MP2RAGE provides new clinically-compatible correlates of mild cognitive deficits in relapsing-remitting multiple sclerosis.

Despite that cognitive impairment is a known early feature present in multiple sclerosis (MS) patients, the biological substrate of cognitive deficits in MS remains elusive. In this study, we assessed whether T1 relaxometry, as obtained in clinically acceptable scan times by the recent Magnetization Prepared 2 Rapid Acquisition Gradient Echoes (MP2RAGE) sequence, may help identifying the structural correlate of cognitive deficits in relapsing-remitting MS patients (RRMS). Twenty-nine healthy controls (HC) and forty-nine RRMS patients underwent high-resolution 3T magnetic resonance imaging to obtain optimal cortical lesion (CL) and white matter lesion (WML) count/volume and T1 relaxation times. T1 z scores were then obtained between T1 relaxation times in lesion and the corresponding HC tissue. Patient cognitive performance was tested using the Brief Repeatable Battery of Neuro-psychological Tests. Multivariate analysis was applied to assess the contribution of MRI variables (T1 z scores, lesion count/volume) to cognition in patients and Bonferroni correction was applied for multiple comparison. T1 z scores were higher in WML (p < 0.001) and CL-I (p < 0.01) than in the corresponding normal-appearing tissue in patients, indicating relative microstructural loss. (1) T1 z scores in CL-I (p = 0.01) and the number of CL-II (p = 0.04) were predictors of long-term memory; (2) T1 z scores in CL-I (β = 0.3; p = 0.03) were independent determinants of long-term memory storage, and (3) lesion volume did not significantly influenced cognitive performances in patients. Our study supports evidence that T1 relaxometry from MP2RAGE provides information about microstructural properties in CL and WML and improves correlation with cognition in RRMS patients, compared to conventional measures of disease burden.

Psychomotor retardation in depression: bradykinesia or paucity of movement?

Objectives: Psychomotor retardation is part of Major Depression (MD) diagnosis criteria and has been assimilated to bradykinesia, even though there is a clear lack of objective measurement of motor activity in MD. We conducted a study to evaluate bradykinesia, posture and gait parameters in MD patients with an ambulatory system, allowing continuous motor measurements. Methods: Patients with DSM-IV MD and healthy controls matched for age and sex were asked to carry on with their usual activities while being recorded for 6 hours by a wireless autonomous ambulatory system, containing miniature gyroscopes, data-logger, battery and flash memory. allowing continuous recording of upper limbs movements (speed, amplitude and activity (% of time with movement)), posture (% of time standing, walking, lying or sitting) and gait parameters (speed, cadence, stance, double support, stride). Results: Hands activity was significantly lower in depressed patients, as compared to controls (MD: 40%, controls: 60%; p<0.05). Speed of hand movements (p= 0.13) and their amplitude (p=0.71) were similar to controls. MD patients had a trend to spend more time lying or sitting than controls (p=0.06) but did not differ in terms of any gait parameters. Conclusion: Patients with MD displayed less hand movements than controls and tended to spend more time lying or sitting over 6 hours, but did not differ in terms of speed and amplitude of movement, nor in gait parameters. These results suggest that psychomotor retardation classically described in MD might be the expression of a paucity of movement rather than a bradykinesia as observed in parkinsonism and might involved different (nondopaminergic) mechanisms.

Membrane interaction of polymyxin B and synthetic analogues studied in biomimetic systems: implications for antibacterial action

Membrane-active antimicrobial peptides, such as polymyxin B (PxB), are currently in the spotlight as potential candidates toovercome bacterial resistance. We have designed synthetic analogs ofPxB in order to determine the structural requirements for membraneaction. Since the mechanism of action of PxB involves interaction withboth the outer membrane and the cytoplasmic membrane of Gramnegative bacteria, we have used an approach based on mimicking theouter layers of these membranes using monolayers, Langmuir-Blodgettfilms and unilamelar vesicles, and applying a battery of biophysicalmethods in order to dissect the different events of membraneinteraction. Collectively, results indicate that the PxB analogues act inthe bacterial membrane by the same mechanism than PxB, and that cationic amphipathicity determines peptide activity.

Diagnóstico de las dificultades de lectura y escritura y de la dislexia basado en la Teoría PASS de lainteligencia utilizando la batería DN-CAS. Origen cognitivo de la dislexia

Las dificultades de lectura y escritura se pueden detectar desde el momento en que los niños y niñas inician el aprendizaje de la lectoescritura en la etapa de Educación Infantil. En algunos casos estos alumnos reciben un apoyo escolar que en muchas ocasiones no conlleva las mejoras esperadas, siendo las técnicas y metodologías de refuerzo aplicadas ineficaces. El problema, desde nuestro punto de vista, empieza con el diagnóstico que se realiza a estos jóvenes, que determina las directrices de la intervención idónea en cada caso. La Teoría PASS de la inteligencia nos permite conocer qué procesos están implicados cuando el niño lee o escribe, y parte de la premisa de que si conocemos el perfil cognitivo de un alumno que presenta dificultades podremos entender como estas se originan. Para conocer este perfil cognitivo (los cuatro procesos cognitivos que describe esta teoría: Planificación, Atención, Simultaneo y Secuencial) utilizamos la batería DN-CAS (Das & Naglieri: Cognitive Assessment System). El perfil obtenido al aplicar el DN-CAS nos permitirá conocer el origen de las dificultades de lectura y escritura, saber cuando está justificada una dislexia, descartar problemas emocionales o la presencia de los mismos y diseñar la intervención más adecuada en cada situación

A new concept of integrated cardiopulmonary bypass circuit.

OBJECTIVE: Standard cardiopulmonary bypass (CPB) circuits with their large surface area and volume contribute to postoperative systemic inflammatory reaction and hemodilution. In order to minimize these problems a new approach has been developed resulting in a single disposable, compact arterio-venous loop, which has integral kinetic-assist pumping, oxygenating, air removal, and gross filtration capabilities (CardioVention Inc., Santa Clara, CA, USA). The impact of this system on gas exchange capacity, blood elements and hemolysis is compared to that of a conventional circuit in a model of prolonged perfusion. METHODS: Twelve calves (mean body weight: 72.2+/-3.7 kg) were placed on cardiopulmonary bypass for 6 h with a flow of 5 l/min, and randomly assigned to the CardioVention system (n=6) or a standard CPB circuit (n=6). A standard battery of blood samples was taken before bypass and throughout bypass. Analysis of variance was used for comparison. RESULTS: The hematocrit remained stable throughout the experiment in the CardioVention group, whereas it dropped in the standard group in the early phase of perfusion. When normalized for prebypass values, both profiles differed significantly (P<0.01). Both O2 and CO2 transfers were significantly improved in the CardioVention group (P=0.04 and P<0.001, respectively). There was a slightly higher pressure drop in the CardioVention group but no single value exceeded 112 mmHg. No hemolysis could be detected in either group with all free plasma Hb values below 15 mg/l. Thrombocyte count, when corrected by hematocrit and normalized by prebypass values, exhibited an increased drop in the standard group (P=0.03). CONCLUSION: The CardioVention system with its concept of limited priming volume and exposed foreign surface area, improves gas exchange probably because of the absence of detectable hemodilution, and appears to limit the decrease in the thrombocyte count which may be ascribed to the reduced surface. Despite the volume and surface constraints, no hemolysis could be detected throughout the 6 h full-flow perfusion period.

La ment forma part de la teva vida, aprèn a cuidar-la!

L’objectiu d’aquest estudi és crear un programa de prevenció de la demència a partir d’activitats i ocupacions significatives. S’utilitzarà la metodologia quantitativa i es realitzarà un estudi experimental i seqüencial. L’estudi es realitzarà al medi rural, concretament a Ripoll (Sant Bernabé). Per tal de poder obtenir la els participants per la realització de l’estudi s’utilitzarà el mostreig aleatori estratificat amb el qual s’obtindrà dos grups de 16 persones de 50 a 55 anys. Els instruments que s’utilitzaran per tal de poder obtenir les dades de l’estudi són el “Qüestionari internacional d’activitat física” (2002), la bateria neuropsicològica anomenada “Test de Barcelona abreviat” (1997), “L’escala de qualitat de vida” (2008), i per acabar s’utilitzarà el “Test KIMED” (2004). Una primera limitació pot ser que l’ajuntament no ens faciliti les dades per tal de poder realitzar el mostreig aleatori estratificat per tal de poder aconseguir la mostra. També pot ser que l’ajuntament no cedeixi el lloc per tal de poder realitzar la intervenció. Un altre possible limitació pot ser el temps atmosfèric. I per acabar també ens podem torbar amb l’abandonament del programa per part d’un o més participants.

Electrical stimulation induces propagated colonic contractions in an experimental model.

BACKGROUND: Direct colonic electrical stimulation may prove to be a treatment option for specific motility disorders such as chronic constipation. The aim of this study was to provoke colonic contractions using electrical stimulation delivered from a battery-operated device. METHODS: Electrodes were inserted into the caecal seromuscular layer of eight anaesthetized pigs. Contractions were induced by a neurostimulator (Medtronic 3625). Caecal motility was measured simultaneously by video image analysis, manometry and a technique assessing colonic transit. RESULTS: Caecal contractions were generated using 8-10 V amplitude, 1000 micros pulse width, 120 Hz frequency for 10-30 s, with an intensity of 7-15 mA. The maximal contraction strength was observed after 20-25 s. Electrical stimulation was followed by a relaxation phase of 1.5-2 min during which contractions propagated orally and aborally over at least 10 cm. Spontaneous and stimulated caecal motility values were significantly different for both intraluminal pressure (mean(s.d.) 332(124) and 463(187) mmHg respectively; P < 0.001, 42 experiments) and movement of contents (1.6(0.9) and 3.9(2.8) mm; P < 0.001, 40 experiments). CONCLUSION: Electrical stimulation modulated caecal motility, and provoked localized and propagated colonic contractions.

SWIVIT - Swiss video-intubation trial evaluating video-laryngoscopes in a simulated difficult airway scenario: study protocol for a multicenter prospective randomized controlled trial in Switzerland.

BACKGROUND: Video-laryngoscopes are marketed for intubation in difficult airway management. They provide a better view of the larynx and may facilitate tracheal intubation, but there is no adequately powered study comparing different types of video-laryngoscopes in a difficult airway scenario or in a simulated difficult airway situation. METHODS/DESIGN: The objective of this trial is to evaluate and to compare the clinical performance of three video-laryngoscopes with a guiding channel for intubation (Airtraq?, A. P. Advance?, King Vision?) and three video-laryngoscopes without an integrated tracheal tube guidance (C-MAC?, GlideScope?, McGrath?) in a simulated difficult airway situation in surgical patients. The working hypothesis is that each video-laryngoscope provides at least a 90% first intubation success rate (lower limit of the 95% confidence interval >0.9). It is a prospective, patient-blinded, multicenter, randomized controlled trial in 720 patients who are scheduled for elective surgery under general anesthesia, requiring tracheal intubation at one of the three participating hospitals. A difficult airway will be created using an extrication collar and taping the patients' head on the operating table to substantially reduce mouth opening and to minimize neck movement. Tracheal intubation will be performed with the help of one of the six devices according to randomization. Insertion success, time necessary for intubation, Cormack-Lehane grade and percentage of glottic opening (POGO) score at laryngoscopy, optimization maneuvers required to aid tracheal intubation, adverse events and technical problems will be recorded. Primary outcome is intubation success at first attempt. DISCUSSION: We will simulate the difficult airway and evaluate different video-laryngoscopes in this highly realistic and clinically challenging scenario, independently from manufacturers of the devices. Because of the sufficiently powered multicenter design this study will deliver important and cutting-edge results that will help clinicians decide which device to use for intubation of the expected and unexpected difficult airway. TRIAL REGISTRATION: NCT01692535.

The effect of n-3 enriched nutrition therapy on post-operative cognitive dysfunction after cardiac surgery

Background: Postoperative cognitive dysfunction (POCD) occurs frequently after cardiac surgery. Some data suggest that inflammation plays a key role in the development of POCD. N-3 fatty acids have been shown to have a beneficial effect on inflammation. We hypothesised that perioperative n-3 enriched nutrition therapy would reduce the incidence of POCD in this group of patients. Methods: Randomized, double blind placebo controlled trial in patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. 2x 250 mL placebo (Ensure Plus™, Abbott Nutrition) or n-3 enriched nutrition therapy (ProSure™ Abbott Nutrition) were administered for ten days starting 5 days prior to surgery. Cognition was assessed preoperatively and 7 days after surgery with the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery (CERAD-NAB) [1]. Results: 16 patients were included. Mean age was 72 } 5.3 for placebo and 75 } 4.8 for ProSure™ respectively. CRP and IL-6 did not differ significantly between groups preoperatively and on postoperative days 1, 3, and 7. Preoperative CERAD total scores were 86 } 10 and 81 } 9 (p = n.s.) for Placebo and ProSure™, respectively. Postoperative scores were 88 } 12, and 77 } 19 (p = n.s.) The change in score was not different between the two groups (Placebo: +3 } 5; ProSure: -5 } 11). Conclusion: In this very small sample no effect of preoperatively started n-3 enriched nutritional supplements on inflammation or cognitive functions were detected. However, there is a large likelihood of a type II error and more patients need to be included to assess possible beneficial effects of this intervention in elderly patients undergoing elective cardiac surgery. 1 Chandler MJ, et al. Neurology. 2005;65:102-6.

Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers.

Substance P (SP), an undecapeptide belonging to the tachykinin family, is released during the activation of sensory nerves, and causes vasodilation, edema and pain through activation of tissular Neurokinin 1 receptors. SP proinflammatory effects are terminated by angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), while the aminopeptidase dipeptidylpeptidase IV (DPPIV) can also play a role. The aim of this randomized, crossover, double-blind study was to assess the cutaneous vasoreactivity (flare and wheal reaction, burning pain sensation) to intradermal injection of ascending doses of SP in six volunteers receiving a single therapeutic dose of the DPPIV inhibitor sitagliptin or a matching placebo. Cutaneous SP challenges produced the expected, dose-dependent flare and wheal response, while eliciting mild to moderate local pain sensation with little dose dependency. However, no differences were shown in the responses observed under sitagliptin compared with placebo, while the study would have been sufficiently powered to detect a clinically relevant increase in sensitivity to SP. The results of this pilot study are in line with proteolytic cleavage of SP by ACE and NEP compensating the blockade of DPPIV to prevent an augmentation of its proinflammatory action.

Wireless Sensor Networks for Infrastructure Monitoring, TR-611, 2010

A good system of preventive bridge maintenance enhances the ability of engineers to manage and monitor bridge conditions, and take proper action at the right time. Traditionally infrastructure inspection is performed via infrequent periodical visual inspection in the field. Wireless sensor technology provides an alternative cost-effective approach for constant monitoring of infrastructures. Scientific data-acquisition systems make reliable structural measurements, even in inaccessible and harsh environments by using wireless sensors. With advances in sensor technology and availability of low cost integrated circuits, a wireless monitoring sensor network has been considered to be the new generation technology for structural health monitoring. The main goal of this project was to implement a wireless sensor network for monitoring the behavior and integrity of highway bridges. At the core of the system is a low-cost, low power wireless strain sensor node whose hardware design is optimized for structural monitoring applications. The key components of the systems are the control unit, sensors, software and communication capability. The extensive information developed for each of these areas has been used to design the system. The performance and reliability of the proposed wireless monitoring system is validated on a 34 feet span composite beam in slab bridge in Black Hawk County, Iowa. The micro strain data is successfully extracted from output-only response collected by the wireless monitoring system. The energy efficiency of the system was investigated to estimate the battery lifetime of the wireless sensor nodes. This report also documents system design, the method used for data acquisition, and system validation and field testing. Recommendations on further implementation of wireless sensor networks for long term monitoring are provided.

Cation Transport Coupled to ATP Hydrolysis By the (Na, K)-ATPase : an integrated, animated model

An Adobe (R) animation is presented for use in undergraduate Biochemistry courses, illustrating the mechanism of Na+ and K+ translocation coupled to ATP hydrolysis by the (Na, K)-ATPase, a P-2c-type ATPase, or ATP-powered ion pump that actively translocates cations across plasma membranes. The enzyme is also known as an E-1/E-2-ATPase as it undergoes conformational changes between the E-1 and E-2 forms during the pumping cycle, altering the affinity and accessibility of the transmembrane ion-binding sites. The animation is based on Horisberger's scheme that incorporates the most recent significant findings to have improved our understanding of the (Na, K)-ATPase structure function relationship. The movements of the various domains within the (Na, K)-ATPase alpha-subunit illustrate the conformational changes that occur during Na+ and K+ translocation across the membrane and emphasize involvement of the actuator, nucleotide, and phosphorylation domains, that is, the "core engine" of the pump, with respect to ATP binding, cation transport, and ADP and P-i release.

Patterns of protein and carbohydrate accumulation during somatic embryogenesis of Acca sellowiana

The aim of this work was to quantify the protein, starch and total sugars levels during histodifferentiation and development of somatic embryos of Acca sellowiana Berg. For histological observations, the samples were dehydrated in a battery of ethanol, embedded in historesin and stained with toluidine blue (morphology), coomassie blue (protein bodies) and periodic acid-Schiff (starch). Proteins were extracted using a buffer solution, precipitated using ethanol and quantified using the Bradford reagent. Total sugars were extracted using a methanol-chloroform-water (12:5:3) solution and quantified by a reaction with anthrone at 0.2%. Starch was extracted using a 30% perchloric acid solution and quantified by a reaction with anthrone at 0.2%. During the somatic embryogenesis' in vitro morphogenesis and differentiation processes, the total protein levels decreased and the soluble sugars levels increased during the first 30 days in culture and remained stable until the 120th day. On the other hand, total protein levels increased according to the progression in the developmental stages of the somatic embryos. The levels of total sugars and starch increased in the heart and cotyledonary stages, and decreased in the torpedo and pre-cotyledonary stages. These compounds play a central role in the development of somatic embryos of Acca sellowiana.

Prevalence of cognitive disorders in HIV plus patients with long-term suppression of viremia

Background: HAART has contributed to decrease the HIV-related mortality and morbidity. However, the prevalence of HIV-associated neurocognitive disorders (HAND) seems to have increased. The aim of this study was to determine the prevalence of cognitive complaint and of HAND in a cohort of aviremic HIV_patients in the South-western part of Switzerland. Design/Methods: Two hundred HIV_ patients who had (1) undetectable HIV RNA concentrations in the plasma for_3 months, (2) no history of major opportunistic infection of the CNS in the past three years, (3) no current use of IV drugs and (4) no signs of major depression according to the DSM-IV criteria, answered a questionnaire designed to elicit cognitive complaints. Cognitive functions of a subset of HIV_ patients with or without cognitive complaints were assessed using the HIV Dementia scale (HDS) and a battery of neuropsychological tests evaluating the sub-cortical functions. Cognitive impairment was defined according to the revised diagnostic criteria for HAND. Non-parametric tests were used for statistics and a Bonferroni corrected standard p level of pB0.002 was applied for multiple comparisons. Results: The prevalence of cognitive complaints was 27% (54 patients) among the 200 questioned patients. At the time of writing this abstract, cognitive functions of 50 complaining and 28 noncomplaining aviremic patients had been assessed with the HDS and the full neuropsychological battery. The prevalence of HAND producing at least mild interference in daily functioning (mild neurocognitive disorders [MND] or HIV-associated dementia [HAD]) was 44% (34/78 patients) in the group who underwent neuropsychological testing. Objective evidences of HAND were more frequent in complaining than in non-complaining patients (pB0.001). Using a ROC curve, a cut-off of 13 on the HDS was found to have a sensitivity of 74% and a specificity of 71% (p_0.001) for the diagnosis of HAND. A trend for lower CNS Penetrating-Effectiveness scores for HAART in patients with MND or HAD as compared to the others was present (1.59 0.6 vs. 1.990.6; p_0.006 [Bonferroni correction]). Conclusions/Relevance: So far, our results suggest that (1) the prevalence of HAND is high in HIV_ patients with a long-term suppression of viremia, and (2) cognitive complaints expressed by aviremic HIV_ patients should be carefully investigated as they correlate with objective evidences of cognitive decline in a neuropsychological testing. HAART with a high CNS penetrating-effectiveness may contribute to prevent HAND. Funding: Swiss HIV Cohort Study.

Persistence of cognitive impairment and its negative impact on psychosocial functioning in lithium-treated, euthymic bipolar patients: a 6-year follow-up study.

BACKGROUND: Previous cross-sectional studies report that cognitive impairment is associated with poor psychosocial functioning in euthymic bipolar patients. There is a lack of long-term studies to determine the course of cognitive impairment and its impact on functional outcome. Method A total of 54 subjects were assessed at baseline and 6 years later; 28 had DSM-IV TR bipolar I or II disorder (recruited, at baseline, from a Lithium Clinic Program) and 26 were healthy matched controls. They were all assessed with a cognitive battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory) twice over a 6-year follow-up period. All patients were euthymic (Hamilton Rating Scale for Depression score lower than 8 and Young mania rating scale score lower than 6) for at least 3 months before both evaluations. At the end of follow-up, psychosocial functioning was also evaluated by means of the Functioning Assessment Short Test. RESULTS: Repeated-measures multivariate analysis of covariance showed that there were main effects of group in the executive domain, in the inhibition domain, in the processing speed domain, and in the verbal memory domain (p<0.04). Among the clinical factors, only longer illness duration was significantly related to slow processing (p=0.01), whereas strong relationships were observed between impoverished cognition along time and poorer psychosocial functioning (p<0.05). CONCLUSIONS: Executive functioning, inhibition, processing speed and verbal memory were impaired in euthymic bipolar out-patients. Although cognitive deficits remained stable on average throughout the follow-up, they had enduring negative effects on psychosocial adaptation of patients.