Alzheimer's disease (AD) is characterized by progressive neurodegeneration leading to loss of cognitive abilities and ultimately to death. Postmortem investigations revealed decreased expression of cerebral insulin-like growth factor (IGF)-1 receptor (IGF-1R) and insulin receptor substrate (IRS) proteins in patients with AD. To elucidate the role of insulin/IGF-1 signaling in AD, we crossed mice expressing the Swedish mutation of amyloid precursor protein (APP(SW), Tg2576 mice) as a model for AD with mice deficient for either IRS-2, neuronal IGF-1R (nIGF-1R(-/-)), or neuronal insulin receptor (nIR(-/-)), and analyzed survival, glucose, and APP metabolism. In the present study, we show that IRS-2 deficiency in Tg2576 mice completely reverses premature mortality in Tg2576 females and delays beta-amyloid (Abeta) accumulation. Analysis of APP metabolism suggested that delayed Abeta accumulation resulted from decreased APP processing. To delineate the upstream signal responsible for IRS-2-mediated disease protection, we analyzed mice with nIGF-1R or nIR deficiency predominantly in the hippocampus. Interestingly, both male and female nIGF-1R(-/-)Tg2576 mice were protected from premature death in the presence of decreased Abeta accumulation specifically in the hippocampus formation. However, neuronal IR deletion had no influence on lethality of Tg2576 mice. Thus, impaired IGF-1/IRS-2 signaling prevents premature death and delays amyloid accumulation in a model of AD.

Objective: To compare the effects of two treatment modalities of testosterone on sexual functioning and mood. Design: Forty men were randomized to receive either parenteral testosterone enanthate (TE) or longacting parenteral testosterone undecanoate (TU) over a period of 30 weeks. Thereafter, 20 men who had received TU and 16 men who had received TE continued with TU and completed another 65 weeks to study longer-term effects of TU. Methods: The following variables of sexual functioning were studied: sexual thoughts and fantasy, sexual interest and desire, satisfaction with sex life, number of erections and ejaculations per week, and number of spontaneous morning erections per week. Also variables related to mood were analyzed. Results: Improvements in these variables were significant and were of a similar magnitude in the group treated with TU and TE for 30 weeks. Improvements were maintained at the same levels over a period of another 65 weeks when all men received TU. Effects on mood were recorded for 30 weeks, but were more difficult to establish in the study population. There were significant differences in baseline values between the two groups and scores showed wide S.D. Conclusions: Both TE and TU were effective in improving sexual functions in hypogonadal men. An advantage of TU over TE is its lower frequency of administration and its better tolerability and safety profile.

Objectives. We evaluated the effectiveness of a community-based healthy lifestyle intervention in improving dietary behaviors of pregnant Latinas from 2004 to 2006 in Detroit, Michigan. Methods. The 11-week, culturally tailored, Spanish-language Healthy Mothers on the Move (MOMs) intervention offered home visits, group classes, related activities, and social support from trained community health workers (CHWs) and peers. Dietary behaviors were measured by food frequency questionnaire. Linear mixed models estimated pre- and post-intervention changes, within and between MOMs intervention and minimal intervention (MI) groups. Results. MOMs (n = 139) and MI (n = 139) participants had similar baseline characteristics and dietary intake. Post-intervention, MOMs participants showed significant improvement in all dietary behaviors, except fruit and fiber consumption. Compared with MI participants, MOMs participants had significantly decreased consumption of added sugar (P = .05), total fat (P < .05), saturated fat (P < .01), percentage of daily calories from saturated fat (P < .001), solid fats and added sugars (P < .001), and had increased vegetable consumption (P < .001). Their increase in fiber consumption (P < .05) was significant relative to MI participants’ decrease in fiber intake. Conclusions. We confirmed the hypothesis that a community-planned, CHW-led healthy lifestyle intervention could improve dietary behaviors of low-income Latina women during pregnancy.

Administration of TU every 12 weeks is at least as safe and efficacious for treatment of hypogonadal men as TE, with a substantially lower frequency of administration. Follow-up over 114 weeks, when all subjects received TU, showed an excellent profile of efficacy and safety.