Reproductive decision-making by women with X-linked hypohidrotic ectodermal dysplasia.

BACKGROUND: In X-linked hypohidrotic ectodermal dysplasia (XLHED), ectodysplasin A1 (EDA1) deficiency results in malformation of hair, teeth and sweat glands. Lack of sweating which can cause life-threatening hyperthermia is amenable to intrauterine therapy with recombinant EDA1. OBJECTIVES: This study aimed at evaluating reproductive decision-making by women with XLHED and at clarifying the potential impact of a prenatal treatment option. METHODS: In a retrospective cross-sectional analysis, a 75-item questionnaire filled in by 50 women with XLHED (age 19-49 years) was assessed. RESULTS: Sixteen women (32%) prevented pregnancies because of the risk to pass on XLHED; 15 considered assisted reproduction for the same reason. Twelve women had a history of miscarriage, stillbirth or abortion, and three women reported on previous abortion of affected fetuses. When imagining to be pregnant, all except one showed interest in prenatal diagnosis of XLHED and in the possibility of treatment before birth. In 13 out of 50 women (26%), XLHED if detected prenatally would have impact on the continuation of pregnancy. Among 35 mothers of at least one affected child, XLHED had rarely been diagnosed during the first pregnancy (17%) but regularly during subsequent pregnancies (77%). Becoming aware of the condition before birth had caused a moral conflict for 50% of these women. Subjects with an affected child less frequently considered assisted reproduction to prevent XLHED (P < 0.05). In 69% of the women who reported an effect of XLHED on family planning, a prenatal treatment option for this disease would influence their decision-making. CONCLUSIONS: Many pregnant XLHED carriers who seek prenatal diagnosis experience moral conflicts. A prenatal treatment option would have strong impact on reproductive decisions, underlining the importance of adequate professional counselling.

[Outpatient laparoscopic hysterectomy in France: A monocentric randomized trial]. / Hystérectomie cœlioscopique ambulatoire en France : étude randomisée unicentrique.

OBJECTIVE: To demonstrate the feasibility of outpatient laparoscopic hysterectomy using the assessment of post-operative quality of life. METHODS: A prospective randomized single-center trial was performed in France between 2013 and 2016. A total of 42 patients needed laparoscopic hysterectomy was included. Postoperative quality of life was assessed using the standardized Euroquol questionnaire. Patients filled the score before the operation and then on the 3rd and 30th postoperative day. Secondary outcomes were assessment of postoperative pain, overall quality of life, analgesic use, and anxiety. The patients were randomized into two groups, group A with a conventional hospital stay of 2 to 3 days and group B with a short stay and a discharge the day after the intervention. RESULTS: Twenty-one patients were randomized to group A as well as group B. We did not find any significant differences between the two groups in our study either on our primary outcome or in the seconds ones. On day 3, the average of Euroquol score was 0.68 for group A against 0.50 for group B (P=0.05). Likewise, the scores for postoperative pain were similar with 70.6 in group A and 61.8 in group B (P=0.21). The trend was the same for quality of life score or anxiety. CONCLUSION: Our study shows the possibility and the safety of outpatient laparoscopic hysterectomy.

Black TiO2 nanotubes: Efficient electrodes for triggering electric field-induced stimulation of stem cell growth.

TiO2 nanostructures represent a key platform for biomedical applications, due to the combination of biocompatibility and high surface area. Especially TiO2 nanotube layers have been widely investigated due to controllable nanotopographic effects as well as for electrodes in electrostimulation experiments. In the present work we produce Ar/H2-reduced 'black' TiO2 nanotube arrays with a strongly enhanced electrical conductivity and explore their interaction with mesenchymal stem cells when used as electrodes to apply electric fields (EF) across the cells. While we observe no significant change in cell adhesion and their focal contact formation on these high conductivity nanotubes, we do observe a rapid stem cell response when EF is engaged using the 'black' TiO2 nanotube arrays as electrodes. Compared to as-formed nanotube arrays, a faster stem cell growth was observed and a lower EF intensity caused an intracellular calcium level elevation. Our results indicate that the increased conductivity in TiO2 nanotubes significantly enhances the early stem cell response to minimal electric field stimuli. STATEMENT OF SIGNIFICANCE: The use of TiO2 nanostructures in biomedical applications is widely investigated, especially considering the nanostructured surface influence on the biomaterial-cell interactions. We have previously shown that an applied electric field (EF) on stem cells grown on TiO2 nanotubes leads to synergistic osteogenic stimulation in the absence of biochemical bone-inducing supplements. Here we report that black (i.e. highly conductive nanotubes obtained by reduction treatments) TiO2 nanotubes enable short-time EF effects on stem cells: we observe a faster stem cell growth and a significantly enhanced early stem cell response to minimal EF stimuli. The application of such nanostructures under electric field is promising for therapeutic interventions for bone regeneration and tissue engineering approaches.

[Beginners' operations and medical specialist standards : Avoidance of criminal liability and civil liability]. / Anfängeroperationen und Facharztstandard : Vermeidung strafrechtlicher Verantwortlichkeit und zivilrechtlicher Haftung.

BACKGROUND: In all phases, patients are entitled to receive medical treatment according to medical specialist standards. This does not mean that patients necessarily have to be treated by a medical specialist. Operations performed by "beginners", e. g. assistant physicians, are permitted. However, there are increased liability risks, both for the specialist and the assistant physician. Furthermore, there are risks of criminal responsibility for causing bodily harm by negligence or negligent manslaughter. OBJECTIVES AND METHODS: This article portrays the requirements of civil liability and criminal responsibility concerning beginners' operations on the basis of cases and judgments of the Federal Court and the Higher Regional Courts in Germany. Additionally, the reception of the jurisprudence by the relevant legal literature will be discussed. RESULTS: Jurisprudence and legal literature categorize breaches of duty of care. Assistant physicians can be subject to contributory negligence liabilities, while specialists can bear liabilities for negligent selection, organization or supervision. Responsible specialist and assistant physicians can protect themselves (and the patient) and avoid legal risks by only performing operations adequate to their educational level or by delegating operations to beginners and ensuring intervention by a specialist by supervision of the operation which is suitable to the assistant physician's level of education.

Evaluating the effect of ward-based outreach teams on primary healthcare performance in North West Province, South Africa: A plausibility design using routine data.

BACKGROUND: North West Province (NWP), South Africa, was an early adopter of the primary healthcare (PHC) ward-based outreach team (WBOT) strategy and has made considerable progress in implementing it. Given the interest in and expectations of greater investment in WBOTs, assessing their impact on and contribution to PHC outputs and health outcomes is becoming increasingly important. OBJECTIVES: To describe the application of a plausibility evaluation design for assessing the contribution of WBOTs to PHC performance in NWP, comparing changes in coverage, utilisation and outcome indicators in facilities with and without WBOTs. METHODS: Routine data from the District Health Information System on both WBOTs and PHC facilities for the period 2011/12 (prior to implementation) to 2014/15 (3 years after implementation began) were extracted. Analysis involved the following three steps: (i) selection of indicators sensitive to community-based action; (ii) data cleaning; and (iii) comparison of the degree of change in median indicator values between 2011/12 and 2014/15 in facilities with and without WBOTs (a difference-in-differences analysis). RESULTS: Changes in indicator values in facilities were grouped into four categories: (i) indicators where there was greater (statistically significant) improvement in facilities with WBOTs (couple year protection rate, measles immunisation coverage in children aged <1 year, incidence of children aged <5 years with severe diarrhoea with dehydration); (ii) indicators that declined or worsened, but less so in facilities with WBOTs at statistically significant levels (antenatal first visits as a percentage of children born in that year, PHC utilisation rate of children aged <5 years); (iii) indicators that improved in all facilities with no significant difference between facilities with and without WBOTs (antenatal attendance before 20 weeks, prophylactic vitamin A coverage to children aged 12 - 59 months); and (iv) indicators that remained unchanged in all facilities (immunisation coverage in children aged <1 year, postnatal mother visits at 6 days, cervical cancer screening coverage in women aged ≥30 years, PHC utilisation rate of children aged ≥5 years). CONCLUSION: Notwithstanding the limitations of routine data and the need to approach the findings with caution, this analysis suggests that WBOTs plausibly had some positive effects on the overall performance of the PHC system. We propose a methodology to monitor the performance of WBOTs using routine PHC indicators that programme managers could apply elsewhere.

X-ray micro-computed-tomography in pediatric surgery: a new tool for studying embryos.

PURPOSE: The embryology of common congenital malformations is discussed controversially. Studies are hampered by a shortage of study material and techniques which require partial or complete preparation and therewith destruction of embryos. X-ray micro-computed-tomography (µCT) is a technical opportunity keeping the embryos intact. Thus, the aim of this study was to assess the applicability of µCT in embryonic research compared to the anatomical information obtained by scanning electron microscopy (SEM). METHODS: Chicken, rat, mouse and sheep embryos, processed either for SEM studies or as whole embryos, were imaged in three-dimensional (3D) using µCT. The obtained two-dimensional (2D) digital datasets were volume rendered by tomographic reconstruction software and studied using analysis software. RESULTS: All embryos were µCT scanned without technical problems. The quality of the µCT images (image contrast, anatomical details) was excellent, but varied depending on age and species studied. µCT imaging allowed a more comprehensive anatomical/morphological analysis but showed less surface details compared to SEM. CONCLUSION: µCT is a technique suitable and innovative for pediatric surgical research, which allows detailed evaluation of entire embryos without time- and specimen-consuming micro-dissection. Samples prepared for SEM can be used for µCT and vice versa.

Ectodysplasin A in Biological Fluids and Diagnosis of Ectodermal Dysplasia.

The tumor necrosis factor (TNF) family ligand ectodysplasin A (EDA) is produced as 2 full-length splice variants, EDA1 and EDA2, that bind to EDA receptor (EDAR) and X-linked EDA receptor (XEDAR/EDA2R), respectively. Inactivating mutations in Eda or Edar cause hypohidrotic ectodermal dysplasia (HED), a condition characterized by malformations of the teeth, hair and glands, with milder deficiencies affecting only the teeth. EDA acts early during the development of ectodermal appendages-as early as the embryonic placode stage-and plays a role in adult appendage function. In this study, the authors measured EDA in serum, saliva and dried blood spots. The authors detected 3- to 4-fold higher levels of circulating EDA in cord blood than in adult sera. A receptor binding-competent form of EDA1 was the main form of EDA but a minor fraction of EDA2 was also found in fetal bovine serum. Sera of EDA-deficient patients contained either background EDA levels or low levels of EDA that could not bind to recombinant EDAR. The serum of a patient with a V262F missense mutation in Eda, which caused a milder form of X-linked HED (XLHED), contained low levels of EDA capable of binding to EDAR. In 2 mildly affected carriers, intermediate levels of EDA were detected, whereas a severely affected carrier had no active EDA in the serum. Small amounts of EDA were also detectable in normal adult saliva. Finally, EDA could be measured in spots of wild-type adult or cord blood dried onto filter paper at levels significantly higher than that measured in EDA-deficient blood. Measurement of EDA levels combined with receptor-binding assays might be of relevance to aid in the diagnosis of total or partial EDA deficiencies.

Outcome, comorbidity, hospitalization and 30-day mortality after closure of acute perforations and postoperative anastomotic leaks by the over-the-scope clip (OTSC) in an unselected cohort of patients.

BACKGROUND: Acute gastrointestinal (GI) wall defects contain a high risk of morbidity and mortality and may be closed endoscopically by a full-thickness over-the-scope clip (OTSC). METHODS: Unselected consecutive patients presenting with acute non-surgical perforations or postoperative anastomotic leaks or perforations underwent attempted OTSC placement as primary closure method after interdisciplinary consensus in three tertiary referral centres. Their clinical data and intervention characteristics were evaluated in an intention to treat analysis during a 24-month period to assess closure rates, 30-day mortality, hospitalization and comorbidity. RESULTS: In total, 34 patients (16 females, 18 males, 69.5 years) were included with 22 non-surgical perforations and 12 postoperative anastomotic leaks or perforations. Definitive closure of the perforations and leaks was achieved in 26/34 patients (76.5 %). Successful closure of the GI wall defect resulted in a significantly shorter hospital stay (8 days, p = 0.03) and was significantly correlated with comorbidity (r = 0.56, p = 0.005). In the group with OTSC failure, hospitalization was 18 days and 6 of 8 patients (75 %) required immediate surgery. Three deaths occurred in the group with successful OTSC closure due to comorbidity, while one death in the OTSC failure group was related to a refractory perforation. Favourable indications and locations for a successful OTSC procedure were identified as PEG complications, endoscopic or postoperative leaks of stomach, colon or rectum, respectively. CONCLUSIONS: In unselected patients, OTSC was effective for closure of acute GI wall defects in more than 75 % of all patients. Clinical success and short hospitalization were best achieved in patients without comorbidity, but closure of the perforation or the anastomotic leak was found to be not the only parameter relevant for patient outcome and mortality.

Noninvasive Prenatal Diagnosis of Hypohidrotic Ectodermal Dysplasia by Tooth Germ Sonography.

PURPOSE: Hypohidrotic ectodermal dysplasia, a potentially life-threatening heritable disorder, may be recognized already in utero by characteristic features such as oligodontia and mandibular hypoplasia. As therapeutic options and prognosis depend on the time point of diagnosis, early recognition was attempted during routine prenatal ultrasound examinations. SUBJECTS AND METHODS: Fetuses of nine pregnant women (one triplet and eight singleton pregnancies) with family histories of hypohidrotic ectodermal dysplasia were investigated by sonography between the 20th and 24th week of gestation. RESULTS: In 4 male and 2 female fetuses reduced amounts of tooth germs were detected, whereas 5 fetal subjects showed the normal amount. Three-dimensional ultrasound evaluation revealed mandibular hypoplasia in 5 of the 6 fetuses with oligodontia. Molecular genetic analysis and/or clinical findings after birth confirmed the prenatal sonographic diagnosis in each subject. CONCLUSION: In subjects with a family history of hypohidrotic ectodermal dysplasia, the diagnosis of this rare condition can be established noninvasively by sonography in the second trimester of pregnancy. Early recognition of the disorder may help to prevent dangerous hyperthermic episodes in infancy and may allow timely therapeutic interventions.

Surprising prenatal toxicity of epidermal lipoxygenase-3.

Metabolites of the epidermal lipoxygenase-3 (eLOX-3) are involved in various metabolic pathways. Most unexpectedly, intra-amniotic delivery of eLOX-3 to mice at gestational day 14.5, both via an adenoviral vector and as recombinant protein, resulted in fetal growth restriction and intrauterine death. Periodic acid-Schiff staining and RT-PCR analysis of placentae from fetuses exposed to eLOX-3 indicated a lack of glycogen trophoblasts in the junctional zone. Placenta-specific gene expression was altered. Thus, the observed prenatal toxicity of eLOX-3 could be due to a strong effect on placental development.

Note: Electrostatic detection of stainless steel dust particles for fusion applications.

Dust accumulation inside next-step fusion devices poses a significant safety concern and dust diagnostics will be needed to assure safe operations. An electrostatic dust detection device has been successfully demonstrated in the National Spherical Torus Experiment, Tore Supra, and the Large Helical Device, and the detector's response to carbon particles was previously characterized in laboratory experiments. This paper presents laboratory results showing that detection of stainless steel particles at levels as low as several µg/cm(2) is also possible.

The effect of the ANKK1/DRD2 Taq1A polymorphism on weight changes of dopaminergic treatment in prolactinomas.

Treatment with dopamine agonists in patients with prolactinomas has been associated with weight loss in short term studies. However, long-term studies on weight changes are lacking. Taq1A is a restriction fragment length polymorphism considered as a gene marker for the DRD2 gene. The presence of at least one A1 allele is linked to reduced brain dopaminergic activity due to reduced receptor binding and lower density of the dopamine 2 receptor. We aimed at testing the hypothesis that the dopaminergic treatment in prolactinoma patients leads to sustained weight loss and that the presence of diminished weight loss response under dopamine agonists is associated with the minor A1 allele of Taq1A.We included n = 44 patients (17 male and 27 female, 26 macroadenomas and 18 microadenomas) with prolactinomas treated with dopamine agonists. Outcome measures were weight and body mass index (BMI) change under dopaminergic treatment after 2 years with regard to Taq1A status and sex. We observed that the dopaminergic treatment leads to a significant mean weight loss of 3.1 ± 6.25 kg after 2 years. Regarding Taq1A polymorphisms, 21 patients were carriers of at least one A1 allele and 23 patients had a genotype of A2/A2. However, the presence of the A1 allele was neither associated with the mean BMI at baseline nor with an altered weight loss response under dopamine agonist therapy. Our results implicate that the dopaminergic treatment leads to a sustained weight loss in patients with prolactinomas after 2 years. However, there was no association to the A1 allele of Taq1A, observation that needs to be analysed in larger cohorts.

Hypophysitis caused by ipilimumab in cancer patients: hormone replacement or immunosuppressive therapy.

Ipilimumab is besides the BRAF inhibitor vemurafenib the first officially approved medical treatment for metastatic melanoma, which results in improved survival. Ipilimumab leads to a release of a CTLA4-mediated inhibition of T-cell immunoreactions. Therefore, patients may also suffer from immune-related adverse events affecting different organs, which are typically treated by high-dose corticosteroids. Ipilimumab-induced hypophysitis (iH) has been reported in up to 17% of melanoma patients in clinical trials.Here we present 5 patients with metastatic melanoma and 2 patients with prostate cancer who developed hypophysitis after ipilimumab therapy. Patients were treated by high-dose corticosteroid therapy resulting in the resolution of local inflammation but not of pituitary deficiencies. Partial or complete hypopituitarism remained in all patients. Pharmacotherapy with high-dose corticosteroids caused complications in 5 patients, necessitating hospitalization in 4. 2 of the 3 patients with progressive disease died, while 3 patients had stable disease and 1 patient showed tumor regression after discontinuation of ipilimumab.In summary, with regard to safety and simplicity of hormonal substitution therapy we have to scrutinize high-dose corticosteroid therapy, though it only improves inflammation but not neuro-endocrine function and may cause further morbidity. Regression of the tumor depends on the ipilimumab-mediated immune events, in which high-dose and long-term corticosteroid therapy for iH appears to be counter-intuitive. Herein, we discuss screening and the diagnostic as well as therapeutic management of iH in metastatic cancer patients from an endocrinologic perspective.

Age-related reference intervals for bone turnover markers from an Australian reference population.

BACKGROUND: This study was performed to establish age-related serum reference intervals for procollagen type I N-propeptide (P1NP) and type I collagen C-telopeptide (CTx) in the Australian population. METHODS: Fasting sera from 1143 males (mean age 60 years; range 20-97 years) and 1246 females (mean age 53 years; range 20-93 years) who participated in the Geelong Osteoporosis Study were analysed for CTx and P1NP using the automated Roche Modular Analytics E170 analyser. RESULTS: Optimal age-related reference intervals were based on the central 90% of the distribution. The male CTx reference interval was divided into three age groups. For men aged 25 to 40 years, the interval was 170-600 ng/L; 40 to 60 years, the interval was 130-600 ng/L; and for men aged greater 60 years the interval was 100-600 ng/L. For P1NP the male reference interval was 15-80 µg/L for men aged between 25 to 70 years. In men greater than 70 years of age values were higher possibly due to increased bone turnover. High values are frequently seen for both CTx and P1NP in males aged younger than 25 years. This is probably due to bone growth that is not completely finalised. The female CTx reference interval was divided into four age groups. For women aged less than 30 years, the interval was 150-800 ng/L; 30-39 years, the interval was 100-700 ng/L; 40-49 years, the interval was 100-600 ng/L; and for women aged 50 years or more the interval was 100-700 ng/L. The female P1NP reference interval was divided into four age groups. For women aged less than 30 years, the interval was 25-90 µg/L; 30-39 years, the interval was 15-80 µg/L; 40-49 years, the interval was 15-60 µg/L; and for women aged 50-69 years the interval was 15-75 µg/L. In women greater than 70 years of age values were higher possibly due to increased bone turnover. CONCLUSION: Values obtained from this large study provide sound age-related reference intervals for serum P1NP and CTx values in the Australian population.

Progesterone--promoter or inhibitor of breast cancer.

Based on the results of a French cohort of postmenopausal women, it has been claimed that micronized progesterone does not enhance breast cancer risk. The impact of reproductive factors on breast cancer risk and a high prevalence of occult breast carcinomas at the time of menopause suggest an involvement of endogenous progesterone in the development of breast cancer. High mammographic density in the luteal phase and during treatment with estrogen/progestogen combinations reflect a change in the composition of mammary stroma and an increased water accumulation in the extracellular matrix which is caused by hygroscopic hyaluronan-proteoglycan aggregates. Proteoglycans are also involved in the regulation of proliferation, migration, and differentiation of epithelial cells and angiogenesis, and may influence malignant transformation of breast cells and progression of tumors. Reports on a lack of effect of estrogen/progesterone therapy on breast cancer risk may be rooted in a selective prescription to overweight women and/or to the very low progesterone serum levels after oral administration owing to a strong inactivation rate. The contradictory results concerning the proliferative effect of progesterone may be associated with a different local metabolism in normal compared to malignant breast tissue. Similar to other progestogens, hormone replacement therapy with progesterone seems to promote the development of breast cancer, provided that the progesterone serum levels have reached the threshold for endometrial protection.

Does heparin coating reduce encrustation of biliary plastic endoprostheses? A prospective randomized trial.

OBJECTIVE: Common bile duct stenting is widely performed for bridging benign and malignant obstructions. A major limitation is early stent occlusion making regular stent exchange necessary. Covalent binding of glycosaminoglycanes to polyethylene stents proved to reduce encrustation in urological implants. Since development of urological and biliary stent occlusion shows parallels, the aim of the study was to evaluate the efficacy of heparin coating of biliary endoprostheses in preventing encrustation. MATERIAL AND METHODS: In a prospective randomized trial, heparin-coated and native stents were endoscopically placed for almost 90 days on average. After removal, all stents were dried (50°C, 24 h), weighed and after longitudinal incision visible encrustation and discoloration recorded. Fifty-three patients (21 females/32 males, 70 ± 12 (42-87) years) were included; 13 patients (4 females/9 males, 58-79 years) completed the study according to the protocol. RESULTS: After removal, mean weight of encrustation in native stents was more than double as high as of covered stents (native: 37.9 ± 19.8 (16-93) mg; covered: 17.6 ± 6.7 (9-33) mg). In 12 of 13 cases, the encrustation weight of the native stent was higher than that of the corresponding covered stent in the same patient. Premature stent explantation became necessary in 3 of 13 native stents, because of recurrent jaundice or cholangitis but only in 1 of 13 covered stents. After longitudinal incision, the three uncovered stents showed excessive encrustation whereas no significant encrustation was found in the covered prosthesis. Altogether, covered stents showed less visible accumulation of clogging material and discoloration than native stents. CONCLUSIONS: Covalent bound heparin is highly effective in preventing encrustation of biliary polyethylene endoprostheses.

Correlation between the functional impairment of bone marrow-derived circulating progenitor cells and the extend of coronary artery disease.

BACKGROUND: Bone marrow-derived circulating progenitor cells (BM-CPCs) in patients with coronary heart disease are impaired with respect to number and functional activity. However, the relation between the functional activity of BM-CPCs and the number of diseased coronary arteries is yet not known. We analyzed the influence of the number of diseased coronary arteries on the functional activity of BM-CPCs in peripheral blood (PB) in patients with ischemic heart disease (IHD). METHODS: The functional activity of BM-CPCs was measured by migration assay and colony forming unit in 120 patients with coronary 1 vessel (IHD1, n = 40), coronary 2 vessel (IHD2, n = 40), coronary 3 vessel disease (IHD3, n = 40) and in a control group of healthy subjects (n = 40). There was no significant difference of the total number of cardiovascular risk factors between IHD groups, beside diabetes mellitus (DM), which was significantly higher in IHD3 group compared to IHD2 and IHD1. RESULTS: The colony-forming capacity (CFU-E: p < 0.001, CFU-GM: p < 0.001) and migratory response to stromal cell-derived factor 1 (SDF-1: p < 0.001) as well as vascular endothelial growth factor (VEGF: p < 0001) of BM-CPCs were reduced in the group of patients with IHD compared to control group. The functional activity of BM-CPCs was significantly impaired in patients with IHD3 as compared to IHD1 (VEGF: p < 0.01, SDF-1: p < 0.001; CFU-E: p < 0.001, CFU-GM: p < 0.001) and to IHD2 (VEGF: p = 0.003, SDF-1: p = 0.003; CFU-E: p = 0.001, CFU-GM: p = 0.001). No significant differences were observed in functional activity of BM-CPCs between patients with IHD2 and IHD1 (VEGF: p = 0.8, SDF-1: p = 0.9; CFU-E: p = 0.1, CFU-GM: p = 0.1). Interestingly, the levels of haemoglobin AIc (HbAIc) correlated inversely with the functional activity of BM-CPCs (VEGF: p < 0.001, r = -0.8 SDF-1: p < 0.001, r = -0.8; CFU-E: p = 0.001, r = -0.7, CFU-GM: p = 0.001, r = -0.6) in IHD patients with DM. CONCLUSIONS: The functional activity of BM-CPCs in PB is impaired in patients with IHD. This impairment increases with the number of diseased coronary arteries. Moreover, the regenerative capacity of BM-CPCs in ischemic tissue further declines in IHD patients with DM. Furthermore, monitoring the level of BM-CPCs in PB may provide new insights in patients with IHD.

[Direct and indirect costs of fractures due to osteoporosis in Austria]. / Direkte und indirekte Kosten von osteoporotisch bedingten Frakturen in Österreich.

OBJECTIVES: We examined the financial burden of osteoporosis in Austria. METHODS: We took both direct and indirect costs into consideration. Direct costs encompass medical costs such as expenses for pharmaceuticals, inpatient and outpatient medical care costs, as well as other medical services (e.g., occupational therapies). Non-medical direct costs include transportation costs and medical devices (e.g., wheel chairs or crutches). Indirect costs refer to costs of productivity losses due to absence of work. Moreover, we included costs for early retirement and opportunity costs of informal care provided by family members. While there exist similar studies for other countries, this is the first comprehensive study for Austria. For our analysis, we combined data of official statistics, expert estimates as well as unique patient surveys that are currently conducted in the course of an international osteoporotic fracture study in Austria. RESULTS: Our estimation of the total annual costs in the year 2008 imposed by osteoporosis in Austria is 707.4 million €. The largest fraction of this amount is incurred by acute hospital treatment. Another significant figure, accounting for 29% of total costs, is the opportunity cost of informal care. CONCLUSIONS: The financial burden of osteoporosis in Austria is substantial. Economic evaluations of preventive and therapeutic interventions for the specific context of Austria are needed to inform health policy decision makers.

Diverse spore rains and limited local exchange shape fern genetic diversity in a recently created habitat colonized by long-distance dispersal.

BACKGROUND AND AIMS: Populations established by long-distance colonization are expected to show low levels of genetic variation per population, but strong genetic differentiation among populations. Whether isolated populations indeed show this genetic signature of isolation depends on the amount and diversity of diaspores arriving by long-distance dispersal, and time since colonization. For ferns, however, reliable estimates of long-distance dispersal rates remain largely unknown, and previous studies on fern population genetics often sampled older or non-isolated populations. Young populations in recent, disjunct habitats form a useful study system to improve our understanding of the genetic impact of long-distance dispersal. METHODS: Microsatellite markers were used to analyse the amount and distribution of genetic diversity in young populations of four widespread calcicole ferns (Asplenium scolopendrium, diploid; Asplenium trichomanes subsp. quadrivalens, tetraploid; Polystichum setiferum, diploid; and Polystichum aculeatum, tetraploid), which are rare in The Netherlands but established multiple populations in a forest (the Kuinderbos) on recently reclaimed Dutch polder land following long-distance dispersal. Reference samples from populations throughout Europe were used to assess how much of the existing variation was already present in the Kuinderbos. KEY RESULTS: A large part of the Dutch and European genetic diversity in all four species was already found in the Kuinderbos. This diversity was strongly partitioned among populations. Most populations showed low genetic variation and high inbreeding coefficients, and were assigned to single, unique gene pools in cluster analyses. Evidence for interpopulational gene flow was low, except for the most abundant species. CONCLUSIONS: The results show that all four species, diploids as well as polyploids, were capable of frequent long-distance colonization via single-spore establishment. This indicates that even isolated habitats receive dense and diverse spore rains, including genotypes capable of self-fertilization. Limited gene flow may conserve the genetic signature of multiple long-distance colonization events for several decades.

Regulation of NF-κB activity by competition between RelA acetylation and ubiquitination.

The nuclear factor (NF)-κB transcription factor has essential roles in inflammation and oncogenesis. Its ubiquitous RelA subunit is regulated by several post-translational modifications, including phosphorylation, ubiquitination and acetylation. Ubiquitination promotes the termination of RelA-dependent transcription, but its regulation is incompletely understood. Through mass spectrometry analysis of ubiquitinated RelA, we identified seven lysines that were attached to degradative and non-degradative forms of polyubiquitin. Interestingly, lysines targeted for acetylation were among the residues identified as ubiquitin acceptor sites. Mutation of these particular sites resulted in decreased polyubiquitination. Acetylation and ubiquitination were found to inhibit each other, consistent with their use of overlapping sites. Reconstitution of rela(-/-) fibroblasts with wild-type and mutant forms of RelA revealed that modifications at these residues can have activating and inhibitory functions depending on the target gene context. Altogether, this study elucidates that ubiquitination and acetylation can modulate each other and regulate nuclear NF-κB function in a gene-specific manner.