The effectiveness of eHealth interventions on physical activity and measures of obesity among working-age women: a systematic review and meta-analysis.

Physical inactivity and obesity are modifiable risk factors for cardiovascular disease, particularly in women. eHealth interventions may increase physical activity and improve obesity-related outcomes among women. The objective of this study was to review the evidence of the effectiveness of eHealth interventions to increase moderate-to-vigorous physical activity among working-age women. The secondary objective was to examine their effectiveness on improving obesity-related outcomes. A comprehensive search strategy was developed for eight electronic databases; through July 2016. All studies consisting of >80% women of working-age (18-65 years) in high income countries were included. Multiple unblinded reviewers determined study eligibility and extracted data. Risk of bias was evaluated using the Cochrane Risk of Bias Tool and data quality using the Grading of Recommendations Assessment, Development and Evaluation approach. Data were pooled using a random-effects model. Sixty studies were included in the review of which 20 were in the meta-analysis. The meta-analysis demonstrated eHealth interventions improved moderate-to-vigorous physical activity (standard mean difference = 1.13, 95% confidence interval: 0.58, 1.68, P < 0.0001); an increase of ~25 min week-1 . No changes were observed in obesity-related outcomes; waist circumference (P = 0.06), body mass (P = 0.05) and body mass index (P = 0.35). eHealth interventions are effective at increasing min week-1 of moderate-to-vigorous physical activity among working-age women from high income countries.

Ultra-High Mass Resolution MALDI Imaging Mass Spectrometry of Proteins and Metabolites in a Mouse Model of Glioblastoma.

MALDI mass spectrometry imaging is able to simultaneously determine the spatial distribution of hundreds of molecules directly from tissue sections, without labeling and without prior knowledge. Ultra-high mass resolution measurements based on Fourier-transform mass spectrometry have been utilized to resolve isobaric lipids, metabolites and tryptic peptides. Here we demonstrate the potential of 15T MALDI-FTICR MSI for molecular pathology in a mouse model of high-grade glioma. The high mass accuracy and resolving power of high field FTICR MSI enabled tumor specific proteoforms, and tumor-specific proteins with overlapping and isobaric isotopic distributions to be clearly resolved. The protein ions detected by MALDI MSI were assigned to proteins identified by region-specific microproteomics (0.8 mm2 regions isolated using laser capture microdissection) on the basis of exact mass and isotopic distribution. These label free quantitative experiments also confirmed the protein expression changes observed by MALDI MSI and revealed changes in key metabolic proteins, which were supported by in-situ metabolite MALDI MSI.

Mass Spectrometry Imaging in Cancer Research: Future Perspectives.

In the last decade mass spectrometry imaging has developed rapidly, in terms of multiple new instrumentation innovations, expansion of target molecules, and areas of application. Mass spectrometry imaging has already had a substantial impact in cancer research, uncovering biomolecular changes associated with disease progression, diagnosis, and prognosis. Many new approaches are incorporating the use of readily available formalin-fixed paraffin-embedded cancer tissues from pathology centers, including tissue blocks, biopsy specimens, and tumor microarrays. It is also increasingly used in drug formulation development as an inexpensive method to determine the distributions of drugs and their metabolites. In this chapter, we offer a perspective in the current and future methodological developments and how these may open up new vistas for cancer research.

Visualization of cellulose synthases in Arabidopsis secondary cell walls.

Cellulose biosynthesis in plant secondary cell walls forms the basis of vascular development in land plants, with xylem tissues constituting the vast majority of terrestrial biomass. We used plant lines that contained an inducible master transcription factor controlling xylem cell fate to quantitatively image fluorescently tagged cellulose synthase enzymes during cellulose deposition in living protoxylem cells. The formation of secondary cell wall thickenings was associated with a redistribution and enrichment of CESA7-containing cellulose synthase complexes (CSCs) into narrow membrane domains. The velocities of secondary cell wall-specific CSCs were faster than those of primary cell wall CSCs during abundant cellulose production. Dynamic intracellular of endomembranes, in combination with increased velocity and high density of CSCs, enables cellulose to be synthesized rapidly in secondary cell walls.

Effects of aerobic exercise, resistance exercise or both, on patient-reported health status and well-being in type 2 diabetes mellitus: a randomised trial.

AIMS/HYPOTHESIS: The Diabetes Aerobic and Resistance Exercise (DARE) study showed that aerobic and resistance exercise training each improved glycaemic control and that a combination of both was superior to either type alone in patients with type 2 diabetes mellitus. Here we report effects on patient-reported health status and well-being in the DARE Trial. METHODS: We randomised 218 inactive participants with type 2 diabetes mellitus in parallel to 22 weeks of aerobic exercise (n = 51), resistance exercise (n = 58), combined aerobic and resistance exercise (n = 57) or no exercise (control; n = 52). Intervention allocation was managed by a central office. Outcomes included health status as assessed by the physical and mental component scores of the Medical Outcomes Trust Short-Form 36-item version (SF-36) and well-being as measured by the Well-Being Questionnaire 12-item version (WBQ-12); these were measured at the Ottawa Hospital. RESULTS: Using a p value of 0.0125 for statistical significance due to multiple comparisons, mixed model analyses indicated that resistance exercise led to clinically but not statistically significant improvements in the SF-36 physical component score compared with aerobic exercise (Delta = 2.7 points; p = 0.048) and control (i.e. no exercise; Delta = 3.3 points; p = 0.015). For mental component scores, there were clinically important improvements favouring no (control) compared with resistance (Delta = 7.6 points; p < 0.001) and combined (Delta = 7.2 points; p < 0.001) exercise. No effects on WBQ-12 scores were noted. Overall, 59/218 (27%) of participants included in this analysis sustained an adverse event during the course of the study, including 16 participants in the combined exercise group, 19 participants in the resistance exercise group, 16 participants in the aerobic exercise group, and eight participants in the control group. All participants were included in the intent-to-treat analyses. The trial is now closed to follow-up. CONCLUSIONS/INTERPRETATION: Resistance exercise was better than aerobic or no exercise for improving physical health status in these patients. No exercise was superior to resistance or combined exercise for improving mental health status. Well-being was unchanged by intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT00195884 FUNDING: This study was funded by the Canadian Institutes of Health Research (grant MCT-44155) and the Canadian Diabetes Association (The Lillian Hollefriend Grant).

Quantifying surface modification events from scanning force microscopy images.

Scanning force microscopy (SFM) is widely used to monitor surfaces and surface modification processes. Some surface modification processes involve the addition (or removal) of discrete entities to (or from) a surface in circumstances where the absolute number of entities is related to some aspect of the process. A two-dimensional surface characterisation parameter - the surface area ratio (SAR) - was previously developed as a means of quantifying such modification and can be readily obtained from SFM images. Simulations have shown that the SAR parameter is superior for quantification purposes to conventional surface roughness parameters such as roughness average S(a), the area equivalent of R(a). Key features of SAR are as follows: its linear dependence with coverage; dependence of linearity slope on coverage mechanism; and its independence from the form, waviness or roughness of the underlying surface. A further advantage of this method is its simplicity given that the SAR parameter is readily obtained from SFM images. Simulations of adsorption onto flat surfaces have been validated using SFM images of polystyrene spheres adsorbed onto mica.

Improving immunoassays based on the analysis of scanning force microscopy images.

Scanning force microscopy has been demonstrated to be an effective binding event detection step for immunoassays. In its simplest form--analysing small area images--the detection limit of the scanning force microscopic immunoassay (SFMIA) has been shown to be comparable to existing techniques. In the present work, we have examined how the performance of image analysis-based SFMIA can be improved. Firstly, we have used a surface analysis parameter that increases linearly with the concentration of binding events. This parameter--the surface area ratio--is the ratio of the surface area after antigen binding to the surface area of the original biospecific surface. With this parameter, SFMIA images can be rapidly analysed and converted into assay units. Secondly, we have demonstrated that by using silicon wafer supports that carry fiducial marks we can relocate to very high accuracy onto the biospecific surfaces and identify the changes due to antigen binding. By relocating in this manner the signal to noise ratio of the technique is enhanced. Thirdly, from simulations we have determined the SFM tip size and image area that optimizes the immunoassay sensitivity.

Atomic force microscopy of BHK-21 cells: an investigation of cell fixation techniques.

The atomic force microscope (AFM) has been used to image a wide variety of biological samples, including cultured cells, in air. Whilst cultured cells have been prepared for AFM analysis using a variety of matrices and fixatives, a definitive study of sample preparation and its effects on cell morphology has not, as far as the authors are aware, previously been reported. Although a considerable number of cell fixatives exist, no single fixative is ideal for all investigations. Prior to the performance of specialised techniques, such as atomic force microscopy of cultured cells in air, the cell fixation method must be investigated and optimised. The fixative abilities of 2% paraformaldehyde-lysine-periodate, 0.25% glutaraldehyde, paraformaldehyde-glutaraldehyde, 4% phosphate-buffered formal saline, 1% formaldehyde, methanol:acetone, formal saline, 4% paraformaldehyde and ethanol:acetic acid were assessed in this study. A qualitative assessment system was used to evaluate the efficacy of the above fixatives using conventional fixation criteria (i.e. the presence of fibroblastic morphology consistent with optical microscopy and the absence of fixation artifacts). The optimal fixative was identified as 4% paraformaldehyde, which was capable of providing optically consistent images of BHK-21 (fibroblastic) cells, whose heights remained within the measurement capability of the AFM instrument used in this study.

Atomic force microscopy analysis of enveloped and non-enveloped viral entry into, and egress from, cultured cells.

Since its invention, the atomic force microscope has been used to image a wide variety of biological samples, including viruses. Viral entry into, and egress from, cultured cells has been extensively studied using numerous scientific techniques and to a limited extent using atomic force microscopy. One of the main structural differences that can exist between viruses is the absence, or presence, of an envelope and this factor has consequences for the mode of viral entry and egress. In this study, the entry into, and egress from, cultured cells of enveloped and non-enveloped viruses were investigated using atomic force microscopy. No significant cell surface changes were observed following infection with enveloped or non-enveloped viruses. Although roughness analysis of viral entry revealed cell smoothing post-infection, no differences between the roughness values of enveloped and non-enveloped viral entry were observed. Line analysis of viral entry revealed minor differences between cells infected with an enveloped rather than a non-enveloped virus. These differences may represent a distinction between the uptake processes of enveloped and non-enveloped viruses. Studies of viral egress revealed that infected cells were undergoing cytopathic changes. Whilst topographic, height and roughness differences clearly occurred between virally- and mock-infected cells, no significant differences were elucidated between enveloped and non-enveloped viral egress.

A method for measuring the size distribution of latex particles by scanning force microscopy.

A methodology has been developed to accurately determine the size distribution of latex particles using the scanning force microscope (SFM). Unlike other workers, who have generally measured the lateral dimensions of monolayers of latex particles using a global quantification method, we have measured the heights of individual latex particles located at the edges of latex monolayers that were immobilised onto mica substrates. In agreement with other work, we noted that the edges of monolayers of latex particles provided stable and reproducible scanning force imaging. Whilst SFM imaging noise, image processing artifacts, tip/sample forces and variations in the mica substrate are sources of measurement error that should not be overlooked, our experience has been that the variation over time of the sensitivity of the Z actuator is the greatest potential uncertainty in determining the heights of latex particles. The methodology that we used requires frequent calibration of the Z actuator of the SFM, typically before and after two or three images, in order to ensure that the uncertainties in the Z sensitivity are known and minimised. This methodology was developed for an SFM instrument that was equipped with open loop piezoelectric actuators following a careful study of the behaviour of those actuators. Using this methodology, we have measured the size distributions of populations of 300-400 latex particles from each of several different latex samples, with the maximum variation in the Z-actuator calibration experienced during the measurement of a sample being less than 2%, often about 1% and occasionally better still. In so doing, we have demonstrated that SFMs equipped with open loop actuators can be used for high confidence quantitative measurements of step heights.

A mini-review of mass spectrometry using high-performance FTICR-MS methods.

Structural characterization of macromolecules is currently delivering new insights into the behavior of individual molecules or molecular ensembles. Technological advances have made it possible to examine smaller and smaller amounts (down to single molecules) of larger and larger molecular systems. Mass spectrometry in particular is capable of the detailed study of extremely small quantities (down to a single molecule) of very large (biological) molecules. The advent of new ionization techniques such as electrospray and matrix-assisted laser desorption are mainly responsible for these advances. As a result, mass spectrometry has evolved into an enabling discipline that plays an increasingly important role in combinatorial chemistry, polymer science, biochemistry, medicine, environmental and marine science, and archaeology and conservation science. This paper will review a selection of methodological developments in the field of high-performance Fourier transform ion cyclotron resonance mass spectrometry for structural analysis of these macromolecules.

A non-contact mode scanning force microscope optimised to image biological samples in liquid.

Given that biological samples are particularly soft in their natural state and that a liquid is the most difficult operating environment for non-contact mode scanning force microscopy, the development of a scanning force microscope that is optimised to image biological samples in vitro presents significant challenges. The performance of the instrument described here has been optimised for such an application by incorporating magnetic excitation and active-Q control of the cantilever. The application of this instrument has been validated by imaging monolayers of immobilised antibodies in liquid and achieving image qualities comparable to those achieved in air for such samples.

Immobilisation of Semliki forest virus for atomic force microscopy.

Semliki Forest virus (SFV), an alphavirus, is a single-stranded positive-sense RNA virus. The RNA genome is surrounded by a protein shell known as the capsid which itself is surrounded by a lipid envelope of host cell origin. In this study, SFV strain L10 enveloped virus and its capsid were immobilised onto silicon wafer supports which had been pre-coated with a monolayer of the relevant anti-viral antibody. After drying, the samples were imaged in air, using non-contact mode atomic force microscopy (AFM). Quantification of the AFM images has revealed that both the strain L10 enveloped virus and capsid collapse when immobilised in this manner. The capsid undergoes more significant collapse compared to the enveloped virus. The dimensions of the immobilised enveloped virus and capsid have been compared to a model where the free spherical particles collapse into ellipsoids during immobilisation. For the immobilised capsid the dimensions are consistent with this model whereas for the enveloped virus the model is less effective. The dimensions of the enveloped virus appear to be affected by the antibody used for immobilisation.

Quantification of red blood cells using atomic force microscopy.

For humans the sizes and shapes of their red blood cells are important indicators of well being. In this study, the feasibility of using the atomic force microscope (AFM) to provide the sizes and shapes of red blood cells has been investigated. An immobilisation procedure has been developed that enabled red blood cells to be reliably imaged by contact AFM in air. The shapes of the red blood cells were readily apparent in the AFM images. Various cell quantification parameters were investigated, including thickness, width, surface area and volume. Excellent correlation was found between the AFM-derived immobilised mean cell volume (IMCV) parameter and the mean cell volume (MCV) parameter used in current haematological practice. The correlation between MCV and IMCV values has validated the immobilisation procedure by demonstrating that the significant cell shrinkage that occurs during immobilisation and drying does not introduce quantification artifacts. Reliable IMCV values were obtained by quantifying 100 red blood cells and this typically required 3-5 AFM images of 100 microm x 100 microm area. This work has demonstrated that the AFM can provide in a single test the red blood cell size and shape data needed in the assessment of human health.

Loglinear models using capture-recapture methods to estimate the size of a measles epidemic.

Cases of measles reported separately by doctors, hospitals, laboratories, and others are treated as separate captures and releases of the population of children aged up to 10 years who have been infected by measles in a recent epidemic. Loglinear models are used to assess the adequacy of fit of various models for capture-recapture and the size of the epidemic in different age groups is estimated.

Measles outbreak in western Sydney. Vaccine failure or failure to vaccinate?

OBJECTIVES: To determine the effectiveness of measles vaccine during a measles outbreak, and to assess whether age at vaccination was a risk factor for measles vaccine failure. DESIGN: A matched case-control study. SETTING: The five primary schools in western Sydney with the largest number of measles cases during the June to December 1993 outbreak. SUBJECTS: Seventy-nine children aged 5-9 years with an illness consistent with a clinical definition for measles. Two controls per case were selected from children in the same classroom. MAIN OUTCOME MEASURES: Estimated measles vaccine effectiveness by age of the child at vaccination and vaccination status: "unvaccinated"; "parental recall" (parents stated the child was vaccinated but no record could be found); and "record" (record including date of vaccination available). RESULTS: The estimated vaccine effectiveness was 94% (95% confidence interval [CI], 83%-98%) in the "record" group, and 81% (95% CI, 46%-93%) in the "parental recall" group. Vaccine effectiveness did not differ significantly with age at vaccination (under 12 months of age 96% [64%-99%]; 12-14 months 95% [81%-99%]; and 15 months and over 93% [80%-98%]). CONCLUSION: Vaccination records should be used to calculate a vaccine's effectiveness as parental recall may not be sufficiently accurate. The high vaccine effectiveness in the "record" group (94%) makes it unlikely that low vaccine effectiveness was the cause of the outbreak. More effort is needed to increase vaccine coverage to at least 95% in all population subgroups.