Alzheimer's disease,neuropeptides, neuropeptidase,and amyloid-beta peptide metabolism

Amyloid-beta peptide (Abeta), the pathogenic agent of Alzheimer's disease (AD), is a physiological metabolite in the brain. We have focused our attention and effort on elucidating the unresolved aspect of Abeta metabolism: proteolytic degradation. Among a number of Abeta-degrading enzyme candidates, we used a novel in vivo paradigm to identify a member of the neutral endopeptidase family, neprilysin, as the major Abeta catabolic enzyme. Neprilysin deficiency results in defects in the metabolism of endogenous Abeta 40 and 42 in a gene dose-dependent manner. Our observations suggest that even partial down-regulation of neprilysin activity, which could be caused by aging, can contribute to AD development by promoting Abeta accumulation. Moreover, we discuss the fact that an aging-dependent decline of neprilysin activity, which leads to elevation of Abeta concentrations in the brain, is a natural process that precedes AD pathology. In this Perspective, we hypothesize that neprilysin down-regulation has a role in sporadic AD (SAD) pathogenesis, and we propose that this knowledge be used for developing preventive and therapeutic strategies through use of a G protein-coupled receptor (GPCR).     

Germline genomes--a biological fountain of youth?

The fusion of male- and female-derived gametes initiates the phenomenal process of producing a highly complex mammalian organism. Successful reproduction is so important that mammals invoke a battery of protective mechanisms for the germ cell lineages that function to maximize genetic integrity while still allowing genetic diversity and adaptation. Protective mechanisms likely include, but are not limited to, robust DNA repair to safeguard genetic integrity and apoptosis to remove cells with intolerable levels of DNA damage. Analyses of spontaneous mutant frequencies are generally consistent with germline DNA being stringently maintained relative to somatic tissues. Despite the rigorous protection afforded germ cells, genetic integrity is observed to decline with increased maternal and paternal age. It is not yet clear whether cells in the germ line truly age or whether other processes decline or become dysfunctional with age. For example, in a younger animal, the differentiation and/or utilization of germ cells with lower genetic integrity might be disallowed, whereas in an older animal, such cells might slip past these quality-control mechanisms.     

Optimizing out-of-school time: the role of free-choice learning

Free-choice learning, a new paradigm for the learning that youth and their families engage in outside school, can play an important role in the healthy development of youth, their families, and communities.     

The Gambling Self-Efficacy Questionnaire: An Initial Psychometric Evaluation

Instruments to assess individuals' self-efficacy for the control of addictive behaviors have been useful for monitoring behavior change, predicting maintenance of treatment gains, and identifying potential relapse situations. The Gambling Self-Efficacy Questionnaire (GSEQ) was developed to assess perceived self-efficacy to control gambling behavior. A demographically diverse sample of 309 adult gamblers completed an initial set of 42 items, of which 16 were selected to form the final version of the GSEQ. The GSEQ showed high internal consistency ( = .96) and good test-retest reliability (r = .86). A factor analysis provided some support for a unitary factor structure. As expected, GSEQ scores were negatively correlated with reports of problematic gambling behavior. Participants experiencing problems related to their gambling behavior scored significantly lower on the GSEQ than those who were not experiencing gambling problems. This psychometric examination of the GSEQ supported its potential utility for treatment planning and outcome evaluation with problem gamblers.     

GAPS between MFT supervision assumptions and common practice: suggested best practices

This article summarizes gaps between assumptions that appear in the literature, research, and accepted standards for marital and family therapy (MFT) supervision, and the common practice of supervisors. Issues that stem from these gaps are highlighted and recommendations are made for closing them. In an effort to refine the standard of practice for MFT supervision, best practice recommendations are offered for MFT supervision.     

The program effect of batterer programs in three cities

Recent meta-analyses and experimental designs of batterer program evaluations suggest little or no program effect. This finding may be compromised by a variety of analytical issues. Instrumental variable analysis addresses some of these issues, especially the relationship of program dropout to batterer reassault. This method of analysis was, therefore, used to test for program effect in a multi-site evaluation. The sites were three well-established batterer programs using a gender-based, cognitive-behavioral approach (n = 640). Completing a batterer program reduced the likelihood of reassault by 44% to 64%, depending on the specification used. Completing a 3-month program appeared to be as effective as completing a 5 1/2- or 9-month program. This moderate effect is an accomplishment considering the problems associated with the program participants and the inconsistency in the criminal justice system at the research sites. The findings remain tentative because of weak instrumental variables for reassault, but do confirm the need for more complex analyses of program effect.     

Human resource issues in university health services

To provide first-rate services to students, college health services need the best possible staff. Managers and supervisors play a critical role in guiding the work of their employees so as to enhance performance. Reference checks for new employees and regular performance appraisal dialogues for ongoing employees are important tools in this process. The author discusses these issues and suggests formats for reference checks and performance appraisals.     

Outbreaks of acute gastroenteritis associated with Norwalk-like viruses in campus settings

Norwalk-like viruses (NLVs) are transmitted by fecally contaminated food, water, fomites, and person-to-person contact. They are a leading cause of acute gastroenteritis epidemics in industrialized countries. NLV outbreaks are characterized by a 12- to 48-hour incubation period; nausea, vomiting, and diarrhea for 24 to 72 hours; and high secondary attack rates. NLV infections spread rapidly on college and university campuses because of close living quarters, shared bathrooms and common rooms, many food handlers, popular self-service salad bars in dining halls, and person-to-person contact through sports and recreational activities. The illness is generally mild and self-limited but an outbreak can strain the resources of campus health services and cause high absenteeism among both students and staff. Treatment is primarily through antiemetic medication and oral rehydration. Prevention and control of NLV outbreaks rests on promoting hand washing; enforcement of strict hygiene in all food preparation areas; and prompt, rigorous cleaning of potentially contaminated areas where someone has been ill.