Tracking physical activity using smart phone apps: assessing the ability of a current app and systematically collecting patient recommendations for future development.

BACKGROUND: Within the United Kingdom's National Health System (NHS), patients suffering from obesity may be provided with bariatric surgery. After receiving surgery many of these patients require further support to continue to lose more weight or to maintain a healthy weight. Remotely monitoring such patients' physical activity and other health-related variables could provide healthworkers with a more 'ecologically valid' picture of these patients' behaviours to then provide more personalised support. The current study assesses the feasibility of two smartphone apps to do so. In addition, the study looks at the barriers and facilitators patients experience to using these apps effectively. METHODS: Participants with a BMI > 35 kg/m2 being considered for and who had previously undergone bariatric surgery were recruited. Participants were asked to install two mobile phone apps. The 'Moves' app automatically tracked participants' physical activity and the 'WLCompanion' app prompted participants to set goals and input other health-related information. Then, to learn about participants' facilitators and barriers to using the apps, some participants were asked to complete a survey informed by the Theoretical Domains Framework. The data were analysed using regressions and descriptive statistics. RESULTS: Of the 494 participants originally enrolled, 274 participants data were included in the analyses about their activity pre- and/or post-bariatric surgery (ages 18-65, M = 44.02, SD ± 11.29). Further analyses were performed on those 36 participants whose activity was tracked both pre- and post-surgery. Participants' activity levels pre- and post-surgery did not differ. In addition, 54 participants' survey responses suggested that the main facilitator to their continued use of the Moves app was its automatic nature, and the main barrier was its battery drain. CONCLUSIONS: The current study tracked physical activity in patients considered for and who had previously undergone bariatric surgery. The results should be interpreted with caution because of the small number of participants whose data meet the inclusion criteria and the barriers participants encountered to using the apps. Future studies should take note of the barriers to develop more user-friendly apps. TRIAL REGISTRATION: ClinicalTrials.gov- NCT01365416 on the 3rd of June 2011.

Quantitative coronary arterial stenosis assessment by multidetector CT and invasive coronary angiography for identifying patients with myocardial perfusion abnormalities.

BACKGROUND: Semi-quantitative stenosis assessment by coronary CT angiography only modestly predicts stress-induced myocardial perfusion abnormalities. The performance of quantitative CT angiography (QCTA) for identifying patients with myocardial perfusion defects remains unclear. METHODS: CorE-64 is a multicenter, international study to assess the accuracy of 64-slice QCTA for detecting ≥50% coronary arterial stenoses by quantitative coronary angiography (QCA). Patients referred for cardiac catheterization with suspected or known coronary artery disease were enrolled. Area under the receiver-operating-characteristic curve (AUC) was used to evaluate the diagnostic accuracy of the most severe coronary artery stenosis in a subset of 63 patients assessed by QCTA and QCA for detecting myocardial perfusion abnormalities on exercise or pharmacologic stress SPECT. RESULTS: Diagnostic accuracy of QCTA for identifying patients with myocardial perfusion abnormalities by SPECT revealed an AUC of 0.71, compared to 0.72 by QCA (P = .75). AUC did not improve after excluding studies with fixed myocardial perfusion abnormalities and total coronary arterial occlusions. Optimal stenosis threshold for QCTA was 43% yielding a sensitivity of 0.81 and specificity of 0.50, respectively, compared to 0.75 and 0.69 by QCA at a threshold of 59%. Sensitivity and specificity of QCTA to identify patients with both obstructive lesions and myocardial perfusion defects were 0.94 and 0.77, respectively. CONCLUSIONS: Coronary artery stenosis assessment by QCTA or QCA only modestly predicts the presence and the absence of myocardial perfusion abnormalities by SPECT. Confounding variables affecting the relationship between coronary anatomy and myocardial perfusion likely account for some of the observed discrepancies between coronary angiography and SPECT results.

Lactoferrin is a survival factor for neutrophils in rheumatoid synovial fluid.

OBJECTIVES: Lactoferrin is an iron-binding protein that is released from activated neutrophils at sites of inflammation and has anti-microbial as well as anti-inflammatory properties. This study set out to determine whether lactoferrin can delay neutrophil apoptosis and could act as a survival factor for neutrophils in SF. METHODS: Human peripheral blood and SF neutrophils were incubated with iron-free lactoferrin and apoptosis determined after 9 h. SF from patients with RA was added to isolated neutrophils, with or without immunodepletion of lactoferrin, and effects on neutrophil apoptosis determined. Levels of lactoferrin in SF were assessed and related to disease duration and markers of disease activity. RESULTS: Iron-free lactoferrin significantly delayed apoptosis of peripheral blood neutrophils, in a concentration-dependent manner after 9 h in culture (P < 0.04). Lactoferrin could also delay apoptosis of neutrophils isolated from SF of patients with RA. SF from patients with established RA delayed apoptosis of peripheral blood neutrophils and this effect was significantly reduced by depletion of lactoferrin (P < 0.03). Lactoferrin levels in SF from patients with established RA did not correlate with disease severity, but did correlate with markers of inflammation (CRP) and with the presence of RF. SF from patients with arthritis of <12 weeks duration did not contain significant levels of lactoferrin. CONCLUSION: Lactoferrin contributes to extended neutrophil survival in the rheumatoid joint in the established phase of RA but not in very early arthritis.

Dissociation of caspase-mediated events and programmed cell death induced via HLA-DR in follicular lymphoma.

Human leukocyte antigens (HLA) class II antigen-mediated apoptosis has been documented in antigen-presenting cells and B lymphoproliferations. Characteristics of the apoptosis include rapidity and selectivity for mature cells. Follicular lymphomas are particularly refractory to apoptosis. The B-cell lymphoma Ramos shares characteristics of this subgroup and is insensitive to apoptosis via simple HLA-DR engagement. However, oligomerization of HLA-DR antigens induced caspase activation followed by phosphatidylserine externalization, activation of PKC-delta and cleavage of nuclear lamin B. Mitochondrial injury was also detected. However, inhibition of caspase activation simply delayed the apoptotic phenotype but neither protected against cell death nor prevented mitochondrial injury. The data in this report demonstrate that the requirements for the initiating signal (oligomerization versus engagement) as well as the molecular pathways varies between different B lymphoproliferations despite their common expression of HLA-DR. Finally, blockade of caspase activation in parallel with HLA-DR mAb stimulation could provide a potent autovaccination stimulus by leading to necrotic death of B-cell lymphomas.

Gliptins: a new class of oral hypoglycaemic agent.

The epidemic of type 2 diabetes worldwide continues unabated. Despite a number of existing therapies, treatment goals are seldom fully achieved. While insulin resistance and beta cell failure remain important in the pathogenesis of the condition, the role of incretin hormones in glucose homeostasis has recently become clearer. Incretins have several glucoregulatory mechanisms, and a novel approach to the treatment of type 2 diabetes focuses on enhancing and prolonging the physiological actions of these hormones. Gliptins inhibit the enzyme dipeptidyl peptidase-IV (DPP-IV), which degrades incretin hormones. These drugs are a promising new class of oral hypoglycaemic medication, which appear to be weight-neutral and have few side-effects, although the published clinical studies are mainly regulatory licensing studies. As these drugs now are available for clinical use, we discuss the mechanism of action, efficacy and potential adverse effects of this new class of oral hypoglycaemic agent.

The isolation and characterisation of guinea-pig polymorphonuclear leucocyte actin and myosin.

The contractile proteins actin and myosin have been isolated from the soluble phase of guinea-pig polymorphonuclear leucocytes and partially characterised. Two forms of actin have been identified, designated 'Mg-actin' and 'KCl-actin'. They have different polymerising properties but their propensity to form synthetic homologous and heterologous actomyosins and to inhibit DNAase-1 does not significantly differ. Both show beta and gamma isoelectric forms in focusing gels and the Mg-actin accounts for about 5% of the soluble-phase protein and te KCl-actin around 2%. Leucocyte myosin has been isolated by affinity chromatography on N6-ADP-Sepharose with a good enrichment of both Ca2+-ATPase and the ATPase activity measured in the absence of Ca2+ or Mg2+ and in the presence of EDTA. This protein, too, has the capacity to form synthetic homologous and hybrid actomyosins with enhancement of the basal Mg2+-ATPase activity. The ratio of actin to myosin in the leucocyte calculated on a molar basis is well in excess of 100, a figure consistent with the findings from other non-muscle cells.

5-Hydroxytryptamine induced excitation and inhibition in the subthalamic nucleus: action at 5-HT(2C), 5-HT(4) and 5-HT(1A) receptors.

Extracellular single-unit recordings in mouse brain slices were used to determine the effect of exogenously applied 5-HT on STN neurones. Recordings were made from 74 STN cells which fired action potentials at a regular rate of 7.19+/-0.5 Hz. In 61 cells (82%), 5-HT application increased STN neurone firing rate (10 microM, 180+/-16.8%, n=35) with an estimated EC(50) of 5.4 microM. The non-specific 5-HT(2) receptor agonist alpha-methyl 5-HT (1-10 microM) mimicked 5-HT induced excitations (15 cells). These excitations were significantly reduced by pre-perfusion with the specific 5-HT(2C) receptor antagonist RS102221 (500 nM, 9 cells) and the 5HT(4) antagonist GR113808 (500 nM, 7 cells). In 6 cells (8%) 5-HT induced biphasic responses where excitation was followed by inhibition, while in 7 cells (9%) inhibition of firing rate was observed alone. Inhibitory responses were reduced by the 5-HT(1A) antagonist WAY100135 (1 microM, 4 cells). No inhibitory responses were observed following alpha-methyl 5-HT applications. Both the excitations and inhibitions were unaffected by picrotoxin (50 microM, n=5) and CNQX (10 microM, n=5) indicative of direct postsynaptic effects. Thus, in STN neurones, 5-HT elicits two distinct effects, at times on the same neurone, the first being an excitation which is mediated by 5-HT(2C) and 5-HT(4) receptors and the second an inhibition which is mediated by 5-HT(1A) receptors.

Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans.

Elderly humans are more susceptible to bacterial infections because of declining immune status. We have investigated the effect of aging on neutrophil bactericidal responses, comparing neutrophil function in healthy, young (23-35 years) and elderly (>65 years) volunteers. Superoxide generation in response to fMLP was slightly increased in neutrophils from elderly donors, and serum from the elderly was able to opsonize E. coli efficiently. In contrast, phagocytic index was significantly lower in neutrophils from the elderly, compared with young donors (P<0.005). CD11a and CD11b expression was not affected by age, but CD16 was significantly reduced in neutrophils from elderly donors (P<0.0001). CD16 expression and phagocytic index were measured in the same neutrophils using FITC-labeled E. coli, PE-conjugated anti-CD16 antibody, and CD16 expression correlated with phagocytic index (r=0.83; P<0.05). In elderly patients with bacterial infection, CD16 expression remained low. We propose that reduced neutrophil CD16 expression and phagocytosis contribute to human immunesenescence.

Antibodies against Mycobacterium paratuberculosis in Crohn's disease.

Until recently the investigation of serological responses to mycobacteria in patients with Crohn's disease has been hindered by the considerable degree of cross-reactivity between antigens of M. paratuberculosis, and other mycobacterial subspecies. We evaluated the serological response of Crohn's disease patients to a recently identified species-specific 18 kDa protease-resistant antigen corresponding to M. paratuberculosis bacterioferritin. The 18 kDa antigen was purified from M. paratuberculosis as previously described. Serum was obtained from 40 patients with Crohn's disease, 15 with ulcerative colitis, 25 coeliac patients, and 21 normal blood donors. Antibody levels were measured by enzyme-linked immunosorbent assay (ELISA), with anti-human IgA and IgG alkaline phosphatase conjugate. Antibody titres were expressed as the dilution giving 1/3 of the plateau binding value of a standard positive serum (MT/3). Disease activity of the Crohn's disease cases was assessed using the Harvey-Bradshaw index. There was no statistically significant elevation of the mean IgG or IgA MT/3 titres of Crohn's disease patients over controls. No patients had antibody titres greater than two standard deviations above the mean control MT/3 titres, and there was no significant correlation between Crohn's disease activity and level of antibody titres. These findings make it unlikely that M. paratuberculosis is of primary pathogenic importance in Crohn's disease.

Modulation by magnesium of N-methyl-D-aspartate receptors in developing human brain.

AIM: To investigate age related alterations in glutamate N-methyl-D-aspartate (NMDA) receptor binding produced by the modulatory compounds glutamate, glycine, and magnesium (Mg2+) sulphate. METHODS: The effects produced by glutamate plus glycine, and Mg2+ on the binding of [3H]MK-801, a ligand for the N-methyl-D-aspartate ion channel phencyclidine site, were measured in membrane preparations made from prefrontal cortex from human neonate (n = 5), infant (n = 6), and adult (n = 6) necropsy brains. RESULTS: Neonatal brains had the least [3H]MK-801 binding, suggesting either a low density of NMDA receptors or a more restricted access of [3H]MK-801 to cation channel sites. Infant brains had the most [3H]MK-801 binding which was stimulated to a greater extent by L-glutamate (100 microM) and glycine (10 microM) than in neonatal and adult brains. MG2+ invariably inhibited [3H]MK-801 binding. However, the Mg2+ IC50 value was higher in neonatal brain (3.6 mM) than infant (1.4 mM) and adult (0.87 mM) brains. CONCLUSION: Infant brain may have excess NMDA receptors which are hyper responsive to glutamate and glycine. The lower potency of Mg2+ to inhibit [3H]MK-801 binding in neonatal cortex may be because newborn babies have NMDA receptors without the normal complement of Mg2+ sites. The findings suggest that therapeutic NMDA receptor block in neonates requires higher concentrations of magnesium sulphate in brain tissue.

The use of cinacalcet in pregnancy to treat a complex case of parathyroid carcinoma.

UNLABELLED: We present the case of a patient with metastatic parathyroid carcinoma whose hypercalcaemia was medically managed through two pregnancies. The diagnosis was made when the patient presented with chronic knee pain and radiological findings consistent with a brown tumour, at the age of 30. Her corrected calcium and parathyroid hormone (PTH) levels were significantly elevated. Following localisation studies, a right parathyroidectomy was performed with histology revealing parathyroid carcinoma, adherent to thyroid tissue. Aged 33, following biochemical recurrence of disease, the patient underwent a second operation. A subsequent CT and FDG-PET revealed bibasal pulmonary metastases. Aged 35, the patient was referred to our unit for treatment of persistent hypercalcaemia. The focus of treatment at this time was debulking metastatic disease using radiofrequency ablation. Despite advice to the contrary, the patient conceived twice while taking cinacalcet. Even though there are limited available data regarding the use of cinacalcet in pregnancy, both pregnancies continued to term with the delivery of healthy infants, using intensive medical management for persistent hypercalcaemia. LEARNING POINTS: Parathyroid carcinoma is a rare cause of primary hyperparathyroidism.Hypercalcaemia during pregnancy can result in significant complications for both the mother and the foetus.The use of high-dose cinacalcet in pregnancy has been shown, in this case, to aid in the management of resistant hypercalcaemia without teratogenicity.

Availability and night-time use of electronic entertainment and communication devices are associated with short sleep duration and obesity among Canadian children.

UNLABELLED: What is already known about this subject Short sleep duration is a risk factor for obesity. Television (TV) in the bedroom has been shown to be associated with excess body weight in children. Children increasingly use other electronic entertainment and communication devices (EECDs) such as video games, computers, and smart phones. What this study adds Access to and night-time use of EECDs are associated with shortened sleep duration, excess body weight, poorer diet quality, and lower physical activity levels. Our findings reinforce existing recommendations pertaining to TV and Internet access by the American Academy of Pediatrics and suggest to have these expanded to restricted availability of video games and smart phones in children's bedrooms. BACKGROUND: While the prevalence of childhood obesity and access to and use of electronic entertainment and communication devices (EECDs) have increased in the past decades, no earlier study has examined their interrelationship. OBJECTIVE: To examine whether night-time access to and use of EECDs are associated with sleep duration, body weights, diet quality, and physical activity of Canadian children. METHODS: A representative sample of 3398 grade 5 children in Alberta, Canada, was surveyed. The survey included questions on children's lifestyles and health behaviours, the Harvard Youth/Adolescent Food Frequency questionnaire, a validated questionnaire on physical activity, and measurements of heights and weights. Random effect models were used to assess the associations of night-time access to and use of EECDs with sleep, diet quality, physical activity, and body weights. RESULTS: Sixty-four percent of parents reported that their child had access to one or more EECDs in their bedroom. Access to and night-time use of EECDs were associated with shortened sleep duration, excess body weight, poorer diet quality, and lower physical activity levels in a statistically significant manner. CONCLUSIONS: Limiting the availability of EECDs in children's bedrooms and discouraging their night-time use may be considered as a strategy to promote sleep and reduce childhood obesity.

The endocrine system and ageing.

Complex changes occur within the endocrine system of ageing individuals. This article explores the changes that occur in the metabolism and production of various hormones and discusses the resulting clinical consequences. As individuals age there is a decline in the peripheral levels of oestrogen and testosterone, with an increase in luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin. Additionally there is a decline in serum concentrations of growth hormone, insulin-like growth factor-I and dehydroepiandrosterone and its sulphate-bound form. Even though there are complex changes within the hypothalmo-pituitary-adrenal/thyroid axis, there is minimal change in adrenal and thyroid function with ageing. The clinical significance of these deficiencies with age are variable and include reduced protein synthesis, decrease in lean body mass and bone mass, increased fat mass, insulin resistance, higher cardiovascular disease risk, increase in vasomotor symptoms, fatigue, depression, anaemia, poor libido, erectile deficiency and a decline in immune function. For each endocrine system, studies have been carried out in an attempt to reverse the effects of ageing by altering the serum hormonal levels of older individuals. However, the real benefits of hormonal treatment in older individuals are still being evaluated.

Effect of age on susceptibility to post-traumatic infection in the elderly.

Previous work has demonstrated an age-related decline in neutrophil function, including a decline in phagocytic capacity, with age in healthy individuals. This decline in function may contribute to increased susceptibility to bacterial infections in the elderly population. The present study has investigated the effects of age on susceptibility to infection and neutrophil function in elderly humans following mild trauma. Specifically, we have measured neutrophil function in 44 patients, all of whom had no significant co-morbidity, were over 65 years old (mean age 82.5 years) and had sustained a fractured neck of femur. We obtained neutrophils and examined the process of microbial engulfment by phagocytosis and the bactericidal mechanism of superoxide production. In the 5-week period after trauma, almost half of the elderly trauma patients succumbed to bacterial or fungal infection, with a predominance of chest and urinary tract infections. When examining neutrophil function, a decline in superoxide production was observed in neutrophils from the elderly trauma group at the time of hip fracture when compared with those from healthy elderly controls, and this was maintained 5 weeks after trauma. This was accompanied by an age-related reduction in phagocytic function during this period. We propose that trauma and an age-related decline in neutrophil function combine to decrease the immune response to bacteria in the elderly.

Gram-negative bacteria, HLA-B27 and inflammatory bowel disease.

Lymphocytes from 48 IBD patients including nine with HLA-B27 were examined for their capacity to absorb Y.enterocolitica 0:9 antiserum. They possessed a range of absorption ability which was unconnected with HLA-B27 status. Samples of lymphocytes from 28 AS patients, 10 RA patients and 28 normal control subjects were included for comparison. The significance of the findings is discussed.