Prospective strategies for cholinergic interventions in Alzheimer's disease

The cholinergic hypothesis of memory dysfunction has guided most of the recent proposals for treating the primary symptoms of AD. The efficacy of these treatments has been severely limited. This review examines two major lines of evidence which suggest that the cholinergic hypothesis may have to be expanded and revised. The cholinergic hypothesis focuses on pre-synaptic defects. It assumes cholinoceptive neurons would function normally with adequate stimulation. Evidence is not sufficient to support this assumption. In addition, dissociations have been demonstrated between muscarinic receptor number and functional response of cholinoceptive neurons. Various measures are proposed to investigate the functional integrity of muscarinic receptors in AD patients. AD often has been characterized as a disorder produced by generalized cholinergic hypoactivity. Evidence for cortisol hypersecretion, abnormal dexamethasone suppression, and the occurrence of depressive symptoms, motoric dysfunction and sleep abnormalities in AD patients is more consistent with regional cholinergic hyperactivity than generalized hypoactivity. Resolution of these discrepancies could shed new light on the pathophysiology and treatment strategies for AD. Cholinoceptive neurons could be hypersensitive, subsensitive or have unaltered responsivity. These options would have very different treatment implications. New developments in outcome assessment which are capable of discriminating varieties of differential response to treatment can spur treatment development and improve quality of care for patients with complex disorders such as AD.     

A sol–gel synthesis to prepare size and shape-controlled mesoporous nanostructures of binary (II–VI) metal oxides

A base-catalyzed sol–gel approach combined with a solvent-driven self-assembly process at low temperature is augmented to make manganese oxide (Mn₃O₄), copper oxide (CuO), and magnesium hydroxide (Mg(OH)₂) nanostructures with size- and shape-controlled morphologies. Nanostructures of Mn₃O₄ with either hexagonal, irregular particle, or ribbon shape morphologies with an average diameter ranged from 100 to 200 nm have been prepared in four different solvent types. In all morphologies of Mn₃O₄, the experimental XRD patterns have indexed the nanocrystal unit cell structure to triclinic. The hexagonal nanoparticles of Mn₃O₄ exhibit high mesoporocity with a BET surface area of 91.68 m² g⁻¹ and BJH desorption average pore diameter of ∼28 nm. In the preparation of CuO nanostructures, highly nanoporous thin sheets have been produced in water and water/toluene solvent systems. The simulated XRD pattern matches the experimental XRD patterns of CuO nanostructures and indexes the nanocrystal unit cell structure to monoclinic. With the smallest desorption total pore volume of 0.09 cm³ g⁻¹, CuO nanosheets have yielded the lowest BET surface area of 18.31 m² g⁻¹ and a BHJ desorption average pore diameter of ∼16 nm. The sol of magnesium hydroxide nanocrystals produces highly nanoporous hexagonal nanoplates in water and water/toluene solvent systems. The wide angle powder XRD patterns show well-defined Bragg''s peaks, indexing to a hexagonal unit cell structure. The hexagonal plates show a significantly high BET surface area (72.31 m² g⁻¹), which is slightly lower than the surface area of Mn₃O₄ hexagonal nanoparticles. The non-template driven sol–gel synthesis process demonstrated herein provides a facile method to prepare highly mesoporous and nanoporous nanostructures of binary (II–IV) metal oxides and their hydroxide derivatives, enabling potential nanostructure platforms with high activities and selectivities for catalysis applications.

A base-catalyzed sol–gel approach combined with a solvent-driven self-assembly process at low temperature is augmented to make highly mesoporous metal oxide nanostructures of manganese and copper, and hydroxide nanostructures of magnesium.     

Hangman's fracture resulting from improper seat belt use

Diagonal seat belt application without accompanying lap belt closure may produce severe cervical spine injuries, including hangman's fracture and decapitation. Seat belts are effective in reducing injury, but they must be worn properly to do so. Passive restraint systems involving a diagonal seat belt may be hazardous if the motorist does not use the accompanying lap belt. We have presented a case in which the driver in a motor vehicle accident sustained a hangman's fracture (bilateral fracture of the pedicles of C-2) caused by use of a diagonal seat belt without accompanying lap belt closure. The mechanism of injury, as classically described in judicial hanging, is hyperextension and distraction, which occurred when the victim "submarined" under the diagonal seat belt and was caught at the neck.     

Surgical treatment of ventricular septal rupture complicating myocardial infarction

A review of postinfarction ventricular septal defects repaired surgically at Providence Hospital over the past 6 years is presented. Although this complication of myocardial infarction carries a high mortality rate, a lower rate can be achieved with early operative intervention. Preoperative pharmacologic reduction of preload, afterload, and intra-aortic balloon pumping are only temporizing measures to allow delineation of concomitant lesions. Operative mortality does not appear to be influenced by posterior location of the ventricular septal defects.     

Human tumor suppressor ARF impedes S-phase progression independent of p53

Using alternative reading frames, the human ARF-INK4a locus encodes two unrelated proteins that both function in tumor suppression. p16(INK4a) maintains the retinoblastoma protein in its growth-suppressive state through inhibition of cyclin D-dependent kinase activity, whereas ARF binds with MDM2 and stabilizes p53. The majority of the activity of ARF to date is ascribed to its ability to activate p53, resulting in a G(1) cell cycle arrest or apoptosis. We show here that ARF colocalizes with DNA replication protein A (RPA32) and that overexpression of ARF reduces the rate of DNA synthesis resulting in accumulation of an S-phase cell population. Impediment of DNA synthesis by ARF can occur and becomes more evident in the absence of p53. Hence, the biological consequence of ARF induction varies dependent on cellular p53 status, inducing predominantly a G(1) arrest or apoptosis in p53-positive cells or causing S-phase retardation when p53 function is comprised.     

Grandparents as Parents: Research Findings and Policy Recommendations

This article presents an overview of research on grandparenthood in the latter decades of the twentieth century. Theories contributing to understanding of the grandparenting role are discussed, and significant factors affecting the grandparenting experience—including sex, age, retirement status, race, and ethnicity—are reviewed. The special case of grandparents raising grandchildren is explored through a review of demographics, outcomes for children in grandparent foster care, and the impact of raising grandchildren on grandparents. Interventions supporting custodial grandparents and the grandchildren in their care are examined. Drawing on the findings and implications of this overview, recommendations for policy, clinical practice, professional education, and future research are offered.     

Some relationships between informant assessment and functional analysis of problem behavior

The strengths and limitations of informant assessment of problem behavior was investigated through examination of such behavior across seven situations and 3 participants. The results of informant assessment were compared to those obtained from functional analysis to determine some of the parameters under which informant assessment might provide a practical alternative to functional analysis. The results showed that informant hypotheses about the function of problem behavior were validated by subsequent functional analyses only when informants identified their hypotheses as involving situations likely to evoke problem behavior. Hypotheses involving situations that informants rated as less likely to evoke problem behavior were not validated by subsequent functional analyses. The implications of these findings for improving the validity of informant assessment are discussed.