Child Health Care Services in Austria.

We describe child health care in Austria, a small country in Central Europe with a population of about 9 million inhabitants of whom approximately 1.7 million are children and adolescents under the age of 20 years. For children and adolescents, few health care indicators are available. Pediatric and adolescent health provision, such as overall health provision, follows a complex system with responsibilities shared by the Ministry of Health, 19 social insurance funds, provinces, and other key players. Several institutions are affiliated with or cooperate with the Ministry of Health to assure quality control. The Austrian public health care system is financed through a combination of income-based social insurance payments and taxes. Pediatric primary health care in Austria involves the services of general pediatricians and general practitioners. Secondary care is mostly provided by the 43 children's hospitals; tertiary care is (particularly) provided in 4 state university hospitals and 1 private university hospital. The training program of residents takes 6 years and is completed by a final examination. Every year, this training program is completed by about 60 residents.

Prevention, management and extent of adverse pregnancy outcomes in women with hereditary antithrombin deficiency.

Antithrombin (AT) deficiency is a rare hereditary thrombophilia with a mean prevalence of 0.02 % in the general population, associated with a more than ten-fold increased risk of venous thromboembolism (VTE). Within this multicenter retrospective clinical analysis, female patients with inherited AT deficiency were evaluated concerning the type of inheritance and extent of AT deficiency, medical treatment during pregnancy and postpartally, VTE risk as well as maternal and neonatal outcome. Statistical analysis was performed with SPPS for Windows (19.0). A total of 18 pregnancies in 7 patients were evaluated, including 11 healthy newborns ≥37th gestational weeks (gw), one small for gestational age premature infant (25th gw), two late-pregnancy losses (21st and 28th gw) and four early miscarriages. Despite low molecular weight heparin (LMWH) administration, three VTE occurred during pregnancy and one postpartally. Several adverse pregnancy outcomes occurred including fetal and neonatal death, as well as severe maternal neurologic disorders occurred. Patients with substitution of AT during pregnancy in addition to LMWH showed the best maternal and neonatal outcome. Close monitoring with appropriate anticoagulant treatment including surveillance of AT levels might help to optimize maternal and fetal outcome in patients with hereditary AT deficiency.

The dynamics of the female microbiome: unveiling abrupt changes of microbial domains across body sites from prepartum to postpartum phases.

The microbial ecosystem of women undergoes enormous changes during pregnancy and the perinatal period. Little is known about the extent of changes in the maternal microbiome beyond the vaginal cavity and its recovery after birth. In this study, we followed pregnant women [maternal prepartum (mpre), n = 30] into the postpartum period [1 month postpartum, maternal postpartum (mpost), n = 30]. We profiled their oral, urinary, and vaginal microbiome; archaeome; mycobiome; and urinary metabolome and compared them with those of nonpregnant (np) women (n = 29). Overall, pregnancy status (np, mpre, and mpost) had a smaller effect on the microbiomes than body site, but massive transitions were observed for the oral and urogenital (vaginal and urinary) microbiomes. While the oral microbiome fluctuates during pregnancy but stabilizes rapidly within the first month postpartum, the urogenital microbiome is characterized by a major remodeling caused by a massive loss of Lactobacillus and thus a shift from Vaginal Community State Type (CST) I (40% of women) to CST IV (85% of women). The urinary metabolome rapidly reached an np-like composition after delivery, apart from lactose and oxaloacetic acid, which were elevated during active lactation. Fungal and archaeal profiles were indicative of pregnancy status. Methanobacterium signatures were found mainly in np women, and Methanobrevibacter showed an opposite behavior in the oral cavity (increased) and vagina (decreased) during pregnancy. Our findings suggest that the massive remodeling of the maternal microbiome and metabolome needs more attention and that potential interventions could be envisioned to optimize recovery and avoid long-term effects on maternal health and subsequent pregnancies. IMPORTANCE: The perinatal microbiome is of specific interest for the health of the mother and infant. We therefore investigate the dynamics of the female microbiome from nonpregnant over prepartum to the postpartum period in urine and the oral and vaginal cavities. A specific focus of this study is put not only on the bacterial part of the microbiome but also on the underinvestigated contribution of fungi and archaea. To our knowledge, we present the first study highlighting those aspects. Our findings suggest that the massive remodeling of the maternal microbiome and metabolome needs more attention and that potential interventions could be envisioned to optimize recovery and avoid long-term effects on maternal health and subsequent pregnancies.

In vitro maturation: a five-year experience.

OBJECTIVE: Although some patients may benefit from reduced follicle-stimulating hormone (FSH) application, in-vitro maturation (IVM) belongs to the rare treatment options in assisted reproduction. We summarize our five-year IVM experience. DESIGN: Retrospective, observational study. SETTING: Reproductive Medicine, University Hospital. SAMPLE: 115 patients with polycystic ovary syndrome (PCOS) as well as patients after ovarian hyperstimulation syndrome (OHSS) from February 2005 to December 2009. MATERIAL AND METHODS: Stimulation started between day 3-10 of the menstrual cycle and FSH dosage was 125IU/day over three days. Ovulation was induced on the third day of FSH injection or one day afterwards and oocyte retrieval was performed 33-38 hours later. Oocytes were cultivated for 24 hours in IVM medium. Fertilization was carried out one day after oocyte retrieval and embryo transfer two days afterwards. MAIN OUTCOME MEASURES: Pregnancy rates. RESULTS: 115 patients were included and 215 oocyte retrievals (intracytoplasmic sperm injection: n=125, 59%; in vitro fertilization: n=73, 34.4%) with 177 embryo transfers performed. The main reasons for IVM were: PCOS (71.7%) and OHSS (15.0%). Mean number of oocytes was 8.9/oocyte retrieval with 5.9 (64%) becoming mature, 2.8 (45.1%) being fertilized and 2.1 transferred. Pregnancy rate per transfer was 15.3% (n=27) with 13 live births (7.3%), one intrauterine death (0.6%), four miscarriages (2.3%) and nine biochemical pregnancies (5.1%). In 61 cases, fertilized oocytes were frozen and 32 cryotransfers were performed, resulting in three pregnancies. CONCLUSIONS: Although the pregnancy rate was low, IVM is very convenient for patients due to low FSH dosages and few appointments at low cost.

Guiding principles for the implementation of non-animal safety assessment approaches for cosmetics: skin sensitisation.

Characterisation of skin sensitisation potential is a key endpoint for the safety assessment of cosmetic ingredients especially when significant dermal exposure to an ingredient is expected. At present the mouse local lymph node assay (LLNA) remains the 'gold standard' test method for this purpose however non-animal test methods are under development that aim to replace the need for new animal test data. COLIPA (the European Cosmetics Association) funds an extensive programme of skin sensitisation research, method development and method evaluation and helped coordinate the early evaluation of the three test methods currently undergoing pre-validation. In May 2010, a COLIPA scientific meeting was held to analyse to what extent skin sensitisation safety assessments for cosmetic ingredients can be made in the absence of animal data. In order to propose guiding principles for the application and further development of non-animal safety assessment strategies it was evaluated how and when non-animal test methods, predictions based on physico-chemical properties (including in silico tools), threshold concepts and weight-of-evidence based hazard characterisation could be used to enable safety decisions. Generation and assessment of potency information from alternative tools which at present is predominantly derived from the LLNA is considered the future key research area.

CLA does not impair endothelial function and decreases body weight as compared with safflower oil in overweight and obese male subjects.

OBJECTIVE: Conjugated linoleic acid (CLA) showed a wide range of beneficial biological effects with relevance for cardiovascular health in animal models and humans. Most human studies used olive oil as a reference. This study assessed the effect of CLA as compared with safflower oil on endothelial function and markers of cardiovascular risk in overweight and obese men. Heated safflower oil and olive oil were given for additional descriptive control. METHODS: Eighty-five overweight men (aged 45-68 years, body mass index 25-35 kg/m(2)) were randomized to receive 4.5 g/d of the CLA isomeric mixture, safflower oil, heated safflower oil, or olive oil in a 4-week double-blind study. Endothelial function was assessed by peripheral arterial tonometry (PAT) index determination in the fasting and postprandial state (i.e., 4 hours after consumption of a fat- and sucrose-rich meal). RESULTS: CLA as compared with safflower oil consumption did not impair fasting or postprandial PAT index but decreased body weight. CLA as compared with safflower oil did not change total, low-density lipoprotein (LDL), or high-density lipoprotein (HDL) cholesterol; triglycerides; insulin sensitivity indices; C-reactive protein; soluble adhesion molecules; oxidized LDL; lipoprotein a (Lp[a]); paraoxonase; or platelet-activating factor acetylhydrolase (PAF-AH) activity, but significantly reduced arylesterase activity and increased concentrations of the F(2)-isoprostane 8-iso-prostaglandin F (PGF)(2α). CONCLUSION: CLA did not impair endothelial function. Other parameters associated with metabolic syndrome and oxidative stress were not changed or were slightly improved. Results suggest that CLA does not increase cardiovascular risk. Increased F(2)-isoprostane concentrations in this context may not indicate increased oxidative stress.

Hysteroscopic findings in women with two and with more than two first-trimester miscarriages are not significantly different.

The purpose of this study was to analyse hysteroscopic results in patients with recurrent miscarriages and to compare the frequency of uterine anomalies in women with a history of exactly two and with more than two consecutive miscarriages. A retrospective analysis of 206 patients undergoing hysteroscopy for repeated early pregnancy losses was performed at two university centres. Late miscarriages were excluded, terminations of pregnancy were not counted. Eighty-seven patients had suffered from exactly two early miscarriages and 119 from more than two. Both groups were comparable with respect to age at admission (32.95+/-4.46 versus 34.06+/-5.02 years) and at first miscarriage (30.43+/-4.24 versus 29.08+/-5.38 years). The prevalence of acquired (adhesions, polyps, fibroids) and congenital uterine anomalies (septate or bicornuate uterus, etc.) did not differ significantly (acquired: 28.7 versus 27.7%; congenital: 9.2 versus 16.8%). The rates of uterine anomalies did not differ significantly overall (36.8 versus 42.9%). In conclusion, uterine anomalies are frequently found in patients with two and with more than two early miscarriages. Due to the high rate of anomalies, their risk for adverse pregnancy outcome and a possible therapeutic approach, hysteroscopy might be a diagnostic option even after two early miscarriages.

Effects of probiotic bacteria and their genomic DNA on TH1/TH2-cytokine production by peripheral blood mononuclear cells (PBMCs) of healthy and allergic subjects.

Among the factors potentially involved in the increased prevalence of allergic diseases, modification of the intestinal flora or lack of microbial exposure during childhood has been proposed. T(H)2-cytokines increase the production of IgE and stimulate mast cells and eosinophils, whereas T(H)1-cytokines, such as IFN-gamma, may suppress IgE synthesis and stimulate the expression of the secretory piece of IgA. Thus, a dysregulation in the expression of T(H)1- and T(H)2-cytokines may contribute to the initiation and maintenance of allergic diseases. Lactobacilli belonging to the natural intestinal microflora were reported to reduce the incidence of atopic dermatitis and the severity of allergic manifestations and to modulate T(H)1/T(H)2 responses. The mechanisms still remain to be elucidated. We sought to assess the effect of different probiotics, Lactobacillus rhamnosus GG, Lactobacillus gasseri (PA16/8), Bifidobacterium bifidum (MP20/5), and Bifidobacterium longum (SP07/3), on the T(H)1 and T(H)2 responses of peripheral blood mononuclear cells (PBMCs) from healthy subjects and from patients with allergy against house dust mite to Staphylococcus enterotoxin A (SEA) and Dermatophagoides pteronyssinus (Dpt). To elucidate the molecular basis of these effects, the effects of bacterial genomic DNA were compared with the effects of viable bacteria. PBMCs from allergic patients and from healthy donors were incubated for 24 or 48 h, respectively, with or without SEA and Dpt allergens. The effects of preincubation with live probiotic bacteria and the effect of their genomic DNA, added simultaneously to cultures and incubated for 24h, were assessed by measuring T(H)1/T(H)2-cytokine production. The tested live Gram-positive probiotic bacteria and their genomic DNA inhibited SEA- and Dpt-stimulated secretion of T(H)2-cytokines (IL-4 and IL-5) and enhanced the stimulation of IFN-gamma. This effect was dose-dependent with a dosage-optimum, which was identical for all lactic acid producing bacteria (LAB) tested (10 bacteria per PBMC) and their DNA (75 ng/ml). Based on the maximal effects achieved with LAB and their DNA, more than 50% of the effects seem to be contributed by DNA. No significant effect was induced by the control, Gram-negative Escherichia coli TG1. Lactobacilli and bifidobacteria reduced SEA-stimulated IL-4 and IL-5 production more effectively in PBMCs from healthy subjects than from allergic patients. In contrast to this, inhibition of Dpt-stimulated IL-4- and IL-5-secretion was more pronounced in cells from allergic subjects. Compared with living LAB, bacterial DNA inhibited IL-4- and IL-5-secretion in a similar manner. SEA- and even more so Dpt-stimulated IFN-gamma stimulation by living LAB was less pronounced in allergic than in healthy subjects, whereas IFN-gamma stimulation by their DNA was more pronounced in allergic subjects. The tested probiotic bacteria as well as their genomic DNA modulated the T(H)1/T(H)2 response to some allergens dose-dependently. DNA seems to contribute to 50% of the effect exerted by living bacteria in this in vitro model. The magnitude of the probiotic effects differed between healthy and allergic subjects. Whether the modulation found for the tested strains might be useful for the prevention and treatment of allergic diseases has to be assessed in clinical trials.

Effect of Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3, B. bifidum MF 20/5 on common cold episodes: a double blind, randomized, controlled trial.

BACKGROUND & AIMS: The aim of this study was to investigate whether the consumption of Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3, B. bifidum MF 20/5 (5 x 10(7) cfu/tablet) during at least 3 months influences the severity of symptoms and the incidence and duration of the common cold. METHODS: A randomized, double-blind, placebo-controlled intervention study was performed over at least 3 months during two winter/spring periods. Four hundred and seventy nine healthy adults (aged 18-67) were supplemented daily with vitamins and minerals with or without the probiotic bacteria. Cellular immune parameters were evaluated in a randomly drawn subgroup of 122 volunteers before and after 14 days of supplementation. During common cold episodes, the participants recorded symptoms daily. Stool samples were collected before and after 14 days of probiotic supplementation to quantify fecal Lactobacilli and Bifidobacteria using qRT-PCR. RESULTS: The total symptom score, the duration of common cold episodes, and days with fever during an episode were lower in the probiotic-treated group than in the control group: 79.3+/-7.4 vs. 102.5+/-12.2 points (P = 0.056), 7.0+/-0.5 vs. 8.9+/-1.0 days (P = 0.045), 0.24+/-0.1 vs. 1.0+/-0.3 days (P = 0.017). A significantly higher enhancement of cytotoxic plus T suppressor cells (CD8+) and a higher enhancement of T helper cells (CD4+) was observed in the probiotic-treated group. Fecal lactobacilli and bifidobacteria increased significantly after probiotic supplementation. CONCLUSIONS: The intake of probiotic bacteria during at least 3 months significantly shortened common cold episodes by almost 2 days and reduced the severity of symptoms.

Evaluation of an optimized protocol using human peripheral blood monocyte derived dendritic cells for the in vitro detection of sensitizers: Results of a ring study in five laboratories.

Allergic contact dermatitis is a delayed T-cell mediated allergic response associated with relevant social and economic impacts. Animal experiments (e.g. the local lymph node assay) are still supplying most of the data used to assess the sensitization potential of new chemicals. However, the 7th amendment to the EU Cosmetic Directive have introduced a testing ban for cosmetic ingredients after March 2013. We have developed and optimized a stable and reproducible in vitro protocol based on human peripheral blood monocyte derived dendritic cells to assess the sensitization potential of chemicals. To evaluate the transferability and the predictivity of this PBMDCs based test protocol, a ring study was organized with five laboratories using seven chemicals with a known sensitization potential (one none-sensitizer and six sensitizers, including one pro-hapten). The results indicated that this optimized test protocol could be successfully transferred to all participating laboratories and allowed a correct assessment of the sensitization potential of the tested set of chemicals. This should allow a wider acceptance of PBMDCs as a reliable test system for the detection of human skin sensitizers and the inclusion of this protocol in the toolbox of in vitro methods for the evaluation of the skin sensitization potential of chemicals.

Maternal factor V Leiden and prothrombin mutations do not seem to contribute to the occurrence of two or more than two consecutive miscarriages in Caucasian patients.

BACKGROUND: We analysed the prevalence of the most common hereditary thrombophilia (hTP) - factor V Leiden (FVL) mutation, prothrombin 20210 G>A substitution (PT) - and the 677 C>T replacement in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene in Caucasian patients with a history of two and more consecutive recurrent miscarriages (RMs) as compared to healthy controls with an identical ethnic background and at least one live birth. METHODS: A multicenter analysis of three hTP was performed in 641 RM patients identically screened at specialized university centres. RESULTS: The study groups consisted of 240 patients with 2 (1) and 401 patients with >2 miscarriages (2) and were compared with 157 controls. There was no significant difference in the prevalence of the hTP between RM patients and controls nor within the two study groups. Subgroup analysis showed that the homozygous MTHFR polymorphism was significantly more prevalent in the study group 2 as compared to study group 1 (13.9 versus 7.9%, P = 0.02). CONCLUSION: In Caucasians, maternal FVL or PT mutations do not seem to contribute to the pathophysiology of RM, irrespective of the number of miscarriages. However, the role of the homozygous MTHFR polymorphism merits further investigation.

Skin sensitisation: the Colipa strategy for developing and evaluating non-animal test methods for risk assessment.

Allergic contact dermatitis is a delayed-type hypersensitivity reaction induced by small reactive chemicals (haptens). Currently, the sensitising potential and potency of new chemicals is usually characterised using data generated via animal studies, such as the local lymph node assay (LLNA). There are, however, increasing public and political concerns regarding the use of animals for the testing of new chemicals. Consequently, the development of in vitro, in chemico or in silico models for predicting the sensitising potential and/or potency of new chemicals is receiving widespread interest. The Colipa Skin Tolerance task force currently collaborates with and/or funds several academic research groups to expand our understanding of the molecular and cellular events occurring during the acquisition of skin sensitisation. Knowledge gained from this research is being used to support the development and evaluation of novel alternative approaches for the identification and characterisation of skin sensitizing chemicals. At present three non-animal test methods (Direct Peptide Reactivity Assay (DPRA), Myeloid U937 Skin Sensitisation Test (MUSST) and human Cell Line Activation Test (hCLAT)) have been evaluated in Colipa interlaboratory ring trials for their potential to predict skin sensitisation potential and were recently submitted to ECVAM for formal pre-validation. Data from all three test methods will now be used to support the study and development of testing strategy approaches for skin sensitiser potency prediction. This publication represents the current viewpoint of the cosmetics industry on the feasibility of replacing the need for animal test data for informing skin sensitisation risk assessment decisions.

Molecular and cellular basis of microflora-host interactions.

Mucosal surfaces represent the main sites in which environmental microorganisms and antigens interact with the host. In particular the intestinal mucosal surfaces are in continuous contact with a heterogeneous population of microorganisms of the endogenous flora and are exposed to food and microbes. As a result, the immune system of the host has to discriminate between pathogenic and commensal microorganisms. This article reviews the types of sentinel cells that continuously sense the environment and coordinate immune defenses as well as the mechanisms of the innate and adaptive immune systems that are activated by bacterial and viral molecular patterns leading to inflammatory, allergic, or regulatory immune response with special emphasis on probiotic bacteria.

Probiotic bacteria reduced duration and severity but not the incidence of common cold episodes in a double blind, randomized, controlled trial.

To investigate the effect of long-term consumption of probiotic bacteria on viral respiratory tract infections (common cold, influenza), a randomized, double blind, controlled intervention study was performed during two winter/spring periods (3 and 5 month). Four hundred and seventy-nine healthy adults were supplemented daily with vitamins plus minerals with or without probiotic lactobacilli and bifidobacteria. The intake of the probiotic had no effect on the incidence of common cold infections (verum=158, control=153 episodes, influenza was not observed), but significantly shortened duration of episodes by almost 2 days (7.0+/-0.5 versus 8.9+/-1.0 days, p=0.045), reduced the severity of symptoms and led to larger increases in cytotoxic T plus T suppressor cell counts and in T helper cell counts.