Brain networks associated with cognitive and hedonic responses to a meal.

BACKGROUND: We recently reported interrelated digestive, cognitive, and hedonic responses to a meal. The aim of this study was to identify brain networks related to the hedonic response to eating. METHODS: Thirty-eight healthy subjects (20-38 age range) were evaluated after a 5-hour fast and after ingestion of a test meal (juice and warm ham and cheese sandwich, 300 mL, 425 kcal). Perceptual and affective responses (satiety, abdominal fullness, digestive well-being, and positive mood), and resting scans of the brain using functional MRI (3T Trio, Siemens, Germany) were evaluated immediately before and after the test meal. A high-order group independent component analysis was performed to investigate ingestion-related changes in the intrinsic connectivity of brain networks, with a focus on thalamic and insular networks. KEY RESULTS: Ingestion induced satiation (3.3±0.4 score increase; P<.001) and abdominal fullness (2.4±0.3 score increase; P<.001). These sensations included an affective dimension involving digestive well-being (2.8±0.3 score increase; P<.001) and positive mood (1.8±0.2 score increase; P<.001). In general, thalamo-cortical connectivity increased with meal ingestion while insular-cortical connectivity mainly decreased. Furthermore, larger meal-induced changes (increase/decrease) in specific thalamic connections were associated with smaller changes in satiety/fullness. In contrast, a larger meal-induced decrease in insular-anterior cingulate cortex connectivity was associated with increased satiety, fullness, and digestive well-being. CONCLUSIONS AND INFERENCES: Perceptual and emotional responses to food intake are related to brain connectivity in defined functional networks. Brain imaging may provide objective biomarkers of subjective effects of meal ingestion.

Neuropsychological profile of bilateral paramedian infarctions: three cases.

INTRODUCTION: The thalamus is one of the strategic diencephalic structures of the human brain. The artery of Percheron, an asymmetrical common trunk arising from a P1 segment of the posterior cerebral artery, is a peculiar presentation of the three variants involved in the irrigation of the paramedian thalamic territory. Occlusion of this artery results in bilateral median thalamic infarction. The paramedian syndrome includes an acute loss or reduction of consciousness, often associated with oculomotor and neuropsychological disturbances. PATIENTS AND METHODS: We present three cases of bilateral paramedian thalamic infarction with onset of acute coma, followed by fluctuations in the level of consciousness, memory, and behavioural alterations. A neuroradiological study with MRI identified individual thalamic nuclei, and a complete neuropsychological study was performed one month after onset of ictus. RESULTS: One of the patients showed severe memory and executive function impairments without improvement of vertical gaze palsy. The other two patients presented with mild executive dysfunction with complete resolution of neurological symptoms. Neuroimaging results showed a bilateral lesion of the dorsomedial nuclei in the three patients. CONCLUSIONS: Severe amnesia has been associated with an affection of the structures of the paramedian thalamic territory. Presently, the role of the dorsomedial nucleus remains controversial, with the suggestion that memory deficits observed in this type of lesion could be secondary to executive function deficits. In our case, the patient with the most severe dysexecutive deficit presented the most severe memory impairments.

Una experiencia más allá de la evaluación continuada: paseo virtual por el jardín medieval de plantas medicinales del monasterio de Pedralbes / An experience beyond continuous assessment activities: virtual tour to the medieval medicinal plant garden of the Pedralbes monastery

El grupo de innovación docente integrado por profesores del área de Botánica (GIBAF) de laUniversidad de Barcelona (UB) se plantea cada curso el diseño de nuevas actividades acreditativas enel marco de la evaluación continuada. Se presenta la experiencia llevada a cabo durante el curso 2008-09 en la asignatura Botánica Farmacéutica. El objetivo ha sido implicar durante un semestre a losestudiantes en la autoría de un proyecto tutorizado de inmediata utilidad y clara perdurabilidad, másallá de su utilidad acreditativa. Como recurso se ha utilizado el Jardín de Plantas Medicinales delMonasterio de Pedralbes y se ha firmado un convenio de colaboración docente entre la UB y elInstituto de Cultura de Barcelona. Los estudiantes han realizado el trabajo utilizando la plataformaMoodle del Campus virtual de la UB en cinco etapas que han incluido la confección de unas fichasque se han ido modificando en función de las diversas retroacciones de los profesores. Al inicio de laactividad, se facilitó a los estudiantes el cronograma completo de la actividad, la pauta para surealización, así como un total de 18 recursos bibliográficos de uso obligado. Finalmente, a través deGoogleSites, se ha realizado una web que permite realizar un paseo virtual por el jardín,documentando de forma referenciada para las 50 plantas medicinales su nomenclatura, descripciónbotánica, distribución, usos (históricos, actuales y futuros) y toxicidad. El resultado de la actividad fuepresentado en un acto público en el Monasterio de Pedralbes y puede consultarse en:http://sites.google.com/site/jardimedievalpedralbes/(AU)

The group of teaching innovation in the area of Botany (GIBAF), University of Barcelona (UB), israised each year to design new accreditation activities under continuous evaluation framework. Wepresent the experience carried out during the academic year 2008-09 in the course of PharmaceuticalBotany. The aim has been to involve students for a semester in the authorship of a tutored projectimmediately useful and of easy permanence, beyond its assessment proving usefulness. The MedicinalPlants Garden of the Monastery of Pedralbes has been used as a resource and a collaborationagreement has been signed between the UB faculty and the Institute of Culture of Barcelona. Thestudents have developed the work using the Moodle platform CampusvirtualUB into five stages whichincluded preparation of files by students that have been modified in some steps following the variousfeedbacks from teachers. At the beginning of the activity, students were provided with a completeschedule of activities, the schedule for its implementation, and a total of 18 forced-use libraryresources. Finally, through Google sites, a website has been implemented, allowing for a virtual tourof the garden, documenting by referenced literature 50 medicinal plants for their nomenclature,botanical description, distribution, uses (historical, current and future) and toxicity. The result of theactivity was presented at a public ceremony in the Monastery of Pedralbes and is available at:http://sites.google.com/site/jardimedievalpedralbes/(AU)

MR imaging findings in 56 patients with Wernicke encephalopathy: nonalcoholics may differ from alcoholics.

BACKGROUND AND PURPOSE: Wernicke encephalopathy (WE) is a severe neurologic disorder resulting from dietary vitamin B(1) deficiency. This study was undertaken to analyze and compare MR imaging findings and neurologic manifestations at clinical presentations of patients with WE with and without a history of alcohol abuse. MATERIALS AND METHODS: WE patients were identified using diagnostic neurologic data bases. Fifty-six patients (29 females, 27 males) diagnosed between 1999 and 2008 with WE who improved within 1 month from the onset of thiamine administration were included in the analysis. Patients' records were reviewed for clinical manifestations and imaging studies' findings. MR imaging was performed in the acute phase of the disease at a field strength of 1T (16 patients) and 1.5T (40 patients). All MR images were of acceptable to good quality and were retrospectively reviewed. We compared imaging findings and clinical presentation in the alcoholic (AL) group versus the non-alcoholic (NA) group using the 2-tailed Fisher exact test and the Phi coefficient as appropriate. RESULTS: Forty-three percent of the patients were in the AL group, whereas 57% were in the NA group. Eighty-nine percent showed changes in consciousness, 75% had ocular manifestations, and 54% had ataxia. On MR imaging, 80% of the patients had evidence of symmetric lesions in the medial thalami and in the periventricular region of the third ventricle; 59%, in the periaqueductal area; 45%, in the mamillary bodies; 36%, in the tectal plate; and 7%, in the periventricular gray matter located anteriorly to the fourth ventricle. Signal-intensity alterations in areas considered atypical for the disease were noted only in the NA group and always in association with the typical findings. Contrast enhancement of the thalamus and mamillary bodies was significantly associated with alcohol abuse. CONCLUSIONS: Contrast enhancement in the mamillary bodies and thalamus is a typical finding of the disease in AL patients. Atypical MR imaging findings characterize NA patients.

The basal ganglia: a substrate for fatigue in multiple sclerosis.

INTRODUCTION: The origin of fatigue in multiple sclerosis (MS) remains uncertain. However, the use of nonconventional magnetic resonance techniques has increased our understanding of this problem. We aimed to study the relationship between fatigue in MS and the presence of focal dysfunction in the basal ganglia and frontal white matter. METHODS: Included in the study were 41 patients with relapsing-remitting MS with mild disability and 20 healthy controls. Fatigue was assessed by the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Patients were classified as "fatigued" when they expressed a subjective feeling of fatigue, and the FSS score was >or=5.0 and/or the MFIS score was >38. Patients with no subjective fatigue were classified as "nonfatigued" when the FSS score was <4.0. Proton magnetic resonance spectra were obtained from two different regions: the frontal white matter and the lentiform nucleus. The relationships between fatigue and NAA/Cr, NAA/Cho and Cho/Cr ratios were analysed. RESULTS: A significant decrease in NAA/Cr in the lentiform nucleus region in patients with fatigue was observed. No differences between the groups were found in the frontal white matter. CONCLUSION: Although confirmatory studies are needed, our results would support the idea that a specific dysfunction or involvement of the basal ganglia might partly contribute to the development of MS-related fatigue.

Preclinical and clinical development of the proteasome inhibitor bortezomib in cancer treatment.

The proteasome is a ubiquitous enzyme complex that plays a critical role in the degradation of many proteins involved in cell cycle regulation, apoptosis and angiogenesis. Since these pathways are fundamental for cell survival and proliferation, particularly in cancer cells, the inhibition of proteasome is an attractive potential anticancer therapy. The present review will focus on the proteasome inhibitor bortezomib (Velcade, formerly PS-341; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA). Bortezomib is an extremely potent and selective proteasome inhibitor that shows strong activity in in vitro and in vivo laboratory studies against many solid and hematologic tumor types. Moreover, bortezomib, mainly by inhibition of the NF-kappaB pathway, has a chemosensitizing effect when administered together with other antitumoral drugs. Based on these results, bortezomib entered clinical phase I trials, alone or in combination with chemotherapy, that showed good tolerance at doses that achieved a desired degree of proteasome inhibition. Phase II studies showed high response rates in refractory multiple myeloma patients, which led to the accelerated approval of bortezomib by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for this indication. A phase III trial comparing bortezomib with dexamethasone in refractory/ relapsed multiple myeloma patients had to be halted due to a survival advantage in the bortezomib arm. Additional studies are focusing on the potential benefit of bortezomib in newly diagnosed multiple myeloma patients. In other solid and hematological malignancies, phase II studies with bortezomib alone or in combination with other agents are ongoing. Encouraging results, particularly in lung cancer and lymphoma, have been observed. The critical molecules or genes responsible for tumor sensitivity to bortezomib continue to be evaluated using novel technologies.

Treating diabetes: a holistic approach

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31Phosphorus magnetic resonance spectroscopy in the assessment of head and neck tumors.

PURPOSE: 31Phosphorus magnetic resonance spectroscopy (31P-MRS) provides biochemical information in a noninvasive way. The aim of this work was: (a) to characterize the 31P spectrum of advanced head and neck tumors, and (b) to evaluate the spectral changes after treatment and to correlate them with the pathologic response. METHODS AND MATERIALS: A total of 20 patients diagnosed with advanced head and neck tumors and 7 healthy controls participated in the study. The tumor mass and its contralateral side were studied by means of 31P-MRS before and after treatment. Neck muscles of a control group were also studied. RESULTS: Tumors presented ratios of phosphomonoesters (PME), phosphodiesters (PDE), and inorganic phosphate (Pi) with respect to the adenosine triphosphate (ATP), significantly higher and a PCr (phosphocreatine)/ATP ratio lower than the neck muscle of volunteers or the contralateral side. The PDE/ATP and PME/ATP ratio values obtained before therapy were similar, independent of the later response to treatment. However, when there was a complete response, the ratios measured after treatment were decreased. CONCLUSION: These results show the existence of significant differences between the 31phosphorus spectrum of tumors and neck muscle, but also between the tumors and their contralateral sides. Moreover, 31P-MRS is able to detect metabolic changes after a complete response. These results suggest that 31P-MRS would be useful in the evaluation of the clinical response of head and neck tumors.