The association of frontal plane alignment to MRI-defined worsening of patellofemoral osteoarthritis: the MOST study.

OBJECTIVE: To determine the sex-specific relation of frontal plane alignment (FPA) to magnetic resonance imaging (MRI)-defined features of patellofemoral osteoarthritis, and also to tibiofemoral osteoarthritis and knee pain. METHOD: The Multicenter Osteoarthritis Study is cohort study comprised of individuals with or at risk of knee osteoarthritis. We determined the sex-specific dose-response relation of baseline FPA to MRI-defined patellofemoral and tibiofemoral structural worsening, and incident knee pain, over 7 years. RESULTS: In women only, greater varus alignment was associated with medial patellofemoral osteophytes (risk ratio [RR] 1.7 [95% CI 1.2, 2.6]) and valgus with lateral patellofemoral osteophytes (RR 1.9 [1.0, 3.6]). In men, greater varus increased risk for medial tibiofemoral cartilage worsening (RR 1.7 [1.1, 2.6]), and valgus for lateral tibiofemoral cartilage worsening (RR 1.8 [1.6, 2.2]). In women, findings were similar for tibiofemoral cartilage, but varus also increased risk for medial bone marrow lesions [BMLs] (RR 2.2 [1.6, 3.1]) and medial osteophytes (RR 1.8 [1.3, 2.5]), and valgus for lateral BMLs (RR 3.3 [2.2, 4.5]) and osteophytes (RR 2.0 [1.2, 3.2]). Varus increased risk of incident pain in men (RR 1.7 [1.4, 2.2]) and women (RR 1.3 [1.0, 1.6]), valgus did so in men only (RR 1.5 [1.1, 1.9]). CONCLUSION: FPA was associated with patellofemoral osteophyte worsening in women, though overall was more strongly associated with tibiofemoral than patellofemoral osteoarthritis feature worsening. FPA in women was more consistently associated with structural worsening, yet men had higher associations with incident pain.

[The heart catheter table is not the operating table : Intraindividual comparison of pulmonary artery pressures]. / Der Herzkathetertisch ist nicht der OP-Tisch : Intraindividueller Vergleich der pulmonalarteriellen Druckwerte.

BACKGROUND: Patients undergoing cardiac surgery need extensive and invasive monitoring, which needs to be individually adapted for each patient and requires a diligent risk-benefit analysis. The use of a pulmonary artery catheter (PAC) seems to be justifiable in certain cases; therefore, the preoperative diagnosis of pulmonary hypertension represents an indication for perioperative monitoring with PAC in the S3 guidelines of the German Society for Anesthesiology and Intensive Care Medicine (DGAI). In many cases, however, this preoperative diagnosis cannot be confirmed intraoperatively. OBJECTIVE: We wanted to find out whether this is just an impression or whether there actually are significant differences between preoperative, intraoperative and postoperative pulmonary artery pressures. MATERIAL AND METHODS: After obtaining ethical approval, we retrospectively compared the pulmonary pressures of cardiac surgery patients with an elevated pulmonary pressure during preoperative right heart catheterization with those obtained intraoperatively and postoperatively by means of a PAC. All patients with a preoperatively documented pulmonary artery pressure of 40 mmHg or above and an intraoperative use of a PAC during a 4-year period were included. Exclusion criteria were intracardiac shunts, cardiogenic shock, emergency procedures, pulmonary hypertension of non-cardiac origin and a time span of more than 1 year between right heart catheterization and surgery. We included 90 patients. RESULTS: In the whole group and in the subgroups (according to diagnosis, time elapsed between heart catheterization and operation and pulmonary pressure), there were significant differences between preoperative and intraoperative pulmonary and systemic pressures. Systemic and pulmonary artery pressures were significantly higher during preoperative catheterization than intraoperatively. The systemic systolic pressure/systolic pulmonary pressure ratio, however, remained constant. The intraoperative and postoperative systemic and pulmonary artery pressures showed no significant differences. As a normal ejection fraction does not exclude heart failure with preserved ejection fraction and as we did not have any information on this condition, we did not group the patients according to the ejection fraction. CONCLUSION: An elevated pulmonary pressure obtained preoperatively during right heart catheterization is not indicative of an elevated pulmonary pressure either intraoperatively or postoperatively. There are various explanations for the differences (e.g., different physiological and pathophysiological settings, such as sedation with potential hypercapnia versus anesthesia with vasodilation when measured; newly prescribed medication coming into effect between the right heart catheterization and surgery; intraoperative positioning). Even though the inherent risks of a PAC seem to be low, we recommend refraining from using a PAC in patients with a once documented elevated pulmonary pressure by default. As an alternative we suggest estimating the pulmonary pressure by transesophageal echocardiography (TEE) as an aid to decide whether the patient will benefit from the use of a PAC. Especially if it is not possible to identify tricuspid valve regurgitation for determining the peak gradient, it is helpful to check for additional signs of pulmonary hypertension. But we also have to bear in mind that in the postoperative period only a PAC can provide continuous measurement of pulmonary pressure.

Histamine receptor 2 modifies iNKT cell activity within the inflamed lung.

BACKGROUND: Histamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H2 R). The aim of this study was to determine the role of H2 R in modulating lung inflammatory responses. METHODS: H2 R was blocked using famotidine or activated using dimaprit in both the ovalbumin (OVA) and house dust mite extract (HDM) murine models of respiratory inflammation. H2 R-deficient animals and CD1d/H2 R-deficient animals were utilized to examine the CD1d presentation of lipid antigens (αGalCer or OCH) to invariant natural killer T (iNKT) cells. RESULTS: Famotidine treatment resulted in more severe airway disease in the OVA model, while dimaprit treatment significantly reduced disease severity. Both OVA and HDM-induced airway diseases were more severe in H2 R-deficient animals. Flow cytometric analysis of lung tissue from H2 R-deficient animals revealed increased numbers of CD1d+ dendritic cells and increased numbers of iNKT cells. In vitro, αGalCer-stimulated iNKT cells from H2 R-deficient mice secreted higher levels of IL-4, IL-5, and GM-CSF. In vivo, αGalCer or OCH administration to the lung resulted in enhanced mucus secretion, inflammatory cell recruitment, and cytokine production in H2 R-deficient or famotidine-treated animals, while dimaprit dampened the lung iNKT cell response to αGalCer. Removal of iNKT cells in H2 R-deficient (CD1d-/- H2 R-/- ) animals normalized the lung response to HDM. CONCLUSION: The deliberate activation of H2 R, or its downstream signaling molecules, may represent a novel therapeutic target for chronic lung inflammatory diseases, especially when CD1d-mediated presentation of lipid antigens to iNKT cells is contributing to the pathology.

Influence of fracture stability on Staphylococcus epidermidis and Staphylococcus aureus infection in a murine femoral fracture model.

Fracture-related infection (FRI) is a major complication in surgically fixed fractures. Instability of the fracture after fixation is considered a risk factor for infection; however, few experimental data are available confirming this belief. To study whether stable fractures led to higher infection clearance, mouse femoral osteotomies were fixed with either stable or unstable fixation and the surgical site was contaminated with either Staphylococcus epidermidis (S. epidermidis)or Staphylococcus aureus (S. aureus)clinical isolates. Infection progression was assessed at different time points by quantitative bacteriology, total cell counts in spleen and lymph node and histological analysis. Operated, non-inoculated mice were used as controls. Two inbred mouse strains (C57BL/6 and BALB/c) were included in the study to determine the influence of different host background in the outcome. Stable fixation allowed a higher proportion of C57BL/6 mice to clear S. epidermidis inoculation in comparison to unstable fixation. No difference associated with fixation type was observed for BALB/c mice. Inoculation with S. aureus resulted in a more severe infection for both stable and unstable fractures in both mouse strains; however, significant osteolysis around the screws rendered the stable group functionally unstable. Our results suggested that fracture stability could have an influence on S. epidermidis infection, although host factors also played a role. No differences were observed when using S. aureus, due to a more severe infection, leading to osteolysis and loss of stability in both groups. Further studies are required in order to address the biological features underlying the differences observed.

X-autosome and X-Y Translocations in Female Carriers: X-chromosome Inactivation Easily Detectable by 5-ethynyl-2-deoxyuridine (EdU).

Here we report one new case each of an X-autosome translocation (maternally derived), and an X-Y-chromosome translocation. Besides characterizing the involved breakpoints and/or imbalances in detail by molecular cyto-genetics, also skewed X-chromosome inactivation was determined on single cell level using 5-ethynyl-2-deoxyuridine (EdU). Thus, we confirmed that the recently suggested EdU approach can be simply adapted for routine diagnostic use. The latter is important, as only by knowing the real pattern of the skewed X-chromosome inactivation, correct interpretation of obtained results and subsequent reliable genetic counseling, can be done.

An exploratory study investigating the metabolic activity and local cytokine profile in patients with melanoma treated with pazopanib and paclitaxel.

BACKGROUND: There is a medical need for new drugs in patients with BRAF wild-type metastatic melanoma. Pazopanib is a multitarget tyrosine kinase inhibitor with antitumour and antiangiogenic activity. OBJECTIVES: The primary aim was to investigate the metabolic response to pazopanib monotherapy and pazopanib plus paclitaxel in patients with BRAF wild-type melanoma. Secondary end points were the early cytokine and chemokine profiles and histological findings. METHODS: Pazopanib (400 mg twice daily) was administered orally from days 1 to 10 and from days 14 to 70. An intravenous infusion with paclitaxel (150 mg m-2 body surface) was administered on days 14, 35 and 56. Metabolic response evaluation was performed before treatment, after treatment with pazopanib (day 10) and after treatment with pazopanib and paclitaxel (day 70). Skin biopsy of metastatic tissue for chemokine and cytokine expression analysis and histology and immunohistochemistry (CD68, CD163) evaluation, and blood samples were taken at the same time points. RESULTS: Two patients failed screening and 17 were dosed. Of 67 adverse events, nine (13%) were grade 3 or 4. Five of 14 evaluable patients had a partial metabolic response at day 10 under pazopanib monotherapy. The response rate at day 70 under combined pazopanib-paclitaxel treatment was 0%. Immunohistochemistry revealed an increase of M2-like macrophages in nonresponders compared with responders. We observed a significant upregulation of five cytokines (CXCL1, CXCL2, CXCL13, CCL22 and SPP1) in responding vs. nonresponding lesions. Overall, the median progression-free survival was 70 days (range 5-331), which did not differ significantly between responders (148 days) and nonresponders (70 days, P = 0·17). CONCLUSIONS: In this patient population pazopanib efficacy was limited. Response is associated with low M2-like macrophage density and increased expression of several chemokines.

siRNA mediated knockdown of tissue factor expression in pigs for xenotransplantation.

Acute vascular rejection (AVR), in particular microvascular thrombosis, is an important barrier to successful pig-to-primate xenotransplantation. Here, we report the generation of pigs with decreased tissue factor (TF) levels induced by small interfering (si)RNA-mediated gene silencing. Porcine fibroblasts were transfected with TF-targeting small hairpin (sh)RNA and used for somatic cell nuclear transfer. Offspring were analyzed for siRNA, TF mRNA and TF protein level. Functionality of TF downregulation was investigated by a whole blood clotting test and a flow chamber assay. TF siRNA was expressed in all twelve liveborn piglets. TF mRNA expression was reduced by 94.1 ± 4.7% in TF knockdown (TFkd) fibroblasts compared to wild-type (WT). TF protein expression in PAEC stimulated with 50 ng/mL TNF-α was significantly lower in TFkd pigs (mean fluorescence intensity TFkd: 7136 ± 136 vs. WT: 13 038 ± 1672). TF downregulation significantly increased clotting time (TFkd: 73.3 ± 8.8 min, WT: 45.8 ± 7.7 min, p < 0.0001) and significantly decreased thrombus formation compared to WT (mean thrombus coverage per viewing field in %; WT: 23.5 ± 13.0, TFkd: 2.6 ± 3.7, p < 0.0001). Our data show that a functional knockdown of TF is compatible with normal development and survival of pigs. TF knockdown could be a valuable component in the generation of multi-transgenic pigs for xenotransplantation.

[OCT Angiography - Is this the Future for Macular Diagnosis?]. / OCT-Angiografie - ist dies die Zukunft der makulären Diagnostik?

Recent developements in OCT technology using high speed acquisition and calculation of consecutive scans (SSADA = split spectrum amplitude decorrelation algorithm) have resulted in the possibility to demonstrate retinal and choroidal vessels in the macula. This new technology of "OCT angiography" thus allows the non-invasive and rapid (within seconds) reconstruction of the three-dimensional structure of the retinal and choroidal vascularisation. There are still limitations caused by movement artefacts, superposition of superficial retinal vessels at the RPE level or insufficient three-dimensional imaging, but the first experience with this new method and especially the correlations with the current standard diagnostic procedure fluorescein angiography shows that especially for vascular changes which are predominantly in one retinal layer (e.g., the inner retina) like in diabetic retinopathy or retinal vein occlusions, a very good correlation can be seen. Also in MacTel type 2 patients the proposed vascular changes in the deeper capillary network of the retina can be visualised very well with OCT angiography. In contrast, more three-dimensional vascular changes like the neovascular complex in exsudative AMD need a more sophisticated diagnostic analysis strategy, which has still to be developed. However, the first experience also demonstrates that fluorescein angiographic differentiation can also be seen in OCT angiography. In addition, the new technology gives additional information about the choroidal and outer retinal changes in these pathologies, which may result in a better understanding of the underlying pathologies.

Everolimus inhibits anti-HLA I antibody-mediated endothelial cell signaling, migration and proliferation more potently than sirolimus.

Antibody (Ab) crosslinking of HLA I molecules on the surface of endothelial cells triggers proliferative and pro-survival intracellular signaling, which is implicated in the process of chronic allograft rejection, also known as transplant vasculopathy (TV). The purpose of this study was to investigate the role of mammalian target of rapamycin (mTOR) in HLA I Ab-induced signaling cascades. Everolimus provides a tool to establish how the mTOR signal network regulates HLA I-mediated migration, proliferation and survival. We found that everolimus inhibits mTOR complex 1 (mTORC1) by disassociating Raptor from mTOR, thereby preventing class I-induced phosphorylation of mTOR, p70S6K, S6RP and 4E-BP1, and resultant class I-stimulated cell migration and proliferation. Furthermore, we found that everolimus inhibits class I-mediated mTORC2 activation (1) by disassociating Rictor and Sin1 from mTOR; (2) by preventing class I-stimulated Akt phosphorylation and (3) by preventing class I-mediated ERK phosphorylation. These results suggest that everolimus is more effective than sirolimus at antagonizing both mTORC1 and mTORC2, the latter of which is critical in endothelial cell functional changes leading to TV in solid organ transplantation after HLA I crosslinking. Our findings point to a potential therapeutic effect of everolimus in prevention of chronic Ab-mediated rejection.

Partial trisomy 2p and partial monosomy 2q arising from a paternal intrachromosomal 2q-into-2p between-arm insertion and paracentric inversion: molecular cytogenetic characterization of a four-break rearrangement.

We report on a 26-month-old boy with an interstitial duplication of 2p22.3p22.2 and an interstitial deletion of 2q14.1q21.2. The abnormality was derived from his father having a balanced paracentric inversion and pericentric insertion. The deletion in the child was identified by cytogenetic analysis and characterized in more detail by molecular cytogenetics and array comparative genomic hybridization. The latter revealed a 20-Mb deletion in the long arm and a 5.6-Mb duplication in the short arm of chromosome 2. Fluorescence in situ hybridization in paternal chromosomes characterized an intrachromosomal insertion of 2q14.1q21.2 into 2p23; additionally a paracentric inversion of 2p13p23 was observed. The boy with the unbalanced karyotype suffered from severe psychomotor retardation, thrombophilia due to protein C deficiency, and hypertrophic cardiomyopathy and also had phenotypic abnormalities. Most of these features have previously been described in individuals with interstitial deletion of 2q14.1.

Genetic regulation of catecholamine synthesis, storage and secretion in the spontaneously hypertensive rat.

Understanding catecholamine metabolism is crucial for elucidating the pathogenesis of hereditary hypertension. Here we integrated transcriptional and biochemical profiling with physiologic quantitative trait locus (eQTL and pQTL) mapping in adrenal glands of the HXB/BXH recombinant inbred (RI) strains, derived from the spontaneously hypertensive rat (SHR) and normotensive Brown Norway (BN.Lx). We found simultaneous down-regulation of five heritable transcripts in the catecholaminergic pathway in young (6 weeks) SHRs. We identified cis-acting eQTLs for Dbh, Pnmt (catecholamine biosynthesis) and Vamp1 (catecholamine secretion); enzymatic activities of Dbh and Pnmt paralleled transcripts, with pQTLs for activities mirroring eQTLs. We also detected trans-regulated expression of Vmat1 and Chga (both involved in catecholamine storage), with co-localization of these trans-eQTLs to the Pnmt locus. Pnmt re-sequencing revealed promoter polymorphisms that result in decreased response of the transfected SHR promoter to glucocorticoid, compared with BN.Lx. Of physiological pertinence, Dbh activity negatively correlated with systolic blood pressure in RI strains, whereas Pnmt activity was negatively correlated with heart rate. The finding of such cis- and trans-QTLs at an age before the onset of frank hypertension suggests that these heritable changes in biosynthetic enzyme expression represent primary genetic mechanisms for regulation of catecholamine action and blood pressure control in this widely studied model of hypertension.

Five novel locations of Neocentromeres in human: 18q22.1, Xq27.1∼27.2, Acro p13, Acro p12, and heterochromatin of unknown origin.

Since the first report in 1993, an ectopic centromere, i.e. neocentromere formation, has been reported in more than 100 small supernumerary marker chromosomes (sSMC), in 7 instances of centromere repositioning, and in about a dozen cases with more complex chromosomal rearrangements. Here we report 2 new cases with centromere repositioning and 3 neocentric sSMC consisting exclusively of heterochromatic material. Yet, no centromere formation was reported for the regions 18q22.1 and Xq27.1∼27.2 as it was observed in the 2 cases with centromere repositioning here; in both cases, cytogenetically an inversion was suggested. Two of the 3 neocentric sSMC were derived from a short arm of an acrocentric chromosome. The remainder neocentric sSMC case was previously reported and was stainable only by material derived from itself.

[Real-life experiences with Brolucizumab in recalcitrant neovascular age-related macular degeneration]. / Erste Erfahrungen mit Brolucizumab bei neovaskulärer altersabhängiger Makuladegeneration und Therapierefraktärität unter der bisherigen Anti-VEGF-Therapie.

BACKGROUND: Pivotal clinical trials have proven brolucizumab to be a potent intravitreal anti-vascular endothelial growth factor (VEGF) drug in patients with neovascular age-related macular degeneration (nAMD). Therefore, it seems to be a promising drug also in patients with recalcitrant nAMD. This article presents the results of patients who were switched to brolucizumab due to persistent fluid under previous anti-VEGF treatment. METHODS: In this study 21 eyes were retrospectively analyzed in which treatment was switched to brolucizumab due to persistent intraretinal (IRF), subretinal (SRF) and/or sub-retinal pigment epithelium (sub-RPE fluid) fluid despite long-term anti-VEGF treatment. Functional and spectral domain optical coherence tomography (SD-OCT) data were investigated at diagnosis of nAMD (I), at switch to brolucizumab (II), 4 weeks after upload of brolucizumab (III) and at first reactivation of macular neovascularization (MNV, IV). RESULTS: There were no significant changes in fluid distribution between (I) and (II). After upload of brolucizumab (III) a significant reduction of central subfield retinal thickness (CSRT, p = 0.0001), SRF (p = 0.004) and sub-RPE fluid (p = 0.04), but no visual acuity improvement (p = 0.56) were observed. CONCLUSION: Intravitreal brolucizumab treatment can achieve significant reductions particularly of SRF and sub-RPE in patients refractory to previous anti-VEGF treatment. Future studies should further investigate the effects of brolucizumab in patients with recalcitrant nAMD.

Cenozoic evolution of deep ocean temperature from clumped isotope thermometry.

Characterizing past climate states is crucial for understanding the future consequences of ongoing greenhouse gas emissions. Here, we revisit the benchmark time series for deep ocean temperature across the past 65 million years using clumped isotope thermometry. Our temperature estimates from the deep Atlantic Ocean are overall much warmer compared with oxygen isotope-based reconstructions, highlighting the likely influence of changes in deep ocean pH and/or seawater oxygen isotope composition on classical oxygen isotope records of the Cenozoic. In addition, our data reveal previously unrecognized large swings in deep ocean temperature during early Eocene acute greenhouse warmth. Our results call for a reassessment of the Cenozoic history of ocean temperatures to achieve a more accurate understanding of the nature of climatic responses to tectonic events and variable greenhouse forcing.

[How physicians inform about colorectal cancer and screening]. / Arztliche Aufklärung über Darmkrebs und Darmkrebsvorsorge.

Screening colonoscopy is an efficient and safe instrument for the early detection of colonic neoplasia. The cumulative participation rate in Germany remains low with 15.5% of eligible men and 17.2% of eligible women. Reasons for this are not well understood. Especially physicians have an important role. The aim of this study was to analyse information and recommendations of primary care physicians, urologists and gynaecologists on colorectal cancer screening. A survey of 239 primary care physicians, urologists and gynaecologists by a structured questionnaire on information concerning colorectal cancer and colorectal cancer prevention was carried out. Statistical analysis was performed by pair-wise comparison of the three groups. There were only small differences between primary care physicians, urologists and gynaecologists. Primary care physicians offer patients more consulting time for this information than the other two groups. In the majority of cases colonoscopy is recommended. Gynaecologists less often recommend the classical guaiac-based faecal occult blood test, but more frequently immunochemical tests. The complication rate of colonoscopy is overestimated at 1.25% (0 - 40%). The majority of physicians have previously participated in colorectal cancer screening. Information about the risk of colorectal cancer and screening has a high priority. The level of knowledge of physicians may be improved.

Intercultural education of nurses and health professionals in Europe (IENE).

AIMS: The study aimed to explore the perceived learning and teaching needs of students and practitioners of health-care professions in relation to preparation for working in another European country and/or in a multicultural environment. The participating countries were: Belgium, Bulgaria, Germany, Romania and the UK. METHODS: Questionnaires, consisting of open questions, were completed by a total of 118 participants. Data analysis adopted both a priori and inductive approaches. The predetermined constructs of cultural awareness, cultural knowledge, cultural sensitivity and cultural competence were used to structure suggestions for theoretical input and practical activities and experiences. Inductive analysis revealed other emergent themes that underpin all four of these constructs. RESULTS: Practical experiences form a fundamental part of preparation for labour mobility and/or for practice within a multicultural environment. However, health-care practitioners need to be adequately prepared for such experiences and value the opportunity to learn about culture, to explore values and beliefs, and to practise intercultural skills within the safe environment of an educational establishment, facilitated by skilled teachers.

Evidence for correlation of fragile sites and chromosomal breakpoints in carriers of constitutional balanced chromosomal rearrangements.

A molecular cytogenetic study of 251 cases with balanced chromosomal rearrangements detected due to infertility of unclear origin or in prenatal diagnostics with a later normal outcome was done. Balanced translocations (127 cases), inversions (105 cases), insertions (three cases), balanced complex rearrangements (four cases), or derivative chromosomes leading to no imbalance (12 cases), were studied by multicolor banding (MCB) and/or subcentromeric multicolor fluorescence in situ hybridization (subcenM-FISH). Five-hundred and twenty-nine break-events were characterized by molecular cytogenetics. Only 150 of these were unique breakpoints, the remainder were observed between two and 10 times. According to the results obtained, there was cytogenetic co-localization of fragile site (FS) in ~71% of the studied 529 break-events. Nine selected cases with evidence for breakpoints within FS were further analyzed by FS-specific bacterial artificial chromosome (BAC) probes; only one did not show a co-localization. Further detailed molecular analysis will be necessary to characterize the mechanisms and genetic basis for this phenomenon.

Naturally occurring fire coral clones demonstrate a genetic and environmental basis of microbiome composition.

Coral microbiomes are critical to holobiont functioning, but much remains to be understood about how prevailing environment and host genotype affect microbial communities in ecosystems. Resembling human identical twin studies, we examined bacterial community differences of naturally occurring fire coral clones within and between contrasting reef habitats to assess the relative contribution of host genotype and environment to microbiome structure. Bacterial community composition of coral clones differed between reef habitats, highlighting the contribution of the environment. Similarly, but to a lesser extent, microbiomes varied across different genotypes in identical habitats, denoting the influence of host genotype. Predictions of genomic function based on taxonomic profiles suggest that environmentally determined taxa supported a functional restructuring of the microbial metabolic network. In contrast, bacteria determined by host genotype seemed to be functionally redundant. Our study suggests microbiome flexibility as a mechanism of environmental adaptation with association of different bacterial taxa partially dependent on host genotype.

First case of a neocentromere formation in an otherwise normal chromosome 7.

According to cytogenetic and molecular cytogenetic characterization, an otherwise not-altered chromosome 7 formed a neocentromere in band 7q32.1 in a clinically normal female. The alpha satellite sequence D7Z1 remained in its place but was not used for formation of the primary chromosomal incision. Similar observations of centromere repositioning have been made for chromosomes 3 (2x), 4, 8 and Y (2x). Even though data is available for some neocentromeres whose positions are correlated with evolutionary new centromeres for 7q32.1, no correlation could be found for an ancestral inactivated centromere in any of the presently living primates. Overall, we report a new case of centromere repositioning at a position not known to harbor an ancestral inactivated centromere.

[Treatment adherence and effectiveness of anti-Vascular Endothelial Growth Faktor(VEGF) treatment of diabetic macular edema in the clinical routine : Comparison between cooperative and unicentric organization of treatment]. / Therapieadhärenz und Effektivität bei der Anti-Vascular Endothelial Growth Faktor(VEGF)-Therapie des diabetischen Makulaödems im klinischen Alltag : Vergleich zwischen einer kooperativen und einer unizentrischen Organisation der Behandlung.

BACKGROUND: Intravitreal injection of anti-vascular endothelial growth factor (VEGF) is an established method for treatment of diabetic macular edema (DME); however, to ensure the best possible functional results continuous treatment of patients over a long period with regular control visits are necessary. The adherence of patients to the treatment is of great importance for success. METHODS: In order to make implementation of treatment easier for patients, an internet-based referral platform was established to enable the follow-up examination to be performed by an ophthalmologist using spectal domain optical coherence tomography (SD-OCT) close to the patients place of residence. Based on 50 patients the effectiveness of this cooperative treatment (IT-Cooperation) was compared to 50 patients who were controlled in the treatment center for DME patients over a period of 2 years. RESULTS: Patients in the IT-Cooperation group received an average of 6.3 injections in the first year of follow-up compared to the lower number of 5.2 injections for patients attending the treatment center. During the second year the average number of injections decreased to 2.7 (IT-Cooperation) and 2.4 (treatment center). Patients of the IT-Cooperation showed an average of 12.0 control visits in contrast to the average number of 9.6 visits (p < 0.01) for patients attending the treatment center in the first year of observation. This difference between the two groups was significant and was confirmed in the second year of follow-up with 8.3 visits in the IT-Cooperation group compared to 4.4 visits in the treatment center group (p < 0.01). CONCLUSION: The greater number of follow-up examinations close to the patient's place of residence for the IT-Cooperation group significantly improved the quality of treatment adherence in DME patients; however, intensive exchange of information between the ophthalmologist performing the control examinations and the treatment center where the injections were carried out is mandatory.