Quality and Quantity of Diffuse and Focal White Matter Disease and Cognitive Disability of Patients with Multiple Sclerosis

BACKGROUND AND PURPOSE Using high-field magnetic resonance imaging (MRI), we investigated the relationships between white matter (WM) lesion volume (LV), normal-appearing WM (NAWM) normalized volume, WM-lesion and NAWM magnetization transfer ratios (MTRs), brain parenchyma fraction (BPF), and cognitive impairment (CI) in multiple sclerosis (MS). METHODS Twenty-four patients and 24 healthy volunteers (age, sex, and years of education-matched) underwent a 3.0 Tesla (3T) scan and evaluation of depression, fatigue, and CI using the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery. RESULTS In this clinically relatively well-preserved cohort of patients (median score on the Expanded Disability Status Scale = 1.5), CI was detected on Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II), and Controlled Oral Word Association Test. MT data were available in 19 pairs on whom correlation analyses were performed. Associations were seen between SDMT and normalized NAWM volume (P = .034, r = .502), CVLT-II long delay and normalized NAWM volume (P = .012, r = .563), WM-LV (P = .024, r = .514), and BPF (P = .002, r = .666). CONCLUSIONS The use of 3T MRI in a sample of clinically stable MS patients shows the importance of WM disease in hampering processing speed and word retrieval

T(1) cortical hypointensities and their association with cognitive disability in multiple sclerosis

Objective: To assess the incidence of T(1) hypointense NLs by 3.0-Tesla magnetic resonance imaging (MRI) in patients with MS and examine neocortical lesion association with cognitive impairment. Methods: In this case-control study, 21 MS patients and 21 age-, sex- and years of education-matched healthy volunteers underwent: (i) a neuropsychological examination rating cognitive impairment (Minimal Assessment of Cognitive Function in MS); (ii) a 3.0-Tesla MRI inclusive of an isotropic 1.0 mm(3) three-dimensional inversion prepared spoiled gradient-recalled-echo (3D-IRSPGR) image and T(1)- and T(2)-weighted images. Hypointensities on 3D-IRSPGR lying in the cortex, either entirely or partially were counted and association between NLs and cognitive impairment investigated. Results: A total of 95 NLs were observed in 14 (66.7%) patients. NL+ patients performed poorer (p = 0.020) than NLpatients only on the delayed recall component of the California Verbal Learning Test. This difference lost statistical significance when a correction for white matter lesion volume was employed. Conclusions: Although T(1) hypointense NLs may be present in a relatively high proportion of multiple sclerosis patients, the impact that they have in cognitive impairment is not independent from white matter disease

On Heidegger on Education and Questioning

Discussions of Heidegger and education, particularly as expressed by those interested in the philosophy of education, take a number of perspectives as thematic foci. Questioning is key to Heidegger’s thinking from the start of his 1927 Being and Time, calling into question the foundations of what we suppose ourselves to know. Thus questioning involves a reflection on education, that is: both teaching and learning. Heidegger himself thematizes education, significantly so in the light of the political circumstances of his 1933 “Rectoral Discourse” as well as, in an inventive mode which would, as we shall see, have been better had it been identified as a speculative \u27reconstruction\u27 of what Heidegger might have said in an essay published as a translation of his postwar reflections on the “Art of Teaching” and, last of all and most importantly, What is Called Thinking? In addition, Heidegger‘s reflections on questioning also include a meditation on both phenomenology and hermeneutics in “The Question Concerning Technology” in which he famously describes “questioning as the piety of thought.

Regulation of muscle growth by multiple ligands signaling through activin type II receptors

Myostatin is a secreted protein that normally functions as a negative regulator of muscle growth. Agents capable of blocking the myostatin signaling pathway could have important applications for treating human muscle degenerative diseases as well as for enhancing livestock production. Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60% in 2 weeks) when injected into wild-type mice. Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in Mstn(-/-) mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to regulate muscle growth in vivo