Visual impairment and eye care among Alaska native people

Purpose: To estimate the prevalence of visual impairment, eye disease and eye care in the Alaska Native (AN) population, by demographic and socioeconomic factors.

Methods: Population-based cross-sectional study of 3,793 AN adults aged 18–94 years enrolled in the Education and Research Towards Health (EARTH) Study from March 2004–March 2006. Data on self-reported visual impairment, cataract, glaucoma, diabetic eye disease and previous dilated eye examinations were collected using audio computer-assisted self-administered questionnaires.

Results: The unadjusted prevalence of self-reported visual impairment was 8.7% (95% confidence interval (CI): 7.9&ndash;9.7), cataract 5.9% (95% CI: 5.2&ndash;6.7), glaucoma 2.5% (95% CI: 2.0&ndash;3.0) and diabetic eye disease 1.3% (95% CI: 0.9&ndash;1.7). In all cases, age-sex adjusted prevalence estimates for the AN population were greater than available estimates for the general U.S. population. Prevalence of visual impairment and each eye disease increased with age (P < 0.01). Additional factors associated with visual impairment were education and annual household income. Overall, 70.0% (95% CI: 68.5&ndash;71.6) of participants reported a dilated eye examination within the previous two years. Dilated eye examination within the previous two years was associated with increasing age (P < 0.001). However, men and participants with lower formal education were less likely to report recent dilated eye examination. Among those with diabetes, only 67.7% (95% CI: 60.8&ndash;74.1) reported a dilated eye examination within the recommended previous one year.

Conclusions: Self-reported visual impairment, cataract, glaucoma and diabetic eye disease are prevalent in the AN population. These data may be useful in healthcare planning and education programs.

Chronic disease and impairment among Alaska native elders : the Alaska Education and Research Towards Health (EARTH) study

Background</b>: Chronic diseases and impairments are prevalent among older Americans. However, prevalence data for Alaska Native (AN) elders are limited, with estimates usually extrapolated from national studies in which AN elders may not be well-represented. The aim of this study was to describe the prevalence of selected chronic diseases, impairments, and measured medical risk factors among a large community sample of AN elders.

Methods: Design, setting, and participants. A community-based cross-sectional study of baseline information from 656 AN elders aged 55 years or over who participated in the Alaska Education and Research Towards Health (EARTH) Study, March 2004 to August 2006. Measurements. Self-reported lifetime prevalence of 17 doctor-diagnosed chronic diseases, and point prevalence of vision, hearing, oral, and general health impairment were estimated from data collected using audio computer-assisted self-administered questionnaires. In addition, height, weight, blood pressure, fasting blood lipids, and fasting blood glucose levels were measured.

Results: The four most prevalent chronic diseases among AN elders were high blood pressure (55%), arthritis (49%), high cholesterol (42%), and adult bone fracture/break (35%). The median number of chronic diseases reported was three (inter-quartile range, 2 to 5). The prevalence of self-reported vision impairment was 15%, hearing impairment 18%, and having had all natural teeth removed 25%. Almost 50% were obese. High blood pressure (systolic ≥ 140 mm Hg and/or diastolic ≥ 90 mm Hg) was measured in 23%, high low density lipoprotein (LDL) cholesterol (≥ 130 mg/dL) in 39%, and high fasting plasma glucose (> 125 mg/dL) in 9%. Obesity was more prevalent among women than men. There were also significant regional differences in rates of obesity and high LDL cholesterol.

Conclusion: These data may be useful in public health programs and health services planning.

Transfection of MDA-MB-231 human breast carcinoma cells with bone sialoprotein (BSP) stimulates migration and invasion in vitro and growth of primary and secondary tumors in nude mice

We have investigated the role of bone sialoprotein (BSP), a secreted glycoprotein normally found in bone, in breast cancer progression. To explore functions for BSP in human breast cancer invasion and metastasis, the full-length BSP cDNA was transfected into the MDA-MB-231-BAG human breast cancer cell line under the control of the CMV promoter. Clones expressing BSP and vector control clones were isolated. BSP producing clones showed increased monolayer wound healing, a faster rate of stellate outgrowth in Matrigel and increased rate of invasion into a collagen matrix when compared to control clones. Clones were also examined in models of breast cancer growth and metastasis in vivo. BSP transfected clones showed an increased rate of primary tumor growth following mammary fat pad injection of nude mice. BSP transfected clones and vector control clones metastasized to soft organs and bone at a similar rate after intra-cardiac injection as determined by real-time PCR and X-ray analysis. Although these organs were targets for both BSP transfected and non-transfected cells, the size of the metastatic lesion was shown to be significantly larger for BSP expressing clones. This was determined by real-time PCR analysis for soft organs and by X-ray analysis of bone lesions. For bone this was confirmed by intra-tibial injections of cells in nude mice. We conclude that BSP acts to drive primary and secondary tumor growth of breast cancers in vivo.

Social network perspectives reveal strength of academic developers as weak ties

Social network perspectives acknowledge the influence of disciplinary cultures on academics’ teaching beliefs and practices with implications for academic developers. The contribution of academic developers in 18 scholarship of teaching and learning (SoTL) projects situated in the sciences are explored by drawing on data from a two-year national project in Australia within a case study research design. The application of a social network lens illuminated the contribution of eight academic developers as weak ties who infused SoTL knowledge within teams. Two heuristic cases of academic developers who also linked across networks are presented. Implications of social network perspective are discussed.

Trials and tribulations of recruiting 2,000 older women onto a clinical trial investigating falls and fractures : vital D study

Background Randomised, placebo-controlled trials are needed to provide evidence demonstrating safe, effective interventions that reduce falls and fractures in the elderly. The quality of a clinical trial is dependent on successful recruitment of the target participant group. This paper documents the successes and failures of recruiting over 2,000 women aged at least 70 years and at higher risk of falls or fractures onto a placebo-controlled trial of six years duration. The characteristics of study participants at baseline are also described for this study.

Methods The Vital D Study recruited older women identified at high risk of fracture through the use of an eligibility algorithm, adapted from identified risk factors for hip fracture. Participants were randomised to orally receive either 500,000 IU vitamin D3 (cholecalciferol) or placebo every autumn for five consecutive years. A variety of recruitment strategies were employed to attract potential participants.

Results Of the 2,317 participants randomised onto the study, 74% (n = 1716/2317) were consented onto the study in the last five months of recruiting. This was largely due to the success of a targeted mail-out. Prior to this only 541 women were consented in the 18 months of recruiting. A total of 70% of all participants were recruited as a result of targeted mail-out. The response rate from the letters increased from 2 to 7% following revision of the material by a public relations company. Participant demographic or risk factor profile did not differ between those recruited by targeted mail-outs compared with other methods.

Conclusion The most successful recruitment strategy was the targeted mail-out and the response rate was no higher in the local region where the study had extensive exposure through other recruiting strategies. The strategies that were labour-intensive and did not result in successful recruitment include the activities directed towards the GP medical centres. Comprehensive recruitment programs employ overlapping strategies simultaneously with ongoing assessment of recruitment rates. In our experience, and others direct mail-outs work best although rights to privacy must be respected.

Annual high-dose oral vitamin D and falls and fractures in older women : a randomized controlled trial

Context Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.

Objective To determine whether a single annual dose of 500 000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture.

Design, Setting, and Participants A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.

Intervention 500 000 IU of cholecalciferol or placebo.

Main Outcome Measures Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.

Results Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing.

Conclusion Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.

Ramipril sensitizes platelets to nitric oxide : implications for therapy in high-risk patients

Objectives
Using 2 sequential studies in HOPE (Heart Outcomes Prevention Evaluation) study&ndash;type patients, the aims of this study were: 1) to test the hypothesis that ramipril improves platelet nitric oxide (NO) responsiveness: and 2) to explore biochemical and physiological effects of ramipril in a cohort selected on the basis of platelet NO resistance.

Background</b>
Ramipril prevents cardiovascular events, but the bases for these effects remain uncertain. NO resistance at both the platelet and vascular levels is present in a substantial proportion of patients with diabetes or ischemic heart disease and is an independent risk factor for cardiovascular events.

Methods
Study 1 was a double-blind, randomized comparison of ramipril (10 mg) with placebo in a cohort of patients (n = 119) with ischemic heart disease or diabetes plus additional coronary risk factor(s), in which effects on platelet responsiveness to NO were compared. Study 2 was a subsequent short-term evaluation of the effects of ramipril in a cohort of subjects (n = 19) with impaired platelet NO responsiveness in whom additional mechanistic data were sought.

Results
In study 1, ramipril therapy increased platelet responsiveness to NO relative to the extent of aggregation (p < 0.001), but this effect occurred primarily in patients with severely impaired baseline NO responsiveness (n = 41). In study 2, ramipril also improved platelet NO responsiveness (p < 0.01), and this improvement was correlated directly with increased NO-stimulated platelet generation of cyclic guanosine monophosphate (p < 0.02) but not with changes in plasma thrombospondin-1 levels.

Conclusions
Ramipril ameliorates platelet NO resistance in HOPE study&ndash;type patients, with associated increases in soluble guanylate cyclase responsiveness to NO. This effect is likely to contribute to treatment benefit and define patients in whom ramipril therapy is particularly effective.

Clozapine reverses schizophrenia-related behaviours in the metabotropic glutamate receptor 5 knockout mouse: association with N-methyl-d-aspartic acid receptor up-regulation

Abnormalities in glutamatergic signalling are proposed in schizophrenia in light of the schizophreniform psychosis elicited by NMDA antagonists. The metabotropic glutamate receptor 5 (mGluR5) interacts closely with the NMDA receptor and is implicated in several behavioural endophenotypes of schizophrenia. We have demonstrated that mice lacking mGluR5 have increased sensitivity to the hyperlocomotive effects of the NMDA antagonist MK-801. Mice lacking mGluR5 also show abnormal locomotor patterns, reduced prepulse inhibition (PPI), and deficits on performance of a short-term spatial memory task on the Y-maze. Chronic administration of the antipsychotic drug clozapine ameliorated the locomotor disruption and reversed the PPI deficit, but did not improve Y-maze performance. Chronic clozapine increased NMDA receptor binding ([3H]MK-801) but did not alter dopamine D2 ([3H]YM-09151), 5-HT2A ([3H]ketanserin), or muscarinic M1/M4 receptor ([3H]pirenzepine), binding in these mice. These results demonstrate behavioural abnormalities that are relevant to schizophrenia in the mGluR5 knockout mouse and a reversal of behaviours with clozapine treatment. These results highlight both the interactions between mGluR5 and NMDA receptors in the determination of schizophreniform behaviours and the potential for the effects of clozapine to be mediated by NMDA receptor regulation.
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