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Manure is widely used as a fertilizer and applied to agricultural land. It may contain highly active chemicals like veterinary medicinal products or biocides, which enter into the environment by this pathway. This is recognized by several regulatory frameworks, however, a detailed method for examining the transformation of chemicals in manure was lacking. This article describes the validation of a method for studying the anaerobic transformation of chemicals in pig and cattle liquid manure. Different steps are covered with an emphasis on the validation ring test and the OECD (Organisation for Economic Cooperation and Development) process that led to the recent adoption of the method as OECD Test Guideline (TG) 320.

International audience; Bioconcentration factors (BCF) for regulatory purposes are conventionally determined experimentally by aqueous exposure bioconcentration fish tests according to OECD test guideline (TG) 305. Fish bioconcentration studies are time consuming, expensive, and use vertebrate organisms in the range of 100-200 organisms per study. The availability of alternative methods may help to reduce the use of fish for BCF testing. The Hyalella azteca Bioconcentration Test (HYBIT) provides a non-vertebrate alternative for fish bioconcentration studies. The suitability of H. azteca as an alternative test organism for bioconcentration studies was recently investigated. Eighteen substances of different hydrophobicity (log KOW 0.7 - 7.8) were tested under flow-through or semi-static conditions to determine steady-state and kinetic bioconcentration factors (BCFSS and BCFK). It has been shown that the BCFs obtained from bioconcentration studies with the freshwater amphipod H. azteca correlate significantly (r²=0.69) with fish BCF values described in the literature. Thus, H. azteca BCF values can be assessed in accordance with the standard B criteria, e.g. BCF > 2000 (REACH), and thereby enable the prediction of B or non-B classification in the standard fish test. Generally, technical (smaller-scale test systems) and economic reasons (less time-consuming, more cost-efficient) favour the use of H. azteca over fish in bioconcentration studies. In addition, significantly smaller amounts of test substance are required compared to the flow-through test with fish. A protocol for carrying out bioconcentration tests with the aquatic invertebrate species H. azteca under standardized conditions has been developed as part of the project CEFIC-LRI ECO40. This protocol includes both, the flow-through and semi-static test design. Validation was needed to confirm the transferability of the test protocols and to prove the reproducibility of the results obtained in order to support the development of a new OECD TG. For this purpose, a multi-laboratory ring trial involving the HYBIT was carried out in 2020. The ring test has confirmed the high potential of the Hyalella azteca Bioconcentration Test (HYBIT) to be used as a non-vertebrate alternative for bioconcentration studies. The transferability of the test protocols (semi-static and flow-through approach) as well as the reproducibility of the results obtained was proven supporting the development of a new OECD TG.

Information about acute fish toxicity is routinely required in many jurisdictions for environmental risk assessment of chemicals. This information is typically obtained using a 96-hour juvenile fish test for lethality according to OECD test guideline (TG) 203 or equivalent regional guidelines. However, TG 203 has never been validated using the criteria currently required for new test methods including alternative methods. Characterization of the practicality and validity of TG 203 is important to provide a benchmark for alternative methods. This contribution systematically summarizes the available knowledge on limitations and uncertainties of TG 203, based on methodological, statistical, and biological considerations. Uncertainties stem from the historic flexibility (e.g., use of a broad range of species) and constraints of the basic test design (e.g., no replication). Other sources of uncertainty arise from environmental safety extrapolation based on TG 203 data. Environmental extrapolation models, combined with data from alternative methods, including mechanistic indicators of toxicity, may provide at least the same level of environmental protection. Yet, most importantly, the 3R advantages of alternative methods allow a better standardization, characterization, and an improved basic study design. This can enhance data reliability and thus facilitate the comparison of chemical toxicity, as well as the environmental classifications and prediction of no-effect concentrations of chemicals. Combined with the 3R gains and the potential for higher throughput, a reliable assessment of more chemicals can be achieved, leading to improved environmental protection., ALTEX, 38 (1), ISSN:1868-8551, ISSN:0946-7785, ISSN:1868-596X

Objective To assess delivery room management of infants born preterm at 4 Level III perinatal centers in 3 European countries.Study design This was a prospective, multicenter observational study. Management at birth was video-recorded and evaluated (Interact version 9.6.1; Mangold-International, Arnstorf, Germany). Data were analyzed and compared within and between centers.Results The infants (n = 138) differed significantly with respect to the median (25%, 75%) birth weight (grams) (Center A: 1200 [700, 1550]; Center B: 990 [719, 1240]; Center C: 1174 [835, 1435]; Center D: 1323 [971, 1515] [B vs A, C, D: P < .05]), gestational week (Center A: 28.4 [26.3, 30.0]; Center B: 27.9 [26.7, 29.6]; Center C: 29.3 [26.4, 31.0]; Center D: 30.3 [28.0, 31.9]), Apgar scores, rates of cesarean delivery, and time spent in the delivery room. Management differed significantly for frequency and drying time, rates of electrocardiographic monitoring, suctioning or stimulation, and for fundamental interventions such as time for achieving a reliable peripheral oxygen saturation signal (seconds) (Center A: 97.6 +/- 79.3; Center B: 65.1 +/- 116.2; Center C: 97.1 +/- 67.0; Center D: 114.4 +/- 140.5; B vs A, C, D: P < .001) and time for intubation (seconds) (Center A: 48.7 +/- 4.2; Center B: 49.0 +/- 30.7; Center C: 69.1 +/- 37.9; Center D: 65.1 +/- 23.8; B vs D, P < .025). Mean procedural times did not meet guideline recommendations. The sequence of interventions was similar at all centers.Conclusions The Video Apgar Study showed great variability in and between 4 neonatal centers in Europe. The study also showed it is difficult to adhere to published guidelines for recommended times for important, basic measures such as peripheral oxygen saturation measurements and intubation.

ZusammenfassungSeit der ersten Publikation der Lernziele für den Querschnittsbereich „Rehabilitation, Physikalische Medizin, Naturheilverfahren (RPMN)“ im Medizinstudium im Jahr 2004 ist auf Grund heterogener Lehrangebote an den Fakultäten sowie neuer Impulse v. a. aus dem „Nationalen Kompetenzbasierten Lernzielkatalog Medizin (NKLM)“ und dem „Masterplan Medizinstudium 2020“ eine Revision sinnvoll. Deshalb haben die Deutsche Gesellschaft für Rehabilitationswissenschaften e. V. und die Deutsche Gesellschaft für Physikalische Medizin und Rehabilitation e. V. in einem strukturierten Konsensprozess nach der DELPHI-Methodik die Lernziele reduziert und übersichtlicher gegliedert. Besonders relevante Lernziele werden hervorgehoben. Alle Lernziele werden der kognitiven und Methodenkompetenz (Level 1 „Kennen und Können“) bzw. der Handlungskompetenz (Level 2 „Beherrschen“) zugeordnet. Auf die Lernziele im weniger detaillierten NKLM wird konkret verwiesen. Mit diesem revidierten Lernzielkatalog wird ein Beitrag zur Weiterentwicklung der kompetenzbasierten und in Kernbereichen homogeneren humanmedizinischen Lehre zu RPMN an den Fakultäten geleistet.

Um die aktuelle Entwicklung der rehabilitationsbezogenen Lehre im Querschnittsbereich Rehabilitation, Physikalische Medizin, Naturheilverfahren (Q12) hinsichtlich Durchfuhrung, Inhalte, Prufungen und Lehrevaluation an den Medizinischen Fakultaten zu erheben, wurde von der DGRW im Sommer 2015 eine weitere Fakultatenbefragung durchgefuhrt. Vertreter aller humanmedizinischen Studiengange in Deutschland (n=41) erhielten postalisch einen pseudonymisierten standardisierten Fragebogen. Der Rucklauf betragt 76% (n=31). Die Halfte (48%) der Einrichtungen gab Lehr-/Forschungsbereiche zu mindestens einem der 3 Teilbereiche des Q12 an, was in Verbindung mit teilweise unterschiedlicher Q12-Gestaltung steht. Modellstudiengange nutzen durchschnittlich 2 Semester mehr fur die Q12-Lehre als die Regelstudiengange. Von mehr als Dreiviertel der Regelstudiengange und allen anderen Studiengangen wird berichtet, dass nicht-arztliche Dozenten an der Durchfuhrung der Lehre beteiligt sind. In Bezug auf Leistungsnachweise sind Multiple-Choice-Klausuren weiterhin die haufigste Prufungsform (94%). Fast alle Studiengange evaluieren ihre rehabilitationsbezogenen Lehrveranstaltungen; fur die Halfte aller Fakultaten hat dies Konsequenzen bzgl. der Vergabe von Leistungsorientierten Mitteln (LOM). Auch mehr als 10 Jahre nach Implementierung des Q12 wird die rehabilitationsbezogene Lehre im Hinblick auf Durchfuhrung, Inhalte und Didaktik sehr unterschiedlich gestaltet. Fur die zukunftige Entwicklung der Q12-Lehre an den humanmedizinischen Studiengangen in Deutschland werden u. a. die Implementierung des Nationalen Kompetenzbasierten Lernzielkatalog Medizin an den einzelnen Standorten und die zunehmenden Studiengange mit auslandischem Abschluss von Interesse sein.

The exposome encompasses an individual's exposure to exogenous chemicals, as well as endogenous chemicals that are produced or altered in response to external stressors. While the exposome concept has been established for human health, its principles can be extended to include broader ecological issues. The assessment of exposure is tightly interlinked with hazard assessment. Here, we explore if mechanistic understanding of the causal links between exposure and adverse effects on human health and the environment can be improved by integrating the exposome approach with the adverse outcome pathway (AOP) concept that structures and organizes the sequence of biological events from an initial molecular interaction of a chemical with a biological target to an adverse outcome. Complementing exposome research with the AOP concept may facilitate a mechanistic understanding of stress-induced adverse effects, examine the relative contributions from various components of the exposome, determine the primary risk drivers in complex mixtures, and promote an integrative assessment of chemical risks for both human and environmental health. Keywords: Exposome, AOP, Systems toxicology, Systems biology, Systems chemistry, Risk assessment

The environmental enrichment (EE) paradigm is regarded as a useful tool to create a physical and intellectual stimulation for laboratory rodents and has been used in a variety of Alzheimer disease (AD) mouse models. However, the results of these studies have been conflicting as EE had inconsistent effects on memory performance, Aβ deposition, inflammatory status and other pathological outcomes depending on the AD model. Here, we studied the influence of a lifelong EE on the widely used 5XFAD mouse model, representing the main pathological features of AD. Although 11 months of enriched housing led to an improved survival rate and a partial rescue of motor performance, no beneficial effects in terms of anxiety phenotype, working memory performance, Aβ plaque load, Aβ1–42 levels, endogenous APP processing and inflammatory status were observed in 5XFAD mice. Concordantly, no changes in expression levels of BACE1 or Aβ-degrading enzymes like neprilysin or insulin-degrading enzyme could be detected in active mice. The 5XFAD model develops a relatively fast and aggressive pathology and therefore presents a model for early onset familial AD. Our results suggest that an intervention like EE might be too mild to counteract the fast disease progression seen in this model. Therefore, our data provide evidence that the effects of physical and cognitive stimulation vary depending on the severity of the pathology of the model and therefore might be more beneficial in models developing a milder AD phenotype.

Malaria recurrences after an initially successful therapy and malarial fever occurring a long time after infection are well-known problems in malariology. Currently, two distinct types of malaria recurrences are defined: recrudescence and relapse. A recrudescence is thought to originate from circulating Plasmodium blood stages which do not cause fever before a certain level of a microscopically detectable parasitemia is reached. Contrary, a relapse is thought to originate from quiescent intracellular hepatic parasite stages called hypnozoites. Recrudescences would typically occur in infections due to Plasmodium falciparum. Plasmodium knowlesi, and Plasmodium malariae, whereas relapses would be caused exclusively by Plasmodium vivax and Plasmodium ovale. This schematic view is, however, insufficiently supported by experimental evidence. For instance, hypnozoites of P. ovale have never been experimentally documented. On the other hand, the nonfinding of P. malariae hypnozoites turned into the proof for the nonexistence of P. malariae hypnozoites. Clinical relapse-type recurrences have been observed in both P. ovale and P. malariae infections, and decade-long incubation times have also been reported in P. falciparum infections. We propose a gradual hypothesis in accordance with the continuity concept of biological evolution: both, relapse and recrudescence may be potentially caused by all Plasmodium spp. We hypothesize that the difference between the various Plasmodium spp. is quantitative rather than qualitative: there are Plasmodium spp. which frequently cause relapses such as P. vivax, particularly the P.v. Chesson strain, species which cause relapses less frequently, such as P. ovale and sometimes P. malariae, and species which may exceptionally cause relapses such as P. falciparum. All species may cause recrudescences. As clinical consequences, we propose that 8-aminquinolines may be considered in a relapse-type recrudescence regardless of the causal Plasmodium sp., whereas primaquine relapse prevention might not be routinely indicated in malaria due to P. ovale.

Brain accumulation and aggregation of amyloid-β (Aβ) peptides is a critical step in the pathogenesis of Alzheimer's disease (AD). Full-length Aβ peptides (mainly Aβ1-40 and Aβ1-42) are produced through sequential proteolytic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. However, studies of autopsy brain samples from AD patients have demonstrated that a large fraction of insoluble Aβ peptides are truncated at the N-terminus, with Aβ4-x peptides being particularly abundant. Aβ4-x peptides are highly aggregation prone, but their origin and any proteases involved in their generation are unknown. We have identified a recognition site for the secreted metalloprotease ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) in the Aβ peptide sequence, which facilitates Aβ4-x peptide generation. Inducible overexpression of ADAMTS4 in HEK293 cells resulted in the secretion of Aβ4-40 but unchanged levels of Aβ1-x peptides. In the 5xFAD mouse model of amyloidosis, Aβ4-x peptides were present not only in amyloid plaque cores and vessel walls, but also in white matter structures co-localized with axonal APP. In the ADAMTS4-/- knockout background, Aβ4-40 levels were reduced confirming a pivotal role of ADAMTS4 in vivo. Surprisingly, in the adult murine brain, ADAMTS4 was exclusively expressed in oligodendrocytes. Cultured oligodendrocytes secreted a variety of Aβ species, but Aβ4-40 peptides were absent in cultures derived from ADAMTS4-/- mice indicating that the enzyme was essential for Aβ4-x production in this cell type. These findings establish an enzymatic mechanism for the generation of Aβ4-x peptides. They further identify oligodendrocytes as a source of these highly amyloidogenic Aβ peptides.

Since the first publication of learning objectives for the interdisciplinary subject "Rehabilitation, Physical Medicine, Naturopathic Treatment" in undergraduate medical education in 2004 a revision is reasonable due to heterogenous teaching programmes in the faculties and the introduction of the National Competence Based Catalogue of Learning Objectives in Medicine as well as the "Masterplan Medical Education 2020". Therefore the German Society of Rehabilitation Science and the German Society of Physical Medicine and Rehabilitation started a structured consensus process using the DELPHI-method to reduce the learning objectives and arrange them more clearly. Objectives of particular significance are emphasised. All learning objectives are assigned to the cognitive and methodological level 1 or to the action level 2. The learning objectives refer to the less detailed National Competence Based Catalogue of Learning Objectives in Medicine. The revised learning objectives will contribute to further progress in competence based and more homogenous medical teaching in core objectives of Rehabilitation, Physical Medicine, and Naturopathic Treatment in the faculties.Seit der ersten Publikation der Lernziele für den Querschnittsbereich „Rehabilitation, Physikalische Medizin, Naturheilverfahren (RPMN)“ im Medizinstudium im Jahr 2004 ist auf Grund heterogener Lehrangebote an den Fakultäten sowie neuer Impulse v. a. aus dem „Nationalen Kompetenzbasierten Lernzielkatalog Medizin (NKLM)“ und dem „Masterplan Medizinstudium 2020“ eine Revision sinnvoll. Deshalb haben die Deutsche Gesellschaft für Rehabilitationswissenschaften e. V. und die Deutsche Gesellschaft für Physikalische Medizin und Rehabilitation e. V. in einem strukturierten Konsensprozess nach der DELPHI-Methodik die Lernziele reduziert und übersichtlicher gegliedert. Besonders relevante Lernziele werden hervorgehoben. Alle Lernziele werden der kognitiven und Methodenkompetenz (Level 1 „Kennen und Können“) bzw. der Handlungskompetenz (Level 2 „Beherrschen“) zugeordnet. Auf die Lernziele im weniger detaillierten NKLM wird konkret verwiesen. Mit diesem revidierten Lernzielkatalog wird ein Beitrag zur Weiterentwicklung der kompetenzbasierten und in Kernbereichen homogeneren humanmedizinischen Lehre zu RPMN an den Fakultäten geleistet.

Disrupted in Schizophrenia 1 (DISC1) is a prominent gene in mental illness research, encoding a scaffold protein known to be of importance in the developing cerebral cortex. Reelin is a critical extracellular protein for development and lamination of the prenatal cortex and which has also been independently implicated in mental illness. Regulation of reelin activity occurs through processing by the metalloproteinases ADAMTS-4 and ADAMTS-5. Through cross-breeding of heterozygous transgenic DISC1 mice with heterozygous reeler mice, which have reduced reelin, pups heterozygous for both phenotypes were generated. From these, we determine that transgenic DISC1 leads to a reduction in the processing of reelin, with implications for its downstream signalling element Dab1. An effect of DISC1 on reelin processing was confirmed in vitro, and revealed that intracellular DISC1 affects ADAMTS-4 protein, which in turn is exported and affects processing of extracellular reelin. In transgenic rat cortical cultures, an effect of DISC1 on reelin processing could also be seen specifically in early, immature neurons, but was lost in calretinin and reelin-positive mature neurons, suggesting cell-type specificity. DISC1 therefore acts upstream of reelin in the perinatal cerebral cortex in a cell type/time specific manner, leading to regulation of its activity through altered proteolytic cleavage. Thus a functional link is demonstrated between two proteins, each of independent importance for both cortical development and associated cognitive functions leading to behavioural maladaptation and mental illness.

A discussion paper was developed by a panel of experts of the German Federal Environment Agency (UBA) contributing to the on-going debate on the identification, assessment and management of endocrine disruptors with a view to protect wildlife according to the EU substance legislation (plant protection products, biocides, industrial chemicals). Based on a critical synthesis of the state-of-the-art regarding regulatory requirements, testing methods, assessment schemes, decision-making criteria and risk management options, we advise an appropriate and consistent implementation of this important subject into existing chemicals legislation in Europe. Our proposal for a balanced risk management of endocrine disruptors essentially advocates transparent regulatory decision making based on a scientifically robust weight of evidence approach and an adequate risk management consistent across different legislations. With respect to the latter, a more explicit consideration of the principle of proportionality of regulatory decision making and socio-economic benefits in the on-going debate is further encouraged.

Quartan malaria due to Plasmodium malariae is commonly regarded as being preventable by current antimalarials. A case of P. malariae infection occurred in spite of previous treatment of Plasmodium falciparum malaria 4 months earlier with a full therapy course of intravenous quinine hydrochloride and oral doxycycline followed by artemether + lumefantrine. Since the patient was not anymore exposed to agents of malaria in the meantime, a new infection by P. malariae after therapy is unlikely. The present observation is difficult to explain by the current view on the origin of latent P. malariae infections and recurrences which are thought to arise from intra-erythrocytic development stages susceptible to common antimalarials. The most likely explanation of our observation is a delayed pre-erythrocytic development. The latency between infection by P. malariae and the quartan malaria fever attack might have been extended further by an initial subclinical circulation of a low number of intra-erythrocytic asexual parasites in the blood stream preceeding the clinical quartan malaria breakthrough.

In 2000, the World Health Organization (WHO) published an ultrasound field protocol for assessing morbidity due to schistosomiasis. The present study aims to review the acceptance of the WHO protocol for Schistosoma haematobium. A PubMed literature research using the keywords "ultrasound OR ultrasonography (US) AND schistosomiasis," "US AND S. haematobium," "US AND urinary schistosomiasis" from 2001 through 2014 was performed. Thirty-eight eligible publications reporting on 17,861 patients from 13 endemic and 2 non-endemic countries were analysed. Of these, 33 referred to field studies on 17,317 patients. The Niamey protocol was applied to 15,367/17,317 (88.74%) patients in 23/33 (69.70%) of field studies (all studies: 15,649/17,861 [87.61%] patients (25/38 [68.42%] studies). The acceptance of the protocol by single country in field studies varied from 0 to 100%. It varied over time between 55.56% (5/9) in the period from 2001 to 2004, to 87.50% (7/8) from 2005 to 2008, to 62.50% (5/8) from 2009 to 2011 and 75.00% (6/8) from 2012 through 2014 (all studies: 50% [5/10], 88.89% [8/9], 62.50% [5/8], 63.64% [7/11], respectively). The Niamey protocol was applied also in 2/5 hospital studies in 282/544 (51.84%) patients.The usefulness of the WHO protocol for S. haematobium infections is confirmed by its worldwide acceptance. Some simplifications might facilitate its use also for focused ultrasound examinations performed by less skilled examiners. Organ abnormalities due to schistosomiasis detectable by ultrasonography not yet covered by the WHO protocol should be added to the additional investigations section.

Stages obtained from two Asian Babesia gibsoni-isolates cultured in vitro were studied by means of transmission electron microscopy and compared to strains of B. canis cultured in vitro. While the developmental stages of the latter preserved their shape in culture, many of the initially small stages of the B. gibsoni strains grew considerably and often looked rather similar to B. canis.

A The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were analytically confirmed for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control) were exposed for 96. h to chemicals. Four apical endpoints were recorded daily as indicators of acute lethality: coagulation of the embryo, lack of somite formation, non-detachment of the tail bud from the yolk sac and lack of heartbeat. Results (LC50 values for 48/96. h exposure) show that the ZFET is a robust method with a good intra- and inter-laboratory reproducibility (CV. 30%) for some very toxic or volatile chemicals, and chemicals tested close to their limit of solubility. The ZFET is now available as OECD Test Guideline 236.Considering the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013) in their retrospective analysis of acute fish toxicity and fish embryo acute toxicity data, the ZFET is ready to be considered for acute fish toxicity for regulatory purposes. © 2014 The Authors.

Anamnese und Diagnostik: Ein 20-jahriger Afrikaner, Asylbewerber aus Sierra Leone, wurde wegen einer Anamie, Eosinophilie, erhohten Leberwerten und Hepatosplenomegalie stationar eingewiesen. Eine arztliche Untersuchung war bei der Einreise nach Deutschland durchgefuhrt worden. Dabei durchgefuhrte Stuhluntersuchungen sowie serologische Untersuchungen auf Lues, HIV und Hepatitis B hatten keine Auffalligkeiten ergeben. Erst die parasitologische Stuhluntersuchung (Anreicherungsverfahren mit Merthiolat-Formaldehyd-Losung [MIF]) erbrachte den Nachweis der Eier von Schistosoma mansoni und somit die Diagnose einer Bilharziose. Zur Wurmeidiagnostik sind haufig wiederholte Stuhluntersuchungen erforderlich, die sich nicht auf die Untersuchung des Nativstuhles beschranken durfen. Das Staging der Erkran-kung ergab den Nachweis einer interstinalen Polyposis, einer periportalen Fibrose und einer portalen Hypertension mit Osophagusvarizen. Therapie und Verlauf: Nach der Therapie mit Praziquantel uber 2 Tage waren keine Parasiten im Stuhl mehr nachweisbar. Die portale Hypertension bedarf der weiteren gastroenterologischen Uberwachung, da die fortgeschrittene Leberfibrose trotz erfolgreicher antiparasitarer Therapie persistiert. Schlussfolgerung: Die zunehmende Mobilitat der Weltbevolkerung wird auch den Arzt in Industrielandern mehr und mehr mit “tropenspezifischen” Erkrankungen konfrontieren.

Tests with vertebrates are an integral part of environmental hazard identification and risk assessment of chemicals, plant protection products, pharmaceuticals, biocides, feed additives and effluents. These tests raise ethical and economic concerns and are considered as inappropriate for assessing all of the substances and effluents that require regulatory testing. Hence, there is a strong demand for replacement, reduction and refinement strategies and methods. However, until now alternative approaches have only rarely been used in regulatory settings. This review provides an overview on current regulations of chemicals and the requirements for animal tests in environmental hazard and risk assessment. It aims to highlight the potential areas for alternative approaches in environmental hazard identification and risk assessment. Perspectives and limitations of alternative approaches to animal tests using vertebrates in environmental toxicology, i.e. mainly fish and amphibians, are discussed. Free access to existing (proprietary) animal test data, availability of validated alternative methods and a practical implementation of conceptual approaches such as the Adverse Outcome Pathways and Integrated Testing Strategies were identified as major requirements towards the successful development and implementation of alternative approaches. Although this article focusses on European regulations, its considerations and conclusions are of global relevance. (C) 2013 Elsevier Inc. All rights reserved.

Symptoms of fecal incontinence and constipation are common in the general population. These can, however, be unreliably reported and are poorly discriminatory for underlying pathophysiology. Furthermore, both symptoms may coexist. In the elderly, fecal impaction always must be excluded. For patients with constipation, colon transit studies, anorectal manometry and defecography may help to identify patients with slow-transit constipation and/or pelvic floor dysfunction. The best documented medical treatments for constipation are the macrogols, lactulose and isphagula. Evolving drugs include lubiprostone, which enhances colonic secretion by activating chloride channels. Surgery is restricted for a highly selected group of patients with severe slow-transit constipation and for those with large rectoceles that demonstrably cause rectal evacuatory impairment. For patients with fecal incontinence that does not resolve on antidiarrheal treatment, functional and structural evaluation with anorectal manometry and endoanal ultrasound or magnetic resonance (MR) of the anal canal may help to guide management. Sacral nerve stimulation is a rapidly evolving alternative when other treatments such as biofeedback and direct sphincter repair have failed. Advances in understanding the pathophysiology as a guide to treatment of patients with constipation and fecal incontinence is a continuing important goal for translational research. The content of this article is a summary of presentations given by the authors at the Fourth Meeting of the Swedish Motility Group, held in Gothenburg in April 2007.

The value of ultrasonography as an adjunct for diagnosis and monitoring malaria was investigated. In all, 118 patients (male/female 65/53; age 2–78 years, median 29 years) with malaria underwent a standardised abdominal ultrasound examination at baseline. In 62 out of 118 patients, ultrasonography was repeated 21 days later. In the results at baseline, huge splenomegaly with firm organ consistency, consistent with hyperreactive malarious splenomegaly syndrome, was observed in two Cameroonese children. In the other 116 patients, the most common finding was non-specific splenomegaly (96/116, 82.76%), occurring more frequently in non-immune patients (71/78, 91.03%) than in patients who had grown up in malaria-endemic areas (25/38, 65.79%; P