Making sense of informant disagreement for overanxious disorder

A community sample of 2798 8-17-year-old twins and their parents completed a personal interview about the child's current psychiatric history on two occasions separated by an average of 18 months. Parents also completed a personal interview about their own lifetime psychiatric history at entry to the study. Results indicate that informant agreement for overanxious disorder (OAD) was no better than chance, and most cases of OAD were based on only one informant's ratings. Disagreement about level of OAD symptoms or presence of another disorder (mostly phobias or depression) accounted for most cases of informant disagreement: 60% of cases based only on child interview, 67% of cases based only on maternal interview, and 100% of cases based only on paternal interview. OAD diagnosed only by maternal interview was also distinguished by an association with maternal alcoholism and increasingly discrepant parental reports of marital difficulties. Given the substantial overlap in case assignments for DSM-III-R OAD and DSM-IV GAD, these findings may identify sources of informant disagreement that generalize to juvenile GAD.     

A new approach to patient-centered care

An opportunity existed at our rehabilitation hospital, in preparation for Medicare's Prospective Payment System (PPS) in acute medical rehabilitation, to develop an integrated inpatient care model using all available resources. The results have been an improved practice of all staff, increased efficiency and productivity, and increased staff and patient satisfaction. This article discusses the drivers for changing the team model within a large rehabilitation hospital. It includes an overview of the process of data gathering prior to changing the team model, how the new team model functions, and follow-up data collection 9 months after to provide evidence on what changes worked and what areas required further change to meet the objectives.     

The consequences of uncontrollable stress are sensitive to duration of prior wheel running

The behavioral consequences of uncontrollable stress, or learned helplessness (LH) behaviors, are thought to involve hyperactivity of serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN). Other brain regions implicated in LH and capable of affecting 5-HT systems, such as the bed nucleus of the stria terminalis (BNST), amygdala, and habenula, could contribute to DRN 5-HT hyperactivity during uncontrollable stress. Six weeks of wheel running prevents LH and attenuates uncontrollable stress-induced c-Fos expression in DRN 5-HT neurons, although the duration of wheel running necessary for these effects is unknown. In the current study, 6 but not 3, weeks of wheel running blocked the shuttle box escape deficit and exaggerated fear produced by uncontrollable tail shock in sedentary rats. Corresponding to the duration-dependent effects of wheel running on LH behaviors, 6 weeks of wheel running was required to attenuate uncontrollable stress-induced 5-HT neural activity, indexed by c-Fos protein expression, in the DRN and c-Fos expression in the lateral ventral region of the BNST. Wheel running, regardless of duration, did not affect c-Fos expression anywhere in the amygdala or habenula. These data indicate that the behavioral effects of uncontrollable stress are sensitive to the duration of prior physical activity and are consistent with the hypothesis that attenuation of DRN 5-HT activity contributes to the prevention of LH by wheel running. The potential role of the BNST in the prevention of LH by wheel running is discussed.     

Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia Aging Study

Antioxidants have been hypothesized to protect against Alzheimer's disease, but studies conducted in late life have been inconsistent. Risk factors measured in midlife may better predict dementia in late life because they are less affected by the disease process. The authors examined the association of midlife dietary intake of antioxidants to late-life dementia and its subtypes. Data were obtained from the Honolulu-Asia Aging Study, a prospective community-based study of Japanese-American men who were aged 45-68 years in 1965-1968, when a 24-hour dietary recall was administered. The analysis included 2,459 men with complete dietary data who were dementia-free at the first assessment in 1991-1993 and were examined up to two times for dementia between 1991 and 1999. The sample included 235 incident cases of dementia (102 cases of Alzheimer's disease, 38 cases of Alzheimer's disease with contributing cerebrovascular disease, and 44 cases of vascular dementia). Relative risks by quartile of intake were calculated using Cox proportional hazards models with age as the time scale, after adjustment for sociodemographic and lifestyle factors, cardiovascular risk factors, other dietary constituents, and apolipoprotein E e4. Intakes of beta-carotene, flavonoids, and vitamins E and C were not associated with the risk of dementia or its subtypes. This analysis suggests that midlife dietary intake of antioxidants does not modify the risk of late-life dementia or its most prevalent subtypes.     

Plasminogen kringle 5-engineered glioma cells block migration of tumor- associated macrophages and suppress tumor vascularization and progres- sion.

Angiostatin, a well-characterized angiostatic agent, is a proteolytic cleavage product of human plasminogen encompassing the first four kringle structures. The fifth kringle domain （K5） of human plasminogen is distinct from angiostatin and has been shown, on its own, to act as a potent endothelial cell inhibitor. We propose that tumor-targeted K5 cDNA expression may act as an effective therapeutic intervention as part of a cancer gene therapy strategy. In this study, we provide evidence that eukaryotically expressed His-tagged human K5 cDNA （hK5His） is exported extracellularly and maintains predicted disulfide bridging conformation in solution. Functionally, hK5His protein produced by retrovirally engineered human U87MG glioma cells suppresses in vitro migration of both human umbilical vein endothelial cells and human macrophages. Subcutaneous implantation of Matrigel-embedded hK5His-producing glioma cells in nonobese diabetic/severe combined immunodeficient mice reveals that hK5His indaces a marked reduction in blood vessel formation and signiticanfly suppresses the recruitment of tumor-infiltrating CD45（＋）Mac3（＋）Grl （-） macrophages. Therapeutically, we show ill a nude mouse orthotopic brain cancer model that tumor-targeted K5 expression is capable of effectively suppressing glioma growth and promotes significant long-term survival （〉120 days） of test animals. These data suggest that plasminogen K5 acts as a novel two-pronged anticancer agent, mediating its inhibitory effect via its action on host-derived endothelial cells and tumor-associated macrophages, resulting in a potent, clinically relevant antitumor effect.     

Melatonin, a potent agent in antioxidative defense: Actions as a natural food constituent, gastrointestinal factor, drug and prodrug

Melatonin, originally discovered as a hormone of the pineal gland, is also produced in other organs and represents, additionally, a normal food constituent found in yeast and plant material, which can influence the level in the circulation. Compared to the pineal, the gastrointestinal tract contains several hundred times more melatonin, which can be released into the blood in response to food intake and stimuli by nutrients, especially tryptophan. Apart from its use as a commercial food additive, supraphysiological doses have been applied in medical trials and pure preparations are well tolerated by patients. Owing to its amphiphilicity, melatonin can enter any body fluid, cell or cell compartment. Its properties as an antioxidant agent are based on several, highly diverse effects. Apart from direct radical scavenging, it plays a role in upregulation of antioxidant and downregulation of prooxidant enzymes, and damage by free radicals can be reduced by its antiexcitatory actions, and presumably by contributions to appropriate internal circadian phasing, and by its improvement of mitochondrial metabolism, in terms of avoiding electron leakage and enhancing complex I and complex IV activities. Melatonin was shown to potentiate effects of other antioxidants, such as ascorbate and Trolox. Under physiological conditions, direct radical scavenging may only contribute to a minor extent to overall radical detoxification, although melatonin can eliminate several of them in scavenger cascades and potentiates the efficacy of antioxidant vitamins. Melatonin oxidation seems rather important for the production of other biologically active metabolites such as N ¹-acetyl-N ²-formyl-5-methoxykynuramine (AFMK) and N ¹-acetyl-5-methoxykynuramine (AMK), which have been shown to also dispose of protective properties. Thus, melatonin may be regarded as a prodrug, too. AMK interacts with reactive oxygen and nitrogen species, conveys protection to mitochondria, inhibits and downregulates cyclooxygenase 2.