code as well as to discuss possible uses and limitations.

'Immunogenetics of Aging': report on the activities of the 15th International HLA and Immunogenetics Working Group and 15th International HLA and Immunogenetics Workshop.

'Immunogenetics of Aging' is a component that was first included in the 14th International HLA and Immunogenetics Workshop (IHIWS) and developed further within the 15th Workshop. The aim of this component was to assess the impact of human leukocyte antigen (HLA) genes, cytokine genes, and some innate immunity genes such as killer-cell immunoglobulin-like receptors (KIRs) and mannose-binding lectin 2 (MBL2) in successful aging and their contribution to the better understanding of immune dysfunction in old age. Within the 15th IHIWS new populations were included in the analysis. Additional cytokine gene polymorphisms were assessed and innate immunity genes were analyzed for possible relevance in longevity. The results showed that longevity might be associated with anti-inflammatory cytokine gene profiles, decreased frequency of interleukin-10 (IL-10) and transforming growth factor-B1 haplotypes associated with a low level of gene expression, and increased frequency of haplotypes determining a high level of expression. Extended tumor necrosis factor-A and IL-12B genotypes were also likely relevant to longevity. Data also showed that innate immunity genes are associated with susceptibility to infections in the elderly and showed that these genes might be an important genetic marker in aging. Decreased frequencies of KIR2DS5 and A1B10 haplotypes, and an increased proportion of MBL2-deficient haplotypes were found in the group with higher cytomegalovirus-specific IgG antibody levels. Together, these studies emphasize the relevance of genes regulating immune functions in maintaining human longevity and stress the importance of further clarifying their impact on successful aging.