Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and glutathione S-transferase-pi expression in ARPE-19 cells

PURPOSE: To determine whether anthocyanin-enriched bilberry extracts modulate pre- or posttranslational levels of oxidative stress defense enzymes heme-oxygenase (HO)-1 and glutathione S-transferase-pi (GST-pi) in cultured human retinal pigment epithelial (RPE) cells. METHODS: Confluent ARPE-19 cells were preincubated with anthocyanin and nonanthocyanin phenolic fractions of a 25% enriched extract of bilberry (10(-6)-1.0 mg/mL) and, after phenolic removal, cells were oxidatively challenged with H(2)O(2). The concentration of intracellular glutathione was measured by HPLC and free radical production determined by the dichlorofluorescin diacetate assay. HO-1 and GST-pi protein and mRNA levels were determined by Western blot and RT-PCR, respectively. RESULTS: Preincubation with bilberry extract ameliorated the intracellular increase of H(2)O(2)-induced free radicals in RPE, though H(2)O(2) cytotoxicity was not affected. By 4 hours, the extract had upregulated HO-1 and GST-pi protein by 2.8- and 2.5-fold, respectively, and mRNA by 5.5- and 7.1-fold, respectively, in a dose-dependent manner. Anthocyanin and nonanthocyanin phenolic fractions contributed similarly to mRNA upregulation. CONCLUSIONS: Anthocyanins and other phenolics from bilberry upregulate the oxidative stress defense enzymes HO-1 and GST-pi in RPE, suggesting that they stimulate signal transduction pathways influencing genes controlled by the antioxidant response element.     

Tachykinins regulate the function of platelets

Evidence has been mounting for peripheral functions for tachykinins, a family of neuropeptides including substance P (SP), neurokinin A, and neurokinin B, which are recognized for their roles in the central and peripheral nervous system. The recent discovery of 4 new members of this family, the endokinins (EKA, B, C, and D), which are distributed peripherally, adds support to the notion that tachykinins have physiologic/endocrine roles in the periphery. In the present study we report a fundamental new function for tachykinins in the regulation of platelet function. We show that SP stimulates platelet aggregation, and underlying this is the intracellular mobilization of calcium and degranulation. We demonstrate the presence of the tachykinin receptors NK1 and NK3 in platelets and present evidence for the involvement of NK1 in SP-mediated platelet aggregation. Platelets were found to contain SP-like immunoreactivity that is secreted upon activation implicating SP-like substances in the autocrine/paracrine regulation of these cells. Indeed, NK1-blocking antibodies inhibited aggregation in response to other agonists. Of particular note is the observation that EKA/B cross-react in the SP immunoassay and are also able to stimulate platelet activation. Together our data implicate tachykinins, specifically SP and EKA/B, in the regulation of platelet function.     

Risk and protective factors for wellbeing in older veterans in New Zealand

Objectives: To compare indicators relating to aging and health among veterans and non-veterans, and identify factors associated with subjective wellbeing (SWB) of older New Zealand veterans.

Methods: Self-reported data were obtained from participants in a longitudinal cohort study of New Zealand older adults. Responses from 352 veterans and 1500 non-veterans (age range of 55–86 and gender matched) were selected as a comparison group on indicators related to health and aging. The association of these indicators with veterans’ SWB were assessed using hierarchical regression.

Results: Apart from being older, smoking more, and having more chronic conditions, veterans did not differ from non-veterans on indicators of health and wellbeing. Mental health, physical health, purpose in life, housing satisfaction, and capabilities (choice and freedom) accounted for a significant amount of variance in veterans’ SWB.

Conclusion: Our results suggest that older veterans do not differ greatly on indices of health and aging from their non-veteran peers. Results support previous findings that lower mental and physical health is associated with lower SWB for veterans. Building upon prior findings, the current results demonstrate that interventions focusing on enhancing a sense of purpose in life, supporting one's capability to achieve, and strengthening social and physical environment through social connectedness, may serve as protective factors for SWB in veterans.     

Improving the prevention and management of chronic disease in low-income and middle-income countries: a priority for primary health care

The burden of chronic diseases, such as heart disease, cancer, diabetes, and mental disorders is high in low-income and middle-income countries and is predicted to increase with the ageing of populations, urbanisation, and globalisation of risk factors. Furthermore, HIV/AIDS is increasingly becoming a chronic disorder. An integrated approach to the management of chronic diseases, irrespective of cause, is needed in primary health care. Management of chronic diseases is fundamentally different from acute care, relying on several features: opportunistic case finding for assessment of risk factors, detection of early disease, and identification of high risk status; a combination of pharmacological and psychosocial interventions, often in a stepped-care fashion; and long-term follow-up with regular monitoring and promotion of adherence to treatment. To meet the challenge of chronic diseases, primary health care will have to be strengthened substantially. In the many countries with shortages of primary-care doctors, non-physician clinicians will have a leading role in preventing and managing chronic diseases, and these personnel need appropriate training and continuous quality assurance mechanisms. More evidence is needed about the cost-effectiveness of prevention and treatment strategies in primary health care. Research on scaling-up should be embedded in large-scale delivery programmes for chronic diseases with a strong emphasis on assessment.     

Osteoporosis and fractures in postmenopausal women using estrogen

BACKGROUND: Previous studies demonstrate that postmenopausal women who use estrogen are somewhat protected from bone loss and fractures compared with nonusers, but the extent to which estrogen users remain at risk for osteoporosis and fractures is uncertain. OBJECTIVE: To determine long-term probabilities for incident fractures among postmenopausal estrogen users. METHODS: We examined data from the Study of Osteoporotic Fractures, a prospective cohort study with 10 years of follow-up (1986-1999). This cohort includes 8816 women 65 years and older from community settings in 4 areas of the United States. MAIN OUTCOME MEASURES: Hip, wrist, vertebral, and nonvertebral fractures. RESULTS: At baseline, using criteria developed by the World Health Organization, 40% of continuous estrogen users were osteopenic and 13% were osteoporotic at the hip or spine. Although women currently using estrogen lost less bone density than past users or those who never used estrogen, all user groups on average lost bone from the hip and calcaneus. During 10 years of observation, the adjusted probability of nonvertebral fractures was 19.6% for continuous estrogen users, similar to current partial users and lower than past users and those who never used estrogen (P<.05). These comparisons were similar for hip, wrist, and vertebral fractures. CONCLUSIONS: Although estrogen use is associated with reduced prevalence of low bone density, less bone loss, and lower probabilities for fractures, osteoporosis and fractures are common in older women who used estrogen continuously since menopause. Estrogen users should be considered in strategies designed to detect, prevent, and treat osteoporosis.     

Pediatric patients who receive antibiotics for fever and neutropenia in less than 60 min have decreased intensive care needs

Background

Antibiotic delivery to patients with fever and neutropenia (F&N) in <60 min is an increasingly important quality measure for oncology centers, but several published reports indicate that a time to antibiotic delivery (TTA) of <60 min is quite difficult to achieve. Here we report a quality improvement (QI) effort that sought to decrease TTA and assess associated clinical outcomes in pediatric patients with cancer and F&N.

Procedure

We used Lean‐Methodology and a Plan‐Do‐Study‐Act approach to direct QI efforts and prospectively tracked TTA measures and associated clinical outcomes (length of stay, duration of fever, use of imaging studies to search for occult infection, bacteremia, intensive care unit (ICU) consultation or admission, and mortality). We then performed statistical analysis to determine the impact of our QI interventions on total TTA, sub‐process times, and clinical outcomes.

Results

Our QI interventions significantly improved TTA such that we are now able to deliver antibiotics in <60 min nearly 100% of the time. All TTA sub‐process times also improved. Moreover, achieving TTA <60 min significantly reduced the need for ICU consultation or admission (P = 0.003) in this population.

Conclusion

Here we describe our QI effort along with a detailed assessment of several associated clinical outcomes. These data indicate that decreasing TTA to <60 min is achievable and associated with improved outcomes in pediatric patients with cancer and F&N. Pediatr Blood Cancer 2015;62:807–815. © 2015 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc.     

Self-care in Heart Failure Hospital Discharge Instructions—Differences Between Nurse Practitioner and Physician Providers

Patients with heart failure (HF) are at risk for frequent readmission potentially due to self-care deficits. Medical doctors (MDs) and nurse practitioners (NPs) both provide discharge instructions. However, each type of provider may emphasize different elements of care. The aim of this study was to analyze and compare the content of the documentation of 50 discharge instructions of heart failure patients written by NPs and MDs. Compared with MDs, NPs placed greater emphasis on symptom identification, and were more likely to advise and schedule follow-up appointments with primary care and cardiology providers rather than advising an appointment was needed without scheduling one.     

Modifiable Failures in the Colorectal Cancer Screening Process and Their Association With Risk of Death

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