Aberrant protective force generation during neural provocation testing and the effect of treatment in patients with neurogenic cervicobrachial pain

Background: Observation of the occurrence of protective muscle activity is advocated in assessment of the peripheral nervous system by means of neural provocation tests. However, no studies have yet demonstrated abnormal force generation in a patient population. Objectives: To analyze whether aberrations in shoulder girdle-elevation force during neural tissue provocation testing for the median nerve (NTPTI) can be demonstrated, and whether possible aberrations can be normalized following cervical mobilization. Study Design: A single-blind randomized comparative controlled study. Setting: Laboratory setting annex in a manual therapy teaching practice. Participants: Twenty patients with unilateral or bilateral neurogenic cervicobrachial pain. Methods: During the NTPTI, we used a load cell and electrogoniometer to record continuously the shoulder-girdle elevation force in relation to the available range of elbow extension. Following randomization, we analyzed the immediate treatment effects of a cervical contralateral lateral glide mobilization technique (experimental group) and therapeutic ultrasound (control group). Results: On the involved side, the shoulder-girdle elevation force occur-red earlier, and the amount of force at the end of the test was substantially, though not significantly, greater than that on the uninvolved side at the corresponding range of motion. Together with a significant reduction in pain perception after cervical mobilization, a clear tendency toward normalization of the force curve could be observed, namely, a significant decrease in force generation and a delayed onset. The control group demonstrated no differences. Conclusions: Aberrations in force generation during neural, provocation testing are present in patients with neurogenic pain and can be normalized with appropriate treatment modalities.

Recombinant Kunjin virus replicon vaccines induce protective T-cell immunity against human papillomavirus 16 E7-expressing tumour

The persistence of the E7 oncoprotein in transformed cells in human papillomavirus (HPV)-associated cervical cancer provides a tumour-specific antigen to which immunotherapeutic strategies may be directed. Self-replicating RNA (replicon) vaccine vectors derived from the flavivirus Kunjin (KUN) have recently been reported to induce T-cell immunity. Here, we report that inclusion of a CTL epitope of HPV16 E7 protein into a polyepitope encoded by a KUN vector induced E7-directed T-cell responses and protected mice against challenge with an E7-expressing epithelial tumour. We found replicon RNA packaged into virus-like particles to be more effective than naked replicon RNA or plasmid DNA constructed to allow replicon RNA transcription in vivo. Protective immunity was induced although the E7 CTL epitope was subdominant in the context of other CTL epitopes in the polyepitope. The results demonstrate the efficacy of the KUN replicon vector system for inducing protective immunity directed towards a virally encoded human tumour-specific antigen, and for inducing multi-epitopic CTL responses. (C) 2004 Elsevier Inc. All rights reserved.

Protective Eyewear Promotion: Applying Principles of Behaviour Change in the Design of a Squash Injury Prevention Programme

Eye injuries in squash have the potential to be severe. Although these injuries can be prevented through the use of protective eyewear, few players wear such eyewear. The aim of this paper is, to outline the behavioural principles guiding the design of a squash eyewear promotion initiative, the Protective Eyewear Promotion (PEP). Ecological principles of behaviour change were used to provide a comprehensive perspective on intrapersonal factors, policies and physical environmental influences of protective eyewear use. Results of baseline player surveys and venue manager inter-views were used to provide relevant and specific intervention content. At baseline, protective eyewear was not found to be readily available, and players' behaviours, knowledge and attitudes did not favour its use. The main components of PEP involved informing and educating both players and squash venue operators of the risk of eye injury and of appropriate protective eyewear, as well as assisting with the availability of the eyewear and offering incentives for players to use it. A structural strength of PEP was the strong collaborative links with the researchers of different disciplines, the squash governing body, eyewear manufacturers, squash venue personnel, as well as players. Attempts were made within the project structure to make provision for the future dissemination and sustainability of more widespread eye injury prevention measures in the sport of squash.

Knowledge beliefs and attitudes of squash venue operators relating to use of protective eyewear

Sports venues are in a position to potentially influence the safety practices of their patrons. This study examined the knowledge, beliefs and attitudes of venue operators that could influence the use of protective eyewear by squash players. A 50% random sample of all private and public squash venues affiliated with the Victorian Squash Federation in metropolitan Melbourne was selected. Face-to-face interviews were conducted with 15 squash venue operators during August 2001. Interviews were transcribed and content and thematic analyses were performed. The content of the interviews covered five topics: (1) overall injury risk perception, (2) eye injury occurrence, (3) knowledge, behaviors, attitudes and beliefs associated with protective eyewear, (4) compulsory protective eyewear and (5) availability of protective eyewear at venues. Venue operators were mainly concerned with the severe nature of eye injuries, rather than the relatively low incidence of these injuries. Some venue operators believed that players should wear any eyewear, rather than none at all, and believed that more players should use protective eyewear. Generally, they did not believe that players with higher levels of experience and expertise needed to wear protective eyewear when playing. Only six venues had at least one type of eyewear available for players to hire or borrow or to purchase. Operators expressed a desire to be informed about correct protective eyewear. Appropriate protective eyewear is not readily available at squash venues. Better-informed venue operators may be more likely to provide suitable protective eyewear.

Membrane insertion of anthrax protective antigen and cytoplasmic delivery of lethal factor occur at different stages of the endocytic pathway

The protective antigen (PA) of anthrax toxin binds to a cell surface receptor, undergoes heptamerization, and binds the enzymatic subunits, the lethal factor (LF) and the edema factor (EF). The resulting complex is then endocytosed. Via mechanisms that depend on the vacuolar ATPase and require membrane insertion of PA, LF and EF are ultimately delivered to the cytoplasm where their targets reside. Here, we show that membrane insertion of PA already occurs in early endosomes, possibly only in the multivesicular regions, but that subsequent delivery of LF to the cytoplasm occurs preferentially later in the endocytic pathway and relies on the dynamics of internal vesicles of multivesicular late endosomes.

Toward the development of a synthetic group A streptococcal vaccine of high purity and broad protective coverage

Using native chemical ligation, we synthesized a group A streptococcal. (GAS) vaccine that contained three different GAS M protein peptide epitopes in a chemically well-characterized construct in high purity. Two of the peptide epitopes represented variable amino terminal serotype determinants, and the third represented a carboxyl terminal conserved region determinant of the GAS M protein. We also synthesized a lipid core peptide (LCP) construct containing the same three peptides. Upon immunization of mice, the non-LCP construct only elicited antibody responses to all three epitopes with the use of adjuvant. The LCP construct, however, elicited excellent antibody responses to all three epitopes without the need for any additional adjuvant or carrier. We have synthesized the LCP synthetic vaccine system with good reproducibility.

Do squash players accurately report use of appropriate protective eyewear?

Self-report surveys are a common method of collecting data on protective equipment use in sport. The aim of this study was to assess the validity of self-reported use of appropriate protective eyewear by squash players. Surveys of squash players' appropriate protective eyewear behaviours were conducted over two consecutive years (2002 and 2003) at randomly-selected squash venues in Melbourne, Australia. Over the two years, 1219 adult players were surveyed (response rate of 92%). Trained observers also recorded the actual on-court appropriate protective eyewear behaviours of all players during the survey sessions. Eyewear use rates calculated from both data sources were compared. The self-reported appropriate protective eyewear use rate (9.4%; 95% CI 7.8, 11.0) was significantly higher (1.6 times more) than the observed rate (5.9%; 95%CI 4.6, 7.2). This suggests that players may over-report their use of appropriate protective equipment, though some may have incorrectly classified their eyewear as being appropriate or suitably protective. Studies that rely only on self-report data on protective equipment use need to take into account that this could lead to biased estimates.

Fusing subunit antigens to interleukin-2 and encapsulating them in liposomes improves their antigenicity but not their protective efficacy

Subunit vaccines commonly lack sufficient immunogenicity to stimulate a comprehensive protective immune response in vivo. We have investigated the potential of specific cytokines (interleukin-2) and particulate delivery systems (liposomes) to enhance antigenicity. Here we report that the IgG1 and IFN-gamma responses to a subunit antigen, consisting of a T and B-cell epitope from Influenza haemagglutinin, can be improved when it is both fused to interelukin-2 and encapsulated in liposomes. However, this vaccine formulation was not able to protect animals against a challenge with live Influenza A/PR/8/34 virus. The addition of more potent immune stimulators may be necessary to improve responses. (c) 2005 Elsevier Ltd. All rights reserved.

Differentiation between protective reflexes: Cardiac defense and startle

Rise time and duration are two parametric characteristics of the eliciting stimulus frequently used to differentiate among psychophysiological reflexes. The present research varied the duration (study 1) and rise time (study 2) of an intense acoustic stimulus to dissociate cardiac defense and cardiac startle using the eyeblink response as the external criterion of startle. In each study, 100 participants were presented with five white noise stimuli of 105 dB under one of five duration (50, 100, 250, 500, and 1000 ms) or rise time (0, 24, 48, 96, and 240 ms) conditions. Cardiac defense was affected by stimulus duration, present only in the 500- and 1000-ms conditions, but not by stimulus rise time, present in all rise time conditions. Rise time affected blink startle, but did not selectively alter the short latency accelerative component of the heart rate response, thus questioning whether it reflects startle.

Health-protective behaviours and risk of fall-related hip fractures: a population-based case-control study

Background: fall-related hip fractures are one of the most common causes of disability and mortality in older age. The study aimed to quantify the relationship between lifestyle behaviours and the risk of fall-related hip fracture in community-dwelling older people. The purpose was to contribute evidence for the promotion of healthy ageing as a population-based intervention for falls injury prevention. Methods: a case-control study was conducted with 387 participants, with a case-control ratio of 1:2. Incident cases of fall-related hip fracture in people aged 65 and over were recruited from six hospital sites in Brisbane, Australia, in 2003-04. Community-based controls, matched by age, sex and postcode, were recruited via electoral roll sampling. A questionnaire designed to assess lifestyle risk factors, identified as determinants of healthy ageing, was administered at face-to-face interviews. Results: behavioural factors which had a significant independent protective effect on the risk of hip fracture included never smoking [adjusted odds ratio (AOR): 0.33 (0.12-0.88)], moderate alcohol consumption in mid- and older age [AOR: 0.49 (0.25-0.95)], not losing weight between mid- and older age [AOR: 0.36 (0.20-0.65)], playing sport in older age [AOR: 0.49 (0.29-0.83)] and practising a greater number of preventive medical care [AOR: 0.54 (0.32-0.94)] and self-health behaviours [AOR: 0.56 (0.33-0.94)]. Conclusion: with universal exposures, clear associations and modifiable behavioural factors, this study has contributed evidence to reduce the major public health burden of fall-related hip fractures using readily implemented population-based healthy ageing strategies.

Isolates of Candida albicans that differ in virulence for mice elicit strain-specific antibody-mediated protective responses

Three distinct isolates of Candida albicans were used to establish systemic and oral infections in inbred mice that are genetically resistant or susceptible to tissue damage. Patterns of infection differed significantly between both yeasts and mouse strains. Systemic infection conferred significant protection against re-challenge with the homologous, but not the heterologous yeast; however, the protective effect was more evident in the tissue-susceptible CBA/CaH mice than in the resistant BALB/c strain. In contrast, oral infection induced protection against both homologous and heterologous oral challenge, although this was significant only in the CBA/CaH mice. CBA/CaH mice produced antibodies of both IgG1 and IgG2a subclasses, whereas BALB/c mice produced predominantly IgG1. Western blotting demonstrated considerable differences between epitopes recognised by serum antibodies from mice of both strains after immunisation with each of the three yeasts. Thus, different strains of yeast show considerable specificity in antibody responses elicited by either systemic or oral infection. (c) 2005 Elsevier SAS. All rights reserved.

Hepatitis B surface antigen vector delivers protective cytotoxic T-lymphocyte responses to disease-relevant foreign epitopes

Although hepatitis B surface antigen (HBsAg) per se is highly immunogenic, its use as a vector for the delivery of foreign cytotoxic T-lymphocyte (CTL) epitopes has met with little success because of constraints on HBsAg stability and secretion imposed by the insertion of foreign sequence into critical hydrophobic/amphipathic regions. Using a strategy entailing deletion of DNA encoding HBsAg-specific CTL epitopes and replacement with DNA encoding foreign CTL epitopes, we have derived chimeric HBsAg DNA immunogens which elicited effector and memory CTL responses in vitro, and pathogen- and tumor-protective responses in vivo, when the chimeric HBsAg DNAs were used to immunize mice. We further show that HBsAg DNA recombinant for both respiratory syncytial virus and human papillomavirus CTL epitopes elicited simultaneous responses to both pathogens. These data demonstrate the efficacy of HBsAg DNA as a vector for the delivery of disease-relevant protective CTL responses. They also suggest the applicability of the approach of deriving chimeric HBsAg DNA immunogens simultaneously encoding protective CTL epitopes for multiple diseases. The DNAs we tested formed chimeric HBsAg virus-like particles (VLPs). Thus, our results have implications for the development of vaccination strategies using either chimeric HBsAg DNA or VLP vaccines. HBsAg is the globally administered vaccine for hepatitis B virus infection, inviting its usage as a vector for the delivery of immunogens from other diseases.