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One of the most disabling symptoms of hepatitis C virus ( HCV) infection is chronic fatigue. While this is accepted for HCV polymerase chain reaction ( PCR)-positive patients, a relationship between HCV infection and chronic fatigue is questioned after successful virus eradication. As fatigue is a subjective criterion, we aimed to evaluate in addition mood alterations and cognitive function in HCV-exposed patients with only mild liver disease and to assess a) possible interrelationships between these factors and health-related quality of life and b) the impact of viremia and former interferon treatment. One hundred and fifty-nine anti- HCV-positive individuals without advanced liver disease answered health-related quality of life ( HRQoL), fatigue and depression questionnaires and underwent a battery of attention and memory tests. Accompanying diseases which could distort the results of the study such as HIV co-infection or drug addiction were exclusion criteria. The patients were subdivided into four groups according to their viremia status and interferon treatment history. Patients' data were evaluated with respect to norms given in the respective test manuals and in addition compared to those of 33 age-matched healthy controls. Eighty-five per cent of the patients had chronic fatigue, 50-60% mild depression or anxiety, 45% memory deficits and 30% attention deficits, irrespective of their HCV viremia status or treatment history. HRQoL correlated negatively with chronic fatigue ( P<.001), while cognitive deficits-especially memory function-were independent from fatigue and depression. HCV infection may cause long-standing cerebral dysfunction that significantly impairs HRQoL and may even persist after clearance of the virus. [ABSTRACT FROM AUTHOR]

Aim The impact of disuse on the loss of skeletal muscle mass and strength has been well documented. Given that most studies have investigated muscle atrophy after more than 2 weeks of disuse, few data are available on the impact of shorter periods of disuse. We assessed the impact of 5 and 14 days of disuse on skeletal muscle mass, strength and associated intramuscular molecular signalling responses. Methods Twenty-four healthy, young (23 ± 1 year) males were subjected to either 5 ( n = 12) or 14 ( n = 12) days of one-legged knee immobilization using a full leg cast. Before and immediately after the immobilization period, quadriceps muscle cross-sectional area ( CSA), leg lean mass and muscle strength were assessed, and biopsies were collected from the vastus lateralis. Results Quadriceps muscle CSA declined from baseline by 3.5 ± 0.5 ( P < 0.0001) and 8.4 ± 2.8% ( P < 0.001), leg lean mass was reduced by 1.4 ± 0.7 ( P = 0.07) and 3.1 ± 0.7% ( P < 0.01) and strength was decreased by 9.0 ± 2.3 ( P < 0.0001) and 22.9 ± 2.6% ( P < 0.001) following 5 and 14 days of immobilization respectively. Muscle myostatin mRNA expression doubled following immobilization ( P < 0.05) in both groups, while the myostatin precursor isoform protein content decreased after 14 days only ( P < 0.05). Muscle MAFBx mRNA expression increased from baseline by a similar magnitude following either 5 or 14 days of disuse, whereas MuRF1 mRNA expression had increased significantly only after 5 days. Conclusion We conclude that even short periods of muscle disuse can cause substantial loss of skeletal muscle mass and strength and are accompanied by an early catabolic molecular signalling response. [ABSTRACT FROM AUTHOR]

Aim Short periods of muscle disuse, due to illness or injury, result in substantial skeletal muscle atrophy. Recently, we have shown that a single session of neuromuscular electrical stimulation ( NMES) increases muscle protein synthesis rates. The aim was to investigate the capacity for daily NMES to attenuate muscle atrophy during short-term muscle disuse. Methods Twenty-four healthy, young (23 ± 1 year) males participated in the present study. Volunteers were subjected to 5 days of one-legged knee immobilization with ( NMES; n = 12) or without ( CON; n = 12) supervised NMES sessions (40-min sessions, twice daily). Two days prior to and immediately after the immobilization period, CT scans and single-leg one-repetition maximum (1 RM) strength tests were performed to assess quadriceps muscle cross-sectional area ( CSA) and leg muscle strength respectively. Furthermore, muscle biopsies were taken to assess muscle fibre CSA, satellite cell content and m RNA and protein expression of selected genes. Results In CON, immobilization reduced quadriceps CSA by 3.5 ± 0.5% ( P < 0.0001) and muscle strength by 9 ± 2% ( P < 0.05). In contrast, no significant muscle loss was detected following immobilization in NMES although strength declined by 7 ± 3% ( P < 0.05). Muscle MAFbx and Mu RF1 m RNA expression increased following immobilization in CON ( P < 0.001 and P = 0.07 respectively), whereas levels either declined ( P < 0.01) or did not change in NMES, respectively. Immobilization led to an increase in muscle myostatin m RNA expression in CON ( P < 0.05), but remained unchanged in NMES. Conclusion During short-term disuse, NMES represents an effective interventional strategy to prevent the loss of muscle mass, but it does not allow preservation of muscle strength. NMES during disuse may be of important clinical relevance in both health and disease. [ABSTRACT FROM AUTHOR]

Background: The introduction of intravenous thrombolysis with recombinant tissue Plasminogen Activator (rt-PA) has greatly improved the effectiveness of acute ischaemic stroke care. However, in most hospitals only 2–10% of all admitted stroke patients are treated with thrombolysis.Aim: The purpose of this study is to identify if available protocols, training and infrastructure influence the thrombolysis rate.Design: Cohort study of 12 hospitals in the Netherlands.Methods: In a cohort of patients admitted with acute stroke within 24 h from onset of symptoms, data were obtained. Stroke service characteristics of 12 hospitals were acquired through structured interviews with intra- and extramural representatives, in order to asses (i) protocols, (ii) training and (iii) complexity of infrastructure. Data were analysed with multi-level logistic regression to relate the likelihood of treatment with thrombolysis to availability and completeness of protocols, training and infrastructure both outside (extramural) and inside (intramural) each centre.Results: Overall 5515 patients were included in the study. Thrombolysis rates varied from 5.7% to 21.7%. An association was observed between thrombolysis rates and extramural training [odds ratio (OR): 1.11; 95% confidence interval (CI): 0.99–1.25] and availability of intramural protocols (OR: 1.46; 95% CI: 1.12–1.91).After adjustment for hospital size and teaching vs. nonteaching hospital, these associations became stronger; extramural training [adjusted OR (aOR): 1.14; 95% CI: 1.01–1.30] and availability of intramural protocols (aOR: 1.77; 95% CI: 1.30–2.39).Conclusions: Extramural training and intramural protocols are important tools to increase thrombolysis rates for acute ischaemic stroke in hospitals. Intramural protocols and extramural training should be aimed at all relevant professionals. [ABSTRACT FROM AUTHOR]

The authors reflect on previously published data about the physiological effect of bed rest. They present a study to test the hypothesis that bed rest would lead to greater muscle loss when compared with single leg immobilization. The authors demonstrate an equivalent decline in leg muscle mass after short-term muscle disuse in both models.

Objective: Several studies indicate that only a small proportion of patients with acute ischaemic stroke are treated with intravenous thrombolysis. Indications and contraindications for this treatment are usually based on the inclusion and exclusion criteria of randomised clinical trials. The trial context of these criteria hampers implementation in real life settings. We therefore aimed to obtain specialist opinion in a Delphi consensus on these contraindications.Methods: We used the Delphi approach on an international group of specialists in the field of thrombolysis. Inclusion and exclusion criteria were reworded into 18 quantitatively phrased propositions. Feedback consisted of the median score, interquartile range and the panellist's own score in the previous round. For each item, we defined consensus as the achievement of an interdecile range within two prespecified clinically relevant units.Results: Thirty-one specialists participated in the first round and 30 completed all three rounds. Consensus was reached on 12 of the 18 propositions: previous ischaemic stroke, head trauma and gastrointestinal tract bleeding should not have taken place earlier than 1.5 months, 2 months and 14 days, respectively; the severity of the neurological deficit is defined as a National Institutes of Health Stroke Scale (NIHSS) score of 2-3 or more, and blood pressure level should not be >185/110 mmHg; platelet count should be >90x10(12)/l, glucose levels 2.7-22 mmol/l, international normalised ratio <1.5 and activated partial thromboplastin time <50 s. No consensus was reached on propositions concerning the stroke onset to treatment time, patient's age, recent medical procedures, spontaneous improvement rate and blood pressure treatment.Conclusions: We present specialists' opinion on contraindications for intravenous thrombolysis in ischaemic stroke. The results of this study may be relevant for routine clinical practice as they may help to increase the number of treated patients. [ABSTRACT FROM AUTHOR]

The increasing incidence of acyclovir ( ACV) and multidrug-resistant strains in patients with Herpetic Stromal Keratitis ( HSK) is a major health problem and often results in blindness. In the study we examined the effectivity of mAb 2c in preventing experimental HSK in BALB/c mice. Mice were infected with HSV-1 ( KOS) and subsequently either systemically or topically treated with mAb 2c. Systemic treatment was performed by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure prophylaxis) or 24, 40, and 56 hours after infection (post-exposure immunotherapy). For topical treatment antibody-containing eye drops or PBS as control was administered (5 times per day). Systemic antibody treatment markedly reduced viral loads and completely protected mice from developing HSK. The administration of antibody prior or post infection was equally effective. Topical treatment had no improving effect on the severity of HSK. In conclusion, our data demonstrate that mAb 2c proved to be effective for the treatment of corneal HSV-infections and for prevention of HSK and blindness. Moreover, the humanized counterpart ( mAb hu2c) was equally potent in protecting mice from HSV-induced HSK when compared to the parental mouse antibody. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection may induce chronic fatigue and cognitive dysfunction. Virus replication was proven within the brain and HCV-positive cells were identified as microglia and astrocytes. We hypothesized that cerebral dysfunction in HCV-afflicted patients is associated with microglia activation. Microglia activation was assessed in vivo in 22 patients with chronic HCV infection compared to six healthy controls using [11C]-PK11195 Positron Emission Tomography (PET) combined with magnetic resonance tomography for anatomical localization. Patients were subdivided with regard to their PCR status, Fatigue Impact Scale score (FIS) and attention test sum score (ATS). A total of 12 patients (54.5%) were HCV PCR positive [of which 7 (58.3%) had an abnormal FIS and 7 (58.3%) an abnormal ATS], 10 patients (45.5%) were HCV PCR negative (5 (50%) each with an abnormal FIS or ATS). Patients without attention deficits showed a significantly higher accumulation of [11C]-PK11195 in the putamen ( P = 0.05), caudate nucleus ( P = 0.03) and thalamus ( P = 0.04) compared to controls. Patients with and without fatigue did not differ significantly with regard to their specific tracer binding in positron emission tomography. Preserved cognitive function was associated with significantly increased microglia activation with predominance in the basal ganglia. This indicates a probably neuroprotective effect of microglia activation in HCV-infected patients. [ABSTRACT FROM AUTHOR]

Hepatitis C virus ( HCV) causes not only liver damage in certain patients but can also lead to neuropsychiatric symptoms. Previous studies have shown that the type 4 allele of the gene for apolipoprotein E ( APOE) is strongly protective against HCV-induced damage in liver. In this study, we have investigated the possibility that APOE genotype is involved in the action of HCV in brain. One hundred HCV-infected patients with mild liver disease underwent a neurological examination and a comprehensive psychometric testing of attention and memory function. In addition, patients completed questionnaires for the assessment of fatigue, health-related quality of life and mood disturbances. Apolipoprotein E gene genotyping was carried out on saliva using buccal swabs. The APOE-ε4 allele frequency was significantly lower in patients with an impairment of working memory, compared to those with a normal working memory test result ( P = 0.003). A lower APOE-ε4 allele frequency was also observed in patients with definitely altered attention ability ( P = 0.008), but here, the P-value missed the level of significance after application of the Bonferroni correction. Our data suggest that the APOE-ε4 allele is protective against attention deficit and especially against poor working memory in HCV-infected subjects with mild liver disease. Considering the role of apolipoprotein E in the life cycle of the virus, the findings shed interesting new light upon possible pathomechanisms behind the development of neuropsychiatric symptoms in hepatitis C infection. [ABSTRACT FROM AUTHOR]

Abstract: The neural mechanisms subserving uni- and bimanual control of movements are not well understood. Nevertheless, recent studies indicate a functional role of oscillatory activity in movement control and point towards a hemispheric asymmetry in motor control. This study specifically addresses the issues of (i) task-relatedness, (ii) hemispheric symmetry, and (iii) frequency specificity of the measures power, cerebro-muscular coherence, and cerebro-cerebral coherence in bilateral primary motor cortex and supplementary motor area (SMA). We have studied 10 right-handed subjects with simultaneous recordings of magnetoencephalography and surface electromyography during different unimanual and bimanual tasks. Using the analysis technique Dynamic Imaging of Coherent Sources (DICS), left and right primary motor cortex and SMA were functionally localized. Power, cerebro-musclar coherence, and cerebro-cerebral coherence between these areas were computed for four frequency bands in each condition and subjected to ANOVA. Results show a task-specific modulation of power and coherence, and further indicate a hemispheric asymmetry in the control of unimanual and bimanual movements. In addition, different frequency bands showed different task-dependent variations. The gamma band (26–40 Hz) showed strongest modulation for cerebro-muscular coherence and was strongest for the isometric contraction conditions. In contrast, the beta band (13–24 Hz) showed the strongest variations between static and dynamic conditions, and seems to play a particular role in movement control. In summary, our results indicate a differential functional role of oscillatory activity and coupling in the motor system. [Copyright &y& Elsevier]

We studied differences in the development of sensitivity to first-versus second-order global motion by comparing the motion coherence thresholds of 5-year-olds and adults tested at three speeds (1.5, 6, and 9°s−1). We used Random–Gabor Kinematograms (RGKs) formed with luminance-modulated (first-order) or contrast-modulated (second-order) concentric Gabor patterns with a sinusoidal spatial frequency of 3c deg−1. To achieve equal visibility, modulation depth was set at 30% for first-order Gabors and at 100% for second-order Gabors. Subjects were 24 adults and 24 5-year-olds. For both first- and second-order global motion, the motion coherence threshold of 5-year-olds was less mature for the slowest speed (1.5°s−1) than for the two faster speeds (6 and 9°s−1). In addition, at the slowest speed, the immaturity was greater for second-order than for first-order global motion. The findings suggest that the extrastriate mechanisms underlying the perception of global motion are different, at least in part, for first- versus second-order signals and for slower versus faster speeds. They also suggest that those separate mechanisms mature at different rates during middle childhood. [Copyright &y& Elsevier]

Abstract: Background: Tattooed persons examined with magnetic resonance imaging (MRI) can develop burning sensation suggested in the literature to be thermal burn from the procedure. MRI‐induced thermal effect and magnetic behavior of known tattoo pigments were examined ex vivo. Materials and Methods: Magnetic resonance imaging effects on 3 commonly used commercial ink stock products marketed for cosmetic tattooing was studied. A main study tested 22 formulations based on 11 pigment raw materials, for example, one line of 11 called pastes and another called dispersions. Samples were spread in petri dishes and tested with a 0.97 T neodymium solid magnet to observe visual magnetic behavior. Before MRI, the surface temperature of the ink was measured using an infrared probe. Samples were placed in a clinical 3T scanner. Two scans were performed, that is, one in the isocenter and one 30 cm away from the center. After scanning, the surface temperature was measured again. Chemical analysis of samples was performed by mass spectroscopy. Results: Mean temperature increase measured in the isocenter ranged between 0.14 and 0.26°C (P < .01) and in the off‐center position from −0.16 to 0.21°C (P < .01). Such low increase of temperature is clinically irrelevant. Chemical analysis showed high concentrations of iron, but also nickel and chrome were found as contaminants. High concentration of iron was not associated with any increase of temperature or any physical draw or move of ink. Conclusion: The study could not confirm any clinically relevant temperature increase of tattoo pigments after MRI. [ABSTRACT FROM AUTHOR]

Examines the neural basis of intermittent motor control in humans. Use of tomographic coherence mapping in determining coherent oscillatory activity; Demonstration of slow finger movements; Modulation of the output of primary motor cortex.

Contexte L’ustekinumab est un anticorps monoclonal dirigé contre la sous-unité p40 de l’interleukine-12/23. Il a été montré supérieur au placebo dans l’induction de la réponse et le maintien de la rémission chez les patients adultes atteints de maladie de Crohn modérée à sévère, mais pas encore étudié en pédiatrie. Buts de l’étude Décrire la sécurité et l’efficacité de l’ustekinumab chez les enfants atteints de maladie de Crohn réfractaire. Méthodes Nous rapportons six patients (4 garçons) qui ont reçu de l’ustekinumab dans notre centre entre février et octobre 2014 pour maladie de Crohn réfractaire aux anti-TNF. Résultats L’âge médian au début de l’ustekinumab était de 16,4 ans (10,7–18,2) et la durée médiane de la maladie était de 3,6 ans (1,0–8,4). La localisation de la maladie distale selon la classification de Paris était L1 chez 1 patient, L3 chez 4 et pas atteinte colique chez 1 ; la localisation haute était : L4a chez 2 patients et L4b chez 2. Le phénotype était non pénétrant non sténosant dans 5 cas et sténosant dans 1. Aucun patient n’avait de maladie périanale. Tous les patients avaient échoué ou étaient intolérants aux immunomodulateurs (5 patients à l’azathioprine, 6 au méthotrexate). Tous avaient eu un échec d’infliximab (2 avaient interrompu pour perte de réponse, 2 pour allergies ou événements indésirables et 2 pour les deux raisons). Cinq patients avaient échoué à l’adalimumab, et un n’en avait pas reçu. Un patient avait eu deux résections intestinales avec stricturoplasties. À l’initiation de l’ustekinumab, quatre patients étaient sous prednisone et 3 sous méthotrexate. L’ustekinumab était administrée par voie sous-cutanée à la dose de 45 mg (si le poids ≤ 45 kg) par semaine ou 90 mg (si le poids > 45 kg) par semaine, pendant trois semaines pendant le traitement d’induction. Après le traitement d’induction, 3 patients ont eu une réponse clinique, 1 était en rémission clinique et 2 n’ont pas eu de réponse. Cinq patients ont continué le traitement d’entretien de 45 mg toutes les 8 semaines ou 90 mg toutes les 8 semaines en fonction de la posologie reçue lors de l’induction. Une augmentation de la dose était nécessaire dans deux cas. Au total, les patients ont reçu une médiane de 6,5 doses (3–9) d’ustekinumab. La réponse au traitement d’entretien a été évaluée après une période médiane de 5,1 mois (3,7 à 7,1) : 1 patient était en rémission clinique, 2 avaient une réponse clinique et 2 n’ont eu aucune réponse, dont l’un a nécessité une colectomie subtotale avec iléostomie. Aucun événement indésirable n’a été noté. Conclusions L’ustekinumab est bien toléré chez les patients pédiatriques. Plus de données sont nécessaires pour confirmer l’efficacité montrée chez l’adulte. [ABSTRACT FROM AUTHOR]