Anaesthesia and PET of the Brain

Although drugs have been used to administer general anaesthesia for more than a century and a half, relatively little was known until recently about the molecular and cellular effects of the anaesthetic agents and the neurobiology of anaesthesia. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have played a valuable role in improving this knowledge. PET studies using 11C-flumazenil binding have been used to demonstrate that the molecular action of some, but not all, of the current anaesthetic agents is mediated via the GABAA receptor. Using different tracers labelled with 18F, 11C and 15O, PET studies have shown the patterns of changes in cerebral metabolism and blood flow associated with different intravenous and volatile anaesthetic agents. Within classes of volatile agents, there are minor variations in patterns. More profound differences are found between classes of agents. Interestingly, all agents cause alterations in the blood flow and metabolism of the thalamus, providing strong support for the hypothesis that the anaesthetic agents interfere with consciousness by interfering with thalamocortical communication.</p

Objective quantification of nanoscale protein distributions

Nanoscale distribution of molecules within small subcellular compartments of neurons critically influences their functional roles. Although, numerous ways of analyzing the spatial arrangement of proteins have been described, a thorough comparison of their effectiveness is missing. Here we present an open source software, GoldExt, with a plethora of measures for quantification of the nanoscale distribution of proteins in subcellular compartments (e.g. synapses) of nerve cells. First, we compared the ability of five different measures to distinguish artificial uniform and clustered patterns from random point patterns. Then, the performance of a set of clustering algorithms was evaluated on simulated datasets with predefined number of clusters. Finally, we applied the best performing methods to experimental data, and analyzed the nanoscale distribution of different pre- and postsynaptic proteins, revealing random, uniform and clustered sub-synaptic distribution patterns. Our results reveal that application of a single measure is sufficient to distinguish between different distributions

Barcoded DNA-Tag Reporters for Multiplex Cis-Regulatory Analysis

Cis-regulatory DNA sequences causally mediate patterns of gene expression, but efficient experimental analysis of these control systems has remained challenging. Here we develop a new version of “barcoded" DNA-tag reporters, “Nanotags" that permit simultaneous quantitative analysis of up to 130 distinct cis-regulatory modules (CRMs). The activities of these reporters are measured in single experiments by the NanoString RNA counting method and other quantitative procedures. We demonstrate the efficiency of the Nanotag method by simultaneously measuring hourly temporal activities of 126 CRMs from 46 genes in the developing sea urchin embryo, otherwise a virtually impossible task. Nanotags are also used in gene perturbation experiments to reveal cis-regulatory responses of many CRMs at once. Nanotag methodology can be applied to many research areas, ranging from gene regulatory networks to functional and evolutionary genomics

A systematic review on the impact of leg ulceration on patients' quality of life

<p>Abstract</p> <p>Background</p> <p>A systematic review was conducted to analyse journal articles that describe or measure the impact of leg ulceration on patients' quality of life (QoL) in order to improve the content of an educational programme that aims to enhance self-care agency in leg ulcer patients.</p> <p>Method</p> <p>Original articles published in English and German between 1990 and 2006 were included if the findings were analysed at the level of patients. Articles were excluded if (1) they investigated the impact of specific treatments or settings on QoL or (2) focused mainly on arterial ulcers or diabetic foot ulcers.</p> <p>Results</p> <p>Twenty-four original research articles met the inclusion criteria; 11 studies used a quantitative, 11 studies a qualitative, and 2 used a mixed method approach. The findings were collapsed into 5 core domains. Quantitative studies commonly investigated the parameters of pain, sleep, social isolation, and physical mobility. Patients had significantly more pain, more restrictions regarding social functioning, less vitality, and limitations with respect to emotional roles compared to the respective controls. Other problem areas identified were restrictions in work capacity, recreation, social interaction, psychological well-being, as well as problems caused by treatment regimes. Inconclusive results were obtained regarding pain intensity, physical restrictions, and gender effects.</p> <p>Limitations</p> <p>Numerous original studies neither undertook a differentiation of participants by ulcer aetiology nor did they analyse the results according to gender differences.</p> <p>Conclusion</p> <p>As leg ulceration has an impact on QoL, national guidelines on the treatment of leg ulceration need to more specifically address these far-ranging effects identified in this review.</p

In search of quality evidence for lifestyle management and glycemic control in children and adolescents with type 2 diabetes: A systematic review

<p>Abstract</p> <p>Background</p> <p>Our purpose was to evaluate the impact of lifestyle behavior modification on glycemic control among children and youth with clinically defined Type 2 Diabetes (T2D).</p> <p>Methods</p> <p>We conducted a systematic review of studies (randomized trials, quasi-experimental studies) evaluating lifestyle (diet and/or physical activity) modification and glycemic control (HbA1c). Our data sources included bibliographic databases (EMBASE, CINAHL^®, Cochrane Library, Medline^®, PASCAL, PsycINFO^®, and Sociological Abstracts), manual reference search, and contact with study authors. Two reviewers independently selected studies that included any intervention targeting diet and/or physical activity alone or in combination as a means to reduce HbA1c in children and youth under the age of 18 with T2D.</p> <p>Results</p> <p>Our search strategy generated 4,572 citations. The majority of citations were not relevant to the study objective. One study met inclusion criteria. In this retrospective study, morbidly obese youth with T2D were treated with a very low carbohydrate diet. This single study received a quality index score of < 11, indicating poor study quality and thus limiting confidence in the study's conclusions.</p> <p>Conclusions</p> <p>There is no high quality evidence to suggest lifestyle modification improves either short- or long-term glycemic control in children and youth with T2D. Additional research is clearly warranted to define optimal lifestyle behaviour strategies for young people with T2D.</p

Between-Monitor Differences in Step Counts Are Related to Body Size: Implications for Objective Physical Activity Measurement

The quantification of the relationships between walking and health requires that walking is measured accurately. We correlated different measures of step accumulation to body size, overall physical activity level, and glucose regulation.Participants were 25 men and 25 women American Indians without diabetes (Age: 20-34 years) in Phoenix, Arizona, USA. We assessed steps/day during 7 days of free living, simultaneously with three different monitors (Accusplit-AX120, MTI-ActiGraph, and Dynastream-AMP). We assessed total physical activity during free-living with doubly labeled water combined with resting metabolic rate measured by expired gas indirect calorimetry. Glucose tolerance was determined during an oral glucose tolerance test.Based on observed counts in the laboratory, the AMP was the most accurate device, followed by the MTI and the AX120, respectively. The estimated energy cost of 1000 steps per day was lower in the AX120 than the MTI or AMP. The correlation between AX120-assessed steps/day and waist circumference was significantly higher than the correlation between AMP steps and waist circumference. The difference in steps per day between the AX120 and both the AMP and the MTI were significantly related to waist circumference.Between-monitor differences in step counts influence the observed relationship between walking and obesity-related traits