An integrated approach to change the outcome part I: neuromuscular screening methods to identify high ACL injury risk athletes

An important step for treatment of a particular injury etiology is the appropriate application of a treatment targeted to the population at risk. An anterior cruciate ligament (ACL) injury risk algorithm has been defined that employs field-based techniques in lieu of laboratory-based motion analysis systems to identify athletes with high ACL injury risk landing strategies. The resultant field-based assessment techniques, in combination with the developed prediction algorithm, allow for low-cost identification of athletes who may be at increased risk of sustaining ACL injury. The combined simplicity and accuracy of the field-based tool facilitate its use to identify specific factors that may increase risk of injury in female athletes. The purpose of this report is to demonstrate novel algorithmic techniques to accurately capture and analyze measures of knee valgus motion, knee flexion range of motion, body mass, tibia length and quadriceps to hamstrings ratio with video analysis software typically used by coaches, strength and conditioning specialists, and athletic trainers. The field-based measurements and software analyses were used in a prediction algorithm to identify those at potential risk of noncontact ACL injury that may directly benefit from neuromuscular training.     

Cytosolic phospholipase A2 alpha inhibition prevents neuronal NMDA receptor-stimulated arachidonic acid mobilization and prostaglandin production but not subsequent cell death

Phospholipase A(2) (PLA(2)) enzymes encompass a superfamily of at least 13 extracellular and intracellular esterases that hydrolyze the sn-2 fatty acyl bonds of phospholipids to yield fatty acids and lysophospholipids. The purpose of this study was to characterize which phospholipase paralog regulates NMDA receptor-mediated arachidonic acid (AA) release. Using mixed cortical cell cultures containing both neurons and astrocytes, we found that [(3)H]-AA released into the extracellular medium following NMDA receptor stimulation (100 microM) increased with time and was completely prevented by the addition of the NMDA receptor antagonist MK-801 (10 microM) or by removal of extracellular Ca(2+). Neither diacylglycerol lipase inhibition (RHC-80267; 10 microM) nor selective inhibition of Ca(2+)-independent PLA(2) [bromoenol lactone (BEL); 10 microM] alone had an effect on NMDA receptor-stimulated release of [(3)H]-AA. Release was prevented by methyl arachidonyl fluorophosphonate (MAFP) (5 microM) and AACOCF(3) (1 microM), inhibitors of both cytosolic PLA(2) (cPLA(2)) and Ca(2+)-independent PLA(2) isozymes. This inhibition effectively translated to block of NMDA-induced prostaglandin (PG) production. An inhibitor of p38MAPK, SB 203580 (7.5 microM), also significantly reduced NMDA-induced PG production providing suggestive evidence for the role of cPLA(2)alpha. Its involvement in release was confirmed using cultures derived from mice deficient in cPLA(2)alpha, which failed to produce PGs in response to NMDA receptor stimulation. Interestingly, neither MAFP, AACOCF(3) nor cultures derived from cPLA(2)alpha null mutant animals showed any protection against NMDA-mediated neurotoxicity, indicating that inhibition of this enzyme may not be a viable protective strategy in disorders of the cortex involving over-activation of the NMDA receptor.     

Interleukin‐1β: a bridge between inflammation and excitotoxicity?

Interleukin-1 (IL-1) is a proinflammatory cytokine released by many cell types that acts in both an autocrine and/or paracrine fashion. While IL-1 is best described as an important mediator of the peripheral immune response during infection and inflammation, increasing evidence implicates IL-1 signaling in the pathogenesis of several neurological disorders. The biochemical pathway(s) by which this cytokine contributes to brain injury remain(s) largely unidentified. Herein, we review the evidence that demonstrates the contribution of IL-1β to the pathogenesis of both acute and chronic neurological disorders. Further, we highlight data that leads us to propose IL-1β as the missing mechanistic link between a potential beneficial inflammatory response and detrimental glutamate excitotoxicity.     

Neuromuscular training techniques to target deficits before return to sport after anterior cruciate ligament reconstruction

Surgical intervention and early-phase rehabilitation after anterior cruciate ligament (ACL) reconstruction have undergone a relatively rapid and global evolution over the past 25 years. Despite the advances that have significantly improved outcomes, decreases in healthcare coverage (limited visits allowed for physical therapy) have increased the role of the strength and conditioning specialist in the rehabilitation of athletes returning to sport after ACL reconstruction. In addition, there is an absence of standardized, objective criteria to accurately assess an athlete's ability to progress through the end stages of rehabilitation and safely return to sport. The purpose of this Scientific Commentary is to present an example of a progressive, end-stage return to sport protocol that is targeted to measured deficits of neuromuscular control, strength, power, and functional symmetry that are rehabilitative landmarks after ACL reconstruction. The proposed return to sport training protocol incorporates quantitative measurement tools that will provide the athlete with objective feedback and targeted goal setting. Objective feedback and targeted goal setting may aid the strength and conditioning specialist with exercise selection and progression. In addition, a rationale for exercise selection is outlined to provide the strength and conditioning specialist with a flexible decision-making approach that will aid in the modification of return to sport training to meet the individual athlete's abilities and to target objectively measured deficits. This algorithmic approach may improve the potential for athletes to return to sport after ACL reconstruction at the optimal performance level and with minimized risk of reinjury.     

苜蓿叶片水杨酸含量与其蓟马抗性的关系

采用不同抗蓟马特性的苜蓿品系,于不同蓟马虫口密度下测定苜蓿水杨酸含量和虫害程度,以明确苜蓿叶片水杨酸含量与其抗蓟马特性的关系.结果表明,苜蓿叶片游离态、结合态水杨酸含量均与苜蓿抗蓟马特性密切相关;高抗品系(抗蓟马品系)的水杨酸初始含量(0.539 mg·g-1)高于低抗品系(0.403 mg·g-1);与较低抗品系相比,高抗品系受害器官(叶)水杨酸含量随虫口密度和危害点面积的增大而增加相对缓慢,而随危害指数的增大而增加较快(3.84倍).可见,水杨酸主要是间接增强苜蓿对蓟马的抗性;高抗蓟马苜蓿品系能通过快速获得较高水杨酸含量来阻碍被危害伤口的扩大,降低其受危害程度,促使自身产量和品质提高.     

The importance of size-frequency relationships for predicting ecological impact of zebra mussel populations

Although most physiological processes of bivalves are highly size-dependent in a non-linear manner, often only total densities of populations of freshwater bivalves such as the zebra mussel are reported rather than size-frequency information. This can cause serious errors when trying to predict or assess the environmental impacts of these filter feeders on planktonic communities or the role of their pseudofeces in transferring materials from the plankton to the benthos. We used a bioenergetics model to examine the effect that differing size-frequency distribution has on influencing total phytoplankton consumption and pseudofeces production. We constructed different size-frequency distributions of 1000 zebra mussels with the same mean length or same mean body mass for comparison. In addition, we used several size-frequency distributions from the published literature. The size-frequency distribution of a population had a tremendous impact on both total consumption and pseudofeces production with rates varying by more than an order of magnitude (43.5 g consumption by 1000 smaller mussels to 654 g for a population dominated by large mussels). These data emphasize the importance of knowing not only population density, but population size structure in order to accurately understand and predict the impacts of zebra mussels, or any filter feeder on pelagic and benthic communities. This work also demonstrates the usefulness of a tool such as our bioenergetics model for partitioning the relative impacts of densities and size on a variety of factors such as consumption and pseudofeces production.     

Neurotoxicity of nitroxyl: insights into HNO and NO biochemical imbalance

Nitroxyl anion (NO-), and/or its conjugate acid, HNO, may be formed in the cellular milieu by several routes under both physiological and pathophysiological conditions. Since experimental evidence suggests that certain reactive nitrogen oxide species can contribute significantly to cerebral ischemic injury, we investigated the neurotoxic potential of HNO/NO- using Angeli's salt (AS), a spontaneous HNO/NO(-)-generating compound. Exposure to AS resulted in a time- and concentration-dependent increase in neural cell death that progressed markedly following the initial exposure. Coadministration of the donor with Tempol (1 mM), a one-electron oxidant that converts NO- to NO, prevented its toxic effect, as did the concomitant addition of Fe(III)TPPS. Media containing various chelators, catalase, Cu/Zn superoxide dismutase, or carboxy-PTIO did not ameliorate AS-mediated neurotoxicity, ruling out the involvement of transition metal complexes, H2O2, O2-, and NO, respectively. A concentration-dependent increase in supernatant protein 3-nitrotyrosine immunoreactivity was observed when cultures were exposed to AS under aerobic conditions, an effect lost in the absence of oxygen. A bell-shaped curve for augmented AS-mediated nitration was observed with increasing Fe(III)TPPS concentration, which contrasted with its linear effect on abating cytotoxicity. Finally, addition of glutamate receptor antagonists, MK-801 (10 microM) and CNQX (30 microM) to the cultures abrogated toxicity when given during, but not following, AS exposure; as did pretreatment with the exocytosis inhibitor, tetanus toxin (300 ng/ml). Taken together, our data suggest that under aerobic conditions, AS toxicity is initiated via HNO/NO- but progresses via secondary excitotoxicity.     

The European Renal Genome Project: An Integrated Approach Towards Understanding the Genetics of Kidney Development and Disease

Rapid progress in genome research creates a wealth of information on the functional annotation of mammalian genome sequences. However, as we accumulate large amounts of scientific information we are facing problems of how to integrate and relate the data produced by various genomic approaches. Here, we propose the novel concept of an organ atlas where diverse data from expression maps to histological findings to mutant phenotypes can be queried, compared and visualized in the context of a three-dimensional reconstruction of the organ. We will seek proof of concept for the organ atlas by elucidating genetic pathways involved in development and pathophysiology of the kidney. Such a kidney atlas may provide a paradigm for a new systems-biology approach in functional genome research aimed at understanding the genetic bases of organ development, physiology and disease.Key Words: EuReGene, kidney, genome, development, pathophysiology, genetics