Uptake routes of microplastics in fishes: practical and theoretical approaches to test existing theories.

Microplastics are frequently detected in the gastrointestinal tracts of aquatic organisms worldwide. A number of active and passive pathways have been suggested for fish, including the confusion of microplastic particles with prey, accidental uptake while foraging and transfer through the food chain, but a holistic understanding of influencing factors is still lacking. The aim of the study was to investigate frequently suggested theories and identify relevant biotic factors, as well as certain plastic properties, affecting microplastic intake in fish. Four species of freshwater fish, each representing a different combination of foraging style (visual/chemosensory) and domestic status (wild/farmed) were exposed to different realistic plastic concentrations and polymer types with and without the provision of genuine food. As most previous investigations of microplastic uptake routes consider only particles large enough to be perceptible to fish, the potential for accidental intake via drinking water has been somewhat neglected. This route is evaluated in the current study using a model approach. The results show that visually oriented fish forage actively on microplastic particles that optically resemble their usual food, while fish with a predominantly chemosensory foraging style are more able to discriminate inedible food items. Even so, the accidental uptake of microplastics while foraging is shown to be relevant pathway, occurring frequently in both visual and chemosensory foragers alike. Several factors were shown to increase plastic uptake, including microplastic concentration in the water, foraging behaviour promoted by availability of genuine food, and fish size. Although both wild and farmed fish ingested microplastic particles, cultured fish showed less discernment in terms of colour and were more likely to forage actively on microplastics when no food was available. Drinking has been identified as a possible source of microplastic intake specifically for large marine fish species. Particles smaller than <5 µm can pass the gastrointestinal tract wall and bioaccumulation could arise when uptake exceeds release or when particles are assimilated in tissues or organs. The effects of accumulation may be significant, especially in long-living species, with implications for food web transfer and fish as food items.

[Patient endangerment due to device diversity? : Discussion of a risk factor based on the results of two surveys of German hospitals]. / Patientengefährdung durch Gerätediversität? : Diskussion eines Risikofaktors anhand der Ergebnisse zweier Befragungen an deutschen Kliniken.

BACKGROUND: The Federal Institute for Drugs and Medical Devices (BfArM) was notified of an event in which it was not possible to sufficiently ventilate a patient suffering a severe asthma attack. It turned out that the ventilation pressures used by the device for pressure-controlled ventilation were below the values set by the user, which the user was not aware of. The ventilation pressures chosen by the user exceeded the preset alarm limits of the ventilator. This pressure and alarm management significantly differed from that of other ventilators used in the hospital. This and similar incident reports suggest that safely operating medical devices for anesthesia and intensive care may be impaired when different models of a device are used within a hospital. If different models are used, more device information needs to be stored in memory. Existing knowledge on human memory suggests that the more individual memory items (e. g. different operating rules) are stored, the greater the risk of memory interference and hence of impaired retrieval, particularly if the different items are associated with overlapping retrieval cues. This is the case when different devices are used for a single functional purpose under identical or similar circumstances. OBJECTIVE: Based on individual incident reports and theoretical knowledge on an association between device diversity and use problems, this study aimed to determine the organizational conditions regarding device diversity that prevail in German hospitals. Additionally, the anesthetists' perspectives and experiences in defined clinical settings were investigated. METHODS: For selected groups of medical devices, the biomedical engineers of German hospitals were surveyed about the different makes used in their hospital. Additionally, questionnaires were sent to a department of anesthesiology of a large University Hospital to investigate the personal experiences of working with different makes and models of a device. RESULTS: Using devices by different manufacturers was particularly frequent for ventilators, but there were also a considerable number of hospitals with syringe pumps and patient monitoring systems from different manufacturers. Almost all participants stated that they work or have worked with different models of a device. The majority of respondents had encountered problems or errors, which they ascribed to the requirement to learn a different method of operation for each device; however, they also listed various benefits, for instance the possibility to optimally address the requirements of specific situations or patient groups. Both biomedical engineers and anesthetists suggested a homogeneous device pool within the hospital and regular and repeated training sessions for each device model used. DISCUSSION: Using different device models for anesthesia and intensive care seems to be common in many German hospitals, particularly for ventilators. An association between device diversity and problems operating a device is plausible, given the functioning of human memory. This topic should be investigated by future studies in order to identify factors that may contribute to such problems and possible solutions for clinical settings. Likewise, the potential benefits of having different device models at one's disposal should be evaluated. To pinpoint the measures that will be most effective given the specific settings of the individual hospital, all underlying clinical and economic considerations must be carefully balanced against the associated potential risks.

Postmarketing cases of eluxadoline-associated pancreatitis in patients with or without a gallbladder.

BACKGROUND: Cases of pancreatitis were identified in the eluxadoline clinical development program, reflected in initial product labelling, and the subject of postmarketing reports. AIM: To analyse postmarketing cases of eluxadoline-associated pancreatitis. METHODS: We retrospectively analysed all US adverse event reports of pancreatitis associated with eluxadoline reported to the FDA Adverse Event Reporting System (FAERS) database from May 27, 2015 through February 15, 2017. RESULTS: The analysis included 119 cases of pancreatitis associated with eluxadoline; one resulted in death and 75 in hospitalisation. Sixty-seven cases reported the presence (n = 12) or absence (n = 55) of the patient's gallbladder. The eluxadoline dose received in the 55 cases of patients without gallbladders was 75 mg (n = 43), 100 mg (n = 5), or not reported (n = 7). Of the 119 cases, 37 reported the patient did not abuse alcohol and 82 did not report the alcohol abuse status. The single fatal case occurred in a patient without a gallbladder who received eluxadoline 75 mg and did not abuse alcohol. Forty-seven cases reported development of pancreatitis within the first or second dose of eluxadoline initiation. The median time to onset for the development of pancreatitis (n = 83) was 1 day, ranging from 1 to 56 days of continued use of eluxadoline. CONCLUSION: The FAERS cases suggest that patients with or without a gallbladder receiving eluxadoline are at risk for the development of pancreatitis. However, patients without a gallbladder, despite receiving the recommended lower dose of eluxadoline 75 mg and screening for alcohol abuse, appear to be overrepresented among patients who developed eluxadoline-associated pancreatitis.

Genetically distinct colour morphs of European perch Perca fluviatilis in Lake Constance differ in susceptibility to macroparasites.

The unusual yellow-finned morph of European perch Perca fluviatilis found in Lake Constance suffers more severely from macroparasite infections, including the tapeworm Triaenophorus nodulosus and the gill worm Ancyrocephalus percae, than conspecifics elsewhere. Microsatellite analysis of yellow-finned P. fluviatilis and red-finned variant recently discovered in Lake Constance revealed significant genetic differentiation. Red-finned P. fluviatilis and fish with mixed fin colour, suggested backcrosses between red and yellow-finned colour morphs, exhibit better resilience to parasite infection, suggesting that the inability of the yellow-finned morph to reject macroparasites may have a genetic basis.

[Medical devices. Regulatory framework and contribution of the German Federal Institute for Drugs and Medical Devices (BfArM) to the safe application]. / Medizinprodukte. Regulatorischer Rahmen und Beitrag des BfArM zur sicheren Anwendung.

Medical devices are of great importance for the prevention, diagnosis and treatment of many diseases. With their broad range and interdisciplinarity, they represent both a very dynamic field of innovation and a significant sector of the economy. The European and thus the German Medical Devices Act aim in this context to make new medical devices for patients and users rapidly available while ensuring safety and performance at the same time. The main responsibility for this lies with the manufacturer. In addition, others are involved in a complex collaboration in the conformity assessment and also later in the marketing phase for the early identification, assessment and minimization of potential risks. This paper presents the legal framework for medical devices and the related roles and responsibilities of various stakeholders, especially the two federal agencies the German Federal Institute for Drugs and Medical Devices (BfArM) and the Paul Ehrlich Institute (PEI). From the perspective of the BfArM the procedure and criteria for risk assessment of incident reports are explained and the experiences and wishes from regulatory practice are described. The active engagement of the BfArM to contribute knowledge from the incident report assessment within the relevant standards organisations and the medical profession is described using examples of medical devices from the field of out-of-hospital ventilation. The paper concludes with a look at future challenges, e.g. in combination products, IT networks and automatization, as well as on current developments to improve risk identification and assessment in a European context.

Genetic diversity of upper Lake Constance whitefish Coregonus spp. under the influence of fisheries: a DNA study based on archived scale samples from 1932, 1975 and 2006.

This investigation examined changes in the genetic diversity of pelagic upper Lake Constance (ULC) whitefish Coregonus wartmanni population before and after the alteration of fishery methods and management from 1932 to 2006. The study spans a period of pronounced changes in trophic status of the lake and transitions from traditional relatively unselective pelagic seine (Klusgarn) fishing to highly size-selective nylon gillnet techniques. In addition, supportive breeding and stocking became most popular during the phase of eutrophication in the 1970s. The main hypothesis is that size-selective fisheries and breeding lead to an overall decrease in genetic variability over time. A total of 215 archived C. wartmanni scale samples from 1932, 1975 and 2006 were analysed by genotyping 11 microsatellite loci. A comparison of population genetic parameters, including allelic richness, observed and expected heterozygosities, and estimates of effective population sizes, suggests that the genetic diversity of C. wartmanni population has not decreased. The appearance of new alleles in the gene pool in 1975 and 2006 may be indicative of admixture with other forms in the lake or with stocked allochthonous forms. Overall, the fisheries management practice in ULC, including the effects of size-selective fisheries, supportive breeding and stocking, have not significantly altered the genetic diversity of Coregonus spp. over an 80 year period.

An invasion record for the swimbladder nematode Anguillicoloides crassus in European eel Anguilla anguilla in a deep warm-monomictic [corrected] lake, from invasion to steady state.

This study is the first account of the establishment and development of the neozoic nematode parasite Anguillicoloides crassus in its host, the European eel Anguilla anguilla, in a deep, warm-monomictic [corrected] lake. A 21 year study of A. crassus took place in Upper Lake Constance (ULC), Europe's second largest pre-alpine lake. The study included two extensive surveys, one in 1991 during the initial parasite invasion phase and the second in 2006 when the infection was well established. The subtropical swimbladder nematode A. crassus was first recorded in A. anguilla in ULC in 1989. Prevalence reached 60% in 1992 and remained at this level until 2007. In 2008, prevalence decreased to 48%. Infection intensity peaked in 1993 at a mean value of 16 adult parasites per host fish. Around 90% of all A. anguilla examined displayed swimbladder lesions, with a significant trend to increasing severity over time. Moreover, heavy swimbladder lesions were seen in c. 10% of A. anguilla ready to migrate to their spawning habitat. Both ruffe Gymnocephalus cernuus and sunfish Lepomis gibbosus serve as paratenic hosts for A. crassus in ULC. Gymnocephalus cernuus seems to be the main vector, and infection is especially frequent in spring possibly caused by reduced immune system efficacy of G. cernuus during winter. In 1991, hypochromic anaemia was prevalent in ULC A. anguilla acutely infected with A. crassus, whereas in 2006 blood values were indicative of chronic infection. The growth and survival rates of A. anguilla during their continental phase were not noticeably altered in infected fish, but damage to the swimbladder probably impairs migration potential and thus the subsequent breeding success of the oceanic phase.

Comparison of powered and conventional air-purifying respirators during simulated resuscitation of casualties contaminated with hazardous substances.

BACKGROUND: Advanced life support of patients contaminated with chemical, biological, radiological or nuclear (CBRN) substances requires adequate respiratory protection for medical first responders. Conventional and powered air-purifying respirators may exert a different impact during resuscitation and therefore require evaluation. This will help to improve major incident planning and measures for protecting medical staff. METHODS: A randomised crossover study was undertaken to investigate the influence of conventional negative pressure and powered air-purifying respirators on the simulated resuscitation of casualties contaminated with hazardous substances. Fourteen UK paramedics carried out a standardised resuscitation algorithm inside an ambulance vehicle, either unprotected or wearing a conventional or a powered respirator. Treatment times, wearer mobility, ease of communication and ease of breathing were determined and compared. RESULTS: In the questionnaire, volunteers stated that communication and mobility were similar in both respirator groups while breathing resistance was significantly lower in the powered respirator group. There was no difference in mean (SD) treatment times between the groups wearing respiratory protection and the controls (245 (19) s for controls, 247 (17) s for conventional respirators and 250 (12) s for powered respirators). CONCLUSIONS: Powered air-purifying respirators improve the ease of breathing and do not appear to reduce mobility or delay treatment during a simulated resuscitation scenario inside an ambulance vehicle with a single CBRN casualty.

Evaluation of bag-valve-mask ventilation in simulated toxic environments.

Bag-valve-mask ventilation is a key component of life support, but only one handheld resuscitator is designed to operate in contaminated or toxic atmospheres. Following Institutional Review Board approval we determined the efficacy of this device. Twenty anaesthetists ventilated a modified manikin, either with or without a combination filter attached to the resuscitator inlet. The mean (SD) maximum minute volume achieved without the filter was 9.3 (3.1) l x min(-1). Use of the inlet filtration system reduced the maximum minute volume significantly to 6.4 (2.2) l x min(-1) (reduction of 30%, p = 0.0017). The achieved maximum minute volumes ranged from 13.4 to 4 l x min(-1) in the controls and from 9.5 to 3 l x min(-1) in the filter group. The delay in refilling of the self-inflatable bag may have resulted in reduced achievable minute volumes. The range of the maximum minute volumes in both groups highlights the need for continuous bag-valve-mask ventilator training.

Respiratory protection during high-fidelity simulated resuscitation of casualties contaminated with chemical warfare agents.

Emergency room personnel are threatened by secondary poisoning when treating victims affected by chemical warfare agents. Therefore, resuscitation skills practised with respiratory protection equipment in place require evaluation. We investigated the influence of wearing air-purifying respirators on the simulated resuscitation of chemical warfare agent casualties. We studied 22 anaesthetic trainees in a simulated resuscitation scenario requiring five set tasks, either unprotected, wearing a binocular visor respirator or a panoramic visor respirator in a randomised, crossover study. Treatment times did not differ between the three groups, with mean (SD) times to complete the tasks being 122 (8) s without a mask, 126 (7) s when wearing the panoramic visor mask and 129 (8) s when wearing the binocular respirator mask. All anaesthetists preferred the panoramic visor in terms of visual orientation but 88% of them rated the binocular mask as being more comfortable. Modern respirators have a negligible effect on simulated resuscitation scenarios for victims affected by chemical warfare agents. Panoramic visor respirators allow better visual orientation for anaesthetists during simulated resuscitation.

New insights into the clinical pharmacokinetics of trofosfamide.

OBJECTIVE: This study focuses on the pharmacokinetics of trofosfamide (TRO) and metabolites after oral administration of TRO. METHODS: Twelve patients with solid tumors and non-Hodgkin lymphomas were treated with 450 mg TRO orally for 7 days. TRO and the stable metabolites ifosfamide (IFO), cyclophosphamide (CYC), 2- and 3-dechloroethylifosfamide (2-DCE, 3-DCE) were determined by GC and the sum of the 4-OH-metabolites was measured by HPLC. RESULTS: A fast metabolism of TRO with a half-life of about 1 h was observed. IFO was the main stable metabolite, whereas CYC was only detected in minor quantities. The peak levels and the AUC of the 4-OH-metabolites were 9.5 and 4.3 times higher than observed after an equimolar IFO dose. Only 6% of the administered dose was recovered in urine within 24 hours as stable metabolites. TRO was under limit of detection. CONCLUSIONS: Our results confirm that dechloroethylation of TRO to IFO is a major metabolic pathway. Additionally, we found considerable 4-hydroxylation not shown previously. With respect to the low levels of IFO and CYC observed, the sum of 4-OH-metabolites cannot be explained by hydroxylation of these metabolites only. Hence, we assume a direct 4-hydroxylation of TRO occurring to a high extent. Bioavailability of TRO could not be calculated directly, because TRO is only available as an oral formulation. The bioavailability of oral IFO, however, is reported to be almost 100%. Therefore, after normalization of the dose, a bioavailability of 32% for IFO after oral TRO could be calculated. Thus, in contrast to previous reports, direct 4-hydroxylation of TRO seems to be the main metabolic pathway.

Retrospective analysis of mortalities associated with medication errors.

The types, causes, contributing factors, and patient demographics of fatal medication errors were reviewed. Case reports of medication errors from hospitals, ambulatory care settings, and patients' homes that were entered in FDA's Adverse Event Reporting System during 1993-98 were the source of information on fatal medication errors. Each report was classified using predefined criteria and a taxonomy developed by the National Coordinating Council for Medication Error Reporting and Prevention. The types, causes, contributing factors, and patient demographics were identified, and the causality of each case was assessed to prevent future fatalities. The data indicated 5,366 medication error reports. Fifty-nine reports were excluded and classified as duplicate reports or intentional overdoses. Of the remaining medication error reports, 68.2% resulted in serious patient outcomes and 9.8% were fatal. Of the 469 fatal medication error reports, 48.6% occurred in patients over 60 years. The most common types of errors resulting in patient death involved administering an improper dose (40.9%), administering the wrong drug (16%), and using the wrong route of administration (9.5%). The most common causes of errors were performance and knowledge deficits (44%) and communication errors (15.8%). Fatal medication errors accounted for approximately 10% of medication errors reported to FDA and were most frequently the result of improper dosing of the intended drug and administration of an incorrect drug. A review of case reports of medication errors from 1993 to 1998 yielded information on the most frequent causes of and contributing factors involved in fatal medication errors.

Dual function of protein confinement in chaperonin-assisted protein folding.

The GroEL/GroES chaperonin system mediates the folding of a range of newly synthesized polypeptides in the bacterial cytosol. Using a rapid biotin-streptavidin-based inhibition of chaperonin function, we show that the cage formed by GroEL and its cofactor GroES can have a dual role in promoting folding. First, enclosure of nonnative protein in the GroEL:GroES complex is essential for folding to proceed unimpaired by aggregation. Second, folding inside the cage can be significantly faster than folding in free solution, independently of ATP-driven cycles of GroES binding and release. This suggests that confinement of unfolded protein in the narrow hydrophilic space of the chaperonin cage smoothes the energy landscape for the folding of some proteins, increasing the flux of folding intermediates toward the native state.