Scoping Review on Brain-Computer Interface-Controlled Electrical Stimulation Interventions for Upper Limb Rehabilitation in Adults: A Look at Participants, Interventions, and Technology.

Purpose: While current rehabilitation practice for improving arm and hand function relies on physical/occupational therapy, a growing body of research evaluates the effects of technology-enhanced rehabilitation. We review interventions that combine a brain-computer interface (BCI) with electrical stimulation (ES) for upper limb movement rehabilitation to summarize the evidence on (1) populations of study participants, (2) BCI-ES interventions, and (3) the BCI-ES systems. Method: After searching seven databases, two reviewers identified 23 eligible studies. We consolidated information on the study participants, interventions, and approaches used to develop integrated BCI-ES systems. The included studies investigated the use of BCI-ES interventions with stroke and spinal cord injury (SCI) populations. All studies used electroencephalography to collect brain signals for the BCI, and functional electrical stimulation was the most common type of ES. The BCI-ES interventions were typically conducted without a therapist, with sessions varying in both frequency and duration. Results: Of the 23 eligible studies, only 3 studies involved the SCI population, compared to 20 involving individuals with stroke. Conclusions: Future BCI-ES interventional studies could address this gap. Additionally, standardization of device and rehabilitation modalities, and study-appropriate involvement with therapists, can be considered to advance this intervention towards clinical implementation.

Objectif: les pratiques de réadaptation actuelles pour améliorer le fonctionnement de la main et du bras reposent sur la physiothérapie et l'ergothérapie, mais de plus en plus de recherches évaluent les effets de la réadaptation améliorée par la technologie. Les chercheurs analysent les interventions qui combinent une interface cerveau-ordinateur (ICO) à la stimulation électrique (SÉ) en réadaptation des mouvements des membres supérieurs pour résumer les données probantes sur 1) les populations de participants aux études, 2) les interventions d'ICO-SÉ et 3) les systèmes d'ICO-SÉ. Méthodologie: après avoir fouillé sept bases de données, deux analystes ont extrait 23 études admissibles. Les chercheurs ont regroupé l'information sur les participants aux études, de même que sur les interventions et les approches utilisées pour mettre au point des systèmes d'ICO-SÉ intégrés. Les études portaient sur l'utilisation des interventions d'ICO-SÉ auprès des populations victimes d'un accident vasculaire cérébral ou d'une lésion médullaire. Toutes faisaient appel à l'électroencéphalographie pour obtenir les signaux cérébraux de l'ICO, et la SÉ fonctionnelle était la SÉ la plus courante. Les interventions d'ICO-SÉ se déroulaient généralement sans thérapeute, et la fréquence et la durée des séances étaient variables. Résultats: sur les 23 études admissibles, seulement trois traitaient de la population victime d'une lésion médullaire, par rapport à 20 de personnes victimes d'un accident vasculaire cérébral. Conclusions: les futures études d'interventions d'ICO-SÉ pourraient corriger cette lacune. De plus, on peut envisager de standardiser les modalités des appareils et de la réadaptation et de prévoir une participation avec les thérapeutes adaptée à l'étude pour faire progresser cette intervention vers la mise en œuvre clinique.

Effectiveness of motor and prefrontal cortical areas for brain-controlled functional electrical stimulation neuromodulation.

Objective. Brain-computer interface (BCI)-controlled functional electrical stimulation (FES) could excite the central nervous system to enhance upper limb motor recovery. Our current study assessed the effectiveness of motor and prefrontal cortical activity-based BCI-FES to help elucidate the underlying neuromodulation mechanisms of this neurorehabilitation approach.Approach. The primary motor cortex (M1) and prefrontal cortex (PFC) BCI-FES interventions were performed for 25 min on separate days with twelve non-disabled participants. During the interventions, a single electrode from the contralateral M1 or PFC was used to detect event-related desynchronization (ERD) in the calibrated frequency range. If the BCI system detected ERD within 15 s of motor imagery, FES activated wrist extensor muscles. Otherwise, if the BCI system did not detect ERD within 15 s, a subsequent trial was initiated without FES. To evaluate neuromodulation effects, corticospinal excitability was assessed using single-pulse transcranial magnetic stimulation, and cortical excitability was assessed by motor imagery ERD and resting-state functional connectivity before, immediately, 30 min, and 60 min after each intervention.Main results. M1 and PFC BCI-FES interventions had similar success rates of approximately 80%, while the M1 intervention was faster in detecting ERD activity. Consequently, only the M1 intervention effectively elicited corticospinal excitability changes for at least 60 min around the targeted cortical area in the M1, suggesting a degree of spatial localization. However, cortical excitability measures did not indicate changes after either M1 or PFC BCI-FES.Significance. Neural mechanisms underlying the effectiveness of BCI-FES neuromodulation may be attributed to the M1 direct corticospinal projections and/or the closer timing between ERD detection and FES, which likely enhanced Hebbian-like plasticity by synchronizing cortical activation detected by the BCI system with the sensory nerve activation and movement related reafference elicited by FES.

Evidence That Brain-Controlled Functional Electrical Stimulation Could Elicit Targeted Corticospinal Facilitation of Hand Muscles in Healthy Young Adults.

OBJECTIVES: Brain-computer interface (BCI)-controlled functional electrical stimulation (FES) has been used in rehabilitation for improving hand motor function. However, mechanisms of improvements are still not well understood. The objective of this study was to investigate how BCI-controlled FES affects hand muscle corticospinal excitability. MATERIALS AND METHODS: A total of 12 healthy young adults were recruited in the study. During BCI calibration, a single electroencephalography channel from the motor cortex and a frequency band were chosen to detect event-related desynchronization (ERD) of cortical oscillatory activity during kinesthetic wrist motor imagery (MI). The MI-based BCI system was used to detect active states on the basis of ERD activity in real time and produce contralateral wrist extension movements through FES of the extensor carpi radialis (ECR) muscle. As a control condition, FES was used to generate wrist extension at random intervals. The two interventions were performed on separate days and lasted 25 minutes. Motor evoked potentials (MEPs) in ECR (intervention target) and flexor carpi radialis (FCR) muscles were elicited through single-pulse transcranial magnetic stimulation of the motor cortex to compare corticospinal excitability before (pre), immediately after (post0), and 30 minutes after (post30) the interventions. RESULTS: After the BCI-FES intervention, ECR muscle MEPs were significantly facilitated at post0 and post30 time points compared with before the intervention (pre), whereas there were no changes in the FCR muscle corticospinal excitability. Conversely, after the random FES intervention, both ECR and FCR muscle MEPs were unaffected compared with before the intervention (pre). CONCLUSIONS: Our results demonstrated evidence that BCI-FES intervention could elicit muscle-specific short-term corticospinal excitability facilitation of the intervention targeted (ECR) muscle only, whereas randomly applied FES was ineffective in eliciting any changes. Notably, these findings suggest that associative cortical and peripheral activations during BCI-FES can effectively elicit targeted muscle corticospinal excitability facilitation, implying possible rehabilitation mechanisms.

A POLD3/BLM dependent pathway handles DSBs in transcribed chromatin upon excessive RNA:DNA hybrid accumulation.

Transcriptionally active loci are particularly prone to breakage and mounting evidence suggests that DNA Double-Strand Breaks arising in active genes are handled by a dedicated repair pathway, Transcription-Coupled DSB Repair (TC-DSBR), that entails R-loop accumulation and dissolution. Here, we uncover a function for the Bloom RecQ DNA helicase (BLM) in TC-DSBR in human cells. BLM is recruited in a transcription dependent-manner at DSBs where it fosters resection, RAD51 binding and accurate Homologous Recombination repair. However, in an R-loop dissolution-deficient background, we find that BLM promotes cell death. We report that upon excessive RNA:DNA hybrid accumulation, DNA synthesis is enhanced at DSBs, in a manner that depends on BLM and POLD3. Altogether our work unveils a role for BLM at DSBs in active chromatin, and highlights the toxic potential of RNA:DNA hybrids that accumulate at transcription-associated DSBs.

Characterizing the stimulation interference in electroencephalographic signals during brain-computer interface-controlled functional electrical stimulation therapy.

INTRODUCTION: The integration of brain-computer interface (BCI) and functional electrical stimulation (FES) has brought about a new rehabilitation strategy: BCI-controlled FES therapy or BCI-FEST. During BCI-FEST, the stimulation is triggered by the patient's brain activity, often monitored using electroencephalography (EEG). Several studies have demonstrated that BCI-FEST can improve voluntary arm and hand function after an injury, but few studies have investigated the FES interference in EEG signals during BCI-FEST. In this study, we evaluated the effectiveness of band-pass filters, used to extract the BCI-relevant EEG components, in simultaneously reducing stimulation interference. METHODS: We used EEG data from eight participants recorded during BCI-FEST. Additionally, we separately recorded the FES signal generated by the stimulator to estimate the spectral components of the FES interference, and extract the noise in time domain. Finally, we calculated signal-to-noise ratio (SNR) values before and after band-pass filtering, for two types of movements practiced during BCI-FEST: reaching and grasping. RESULTS: The SNR values were greater after filtering across all participants for both movement types. For reaching movements, mean SNR values increased between 1.31 dB and 36.3 dB. Similarly, for grasping movements, mean SNR values increased between 2.82 dB and 40.16 dB, after filtering. CONCLUSIONS: Band-pass filters, used to isolate EEG frequency bands for BCI application, were also effective in reducing stimulation interference. In addition, we provide a general algorithm that can be used in future studies to estimate the frequencies of FES interference as a function of the selected stimulation pulse frequency, FSTIM , and the EEG sampling rate, FS .

Comparing preference related to comfort in torque-matched muscle contractions between two different types of functional electrical stimulation pulses in able-bodied participants.

CONTEXT/OBJECTIVE: Functional electrical stimulation (FES) is commonly used in rehabilitation to generate electrically-induced muscle contractions. FES has been shown to assist in the recovery of voluntary motor functions after stroke or spinal cord injury. However, discomfort associated with FES can motivate patients to withdraw their participation from FES therapy despite its benefits. To address this issue, a functional electrical stimulator, called MyndMove™ (MyndTec Inc., Canada), has been developed to generate more comfortable contractions than conventional stimulators. DESIGN: Cross-sectional, interventional, with two treatment arms. SETTING: A laboratory within a rehabilitation center. PARTICIPANTS: Twelve able-bodied participants. INTERVENTION: FES delivered with two different stimulators, MyndMove™ and Compex Motion (Compex, Switzerland), during muscle contractions of high, moderate and low stimulation intensity. OUTCOME MEASURES: Comfort-related preference to a given stimulator and the discomfort score rated through a Numeric Rating Scale (NRS-101) for both stimulators. RESULTS: Participants perceived a reduction in discomfort during high-intensity stimulation generated using MyndMove™. In addition, MyndMove™ stimulations were preferred in 60% of all contractions. The reduction in discomfort associated with MyndMove™ might be due the fact that MyndMove™ delivers less charge to generate contractions of equivalent intensity, compared to Compex Motion. CONCLUSION: Reducing discomfort during FES may help in generating stronger and more clinically useful contractions, increasing accessibility of FES therapy to include individuals with low tolerance to FES.

KITE-BCI: A brain-computer interface system for functional electrical stimulation therapy.

CONTEXT/OBJECTIVE: Integrating brain-computer interface (BCI) technology with functional electrical stimulation therapy (FEST) is an emerging strategy for upper limb motor rehabilitation after spinal cord injury (SCI). Despite promising results, the combined use of these technologies (BCI-FEST) in clinical practice is minimal. To address this issue, we developed KITE-BCI, a BCI system specifically designed for clinical application and integration with dynamic FEST. In this paper, we report its technical features and performance. In addition, we discuss the differences in distributions of the BCI- and therapist-triggered stimulation latencies. DESIGN: Two single-arm 40-session interventional studies to test the feasibility of BCI-controlled FEST for upper limb motor rehabilitation in individuals with cervical SCI. SETTING: Rehabilitation programs within the University and Lyndhurst Centres of the Toronto Rehabilitation Institute - University Health Network, Toronto, Canada. PARTICIPANTS: Five individuals with sub-acute (< 6 months post-injury) SCI at the C4-C5 level, AIS B-D, and three individuals with chronic (> 24 months post-injury) SCI at C4 level, AIS B-C. OUTCOME MEASURES: We measured BCI setup duration, and to characterize the performance of KITE-BCI, we recorded BCI sensitivity, defined as the percentage of successful BCI activations out of the total number of cued movements. RESULTS: The overall BCI sensitivities were 74.46% and 79.08% for the sub-acute and chronic groups, respectively. The average KITE-BCI setup duration across the two studies was 11 min and 13 s. CONCLUSION: KITE-BCI demonstrates a clinically viable single-channel BCI system for integration with FEST resulting in a versatile technology-enhanced upper limb motor rehabilitation strategy after SCI.

Brain-computer interface-triggered functional electrical stimulation therapy for rehabilitation of reaching and grasping after spinal cord injury: a feasibility study.

STUDY DESIGN: Feasibility and preliminary clinical efficacy analysis in a single-arm interventional study. OBJECTIVES: We developed a brain-computer interface-triggered functional electrical stimulation therapy (BCI-FEST) system for clinical application and conducted an interventional study to (1) assess its feasibility and (2) understand its potential clinical efficacy for the rehabilitation of reaching and grasping in individuals with sub-acute spinal cord injury (SCI). SETTING: Spinal cord injury rehabilitation hospital-Toronto Rehabilitation Institute-Lyndhurst Centre. METHODS: Five participants with sub-acute SCI completed between 12 and 40 1-hour sessions using BCI-FEST, with up to 5 sessions a week. We assessed feasibility by measuring participants' compliance with treatment, the occurrence of adverse events, BCI sensitivity, and BCI setup duration. Clinical efficacy was assessed using Functional Independence Measure (FIM) and Spinal Cord Independence Measure (SCIM), as primary outcomes. In addition, we used two upper-limb function tests as secondary outcomes. RESULTS: On average, participants completed 29.8 sessions with no adverse events. Only one of the 149 sessions was affected by technical challenges. The BCI sensitivity ranged between 69.5 and 80.2%, and the mean BCI setup duration was ~11 min. In the primary outcomes, three out of five participants showed changes greater than the minimal clinically important differences (MCIDs). Additionally, the mean change in secondary outcome measures met the threshold for detecting MCID as well; four out of five participants achieved MCID. CONCLUSIONS: The new BCI-FEST intervention is safe, feasible, and promising for the rehabilitation of reaching and grasping after SCI.

Haploinsufficiency of X-linked intellectual disability gene CASK induces post-transcriptional changes in synaptic and cellular metabolic pathways.

Heterozygous mutations in the X-linked gene CASK are associated with intellectual disability, microcephaly, pontocerebellar hypoplasia, optic nerve hypoplasia and partially penetrant seizures in girls. The Cask+/- heterozygous knockout female mouse phenocopies the human disorder and exhibits postnatal microencephaly, cerebellar hypoplasia and optic nerve hypoplasia. It is not known if Cask+/- mice also display seizures, nor is known the molecular mechanism by which CASK haploinsufficiency produces the numerous documented phenotypes. 24-h video electroencephalography demonstrates that despite sporadic seizure activity, the overall electrographic patterns remain unaltered in Cask+/- mice. Additionally, seizure threshold to the commonly used kindling agent, pentylenetetrazol, remains unaltered in Cask+/- mice, indicating that even in mice the seizure phenotype is only partially penetrant and may have an indirect mechanism. RNA sequencing experiments on Cask+/- mouse brain uncovers a very limited number of changes, with most differences arising in the transcripts of extracellular matrix proteins and the transcripts of a group of nuclear proteins. In contrast to limited changes at the transcript level, quantitative whole-brain proteomics using iTRAQ quantitative mass-spectrometry reveals major changes in synaptic, metabolic/mitochondrial, cytoskeletal, and protein metabolic pathways. Unbiased protein-protein interaction mapping using affinity chromatography demonstrates that CASK may form complexes with proteins belonging to the same functional groups in which altered protein levels are observed. We discuss the mechanism of the observed changes in the context of known molecular function/s of CASK. Overall, our data indicate that the phenotypic spectrum of female Cask+/- mice includes sporadic seizures and thus closely parallels that of CASK haploinsufficient girls; the Cask+/- mouse is thus a face-validated model for CASK-related pathologies. We therefore surmise that CASK haploinsufficiency is likely to affect brain structure and function due to dysregulation of several cellular pathways including synaptic signaling and cellular metabolism.

Restoration of Upper Limb Function After Chronic Severe Hemiplegia: A Case Report on the Feasibility of a Brain-Computer Interface-Triggered Functional Electrical Stimulation Therapy.

Functional electrical stimulation therapy (FEST) is a state-of-the-art treatment for retraining motor function after neurological injuries. Recent literature suggests that FEST can be further improved with brain-computer interface (BCI) technology. In this case study, we assessed the feasibility of using BCI-triggered FEST (BCI-FEST) to restore upper limb function in a 57-yr-old man with severe left hemiplegia resulting from a stroke 6 yrs before enrollment in the study. The intervention consisted of two blocks of forty 1-hr BCI-FEST sessions, with three sessions delivered weekly. During therapy, a single-channel BCI was used to trigger the stimulation programmed to facilitate functional movements. The measure of the feasibility of the BCI-FEST included assessing the implementation and safety of the intervention. Clinical improvements were assessed using (a) Functional Independence Measure, (b) Action Research Arm Test, (c) Toronto Rehabilitation Institute - Hand Function Test, and (d) Fugl-Meyer Assessment Upper Extremity test. Upon completion of 80 therapy sessions, 14-, 17-, and 18-point changes were recorded on Action Research Arm Test, Fugl-Meyer Assessment Upper Extremity test, and Toronto Rehabilitation Institute - Hand Function Test, respectively. The participant also indicated improvement as demonstrated by his ability to perform various day-to-day tasks. The results suggest that BCI-FEST is safe and viable.

Impact of conversion from an open ward design paediatric intensive care unit environment to all isolated rooms environment on incidence of bloodstream infections and antibiotic resistance in Southern Israel (2000 to 2008).

We studied the epidemiology, microbiology, clinical aspects and outcome of bloodstream infections (BSI) in a tertiary paediatric intensive care unit. All BSI episodes were prospectively identified and analysed. The paediatric intensive care unit moved in 2006 from an open-plan unit to a new (all single room) unit. Three hundred and fifty-three BSI episodes occurred in 299 of 4162 patients. Overall, BSI incidence was 85 per 1000 hospitalised children. Fewer BSI episodes occurred during the last two years of the study (2007 to 2008), compared with 2000 to 2006 (70 of 1061 admissions, 6.5% versus 283 of 3101 admissions, 9.1%, respectively, P=0.01). There were 127 of 340 (37.4%) community-acquired and 213 of 340 (62.6%) nosocomial BSI episodes (31 of 1000 and 51 of 1000, respectively). Nosocomial BSI episodes decreased during 2007 to 2008 versus 2000 to 2006 (37.7% versus 55.8%, P=0.03). In 448 instances, pathogens were isolated, 231 (52%) Gram-positive and 188 (42%) Gram-negative. Coagulase-negative Staphylococci, S. pneumoniae and S. aureus (41.1%, 19.9% and 11.7%, respectively) were the most common Gram-positive and Enterobacteriaceae spp. the most frequent Gram-negative organisms (45.2%, of them Klebsiella spp. and E. coli 40% and 29.4%, respectively). A significant decrease was recorded during 2007 to 2008 in Enterobacteriaceae resistance to piperacillin, gentamicin and ciprofloxacin. Thirty of 299 (10%, 9 with S. pneumoniae-BSI) patients died. A significant decrease in BSI and nosocomial incidence and Enterobacteriaceae spp. antibiotic resistance was recorded following the conversion of the paediatric intensive care unit from an open ward to an all isolated rooms environment.

Horner's syndrome in patients admitted to the paediatric intensive care unit: epidemiology, diagnosis and clinical practice.

Horner's syndrome appears when the three-neuron sympathetic pathway is interrupted anywhere from the posterior-lateral nuclei of the hypothalamus through the spinal cord to the eye. In children, Horner's syndrome can be either congenital or acquired, but overall it is a rare finding. There are several causes of Horner's syndrome, some of iatrogenic. Although uncommon in the paediatric population, prompt recognition of the syndrome and immediate treatment may prevent permanent damage to the neuronal pathway. Awareness of the risk of developing iatrogenic Horner's syndrome and early detection of signs are recommended to minimise future disability.

Automatic exudate detection using active contour model and regionwise classification.

Diabetic retinopathy is one the most common cause of blindness in the world. Exudates are among the early signs of this disease, so its proper detection is a very important task to prevent consequent effects. In this paper, we propose a novel approach for exudate detection. First, we identify possible regions containing exudates using grayscale morphology. Then, we apply an active contour based method to minimize the Chan-Vese energy to extract accurate borders of the candidates. To remove those false candidates that have sufficient strong borders to pass the active contour method we use a regionwise classifier. Hence, we extract several shape features for each candidate and let a boosted Naïve Bayes classifier eliminate the false candidates. We considered the publicly available DiaretDB1 color fundus image set for testing, where the proposed method outperformed several state-of-the-art exudate detectors.

Selective oncolytic effect of an attenuated Newcastle disease virus (NDV-HUJ) in lung tumors.

Newcastle disease virus (NDV), an avian paramyxovirus, has a potential oncolytic effect that may be of significance in the treatment of a variety of cancer diseases. An attenuated lentogenic isolate of NDV (HUJ) demonstrated a selective cytopathic effect upon a panel of human and mouse lung tumor cells, as compared to human nontumorigenic lung cells. The virus-selective oncolytic effect is apoptosis dependent, and related to higher levels of viral transcription, translation and progeny virus formation. Furthermore, NDV-HUJ oncolytic activity is directed in-cis and not through induction of cytokines, that may act in-trans on neighboring cells. Development of primary lung tumors and of the consequent metastasis in mice inoculated with mouse lung tumor cells 3LL-D122 was decreased following treatment with NDV-HUJ. The preferential killing of the tumor cells is not due to a deficiency in the interferon (IFN) system, as expression of the IFN-beta gene, in the infected cells, is properly induced. Moreover, pretreatment with IFN effectively protected the tumor cells from the virus oncolytic effect. We conclude therefore, that NDV-HUJ should have a significant benefit in the treatment of lung cancer as well as other malignancies.

[Prediction of intrauterine growth retardation using the integrated test markers]. / Predikcia intrauterinnej rastovej retardácie plodu pomocou markerov integrovaného testu.

OBJECTIVE: Author's objective was to ascertain the option for prediction of intrauterine growth retardation using the integrated test markers on the population of pregnant women in Kosice city. DESIGN: Retrospective, longitudinal, multicenter study. SETTING: 2nd Department of Obstetrics and Gynecology University of P. J. Safárik, Kosice, Slovak Republic. METHODS: The study group comprised 578 pregnant patients of 2nd Department of Obstetrics and Gynecology, in the period from 01.11.2001 until 31.01.2005 for integrated test consisting of (examination of the gestation age using CRL, concentration of PAPP-A, NT, AFP, uE3, hCG). Information on birth weight, gender, gestation age at the time of delivery, occurrence of preeclampsia and other pregnancy complications were found in 578 patients retrospectivelly. We have designed two outcome criteria: 1. intrauterine growth retardation <5th fetal weight percentile - IUGR 5 - and intrauterine growth retardation <10th percentile - IUGR 10. In order to make use of the summary information provided by the markers, we have used the method of logistic regression to identify statistically significant predictors of individual binary outcomes (IUGR 5 and IUGR 10). First we developed an equation based on all available predictors. Statistically insignificant predictors were gradually eliminated from the model (Stepwise regression) until the final model remained, for which a ROC curve was developed and values of sensitivity, specificity, positive and negative predictive values at 5% FP (false positivity) were calculated. RESULTS: The final model of IUGR 5, containing only statistically significant markers of integrated test achieved - at 5% FP level and 95% specificity level - a 34.8% sensitivity, 24.1% positive and 97.0% negative predictive value - in prediction of birth weight under 5th percentile with respect to gestation age and gender. The final model of IUGR 10, containing only statistically significant markers achieved - at 5% FP level and 95% specificity level - a 36.4% sensitivity, 32.1% positive and 95.8% negative predictive value - in prediction of birth weight under 10th percentile with respect to gestation age and gender. CONCLUSION: Our results, as well as the results of other studies, lead to the conclusion, that in spite of the multitude of biochemical markers and various options for their combination with ultrasound markers, so far it has been impossible to find a combination which would meet the following criteria: 1. high sensitivity and specificity at low false positive values and high positive and negative predictive value, 2. application as a screening method for prediction of intrauterine growth retardation and preeclampsia in unselected population of pregnant women.

Contractile effect of ghrelin on isolated guinea-pig renal arteries.

Ghrelin, a 28-amino acid peptide, known to exist in both acylated and des-acylated varieties, was identified as the first endogenous ligand of growth hormone secretagogue receptor in 1999. Various arteries are known to express ghrelin receptors, but the direct action of ghrelin on blood vessels has been unclear. In the present study we show that ghrelin concentration-dependently potentiates endothelin-1 (ET-1) induced tension development of guinea-pig renal artery, as measured using a wire-type isometric myography of vascular segments. In vascular smooth muscle cells (SMC) ghrelin caused activation of potassium outward currents via phospholipase C (PLC)-->inositol-1,4,5-trisphosphate (IP3) and PLC-->protein kinase C (PKC) signalling cascade, resulting in hyperpolarizaton of the cell membrane. On a tissue level ghrelin by itself had no effect on isometric tone, but augmented ET-1 induced contraction by a mechanism, involving PLC, Rho-kinase and intracellular IP3 -sensitive Ca2+ release, and not nucleotide-sensitive protein kinases or PKC. Together with our previous findings the data in this study suggest that ghrelin exerts its contractile activity on guinea-pig renal artery by facilitation of ET-1 triggered intracellular signalling in SMC, and/or by stimulating the release of a yet unknown contractile mediator from endothelium.

[Prediction of preeclampsia using the integrated test markers]. / Predikcia preeklampsie pomocou markerov integrovaného testu.

OBJECTIVE: Author's objective was to ascertain the option for prediction of preeclampsia using the integrated test markers on the population of pregnant women in Kosice city. DESIGN: Retrospective, longitudinal, multicenter study. SETTING: 2nd Department of Obstetrics and Gynecology University of P. J. Safárik, Kosice, Slovak Republic. METHODS: The study group comprised 578 pregnant patients of 2nd Department of Obstetrics and Gynecology, the period from 01.11.2001 until 31.01.2005 for integrated test consisting of (CRL, NT, concentration of PAPP-A, uE3, hCG, AFP). Primary outcome was defined as incidence of preeclampsia during pregnancy. Data on incidence of preeclampsia was collected from birth journals and records in 578 patients retrospectivelly. In order to make use of the summary information provided by the markers we have used the method of logistic regression to identify statistically significant predictors of the binary outcome measure of preeclampsia. First we developed an equation based on all available predictors. Statistically insignificant predictors were gradually eliminated from the model (Stepwise regression) until the final model remained, for which a ROC curve was developed and values of sensitivity, specificity, positive and negative predictive values at 5% FP (false positivity) were calculated. RESULTS: The final model of preeclampsia, which is based only on statistically significant markers of integrated test achieved--at 5% FP and 95% specificity--36.4% sensitivity and 22.7% positive and 97,4 negative predictive value for prediction of preeclampsia in pregnant women. CONCLUSION: Our results, as well as the results of other studies, lead to the conclusion, that in spite of the multitude of biochemical markers and various options for their combination with ultrasound markers for prediction of preeclampsia, so far it has been impossible to find a combination which would meet the following criteria: (1) high sensitivity and specificity at low false positive values and high positive and negative predictive value, (2) application as a screening method for prediction of preeclampsia in unselected population of pregnant women.

Dysfunction of the auditory efferent system in patients with traumatic brain injuries with tinnitus and hyperacusis.

OBJECTIVES: Tinnitus, hyperacusis and difficulty listening in background noise are common symptoms reported by patients with traumatic brain injury (TBI). The aim of this study was to explore the function of the auditory system in TBI patients with and without auditory complaints but having normal pure-tone audiograms. METHODS: The study consisted of 24 TBI patients with and 10 TBI patients without auditory complaints. In addition, 15 normal controls were included in the study. The function of the auditory system was tested by recording transient otoacoustic emissions (TEOAE) during the presentation of increasing levels of white noise in the contralateral ear. RESULTS: Most of the TBI patients with auditory complaints (87%) showed absent or significantly reduced effect of the auditory efferent system as compared with the TBI patients without auditory complaints and to normal controls. However, the global amplitude of the TEOAE was significantly higher in TBI patients with auditory complaints compared to those without. CONCLUSIONS: Due to its role in peripheral and central auditory activity, dysfunction of the efferent system may be at least partially responsible for these auditory complaints. This study underscores the importance of testing and evaluating the functional integrity of the medial efferent system by an objective and non-invasive method in patients with TBI.

Role of imaging in the diagnosis of acute appendicitis in children.

The aim of the study was to investigate the place of imaging in the diagnosis and treatment of acute appendicitis. The files of 2,427 children with suspected acute appendicitis were reviewed for clinical management and operative findings. The sample was divided into 3 groups at time of admission: (1) before diagnostic imaging was available in our department (1991-1994); (2) after the introduction of imaging studies on a random basis in equivocal cases (1995-1998); and (3) after a policy was formulated for ultrasound use in all equivocal cases followed by computed tomography if necessary (1999-2000). Results showed that the rate of misdiagnosis decreased from 13.2% in group 1 to 6.5% in group 2 and 6.1% in group 3. False-positive findings (normal appendix with positive scan) were noted in 16.7% of group 2 and 25% of group 3; false-negative findings (appendicitis at surgery with negative scan) in 23.8% and 9.5%, respectively. Computed tomography was performed in 8 children and prevented unnecessary surgery in 4 of them. We conclude that in equivocal cases of acute appendicitis, imaging studies performed by skilled operators can improve the accuracy of diagnosis, saving patients unnecessary surgery, and identifying other conditions that mimic appendicitis.