Alpha-Particle Exposure Induces Mainly Unstable Complex Chromosome Aberrations which do not Contribute to Radiation-Associated Cytogenetic Risk.

The mechanism underlying the carcinogenic potential of α radiation is not fully understood, considering that cell inactivation (e.g., mitotic cell death) as a main consequence of exposure efficiently counteracts the spreading of heritable DNA damage. The aim of this study is to improve our understanding of the effectiveness of α particles in inducing different types of chromosomal aberrations, to determine the respective values of the relative biological effectiveness (RBE) and to interpret the results with respect to exposure risk. Human peripheral blood lymphocytes (PBLs) from a single donor were exposed ex vivo to doses of 0-6 Gy X rays or 0-2 Gy α particles. Cells were harvested at two different times after irradiation to account for the mitotic delay of heavily damaged cells, which is known to occur after exposure to high-LET radiation (including α particles). Analysis of the kinetics of cells reaching first or second (and higher) mitosis after irradiation and aberration data obtained by the multiplex fluorescence in situ hybridization (mFISH) technique are used to determine of the cytogenetic risk, i.e., the probability for transmissible aberrations in surviving lymphocytes. The analysis shows that the cytogenetic risk after α exposure is lower than after X rays. This indicates that the actually observed higher carcinogenic effect of α radiation is likely to stem from small scale mutations that are induced effectively by high-LET radiation but cannot be resolved by mFISH analysis.

[Total Hip and Knee Arthroplasty - Utilization of Postoperative Rehabilitation]. / Implantation einer Hüft- oder Knietotalendoprothese und die Inanspruchnahme einer Anschlussrehabilitation.

BACKGROUND: After total hip and knee arthroplasty, patients have different options of subsequent treatment: an early postoperative rehabilitation, with or without a period at home, or only outpatient services. The aim of this study was to identify factors predicting the utilization of an early postoperative rehabilitation. METHODS: This cross-sectoral analysis is based on claims data of AOK Baden-Württemberg (Statutory Health Insurance), Deutsche Rentenversicherung Bund and Deutsche Rentenversicherung Baden-Württemberg (German Pension Insurance). Predictors for participation in an early postoperative rehabilitation and for an interim period were determined using logistic regression analysis. RESULTS: 82.6% of 9 232 patients were going to an early postoperative rehabilitation after total hip arthroplasty. After total knee arthroplasty, 83.9% of 7 656 patients were utilizing postoperative rehabilitation. Moreover, there was less utilization of postoperative rehabilitation in young, male and foreign patients. The analysis shows that the utilization of post-acute rehabilitation was significantly predicted by sociodemographic variables (age, sex, nationality) as well as comorbidity, outpatient treatment and medication. CONCLUSION: The results provide an indication of higher severity of patients in group "postoperative rehabilitation without a period at home". Nevertheless there are some indications for under-utilization of certain patient groups.

Estimating the residual risk for HIV, HCV and HBV in different types of platelet concentrates in Germany.

BACKGROUND AND OBJECTIVES: We estimated and compared the residual risks due to window-period donations for pooled and apheresis platelets in Germany using a modification of a previously described statistical model. This model directly utilizes the reported interdonation intervals before a positive donation and reflects in this aspect the look-back procedures used in haemovigilance. MATERIALS AND METHODS: Data from the German National Blood Donor Surveillance System for the years 2006-2012, including reports about donations from repeat donors with confirmed positive test results for HIV, HCV and HBV, were used to estimate the risk of undetected infectious units for both pooled and apheresis platelets. RESULTS: Demographics of whole-blood and apheresis donors differed in age, gender, catchment area and interdonation interval. These differences impact on the prevalence and incidence of transfusion relevant infections and consequently the residual risk. The estimates for the residual risks for pooled and apheresis platelets were comparable. For HIV, there was no significant difference, for HCV apheresis platelets had a lower residual risk, whereas pooled platelets had a lower risk for undetected HBV infections. CONCLUSION: These findings do not support calls for a shift to an apheresis platelets-only policy in Germany.

Heterogeneous nucleation for synthesis of sub-20nm ZnO nanopods and their application to optical humidity sensing.

We present a novel method for colloidal synthesis of one-dimensional ZnO nanopods by heterogeneous nucleation on zero-dimensional ZnO nanoparticle 'seeds'. Ultra-small ZnO nanopods, multi-legged structures with sub-20 nm individual leg diameters, can be synthesized by hydrolysis of a Zn2+ precursor growth solution in presence of ∼4 nm ZnO seeds under hydrothermal conditions via microwave-assisted heating in as little as 20 min of reaction time. One-dimensional ZnO nanorods are initially generated in the reaction mixture by heterogeneous nucleation and growth along the [0001] direction of the ZnO crystal. Growth of one-dimensional nanorods subsequently yields to an 'attachment' and size-focusing phase where individual nanorods fuse together to form multi-legged nanopods having diameters ∼15 nm. ZnO nanopods exhibit broad orange-red defect-related photoluminescence in addition to a near-band edge emission at 373 nm when excited above the band-gap at 350 nm. The defect-related photoluminescence of the ZnO nanopods has been applied towards reversible optical humidity sensing at room temperature. The sensors demonstrated a linear response between 22% and 70% relative humidity with a 0.4% increase in optical intensity per % change in relative humidity. Due to their ultra-small dimensions, ZnO nanopods exhibit a large dynamic range and enhanced sensitivity to changes in ambient humidity, thus showcasing their ability as a platform for optical environmental sensing.

Fate of D3 mouse embryonic stem cells exposed to X-rays or carbon ions.

The risk of radiation exposure during embryonic development is still a major problem in radiotoxicology. In this study we investigated the response of the murine embryonic stem cell (mESC) line D3 to two radiation qualities: sparsely ionizing X-rays and densely ionizing carbon ions. We analyzed clonogenic cell survival, proliferation, induction of chromosome aberrations as well as the capability of cells to differentiate to beating cardiomyocytes up to 3 days after exposure. Our results show that, for all endpoints investigated, carbon ions are more effective than X-rays at the same radiation dose. Additionally, in long term studies (≥8 days post-irradiation) chromosomal damage and the pluripotency state were investigated. These studies reveal that pluripotency markers are present in the progeny of cells surviving the exposure to both radiation types. However, only in the progeny of X-ray exposed cells the aberration frequency was comparable to that of the control population, while the progeny of carbon ion irradiated cells harbored significantly more aberrations than the control, generally translocations. We conclude that cells surviving the radiation exposure maintain pluripotency but may carry stable chromosomal rearrangements after densely ionizing radiation.

[Operative treatment of claw deformity by lassoplasty]. / Operative Behandlung der Krallenhand mittels Lassoplastik.

OBJECTIVES: The aim is correction of claw deformity of the fingers by intrinsic paralysis. INDICATIONS: Indications are claw deformity of fingers caused by palsy or functional loss of the interosseus or lumbrical muscles as far as the function of the superficial and deep flexors of the finger is intact. CONTRAINDICATIONS: Contraindications are loss or paralysis of finger flexors supplied by the median nerve, fixed extension or flexion contracture of the finger joints, osteoarthritis and other malfunctions of the finger joints, no active flexion and extension of the interphalangeal joints due to compromised tendon gliding. Relative: Upper ulnar nerve palsy with functional loss of the deep flexor of the small and ring finger and possibly of the middle finger. SURGICAL TECHNIQUE: The operation technique involves detachment of the flexor digitorum superficialis IV tendon (FDS IV) distal to Camper's chiasm, division of the tendon into separate strips, interweaving of each tendon strip into the proximal part of the A2 pulley of the affected fingers. In cases of claw deformity of all fingers it may be advantageous to apply the superficial flexor tendon of the long finger in addition to the FDS IV tendon as otherwise the FDS IV tendon has to be divided into four strips resulting in relatively thin tendon strips. If the FDS III and IV tendons are applied, the two strips of the FDS IV tendon are used for lassoplasty of the small and ring fingers and the FDS III tendon for lassoplasty of the middle and index fingers. POSTOPERATIVE MANAGEMENT: Postoperative management includes immobilization of the operated fingers by a dorsoulnar forearm plaster cast including the metacarpophalangeal joints which are flexed to 70°. After 2 weeks replacement of the cast by a thermoplastic splint for another 4 weeks. During the whole period exercises for the finger and thumb should be carried out. RESULTS: From April 2003 to June 2012 a total of 17 patients, 8 female and 9 male were surgically treated for claw deformity. The dominant hand was affected in seven patients. The average age was 46 ± 15 (22-80) years, the average interval from onset of ulnar palsy to lassoplasty was 61 ± 91 (3-288) months. The final follow-up was performed after an average of 42 ± 32 (2-112) months. Claw deformity was resolved in 14 out of the 17 patients. The grip strength was on average 58 ± 28 % (11-96 %) of the unaffected hand, the mean disabilities of the arm, shoulder and hand (DASH) score was 32 ± 18 (5-68) points and the degree of patient satisfaction 7 ± 2 (0-10). According to own results and those in the literature lassoplasty can be recommended for the treatment of claw deformity.

The fate of a normal human cell traversed by a single charged particle.

The long-term "fate" of normal human cells after single hits of charged particles is one of the oldest unsolved issues in radiation protection and cellular radiobiology. Using a high-precision heavy-ion microbeam we could target normal human fibroblasts with exactly one or five carbon ions and measured the early cytogenetic damage and the late behaviour using single-cell cloning. Around 70% of the first cycle cells presented visible aberrations in mFISH after a single ion traversal, and about 5% of the cells were still able to form colonies. In one third of selected high-proliferative colonies we observed clonal (radiation-induced) aberrations. Terminal differentiation and markers of senescence (PCNA, p16) in the descendants of cells traversed by one carbon ion occurred earlier than in controls, but no evidence of radiation-induced chromosomal instability was found. We conclude that cells surviving single-ion traversal, often carrying clonal chromosome aberrations, undergo accelerated senescence but maintain chromosomal stability.

[HIV, HCV, HBV and syphilis surveillance among blood donors in Germany 2008-2010]. / HIV-, HCV-, HBV- und Syphilissurveillance unter Blutspendern in Deutschland 2008-2010.

The Robert Koch Institute collects and evaluates data on the prevalence and incidence of HIV, hepatitis C (HCV), hepatitis B (HBV) and syphilis infections among blood and plasma donors in Germany according to article 22 of the Transfusion Act. This report includes data from all blood donation services in Germany for 2008-2010. The prevalence for HIV ranged from 6.6-7.0/100,000, for HCV from 68.9-81.6/100,000, for HBV from 116.2-136.6/100,000 and for syphilis from 31.0-42.1/100,000 donations. The proportion of incident infections per 100,000 donations ranged from 0.8-0.9 for HIV, 0.8-1.0 for HCV, 0.3-0.5 for HBV and 1.4-1.6 for syphilis. Since 2001 the prevalence and incidence of HBV and HCV among blood has declined whereas incident HIV infections reached a peak in 2008 and 2010 and show an increasing trend. Also, the proportion of syphilis infections among first time donors was highest in 2010. Significant differences in infection prevalence and incidence were found between the sexes, different age groups and different donation types. In order to optimise donor selection a validated donor questionnaire should be used and confidentiality in all steps of donation should be assured. The possibility of a confidential self-exclusion should be explicitly pointed out to donors.

[Demography and donation frequencies of blood and plasma donor populations in Germany. Update 2010 and 5-year comparison]. / Demografie und Spendeaktivität von Blut- und Plasmaspendern in Deutschland. Update 2010 und 5-Jahres-Vergleich.

The Robert Koch Institute collects and evaluates nationwide data on the incidence and prevalence of transfusion-relevant infections among blood and plasma donors in Germany. Since 2006 data not only on the number of donations tested but also on the number of the respective donors have become available. The demographic profile and donation frequencies of German whole blood, plasma and platelet donors in 2010 and the percentages among the general population are described and compared to data from 2006. Although the general population eligible to donate blood is on the decline since 2003, with a loss of 2% between 2006 and 2010, this has not led to a decrease in the number of blood donors and donations. Instead, the number of new and repeat whole blood donors increased by 8% and 7%, respectively. At the same time, the number of new plasma donors grew by 23%, that of repeat plasma donors by 41%. In 2010 more than 4.3% of the population aged 18-68 years was active as repeat whole blood donors; 0.4% repeatedly donated plasma or platelets. Since 2006 the percentage of donors among the general population increased significantly, especially among the youngest age group (18-24 years). Donation frequency varied depending on donor age and sex, with an average of 1.9 per year for whole blood donations, 12.5 for plasmapheresis and 5.0 for plateletpheresis. While the donation frequency for whole blood remained unchanged since 2006, the frequency of apheresis donations increased, especially among older donors. By recruiting more new donors and retaining and reactivating existing ones more effectively, the number of whole blood and apheresis donations was augmented.

Circadian integration of sleep-wake and feeding requires NPY receptor-expressing neurons in the mediobasal hypothalamus.

Sleep and feeding rhythms are highly coordinated across the circadian cycle, but the brain sites responsible for this coordination are unknown. We examined the role of neuropeptide Y (NPY) receptor-expressing neurons in the mediobasal hypothalamus (MBH) in this process by injecting the targeted toxin, NPY-saporin (NPY-SAP), into the arcuate nucleus (Arc). NPY-SAP-lesioned rats were initially hyperphagic, became obese, exhibited sustained disruption of circadian feeding patterns, and had abnormal circadian distribution of sleep-wake patterns. Total amounts of rapid eye movement sleep (REMS) and non-REMS (NREMS) were not altered by NPY-SAP lesions, but a peak amount of REMS was permanently displaced to the dark period, and circadian variation in NREMS was eliminated. The phase reversal of REMS to the dark period by the lesion suggests that REMS timing is independently linked to the function of MBH NPY receptor-expressing neurons and is not dependent on NREMS pattern, which was altered but not phase reversed by the lesion. Sleep-wake patterns were altered in controls by restricting feeding to the light period, but were not altered in NPY-SAP rats by restricting feeding to either the light or dark period, indicating that disturbed sleep-wake patterns in lesioned rats were not secondary to changes in food intake. Sleep abnormalities persisted even after hyperphagia abated during the static phase of the lesion. Results suggest that the MBH is required for the essential task of integrating sleep-wake and feeding rhythms, a function that allows animals to accommodate changeable patterns of food availability. NPY receptor-expressing neurons are key components of this integrative function.

Remote entanglement between a single atom and a Bose-Einstein condensate.

Entanglement between stationary systems at remote locations is a key resource for quantum networks. We report on the experimental generation of remote entanglement between a single atom inside an optical cavity and a Bose-Einstein condensate (BEC). To produce this, a single photon is created in the atom-cavity system, thereby generating atom-photon entanglement. The photon is transported to the BEC and converted into a collective excitation in the BEC, thus establishing matter-matter entanglement. After a variable delay, this entanglement is converted into photon-photon entanglement. The matter-matter entanglement lifetime of 100 µs exceeds the photon duration by 2 orders of magnitude. The total fidelity of all concatenated operations is 95%. This hybrid system opens up promising perspectives in the field of quantum information.

[Epidemiological data on infections among blood donors in Germany 2007]. / Infektionsepidemiologische Daten von Blutspendern in Deutschland 2007.

The Robert Koch Institute collects and evaluates data on the prevalence and incidence of HIV, hepatitis C (HCV), hepatitis B (HBV), and syphilis infections among blood and plasma donors in Germany according to §22 of the Transfusion Act ("Transfusiongesetz"). The surveillance data permit an assessment of the occurrence of infections in the blood donor population and consequently the safety of the collected donations. This report includes data from all blood donation services in Germany for 2007. Due to the revision of the Transfusion Act in 2005, not only the number of donations but also the number of donors is now available for analysis. Nearly 550,000 donations or blood samples from new donors and more than 6.24 million donations collected from approximately 2.43 million repeat donors were tested for transfusion-relevant infections in 2007. The prevalence for HIV was 8.0/100,000, for HCV 70.0/100,000, for HBV 132.5/100,000, and for syphilis 36.8/100,000 donations. The proportion of seroconversions/100,000 donations was 0.6 for HIV, 1.1 for HCV, 0.6 for HBV, and 1.7 for syphilis. The analysis showed a very low incidence of HIV, HBV, and syphilis with marginal changes compared to previous years. The prevalence and incidence of HCV among blood donors was once again declining.

Lossless state detection of single neutral atoms.

We introduce lossless state detection of trapped neutral atoms based on cavity-enhanced fluorescence. In an experiment with a single 87Rb atom, a hyperfine-state-detection fidelity of 99.4% is achieved in 85 µs. The quantum bit is interrogated many hundreds of times without loss of the atom while a result is obtained in every readout attempt. The fidelity proves robust against atomic frequency shifts induced by the trapping potential. Our scheme does not require strong coupling between the atom and cavity and can be generalized to other systems with an optically accessible quantum bit.

Inversions in chromosome 10 of human thyroid cells induced by accelerated heavy ions.

Papillary thyroid carcinoma (PTC) is a known radiation-induced tumor. Rearrangements in human chromosome 10 and in particular intrachromosomal exchanges are often associated with PTC formation. In this study we measured intrachromosomal exchanges in human thyroid follicular cells exposed to sparsely or densely ionizing radiation. Assuming that inversions in chromosome 10 are a biomarker of PTC risk, we estimated the relative biological effectiveness (RBE) of heavy ions using a molecular marker in vitro. The analysis of chromosomal aberrations was performed with the mBAND technique, which allows detection of both inter- and intrachromosomal exchanges. Our results do not show any significant increase in the yield of intrachanges in samples exposed to heavy ions compared to X rays. Within the constraints imposed by the experimental model we used, we conclude that heavy ions would not necessarily be more effective than X rays in the induction of thyroid cancer.

Influence of nuclear geometry on the formation of genetic rearrangements in human cells.

Interphase chromosomes are divided into discrete domains, with limited overlapping and movement. We explored the role of nuclear topology in the formation of chromosome aberrations by irradiating normal human fibroblasts with high-energy heavy ions from different directions. Cells with elliptical nuclei were grown in an aligned manner onto micrometer grooved culturing substrates to have a predetermined orientation with respect to the accelerated iron ions. Particles were directed either perpendicular to the cell layer or along the major or minor axis of the nucleus. Analysis of chromosome aberrations by mFISH showed that, at the same radiation dose, the yield of chromosomal damage and its complexity are largely modified by the irradiation geometry. The results demonstrate that the architecture of the cell nucleus determines the formation of chromosomal rearrangements.

Emission properties and photon statistics of a single quantum dot laser.

A theoretical description for a single quantum-dot emitter in a microcavity is developed.We analyze for increasing steady-state pump rate the transition from the strong-coupling regime with photon antibunching to the weak-coupling regime with coherent emission. It is demonstrated how Coulomb interaction of excited carriers and excitation-induced dephasing can strongly modify the emission properties. Our theoretical investigations are based on a direct solution of the Liouville-von Neumann equation for the coupled carrier-photon system. We include multiple carrier excitations in the quantum dot, their Coulomb interaction, as well as excitation-induced dephasing and screening. Similarities and differences to atomic systems are discussed and results in the regime of recent experiments are interpreted.

No evidence for DNA and early cytogenetic damage in bystander cells after heavy-ion microirradiation at two facilities.

The occurrence of bystander effects has challenged the evaluation of risk for heavy ions, mainly in the context of space exploration and the increasing application of carbon ions in radiotherapy. In the present study, we addressed whether heavy-ion-induced DNA and cytogenetic damage is detectable in bystander cells. The formation of gamma-H2AX foci, sister chromatid exchanges and micronuclei were used as markers of damage to DNA. Normal human fibroblasts were exposed to low fluences of carbon and uranium ions, and alternatively single cells were targeted with heavy ions using the GSI microbeam. We did not observe a significant increase in the bystander formation of gamma-H2AX foci, sister chromatid exchanges or micronuclei. In addition, we performed for the first time parallel experiments at two microbeam facilities (GSI, JAEA) using the same cell line, culture conditions and irradiation protocols. No significant enhancement of the micronucleus frequencies in bystander cells was detected after targeted carbon-ion irradiation, confirming the results. Details regarding the history, culture conditions or support of the cells might be affecting the detection of bystander effects. On the other hand, the potential X-ray- and heavy-ion-induced bystander effects investigated herein clearly do not exceed the experimental error and thus are either lacking or are less pronounced than the effects reported in the literature for similar end points after alpha-particle and X-ray exposure.

A susceptibility gene for type 2 diabetes confers substantial risk for diabetes complicating cystic fibrosis.

AIMS/HYPOTHESIS: Insulin-requiring diabetes affects 25-50% of young adults with cystic fibrosis (CF). Although the cause of diabetes in CF is unknown, recent heritability studies in CF twins and siblings indicate that genetic modifiers play a substantial role. We sought to assess whether genes conferring risk for diabetes in the general population may play a risk modifying role in CF. METHODS: We tested whether a family history of type 2 diabetes affected diabetes risk in CF patients in 539 families in the CF Twin and Sibling family-based study. A type 2 diabetes susceptibility gene (transcription factor 7-like 2, or TCF7L2) was evaluated for association with diabetes in CF using 998 patients from the family-based study and 802 unrelated CF patients in an independent case-control study. RESULTS: Family history of type 2 diabetes increased the risk of diabetes in CF (OR 3.1; p = 0.0009). A variant in TCF7L2 associated with type 2 diabetes (the T allele at rs7903146) was associated with diabetes in CF in the family study (p = 0.004) and in the case-control study (p = 0.02; combined p = 0.0002). In the family-based study, variation in TCF7L2 increased the risk of diabetes about three-fold (HR 1.75 per allele, 95% CI 1.3-2.4; p = 0.0006), and decreased the mean age at diabetes diagnosis by 7 years. In CF patients not treated with systemic glucocorticoids, the effect of TCF7L2 was even greater (HR 2.9 per allele, 95% CI 1.7-4.9, p = 0.00011). CONCLUSIONS/INTERPRETATION: A genetic variant conferring risk for type 2 diabetes in the general population is a modifier of risk for diabetes in CF.

[HIV, HCV, HBV and syphilis infections among blood donors in Germany 2006. Report from the Robert Koch Institute in accordance with Article 22 of the Transfusion Act]. / Infektionsepidemiologische Daten von Blutspendern 2006 : Bericht des Robert Koch-Instituts zu den Meldungen nach section sign 22 Transfusionsgesetz.

The Robert Koch Institute collects and evaluates data on the prevalence and incidence of HIV, hepatitis C (HCV), hepatitis B (HBV) and syphilis infections among blood and plasma donors in Germany according to Article 22 of the Transfusion Act. The surveillance data permit an assessment of the occurrence of infections in the blood donor population and consequently the safety of the collected donations. This report includes data from all blood donation services in Germany for 2006. Due to the revision of the Transfusion Act in 2005 not only the number of donations but also the number of donors has become available for analysis. More than 500,000 donations or blood samples from new donors and about 6 million donations collected from ca. 2.3 million repeat donors were screened in 2006. The prevalence for HIV was 6.2/100,000, for HCV 76.2/100,000, for HBV 150.2/100,000 and for syphilis 34.4/100,000 donations. The rate of seroconversions/100,000 donations was 0.8 for HIV, 1.1 for HCV, 0.7 for HBV and 1.6 for syphilis. The analysis showed a very low incidence of HIV, HBV und syphilis with marginal changes compared to previous years. The prevalence and incidence of HCV among blood donors was once again declining.

[HIV, HCV, HBV and syphilis infections among blood donors in Germany 2005. Report from the Robert Koch Institute in accordance with Article 22 of the Transfusion Act]. / Infektionsepidemiologische Daten von Blutspendern 2005. Bericht des Robert Koch-Instituts zu den Meldungen nach Paragraph 22 Transfusionsgesetz.

The Robert Koch Institute collects and evaluates data on the prevalence and incidence of HIV, hepatitis C (HCV), hepatitis B (HBV) and syphilis infections among blood and plasma donors in Germany according to article 22 of the Transfusion Act. The surveillance data permit an assessment of the occurrence of infections in the blood donor population and consequently the safety of the collected donations. This report includes data from all blood donation services in Germany for 2005. In total, 6.26 million donations or blood samples from prospective donors were screened. The prevalence of the relevant infections was 6.1/100,000 for HIV, 81.2/100,000 for HCV, 143.9/100,000 for HBV and 35.6/100,000 donations for syphilis. The rate of seroconversions/100,000 donations was 0.9 for HIV, 1.4 for HCV, 0.9 for HBV and 2.3 for syphilis. The analysis showed a very low incidence of infections with a decreasing trend for HCV infections among first time donors and an increase in incident HIV and syphilis infections since 1999. The latter has to be monitored carefully and possible causes need to be evaluated.