Isokinetic profiling of elite youth footballers: informing selection of a practicable and efficacious isokinetic screening test

Isokinetic dynamometry represents the clinical gold standard for strength assessment but testing lack consensus. Elite youth male football players (n = 28) completed 20 repetitions (analysed as four epochs) of eccentric knee flexor (eccKF) and concentric knee extensor (conKE) trials at 60, 180 and 270°∙s-1, quantifying peak torque (PT) and functional range (FR). There was a significant (P < 0.001) main effect for fatigue and angular velocity in conKE PT; eccKF PT was not significant across epoch (P = 0.35) and velocity (P = 0.12) and a velocity x epoch interaction highlighted more repetitions were required to elicit fatigue as velocity increased. FR decreased with fatigue (P < 0.001) and velocity (P < 0.01) in conKE and eccKF, indicative of a narrowing of the strength curve. Clinical interpretation advocates an isokinetic test comprising at least 15 reps at a velocity ≥ 180°∙s-1 and analysis beyond the peak of the strength curve (PT) to inform clinical reasoning and individualized exercise prescription

The Effects of Danofloxacin and Tilmicosin on Neutrophil Function and Lung Consolidation in Beef Heifer Calves with Induced Pasteurella (Mannheimia) haemolytica Pneumonia

Pneumonia caused by Pasteurella (Mannheimia) haemolytica was induced in weaned beef heifer calves, approximately 6 months of age. Calves were treated at 20 h after challenge with therapeutic doses of danofloxacin or tilmicosin. Peripheral blood neutrophils were collected at 3, 24 and 48 h after treatment. The ex vivo effects on neutrophil function, neutrophil apoptosis, and hematological parameters were examined, as was the effect on percentage lung consolidation. Neutrophil function assays included random migration under agarose, cytochrome C reduction, iodination, Staphylococcus aureus ingestion, chemotaxis, and antibody-dependent and antibody-independent cell-mediated cytotoxicity. Apoptosis was determined using a cell death detection kit. Killing was performed at 72 h after treatment. Statistical comparisons were made among the three groups of challenged–treated animals: saline, danofloxacin, and tilmicosin. Comparisons were also made between nonchallenged nontreated animals (NCH) and challenged saline-treated animals. There were no significant differences for any of the neutrophil function assays or neutrophil apoptosis among the challenged–treated groups. This suggests that danofloxacin and tilmicosin have no clinically significant effects on neutrophil function or apoptosis. There were also no significant differences in percentage lung consolidation among the challenged–treated groups. Significant differences were found between the NCH calves and the challenged saline-treated calves in several neutrophil assays, which were attributed to effects of P. haemolyticainfectio

Antimicrobial Peptides and Skin: A Paradigm of Translational Medicine

Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a `two-way road' - from bench to bedside and backwards from bedside to bench. Copyright (c) 2012 S. Karger AG, Base

Pharmacokinetics and pharmacodynamics of fenoldopam mesylate for blood pressure control in pediatric patients

<p>Abstract</p> <p>Background</p> <p>Fenoldopam mesylate, a selective dopamine1-receptor agonist, is used by intravenous infusion to treat hypertension in adults. Fenoldopam is not approved by the FDA for use in children; reports describing its use in pediatrics are limited. In a multi-institutional, placebo controlled, double-blind, multi-dose trial we determined the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and side-effect profile of fenoldopam in children.</p> <p>Methods</p> <p>Seventy seven (77) children from 3 weeks to 12 years of age scheduled for surgery in which deliberate hypotension would be induced were enrolled. Patients were randomly assigned to one of five, blinded treatment groups (placebo or fenoldopam 0.05, 0.2, 0.8, or 3.2 mcg/kg/min iv) for a 30-minute interval after stabilization of anesthesia and placement of vascular catheters. Following the 30-minute blinded interval, investigators adjusted the fenoldopam dose to achieve a target mean arterial pressure in the open-label period until deliberate hypotension was no longer indicated (e.g., muscle-layer closure). Mean arterial pressure and heart rate were continuously monitored and were the primary endpoints.</p> <p>Results</p> <p>Seventy-six children completed the trial. Fenoldopam at doses of 0.8 and 3.2 mcg/kg/min significantly reduced blood pressure (p < 0.05) during the blinded interval, and doses of 1.0–1.2 mcg/kg/min resulted in continued control of blood pressure during the open-label interval. Doses greater than 1.2 mcg/kg/min during the open-label period resulted in increasing heart rate without additional reduction in blood pressure. Fenoldopam was well-tolerated; side effects occurred in a minority of patients. The PK/PD relationship of fenoldopam in children was determined.</p> <p>Conclusion</p> <p>Fenoldopam is a rapid-acting, effective agent for intravenous control of blood pressure in children. The effective dose range is significantly higher in children undergoing anesthesia and surgery (0.8–1.2 mcg/kg/min) than as labeled for adults (0.05–0.3 mcg/kg/min). The PK and side-effect profiles for children and adults are similar.</p

The development of policing in Britain in the next five years.

The British police service is currently going through a radical transformation phase. The present Tory-led coalition government has set out an agenda to bring about drastic changes in policing. These proposed changes are unprecedented in the history of policing since 1829. The police service is governed by a tripartite arrangement of checks and balances laid down under the Police Act 1964. By this I mean that there are three key players in relation to police governance in Britain: the Home Secretary, the local police authority and the chief constable. The future of policing in the next five years is set out clearly by the Home Secretary, Theresa May MP, under the Police Reform and Social Responsibility Bill, which is currently being reviewed in the House of Lords. The recent phone hacking scandal has made it imperative for the British public to have a closer look at the police service in relation to proper accountability. There have been references to police corruption as far back as the era of 'parish constables', dating back to 1800, when it was alleged that police officers took bribes, got drunk whilst on duty and lacked moral credibility to protect and serve us (Critchley, 1978). In the seventies and eighties the British public was informed of another scandal involving members of Scotland Yard and criminal gangs in the East End of London. In this article, I shall argue that the issue of police corruption is not a new phenomenon. It is has been an ongoing issue that has haunted the police for over a century. This article is divided into three parts. In the first part of the article I present the following issues: the Metropolitan Police policing plan 2011-2014; the merits and demerits of the policing plan; tripartite police accountability and its shortcomings; democratic accountability and localisation of policing; the professionalisation of policing and the creation of the Police Body; review of police pay and benefits; and the impact of this on police officers' morale. In the second part of my article I present some of the criticisms levelled against the ongoing police reforms. I will look at the criticisms from both internal and external perspectives. By internal criticism, I mean police officers' opposition to the reforms. By external criticism, I mean criticisms from criminologists and members of the British public. In the third part of my article I made my position clear on where I stand in relation to the ongoing police reforms. I shall argue that the current ongoing job cuts in the police service are a disaster waiting to happen, and that our safety has been compromised by politicians. We are now living at the mercy of criminals and law breakers due to manpower shortage. We are all living witnesses to the ongoing public disturbances in Tottenham, Enfield, Brixton, Peckham, Walthamstow and Croydon, in London. The speed of the spread of these riots to other cities like Bristol, Birmingham, Manchester and Liverpool occurred on an unimaginable scale. We all watched how difficult it was for the police to restore order and normality. Rioters looted and plundered goods and burnt down buildings as if no laws existed in our country. A complete breakdown of law and order put the lives of citizens at risk. My article makes a passionate appeal to the present coalition government to rethink the issue of reducing the numbers of police officers protecting us. I shall argue that we need more police officers in Britain not fewer. The level of anger and social discontent is higher than the government ever anticipated, partly because of economic hardship. My argument is that economic hardship is not an excuse to commit burglary, theft, arson, murder and criminal damage with intent to endanger life. Rioters are shameless opportunists, a bunch of hoodlums, criminals who have no place in any civilised society, who should be made to face the due process of law

The Importance of Context and Cognitive Agency in Developing Police Knowledge: Going Beyond the Police Science Discourse

This paper argues the current exposition of police knowledge through the discourses of police science and evidenced based policing (EBP) leads to exaggerated claims about what is, and can be, known in policing. This new orthodoxy underestimates the challenges of applying knowledge within culturally-mediated police practice. The paper draws upon virtue epistemology highlighting the role cognitive agency plays in establishing knowledge claims. We challenge the assumption that it is possible to derive what works in all instances of certain aspects of policing and suggest it would be more apt to speak about what worked within a specific police context

Oral Antimicrobial Peptides and Biological Control of Caries

The presence of antimicrobial peptides (AMPs) in saliva may be a biological factor that contributes to susceptibility or resistance to caries. This manuscript will review AMPs in saliva, consider their antimicrobial and immunomodulatory functions, and evaluate their potential role in the oral cavity for protection of the tooth surface as well as the oral mucosa. These AMPs are made in salivary gland and duct cells and have broad antimicrobial activity. Alpha-defensins and LL37 are also released by neutrophils into the gingival crevicular fluid. Both sources may account for their presence in saliva. A recent study in middle school children aimed to determine a possible correlation between caries prevalence in children and salivary concentrations of the antimicrobial peptides human beta-defensin-3 (hBD-3), the cathelicidin, LL37, and the alpha-defensins. The levels of these AMPs were highly variable in the population. While levels of LL37 and hBD-3 did not correlate with caries experience, the mean alpha-defensin level was significantly higher in children with no caries than in children with caries (p < 0.005). We conclude that several types of AMPs that may have a role in oral health are present in unstimulated saliva. Low salivary levels of alpha-defensin may represent a biological factor that contributes to caries susceptibility. Our observation could lead to new ways to prevent caries and to a new tool for caries risk assessment

Combined systems approaches reveal highly plastic responses to antimicrobial peptide challenge in Escherichia coli

Obtaining an in-depth understanding of the arms races between peptides comprising the innate immune response and bacterial pathogens is of fundamental interest and will inform the development of new antibacterial therapeutics. We investigated whether a whole organism view of antimicrobial peptide (AMP) challenge on Escherichia coli would provide a suitably sophisticated bacterial perspective on AMP mechanism of action. Selecting structurally and physically related AMPs but with expected differences in bactericidal strategy, we monitored changes in bacterial metabolomes, morphological features and gene expression following AMP challenge at sub-lethal concentrations. For each technique, the vast majority of changes were specific to each AMP, with such a plastic response indicating E. coli is highly capable of discriminating between specific antibiotic challenges. Analysis of the ontological profiles generated from the transcriptomic analyses suggests this approach can accurately predict the antibacterial mode of action, providing a fresh, novel perspective for previous functional and biophysical studies

Modelling study of dimerization in mammalian defensins

BACKGROUND: Defensins are antimicrobial peptides of innate immunity functioning by non-specific binding to anionic phospholipids in bacterial membranes. Their cationicity, amphipathicity and ability to oligomerize are considered key factors for their action. Based on structural information on human β-defensin 2, we examine homologous defensins from various mammalian species for conserved functional physico-chemical characteristics. RESULTS: Based on homology greater than 40%, structural models of 8 homologs of HBD-2 were constructed. A conserved pattern of electrostatics and dynamics was observed across 6 of the examined defensins; models backed by energetics suggest that the defensins in these 6 organisms are characterized by dimerization-linked enhanced functional potentials. In contrast, dimerization is not energetically favoured in the sheep, goat and mouse defensins, suggesting that they function efficiently as monomers. CONCLUSION: β-defensin 2 from some mammals may work as monomers while those in others, including humans, work as oligomers. This could potentially be used to design human defensins that may be effective at lower concentrations and hence have therapeutic benefits