Aphid specialization on different summer hosts is associated with strong genetic differentiation and unequal symbiont communities despite a common mating habitat.

Specialization on different host plants can promote evolutionary diversification of herbivorous insects. Work on pea aphids (Acyrthosiphon pisum) has contributed significantly to the understanding of this process, demonstrating that populations associated with different host plants exhibit performance trade-offs across hosts, show adaptive host choice and genetic differentiation and possess different communities of bacterial endosymbionts. Populations specialized on different secondary host plants during the parthenogenetic summer generations are also described for the black bean aphid (Aphis fabae complex) and are usually treated as different (morphologically cryptic) subspecies. In contrast to pea aphids, however, host choice and mate choice are decoupled in black bean aphids, because populations from different summer hosts return to the same primary host plant to mate and lay overwintering eggs. This could counteract evolutionary divergence, and it is currently unknown to what extent black bean aphids using different summer hosts are indeed differentiated. We addressed this question by microsatellite genotyping and endosymbiont screening of black bean aphids collected in summer from the goosefoot Chenopodium album (subspecies A. f. fabae) and from thistles of the genus Cirsium (subspecies A. f. cirsiiacanthoides) across numerous sites in Switzerland and France. Our results show clearly that aphids from Cirsium and Chenopodium exhibit strong and geographically consistent genetic differentiation and that they differ in their frequencies of infection with particular endosymbionts. The dependence on a joint winter host has thus not prevented the evolutionary divergence into summer host-adapted populations that appear to have evolved mechanisms of reproductive isolation within a common mating habitat.

Trabectedin Followed by Irinotecan Can Stabilize Disease in Advanced Translocation-Positive Sarcomas with Acceptable Toxicity.

Background. Preclinical data indicate that trabectedin followed by irinotecan has strong synergistic effects on Ewing sarcoma. This is presumably due to hypersensitization of the tumor cells to the camptothecin as an effect of trabectedin in addition to synergistic suppression of EWS-FLI1 downstream targets. A strong effect was also reported in a human rhabdomyosarcoma xenograft. Procedure. Twelve patients with end-stage refractory translocation-positive sarcomas were treated with trabectedin followed by irinotecan within a compassionate use program. Eight patients had Ewing sarcoma and four patients had other translocation-positive sarcomas. Results. Three-month survival rate was 0.75 after the start of this therapy. One patient achieved a partial response according to RECIST criteria, five had stable disease, and the remaining six progressed through therapy. The majority of patients experienced significant hematological toxicity (grades 3 and 4). Reversible liver toxicity and diarrhea also occurred. Conclusions. Our experience with the combination of trabectedin followed with irinotecan in patients with advanced sarcomas showed promising results in controlling refractory solid tumors. While the hematological toxicity was significant, it was reversible. Quality of life during therapy was maintained. These observations encourage a larger clinical trial.

Residual Force Enhancement Following Eccentric Contractions: A New Mechanism Involving Titin.

Eccentric muscle properties are not well characterized by the current paradigm of the molecular mechanism of contraction: the cross-bridge theory. Findings of force contributions by passive structural elements a decade ago paved the way for a new theory. Here, we present experimental evidence and theoretical support for the idea that the structural protein titin contributes to active force production, thereby explaining many of the unresolved properties of eccentric muscle contraction.

Seafarer deaths at sea: a German mortality study.

BACKGROUND: Seafarers face numerous hazards during their work at sea. AIMS: To demonstrate the frequency and causes of mortality in German seafarers. METHODS: The deaths of all German seafarers from 1998 to 2008 were counted and evaluated using the German central civil register in Berlin. RESULTS: The study cohort comprised a total of 159588 seafarer-years. During the 11 year period, 68 male seafarers died on board. The average age was 48.5 years (SD 12.7 years) and comprised 35 deck officers, 16 engine officers and 17 general crew members (i.e. non-officers from the deck and engine room crew and galley staff). Cause of death was documented in 45 cases (66%): 26 were due to unnatural causes (occupational accidents, suicides) and 19 due to natural causes (particularly, ischaemic heart disease). The crude annual mortality rate for German seamen was 65 per 100000 seafarer-years. For cardiac causes, this rate was significantly higher among deck and engine officers (24 and 38) than among crew ranks (7 per 100000 seafarer-years) (P < 0.05). Deck and engine offi-cers also showed a higher mortality rate for accidents (28 and 22) than crew ranks (15) (P < 0.05). The age-stratified fatal accident rate of German seafarers aboard was 10 times higher than the mortality of the German general population on shore. CONCLUSIONS: Seafaring constitutes an occupation with a high risk for serious accidents. Due to the unexpectedly high mortality rate among officers associated with work-related accidents, this occupational group should receive more effective education on safety behaviour on board.

The prevalence of BRCA1 and BRCA2 mutations among young Mexican women with triple-negative breast cancer.

Various guidelines recommend that women with triple-negative breast cancer should be tested for BRCA1 mutations, but the prevalence of mutations may vary with ethnic group and with geographic region, and the optimal cutoff age for testing has not been established. We estimated the frequencies of BRCA1 and BRCA2 (BRCA) mutations among 190 women with triple-negative breast cancer, unselected for family history, diagnosed at age 50 or less at a single hospital in Mexico City. Patients were screened for 115 recurrent BRCA mutations, which have been reported previously in women of Hispanic origin, including a common large rearrangement Mexican founder mutation (BRCA1 ex9-12del). A BRCA mutation was detected in 44 of 190 patients with triple-negative breast cancer (23 %). Forty-three mutations were found in BRCA1 and one mutation was found in BRCA2. Seven different mutations accounted for 39 patients (89 % of the total mutations). The Mexican founder mutation (BRCA1 ex9-12del) was found 18 times and accounted for 41 % of all mutations detected. There is a high prevalence of BRCA1 mutations among young triple-negative breast cancer patients in Mexico. Women with triple-negative breast cancer in Mexico should be screened for mutations in BRCA1.

Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Peru.

The prevalence of BRCA1 and BRCA2 mutations among breast cancer patients in Peru has not yet been explored. We enrolled 266 women with breast cancer from a National cancer hospital in Lima, Peru, unselected for age or family history. DNA was screened with a panel of 114 recurrent Hispanic BRCA mutations (HISPANEL). Among the 266 cases, 13 deleterious mutations were identified (11 in BRCA1 and 2 in BRCA2), representing 5% of the total. The average age of breast cancer in the mutation-positive cases was 44 years. BRCA1 185delAG represented 7 of 11 mutations in BRCA1. Other mutations detected in BRCA1 included: two 2080delA, one 943ins10, and one 3878delTA. The BRCA2 3036del4 mutation was seen in two patients. Given the relatively low cost of the HISPANEL test, one should consider offering this test to all Peruvian women with breast or ovarian cancer.

Titin (visco-) elasticity in skeletal muscle myofibrils.

Titin is the third most abundant protein in sarcomeres and fulfills a number of mechanical and signaling functions. Specifically, titin is responsible for most of the passive forces in sarcomeres and the passive visco-elastic behaviour of myofibrils and muscles. It has been suggested, based on mechanical testing of isolated titin molecules, that titin is an essentially elastic spring if Ig domain un/refolding is prevented either by working at short titin lengths, prior to any un- folding of Ig domains, or at long sarcomere (and titin) lengths when Ig domain un/refolding is effectively prevented. However, these properties of titin, and by extension of muscles, have not been tested with titin in its natural structural environment within a sarcomere. The purpose of this study was to gain insight into the Ig domain un/refolding kinetics and test the idea that titin could behave essentially elastically at any sarcomere length by preventing Ig domain un/refolding during passive stretch-shortening cycles. Although not completely successful, we demonstrate here that titin's visco-elastic properties appear to depend on the Ig do- main un/refolding kinetics and that indeed, titin (and thus myofibrils) can become virtually elastic when Ig domain un/refolding is prevented.

Kinematic effects of subthalamic stimulation on reach-to-grasp movements in Parkinson's disease.

BACKGROUND: Parkinsonian patients demonstrate particular difficulties when performing sequential motor tasks compared to simple movements indicating an important role of the basal ganglia in switching between different motor programs. OBJECTIVE: To investigate the impact of subthalamic stimulation on the kinematics of composed reach-to-grasp movements and on isolated movement segments. METHODS: 11 age matched controls and 16 PD patients with subthalamic stimulation were examined without medication with stimulation switched on and off. All subjects were instructed to perform three different externally cued hand movements: 1) The complete reach-to-grasp movement consisting of hand transport to and precision grip around a target. 2) The isolated reach movement to the grip device 3) The isolated precision grip and button press. Kinematic data were recorded with a 3D ultrasound movement analysis system (CMS 70 P4-V5, Zebris, Germany). RESULTS: The effect of subthalamic stimulation was accentuated during the reach phase compared to the grip formation during the composed movement. Stimulation induced kinematic changes of the composed movement were comparable to those of both isolated submovements. CONCLUSION: Subthalamic stimulation improved certain aspects of all three hand movement types but did not differentially impact the composed reach-to-grasp task compared to the simple submovements. We assume that the complete reach-to-grasp task is encoded in a single generalised motor program which is affected by stimulation.

[Endoscopic therapy for tumours of the papilla of vater]. / Endoskopische Interventionsmöglichkeiten bei Tumoren der Papille.

BACKGROUND: Ampullary tumours are rare and can be separated in benign and malignant lesions. There are non-invasive diagnostic methods in order to detect ampullary tumours like abdominal ultrasound, computed tomography and MRCP (magnetic resonance cholangiopancreaticography) as well as invasive methods, e. g., gastroscopy, duodenoscopy, endosonography, intraductal ultrasound, ERCP and cholangioscopy. Endoscopy is the method of choice for this indication, whereas a combination of the different diagnostic methods is common. MATERIAL AND METHODS: A selective literature research with descriptive survey has been carried out. RESULTS: The standard method to treat benign tumours of the papilla is endoscopic papillectomy. For malignant tumours surgery is preferred. But in some certain circumstances it is also possible to treat carcinomas of the papilla endoscopically. DISCUSSION: This overview should assist surgeons and endoscopists to choose the right diagnostic approach and to treat adenomas as well as carcinomas of the Papilla of Vater appropriately. CONCLUSION: The treatment of papilla tumours depends primarily on the dignity, the morphology of the findings and the extension of the tumour (extraductal vs. intraductal).

Primary sarcoma of the anterior cruciate ligament - a case report.

Clear cell sarcoma of tendons and aponeuroses (CCSTA) is a rare, aggressive soft tissue malignancy, which is found in intimate association with tendon, aponeurosis or fascia. It has not previously been reported in association with intraarticular ligaments. We report the first case of an intraarticular CCSTA, in this case of the anterior cruciate ligament and describe the diagnostic and treatment challenges of intraarticular tumours of the knee.

Effect of controlled-release levodopa on the microstructure of sleep in Parkinson's disease.

BACKGROUND: Dopamine is an important neurotransmitter in the regulation of the sleep-wake cycle, and parkinsonian patients suffer from prominent sleep abnormalities. Hence, the question arises whether the disrupted sleep pattern in Parkinson's disease (PD) is responsive to dopaminergic treatment. METHODS: Thirty-two patients (18 women, 45-82 years old; mean 61 ± 8 years) with dopamine-responsive, akinetic-rigid PD, not taking neuroleptic medication or suffering from dementia were randomized into two groups. Both groups had to withhold their usual dopaminergic medication after noon. At bedtime, one group received 200 mg controlled-release (CR) levodopa/carbidopa, whilst the other group spent the night in the 'off'-state. Polysomnographic recordings were obtained in all patients and 16 age-matched, healthy controls. RESULTS: Compared to healthy controls, patients with PD suffered from significantly decreased total sleep time, REM sleep and slow wave sleep (SWS), whilst the time spent awake was increased. The administration of levodopa/carbidopa CR had no impact on any of these variables. CONCLUSION: Levodopa/carbidopa CR has previously been found effective for treating night-time akinesia, but according to this study, it has no impact on the altered sleep structure in PD.

[Deep brain stimulation for Parkinson's disease]. / Tiefe Hirnstimulation bei der Parkinson-Krankheit.

Deep brain stimulation (DBS) is an effective neurosurgical therapy for treatment of motor symptoms in Parkinson's disease (PD). DBS of the subthalamic nucleus (STN-DBS) leads to a significant reduction of hypokinetic and hyperkinetic symptoms and improvement in quality of life. STN-DBS is, however, associated with severe adverse effects including psychiatric symptoms, such as depression, apathy and increased suicidal tendencies. Pallidal DBS might be just as efficacious with fewer adverse effects. Future studies will prospectively compare the clinical effects of STN and pallidal DBS. Alternative targets for treatment of PD have to be considered including the pedunculopontine nucleus, thalamic CM/Pf complex and zona incerta.

Deep brain stimulation of the internal globus pallidus in dystonia: target localisation under general anaesthesia.

UNLABELLED: Deep brain stimulation (DBS) of the internal globus pallidus (Gpi) is an effective therapy for various types of dystonia. The authors describe their technical approach for securing appropriate placement of the stimulating electrodes within the Gpi under general anaesthesia, including MRI based individualised anatomical targeting combined with electrophysiological mapping of the Gpi using micro-recording (MER) as well as macrostimulation and report the subsequent clinical outcome and complications using this method. METHOD: We studied 42 patients (male-female ratio 25:17; mean age 43.6 years, range 9 to 74 years) consecutively operated at the Department of Neurosurgery, University Hospital Schleswig-Holstein, Campus Kiel, between 2001 - 2006. One patient underwent unilateral implantation after a right-sided pallidotomy 30 years before and strictly unilateral symptoms; all other implantations were bilateral. Two patients had repeat surgery after temporary removal of uni- or bilateral implants secondary to infection. Overall, 86 DBS electrodes were implanted. In 97% of the implantations, at least three microelectrodes were inserted simultaneously for MER and test stimulation. Initial anatomical targeting was based on stereotactic atlas coordinates and individual adaptation by direct visualisation of the Gpi on the stereotactic T2 or inversion-recovery MR images. The permanent electrode was placed according to the results of MER and test stimulations for adverse effects. FINDINGS: The average improvement from baseline in clinical ratings using either the Burke-Fahn-Marsden-Dystonia (BFMDRS) or Toronto-Western-Spasmodic-Torticollis (TWSTR) rating scale at the last post-operative follow-up (mean 16.4 ; range 3-48 months) was 64.72% (range 20.39 to 98.52%). The post-operative MRI showed asymptomatic infarctions of the corpus caudatus in three patients and asymptomatic small haemorrhages in the lateral basal ganglia in two patients. One patient died due to a recurrent haemorrhage which occurred three months after the operation. The electrodes were implanted as follows: central trajectory in 64%, medial trajectory in 20%, anterior in 9% and lateral dorsal trajectories in 3.5% each. The reduction in BFMDRS or TWSTR motor score did not differ between the group implanted in the anatomically defined (central) trajectory bilateral (-64.15%, SD 23.8) and the physiologically adopted target (uni- or bilateral) (-63.39%, SD 23.1) indicating that in both groups equally effective positions were chosen within Gpi for chronic stimulation (t-test, p > 0.4). CONCLUSIONS: The described technique using stereotactic MRI for planning of the trajectory and direct visualisation of the target, intra-operative MER for delineating the boundaries of the target and macrostimulation for probing the distance to the internal capsule by identifying the threshold for stimulation induced tetanic contractions is effective in DBS electrode implantation in patients with dystonia operated under general anaesthesia. The central trajectory was chosen in only 64%, despite individual adaptation of the target due to direct visualisation of the Gpi in inversion recovery MRI in 43% of the patients, demonstrating the necessity of combining anatomical with neurophysiological information.

Neuronal activity of the human subthalamic nucleus in the parkinsonian and nonparkinsonian state.

We recorded resting-state neuronal activity from the human subthalamic nucleus (STN) during functional stereotactic surgeries. By inserting up to five parallel microelectrodes for single- or multiunit recordings and applying statistical spike-sorting methods, we were able to isolate a total of 351 single units in 65 patients with Parkinson's disease (PD) and 33 single units in 9 patients suffering from essential tremor (ET). Among these were 93 pairs of simultaneously recorded neurons in PD and 17 in ET, which were detected either by the same (n = 30) or neighboring microelectrodes (n = 80). Essential tremor is a movement disorder without any known basal ganglia pathology and with normal dopaminergic brain function. By comparing the neuronal activity of the STN in patients suffering from PD and ET we intended to characterize, for the first time, changes of basal ganglia activity in the human disease state that had previously been described in animal models of Parkinson's disease. We found a significant increase in the mean firing rate of STN neurons in PD and a relatively larger fraction of neurons exhibiting burstlike activity compared with ET. The overall proportion of neurons exhibiting intrinsic oscillations or interneuronal synchronization as defined by significant spectral peaks in the auto- or cross-correlations functions did not differ between PD and ET when considering the entire frequency range of 1-100 Hz. The distribution of significant oscillations across the theta (1-8 Hz), alpha (8-12 Hz), beta (12-35 Hz), and gamma band (>35 Hz), however, was uneven in ET and PD, as indicated by a trend in Fisher's exact test (P = 0.05). Oscillations and pairwise synchronizations within the 12- to 35-Hz band were a unique feature of PD. Our results confirm the predictions of the rate model of Parkinson's disease. In addition, they emphasize abnormalities in the patterning and dynamics of neuronal discharges in the parkinsonian STN, which support current concepts of abnormal motor loop oscillations in Parkinson's disease.

Accuracy and distortion of deep brain stimulation electrodes on postoperative MRI and CT.

OBJECTIVE: Postoperative monitoring of the electrode position is important to evaluate the best stimulation site in deep brain stimulation. MR imaging is excellent for ruling out postoperative complications e.g. haemorrhage, but its accuracy in electrode localisation is still controversial. The reasons for this are the size of the artefact around the electrode and its unclear relation to the electrode position (concentric or eccentric). The goal of this study was to determine the relation and size of these artefacts to the electrodes by comparing the position of the electrodes in postoperative MR and CT imaging. MATERIAL AND METHODS: Five patients underwent deep brain stimulation of the subthalamic nucleus due to levodopa-induced motor complications in Parkinson's disease. A stereotactic CT and a non-stereotactic MR were performed for postoperative localisation of the electrode position. The stereotactic MR for planning of the trajectories and targets was done under general anaesthesia. The latter two were fused to the stereotactic MR and the position of the DBS electrode contacts was determined on CT and MRI. The size of the artefact was measured at the level of each contact in two directions, anterior to posterior (AP) and lateral. Altogether 40 contacts were evaluated. RESULTS: Mean size of the CT-artefact was 2.6 mm AP (range, 2.0-3.2 mm) and 2.6 mm laterally (range, 2.0-3.8 mm). In comparison, mean size on the MRI was 3.5 mm AP (range, 2.9-5.3 mm) and 3.8 mm laterally (range, 2.9-4.8 mm). A trajectory with a 1.2 mm diameter (size of the DBS electrode) was centred on the electrodes' artefact of the CT and the MRI. The difference between the contact coordinates was calculated as deviation of the artefact around the electrode on the MR. Mean deviation was 0.2 mm on the x-axis (range, 0-0.5 mm), 0.5 mm on the y-axis (range, 0-1.1 mm) and 0.3 mm on the z-axis (range, 0-0.7 mm). There were no significant differences (t-test, p > 0.4). CONCLUSION: The size of the electrodes' artefact was smaller on CT compared to MR. Furthermore, the position was not precisely concentric around the electrode. Nevertheless, the mean deviation after measuring the contact position in both CT and MR was less than 1 mm in all three planes. Both techniques are eligible for postoperative localisation of DBS electrodes, with a small imprecision of the non-stereotactic MR compared to the stereotactic CT. This might be compensated by the fact that postoperative MR can rule out asymptomatic postoperative complications e.g. haemorrhages or infarctions, without radiation exposure of the patient.

Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism.

OBJECTIVES: To study the frequency of different gene mutations in patients with early-onset parkinsonism and bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and the short- and long-term surgical outcome in mutation-positive (MUT+) and -negative (MUT-) patients. METHODS: Eighty patients with disease onset at age

Subthalamic nucleus stimulation modulates audiospinal reactions in Parkinson disease.

BACKGROUND: Axial symptoms of Parkinson disease (PD) may result from dysfunctional basal ganglia-brainstem connections. In this study, we assessed whether modulation of basal ganglia activity by high-frequency stimulation of the subthalamic nucleus (STN-HFS) in PD had an impact on the brainstem-controlled startle system. METHODS: We assessed auditory startle responses (recorded from right orbicularis oculi, masseter, sternocleidomastoid, biceps brachii, and soleus muscle) and audiospinal facilitation (startle conditioned soleus H-reflexes at interstimulus intervals of 0-250 msec) in 24 patients with PD with chronically implanted, bilateral STN electrodes in the stimulation on (STIM ON) and off condition (STIM OFF) and 20 healthy controls. RESULTS: The mixed linear analysis of variance model revealed a significant effect for the startle onset latency in the orbicularis oculi muscle for the factors GROUP (patients with PD vs controls; p < 0.0001, F = 44.66) and STIM (nested within GROUP) (p = 0.0034, F = 8.79). Audiospinal facilitation was modulated by STN-HFS as shown by highly significant effects for STIM [GROUP] (p < 0.0001, F = 15.9), ISI [GROUP] (p < 0.0001, F = 3.5), and the interaction of ISI x STIM [GROUP] (p = 0.0085, F = 2.65) in the mixed linear model. CONCLUSION: High-frequency stimulation of the subthalamic nucleus alters the excitability of the brainstem startle system in Parkinson disease, most likely by releasing the reticular motor system from abnormal descending input of the basal ganglia via pallidotegmental pathways.

Electrode implantation for deep brain stimulation in dystonia: a fast spin-echo inversion-recovery sequence technique for direct stereotactic targeting of the GPI.

OBJECTIVE: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective treatment for medically refractory primary dystonia. We present our technique for direct preoperative visualization of the target using a fast spin-echo inversion-recovery (FSE-IR) sequence. METHODS: Twenty-three consecutive patients (mean age 41 years, range 9-68 years, male to female ratio 11:12) with severe dystonia were operated using a combination of FSE-IR imaging for direct visualization of the globus pallidus internus with stereotactic, gadolinium-enhanced T1-MPRage images. The complete procedure, including stereotactic MRI, was performed under general anesthesia with propofol and remifentanyl. We used multichannel microdrive systems (Medtronic; Alpha-Omega) to introduce up to five parallel microelectrodes for microelectrode recordings (MER) and test stimulation with the central trajectory directed at the anatomically predefined target. The initial standard coordinates in relation to the mid-commissural point (mid-AC-PC) were as follows: lateral 21 mm, anterior 3 mm, and inferior 2 mm, which were then adapted to the individual case based on direct visualization of the target area and further refined by the intraoperative neurophysiology. RESULTS: In ten patients (43%) atlas-based standard coordinates were modified based on the direct visualization of the GPi in the FSE-IR images (bilaterally in seven patients, unilaterally in three). The modified targets ranged from 18.5 to 23.5 mm (mean 20.76 mm) laterally, 1-7 mm (mean 2.75 mm) anteriorly and 1-2 mm (mean 1.95 mm) inferiorly to the mid-AC-PC. We implanted the permanent electrode based on the results of MER and intraoperative stimulation performed to determine the threshold for pyramidal tract responses on the central trajectory in 67%, medially in 16%, anteriorly in 11%, laterally in 4%, dorsally in 2%. The procedure resulted in excellent clinical benefits (average reduction of the Burke-Fahn-Marsden Dystonia Rating Score (BFMDRS) or the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) were respectively 65.9%, range 20.9-91.4%) within the first year after surgery. Safety was demonstrated by the absence of intracranial bleeding or other surgical complications causing neurological morbidity. CONCLUSION: Inversion recovery sequences are an excellent tool for direct visualization of the GPi. These images can be fused to stereotactic MRI or CCT and may help to improve anatomical targeting of the GPi for the implantation of DBS electrodes.