Renal Cell Carcinoma Perfusion before and after Radiofrequency Ablation Measured with Dynamic Contrast Enhanced MRI: A Pilot Study

Aim: To investigate if the early treatment effects of radiofrequency ablation (RFA) on renal cell carcinoma (RCC) can be detected with dynamic contrast enhanced (DCE)-MRI and to correlate RCC perfusion with RFA treatment time. Materials and methods: 20 patients undergoing RFA of their 21 RCCs were evaluated with DCE-MRI before and at one month after RFA treatment. Perfusion was estimated using the maximum slope technique at two independent sittings. Total RCC blood flow was correlated with total RFA treatment time, tumour location, size and histology. Results: DCE-MRI examinations were successfully evaluated for 21 RCCs (size from 1.3 to 4 cm). Perfusion of the RCCs decreased significantly (p < 0.0001) from a mean of 203 (±80) mL/min/100 mL before RFA to 8.1 (±3.1) mL/min/100 mL after RFA with low intra-observer variability (r ≥ 0.99, p < 0.0001). There was an excellent correlation (r = 0.95) between time to complete ablation and pre-treatment total RCC blood flow. Tumours with an exophytic location exhibit the lowest mean RFA treatment time. Conclusion: DCE-MRI can detect early treatment effects by measuring RCC perfusion before and after RFA. Perfusion significantly decreases in the zone of ablation, suggesting that it may be useful for the assessment of treatment efficacy. Pre-RFA RCC blood flow may be used to predict RFA treatment time

Combining Membrane Potential Imaging with l-Glutamate or GABA Photorelease

Combining membrane potential imaging using voltage sensitive dyes with photolysis of l-glutamate or GABA allows the monitoring of electrical activity elicited by the neurotransmitter at different sub-cellular sites. Here we describe a simple system and some basic experimental protocols to achieve these measurements. We show how to apply the neurotransmitter and how to vary the dimension of the area of photolysis. We assess the localisation of photolysis and of the recorded membrane potential changes by depolarising the dendrites of cerebellar Purkinje neurons with l-glutamate photorelease using different experimental protocols. We further show in the apical dendrites of CA1 hippocampal pyramidal neurons how l-glutamate photorelease can be used to calibrate fluorescence changes from voltage sensitive dyes in terms of membrane potential changes (in mV) and how GABA photorelease can be used to investigate the phenomenon of shunting inhibition. We also show how GABA photorelease can be used to measure chloride-mediated changes of membrane potential under physiological conditions originating from different regions of a neuron, providing important information on the local intracellular chloride concentrations. The method and the proof of principle reported here open the gateway to a variety of important applications where the advantages of this approach are necessary

Genotyping Performance Assessment of Whole Genome Amplified DNA with Respect to Multiplexing Level of Assay and Its Period of Storage

Whole genome amplification can faithfully amplify genomic DNA (gDNA) with minimal bias and substantial genome coverage. Whole genome amplified DNA (wgaDNA) has been tested to be workable for high-throughput genotyping arrays. However, issues about whether wgaDNA would decrease genotyping performance at increasing multiplexing levels and whether the storage period of wgaDNA would reduce genotyping performance have not been examined. Using the Sequenom MassARRAY iPLEX Gold assays, we investigated 174 single nucleotide polymorphisms for 3 groups of matched samples: group 1 of 20 gDNA samples, group 2 of 20 freshly prepared wgaDNA samples, and group 3 of 20 stored wgaDNA samples that had been kept frozen at −70°C for 18 months. MassARRAY is a medium-throughput genotyping platform with reaction chemistry different from those of high-throughput genotyping arrays. The results showed that genotyping performance (efficiency and accuracy) of freshly prepared wgaDNA was similar to that of gDNA at various multiplexing levels (17-plex, 21-plex, 28-plex and 36-plex) of the MassARRAY assays. However, compared with gDNA or freshly prepared wgaDNA, stored wgaDNA was found to give diminished genotyping performance (efficiency and accuracy) due to potentially inferior quality. Consequently, no matter whether gDNA or wgaDNA was used, better genotyping efficiency would tend to have better genotyping accuracy

Disentangling manual muscle testing and Applied Kinesiology: critique and reinterpretation of a literature review

Cuthbert and Goodheart recently published a narrative review on the reliability and validity of manual muscle testing (MMT) in the Journal. The authors should be recognized for their effort to synthesize this vast body of literature. However, the review contains critical errors in the search methods, inclusion criteria, quality assessment, validity definitions, study interpretation, literature synthesis, generalizability of study findings, and conclusion formulation that merit a reconsideration of the authors' findings. Most importantly, a misunderstanding of the review could easily arise because the authors did not distinguish the general use of muscle strength testing from the specific applications that distinguish the Applied Kinesiology (AK) chiropractic technique. The article makes the fundamental error of implying that the reliability and validity of manual muscle testing lends some degree of credibility to the unique diagnostic procedures of AK. The purpose of this commentary is to provide a critical appraisal of the review, suggest conclusions consistent with the literature both reviewed and omitted, and extricate conclusions that can be made about AK in particular from those that can be made about MMT. When AK is disentangled from standard orthopedic muscle testing, the few studies evaluating unique AK procedures either refute or cannot support the validity of AK procedures as diagnostic tests. The evidence to date does not support the use of MMT for the diagnosis of organic disease or pre/subclinical conditions

Can a standard dose of eicosapentaenoic acid (EPA) supplementation reduce the symptoms of delayed onset of muscle soreness?

Unaccustomed exercise can result in delayed onset of muscle soreness (DOMS) which can affect athletic performance. Although DOMS is a useful tool to identify muscle damage and remodelling, prolonged symptoms of DOMS may be associated with the over-training syndrome. In order to reduce the symptoms of DOMS numerous management strategies have been attempted with no significant effect on DOMS-associated cytokines surge. The present study aimed to investigate the acute and chronic effects of a 2x180 mg per day dose of eicosapentaenoic acid (EPA) on interleukin-6 (IL-6) mediated inflammatory response and symptoms associated with DOMS. Methods: Seventeen healthy non-smoking females (age 20.4 +/- 2.1 years, height 161.2 +/- 8.3cm and mass 61.48 +/- 7.4kg) were randomly assigned to either placebo (N = 10) or EPA (N = 7). Serum IL-6, isometric and isokinetic (concentric and eccentric) strength, and rating of perceived exertion (RPE) were recorded on four occasions: i-prior to supplementation, ii-immediately after three weeks of supplementation (basal effects), iii-48 hours following a single bout of resistance exercise (acute training response effects), and iv-48 hours following the last of a series of three bouts of resistance exercise (chronic training response effects). Results: There was only a group difference in the degree of change in circulating IL-6 levels. In fact, relative to the first baseline, by the third bout of eccentric workout, the EPA group had 103 +/- 60% increment in IL-6 levels whereas the placebo group only had 80 +/- 26% incremented IL-6 levels (P = 0.020). We also describe a stable multiple linear regression model which included measures of strength and not IL-6 as predictors of RPE scale. Conclusion: The present study suggests that in doubling the standard recommended dose of EPA, whilst this may still not be beneficial at ameliorating the symptoms of DOMS, it counter intuitively appears to enhance the cytokine response to exercise. In a context where previous in vitro work has shown EPA to decrease the effects of inflammatory cytokines, it may in fact be that the doses required in vivo is much larger than current recommended amounts. An attempt to dampen the exercise-induced cytokine flux in fact results in an over-compensatory response of this system

The reliability of three-dimensional scapular attitudes in healthy people and people with shoulder impingement syndrome

<p>Abstract</p> <p>Background</p> <p>Abnormal scapular displacements during arm elevation have been observed in people with shoulder impingement syndrome. These abnormal scapular displacements were evaluated using different methods and instruments allowing a 3-dimensional representation of the scapular kinematics. The validity and the intrasession reliability have been shown for the majority of these methods for healthy people. However, the intersession reliability on healthy people and people with impaired shoulders is not well documented. This measurement property needs to be assessed before using such methods in longitudinal comparative studies. The objective of this study is to evaluate the intra and intersession reliability of 3-dimensional scapular attitudes measured at different arm positions in healthy people and to explore the same measurement properties in people with shoulder impingement syndrome using the Optotrak Probing System.</p> <p>Methods</p> <p>Three-dimensional scapular attitudes were measured twice (test and retest interspaced by one week) on fifteen healthy subjects (mean age 37.3 years) and eight subjects with subacromial shoulder impingement syndrome (mean age 46.1 years) in three arm positions (arm at rest, 70° of humerothoracic flexion and 90° of humerothoracic abduction) using the Optotrak Probing System. Two different methods of calculation of 3-dimensional scapular attitudes were used: relative to the position of the scapula at rest and relative to the trunk. Intraclass correlation coefficient (ICC) and standard error of measure (SEM) were used to estimate intra and intersession reliability.</p> <p>Results</p> <p>For both groups, the reliability of the three-dimensional scapular attitudes for elevation positions was very good during the same session (ICCs from 0.84 to 0.99; SEM from 0.6° to 1.9°) and good to very good between sessions (ICCs from 0.62 to 0.97; SEM from 1.2° to 4.2°) when using the method of calculation relative to the trunk. Higher levels of intersession reliability were found for the method of calculation relative to the trunk in anterior-posterior tilting at 70° of flexion compared to the method of calculation relative to the scapula at rest.</p> <p>Conclusion</p> <p>The estimation of three-dimensional scapular attitudes using the method of calculation relative to the trunk is reproducible in the three arm positions evaluated and can be used to document the scapular behavior.</p

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

The Spectacular Ultraviolet Flash from the Peculiar Type Ia Supernova 2019yvq

Early observations of Type Ia supernovae (SNe Ia) provide essential clues for understanding the progenitor system that gave rise to the terminal thermonuclear explosion. We present exquisite observations of SN 2019yvq, the second observed SN Ia, after iPTF 14atg, to display an early flash of emission in the ultraviolet (UV) and optical. Our analysis finds that SN 2019yvq was unusual, even when ignoring the initial flash, in that it was moderately underluminous for an SN Ia (${M}_{g}\approx -18.5$ mag at peak) yet featured very high absorption velocities ($v\approx 15{\rm{,0}}00$ km s−1 for Si ii λ6355 at peak). We find that many of the observational features of SN 2019yvq, aside from the flash, can be explained if the explosive yield of radioactive 56Ni is relatively low (we measure ${M}_{{56}_{\mathrm{Ni}}}=0.31\pm 0.05\,{M}_{\odot }$) and it and other iron-group elements are concentrated in the innermost layers of the ejecta. To explain both the UV/optical flash and peak properties of SN 2019yvq we consider four different models: interaction between the SN ejecta and a nondegenerate companion, extended clumps of 56Ni in the outer ejecta, a double-detonation explosion, and the violent merger of two white dwarfs. Each of these models has shortcomings when compared to the observations; it is clear additional tuning is required to better match SN 2019yvq. In closing, we predict that the nebular spectra of SN 2019yvq will feature either H or He emission, if the ejecta collided with a companion, strong [Ca ii] emission, if it was a double detonation, or narrow [O i] emission, if it was due to a violent merger

Detection methods predict differences in biology and survival in breast cancer patients

BackgroundThe aim of this study was to measure the biological characteristics involved in tumorigenesis and the progression of breast cancer in symptomatic and screen-detected carcinomas to identify possible differences.MethodsFor this purpose, we evaluated clinical-pathological parameters and proliferative and apoptotic activities in a series of 130 symptomatic and 161 screen-detected tumors.ResultsAfter adjustment for the smaller size of the screen-detected carcinomas compared with symptomatic cancers, those detected in the screening program presented longer disease-free survival (RR = 0.43, CI = 0.19-0.96) and had high estrogen and progesterone receptor concentrations more often than did symptomatic cancers (OR = 3.38, CI = 1.72-6.63 and OR = 3.44, CI = 1.94-6.10, respectively). Furthermore, the expression of bcl-2, a marker of good prognosis in breast cancer, was higher and HER2/neu expression was lower in screen-detected cancers than in symptomatic cancers (OR = 1.77, CI = 1.01-3.23 and OR = 0.64, CI = 0.40-0.98, respectively). However, when comparing prevalent vs incident screen-detected carcinomas, prevalent tumors were larger (OR = 2.84, CI = 1.05-7.69), were less likely to be HER2/neu positive (OR = 0.22, CI = 0.08-0.61) and presented lower Ki67 expression (OR = 0.36, CI = 0.17-0.77). In addition, incident tumors presented a shorter survival time than did prevalent ones (RR = 4.88, CI = 1.12-21.19).ConclusionsIncident carcinomas include a variety of screen-detected carcinomas that exhibit differences in biology and prognosis relative to prevalent carcinomas. The detection method is important and should be taken into account when making therapy decisions

Ubiquitous molecular substrates for associative learning and activity-dependent neuronal facilitation.

Recent evidence suggests that many of the molecular cascades and substrates that contribute to learning-related forms of neuronal plasticity may be conserved across ostensibly disparate model systems. Notably, the facilitation of neuronal excitability and synaptic transmission that contribute to associative learning in Aplysia and Hermissenda, as well as associative LTP in hippocampal CA1 cells, all require (or are enhanced by) the convergence of a transient elevation in intracellular Ca2+ with transmitter binding to metabotropic cell-surface receptors. This temporal convergence of Ca2+ and G-protein-stimulated second-messenger cascades synergistically stimulates several classes of serine/threonine protein kinases, which in turn modulate receptor function or cell excitability through the phosphorylation of ion channels. We present a summary of the biophysical and molecular constituents of neuronal and synaptic facilitation in each of these three model systems. Although specific components of the underlying molecular cascades differ across these three systems, fundamental aspects of these cascades are widely conserved, leading to the conclusion that the conceptual semblance of these superficially disparate systems is far greater than is generally acknowledged. We suggest that the elucidation of mechanistic similarities between different systems will ultimately fulfill the goal of the model systems approach, that is, the description of critical and ubiquitous features of neuronal and synaptic events that contribute to memory induction