The impact of concomitant chronic total occlusion on clinical outcomes in patients undergoing transcatheter aortic valve replacement: a large single-center analysis.

Background: Coronary artery disease (CAD) is a common finding in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). However, the impact on prognosis of chronic total occlusions (CTOs), a drastic expression of CAD, remains unclear. Methods and results: We retrospectively reviewed 1,487 consecutive TAVR cases performed at a single tertiary care medical center. Pre-TAVR angiograms were analyzed for the presence of a CTO. At the time of TAVR, 11.2% (n = 167) patients had a CTO. There was no significant association between the presence of a CTO and in-hospital or 30-day mortality. There was also no difference in long-term survival. LV ejection fraction and mean aortic gradients were lower in the CTO group. Conclusions: Our analysis suggests that concomitant CTO lesions in patients undergoing TAVR differ in their risk profile and clinical findings to patients without CTO. CTO lesion per se were not associated with increased mortality, nevertheless CTOs which supply non-viable myocardium in TAVR population were associated with increased risk of death. Additional research is needed to evaluate the prognostic significance of CTO lesions in TAVR patients.

["That One Can See How it is Supposed to be." Conception, Piloting and Evaluation of an Interprofessional Rehabilitation-Related Module for the Training Courses in Medicine, Nursing, and Physiotherapy]. / "Dass man mal sieht, wie es eigentlich sein sollte." Konzeption, Pilotierung und Evaluation eines interprofessionellen rehabilitationsbezogenen Moduls für die Medizin, Pflege und Physiotherapie.

BACKGROUND: Considering the growing rehabilitative care requirements, good interprofessional cooperation is of central relevance for health care professions and is increasingly demanded. Interprofessional cooperation does not yet play a significant role in health professions' education, despite the fact that it is considered an important element of success in outcome- and patient-centered health care. The field of rehabilitation lacks interprofessional teaching concepts and material. METHODS: An interprofessional team of instructors developed the didactic and thematic concept for the module. The module focuses on rehabilitation and discharge management. The learning objectives were developed based on the National Competency-Based Catalogue of Learning Objectives for Medicine. The formative evaluation was based on a questionnaire filled out by the students and the learning guides. RESULTS: 47 participants took part in three runs. The results of the formative evaluation demonstrate that the module was overall well received. The trainees rated the module more favorably than the medical students. While participants emphasized the good practical eye-to-eye interaction between the professions and the honest feedback conversation, they also pointed to the contrast they perceived to their everyday practice. They also wished for more time having verbal interprofessional exchange. The medical students criticized that interprofessional modules were only offered in their final year. CONCLUSION: To the author's knowledge, this is the first publication of an interprofessional module on rehabilitation and discharge management including piloting and positive evaluation for the three professional groups of medicine, nursing and physical therapy. Improvement suggestions of the participants led to modifications that will be realized in the next version of the module. The course sets important impulses for the further development of interprofessional cooperation and the teaching of rehabilitation-related skills. The modular package is available to other lecturers in a free online platform for rehabilitation-related teaching materials.

Emergency transvenous temporary pacing during rotational atherectomy.

Background: Rotational atherectomy (RA) during percutaneous coronary intervention may cause transient bradycardia or a higher-degree heart block. Traditionally, some operators use prophylactic transvenous pacing wire (TPW) to avoid haemodynamic complications associated with bradycardia. Objective: We sought to establish the frequency of bail-out need for emergency TPW insertion in patients undergoing RA that have received no upfront TPW insertion. Methods: We performed a single-centre retrospective study of all patients undergoing RA between October 2009 and October 2022. Patient characteristics, procedural variables, and in-hospital complications were registered. Results: A total of 331 patients who underwent RA procedure were analysed. No patients underwent prophylactic TPW insertion. The mean age was 73.3 ± 9.1 years, 71.6% (n = 237) were male, while nearly half of the patients were diabetic [N = 158 (47.7%)]. The right coronary artery was the most common target for RA (40.8%), followed by the left anterior descending (34.1%), left circumflex (14.8%), and left main stem artery (10.3%). Altogether 20 (6%) patients required intraprocedural atropine therapy. Emergency TPW insertion was needed in one (0.3%) patient only. Eight (2.4%) patients died, although only one (0.3%) was adjudicated as being possibly related to RA-induced bradycardia. Five patients (1.5%) had ventricular fibrillation arrest, while nine (2.7%) required cardiopulmonary resuscitation. Six (1.8%) procedures were complicated by coronary perforation, two (0.6%) were complicated by tamponade, while 17 (5.1%) patients experienced vascular access complications. Conclusions: Bail-out transvenous temporary pacing is very rarely required during RA. A standby temporary pacing strategy seems reasonable and may avoid unnecessary TPW complications compared with routine use.

Diversity of Borrelia burgdorferi sensu lato in ticks and small mammals from different habitats.

BACKGROUND: Ixodid ticks are important vectors for zoonotic pathogens, with Ixodes ricinus being the most important in Europe. Rodents are hosts of immature life stages of I. ricinus ticks and are considered main reservoirs for tick-borne pathogens, e.g. Borrelia burgdorferi. The aim of this study was to analyse the prevalence as well as genospecies and sequence type (ST) diversity of Borrelia burgdorferi sensu lato in ticks and small mammals from central Germany and to elaborate on the influence of environmental and/or individual host and vector factors on Borrelia prevalence. METHODS: After species identification, 1167 small mammal skin samples and 1094 ticks from vegetation were screened by B. burgdorferi sensu lato real-time polymerase chain reaction, and positive samples were characterized by multilocus sequence typing. Generalized linear (mixed) models were used to estimate how seasonality, small mammal species/tick life stage and habitat affect individual infection status. RESULTS: In total, 10 small mammal species and three tick species, Ixodes ricinus, Ixodes inopinatus (both considered members of the I. ricinus complex) and Dermacentor reticulatus, were investigated. Borrelia DNA was detected in eight host species, i.e. the striped field mouse (Apodemus agrarius), the yellow-necked field mouse (Apodemus flavicollis), the wood mouse (Apodemus sylvaticus), the water vole (Arvicola amphibius), the bank vole (Clethrionomys glareolus), the field vole (Microtus agrestis), the common vole (Microtus arvalis), and the common shrew (Sorex araneus). Two species were Borrelia negative, the greater white-toothed shrew (Crocidura russula) and the pygmy shrew (Sorex minutus). The average prevalence was 6.2%, with two genospecies detected, Borrelia afzelii and Borrelia garinii, and at least three STs that had not been previously reported in small mammals. Borrelia prevalence in small mammals did not differ between seasons. Six genospecies of Borrelia-Borrelia afzelii, Borrelia valaisiana, Borrelia garinii, Borrelia lusitaniae, Borrelia spielmanii, and Borrelia burgdorferi sensu stricto-and 25 STs of Borrelia, of which 12 have not been previously described at all and five have not been previously reported in Germany, were detected in 13% of I. ricinus complex ticks. Prevalence was highest in adult females (25.3%) and lowest in nymphs (11.4%). Prevalence was significantly higher in ticks from grassland (16.8%) compared to forests (11.4%). CONCLUSIONS: The high level of small mammal diversity in this region of Germany seems to be reflected in a wide variety of genospecies and STs of B. burgdorferi.

Influence of Season, Population and Individual Characteristics on the Prevalence of Leptospira spp. in Bank Voles in North-West Germany.

Leptospirosis is a worldwide zoonotic disease with more than 1 million human cases annually. Infections are associated with direct contact to infected animals or indirect contact to contaminated water or soil. As not much is known about the prevalence and host specificity of Leptospira spp. in bank voles (Clethrionomys glareolus), our study aimed to evaluate Leptospira spp. prevalence and genomospecies distribution as well as the influence of season, host abundance and individual characteristics on the Leptospira prevalence. Bank voles, which are abundant and widely distributed in forest habitats, were collected in the years 2018 to 2020 in North-West Germany, covering parts of North Rhine-Westphalia and Lower Saxony. The DNA of 1817 kidney samples was analyzed by real-time PCR targeting the lipl32 gene. Positive samples were further analyzed by targeting the secY gene to determine Leptospira genomospecies and multilocus sequence typing (MLST) to determine the sequence type (ST). The overall prevalence was 7.5% (95% confidence interval: 6.4-8.9). Leptospira interrogans (83.3%), L. kirschneri (11.5%) and L. borgpetersenii (5.2%) were detected in bank voles. Increasing body weight as a proxy for age increased the individual infection probability. Only in years with high bank vole abundance was this probability significantly higher in males than in females. Even if case numbers of human leptospirosis in Germany are low, our study shows that pathogenic Leptospira spp. are present and thus a persisting potential source for human infection.

[Impact of the COVID-19 pandemic on outpatient physical therapy in Germany]. / Einfluss der COVID-19 Pandemie auf die ambulante Physiotherapie.

INTRODUCTION: Due to the COVID-19 pandemic, the German health system has faced major challenges since spring 2020. In addition to restrictions in the inpatient health care sector, the maintenance of outpatient care by health care providers has also been affected by the pandemic-related restrictions. Both a decline in treatment frequencies and temporary practice closures have been observed. The aim of the study was to survey the work and care situation in outpatient physiotherapy practices during the first wave of the pandemic. METHODS: An anonymous online survey including quantitative and qualitative items was conducted among physiotherapists in the outpatient sector in Germany between June 1 and August 31, 2020. The survey is part of the mixed-methods study "ArTheCo", which was conducted throughout Germany including outpatient therapists and patients in physiotherapy, speech therapy and occupational therapy. RESULTS: In total, 577 physiotherapists from all over Germany took part in the survey. During the first wave of the pandemic, the occupancy rate fell below 50% at 45% of the facilities. 15% of the facilities had to close temporarily. Short-time work was announced at 58% of the respondents' practices. This and the implementation of hygiene measures restricted the provision of physiotherapy. This mainly affected patients with a higher risk of a severe clinical course of disease, such as nursing home patients. Due to complex changes in practice organisation and patient care, many of the interviewees felt that their economic existence was threatened and also described a large physical and psychological burden. Existing dissatisfaction seemed to have increased by the pandemic. DISCUSSION: To maintain continuous physical therapy, a reorganisation of the reimbursement system as well as easily accessible, consistent and feasible action plans for practices are needed. In combination with threats to existence due to the pandemic and increasing skill shortage, the outpatient physiotherapeutic care also appears to be threatened beyond the pandemic. CONCLUSION: The current pandemic has highlighted long-standing challenges causing dissatisfaction and making the profession increasingly unattractive for some of the respondents. Political action to support physiotherapists needs to be initiated. This study indicates potential starting points.

Mitigating passive fatigue during monotonous drives with thermal stimuli: Insights into the effect of different stimulation durations.

Driving on monotonous roads has been shown to cause passive fatigue as even non-sleep-deprived drivers suffer from the lack of stimuli. Consequently, alertness is reduced and the risk of accidents increases. To counteract this risk, measures need to be taken to mitigate driver fatigue. While in the past, some studies have been focused on the potential of thermal stimuli to reduce fatigue, their results seem inconclusive. Examining the study conditions in which the thermal stimuli were studied, it becomes obvious that the duration of the thermal stimulus strongly affects perceived fatigue. To better understand this relation, a driving simulator study (n=33) was conducted investigating both a 2min and a 4min thermal stimulus (15öC), where air was circulated on non-sleep-deprived drivers. For the 4min stimulus, patterns of increased sympathetic activity (i.e. significant pupil dilatation and bradycardia) were recorded. Furthermore, participants subjectively rated fatigue significantly lower when the stimuli were applied, and preferred driving with the stimulus. The superior performance of the 4min stimulus can be derived from a longer effect on the physiological data as well as even lower subjective fatigue ratings. Results also point to the limits of thermal stimulation: 6min after the stimuli, the participants no longer feel an effect (based on subjective ratings). Future research on passive fatigue countermeasures should hence build on the identified effect of a 4min cooling stimulus to increase physiological arousal and focus on the opportunities to increase effect duration.

Psychophysiological responses to short-term cooling during a simulated monotonous driving task.

For drivers on monotonous routes, cognitive fatigue causes discomfort and poses an important risk for traffic safety. Countermeasures against this type of fatigue are required and thermal stimulation is one intervention method. Surprisingly, there are hardly studies available to measure the effect of cooling while driving. Hence, to better understand the effect of short-term cooling on the perceived sleepiness of car drivers, a driving simulator study (n = 34) was conducted in which physiological and vehicular data during cooling and control conditions were compared. The evaluation of the study showed that cooling applied during a monotonous drive increased the alertness of the car driver. The sleepiness rankings were significantly lower for the cooling condition. Furthermore, the significant pupillary and electrodermal responses were physiological indicators for increased sympathetic activation. In addition, during cooling a better driving performance was observed. In conclusion, the study shows generally that cooling has a positive short-term effect on drivers' wakefulness; in detail, a cooling period of 3 min delivers best results.

Pathological Vaginal Discharge among Pregnant Women: Pattern of Occurrence and Association in a Population-Based Survey.

This study aimed to assess the prevalence of pathological vaginal discharge and to describe risk factors associated with pregnant women. All women living in the city of Rio Grande, Southern Brazil, who gave birth in 2010 were included in the study. A standardized questionnaire was administered to collect information on demographic, reproductive, and health-related factors and morbidity during pregnancy. The chi-square test was used to compare proportions, and multivariate Poisson regression with robust variance was performed. Of the 2,395 women studied, 43% had pathological vaginal discharge during pregnancy. The adjusted analysis showed that younger women of lower socioeconomic condition, those with a past history of abortion, vaginal discharge in a previous pregnancy, and treated for depression, anemia, and urinary tract infection during their current pregnancy, were more likely to have pathological vaginal discharge. Vaginal discharge during pregnancy was highly prevalent in the sample studied calling for proper risk factor management at the primary care level.

Increased plasma zonulin in patients with sepsis.

INTRODUCTION: Zonulin is a eukaryotic protein structurally similar to Vibrio cholerae's zonula occludens toxin. It plays an important role in the opening of small intestine tight junctions. The loss of gut wall integrity during sepsis might be pivotal and has been described in various experimental as well as human studies. Increased levels of zonulin could be demonstrated in diseases associated with increased intestinal inflammation, such as celiac disease and type 1 diabetes. We therefore investigated the role of plasma levels of zonulin in patients with sepsis as a non-invasive marker of gut wall integrity. MATERIALS AND METHODS: Plasma level of zonulin was measured in 25 patients with sepsis, severe sepsis or septic shock according to ACCP/SCCM criteria at the first day of diagnosed sepsis. 18 non-septic post-surgical ICU-patients and 20 healthy volunteers served as control. Plasma levels were determined by using commercially available ELISA kit. Data are given as median and interquartile range (IQR). RESULTS: Significantly higher plasma concentration of zonulin were found in the sepsis group: 6.61 ng/mL (IQR 3.51-9.46), as compared to the to the post-surgical control group: 3.40 ng/mL (IQR 2.14-5.70) (P = 0.025), as well as to the healthy group: 3.55 ng/mL (IQR 3.14-4.14) (P = 0.008). CONCLUSION: We were able demonstrate elevated levels of plasma zonulin, a potential marker of intestinal permeability in septic patients. Increased zonulin may serve as an additional mechanism for the observed increased intestinal permeability during sepsis and SIRS.

HSP27 and HSP70 serum and urine levels in patients suffering from chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a condition associated with inflammation and high levels of uremic toxins and reactive oxygen species. As a counterregulation to systemic stress heat shock proteins (HSP) are increased expressed to minimize cell death and preserve cell integrity by inhibiting apoptotic pathways. The aim of this study was to determine HSP27 and HSP70 concentrations in sera and urine of patients suffering from CKD. METHODS: Concentrations of HSP27 and HSP70 in urine and serum were determined in 119 patients with CKD stages 1 to 5 and 23 healthy volunteers by using ELISA technique. RESULTS: HSP27 serum levels were significantly elevated in patients suffering from CKD stages 3 to 5 as well as fractional HSP27 excretion in stages 2-5 versus healthy controls. Absolute HSP70 urinary values were significantly elevated in stages 4 and 5 and fractional HSP70 excretion was increased in stage 5 compared to controls. Moreover, ROC curve analysis showed the potential of urine and especially serum HSP levels to identify various stages of CKD. CONCLUSION: We provide evidence for elevated HSP27 concentrations in serum and urine and increased HSP70 excretion levels in patients suffering from CKD. Moreover, our results show that HSP levels might offer potential to examine the stages of CKD as well as the disease course which could further promote individually adjusted treatment planning.

[Percutaneous endoscopic gastrostomy-tube for a patient with glioblastoma to enable his admission into a nursing home]. / PEG-Sonde für einen Patienten mit Glioblastom, um seine Aufnahme in ein Pflegeheim zu ermöglichen?

The medical care for people in the end-stage of their carcinoma-disease demands extensive medical and nursing resources. If the admission to a hospice is not possible because of financial and personal reasons, or the medical care at home cannot be fulfilled personnel, a medical care in a nursing home would be possible for some patients on condition that a stable general condition and the support of mobile palliative teams are given. Besides a practicable pain therapy and the control of symptoms the hydration and ingestion are the criteria for the approval to a possible admission to a nursing home. If the ingestion is only limited possible respectively impossible and no advance directive respectively nor provision full power can be submitted, the admission is often denied, because mainly the people occupying a nursing profession are afraid to be situated in an ethic or lawful dispute situation, despite comprehensive information.

The use of reconstructed human epidermis for skin absorption testing: Results of the validation study.

A formal validation study was performed, in order to investigate whether the commercially-available reconstructed human epidermis (RHE) models, EPISKIN, EpiDerm and SkinEthic, are suitable for in vitro skin absorption testing. The skin types currently recommended in the OECD Test Guideline 428, namely, ex vivo human epidermis and pig skin, were used as references. Based on the promising outcome of the prevalidation study, the panel of test substances was enlarged to nine substances, covering a wider spectrum of physicochemical properties. The substances were tested under both infinite-dose and finite-dose conditions, in ten laboratories, under strictly controlled conditions. The data were subjected to independent statistical analyses. Intra-laboratory and inter-laboratory variability contributed almost equally to the total variability, which was in the same range as that in preceding studies. In general, permeation of the RHE models exceeded that of human epidermis and pig skin (the SkinEthic RHE was found to be the most permeable), yet the ranking of substance permeation through the three tested RHE models and the pig skin reflected the permeation through human epidermis. In addition, both infinite-dose and finite-dose experiments are feasible with RHE models. The RHE models did not show the expected significantly better reproducibility, as compared to excised skin, despite a tendency toward lower variability of the data. Importantly, however, the permeation data showed a sufficient correlation between all the preparations examined. Thus, the RHE models, EPISKIN, EpiDerm and SkinEthic, are appropriate alternatives to human and pig skin, for the in vitro assessment of the permeation and penetration of substances when applied as aqueous solutions.

The automated, accurate and reproducible determination of steady-state permeation parameters from percutaneous permeation data.

Procedures for the in vitro determination of percutaneous permeation with Franz diffusion cells are widely accepted. However, the calculation of relevant endpoints, such as the steady-state flux (J) and the permeation coefficient (P(app)), still depends on visual data inspection or an approximation of the steady-state flux as the maximum observed absorption rate. As both these approaches must be considered inappropriate, an automated and reproducible algorithm to analyse permeation data is presented. The method detects both lag-times and non-linear data resulting from substance accumulation in the acceptor compartment of static diffusion cells. It was evaluated by using simulated data, and data from experiments with caffeine and testosterone on bovine udder skin and human reconstituted epidermis (SkinEthic), which represent model barriers with high and low barrier strengths, respectively. It was shown that the algorithm is a suitable method for the identification of steady-state ranges in permeation data. If used on data generated with appropriate experimental approaches, it is a reproducible and time-saving alternative to the visual analysis of diffusion data.

Multicompartmental fate of persistent substances. Comparison of predictions from multi-media box models and a multicompartment chemistry-atmospheric transport model.

BACKGROUND, AIM AND SCOPE: Modelling of the fate of environmental chemicals can be done by relatively simple multi-media box models or using complex atmospheric transport models. It was the aim of this work to compare the results obtained for both types of models using a small set of non-ionic and non-polar or moderately polar organic chemicals, known to be distributed over long distances. MATERIALS AND METHODS: Predictions of multimedia exposure models of different types, namely three multimedia mass-balance box models (MBMs), two in the steady state and one in the non-steady state mode, and one non-steady state multicompartment chemistry-atmospheric transport model (MCTM), are compared for the first time. The models used are SimpleBox, Chemrange, the MPI-MBM and the MPI-MCTM. The target parameters addressed are compartmental distributions (i.e. mass fractions in the compartments), overall environmental residence time (i.e. overall persistence and eventually including other final sinks, such as loss to the deep sea) and a measure for the long-range transport potential. These are derived for atrazine, benz-[a]-pyrene, DDT, alpha and gamma-hexachlorocyclohexane, methyl parathion and various modes of substance entry into the model world. RESULTS AND DISCUSSION: Compartmental distributions in steady state were compared. Steady state needed 2-10 years to be established in the MCTM. The highest fraction of the substances in air is predicted by the MCTM. Accordingly, the other models predict longer substance persistence in most cases. The results suggest that temperature affects the compartmental distribution more in the box models, while it is only one among many climate factors acting in the transport model. The representation of final sinks in the models, e.g. burial in the sediment, is key for model-based compartmental distribution and persistence predictions. There is a tendency of MBMs to overestimate substance sinks in air and to underestimate atmospheric transport velocity as a consequence of the neglection of the temporal and spatial variabilities of these parameters. Therefore, the long-range transport potential in air derived from MCTM simulations exceeds the one from Chemrange in most cases and least for substances which undergo slow degradation in air. CONCLUSIONS AND PERSPECTIVES: MBMs should be improved such as to ascertain that the significance of the atmosphere for the multicompartmental cycling is not systematically underestimated. Both types of models should be improved such as to cover degradation in air in the particle-bound state and transport via ocean currents. A detailed understanding of the deviations observed in this work and elsewhere should be gained and multimedia fate box models could then be 'tuned in' to match better the results of comprehensive multicompartmental transport models.

Assessment of the skin irritation potential of chemicals by using the SkinEthic reconstructed human epidermal model and the common skin irritation protocol evaluated in the ECVAM skin irritation validation study.

Currently, two reconstructed human skin models, EpiDerm and EPISKIN are being evaluated in an ECVAM skin irritation validation study. A common skin irritation protocol has been developed, differing only in minor technical details for the two models. A small-scale study, applying this common skin irritation protocol to the SkinEthic reconstructed human epidermis (RHE), was performed at ZEBET at the BfR, Berlin, Germany, to consider whether this protocol could be successfully transferred to another epidermal model. Twenty substances from Phase III of the ECVAM prevalidation study on skin irritation were tested with the SkinEthic RHE. After minor, model-specific adaptations for the SkinEthic RHE, almost identical results to those obtained with the EpiDerm and EPISKIN models were achieved. The overall accuracy of the method was more than 80%, indicating a reliable prediction of the skin irritation potential of the tested chemicals when compared to in vivo rabbit data. As a next step, inter laboratory reproducibility was assessed in a study conducted between ZEBET and the Department of Experimental Toxicology, Schering AG, Berlin, Germany. Six coded substances were tested in both laboratories, with three different batches of the SkinEthic model. The assay results showed good reproducibility and correct predictions of the skin irritation potential for all six test chemicals. The results obtained with the SkinEthic RHE and the common protocol were reproducible in both phases, and the overall outcome is very similar to that of earlier studies with the EPISKIN and EpiDerm models. Therefore, the SkinEthic skin irritation assay test protocol can now be evaluated in a formal "catch-up" validation study.

Reconstructed human epidermis for skin absorption testing: results of the German prevalidation study.

Exposure to chemicals absorbed by the skin can threaten human health. In order to standardise the predictive testing of percutaneous absorption for regulatory purposes, the OECD adopted guideline 428, which describes methods for assessing absorption by using human and animal skin. In this study, a protocol based on the OECD principles was developed and prevalidated by using reconstructed human epidermis (RHE). The permeation of the OECD standard compounds, caffeine and testosterone, through commercially available RHE models was compared to that of human epidermis and animal skin. In comparison to human epidermis, the permeation of the chemicals was overestimated when using RHE. The following ranking of the permeation coefficients for testosterone was obtained: SkinEthic > EpiDerm, EPISKIN > human epidermis, bovine udder skin, pig skin. The ranking for caffeine was: SkinEthic, EPISKIN > bovine udder skin, EpiDerm, pig skin, human epidermis. The inter-laboratory and intra-laboratory reproducibility was good. Long and variable lag times, which are a matter of concern when using human and pig skin, did not occur with RHE. Due to the successful transfer of the protocol, it is now in the validation process.

Assessment of the human epidermis model SkinEthic RHE for in vitro skin corrosion testing of chemicals according to new OECD TG 431.

Based on two successfully completed ECVAM validation studies for in vitro skin corrosion testing of chemicals, the National Co-ordinators of OECD Test Guideline Programme endorsed in 2002 two new test guidelines: TG 430 'Transcutaneous Electrical Resistance assay' and TG 431 'Human Skin Model Test'. To allow all suitable in vitro human reconstructed (dermal or epidermal) models to be used for skin corrosion testing, the OECD TG 431 defines general and functional conditions that the model must meet before it will be routinely used for skin corrosion testing. In addition, the guideline requires correct prediction of 12 reference chemicals and assessment of intra- and inter-laboratory variability. To show that the OECD TG 431 concept works, in 2003 ZEBET tested several chemicals from the ECVAM validation trials on the SkinEthic reconstituted human epidermal (RHE) model. Based on knowledge that reconstructed human skin models perform similarly in toxicological studies, it was decided to adopt the validated EpiDerm skin corrosion test protocol and prediction model to the SkinEthic model. After minor technical changes, classifications were obtained in concordance with those reported for the validated human skin models EPISKIN and EpiDerm. To allow adequate determination of inter-laboratory reproducibility, a blind trial was conducted in three laboratories -- ZEBET (D), Safepharm (UK) and BASF (D), in which the 12 endorsed reference chemicals were tested. Results obtained with the SkinEthic epidermal model were reproducible, both within and between laboratories, and over time. Concordance between the in vitro predictions of skin corrosivity potential obtained with the SkinEthic model and the predictions obtained with the accepted tests of OECD TG 430 and TG 431 was very good. The new test was able to distinguish between corrosive and non-corrosive reference chemicals with an accuracy of 93%.

Freedom in responsibility: on the relevance of "sin" as a hermeneutic guiding principle in bioethical decision making.

This essay deals with questions of responsibility concerning technology, in particular, gene technology and the special problem of research on embryos. I raise issues concerning the extent of humans' authority to act and the limits of human freedom. In what way is that freedom given, and what kind of responsibility results from it? By discussing various concepts of human freedom in the tradition of European philosophy, as juxtaposed to the Protestant understanding of freedom, this essay discusses the restricting limits, and the obligation to take responsibility. It will turn out that the question concerning freedom cannot be answered without understanding what being human involves. From a Christian perspective, this implies that the foundational relationship between human freedom and sin will be central to an assessment of the human ability to take responsibility. By obliterating the limits of human freedom, sin jeopardizes the very essence of that freedom. The project of taking into account the sinful state of the human condition thus aims at developing a realistic picture of the authority of humans in action, even in view of the human tasks of promoting science and research.