IL-21 receptor expression in human tendinopathy

The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward and early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly up regulated by proinflammatory cytokines (TNFα/IL-1β) in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy

Pituitary Adenylate-Cyclase Activating Polypeptide Regulates Hunger- and Palatability-Induced Binge Eating

While pituitary adenylate cyclase activating polypeptide (PACAP) signaling in the hypothalamic ventromedial nuclei (VMN) has been shown to regulate feeding, a challenge in unmasking a role for this peptide in obesity is that excess feeding can involve numerous mechanisms including homeostatic (hunger) and hedonic-related (palatability) drives. In these studies, we first isolated distinct feeding drives by developing a novel model of binge behavior in which homeostatic-driven feeding was temporally separated from feeding driven by food palatability. We found that stimulation of the VMN, achieved by local microinjections of AMPA, decreased standard chow consumption in food-restricted rats (e.g., homeostatic feeding); surprisingly, this manipulation failed to alter palatable food consumption in satiated rats (e.g., hedonic feeding). In contrast, inhibition of the nucleus accumbens (NAc), through local microinjections of GABA receptor agonists baclofen and muscimol, decreased hedonic feeding without altering homeostatic feeding. PACAP microinjections produced the site-specific changes in synaptic transmission needed to decrease feeding via VMN or NAc circuitry. PACAP into the NAc mimicked the actions of GABA agonists by reducing hedonic feeding without altering homeostatic feeding. In contrast, PACAP into the VMN mimicked the actions of AMPA by decreasing homeostatic feeding without affecting hedonic feeding. Slice electrophysiology recordings verified PACAP excitation of VMN neurons and inhibition of NAc neurons. These data suggest that the VMN and NAc regulate distinct circuits giving rise to unique feeding drives, but that both can be regulated by the neuropeptide PACAP to potentially curb excessive eating stemming from either drive

Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study.

BackgroundEnrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors.MethodsIn a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies.Measurements and main resultsAn admission sTNFR1 concentration > 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration > 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level > 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor.ConclusionsThresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials

Child and parental sleep in young children with epilepsy: A population-based case-control study

Objective: To determine the prevalence of parent‐reported sleep problems in young children with epilepsy and their parents, and to compare findings with those in a non–epilepsy‐related neurodisability (neurodevelopmental/neurological difficulties) group. Method: Parents of young children (1–7 years) with epilepsy (n = 48 [91% ascertainment]) completed the Child Sleep Habits Questionnaire (CSHQ). Parents (mothers and fathers) also completed the Pittsburgh Sleep Quality Index (PSQI) and the Iowa Fatigue Scale (IFS) in relation to their own functioning. The responses of parents of children with epilepsy were compared with parents of developmental‐, age‐, and gender‐matched children with nonepilepsy‐related neurodisability (n = 48). Results: There was not a significant difference in the proportion of children with epilepsy and the children with neurodisability scoring in the at‐risk range on the CSHQ (81% vs. 71% respectively) (p = 0.232). 62% of mothers and 44% of fathers of children with epilepsy had ‘poor quality sleep’ on the PSQI; there was not a significant difference between mothers of children with epilepsy and those of children with neurodisability (p = 0.526) or IFS (p = 0.245) total scores. However, mothers of children with epilepsy had significantly more difficulties on the productivity subscale of the IFS (p = 0.004). There were no significant differences between fathers’ scores on either measure. In the epilepsy group, child behavioral problems (p = 0.001) were independently associated with child sleep difficulties and maternal mental health problems were associated with parental sleep difficulties (p = 0.04) and fatigue (p = 0.018). Significance: Young children with epilepsy and their parents have a high rate of sleep difficulties. There is a need to develop effective interventions for this population, taking into consideration of the role of child behavioral problems and parental mental health difficulties

Plutonium coordination and redox chemistry with the CyMe4-BTPhen polydentate N-donor extractant ligand

Complexation of Pu(IV) with the actinide extractant CyMe4-BTPhen (2,9-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-1,10-phenanthroline) was followed by vis-NIR spectroscopy in acetonitrile solution. The solid-state structure of the crystallized product suggests that Pu(IV) is reduced to Pu(III) upon complexation. Analysis by DFT modeling is consistent with metal-based rather than ligand-based reduction

An inventory of vertebrate roadkill in the Greater Mapungubwe Transfrontier Conservation Area, South Africa

Using a standard protocol, we conducted vertebrate roadkill surveys in the Greater Mapungubwe Transfrontier Conservation Area (GMTFCA), South Africa, which is a World Heritage Site. A total of 991 roadkill were recorded on the paved roads and 36 roadkill on the unpaved roads. Identifiable roadkill comprised 162 species from 24 orders and 65 families. Ninety-three roadkill could not be identified to species level. Roadkill counts were strongly influenced by road type and season. More roadkill was recorded on the paved than the unpaved roads. Irrespective of road type, the proportion of roadkill was greatest in the hot/wet season (4.3 paved roadkill/km/day paved and 1.3 roadkill/km/day unpaved) and lowest in the cold/dry season (2.0 roadkill/km/day paved and 0.1 roadkill/km/day unpaved). The high numbers of vertebrates identified as roadkill suggests that road traffic has the potential to directly and negatively affect biodiversity conservation in this part of South Africa. We recommend continued roadkill data collection across South Africa to assist with creating an inventory of species most likely to be at risk from roads. This will, in turn, better inform the implementation of potential mitigation measures.This research was initiated by the Endangered Wildlife Trust, with funding from Bridgestone South Africa.http://www.sawma.co.zaam201

The Grizzly, November 10, 1978

Physical Education Program To Change • Task Force Continues Recommendations • No Funds For Bomberger • Forum: High Strung • Hockey Not Safe • Staffer Clears Misinterpretation • Dining Service Transitions • Letters to the Editor • Portrait of the Professor: Gayle A. Byerly • For Whom The Walls Toil • Egdon Heath - A New Look For Monday Night • The Good Doctor Makes House Call To Protheatre • Eighteen Named to Who\u27s Who • Free V. D. Clinic • GM: Looking Good For \u2779 • Sports Profile: Keith Kemper • Thinclads Nab Third At MAC\u27s • Soccer Kicks Moravian • Bears Blast Dickinson • Gymnastics Get New Coach • Hockey Ends • Women\u27s B-Ball Preview • News in Brief: Senior Symposium Cancelled; Deans Attend State Conventionhttps://digitalcommons.ursinus.edu/grizzlynews/1006/thumbnail.jp

Management of hybridization in an endemic species : decision making in the face of imperfect information in the case of the black wildebeest-Connochaetes gnou

Hybridization between introduced and endemic ungulates, resulting from Anthropogenic actions, have been reported for several species. Several studies of such events contain the common themes of extralimital movements, problematic phenotypic and genetic detection, and imperfect management. In southern Africa, the endemic black wildebeest (Connochaetes gnou) currently faces a serious threat of hybridization and introgression. This species survived near extinction and consequent genetic bottlenecks in the late 1800s and in the 1930s. Initiatives by private farmers followed by conservation authorities led to a dramatic recovery in numbers of this species. However, in an ironic twist, the very same advances in conservation and commercial utilisation which lead to the recovery of numbers are now themselves threatening the species. Injudicious translocation has brought the species into contact with its congener, the blue wildebeest (Connochaetes taurinus), and in recent times, hybridization between the species has occurred at numerous localities in South Africa. Consequently, a significant proportion of the national black wildebeest population potentially carries a proportion of introgressed blue wildebeest genetic material. We discuss completed and ongoing attempts to find molecular markers to detect hybrids and highlight the difficulty of detecting advanced backcrosses. Additional avenues of research, such as work on morphology (cranial and postcranial elements), estimating of the probability of introgression and modelling of diffusion rates are also introduced. In addition to the difficulty in detecting hybrid animals or herds, the lack of consensus on the fate of hybrid herds is discussed. Finally, in an environment of imperfect information, we caution against implementation of management responses that will potentially induce a new genetic bottleneck in C. gnou.http://www.springerlink.com/content/110828/nf201