Helping Families Change Childhood Obesity

The prevalence of childhood obesity is increasing at an alarming rate and is implicated in the onset of serious and life threatening health problems of both a physical and psychological nature. The current research comprised of three main components. Firstly, the reliability of a readiness to change questionnaire was examined, which had been completed by parents of obese children enrolled in the Bodywise childhood obesity programme. Secondly, an analysis of outcome data from 36 families who completed the above programme was also undertaken in order to determine if the data identified their stage of change, as defined by the questionnaire Thirdly, four semi-structured interviews were conducted with families involved with the Bodywise programme. These parents provided information related to their experiences of lifestyle change, including what initiated change, what assisted change, and what barriers to change they had encountered. Findings revealed that in accordance with the transtheoretical model the readiness to change questionnaire was a reasonably reliable instrument for indentifying parents' readiness to change their child's eating patterns and physical activity levels. Analysis of the outcome data from the 36 families revealed individuals in the action stage of change for both eating and physical activity made more rapid change at the outset of the programme than individuals in earlier stages of change. In addition, information derived from the interviews with families identified several promoters and barriers to change, many of which were similar across families. Until now no studies have examined the application of the transtheoretical model to an intervention for childhood obesity. Previous research has shown support for the model's use with other health problems. Overall this study lends support for the utility of the transtheoretical model in childhood obesity intervention

Parton models

We discuss the successes and failures of the naive quark and Parton models and offer a possible remedy for the resonance symmetry versus vertex symmetry dilemma. Using the concept of current and constituent quarks related by a general Melosh-type transformation, we calculate matrix elements for excitation of the baryon octet ground state by weak and electromagnetic currents and find that the theory compares well with experiment except in the low ῲ region. Here some further SU (6) breaking mechanism is necessary for a good fit. An alternative to the current and constituent quarks idea is to attempt a relativistic treatment of quarks, assuming current and constituent quarks to be fundamentally identical. Several models are discussed and a new model for mesons is presented. The solutions are similar to those obtained in other models apart from the inclusion of spin-orbit coupling terms, which have not previously appeared naturally in relativistic wave functions. We calculate some decay widths and find reasonable agreement with the data

Peripheral inflammation is associated with remote global gene expression changes in the brain

Background: Although the central nervous system (CNS) was once considered an immunologically privileged site, in recent years it has become increasingly evident that cross talk between the immune system and the CNS does occur. As a result, patients with chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease or psoriasis, are often further burdened with neuropsychiatric symptoms, such as depression, anxiety and fatigue. Despite the recent advances in our understanding of neuroimmune communication pathways, the precise effect of peripheral immune activation on neural circuitry remains unclear. Utilizing transcriptomics in a well-characterized murine model of systemic inflammation, we have started to investigate the molecular mechanisms by which inflammation originating in the periphery can induce transcriptional modulation in the brain.<p></p> Methods: Several different systemic and tissue-specific models of peripheral toll-like-receptor-(TLR)-driven (lipopolysaccharide (LPS), lipoteichoic acid and Imiquimod) and sterile (tumour necrosis factor (TNF) and 12-O-tetradecanoylphorbol-13-acetate (TPA)) inflammation were induced in C57BL/6 mice. Whole brain transcriptional profiles were assessed and compared 48 hours after intraperitoneal injection of lipopolysaccharide or vehicle, using Affymetrix GeneChip microarrays. Target gene induction, identified by microarray analysis, was validated independently using qPCR. Expression of the same panel of target genes was then investigated in a number of sterile and other TLR-dependent models of peripheral inflammation.<p></p> Results: Microarray analysis of whole brains collected 48 hr after LPS challenge revealed increased transcription of a range of interferon-stimulated genes (ISGs) in the brain. In addition to acute LPS challenge, ISGs were induced in the brain following both chronic LPS-induced systemic inflammation and Imiquimod-induced skin inflammation. Unique to the brain, this transcriptional response is indicative of peripherally triggered, interferon-mediated CNS inflammation. Similar models of sterile inflammation and lipoteichoic-acid-induced systemic inflammation did not share the capacity to trigger ISG induction in the brain.<p></p> Conclusions: These data highlight ISG induction in the brain as being a consequence of a TLR-induced type I interferon response. As considerable evidence links type I interferons to psychiatric disorders, we hypothesize that interferon production in the brain could represent an important mechanism, linking peripheral TLR-induced inflammation with behavioural changes.<p></p&gt

Therapeutic drug monitoring in the past 40 years of the JAC

Since the Journal was first published in 1975, papers addressing therapeutic drug monitoring (TDM) have been a regular feature. Initially they focused on laboratory aspects of drug concentration measurement then they changed more to the application of TDM in a clinical setting. Over its history, the Journal has provided its readership with the latest technological and scientific advances in TDM and has helped to drive changes in TDM that have directly impacted on patient care. These have varied from improvement in the quality of antimicrobial measurements through better identification of dosage regimens and TDM targets that help predict outcome and adverse events

Sustained exposure to systemic endotoxin triggers chemokine induction in the brain followed by a rapid influx of leukocytes

Background: Recent years have seen an explosion of research pertaining to biological psychiatry, yet despite subsequent advances in our understanding of neuroimmune communication pathways, how the brain senses and responds to peripheral inflammation remains poorly understood. A better understanding of these pathways may be important for generating novel therapeutics to treat many patients with chronic inflammatory diseases who also suffer from neuropsychiatric comorbidities. Here we have systematically assessed the leukocyte infiltrate to the brain following systemic endotoxin exposure to better understand this novel route of neuroimmune communication. Methods: Mice were injected intraperitoneally with LPS daily for 2, 5 or 7 consecutive days. We systematically interrogated the subsequent induction of chemokine transcription in the brain using TaqMan low-density arrays. A combination of flow cytometry and immunohistochemistry was then used to characterise the accompanying leukocyte infiltrate Result: Repeated LPS challenges resulted in prolonged activation of brain-resident microglia, coupled with an increased local transcription of numerous chemokines. After 2 days of administering LPS, there was a marked increase in the expression of the neutrophil chemoattractants CXCL1 and CXCL2; the monocyte chemoattractants CCL2, CCL5, CCL7 and CCL8; and the lymphocyte chemoattractants CXCL9, CXCL10 and CXCL16. In a number of cases, this response was sustained for several days. Chemokine induction was associated with a transient recruitment of neutrophils and monocytes to the brain, coupled with a sustained accumulation of macrophages, CD8+ T cells, NK cells and NKT cells. Strikingly, neutrophils, monocytes and T cells appeared to extravasate from the vasculature and/or CSF to infiltrate the brain parenchyma. Conclusions: Prolonged exposure to a peripheral inflammatory stimulus triggers the recruitment of myeloid cells and lymphocytes to the brain. By altering the inflammatory or metabolic milieu of the brain, this novel method of immune-to-brain communication may have profound implications for patients with chronic inflammatory diseases, potentially leading to neuropsychiatric comorbidities

Contact-induced apical asymmetry drives the thigmotropic responses of Candida albicans hyphae

Acknowledgements We thank Marco Thiel for assistance with data interpretation, Peter Sudbery for the provision of strains and Jeremy Craven for useful discussions. This work was supported by a BBSRC-DTG to D. D. T., NIH award DK083592 to F. J. B. and P. A. J., and a Royal Society URF UF080611 and MRC NIRG 90671 to A. C. B.Non peer reviewedPublisher PD

Timing of the first vancomycin maintenance dose in an acute hospital setting - room for improvement?

Introduction Intravenous vancomycin therapy typically starts with a loading dose followed by a maintenance dose 12 to 24 hours later. In the acute hospital setting, this often results in doses being administered in the middle of the night, which is impractical for both patients and staff. This audit examined current practice and developed new guidelines to support greater flexibility in the timing of the first maintenance dose. Methods Data recording forms used by pharmacists to support the therapeutic drug monitoring of vancomycin were collected from two hospital sites over six weeks. Forms containing at least two vancomycin concentrations were selected and the time of administration of the first maintenance dose was recorded. Individual vancomycin pharmacokinetic parameter estimates were obtained using MAP Bayesian analysis then used to predict vancomycin concentrations 6, 8, 10, 12 and 14 hours after a banded loading dose and 20 mg/kg (capped at 3000 mg). Predicted concentrations were compared with a target range of 10 – 20 mg/L. Results Data were obtained from 49 patients with a mean (SD) age of 63.1 (16.7) years and weight 80.1 (27.6) kg. In all patients, creatinine clearance estimates were >40 mL/min and, according to current practice guidelines, all patients required 12 hourly maintenance dosing. The time recorded for the administration of the first maintenance dose was between 11 pm and 7 am in 30 (61%) of these patients. In 14 patients (29%), the first maintenance dose was administered >12 hours after loading. The target range was achieved with banded doses (20 mg/kg) in 65% (71%) of concentrations at 6 hours, 74% (84%) at 8 hours, 57% (67%) at 10 hours, 53% (55%) at 12 hours and 39% (43%) at 14 hours. Conclusions This audit has shown that current practice results in a high proportion of vancomycin maintenance doses being administered at impractical times. Allowing a more flexible time window of 6-12 hours after the loading dose for administration of the first vancomycin maintenance dose could help to alleviate this problem and reduce the risk of early subtherapeutic vancomycin trough concentrations