Citrulline as a Diagnostic Parameter and a Major Amino Acid Constituent of Cerebrospinal Fluid in Hepatic Coma

Peer Reviewe

Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

<p>Abstract</p> <p>Background</p> <p>The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis.</p> <p>Methods</p> <p>Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl_<b>4</b>, rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups.</p> <p>Results</p> <p>Histopathological examination of liver tissue from animals which received DENA-CCl₄only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated <it>β-catenin</it>, proliferating cell nuclear antigen (<it>PCNA</it>), <it>cyclin D </it>and <it>survivin </it>genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect.</p> <p>Conclusions</p> <p>Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation and cell cycle regulation, with subsequent amelioration of liver histopathological picture and liver function.</p

Interpersonal dynamics in baseline rallies in tennis

In tennis, the relative positioning of players on court constrains their opportunities to perform successful actions. In this study we proposed and validated an empirical function that captures the spatial-temporal relationship between tennis players during competitive performance. This parameter, termed goal-directed displacement index (GDD Index), is defined over time by the product of both players' distances to the central line of the court and to the centre of the net. Results showed that the GDD index successfully described tennis players' patterns of interaction, as well as identified breaks in patterns of play during competitive performance, due to changes in relative positioning on court. Our analysis revealed two different patterns of interpersonal interactions, cross and down-the-line rallies, and two ways for a break to emerge in game dynamics, parallel variation (transition from a cross court rally to a down-the-line rally) and angle opening (lateral displacement). Data suggest that the elaboration of specific individual profiles of performance for different players, using the GDD index, could improve performance analysis in tennis

The value of the central vein sign at 3T to differentiate MS from seropositive-NMOSD.

Objective: To assess the value of the central vein sign (CVS) on a clinical 3T scanner to distinguish between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). / Methods: Eighteen aquaporin-4-antibody-positive patients with NMOSD, 18 patients with relapsing-remitting MS, and 25 healthy controls underwent 3T MRI. The presence of a central vein in white matter lesions on susceptibility-weighted imaging, defined as a thin hypointense line or a small dot, was recorded. / Results: The proportion of lesions with the CVS was higher in MS than NMOSD (80% vs 32%, p < 0.001). A greater proportion of lesions with the CVS predicted the diagnosis of MS, rather than NMOSD (odds ratio 1.10, 95% confidence interval [CI] 1.04 to 1.16, p = 0.001), suggesting that each percent unit increase in the proportion of lesions with the CVS in an individual patient was associated with a 10% increase in the risk of the same patient having MS. If more than 54% of the lesions on any given scan show the CVS, then the patient can be given a diagnosis of MS with an accuracy of 94% (95% CIs 81.34, 99.32, p < 0.001, sensitivity/specificity 90%/100%). / Conclusion: The clinical value of the CVS in the context of the differential diagnosis between MS and NMOSD, previously suggested using 7T scanners, is now extended to clinical 3T scanners, thereby making a step towards the use of CVS in clinical practice. / Classification of evidence: This study provides Class III evidence that the CVS on 3T MRI accurately distinguishes patients with MS from those with seropositive NMOSD

Emissions Trends and Drivers (Chapter 2)

Global net anthropogenic greenhouse gas (GHG) emissions during the last decade (2010–2019) were higher than at any previous time in human history (high confidence). Since 2010, GHG emissions have continued to grow, reaching 59 ± 6.6 GtCO2-eq in 2019,1 but the average annual growth in the last decade (1.3%, 2010–2019) was lower than in the previous decade (2.1%, 2000–2009) (high confidence). Average annual GHG emissions were 56 ± 6.0 GtCO2-eq yr –1 for the decade 2010–2019 growing by about 9.1 GtCO2-eq yr –1 from the previous decade (2000–2009) – the highest decadal average on record (high confidence)

Multi-camera real-time three-dimensional tracking of multiple flying animals

Automated tracking of animal movement allows analyses that would not otherwise be possible by providing great quantities of data. The additional capability of tracking in real time—with minimal latency—opens up the experimental possibility of manipulating sensory feedback, thus allowing detailed explorations of the neural basis for control of behaviour. Here, we describe a system capable of tracking the three-dimensional position and body orientation of animals such as flies and birds. The system operates with less than 40 ms latency and can track multiple animals simultaneously. To achieve these results, a multi-target tracking algorithm was developed based on the extended Kalman filter and the nearest neighbour standard filter data association algorithm. In one implementation, an 11-camera system is capable of tracking three flies simultaneously at 60 frames per second using a gigabit network of nine standard Intel Pentium 4 and Core 2 Duo computers. This manuscript presents the rationale and details of the algorithms employed and shows three implementations of the system. An experiment was performed using the tracking system to measure the effect of visual contrast on the flight speed of Drosophila melanogaster. At low contrasts, speed is more variable and faster on average than at high contrasts. Thus, the system is already a useful tool to study the neurobiology and behaviour of freely flying animals. If combined with other techniques, such as ‘virtual reality’-type computer graphics or genetic manipulation, the tracking system would offer a powerful new way to investigate the biology of flying animals

Activity profile of top-class association football referees in relation to fitness test performance and match standard

The aim of this study was to examine the kinematic activity profiles, cardiovascular responses and physical fitness of top-class football referees (n=11) during the FIFA Confederations Cup 2005. Computerised match-analyses (n=9) were performed with a two-dimensional photogrammetric video system, and the cardiovascular demand imposed on the referees (n=12) was measured using heart rate recordings. Total distance covered was 10,218, s=643 m of which 3531, s=510 m was covered at high intensities (>3.6 m.s(-1)). Both total distance covered (r2=0.59; P=0.02) and high-intensity activities (r2=0.44; P=0.05) were related to the distance covered by the ball in the same match. The referees ran at high speed 37% further (P=0.01) in the actual tournament than during under-17 top-level officiating. After the 5-min interval during which high-speed running peaked, in the following 5 min the performance was reduced by 19% (P=0.01) in relation to the mean of the game. Mean heart rate was 161, s=9 b.min(-1) (86, s=3% of maximal heart rate (HRmax)). Mean heart rate (expressed as percentage of HRmax) was related in part (r2=0.36; P5 m.s(-1)) best describes the physical performance of referees; (3) heart rate recording can be a useful tool to determine the most intense periods of a match and (4) the new fitness tests adopted by FIFA were poor predictors of match activities

Reproductive Strategy of the Giant Electric Ray in the Southern Gulf of California

The objective of the present study was to describe and characterize macroscopic and microscopic aspects of the reproductive biology of the Giant Electric Ray Narcine entemedor, a viviparous elasmobranch targeted by commercial fishers in Mexico. A total of 305 individual rays were captured (260 females, 45 males); all males were sexually mature. The median size at maturity for females was estimated to be 58.5 cm TL, the median size at pregnancy was 63.7 cm TL, and the median size at maternity was 66.2 cm TL. The range of ovarian follicles recorded per female was 1–69; the maximum ovarian fecundity of fully grown vitellogenic oocytes was 17, and uterine fecundity ranged from 1 to 24 embryos per female. The lengths of the oblong ovarian follicles varied significantly among months, and the largest ovarian follicles were found in July, August, and September. Median embryo size was largest in August, and the size at birth was between 12.4 and 14.5 cm TL. Histological evidence of secretions from the glandular tissue of the uterine villi indicate that this species probably has limited histotrophy as a reproductive mode. Vitellogenesis in the ovary occurred synchronously with gestation in the uterus. The Giant Electric Ray has a continuous annual reproductive cycle; a period of ovulation occurs between May and September and two peaks of parturition, one in January and one in August, occur, suggesting that embryonic diapause occurs in some individuals. These results provide useful information for the management of this important commercial species in Bahía de La Paz, Mexico, and will allow possible modification of the current Mexican regulations to enable better protection of this species

Therapeutic validation of an orphan G protein-coupled receptor: the case of GPR84

Despite the importance of members of the G protein‐coupled receptor (GPCR) superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. In certain cases even the endogenous ligand(s) that activates them remains undefined or uncertain. Such GPCRs are designated as orphan receptors and although this is frequently also associated with a limited pharmacological palette of selective ligands, this does not mean that there is a lack of interest in better understanding and assessing specific orphan GPCRs as novel therapeutic opportunities. GPR84 is an example. Expression of GPR84 is strongly upregulated in immune cells in a range of pro‐inflammatory settings and clinical trials to treat idiopathic pulmonary fibrosis are currently ongoing using ligands with differing levels of selectivity and affinity as GPR84 antagonists. Although blockade of GPR84 may potentially prove effective also in diseases associated with inflammation of the lower gut there is emerging interest in defining if agonists of GPR84 might find utility in conditions in which regulation of metabolism or energy sensing is compromised. Here, we consider the physiological and pathological expression profile of GPR84 and, in the absence of direct structural information, recent developments and use of GPR84 pharmacological tool compounds to study its broader role and biology