Geographic location, physical activity and perceptions of the environment in Queensland adults

This study examines how physical activity and perceptions of the built environment differ by degree of urbanisation in Queensland, Australia. A statewide sample of adults (n=1208) completed a CATI survey assessing physical activity and perceptions of the environment in July-August 2005. Results indicate that residents in metropolitan areas were more likely to report the presence of shops and services, footpaths, heavy traffic and physical activity facilities than non-metropolitan residents. Although geographic location was not associated with achievement of sufficient levels of physical activity or walking, a notable interaction in the associations between both physical activity measures and the presence of footpaths in metropolitan and non-metropolitan areas was observed. This finding suggests the presence of a differential mechanism in terms of the relationships between physical activity and environmental supports by geographical location. Such effects require future investigation in terms of replication and understanding.     

In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: microbiology profiling studies with staphylococci and streptococci

We present data from antimicrobial assays performed in vitro that pertain to the potential clinical utility of a novel rifamycin-quinolone hybrid antibiotic, CBR-2092, for the treatment of infections mediated by gram-positive cocci. The MIC(90)s for CBR-2092 against 300 clinical isolates of staphylococci and streptococci ranged from 0.008 to 0.5 mug/ml. Against Staphylococcus aureus, CBR-2092 exhibited prolonged postantibiotic effects (PAEs) and sub-MIC effects (SMEs), with values of 3.2, 6.5, and >8.5 h determined for the PAE (3x MIC), SME (0.12x MIC), and PAE-SME (3x MIC/0.12x MIC) periods, respectively. Studies of genetically defined mutants of S. aureus indicate that CBR-2092 is not a substrate for the NorA or MepA efflux pumps. In minimal bactericidal concentration and time-kill studies, CBR-2092 exhibited bactericidal activity against staphylococci that was retained against rifampin- or intermediate quinolone-resistant strains, with apparent paradoxical cidal characteristics against rifampin-resistant strains. In spontaneous resistance studies, CBR-2092 exhibited activity consistent with balanced contributions from its composite pharmacophores, with a mutant prevention concentration of 0.12 mug/ml and a resistance frequency of <10(-12) determined at 1 mug/ml in agar for S. aureus. Similarly, CBR-2092 suppressed the emergence of preexisting rifamycin resistance in time-kill studies undertaken at a high cell density. In studies of the intracellular killing of S. aureus, CBR-2092 exhibited prolonged bactericidal activity that was superior to the activities of moxifloxacin, rifampin, and a cocktail of moxifloxacin and rifampin. Overall, CBR-2092 exhibited promising activity in a range of antimicrobial assays performed in vitro that pertain to properties relevant to the effective treatment of serious infections mediated by gram-positive cocci.     

Unmet symptom management needs of nursing home residents with cancer

Nursing home residents living with cancer have unacceptably high percentages of unrelieved pain and other symptoms. However, residents with cancer have received relatively little attention in the literature to date. This article provides an overview of previous symptom research for residents with cancer, explores clinical and organizational factors that impede effective symptom management, and proposes an agenda for future research and clinical practice. Residents with cancer have numerous symptoms that tend to be different from the symptoms of other nursing home residents. Symptom management for residents with cancer is often complicated by cognitive impairment, declining physical functioning, and comorbid illnesses. Barriers to symptom management include underuse of analgesics and hospice, nursing home staffing patterns, and lack of resources. Additional research is necessary to provide a more comprehensive understanding of residents with cancer, explore how organizational factors affect the care of residents with cancer, and evaluate interventions for effective symptom assessment and management. Collaboration of oncology nurses with clinicians and researchers in nursing home settings is needed to improve care for residents with cancer.     

Dextrin–rhEGF conjugates as bioresponsive nanomedicines for wound repair

Growth factors are known to act in concert to promote wound repair, but their topical application rarely leads to a significant clinical improvement of chronic wounds due to premature inactivation in wound environment. The aim of this study was to synthesise a polymer–growth factor conjugate and investigate whether the novel concept called Polymer-masking-UnMasking-Protein Therapy (PUMPT) might be used to generate bioresponsive polymer therapeutics as nanomedicines able to promote tissue repair. Succinoylated dextrin ( 85,000 g/mol;  19 mol% succinoylation), and rhEGF were chosen as a first model combination. The conjugate synthesised contained  16%wt rhEGF and < 1% free protein. It exhibited increased stability towards proteolytic degradation by trypsin and the clinically relevant enzyme neutrophil elastase. The dextrin component was degraded on addition of α-amylase leading to sustained release of free rhEGF over time (52.7% release after 168 h). When biological activity was assessed (± α-amylase) in proliferation assays using epidermoid carcinoma (HEp2) cells and HaCaT keratinocytes, as anticipated, polymer conjugation reduced rhEGF bioactivity (p = 0.0035). However, exposure to physiological concentrations of α-amylase triggered dextrin degradation and this led to protein unmasking with restoration of bioactivity to the level seen for unmodified rhEGF. Indeed, prolongation of HEp2 proliferation was observed over 8 days. The inability of dextrin, succinoylated dextrin or α-amylase alone to induce proliferative effects, and the ability of α-amylase-exposed dextrin–rhEGF to induce phosphorylation of the epidermal growth factor receptor (EGFR) in HEp2 cells confirmed a mechanism of action by stimulation of classical signal transduction pathways. These observations suggest that this dextrin–rhEGF, and other dextrin-growth factor conjugates have potential for further development as bioresponsive nanomedicines for tissue repair.     

The acute impact of ingestion of breads of varying composition on blood glucose, insulin and incretins following first and second meals

Structural characteristics and baking conditions influence the metabolic responses to carbohydrate-containing foods. We hypothesized that consumption of whole wheat or sourdough breads would have a favourable effect on biomarkers of glucose homeostasis after first and second meals, compared with those for white bread. Ten overweight volunteers consumed 50 g available carbohydrate of each of the four breads (white, whole wheat, sourdough, whole wheat barley) followed 3 h later by a standard second meal. Blood was sampled for 3 h following bread ingestion and a further 2 h after the second meal for determination of glucose, insulin, paracetamol (indirect marker of gastric emptying), glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Glucose and GLP-1 responses to sourdough bread were lower (P < 0.05) than whole wheat and whole wheat barley breads. Glucose area under the curve (AUC) for sourdough bread was lower than those for whole wheat (P < 0.005) and whole wheat barley (P < 0.03) breads for the entire study. GIP AUC after sourdough bread ingestion was lower compared to white (P < 0.004) and whole wheat barley (P < 0.002) breads following the second meal. There were no significant differences in insulin and paracetamol concentrations among the test breads. Ultra-fine grind whole wheat breads did not result in postprandial responses that were lower than those of white bread, but sourdough bread resulted in lower glucose and GLP-1 responses compared to those of these whole wheat breads following both meals.     

Broadening the age restriction for initiating rotavirus vaccination in regions with high rotavirus mortality: Benefits of mortality reduction versus risk of fatal intussusception

Introduction

Recently developed rotavirus vaccines have the potential to reduce diarrhea mortality in children in developing countries. Available data to date do not indicate risk of intussusception with these new vaccines. To avoid a potential unanticipated risk post-licensure, it is recommended that rotavirus immunization be initiated before 12 weeks of age when background intussusception rates are low. This policy could exclude a substantial number of children from vaccination, especially in developing countries where delays in vaccination are common.

Methods

We conducted a scenario analysis to assess the potential benefits of mortality reduction from rotavirus versus the risk of fatal intussusception when the first dose of the vaccine is strictly administered by 12 weeks of age compared with a free strategy with vaccine administered before 1 year of age using data on rotavirus disease, vaccine safety and efficacy, and current diphtheria–tetanus–pertussis vaccination rates, and by incorporating hypothetical risks of intussusception.

Results

In developing countries, assuming vaccine efficacy of 50% and 75% for doses 1 and 2, respectively, and a hypothetical sixfold and threefold increased relative risk of intussusception within 7 days of doses 1 and 2, respectively, initiating rotavirus immunization before 12 weeks of age would prevent 194,564 of the 517,959 annual rotavirus-associated deaths among children <5 years, while potentially resulting in 1106 fatal intussusception events. Administration of the first dose to infants up to 1 year of age would prevent an additional 54,087 rotavirus-associated deaths (total = 248,651) while potentially resulting in an additional 1226 intussusception deaths (total = 2332).

Conclusion

In developing countries, the additional lives saved by broadening the age restrictions for initiation of rotavirus vaccination would far outnumber the hypothetical excess intussusception deaths that would accompany such an approach.     

Noninvasive measurement of the cerebral blood flow response in human lateral geniculate nucleus with arterial spin labeling fMRI

To date, functional magnetic resonance imaging (fMRI) studies of the lateral geniculate nucleus (LGN) have primarily focused on measures of the blood oxygenation level dependent (BOLD) signal. Arterial spin labeling (ASL) is an MRI method that can provide direct measures of functional cerebral blood flow (CBF) changes. Because CBF is a well-defined physiological quantity that contributes to BOLD contrast, CBF measures can be used to improve the quantitative interpretation of fMRI studies. However, due in part to the low intrinsic signal-to-noise ratio of the ASL method, measures of functional CBF changes in the LGN are challenging and have not previously been reported. In this study, we demonstrate the feasibility of using ASL fMRI to measure the CBF response of the LGN to visual stimulation on a 3 T MRI system. The use of background suppression and physiological noise reduction techniques allowed reliable detection of LGN activation in all five subjects studied. The measured percent CBF response during activation ranged from 40 to 100%, assuming no interaction between the left and right LGN.