Discovery pipelines for marine resources: an ocean of opportunity for biotechnology?

Marine microbial diversity offers enormous potential for discovery of compounds of crucial importance in healthcare, food security and bioindustry. However, access to it has been hampered by the difficulty of accessing and growing the organisms for study. The discovery and exploitation of marine bioproducts for research and commercial development requires state-of-the-art technologies and innovative approaches. Technologies and approaches are advancing rapidly and keeping pace is expensive and time consuming. There is a pressing need for clear guidance that will allow researchers to operate in a way that enables the optimal return on their efforts whilst being fully compliant with the current regulatory framework. One major initiative launched to achieve this, has been the advent of European Research Infrastructures. Research Infrastructures (RI) and associated centres of excellence currently build harmonized multidisciplinary workflows that support academic and private sector users. The European Marine Biological Research Infrastructure Cluster (EMBRIC) has brought together six such RIs in a European project to promote the blue bio-economy. The overarching objective is to develop coherent chains of high-quality services for access to biological, analytical and data resources providing improvements in the throughput and efficiency of workflows for discovery of novel marine products. In order to test the efficiency of this prototype pipeline for discovery, 248 rarely-grown organisms were isolated and analysed, some extracts demonstrated interesting biochemical properties and are currently undergoing further analysis. EMBRIC has established an overarching and operational structure to facilitate the integration of the multidisciplinary value chains of services to access such resources whilst enabling critical mass to focus on problem resolution.

[Total hip arthroplasty by neuromuscular impairment: functional outcome]. / Hüftendoprothetik bei neuromuskulärem Impairment: Funktionelles Outcome.

INTRODUCTION: Studies which deal with the problems of total hip arthoplasty (THA) in patients with neuromuscular impairments are rare. The aim of this study was to examine whether THA for painful coxarthrosis in such patients relieved pain and improved functional outcome and how high the complication rate was. MATERIAL AND METHODS: For this study 10 patients (13 hips) with neuromuscular impairment who had received a total hip arthroplasty for painful coxarthrosis were retrospectively identified. A chart review determined the preoperative functional level. For postoperative evaluation all patients completed a questionnaire, including a self-created modified hip score. RESULTS: The average age of the patients at the time of follow-up was 42.1 years (range 26.5-62.2 years, standard deviation SD 9.9 years) and the minimum follow-up was 24 months (average 80.3 months, range 24-143 months, SD 47 months). Pain relief was obtained for all patients but two patients had a postoperative dislocation and four patients had a major complication (infection) requiring removal of the implant. Therefore, the follow-up rate at the final examination with completed questionnaires was 69% (9 out of 13 excluding patients with removal of THA). These patients showed an improved function from 42.2-83.66 points in the hip score (p=0.0006) and there was general satisfaction with the procedure. DISCUSSION: Total hip arthroplasty can provide improved function in patients with neuromuscular impairment and severe coxarthrosis. The rate of complications was moderate in this series; however, the high infection rate in these patients should be kept in mind.

Enemies in low places - insects avoid winter mortality and egg parasitism by modulating oviposition height.

Oviposition site selection in insects is essential in terms of low egg mortality, high offspring survival and therefore a high reproductive output. Although oviposition height could be a crucial factor for the fitness of overwintering eggs, it has rarely been investigated. In this study the oviposition height of a polyphagous leaf beetle, Galeruca tanaceti Linnaeus in different habitats and at different times of the season was examined and its effect on egg clutch mortality was recorded. The leaf beetle occurs as an occasional pest on several agricultural plants. It deposits its eggs within herbaceous vegetation in autumn. Eggs are exposed to numerous biotic and abiotic mortality factors summarized as egg parasitism and winter mortality. Oviposition height of the leaf beetle was not uniform, but changed significantly with the structure of the habitat and during the season. Mean oviposition height per site (70.2+/-4.9 cm) was significantly higher than mean vegetation height (28.4+/-2.4 cm). Height of plants with egg clutches attached and oviposition height were significantly positively correlated. The results suggest that females try to oviposit as high as possible in the vegetation and on the plants selected. In accordance with this, the probability of egg parasitism and of winter egg clutch mortality significantly declined with increasing oviposition height. A preference of G. tanaceti for oviposition sites high up in the vegetation might therefore have evolved due to selection pressures by parasitoids and winter mortality.

[Surgery for fractures of the lower extremities in cases of chronic spinal cord injury]. / Operative Therapie von Frakturen der unteren Extremitäten bei chronischen Querschnittlähmungen.

According to the literature, the need for surgical treatment of fractures of the lower extremity in patients with chronic spinal cord injury (SCI) is very limited. Conservative management is usually presented as the treatment of choice. We present the results of a retrospective review of 55 fractures in 44 patients from 1996 to 2000 which were managed surgically. Rating of the outcome was based on basic clinical and radiological criteria. The results of the radiological investigation on bone remodeling and bone positioning after healing were rated as good or excellent in 43 and fair in five limbs. In five cases, the treatment failed. For 53 of the 55 fractures, the patients regained their normal level of independence. Comparing our results to those presented in the literature, we clearly had fewer complications as well as better clinical and radiological results. We therefore advocate surgical treatment as an appropriate choice of treatment for lower extremity fractures of patients with chronic SCI.

[Analysis of FIM-values during the hospital treatment of patients with acute spinal cord injury]. / Analyse von FIM-Werten während der stationären Behandlung nach akuter Querschnittlähmung.

The cost pressures in the German health care system continue to rise. In the context of the introduction of the DRG system, adequate treatment of paraplegic and tetraplegic patients within the financial limits will become even more difficult. In dispute with health care insurance companies, scientifically sound studies have been lacking to justify a treatment lasting up to six months as an in-patient of individuals with acute spinal cord injury or disease. The FIM (Functional Independence Measurement), established as a reliable tool in the evaluation of the functional development of patients presenting with acute spinal cord lesions, has been used as the basic tool in our study. Under the conditions of a specialized spinal cord injury centre the FIM showed a statistically highly significant increase of functional independence during the entire course of treatment. No therapeutic standstill could be detected in order to determine a point of discharge. Even in the last six weeks of treatment significant progress in functional independence can be observed.

LC-MS determination of Taxus alkaloids in biological specimens.

A semi-quantitative LC-MS method was developed for the detection of the pseudo alkaloids of Taxus baccata (yew) from human body fluids and tissue samples. This method was used to examine the cause of death of a 43-year-old man who died several hours after he drank a decoction of taxus leaves. Autopsy and histology demonstrated early signs of myocardial hypoxia. Since investigation of the stomach content did not yield evidence of taxus ingestion, the taxus alkaloids were determined in blood, stomach content and tissue samples of the deceased by LC-MS. The samples were prepared by solid phase extraction on RP-18 columns. Chromatographic separation was achieved by HPLC on a RP-8 column, coupled to an ion trap mass spectrometer (Finnigan LCQ). An atmospheric pressure electrospray ionisation was performed. Spectra of the alkaloids were recorded in the single MS mode and in the MS-MS mode and compared with reference spectra obtained from an extract of yew leaves. In the stomach content, the kidneys, the liver and a heart blood sample of the deceased, alkaloids of Taxus baccata, predominantly taxine B and iso-taxine B, were identified. The semi-quantitative evaluation of the heart blood revealed a taxine concentration of 11 micro g taxine/g. As far as we know this is the first case in which a semi-quantitative analysis of taxine alkaloids has been performed.

[Suggestions for implementation of DRG in the fields of Orthopaedics and Trauma Surgery for 2004]. / DRG-Anpassungsvorschläge der Fachgebiete Orthopädie und Unfallchirurgie für 2004.

OBJECTIVE: The Implementation of a DRG-Variant in Germany - voluntarily since January 1 st, 2003 and obligatory from January 1 st, 2004 - has been leading to uncertainty, particularly in the hospitals, due to fears that currently practised German diagnostic and therapeutic measures will not be financed properly by a DRG-Variant. The G-DRG-Version 1.0 that was drawn up in connection with an executive order law is to a large degree identical to the Australian AR-DRG-Version 4.1. Adjustments to German requirements were made only marginally. Therefore it is necessary for every medical field to investigate by stock-taking to what extent currently practised German diagnostic and therapeutic measures are considered in the G-DRG-Version 1.0 and whether and where modifications and adaptations need to be made. In order to make qualified statements scientific evaluations of possible problems have to be made based German data. Therefore an evaluation was made of the mapping of the medical fields of orthopaedics and trauma surgery. The German Society of Trauma Surgery (DGU), the German Society of Orthopaedy and Orthopaedic Surgery (DGOOC) in cooperation with the DRG-Research-Group of the University Hospital Muenster, the German Hospital Federation (DKG) and the German Medical Association carried out a DRG evaluation project in order to investigate the medical and economical homogeneity of the case groups. METHOD: 12,645 orthopaedic and trauma surgery cases from 23 hospitals - 11 university hospitals and 12 non-university hospitals - were collected within an period of three months and were scientifically evaluated with regard to their performance homogeneity and length of stay homogeneity. RESULTS: The data formed the basis for the proof of suspected deficiencies of mapping of orthopaedic and trauma surgery cases within the G-DRG-Variant. Based on the data and additionally on conclusions of medical experts when the number of cases were small, 14 suggestions for adaptation were proposed and submitted by the deadline of March 31 st, 2003 to the InEK. CONCLUSION: The results of the DRG-Evaluation Project demonstrate the problems of mapping the very heterogenous and complex medical performances of orthopaedy and trauma surgery to a flat rate financing system that is not adapted properly to German conditions. The G-DRG-Variant Version 1.0 does not offer the sufficient possibilities of differentiation that are needed to map the various orthopaedical and trauma surgical measures in Germany.

Parasitic wasps learn and report diverse chemicals with unique conditionable behaviors.

Parasitoids exploit numerous chemical cues to locate hosts and food. Whether they detect and learn chemicals foreign to their natural history has not been explored. We show that the parasitoid Microplitis croceipes can associate, with food or hosts, widely different chemicals outside their natural foraging encounters. When learned chemicals are subsequently detected, this parasitoid manifests distinct behaviors characteristic with expectations of food or host, commensurate with prior training. This flexibility of parasitoids to rapidly link diverse chemicals to resource needs and subsequently report them with recognizable behaviors offers new insights into their foraging adaptability, and provides a model for further dissection of olfactory learning related processes.

Use of a latissimus dorsi flap for treatment of infection in a neuropathic shoulder joint.

STUDY DESIGN: Case report. OBJECTIVES: To demonstrate the difficulties that can be encountered in diagnosis and treatment of an infected neuropathic shoulder in a paraplegic man. SETTING: Spinal cord injury center in Germany. METHOD: Ultimately, radical debridement and transplantation of a latissimus dorsi muscle flap. RESULTS: Successful treatment of the infection, partial weight bearing, and limited restriction of range of motion in the affected shoulder. CONCLUSION: The latissimus dorsi muscle flap can resolve the infection of a neuropathic shoulder.

Dysphagia in patients with acute cervical spinal cord injury.

STUDY DESIGN: Longitudinal observational. OBJECTIVES: (a) To establish a reliable and feasible method to indicate the presence and severity of dysphagia and (b) to establish a course of treatment in individuals presenting with cervical spinal cord injury (CSCI). SETTING: Spinal Cord Injury Center, Werner Wicker Klinik, Bad Wildungen, Germany. PATIENTS AND METHODS: This is a cross-sectional study of 51 patients consecutively admitted to the Intensive Care Unit of the SCI in-patient service. They were subjected to neurological and fiberoptic endoscopic examination of swallowing (FEES). Data concerning artificial respiration, presence of tracheostomy, oral or non-oral feeding were obtained from the medical charts. Statistics were carried out by a calculation of a nonparametric correlation (Spearman). RESULTS: Five levels of dysphagia could be distinguished. At levels 1 and 2, patients presented with a severe impairment of swallowing, in level 3 aspiration was met by a powerful coughing reflex, level 4 comprised a laryngeal edema and/or a mild aspiration of fluids only and at level 5 laryngeal function was not compromised. On admission, 20 patients with CSCI presented with mild (level 4), eight with moderate (level 3) and 13 with severe dysphagia (levels 1 and 2). In 10 no signs of dysphagia could be detected. After treatment, level 1 was no longer detected, one patient showed level 2, two patients showed level 3, all other patients showed only mild or no signs of dysphagia any longer. CONCLUSIONS: Dysphagia of various severities was present in the majority of these patients with CSCI together with respiratory insufficiency. FEES allows for the detection and classification of dysphagia as well as for an evaluation of the therapeutic management. Under interdisciplinary treatment the prognosis of dysphagia is good.

Management of degenerative changes and stenosis of the lumbar spinal canal secondary to cervical spinal cord injury.

We describe the case of a 47-year-old female who sustained a C5/6 fracture with C6 complete spinal cord injury 26 years ago. She presented with increased spasticity of the lower extremities, the abdominal wall and episodes of autonomic dysreflexia. Imaging of the spine revealed post-traumatic kyphosis at the level of the injury and degenerative changes of the lumbar spine with marked facet joint hypertrophy at the level of L4/5 causing severe spinal canal stenosis. Discussants of this case comment on the possible pathophysiological mechanisms causing autonomic dysreflexia, especially the development of degenerative changes, Charcot arthropathy and the role of tethering mechanisms. The diagnostic options and management approaches are also discussed.

[Sequelae of diabetes mellitus in the vertebral column and spinal cord]. / Folgen des Diabetes mellitus an Wirbelsäule und Rückenmark.

Diffuse idiopathic skeletal hyperostosis (DISH) is a chronic disease of the spine characterized by a significant association with metabolic alterations such as diabetes mellitus. Diabetes decreases the immunocompetence and increases the susceptibility to infections such as spondylitis, spondylodiscitis, and epidural abscess with spinal cord lesions in a high percentage of the cases. Microangiopathic changes of the intrinsic vasculature of the spinal cord are rare and mild. In a retrospective study of 784 acute spinal cord lesions, suspected diabetes could be found in only 13 patients. Neurophysiological and animal experiments as well as pathological studies have provided proof for the presence of diabetic myelopathy. Diabetic neuroarthropathy of the spine is rare, but important in the differential diagnosis of spinal disorders.

Use of the ring fixator in the treatment of fractures of the lower extremity in long-term paraplegic and tetraplegic patients.

STUDY DESIGN: Retrospective study. OBJECTIVES: To examine the value of operative fracture stabilization by means of the ring fixator in fractures of the lower extremity in the presence of chronic paralysis caused by transverse lesions of the spinal cord. SETTING: A specialist center for the treatment of spinal cord injuries in Germany. METHODS: Clinical examination of the lower extremities with side-for-side comparison, radiological investigation of the fractures, patient survey. PATIENTS: In 21 patients with chronic spinal cord lesions, 22 fractures of the lower extremities were treated with the ring fixator. RESULTS: At follow-up a mean of 41.5 months after fracture healing it could be shown that movement in the knee and ankle joints on the same side as the fracture was not restricted by more than 10 degrees in any of our patients. No losses affecting activities of daily living were reported, and 19 of the 21 patients were satisfied with the result achieved with this technique. After four of the 22 operations there were complications. Malalignments were visible radiologically following five of the fractures. CONCLUSIONS: In osteoporosis-induced fractures of the lower extremities in chronically paraplegic and tetraplegic patients, fracture stabilization with the ring fixator, with fewer complications and better results in terms of joint mobility, is superior to the conservative treatment so far given preference in the literature. It should be offered as an alternative to conservative treatment in the case of pathological fractures.

Improvements in activities of daily living following functional hand surgery for treatment of lesions to the cervical spinal cord: self-assessment by patients.

STUDY DESIGN: Tetraplegic patients were tested for hand strength before and after hand surgery. They also answered questions about how they rated the results of surgery. OBJECTIVES: Presentation of the efficacy of reconstruction of hand raising, lateral grip, and cylindrical grip in the tetraplegic hand. SETTING: The study was conducted in the Werner Wicker Clinic, Bad Wildungen, Germany, from 1991 to 1998. METHODS: The results of reconstruction surgery performed on 23 tetraplegic hands, as reflected in lifting the hand (n=3), lateral grip (n=21), and cylindrical grip (n=14), are presented. In a follow-up study in 22 patients, their management of activities of daily living 34.1 months (9-51 months) after the surgery is compared with the preoperative situation. Subjective satisfaction levels were elicited for each of the 22 patients by means of a questionnaire. RESULTS: The gain in force corresponded to 893 g (150-1500 g) for cyclindrical grip and 488 g (100-1200 g) for lateral grip, while they were able to develop grade 4 force for lifting the hand. After the operation 28 aids/appliances that patients had formerly used regularly were no longer necessary. There were 75 separate activities listed in the questionnaire, and on average the 22 patients were able to perform 8.7 (0-20) more of these. Most patients (19) said they would advise others to have the operation and 18, that they would have the operation again. There were 12 complications in nine patients. CONCLUSION: Reconstructive surgery on the hands of tetraplegic patients leads to gains in both cylindrical grip and lateral grip force and to increased manual dexterity. Patient satisfaction with the procedure is high.

[Amputation of the lower extremity in paraplegic patients. Etiology, sequelae and patient management]. / Amputation der unteren Extremitäten bei Querschnittgelähmten. Ursache, Folgen und Versorgung.

Up to now, there are not many reports about indications and guidelines for prosthetic fitting in amputated paraplegics and tetraplegics. In a review of 35 spinal cord patients with 42 amputations of the lower extremity, data on the neurological level, cause of injury, level of amputation, long-term complications, prosthetic fitting, and usage of the prostheses in daily life are presented. Everyday usage of the prostheses is reported for 15 patients.

Analysis of volatiles induced by oviposition of elm leaf beetle Xanthogaleruca luteola on Ulmus minor.

Egg deposition of the elm leaf beetle Xanthogaleruca luteola causes the emission of volatiles from its food plant, Ulmus minor. These volatiles are exploited by the egg parasitoid, Oomyzus gallerucae, to locate its host. In contrast to other tritrophic systems, the release of volatiles is not induced by feeding but by egg deposition. Previous investigations showed that the release is systemic and can be triggered by jasmonic acid. Comparison of headspace analysis revealed similarities in the blend of volatiles emitted following egg deposition and feeding. The mixture consists of more than 40 compounds; most of the substances are terpenoids. Leaves next to those carrying eggs emit fewer compounds. When treated with jasmonic acid, leaves emit a blend that consists almost exclusively of terpenoids. Dichloromethane extracts of leaves treated with jasmonic acid were also investigated. After separation of extracts of jasmonate induced elm leaves on silica, we obtained a fraction of terpenoid hydrocarbons that was attractive to the parasitoids. This indicates that jasmonic acid stimulates the production of terpenoid hydrocarbons that convey information of egg deposition to the parasitoid.

[Pressure distribution measurements during use of wheelchairs]. / Druckverteilungsmessungen bei Rollstuhlversorgungen.

There is a growing number of mobility-impaired and wheelchair-dependent patients caused by diseases and injuries of the central nervous system. The risk is high for pressure sores to develop due to disturbances of the motor, sensory, and autonomic nervous system. Numerous seating systems for prophylaxis and treatment of decubitus ulcer are available. To identify risk parameters, the literature on animal experiments regarding pressure ulcers was reviewed. A study on the reproducibility of the analysis method with capacitive sensors tested in ten paraplegics with 470 measurements is presented. It shows the reliability of the procedure.

Electromyogram-controlled functional electrical stimulation for treatment of the paralyzed upper extremity.

Spinal cord lesions at level C5 to C6 lead to loss of hand functions and lesions at C4 to additional deficits of arm functionality. The presented dual channel surface stimulator with dual channel electromyogram (EMG) measurement was developed to investigate control strategies for an EMG-controlled implantable stimulation system and serves in addition as a therapy device for patients with partial innervation but weak muscle force. Four different control strategies for stimulation amplitude are available. The amplitude can be preset manually or can follow the preprocessed EMG signals proportionally. The shoulder control program allows proportional control of both stimulation channels with one EMG channel while the second EMG channel serves as the channel selector. Finally, a special feedback training program triggers a stimulation burst when EMG activity is detected. During a 2 year patient study, 18 patients from 2 hospitals and 1 rehabilitation center performed the feedback training. Almost all patients obtained an improvement of functionality. Apart from muscle strengthening, the feedback effect led to an improvement of proprioception and supported relearning of motions. For the documentation of the training status, functional muscle test (British Medical Research Council) and measurements of power, angle, torque, muscle fatigue, and EMG were performed. Obviously, EMG triggered stimulation provides several advantages compared to conventional passive electrical stimulation.

Residual deformity of the spinal canal in patients with traumatic paraplegia and secondary changes of the spinal cord.

INTRODUCTION: The effect of spinal deformity with posttraumatic kyphosis and stenosis of the spinal canal in producing secondary changes of the spinal cord has been discussed for quite some time. Since the advent of magnetic resonance imaging (MRI), 20-40% of patients with posttraumatic paraplegia are found to develop hydromyelia. PURPOSE OF OUR STUDY: To evaluate the influence of residual spinal deformity, defined by the extent of the posttraumatic kyphosis and stenosis, in the development of posttraumatic hydromyelia. MATERIAL AND METHODS: Two hundred and seven cases of traumatic paraplegia with MRI follow-up were reviewed retrospectively. A minimum of 3 years duration between trauma and MRI study was required (mean 10.6 years [3.2-38.3]). For statistical analysis two groups of patients were formed: with hydromyelia and without hydromyelia. After healing of the fracture, the extent of the kyphosis and stenosis, as well as the characteristics of the paraplegia were noted. RESULTS: We found that 53 patients had hydromyelia. A highly significant correlation was found for the extent of spinal stenosis and the amount of kyphosis. Cluster analysis indicated that patients with more than 15 degrees of posttraumatic kyphosis and more than 25% of stenosis were twice as likely to develop hydromyelia. The level of the lesion and the remaining neurological function was not proven to have any influence towards the development of hydromyelia. CONCLUSIONS: These results support the idea that chronic mechanical stress to the spinal cord increases the risk for the development of hydromyelia. Surgical reconstruction should be considered for all patients to prevent secondary changes of the spinal cord.