Lifetime excess absolute risk for lung cancer due to exposure to radon: results of the pooled uranium miners cohort study PUMA.

The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18-64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10-4 or 5.57 × 10-4 in the full PUMA cohort and 7.50 × 10-4 or 7.66 × 10-4 in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10-4 to 9.2 × 10-4. PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes.

Updated risk models for lung cancer due to radon exposure in the German Wismut cohort of uranium miners, 1946-2018.

UNSCEAR recently recommended that future research on the lung cancer risk at low radon exposures or exposure rates should focus on more contemporary uranium miners. For this purpose, risk models in the German Wismut cohort of uranium miners were updated extending the follow-up period by 5 years to 1946-2018. The full cohort (n = 58,972) and specifically the 1960 + sub-cohort of miners first hired in 1960 or later (n = 26,764) were analyzed. The 1960 + sub-cohort is characterized by low protracted radon exposure of high quality of measurements. Internal Poisson regression was used to estimate the excess relative risk (ERR) for lung cancer per cumulative radon exposure in Working Level Months (WLM). Applying the BEIR VI exposure-age-concentration model, the ERR/100 WLM was 2.50 (95% confidence interval (CI) 0.81; 4.18) and 6.92 (95% CI < 0; 16.59) among miners with attained age < 55 years, time since exposure 5-14 years, and annual exposure rates < 0.5 WL in the full (n = 4329 lung cancer deaths) and in the 1960 + sub-cohort (n = 663 lung cancer deaths), respectively. Both ERR/WLM decreased with older attained ages, increasing time since exposure, and higher exposure rates. Findings of the 1960 + sub-cohort are in line with those from large pooled studies, and ERR/WLM are about two times higher than in the full Wismut cohort. Notably, 20-30 years after closure of the Wismut mines in 1990, the estimated fraction of lung cancer deaths attributable to occupational radon exposure is still 26% in the full Wismut cohort and 19% in the 1960 + sub-cohort, respectively. This demonstrates the need for radiation protection against radon.

Marginal bone loss one year after implantation: a systematic review of different loading protocols.

The aim of this study was to analyse the influence of different loading protocols on marginal bone loss (MBL). The outcomes of different implant loading protocols were assessed at 1year after implantation, with focus on MBL; protocols included immediate, immediate non-occlusal, early, and conventional loading. The search strategy resulted in 889 studies. Twenty-two of these studies fulfilled the inclusion criteria. Among the included studies, the lowest MBL was for immediately loaded implants (0.05±0.67mm) and the highest for immediate non-occlusally loaded implants (1.37±0.5mm). The results of the meta-analysis showed an estimated mean MBL of 0.457mm (95% confidence interval (CI) 0.133-0.781) for immediate loading, 0.390mm (95% CI 0.240-0.540) for immediate non-occlusal loading, 0.488mm (95% CI 0.289-0.687) for early loading (>2 days to <3 months), and 0.852mm (95% CI 0.429-1.275) for conventional loading (>3 months) implant protocols. The lowest decrease in 1-year implant survival per millimetre increase in MBL was observed for immediate loading and the highest for conventional loading. Conventional loading showed a significantly higher MBL than the other three loading protocols. This systematic review and meta-analysis indicates that the immediate loading protocol is a reasonable alternative to the conventional loading protocol.

Giardia in a selected population of dogs and cats in Germany - diagnostics, coinfections and assemblages.

Infections with the zoonotic endoparasite Giardia duodenalis are widely spread among dogs and cats worldwide. Since the question whether the infection might be transmitted from domestic animals to their owners is still an important topic, a reliable detection of patent Giardia infections and the determination of the associated Giardia assemblages is of major concern. The objectives of the present study were to determine the prevalence of Giardia infections in dogs and cats living in Germany using different diagnostic tests and to identify the Giardia assemblages of infected animals. Furthermore, a possible correlation of coinfections with other endoparasites was analysed. All samples were investigated by enzyme-linked immunosorbent assay (ELISA), merthiolate-iodine-formalin concentration technique (MIFC) and zinc chloride flotation. ELISA-positive samples were additionally screened with a direct immunofluorescence assay (IFA). Faecal DNA was extracted from all Giardia cyst-positive samples and used for multilocus sequence typing with nested PCRs targeting the following gene loci: SSU rRNA (SSU), glutamate dehydrogenase (gdh) and triosephosphate isomerase (tpi). Samples from dogs and cats tested positive for Giardia coproantigen (ELISA) in 30.6% and 17.9%, respectively. The MIFC technique revealed Giardia cysts in 33.9% of canine and in 34.6% of feline ELISA-positive samples, while using IFA, cysts were present in 90.4% of canine and in 76.9% of feline ELISA-positive samples. Coinfections with other endoparasites besides Giardia were found in both dogs and cats, yet a statistically significant correlation could solely be drawn for the canine samples. The success rate of the different PCR protocols varied between 23.1% (tpi) and 91.3% (SSU) for dogs and between 25.0% (gdh) and 90.0% (SSU) for cats. Dog-specific Giardia assemblages C and D were detected in 42 and 55 canine isolates, respectively. The cat-specific Giardia assemblage F was detected in 14 feline isolates. Two canine and two feline samples harboured the zoonotic assemblage A. According to the results of the study, Giardia is a common endoparasite in dogs and cats from Germany. The exclusive application of MIFC is insufficient for a reliable identification of patent Giardia infections since the IFA revealed a higher sensitivity for the detection of Giardia cysts in feline and canine faecal samples. Even though the majority of investigated animals harboured the species-specific Giardia assemblages C, D and F, a zoonotic potential arising from assemblage A could not be excluded.

ENVIRONMENTAL DOSIMETRY WITH THE BeOSL PERSONAL DOSEMETER.

In the course of this work, a dosemeter for measurement of ambient dose equivalent H*(10) based on the BeOSL dosimetry system was designed. Calculations of the energy response of the two-element BeOSL personal dosemeter in terms of H*(10) showed that the response does not fulfil the requirements of IEC 62387 Especially, the response for photon energies of 60-100 keV is too low. It is possible to correct this under-response using a BeOSL two-element dosemeter, a linear algorithm and an additional cover for the dosemeter. The Hp(0.07) element is shielded with lead, and with the help of a linear algorithm, corrections of the energy response are possible. So, the national requirements for an H*(10) area dosemeter in Germany can be fulfilled. The requirements of IEC 62387 are fulfilled for angles of radiation incidence from 0° to 60° for a rotation around the vertical and horizontal axis through the dosemeter, whereas for angles of incidence from 75° to 90°, the requirements are only fulfilled for rotation around the vertical axis through both elements.

PROPERTIES OF THE BEOSL DOSIMETRY SYSTEM IN THE FRAMEWORK OF A LARGE-SCALE PERSONAL MONITORING SERVICE.

The Individual Monitoring Service of the Helmholtz Zentrum München is currently using the BeOSL dosimetry system for monitoring ∼15 000 persons per month. This dosimetry system has a modular structure and represents a complete new concept on handling dosemeters in a large-scale dosimetry service. It is based on optically stimulated luminescence dosemeters made of beryllium oxide. The dosimetric and operational properties of the system are shown and discussed.

Potassium polytitanate gas-sensor study by impedance spectroscopy.

Nanocrystalline potassium polytitanates K2O·nTiO2·mH2O represent a new type of semiconducting compounds which are characterized by a high specific surface that makes them promising for use in gas sensors. In this work, we have studied potassium polytitanate mesoporous nanoparticle agglomerates placed over a SiO2/Si substrate equipped with multiple coplanar electrodes to measure the electrical response to various organic vapors, 1000 ppm of concentration, mixed with air by impedance spectrometry in range of the 10(-2)-10(6) Hz. The recorded impedance data for each sensor segment are associated with RC components of an equivalent circuit which are applied to selectively recognize the test vapors exploiting a "multisensor array" approach.

Multilocus sequence typing of canine Giardia duodenalis from South Eastern European countries.

Giardia duodenalis is a worldwide occurring protozoan that can infect various mammalian hosts. While living conditions are getting closer between pet animals and owners, there is discussion whether dogs may contribute to the transmission of these pathogens to humans. The present study was conducted in order to identify the Giardia assemblages in dogs from South Eastern Europe. For this purpose, 1645 faecal samples of household and shelter dogs from Albania, Bulgaria, Hungary, Macedonia, Romania and Serbia were tested for Giardia coproantigen by enzyme-linked immunosorbent assay (ELISA). A subset of 107 faecal samples demonstrating Giardia cysts by direct immunofluorescence assay (IFA) or microscopy (15-22 per country) plus 26 IFA-positive canine faecal samples from Croatia were used for DNA extraction and multilocus sequence typing with nested PCRs targeting five different gene loci: SSU rRNA, ITS1-5.8S-ITS2, beta giardin (bg), glutamate dehydrogenase (gdh) and triosephosphate isomerase (tpi). One third (33.7%) of the samples tested positive for Giardia antigen in the coproantigen ELISA. Shelter dogs were infected more frequently than household dogs (57.2 vs. 29.7%, p < 0.01). Amplification was obtained in 82.0, 12.8, 11.3, 1.5, and 31.6%, of the investigated samples at the SSU rRNA, bg, gdh and tpi loci and the ITS1-5.8S-ITS2 region, respectively. The dog-specific assemblages C and D were identified in 50 and 68 samples, respectively. The results demonstrate that G. duodenalis should be considered as a common parasite in dogs from South Eastern Europe. However, there was no evidence for zoonotic Giardia assemblages in the investigated canine subpopulation.

[Inpatient pain consultation service at a university hospital: a retrospective analysis of patient characteristics and the rate of the implementation of recommendations]. / Stationäre Schmerzkonsile einer universitären Schmerzambulanz : Eine retrospektive Analyse der Patientencharakteristika und der Umsetzungsrate der Empfehlungen.

BACKGROUND: The aim of this study was to conduct an audit of a university inpatient pain consultation service and to examine the quality and the implementation of the recommended therapeutic measures. Factors that influenced the implementation should be identified. PATIENTS AND METHODS: All inpatients treated by the consultation service in the years 2009 and 2010 were analyzed retrospectively. Demographic patient characteristics as well as quality parameters of the consultation service and pharmacological and non-pharmacological recommendations and their implementation were analyzed. RESULTS: In total 1,048 requests for the consultation service were processed of which 39.7% of the requests were for patients with acute pain, 33.8% with chronic and 19.9% with tumor-associated pain. Measures recommended most were medication, physiotherapy and psychological treatment. Recommended medications were actually prescribed in more than 80%, physiotherapy recommended in about 75% and psychological treatment recommended in 47% of the cases. Only a few influencing factors for the implementation of the recommended measures could be identified. CONCLUSION: Many different pain states are seen in an inpatient pain consultation service. The recommendations given are implemented in most cases especially concerning the medication.

Predictors of physical and emotional recovery 6 and 12 months after surgery.

BACKGROUND: A proportion of patients do not recover fully from surgery or they develop chronic postsurgical pain. The aim of this study was to examine the incidence and predictors of unfavourable long-term outcome after surgery using a prospective cohort design. METHODS: Some 401 patients undergoing various elective surgical procedures filled in the RAND 36-item Health Survey 1.0 health-related quality-of-life questionnaire before operation and at 6 and 12 months of follow-up to assess changes in pain, physical functioning, mental health and vitality. Preoperative psychological assessment was obtained. RESULTS: Most patients showed improvement in the various aspects of health-related quality of life after surgery, but a considerable proportion (14-24 per cent) still showed deterioration at 6 and 12 months. Multivariable linear regression analysis identified acute postoperative pain, duration of the operation and preoperative physical condition as the most important predictors of long-term pain and physical functioning. Preoperative surgical fear also had a small but significant contribution. The main predictors of mental health and vitality were physical condition before surgery, surgical fear and optimism. CONCLUSION: Up to a quarter of patients experienced suboptimal recovery after surgery. Both somatic and psychological factors were associated with the long-term outcome. Optimal recovery could be promoted by effective interventions on malleable factors.

Succinyl-CoA ligase deficiency: a mitochondrial hepatoencephalomyopathy.

This patient presented on the first day of life with pronounced lactic acidosis with an elevated lactate/pyruvate ratio. Urine organic acids showed Krebs cycle metabolites and mildly elevated methylmalonate and methylcitrate. The acylcarnitine profile showed elevated propionylcarnitine and succinylcarnitine. Amino acids showed elevated glutamic acid, glutamine, proline, and alanine. From the age 2 of mo on, she had elevated transaminases and intermittent episodes of liver failure. Liver biopsy showed steatosis and a decrease of mitochondrial DNA to 50% of control. She had bilateral sensorineural hearing loss. Over the course of the first 2 y of life, she developed a progressively severe myopathy with pronounced muscle weakness eventually leading to respiratory failure, Leigh disease, and recurrent hepatic failure. The hepatic symptoms and the metabolic parameters temporarily improved on treatment with aspartate, but neither muscle symptoms nor brain lesions improved. Laboratory testing revealed a deficiency of succinyl-CoA ligase enzyme activity and protein in fibroblasts because of a novel homozygous mutation in the SUCLG1 gene: c.40A>T (p.M14L). Functional analysis suggests that this methionine is more likely to function as the translation initiator methionine, explaining the pathogenic nature of the mutation. Succinyl-CoA ligase deficiency due to an SUCLG1 mutation is a new cause for mitochondrial hepatoencephalomyopathy.

[Leipzig fast-track protocol for cardio-anesthesia. Effective, safe and economical]. / Leipziger "Fast-track"-Protokoll in der Kardioanästhesie. Effektiv, sicher und ökonomisch sinnvoll.

BACKGROUND: In November 2005 a complex, multimodal anesthesia fast-track protocol (FTP) was introduced for elective cardiac surgery patients in the Cardiac Center of the University of Leipzig which included changing from an opioid regime to remifentanil and postoperative treatment in a special post-anesthesia recovery and care unit. The goal was to speed up recovery times while maintaining safety and improving costs. METHOD: A total of 421 patients who underwent the FTP and were treated in the special recovery room were analyzed retrospectively. These patients were compared with patients who had been treated by a standard protocol (SP) prior to instituting the FTP. Primary outcomes were time to extubation, length of stay in the intensive care unit (ICU) and treatment costs. RESULTS: The times to extubation were significantly shorter in the FTP group with 75 min (range 45-110 min) compared to 900 min (range 600-1140 min) in the SP group. Intensive care unit stay and hospital length of stay were also significantly shorter in the FTP group (p<0.01). The reduction of treatment costs of intensive care for FTP patients was 53.5% corresponding to savings of EUR 738 per patient in the FTP group compared with the SP group. CONCLUSIONS: The Leipzig fast-track protocol for cardio-anesthesia including the central elements of switching opiate therapy to remifentanil and switching patient recovery to a special post-anesthesia recovery and care unit, shortened therapy times, is safe and economically effective.

Optimizing BM harvesting from normal adult donors.

The experience at a single institution of BM harvesting (BMH) in general anesthetic for allogeneic transplantation from 49 healthy adult donors since March 2002 is presented in detail, together with an analysis of all the donor complications. In this study, we analyzed the advantages through the change from an aspiration needle with one hole (group A, n=18) to a system with additional five side holes (group B, n=31) in April 2005 for faster aspiration of large volumes of BM. In group B, the operation time was reduced by 50%, which is 12 min to date (1006 ml BM). Furthermore, the collection rate (volume BM/time) was significantly increased, namely to 81.9 ml/min in group B. The yields of total nucleated cells and CD34+ cells are nearly identical and adequate in both systems. The proportion of donors treated as day cases--that is, able to be discharged on the same day as the procedure--was 56% in group A and 81% in group B. There was no significant operative site morbidity. BMH accomplished by trained personal is a safe procedure for healthy adult donors on an outpatient basis as standard in our collection center.

The prevalence of postoperative pain in a sample of 1490 surgical inpatients.

BACKGROUND AND OBJECTIVE: To measure the prevalence of postoperative pain, an assessment was made of 1490 surgical inpatients who were receiving postoperative pain treatment according to an acute pain protocol. METHODS: Measurements of pain (scores from 0 to 100 on a visual analogue scale) were obtained three times a day on the day before surgery and on days 0-4 postoperatively; mean pain intensity scores were calculated. Patients were classified as having no pain (score 0-5), mild pain (score 6-40), moderate pain (score 41-74) or severe pain (score 75-100). RESULTS: Moderate or severe pain was reported by 41% of the patients on day 0, 30% on days 1 and 19%, 16% and 14% on days 2, 3 and 4. The prevalence of moderate or severe pain in the abdominal surgery group was high on postoperative days 0-1 (30-55%). A high prevalence of moderate or severe pain was found during the whole of days 1-4 in the extremity surgery group (20-71%) and in the back/spinal surgery group (30-64%). CONCLUSION: We conclude that despite an acute pain protocol, postoperative pain treatment was unsatisfactory, especially after intermediate and major surgical procedures on an extremity or on the spine.

Collagen type VIII expression in human diabetic nephropathy.

BACKGROUND: Collagen type VIII is a non-fibrillar short-chain collagen that may modulate migration, proliferation and adherence of various cells. Only very sparse information exists on collagen type VIII expression in human diabetic nephropathy. MATERIAL AND METHODS: We retrospectively studied mRNA expression for the two collagen type VIII chains (COL8A1 and COL8A2) in 20 biopsies with histologically confirmed diabetic nephropathy by real-time PCR, and compared glomerular and tubular expression with normal kidney [pre-transplant biopsies (n = 10)]. Expression of collagen type VIII was also studied in biopsies from patients with benign nephrosclerosis (BNS; n = 16) and focal-segmental glomerulosclerosis (FSGS; n = 9). RESULTS: A strong specific induction of COL8A1 mRNA was found in diabetic nephropathy in both glomerular and tubular compartments. There was also a robust induction of COL8A2 in diabetic nephropathy, but overall expression was lower than that of COL8A1 transcripts. No significant increase in COL8A1 and COL8A2 mRNAs expression was found in biopsies from patients with BNS and FSGS compared with normal kidneys. The cross-reactivity of the used anti-alpha1(VIII) antibody with human tissue was confirmed by Western blots. Immunohistological analysis revealed only little staining for collagen type VIII in the normal kidney, localized to vessels. There was an up-regulation of collagen type VIII protein expression as shown by immunohistochemistry in the diabetic nephropathy biopsies mainly localized to mesangial cells, tubules and the interstitium. Proteinuria and serum creatinine did not correlate with glomerular or tubular COL8A1 and COL8A2 mRNA expression in diabetic patients. CONCLUSION: Our study systemically investigates collagen type VIII expression in human biopsies. Induction of collagen type VIII was specific for diabetic nephropathy and did not occur in the other renal diseases studied. More specific factors of the diabetic environment are likely involved in the stimulated expression because there was no correlation of collagen type VIII mRNA expression with proteinuria. Since collagen type VIII may influence proliferation and migration of cells, it is possible that an increase in renal expression of collagen type VIII initiates other pathophysiological processes (e.g. proliferation of renal fibroblasts) involved in diabetic nephropathy.

Quantification of beta+ activity generated by hard photons by means of PET.

Positron emission tomography (PET) as a method for quality assurance in radiotherapy is well investigated in the case of therapy with carbon ion beams and successfully applied at the Heavy Ion Medical Accelerator at Chiba (HIMAC), Japan, and the Gesellschaft für Schwerionenforschung (GSI), Germany. By measuring the beta(+) activity distribution during the irradiation (in-beam PET), valuable information on the precision of the dose deposition can be obtained. To extend this efficient technique to other radiation treatment modalities may be worthwhile. For example, since positron emitters are generated by high-energy photons with energies above 20 MeV due to (gamma, n) reactions (predominantly (11)C and (15)O in tissue), in-beam PET seems to be feasible for radiation therapy with high-energy photons as also shown in Geant4 simulations. Quantitative results on the activation of tissue-equivalent materials at hard photon beams were obtained by performing off-beam PET experiments. Homogeneous PMMA phantoms as well as inhomogeneous phantoms were irradiated with high-energy bremsstrahlung. After the irradiation the distributions of the generated positron emitters in the phantoms were measured using a conventional PET scanner. Furthermore, the depth-dose distributions were determined by means of optically stimulated luminescence detectors. In the experiments an activity per dose comparable to that produced in a typical patient irradiation with carbon ions could be achieved for 34 MV bremsstrahlung. In addition, a high contrast in the PET images for materials with different density and stoichiometry could be detected. Thus, further research concerning the development of in-beam PET seems to be worthwhile.

Transdifferentiation of endothelial and renal tubular epithelial cells into myofibroblast-like cells under in vitro conditions: a morphological analysis.

Renal fibrosis is a hallmark of progressive kidney disease and is characterized by an accumulation of extracellular-matrix-synthesizing cells in the glomerulus and tubulointerstitium. This population of myofibroblast-like cells (MFLC) is heterogeneous. It has been experimentally shown, for example, that tubular epithelial cells could change their phenotype into MFLC under certain circumstances, a process called epithelial-mesenchymal transdifferentiation. However, MFLC may also originate from other sources. Therefore, we examined whether endothelial cells (EDC) are able to transdifferentiate into MFLC in vitro. We compared potential differences between syngeneic tubular epithelial cells (EPC) and EDC during transdifferentiation into MFLC using bovine and porcine EDC isolated from pulmonary arteries, and glomerular capillaries. Renal tubular EPC were prepared from bovine renal cortical tissue by collagenase digestion and isolation from homogeneous cell monolayers. Bovine renal tubular EPC stained positive for cytokeratin. Furthermore, tubular EPC selectively incorporated labeled bovine serum albumin, a typical property of differentiated renal tubular cells. EDC were characterized by the absence of epithelial markers (e.g. cytokeratin), but stained positive for vWF. The transdifferentiation of EDC into MFLC occurs sequentially in two steps: First, by a rapid reversible transformation in postconfluent or clonal cultures without the need of cytokine stimulation and second, by a prolonged secondary step in the presence of the transformation-accelerating cytokines and the absence of adherently growing EDC. Thus, EDC that are able to sprout can also irreversibly transdifferentiate into MFLC. On the other hand, prolonged incubation of EPC in the presence of cytokines such as transforming growth factor-beta1 and tumor necrosis factor-alpha leads only to a very small number of MFLC without the ability to further proliferate. Our in vitro data suggest that EDC can more easily transdifferentiate into MFLC than syngeneic renal tubular EPC.

Bilateral hypoglossal nerve injury following the use of the laryngeal mask without the use of nitrous oxide.

Hypoglossal nerve injury is a rare complication of anaesthesia airway management in adults. Until now the use of nitrous oxide for anaesthesia supposedly contributed to this complication. We present a case of bilateral hypoglossal nerve injury following the use of a laryngeal mask airway without the use of nitrous oxide. At the conclusion of 3 h of surgery in extreme side rotation, a 15-year-old boy of 88 kg could not extend his tongue beyond his teeth. An MRI confirmed the absence of pharyngeal haematoma and the absence of thrombosis of the basilar artery. We conclude that even when patients have no medical history and nitrous oxide is not being used, prolongation of the operation in an extreme position might increase the risk of major complications with a laryngeal mask.