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Examination of the AAMC CurrMIT database, individual medical school web sites, results from the AAMC Medical School Graduation Questionnaire, and published literature produced little systematic information about how and where stroke education is provided in undergraduate medical school curricula. In 31 US medical schools that met criteria for inclusion in this review, cerebrovascular disease is directly addressed in an average of 4.8 sessions during the preclerkship curriculum. Fewer than 20% of these schools report that they address stroke prevention. Less data are available about the amount and content of stroke education in required clerkships. Approximately 80% of all US medical schools require a neurology clerkship or a clerkship in which neurologists participate; about half are scheduled in Year 3. Recommendations include defining a core competency in stroke for all graduating medical students, developing new approaches to enhance undergraduate training in stroke, and systematically gathering data about stroke education and its outcomes from multiple sources.

The local dynamics of poly(dimethylsiloxane) (PDMS) has been investigated by quasi-elastic neutron scattering (QENS). Methyl group reorientations dominate the QENS spectra up to 215 K (i.e., below the melting temperature, Tm ≈ 235 K). The dynamics of the CH3 groups is interpreted in terms of a model function consisting of elastic and quasi-elastic components, the latter given by a Gaussian distribution of Lorentzian lines. Above Tm, the QENS spectra are analyzed considering two processes:  (a) the methyl group rotation and (b) the segmental motion. The activation energy for the latter is 14.6 kJ/mol, in excellent agreement with rheological data. Moreover, in agreement with the latter, the intermediate scattering function, I(Q,t), computed via the inverse Fourier transform, follows time−temperature superposition according to the rheological shift factor. The contribution of the segmental motion to the scattering function I(Q,t) was fitted with a stretched exponential function (or its Fourier transform in the frequency domain). The fitted stretching exponent β for segmental motion is 0.61 in both frequency and time domain, much higher than 0.5 (Rouse model), but in agreement with theoretical results realistically accounting for the chain stiffness. QENS studies of segmental motion in PDMS had indicated that the experimental data followed the Rouse model up to a very large Q, well beyond the validity range of the model. We suggest that the rotational motion of the methyl groups is responsible for this observation.

Epidermal growth factor-responsive neural precursor cells were used as donor cells for transplantation into wild-type and myelin-deficient shiverer (shi) mice. The cells engrafted robustly within the CNS following intracerebroventricular and cisternal transplantation in neonatal mice. The cells adopted glial phenotypes, and some functioned as oligodendrocytes, producing myelin basic protein and morphologically normal internodal myelin sheaths. When individual shi mice received two transplants (on post-natal days 1 and 3), donor-derived cells disseminated widely and expressed myelin basic protein in central white matter tracts throughout the brain.

A stepwise chemical modification from human neurokinin-3 receptor (hNK-3R)-selective antagonists to potent and combined hNK-3R and hNK-2R antagonists using the same 2-phenylquinoline template is described. Docking studies with 3-D models of the hNK-3 and hNK-2 receptors were used to drive the chemical design and speed up the identification of potent and combined antagonsits at both receptors. (S)-(+)-N-(1-Cyclohexylethyl)-3-[(4-morpholin-4-yl)piperidin-1-yl]methyl-2-phenylquinoline-4-carboxamide (compound 25, SB-400238:  hNK-3R binding affinity, Ki = 0.8 nM; hNK-2R binding affinity, Ki = 0.8 nM) emerged as the best example in this approach. Further studies led to the identification of (S)-(+)-N-(1,2,2-trimethylpropyl)-3-[(4-piperidin-1-yl)piperidin-1-yl]methyl-2-phenylquinoline-4-carboxamide (compound 28, SB-414240:  hNK-3R binding affinity, Ki = 193 nM; hNK-2R binding affinity, Ki = 1.0 nM) as the first hNK-2R-selective antagonist belonging to the 2-phenylquinoline chemical class. Since some members of this chemical series showed a significant binding affinity for the human μ-opioid receptor (hMOR), docking studies were also conducted on a 3-D model of the hMOR, resulting in the identification of a viable chemical strategy to avoid any significant μ-opioid component. Compounds 25 and 28 are therefore suitable pharmacological tools in the tachykinin area to elucidate further the pathophysiological role of NK-3 and NK-2 receptors and the therapeutic potential of selective NK-2 (28) or combined NK-3 and NK-2 (25) receptor antagonists.

The macrolide antibiotic bafilomycin A1 is a highly potent and selective inhibitor of all the vacuolar ATPases (V-ATPases). With the aim of obtaining novel analogues specific for the osteoclast subclass of vacuolar ATPase, 31 derivatives of bafilomycin A1 were synthesized and tested for their ability to inhibit differentially the V-ATPase-driven proton transport in membrane vesicles derived from chicken osteoclasts (cOc) and bovine chromaffin granules (bCG). Although none of the new analogues were more potent than the parent compound, the obtained data provided a significant amount of information about the structural requirements for the inhibitory activity of bafilomycin A1. The different effects of a few analogues on the two enzymes could also suggest the possibility of a selective modulation of the V-ATPases in different tissues.

The vacuolar H⁺-ATPase (V-ATPase), located on the ruffled border of the osteoclast, is a proton pump which is responsible for secreting the massive amounts of protons that are required for the bone resorption process. With the aim to identify new agents which are able to prevent the excessive bone resorption associated with osteoporosis, we have designed a novel class of potent and selective inhibitors of the osteoclast proton pump, starting from the structure of the specific V-ATPase inhibitor bafilomycin A1. Compounds 3a−d potently inhibited the V-ATPase in chicken osteoclast membranes (IC50 = 60−180 nM) and were able to prevent bone resorption by human osteoclasts in vitro at low-nanomolar concentrations. Notably, the EC50 of compound 3c in this assay was 45-fold lower than the concentration required for half-maximal inhibition of the V-ATPase from human kidney cortex. These results support the validity of the osteoclast proton pump as a useful molecular target to produce novel inhibitors of bone resorption, potentially useful as antiosteporotic agents.

Numerous small and medium-sized neuronal perikarya in layers III and IV of the visual cortex display an unusual pattern of ribosomal distribution. Instead of being aggregated in clusters, spirals, rows, and other regular polysomal configurations, the ribosomes, whether free or attached to the endoplasmic reticulum, are randomly dispersed, with no discernible pattern. The endoplasmic reticulum in such cells is reduced to a few (perhaps only one) meandering, broad cisternae, which delimit broad fields of cytoplasmic matrix occupied almost solely by scattered, single ribosomes. The Golgi apparatus is elaborate. Mitochondria are either small and numerous or large and infrequent. The other organelles, including the nucleus and nucleolus, are not remarkable. Axonal terminals synapse in the normal fashion on the surfaces of these cells and their dendrites. Associated with these cells are more numerous intermediate cells in which a few to many polysomal clusters can be found. It is proposed that the neurons with dispersed, single ribosomes are inactive in protein synthesis and that the suspension of such an important metabolic activity is probably temporary. Thus, these cells are considered to be part of a population undergoing cyclic fluctuations in the intensity of protein synthesis that should be correlated with their specific neural behavior.

Earlier reports suggested that injecting normal optic nerve into organotypic cerebellar cultures from three of the central nervous system hypomyelinated mutant mice resulted in striking local increases in myelination of mutant axons. It has been questioned whether this myelin was produced by the introduced normal glia because there was no "marker" by which the genotype of an individual myelin sheath could be rigorously determined. The present study shows that the myelin sheaths of the central nervous system hypomyelinated mutant shiverer (shi/shi) can be distinguished in vitro from genetically normal myelin by their immunocytochemical reactions and ultrastructure. When shi/shi cultures are injected with normal optic nerve, they produce two kinds of myelin as distinguished by these techniques: shi/shi myelin throughout and, in addition, ultrastructurally and immunocytochemically normal myelin near the optic nerve. These results suggest that the primary defect of the shi/shi mutation involves the oligodendrocyte and support the earlier conclusion that in all of the glial injection experiments to date the genotype of the oligodendrocyte determines the phenotype of the myelin produced.

It is argued that some organic materials play an important role in preventing the formation of nonemissive species and enhancing the intrinsic stability of Alq 3 thin films. In the present work, films (Alq 3 pure, Alq 3 +ORGMAT (top), and Alq 3 doped with same) were grown on glass and silica substrates by thermal evaporation. Excitation, fluorescence, and transmission spectra have been measured, and the intensity of the green photoluminescence as a function of time has been monitored. Preliminary results show an improved stability of the emission in the doped Alq 3 films compared with the undoped ones.