Neuroendocrine and inflammatory responses to DHEA administration in young healthy women.

DHEA is reported to have beneficial effects for the elderly and for several pathologies because of its behavioral and anti-inflammatory properties. However, these properties have never been investigated in a young healthy population. The purpose of this double-blind, randomized study was therefore to investigate the effects of short-term DHEA administration (100 mg/day/4 weeks) on neuroendocrine (i.e., beta-endorphin and prolactin) and inflammatory (i.e., interleukin-6 and TNF-alpha) parameters in 10 young healthy female volunteers with regular sports practice. In parallel, the stress state was assessed with the Profile of Mood States (POMS) questionnaire. DHEA administration did not alter prolactin, interleukin-6 or TNF-alpha, and no significant change in tension, depression, anger, vigor, fatigue or confusion was noted. However, beta-endorphin levels increased significantly (p < 0.05) with the DHEA treatment. The results of this investigation indicate that short-term DHEA administration improves neuroendocrine modulation but does not affect the inflammatory status or psychological state in recreationally trained female athletes. Further studies are needed to determine the exact mechanisms and the responses of these parameters to DHEA administration at higher dosages and/or for longer durations, especially in response to physical/psychological stress.

Repeatability of quantitative 18F-FLT uptake measurements in solid tumors: an individual patient data multi-center meta-analysis.

INTRODUCTION: 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative 18F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of 18F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts. METHODS: A systematic search in PubMed, EMBASE.com and the Cochrane Library from inception-October 2016 yielded five 18F-FLT repeatability cohorts in solid tumors. 18F-FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUVmax, SUVmean, SUVpeak, proliferative volume and total lesion uptake (TLU) were calculated. Repeatability was assessed using the repeatability coefficient (RC = 1.96 × SD of test-retest differences), linear regression analysis, and the intra-class correlation coefficient (ICC). The impact of different lesion selection criteria was also evaluated. RESULTS: Images from four cohorts containing 30 patients with 52 lesions were obtained and analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma, and 33 in non-small cell lung cancer patients). A good correlation was found between test-retest data for all 18F-FLT uptake metrics (R2 ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUVpeak (RC: 23.1%), without significant differences in RC between different SUV metrics. Repeatability of proliferative volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection methods based on SUVmax ≥ 4.0 improved the repeatability of volumetric metrics (RC: 26-28%), but did not affect the repeatability of SUV metrics. CONCLUSIONS: In multi-center studies, differences ≥ 25% in 18F-FLT SUV metrics likely represent a true change in tumor uptake. Larger differences are required for FLT metrics comprising volume estimates when no lesion selection criteria are applied.

The meaning, measurement and modification of hypoxia in the laboratory and the clinic.

Hypoxia was identified as a microenvironmental component of solid tumours over 60 years ago and was immediately recognised as a potential barrier to therapy through the reliance of radiotherapy on oxygen to elicit maximal cytotoxicity. Over the last two decades both clinical and experimental studies have markedly enhanced our understanding of how hypoxia influences cellular behaviour and therapy response. Furthermore, they have confirmed early assumptions that low oxygenation status in tumours is an exploitable target in cancer therapy. Generally such approaches will be more beneficial to patients with hypoxic tumours, necessitating the use of biomarkers that reflect oxygenation status. Tissue biomarkers have shown utility in many studies. Further significant advances have been made in the non-invasive measurement of tumour hypoxia with positron emission tomography, magnetic resonance imaging and other imaging modalities. Here, we describe the complexities of defining and measuring tumour hypoxia and highlight the therapeutic approaches to combat it.

Impact of excess skin from massive weight loss on the practice of physical activity in women.

BACKGROUND: Over 70% of people who undergo bariatric surgery (BS) develop excess skin (ES). The physical and psychosocial consequences of ES may become a barrier to the practice of physical activity (PA), which is highly recommended to optimize the results of BS. The purpose of this study was to evaluate the impact of ES on the practice of PA in women who have undergone BS. METHODS: Questionnaires administered to 26 women having undergone BS 2 ± 0.2 years before (BMI = 29.1 ± 0.8 kg/m2) evaluated the impacts of ES, the practice of PA, physical self-perception, and physical exercise beliefs. We also used the 6-min walking test and muscular endurance tests to evaluate physical fitness and photographs with anatomical markers to quantify ES. RESULTS: Of the women, 76.9% declared mobility limitations due to ES during the practice of PA and 45.2% stated avoiding PA because of ES which caused flapping and unwelcome stares from others. The women who stated that they avoided PA because of ES had significantly lower physical self-perception and physical fitness and reported experiencing more embarrassment during PA despite no significant difference in the magnitude of ES (p = 0.06), BMI, daily life inconveniences, and energy expenditure compared to those women who did not avoid PA. CONCLUSION: Although ES after BS is a barrier to the practice of PA for some women, it does not in itself prevent the regular practice of PA. The main reason women with ES avoid PA seems to have less to do with the magnitude of ES itself and more with psychosocial inconveniences.

Optimization of methods for quantification of rCBF using high-resolution [¹5O]H2O PET images.

This study aimed to derive accurate estimates of regional cerebral blood flow (rCBF) from noisy dynamic [¹5O]H2O PET images acquired on the high-resolution research tomograph, while retaining as much as possible the high spatial resolution of this brain scanner (2-3 mm) in parametric maps of rCBF. The PET autoradiographic method and generalized linear least-squares (GLLS), with fixed or extended to include spatially variable estimates of the dispersion of the measured input function, were compared to nonlinear least-squares (NLLS) for rCBF estimation. Six healthy volunteers underwent two [¹5O]H2O PET scans with continuous arterial blood sampling. rCBF estimates were obtained from three image reconstruction methods (one analytic and two iterative, of which one includes a resolution model) to which a range of post-reconstruction filters (3D Gaussian: 2, 4 and 6 mm FWHM) were applied. The optimal injected activity was estimated to be around 11 MBq kg⁻¹ (800 MBq) by extrapolation of patient-specific noise equivalent count rates. Whole-brain rCBF values were found to be relatively insensitive to the method of reconstruction and rCBF quantification. The grey and white matter rCBF for analytic reconstruction and NLLS were 0.44 ± 0.03 and 0.15 ± 0.03 mL min⁻¹ cm⁻³, respectively, in agreement with literature values. Similar values were obtained from the other methods. For generation of parametric images using GLLS or the autoradiographic method, a filter of ≥ 4 mm was required in order to suppress noise in the PET images which otherwise produced large biases in the rCBF estimates.

Bias in iterative reconstruction of low-statistics PET data: benefits of a resolution model.

Iterative image reconstruction methods such as ordered-subset expectation maximization (OSEM) are widely used in PET. Reconstructions via OSEM are however reported to be biased for low-count data. We investigated this and considered the impact for dynamic PET. Patient listmode data were acquired in [(11)C]DASB and [(15)O]H(2)O scans on the HRRT brain PET scanner. These data were subsampled to create many independent, low-count replicates. The data were reconstructed and the images from low-count data were compared to the high-count originals (from the same reconstruction method). This comparison enabled low-statistics bias to be calculated for the given reconstruction, as a function of the noise-equivalent counts (NEC). Two iterative reconstruction methods were tested, one with and one without an image-based resolution model (RM). Significant bias was observed when reconstructing data of low statistical quality, for both subsampled human and simulated data. For human data, this bias was substantially reduced by including a RM. For [(11)C]DASB the low-statistics bias in the caudate head at 1.7 M NEC (approx. 30 s) was -5.5% and -13% with and without RM, respectively. We predicted biases in the binding potential of -4% and -10%. For quantification of cerebral blood flow for the whole-brain grey- or white-matter, using [(15)O]H(2)O and the PET autoradiographic method, a low-statistics bias of <2.5% and <4% was predicted for reconstruction with and without the RM. The use of a resolution model reduces low-statistics bias and can hence be beneficial for quantitative dynamic PET.

Abnormal prefrontal activation directly related to pre-synaptic striatal dopamine dysfunction in people at clinical high risk for psychosis.

Schizophrenia is characterized by altered prefrontal activity and elevated striatal dopaminergic function. To investigate the relationship between these abnormalities in the prodromal phase of the illness, we combined functional Magnetic Resonance Imaging and (18)F-Dopa Positron Emission Tomography. When performing a verbal fluency task, subjects with an At-Risk Mental State showed greater activation in the inferior frontal cortex than controls. Striatal dopamine function was greater in the At-Risk group than in controls. Within the At-Risk group, but not the control group, there was a direct correlation between the degree of left inferior frontal activation and the level of striatal dopamine function. Altered prefrontal activation in subjects with an At-Risk Mental State for psychosis is related to elevated striatal dopamine function. These changes reflect an increased vulnerability to psychosis and predate the first episode of frank psychosis.

Development and validation of a variance model for dynamic PET: uses in fitting kinetic data and optimizing the injected activity.

The precision of biological parameter estimates derived from dynamic PET data can be limited by the number of acquired coincidence events (prompts and randoms). These numbers are affected by the injected activity (A(0)). The benefits of optimizing A(0) were assessed using a new model of data variance which is formulated as a function of A(0). Seven cancer patients underwent dynamic [(15)O]H(2)O PET scans (32 scans) using a Biograph PET-CT scanner (Siemens), with A(0) varied (142-839 MBq). These data were combined with simulations to (1) determine the accuracy of the new variance model, (2) estimate the improvements in parameter estimate precision gained by optimizing A(0), and (3) examine changes in precision for different size regions of interest (ROIs). The new variance model provided a good estimate of the relative variance in dynamic PET data across a wide range of A(0)s and time frames for FBP reconstruction. Patient data showed that relative changes in estimate precision with A(0) were in reasonable agreement with the changes predicted by the model: Pearson's correlation coefficients were 0.73 and 0.62 for perfusion (F) and the volume of distribution (V(T)), respectively. The between-scan variability in the parameter estimates agreed with the estimated precision for small ROIs (<5 mL). An A(0) of 500-700 MBq was near optimal for estimating F and V(T) from abdominal [(15)O]H(2)O scans on this scanner. This optimization improved the precision of parameter estimates for small ROIs (<5 mL), with an injection of 600 MBq reducing the standard error on F by a factor of 1.13 as compared to the injection of 250 MBq, but by the more modest factor of 1.03 as compared to A(0) = 400 MBq.

Evidence for endogenous opioid release in the amygdala during positive emotion.

Endogenous opioid release has been linked to relief from aversive emotional memories, thereby promoting a euphoric state and subsequent interactions towards social stimuli resulting in the formation of social preferences. However, this theory remains controversial. Using positron emission tomography and [(11)C]diprenorphine (DPN) in healthy volunteers, we found significantly reduced DPN binding to opioid receptor in the hippocampus during positive mood induction compared to neutral mood. Furthermore, the magnitude of positive mood change correlated negatively with DPN binding in the amygdala bilaterally. Our finding of reduced DPN binding is consistent with increased release of endogenous opioids, providing direct evidence that localised release of endogenous opioids is involved in the regulation of positive emotion in humans.

Multi-resolution Bayesian regression in PET dynamic studies using wavelets.

In the kinetic analysis of dynamic PET data, one usually posits that the variation of the data through one dimension, time, can be described by a mathematical model encapsulating the relevant physiological features of the radioactive tracer. In this work, we posit that the remaining dimension, space, can also be modeled as a physiological feature, and we introduce this concept into a new computational procedure for the production of parametric maps. An organ and, in the instance considered here, the brain presents similarities in the physiological properties of its elements across scales: computationally, this similarity can be implemented in two stages. Firstly, a multi-scale decomposition of the dynamic frames is created through the wavelet transform. Secondly, kinetic analysis is performed in wavelet space and the kinetic parameters estimated at low resolution are used as priors to inform estimates at higher resolutions. Kinetic analysis in the above scheme is achieved by extension of the Patlak analysis through Bayesian linear regression that retains the simplicity and speed of the original procedure. Application to artificial and real data (FDG and FDOPA) demonstrates the ability of the procedure to reduce remarkably the variance of parametric maps (up to 4-fold reduction) without introducing sizeable bias. Significance of the methodology and extension of the procedure to other data (fMRI) and models are discussed.

What you need to know about the new BLS guidelines. Now you'll give stroke victims the same priority as those having an MI. Here's what else has changed.

Major changes to basic life support (BLS) and advanced cardiac life support (ACLS) practice have been approved, and you'll soon be receiving official update training. In this summary of the recommendations, we'll give you a head start on learning about changes to BLS protocols for health care professionals. Next month, we'll cover changes to ACLS guidelines.

Localization of neurotensin NTS2 receptors in rat brain, using.

The brain localization of the neurotensin receptor NTS2 was studied with [3H]levocabastine, using an autoradiographic procedure. This study suggests that NTS2 receptors are mainly intracellular. High densities of binding sites were observed in the cingulate, insular, temporal, occipital, enthorhinal cortex, amygdaloid complex, septohippocampal nuclei, medial thalamus, mammillary bodies and superior colliculi; a moderate labelling was observed in the anterior and medial hippocampus, olfactory tubercle, hypothalamus, periaqueductal gray matter, caudate putamen, nucleus accumbens, septum, lateral thalamus, dorsal raphe nucleus and cerebellum; finally, a low labelling was apparent in the ventral tegmentum area and substantia nigra. Thus it appears that NTS2 receptors are particularly abundant in the cerebral cortex, the limbic areas and some areas involved in pain perception.

Knowledge utilization among experienced staff nurses.

The purpose of this descriptive exploratory study was to describe the processes staff nurses use to select and transfer new knowledge to practice. Eleven experienced staff nurses shared 29 examples in which gaining new knowledge resulted in changes in thinking or acting in a clinical situation. Findings indicated that knowledge utilization originated with the nurse who was active in selecting and using new knowledge. Nurses used multiple knowledge utilization processes primarily involving factual knowledge and instrumental utilization. Often, the decision to move knowledge to practice was based on comparison by similarity. There were no variations in utilization processes as nurses floated across units. Sources of new knowledge were primarily informal and unit based. Implications for staff development focus on developing unit-based resources and resource personnel, using innovative ways to introduce new knowledge on the unit, and providing time in formal classes for exchange of ideas on using new knowledge in practice.

How a work group facilitator can help units reach goals.

Nurse managers have many demands on their time, and many unit and organizational goals to meet. This article describes skills for facilitating work groups and reaching goals by focusing others' talents.

Making the transition to a hospital-wide department of education: strategies for success.

In today's healthcare environment, staff development specialists have experienced a shift from a nursing-focused approach to education to an organization-wide approach. The change fosters both challenges and opportunities for the staff development specialist. This article describes the strategies used by a department of nursing education to successfully transition to a hospital-wide department of education.

Time to wear a third hat?

You have so many demands on your time, so many unit and organizational goals to meet. Learn the skills that can make you a top-notch work group facilitator and you'll reach your goals by focusing others' talents.

Equilibration of 6-[18F]fluoro-L-m-tyrosine between plasma and erythrocytes.

UNLABELLED: Intracranial or intraventricular blood pools have been suggested as noninvasive sources of an input function for quantitative PET. These techniques measure the concentration of the tracer in whole blood, but the concentration in plasma depends on the equilibration of the tracer between plasma and erythrocytes. METHODS: FDG, 6-[18F]fluoro-L-m-tyrosine (FmT), or its major metabolite, 6-[18F]fluoro-3-hydroxyphenylacetic acid (FHPAA), was added to blood samples obtained from healthy fasting volunteers along with radioiodinated human serum albumin (RIHSA). Samples were incubated at 37 degrees C for times between 10 s and 2 h and then plunged into an ice bath and centrifuged. Whole blood and plasma were counted for 18F and 125I activities. The resulting time courses were fit to successively more complex models, evaluated using an F test. RESULTS: All radioactivity associated with RIHSA remained in the plasma, whereas FDG equilibrated instantaneously between plasma and erythrocytes. FmT took about 1 h to equilibrate between plasma and erythrocytes; this time course could be described by a single exponential with a half-life of 10 min. FHPAA equilibrated within the first 5 min of the study. CONCLUSION: Our results show that, unlike FDG, the partitioning of FmT between plasma and erythrocytes is a relatively slow process. We present an analytic correction that may be applied to the measured time course of radioactivity in whole blood to obtain the time course of the tracer in plasma.

Novel and selective calcitonin-inducing agents.

A series of xanthine sulfonamides is presented as a class of calcitonin (CT) inducers - a potentially new method for treating diseases associated with postmenopausal bone loss such as osteoporosis. We have found that certain di-n-butylxanthine sulfonamides 4 upregulate CT transcription in a CT-luciferase reporter gene assay (CT-luci) and increase the production and release of CT in a CT secretion/RIA assay (CTS). In addition, these compounds do not have potent PDE4 inhibitory activity as do the related xanthine methylene ketones such as denbufyllene (2). One compound in particular (9) shows a transcription activation ratio (TAR) of 2.1 in CT-luci, a CTS increase of 3.6-fold, and a PDE4 (phosphodiesterase type IV) IC(50) = 4.1 microM. In addition, this compound showed a statistically significant 47% trabecular bone protection in ovariectomized-induced osteopenia (OVX) rats as determined by assay when administered for 4 weeks at 30 mg/kg/day, i. p. by quantitative computed tomography (QCT). When administered p.o., compound 9 shows 50% trabecular bone protection when administered for 3 weeks at 50 mg/kg/day, i.p. This compared with salmon CT which shows 62% trabecular bone protection when administered at 50 IU/kg/day for 4 weeks.

Regions of interest in the venous sinuses as input functions for quantitative PET.

UNLABELLED: As clinical PET becomes increasingly available, quantitative methods that are feasible in busy clinical settings are becoming necessary. We investigated the use of intracranial blood pools as sources of an input function for quantitative PET. METHODS: We studied 25 patients after the intravenous injection of [18F]6-fluoro-L-m-tyrosine and compared sampled blood time-activity curves with those obtained in small regions of interest (ROIs) defined in the blood pools visible in the PET images. Because of the comparatively large dimensions of the blood pool at the confluence of the superior sagittal, straight and transverse sinuses, a venous ROI input function was chosen for further analysis. We applied simple corrections to the ROI-derived time-activity curves, deriving expressions for partial volume, spillover and partition of tracer between plasma and red blood cells. The results of graphic and compartmental analysis using both sampled [Cs(t)] and ROI [Cr(t)] venous input functions for each patient were compared. We also used an analytic approach to examine possible differences between venous and arterial input functions in the cerebral circulation. RESULTS: Cr(t) peaked significantly earlier and higher than Cs(t) in this patient population, although the total integral under the curves did not differ significantly. We report some apparent differences in the results of modeling using the two input functions; however, neither the graphically determined influx constant, Ki, nor the model parameter that reflects presynaptic dopaminergic metabolism, k3, differed significantly between the two methods. The analytic results suggest that the venous ROI input function may be closer to the arterial supply of radiotracer to the brain than arterialized venous blood, at least in some patient populations. CONCLUSION: We present a simple method of obtaining an input function for PET that is applicable to a wide range of tracers and quantitative methods and is feasible for diagnostic PET imaging.

An educational fair and poster approach to organization-wide mandatory education.

BACKGROUND: An educational fair and poster approach was developed to meet organization-wide mandatory education requirements. METHOD: A multidisciplinary task force identified 25 mandatory topics. Task force members utilized posters to indicate key points (principles) and questions for each topic. Two interactive stations, body mechanics and fire safety, were developed to allow staff to actively participate and obtain immediate feedback on competency. This educational activity was presented in a fair-like atmosphere continuously over 3 days to reach a majority of staff. RESULTS: Ninety-three percent of the staff attended the educational activity. Department directors received immediate feedback on attendance, test scores, evaluation summaries and problem areas. Post-fair evaluation comments from department directors and staff were very positive. There was a major savings in both staff and staff development work hours. CONCLUSION: An educational fair and poster approach is an efficient method of providing organization-wide mandatory education. This approach can be adapted easily to any organization.