Static balance has a relevant influence on athletic performance as well as on reducing the risk of injury. The main goal of this study was to assess soccer athlete versus non-athlete balance ...performance via displacement and velocity parameters extracted from the center-of-pressure (COP) position time series. In order to accomplish our goal, we investigated standing balance in two male groups with unimpaired balance: non-athletes (
= 12) and collegiate varsity soccer athletes (
= 12). In order to make the standing balancing task more or less difficult, we altered participant base-of-support, as well as vision, yielding static (quiet stance) test conditions increasing in difficulty. From the COP position time series, displacement and velocity parameters were computed and plotted as a function of increasing test condition difficulty level. COP parameters showed steeper increases with increased test difficulty in non-athletes compared to athletes; this demonstrated athletes' better ability to control their balance. We concluded that balance performance could be characterized via COP displacement and velocity response curves. This study lends new insights into how COP parameters can be utilized to determine and characterize improvements in balance between un-impaired subject populations (athletes versus non-athletes).
The continued rise of antibiotic-resistant infections coupled with the limited pipeline of new antimicrobials highlights the pressing need for the development of new antibacterial agents. One ...potential pathway for new agents is de novo purine biosynthesis as studies have shown that bacteria and lower eukaryotes synthesize purines differently than humans. Microorganisms utilize two enzymes, N
-CAIR synthetase and N
-CAIR mutase, to convert 5-aminoimidazole ribonucleotide (AIR) into 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) through the intermediate N
-carboxy-5-aminoimidazole ribonucleotide (N
-CAIR). In contrast, vertebrates directly convert AIR to CAIR via the enzyme AIR carboxylase. A high-throughput screen against N
-CAIR synthetase identified a group of compounds with a 2,3-indolinedione (isatin) core that inhibited the enzyme. While initial studies suggested that isatins inhibited the enzyme by a noncompetitive mechanism, here we show that isatins inhibit N
-CAIR synthetase by a substrate depletion mechanism. Unexpectedly, we found that isatin reacts rapidly and reversibly with the substrate AIR. The rate of the reaction is dependent upon the substituents on the phenyl moiety of isatin, with 5- and 7-bromoisatin being faster than 4-bromoisatin. These studies suggest that care should be taken when exploring isatin compounds because the biological activity could be a result of their reactivity.
The continued rise of antibiotic-resistant infections coupled with the limited pipeline of new antimicrobials highlights the pressing need for the development of new antibacterial agents. One ...potential pathway for new agents is de novo purine biosynthesis as studies have shown that bacteria and lower eukaryotes synthesize purines differently than humans. Microorganisms utilize two enzymes, N5-CAIR synthetase and N5-CAIR mutase, to convert 5-aminoimidazole ribonucleotide (AIR) into 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) through the intermediate N 5-carboxy-5-aminoimidazole ribonucleotide (N5-CAIR). In contrast, vertebrates directly convert AIR to CAIR via the enzyme AIR carboxylase. A high-throughput screen against N5-CAIR synthetase identified a group of compounds with a 2,3-indolinedione (isatin) core that inhibited the enzyme. While initial studies suggested that isatins inhibited the enzyme by a noncompetitive mechanism, here we show that isatins inhibit N5-CAIR synthetase by a substrate depletion mechanism. Unexpectedly, we found that isatin reacts rapidly and reversibly with the substrate AIR. The rate of the reaction is dependent upon the substituents on the phenyl moiety of isatin, with 5- and 7-bromoisatin being faster than 4-bromoisatin. These studies suggest that care should be taken when exploring isatin compounds because the biological activity could be a result of their reactivity.
OBJECTIVES
Thoracoscore is incorporated in the new British Thoracic Society and National Institute of Health and clinical Excellence guidelines to evaluate the operative mortality risk of patients ...undergoing thoracic surgery. This study examines the accuracy of Thoracoscore in predicting postoperative mortality in patients undergoing pneumonectomy.
METHODS
All patients who underwent pneumonectomy from January 1998 to March 2008 were included. Thoracoscore was calculated based on the following variables: age, sex, American Society of Anaesthesiologists' class, performance status classification, dyspnoea score, priority of surgery, procedure class, Diagnosis group and comorbidities score.
RESULTS
Two hundred and forty-three patients with a mean age of 63 ± 9 years were included and 81% were male. The predicted postoperative mortality based on Thoracoscore was 8 ± 2.6% (95% confidence interval (CI) 4.56-11.43), while actual in-hospital mortality was 4.5% (11/243) (95% CI 1.87-7.12). 54% (6/11) of in-hospital mortality was of those who were >70 years old and 73% (8/11) of patients who died in hospital were male. Nine of 11 (82%) patients had pneumonectomy for malignancy. Thoracoscore was divided into four risk groups: low (0-3), moderate (3.1-5), high (5.1-8) and very high (>8). It underestimated mortality in low-risk group while overestimated in high-risk groups. The 30-day, 1-year, 2-year and 3-year observed mortalities were 5.3, 29, 43 and 55%, respectively.
CONCLUSIONS
Although advanced age, the male sex and malignancy proved to be strong predictors of in-hospital mortality in our study, Thoracoscore failed to predict accurate risk of in-hospital mortality in pneumonectomy patients in this study. Further studies are required to validate the Thoracoscore in different subgroups of thoracic surgery.
Many patients with anterior cruciate ligament (ACL) injuries have persistent quadriceps muscle atrophy, even after considerable time in rehabilitation. Understanding the factors that regulate muscle ...mass, and the time course of atrophic events, is important for identifying therapeutic interventions. With a noninvasive animal model of ACL injury, a longitudinal study was performed to elucidate key parameters underlying quadriceps muscle atrophy. Male Long-Evans rats were euthanized at 6, 12, 24, or 48 h or 1, 2, or 4 wk after ACL injury that was induced via tibial compression overload; controls were not injured. Vastus lateralis muscle size was determined by wet weight and fiber cross-sectional area (CSA). Evidence of disrupted neuromuscular communication was assessed via the expression of neural cell adhesion molecule (NCAM) and genes associated with denervation and neuromuscular junction instability. Abundance of muscle RING-finger protein-1 (MuRF-1), muscle atrophy F-box (MAFbx), and 45 s pre-rRNA along with 20S proteasome activity were determined to investigate mechanisms related to muscle atrophy. Finally, muscle damage-related parameters were assessed by measuring IgG permeability, centronucleation, CD68 mRNA, and satellite cell abundance. When compared with controls, we observed a greater percentage of NCAM-positive fibers at 6 h postinjury, followed by higher MAFbx abundance 48 h postinjury, and higher 20S proteasome activity at 1 wk postinjury. A loss of muscle wet weight, smaller fiber CSA, and the elevated expression of run-related transcription factor 1 (Runx1) were also observed at the 1 wk postinjury timepoint relative to controls. There also were no differences observed in any damage markers. These results indicate that alterations in neuromuscular communication precede the upregulation of atrophic factors that regulate quadriceps muscle mass early after noninvasive ACL injury.
A novel preclinical model of ACL injury was used to establish that acute disruptions in neuromuscular communication precede atrophic events. These data help to establish the time course of muscle atrophy after ACL injury, suggesting that clinical care may benefit from the application of acute neurogenic interventions and early gait reloading strategies.
Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and for genetic pathway discovery via dose-dependent suppressor and enhancer screens. ...More recently, it has become clear that deviations from normal gene dosage are associated with multiple disorders in a range of species including humans. While we are beginning to understand some of the transcriptional effects brought about by gene dosage changes and the chromosome rearrangement breakpoints associated with them, much of this work relies on isolated examples. We have systematically examined deficiencies of the left arm of chromosome 2 and characterize gene-by-gene dosage responses that vary from collapsed expression through modest partial dosage compensation to full or even over compensation. We found negligible long-range effects of creating novel chromosome domains at deletion breakpoints, suggesting that cases of gene regulation due to altered nuclear architecture are rare. These rare cases include trans de-repression when deficiencies delete chromatin characterized as repressive in other studies. Generally, effects of breakpoints on expression are promoter proximal (~100bp) or in the gene body. Effects of deficiencies genome-wide are in genes with regulatory relationships to genes within the deleted segments, highlighting the subtle expression network defects in these sensitized genetic backgrounds.
Background The United States has established aortic supercenters, which have demonstrated clear improvements in the short-term and long-term outcomes after surgery on the thoracic aorta. This model ...of care does not exist in the United Kingdom. We have looked at our recent experience of emergency and elective thoracic aortic surgery and describe and compare our operative outcomes and 10-year survival with other regional centers and supercenters worldwide. Methods This was a retrospective analysis of data collected prospectively from our cardiac database on patients who underwent surgery on the thoracic aorta (n = 318) between November 1999 and November 2012. The outcome measures were adjusted operative mortality, postoperative complications, and long-term survival. Results Type A dissection was carried out on 23.90% of the patients and 76.10% had surgery on the aortic root and thoracic aorta for nondissection. The mean age of the patients was 62.21 ± 14.1 years. The mean logistic EuroSCORE was 26 in the dissection group and 19 in the nondissection group. Hospital mortality was significantly greater ( P < .05) in the dissection group compared with the nondissection group (23.7% vs 12.8%). Survival after dissection and nondissection surgery was 66.3% ± 5.6% versus 77.4% ± 2.8%, respectively, at 3 years, 63.9% ± 5.9% versus 71.8% ± 3.2% at 5 years, and 53.7% ± 7.4% versus 47.1% ± 6.0% at 10 years. Conclusions Our outcomes are comparable with other regional centers worldwide; however, they are not as good as those reported from the aortic supercenters. There should be continued impetus regarding the establishment of thoracic aortic surgery guidelines and specialist aortic centers in the United Kingdom.
Many species of longhorn beetles (Coleoptera: Cerambycidae) utilize male-produced aggregation-sex pheromones that attract both sexes. However, the reasons why and the details of how this type of ...pheromone is used by cerambycids and other coleopteran species that utilize analogous male-produced pheromones remain unclear. Thus, our goals were to test the hypotheses that 1) cerambycids respond to pheromones in a dose-dependent (= release rate-dependent) manner and 2) pheromone emission is density-dependent. If true, these characteristics of pheromone use could suggest that cerambycids utilize an optimal density strategy to limit competition for scarce and ephemeral hosts, i.e., the stressed or dying trees that typically constitute their larval hosts. Attraction of beetles to a range of release rates of two common pheromone components – 2-methylbutanol and 3-hydroxyhexan-2-one – was tested in field trials. Responses, as measured by the number of beetles caught in pheromone-baited traps, increased with release rates for five endemic species, even at the highest rates tested (~1450 μg/h for 2-methylbutanol and ~720 μg/h for 3-hydroxyhexan-2-one). The effect of density of conspecific males on per capita pheromone production was tested by collecting the volatiles produced by individuals, pairs, or groups of three or four male
Phymatodes grandis
Casey. Frequency of pheromone production was significantly different among the treatment densities, and emission rates of the pheromone (
R
)-2-methylbutanol decreased with increasing density. These results are discussed in the context of a possible optimal density strategy used by cerambycids, and more broadly, in relation to the use of male-produced aggregation-sex pheromones by other coleopterans. In addition, we report the identification of the pheromones of four of our five test species, specifically,
Phymatodes obliquus
Casey,
Brothylus conspersus
LeConte,
Brothylus gemmulatus
LeConte, and
Xylotrechus albonotatus
Casey.
Animal studies have shown that pretreatment with hyperbaric oxygen can induce central nervous system ischemic tolerance and also modulate the inflammatory response. We evaluated this therapy in ...patients undergoing cardiopulmonary bypass.
Sixty-four patients were prospectively randomized to group A (n = 31; atmospheric air, 1.5 atmospheres absolute) or group B (n = 33; hyperbaric oxygen, 2.4 atmospheres absolute) before on-pump coronary artery bypass grafting. Age, sex, body mass index, diabetes, hypertension, smoking, coronary disease severity, left ventricular function, Parsonnet score, Euroscore, bypass time, myocardial ischemia time, and number of grafts were comparable in both groups. Canadian Cardiovascular Society angina, New York Heart Association dyspnea, and previous myocardial infarction were significantly higher in group B. Inflammatory markers were analyzed before surgery and 2 and 24 hours after bypass. Neuropsychometric testing was performed 48 hours before surgery and 4 months after surgery and included trail making A and B, the Rey auditory verbal learning test, grooved peg board, information processing table A, and digit span forward and backward. Neuropsychometric dysfunction was defined as more than 1 SD deterioration in more than 2 neuropsychometric tests. Chi-square tests, Fisher tests,
t tests, and analysis of variance were used as appropriate for statistical analysis.
Group A had a significant postoperative increase in the inflammatory markers soluble E-selectin, CD18, and heat shock protein 70. This was not observed in group B. Neuropsychometric dysfunction was also significantly higher in group A compared with group B. There was no difference in any other early postoperative clinical outcome.
Our results seem to indicate that pretreatment with hyperbaric oxygen can reduce neuropsychometric dysfunction and also modulate the inflammatory response after cardiopulmonary bypass. However, further multicenter randomized trials are needed to clinically evaluate this form of therapy.
Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the ...nematode
, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the
connectome and fit to a large-scale kinematic analysis of
behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in
can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding
locomotion and a testable neuronal model of random search that can be applied to other organisms.
PDF
