The Minnesota DARE PLUS Project: creating community partnerships to prevent drug use and violence

The research community has criticized Drug Abuse Resistance Education (D.A.R.E.) because the extant literature indicates a lack of evidence that the elementary school program prevents drug use. Yet D.A.R.E. continues to be the most widely implemented drug use prevention program in the United States and has considerable community support. To date, the junior high D.A.R.E. program has not been evaluated. The Minnesota DARE PLUS Project is a randomized trial of 24 schools and communities. During 1999-2001, students in eight schools will receive the junior high D.A.R.E. curriculum in 7th grade; eight schools also will receive the curriculum as well as additional parent involvement, peer leadership, and community components in the 7th and 8th grades; and eight schools will serve as controls. This article describes the background and conceptualization, the curriculum and additional intervention components, and the evaluation methods of the DARE PLUS Project.     

Levels of the DNA repair enzyme human apurinic/apyrimidinic endonuclease (APE1, APEX, Ref-1) are associated with the intrinsic radiosensitivity of cervical cancers.

A study was made of the relationship between the intrinsic radiosensitivity of human cervical tumours and the expression of the DNA repair enzyme human apurinic/apyrimidinic endonuclease (HAP1). The radiosensitivity of clonogenic cells in tumour biopsies was measured as surviving fraction at 2 Gy (SF2) using a soft agar assay. HAP1 expression levels were determined after staining of formalin-fixed paraffin-embedded tumour sections with a rabbit antiserum raised against recombinant HAP1. Both measurements were obtained on pretreatment biopsy material. All 25 tumours examined showed positive staining for HAP1, but there was heterogeneity in the level of expression both within and between tumours. The average coefficients of variation for intra- and intertumour heterogeneity were 62% and 82% respectively. There was a moderate but significant positive correlation between the levels of HAP1 expression and SF2 (r = 0.60, P = 0.002). Hence, this study shows that there is some relationship between intrinsic radiosensitivity and expression of a DNA repair enzyme in cervical carcinomas. The results suggest that this type of approach may be useful in the development of rapid predictive tests of tumour radiosensitivity.     

Mortality following surgery for proximal femoral fractures in centenarians

Although the number of centenarians in our population is increasing, mortality rates following hip fracture in this group of patients has not yet been reported. The medical records of a consecutive series of 13 centenarians with proximal femoral fractures who presented to the Derbyshire Royal Infirmary over a 20 year period were retrospectively reviewed. The majority of patients were female (M:F 2:11) and had suffered intertrochanteric fractures. The recorded incidence of surgical complications was low. The mortality at 30 days, 6 months and 1 year were 31%, 50% and 56%, respectively representing a 20% increase in mortality at 1 year when compared to the expected mortality rates among their non-injured peers. When compared with over 1000 hip fracture patients of all ages in previous prospective studies, the centenarians in this series were found to have a significantly higher mortality during hospital admission (p<0.001) and at 1 year (p=0.002). The treatment of hip fractures in centenarians poses a challenge. Optimal anaesthesia, expeditious surgery and a co-ordinated multidisciplinary approach to care is essential in these patients.     

18F]fluorodeoxyglucose uptake by positron emission tomography predicts outcome of non-small-cell lung cancer.

PURPOSE: To determine whether the standardized uptake value (SUV) of [(18)F]fluorodeoxyglucose uptake by positron emission tomography could be a prognostic factor for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred sixty-two patients with stage I to IIIb NSCLC were analyzed. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local-regional control (LRC) were calculated by the Kaplan-Meier method and evaluated with the log-rank test. The prognostic significance was assessed by univariate and multivariate analyses. RESULTS: There were 93 patients treated with surgery and 69 patients treated with radiotherapy. A cutoff of 5 for the SUV for the primary tumor showed the best discriminative value. The SUV for the primary tumor was a significant predictor of OS (P = .02) in both groups. Low SUVs ( 5.0; surgery group, P = .02; radiotherapy group, P = .0005). Low SUVs ( 5.0; stage I or II, P = .02; stage IIIa or IIIb, P = .004). However, using the same cutoff point of 5, the SUV for regional lymph nodes was not a significant indicator for DFS (P = .19), LRC (P = .97), or DMFS (P = .17). The multivariate analysis showed that the SUV for the primary tumor was a significant prognostic factor for OS (P = .03) and DFS (P = .001). CONCLUSION: The SUV of the primary tumor was the strongest prognostic factor among the patients treated by curative surgery or radiotherapy.     

The orienting of attention during eye and hand movements: ERP evidence for similar frame of reference but different spatially specific modulations of tactile processing

To investigate which frames of reference guide shifts of attention triggered during eye and hand movement preparation and the specificity of their effects on somatosensory processing, we recorded event-related brain potentials (ERPs) in a Go/Nogo task where a cue indicated to prepare an eye movement toward - or a hand movement with - the left or right hand. Before the imperative stimulus, a tactile probe was presented to one hand. Spatially selective modulations of tactile processing were more sustained for hand than eye movements, indicating stronger attentional modulations for the modality of the effector's sensory organ. Importantly, attentional modulations of somatosensory processing as well as lateralized ERP components in the preparation interval were virtually identical under uncrossed and crossed hands conditions, suggesting that shifts of attention triggered during hand and eye movement preparation are guided by a common external reference frame.     

Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation

Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under consideration as a treatment for age-associated neurodegenerative conditions. However, no studies have determined if supplementation, initiated relatively late in life, could have beneficial effects on mild functional impairments associated with normal brain aging. Accordingly, the current study assessed the effect of CoQ intake in older mice for which cognitive and psychomotor impairments were already evident. Separate groups of young (3.5 months) and relatively old mice (17.5 months) were fed a control diet or a diet supplemented with low (0.72 mg/g) or high (2.81 mg/g) concentrations of CoQ for 15 weeks. After 6 weeks, the mice were given tests for spatial learning (Morris water maze), spontaneous locomotor activity, motor coordination, and startle reflex. Age-related impairments in cognitive and psychomotor functions were evident in the 17.5-month-old mice fed the control diet, and the low-CoQ diet failed to affect any aspect of the impaired performance. However, in the Morris water maze test, old mice on the high-CoQ diet swam to the safe platform with greater efficiency than the mice on the control diet. The old mice supplemented with the high-CoQ diet did not show improvement when spatial performance was measured using probe trials and failed to show improvement in other tests of behavioral performance. Protein oxidative damage was decreased in the mitochondria from the heart, liver, and skeletal muscle of the high-CoQ-supplemented mice and, to some extent, in the brain mitochondria. Contrasting with the deleterious effect of long-term CoQ supplementation initiated during young adulthood previously published, this study suggests that CoQ improves spatial learning and attenuates oxidative damage when administered in relatively high doses and delayed until early senescence, after age-related declines have occurred. Thus, in individuals with age-associated symptoms of cognitive decline, high-CoQ intake may be beneficial.     

A view of geriatrics through hormones. What is the relation between andropause and well-known geriatric syndromes?

Age related male hypogonadism, or “andropause”, is increasingly recognized as of frequent occurrence in older patients. Diagnosis requires both the presence of clinical symptoms and low testosterone levels. However, diagnosing andropause in this age group may be challenging since symptoms are frequently non specific and testosterone levels are influenced by a multitude of parameters such as lifestyle factors and chronic diseases. In this article we discuss the pathophysiology, definition and diagnostic difficulties of andropause in geriatric patients. Moreover, we review the relation between testosterone levels and frequent geriatric syndromes such as falls, osteoporosis, cognitive and mood disorders, anemia and cardiovascular disease. Finally, we examine the potential benefits and risks of testosterone replacement therapy in this age group.     

TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved

The newly identified tripartite motif (TRIM) family of proteins mediate innate immunity and other critical cellular functions. Here we show that TRIM21, which mediates the autoimmune diseases rheumatoid arthritis, systemic lupus erythematosus, and Sjögren''s syndrome, is a previously undescribed IgG receptor with a binding mechanism unlike known mammalian Fcγ receptors. TRIM21 simultaneously targets conserved hot-spot residues on both Ig domains of the Fc fragment using a PRYSPRY domain with a preformed multisite interface. The binding sites on both TRIM21 and Fc are highly conserved to the extent that the proteins are functionally interchangeable through murine, canine, primate, and human species. Pre-steady-state analysis exposes mechanistic conservation at the level of individual residues, which make the same energetic and kinetic contributions to binding despite varying in sequence. Together, our results reveal that TRIM21 is a previously undescribed type of IgG receptor based on a non-Ig scaffold whose interaction at the fundamental level—structural, thermodynamic, and kinetic—is evolutionarily conserved.