Systemic pro-inflammatory cytokine status following therapeutic hypothermia in a piglet hypoxia-ischemia model

BACKGROUND: Inflammatory cytokines are implicated in the pathogenesis of perinatal hypoxia-ischemia (HI). The influence of hypothermia (HT) on cytokines after HI is unclear. Our aim was to assess in a piglet asphyxia model, under normothermic (NT) and HT conditions: (i) the evolution of serum cytokines over 48 h and (ii) cerebrospinal fluid (CSF) cytokine levels at 48 h; (iii) serum pro/anti-inflammatory cytokine profile over 48 h and (iv) relation between brain injury measured by magnetic resonance spectroscopy (MRS) and brain TUNEL positive cells with serum cytokines, serum pro/anti-inflammatory cytokines and CSF cytokines. METHODS: Newborn piglets were randomized to NT (n = 5) or HT (n = 6) lasting 2-26 h after HI. Serum samples were obtained 4-6 h before, during and at 6-12 h intervals after HI; CSF was obtained at 48 h. Concentrations of interleukin (IL)-1beta, -4, -6, -8, -10 and TNF-alpha were measured and pro/anti-inflammatory status compared between groups. White matter and thalamic voxel lactate/N-acetyl aspartate (Lac/NAA) (a measure of both oxidative metabolism and neuronal loss) were acquired at baseline, after HI and at 24 and 36 h. RESULTS: Lac/NAA was reduced at 36 h with HT compared to NT (p = 0.013 basal ganglia and p = 0.033 white matter). HT showed lower serum TNF-alpha from baseline to 12 h (p < 0.05). Time-matched (acquired within 5 h of each other) serum cytokine and MRS showed correlations between Lac/NAA and serum IL-1beta and IL-10 (all p < 0.01). The pro/anti-inflammatory ratios IL-1beta/IL-10, IL-6/IL-10, IL-4/IL-10 and IL-8/IL-10 were similar in NT and HT groups until 36 h (24 h for IL-6/IL-10); after this, 36 h pro/anti-inflammatory cytokine ratios in the serum were higher in HT compared to NT (p < 0.05), indicating a pro-inflammatory cytokine surge after rewarming in the HT group. In the CSF at 48 h, IL-8 was lower in the HT group (p < 0.05). At 48 h, CSF TNF-alpha correlated with Lac/NAA (p = 0.02) and CSF IL-8 correlated with white matter TUNEL positive cell death (p = 0.04). CONCLUSIONS: Following cerebral HI, there was a systemic pro-inflammatory surge after rewarming in the HT group, which is counterintuitive to the putative neuroprotective effects of HT. While serum cytokines were variable, elevations in CSF inflammatory cytokines at 48 h were associated with MRS Lac/NAA and white matter cell death

New explanation of the GAMS results on the f0(980)f_0(980) production in the reaction π−p→π0π0n\pi^-p\to \pi^0\pi^0n

The observed alteration of the S-wave $\pi^0\pi^0$ mass spectrum in the reaction $\pi^-p\to\pi^0\pi^0n$ with increasing $-t$, i.e., the disappearance of a dip and the appearance of a peak in the region of the $f_0(980)$ resonance as $-t$ increases, is explained by the contribution of the $\pi^-p\to f_0(980)n$ reaction amplitude with the quantum numbers of the $a_1$ Regge pole in the $t$ channel. It is very interesting that nontrivial evidence for the $a_1$ exchange mechanism in the reaction $\pi^-p\to \pi^0\pi^0n$ follows for the first time from the experiment on an unpolarized target. The explanation of the GAMS results suggested by us is compared with that reported previously. Two ways of experimentally testing these explanations are pointed out.Comment: 20 pages (RevTex), 5 figures (PS), minor typos corrected (in particular in Fig. 4), replaced to match the version accepted in Phys. Rev.

Clinical approach for the classification of congenital uterine malformations

A more objective, accurate and non-invasive estimation of uterine morphology is nowadays feasible based on the use of modern imaging techniques. The validity of the current classification systems in effective categorization of the female genital malformations has been already challenged. A new clinical approach for the classification of uterine anomalies is proposed. Deviation from normal uterine anatomy is the basic characteristic used in analogy to the American Fertility Society classification. The embryological origin of the anomalies is used as a secondary parameter. Uterine anomalies are classified into the following classes: 0, normal uterus; I, dysmorphic uterus; II, septate uterus (absorption defect); III, dysfused uterus (fusion defect); IV, unilateral formed uterus (formation defect); V, aplastic or dysplastic uterus (formation defect); VI, for still unclassified cases. A subdivision of these main classes to further anatomical varieties with clinical significance is also presented. The new proposal has been designed taking into account the experience gained from the use of the currently available classification systems and intending to be as simple as possible, clear enough and accurate as well as open for further development. This proposal could be used as a starting point for a working group of experts in the field

Quantitative Serial MRI of the Treated Fibroid Uterus

There are no long-term medical treatments for uterine fibroids, and non-invasive biomarkers are needed to evaluate novel therapeutic interventions. The aim of this study was to determine whether serial dynamic contrast-enhanced MRI (DCE-MRI) and magnetization transfer MRI (MT-MRI) are able to detect changes that accompany volume reduction in patients administered GnRH analogue drugs, a treatment which is known to reduce fibroid volume and perfusion. Our secondary aim was to determine whether rapid suppression of ovarian activity by combining GnRH agonist and antagonist therapies results in faster volume reduction.Forty women were assessed for eligibility at gynaecology clinics in the region, of whom thirty premenopausal women scheduled for hysterectomy due to symptomatic fibroids were randomized to three groups, receiving (1) GnRH agonist (Goserelin), (2) GnRH agonist+GnRH antagonist (Goserelin and Cetrorelix) or (3) no treatment. Patients were monitored by serial structural, DCE-MRI and MT-MRI, as well as by ultrasound and serum oestradiol concentration measurements from enrolment to hysterectomy (approximately 3 months).A volumetric treatment effect assessed by structural MRI occurred by day 14 of treatment (9% median reduction versus 9% increase in untreated women; P = 0.022) and persisted throughout. Reduced fibroid perfusion and permeability assessed by DCE-MRI occurred later and was demonstrable by 2-3 months (43% median reduction versus 20% increase respectively; P = 0.0093). There was no apparent treatment effect by MT-MRI. Effective suppression of oestradiol was associated with early volume reduction at days 14 (P = 0.041) and 28 (P = 0.0061).DCE-MRI is sensitive to the vascular changes thought to accompany successful GnRH analogue treatment of uterine fibroids and should be considered for use in future mechanism/efficacy studies of proposed fibroid drug therapies. GnRH antagonist administration does not appear to accelerate volume reduction, though our data do support the role of oestradiol suppression in GnRH analogue treatment of fibroids.ClinicalTrials.gov NCT00746031

Development and reproductive performance of Hereford heifers of different frame sizes up to mating at 14-15 months of age

ABSTRACT Body development and reproductive performance of a hundred forty-two 14 to 15-month-old heifers, classified at weaning according to frame size as small, medium, and large, were evaluated. The parameters evaluated were: body weight, hip height, body condition score, weight gain, ovarian activity, and pregnancy rate. At weaning, body weight and hip height were significantly different among frame scores, (small – 133.0 kg, 92.2 cm; medium – 158.5 kg, 96.6 cm; and large – 185.2 kg; 100.2 cm). After weaning, heifers grazed together on natural pastures during the autumn and on ryegrass (Lolium multiflorum La.) during the winter and spring. Frame score differences remained until the beginning of the breeding season (BS), starting on average at 14 months of age. Weight gain between weaning and the beginning of BS was not different among frame scores (0.740 kg/day, on average). Body weights at the beginning of the BS were significantly different, of 255.7 kg (53.3% of the mature weight) for small heifers, 285.0 kg (59.4%) for medium heifers, and 307.6 kg (64.1%) for large heifers. Ovarian activity at the beginning of the BS was not different among the three groups. The average weight gain values during the BS of 0.492, 0.472, and 0.421 kg/day for small, medium, and large heifers, respectively, were significantly different. Pregnancy rates were not different among groups (small, 71.4%; medium, 76.4%; and large, 76.5%). Frame score did not influence the reproductive performance of heifers, but the small and medium heifers conceived 29 and 20 days earlier, respectively, than the large heifers

Motivations for Selling Ecstasy among Young Adults in the Electronic Dance Music Club Culture in Brazil

This article describes data on the motivations for selling ecstasy among young adults in the electronic dance music (EDM) club culture in Brazil. Individual interviews were conducted with 20 individuals recruited for their involvement in the EDM club scene. Eligible participants were aged 18–39 and reported ecstasy and/or LSD use one or more times in the past 90 days. Exclusion criteria included current treatment for drug/alcohol problems and cognitive impairment or clinically evident psychiatric disorder. Mean age was 22.92 (SD 2.77), 60% were male, 45% reported 12 or more years of education, 50% did not have a primary partner, 50% were living alone, and all had friends who also used ecstasy. Three main themes emerged: (1) “easy” transition from ecstasy user to seller; (2) desire to achieve popularity and fame; and (3) need to sell ecstasy to maintain the high cost of EDM club scene participation. This is one of the first studies of ecstasy sellers in Brazil. The results demonstrate the ease with which the participants transition from ecstasy user to seller. Given the potential health and social dangers associated with ecstasy use, public health campaigns to prevent ecstasy use and policy initiatives to limit the ecstasy supply are warranted

TEST-RETEST RELIABILITY AND MEASUREMENT ERROR OF UNCONTROLLED MANIFOLD ANALYSIS IN FINGER PRESSING TASK

Adrien M. Buttram1, Stephanie Gibson1, Joel Hager1, Karlie Abernathy1, José Canelon1, Benjamin Thomas1, Damon Knighton1, Daniele Piscitelli2, Stanislaw Solnik1. 1University of North Georgia, Dahlonega, GA. 2University of Connecticut, Mansfield, CT. BACKGROUND: The central nervous system organizes motor elements (e.g. muscles, joints, fingers) into task-specific synergies to stabilize motor task performance. The Uncontrolled Manifold (UCM) hypothesis quantifies synergies using analysis of covariation between motor elements. Recently, the UCM has been proposed as a biomarker of movement quality to investigate sensorimotor impairments. However, methodological limitations, including unknown measurement properties, hinder the practical application of UCM in clinical practice. This study aimed to investigate the reliability (i.e., test-rest and measurement error) of UCM parameters in healthy young adults. METHODS: 15 subjects (24.8 ± 1.2 yrs old) used both hands index and middle fingers to press on four force sensors. At four experimental sessions separated by 1 hour, one day, and one week, subjects performed three 2-minute trials of cyclic total force production at 20% of maximal voluntary contraction (MVC). Each trial consisted of 2-second force production separated by 2-seconds rest intervals, with visual feedback on the target force. We computed the synergy index (ΔV) for all testing sessions to quantify between-hand synergies stabilizing the target force. We averaged ΔV values from trials within each session. We investigated the test-retest reliability of ΔV with the Intraclass Correlation Coefficient (ICC3,k) with 95% confidence intervals (95% CI). Standard Error of Measurement (SEM) and Minimal Detectable Change (MDC) were determined. RESULTS: The mean number of force cycles was 29 in all testing sessions. The average ΔV for all subjects across all sessions was 0.87±0.29. The test-retest reliability reported an ICC3,k = 0.88 (95%CI: 0.72, 0.95; F(14,42)=7.91, p\u3c0.001), with SEM = 0.10, and MDC = 0.28. CONCLUSIONS: The test-retest reliability was excellent, with a value close to acceptable for clinical measures (i.e., ICC \u3e 0.9). The findings show that ΔV values were consistent across 1-hour, 1-day, and 1-week testing sessions. Our study supports using UCM-based biomarkers of movement quality in healthy young adults. Our results may advance the incorporation of UCM into clinical assessment of movement quality and for tracking recovery over time. This will help bridge neuroscience with the study of movement quality for a variety of populations and impairments