Combination of MEK-ERK inhibitor and hyaluronic acid has a synergistic effect on anti-hypertrophic and pro-chondrogenic activities in osteoarthritis treatment

We hypothesised that a potentially disease-modifying osteoarthritis (OA) drug such as hyaluronic acid (HA) given in combination with anti-inflammatory signalling agents such as mitogen-activated protein kinase kinase–extracellular signal-regulated kinase (MEK-ERK) signalling inhibitor (U0126) could result in additive or synergistic effects on preventing the degeneration of articular cartilage. Chondrocyte differentiation and hypertrophy were evaluated using human OA primary cells treated with either HA or U0126, or the combination of HA + U0126. Cartilage degeneration in menisectomy (MSX) induced rat OA model was investigated by intra-articular delivery of either HA or U0126, or the combination of HA + U0126. Histology, immunostaining, RT-qPCR, Western blotting and zymography were performed to assess the expression of cartilage matrix proteins and hypertrophic markers. Phosphorylated ERK (pERK)1/2-positive chondrocytes were significantly higher in OA samples compared with those in healthy control suggesting the pathological role of that pathway in OA. It was noted that HA + U0126 significantly reduced the levels of pERK, chondrocyte hypertrophic markers (COL10 and RUNX2) and degenerative markers (ADAMTs5 and MMP-13), however, increased the levels of chondrogenic markers (COL2) compared to untreated or the application of HA or U0126 alone. In agreement with the results in vitro, intra-articular delivery of HA + U0126 showed significant therapeutic improvement of cartilage in rat MSX OA model compared with untreated or the application of HA or U0126 alone. Our study suggests that the combination of HA and MEK-ERK inhibition has a synergistic effect on preventing cartilage degeneration.

Testing a model of physical activity among mothers and fathers of young children: integrating self-determined motivation, planning, and the theory of planned behavior

Parents are at risk for inactivity; however, research into understanding parental physical activity (PA) is scarce. We integrated self-determined motivation, planning, and the theory of planned behavior (TPB) to better understand parental PA. Parents (252 mothers, 206 fathers) completed a main questionnaire assessing measures underpinning these constructs and a 1-week follow-up of PA behavior to examine whether self-determined motivation indirectly influenced intention via the TPB variables (i.e., attitude, subjective norm, and perceived behavioral control) and intention indirectly influenced behavior via planning. We found self-determined motivation on intention was fully mediated by the TPB variables and intention on behavior was partially mediated by the planning variables. In addition, slight differences in the model’s paths between the sexes were revealed. The results illustrate the range of important determinants of parental PA and provide support for the integrated model in explaining PA decision making as well as the importance of examining sex differences.

Things that fall over : Women's playwriting, poetics and the (anti-)musical

Abstract: This study explores the contradictions and ambivalences experienced by a working artist at a time when her age, her gender, and broader cultural shifts are all potential obstacles or liabilities to creative flourishing. It is the product of practice-led research into the creative process from the perspective of the female "late bloomer". In this phrase, I have in mind the mature-aged woman who is, in mid-life, suddenly seized with inspiration and fired with creative energy. At its heart is the question: If an Elizabeth Jolley were in our midst today, would we hear from her? The result is a full-length libretto and accompanying exegetical binoculars in the form of a Preface and an Afterword. The creative work, Things That Fall Over (TTFO) is conceived in two parts: a libretto and oratorio for performance. It begins as a play, but over three acts and into a coda, the work becomes something entirely other - an (anti-) musical. The work grew from a personal interest in the nexus between women, ageing and creative practice, via investigation into the oeuvre of two Australian artists, Elizabeth Jolley, author, first published at age 53, and Rosalie Gascoigne, sculptor, first exhibited at 58. A second strand of the research grew from a fascination for the stage musical, especially in its more alternative modes as in the hands of Stephen Sondheim, or in more provocative manifestations as witnessed in recent Tony Award winners Avenue Q and The Book of Mormon. Contextually, this research is conducted at a time when anecdotal evidence suggests that women’s work in the performing arts and in literature is being pushed to the margins after a late twentieth century Golden Age on page and stage. Using hybrid practice-led methodologies - bricolage, log-keeping - and working within queer and feminist paradigms, this study seeks to counter that push with a new work that is all-female, part-pantomime, part monstrous allegory. In illuminating the creative process of a mature-aged playwright it concludes that hybrid and interstitial forms still offer an inclusive and democratic space in which voices that may otherwise be muted will continue to be heard.

Travel behavior of workers in Dhaka and their attitude towards road pricing

Dhaka, the capital of Bangladesh, is facing severe traffic congestion. Owing to the flaws in past land use and transport planning decisions, uncontrolled population growth and urbanization, Dhaka’s traffic condition is worsening. Road space is widely regarded in the literature as a utility, so a common view of transport economists is that its usage ought to be charged. Road pricing policy has proven to be effective in managing travel demand, in order to reduce traffic congestion from road networks in a number of cities including London, Stockholm and Singapore. Road pricing as an economic mechanism to manage travel demand can be more effective and user-friendly when revenue is hypothecated into supply alternatives such as improvements to the transit system. This research investigates the feasibility of adopting road pricing in Dhaka with respect to a significant Bus Rapid Transit (BRT) project. Because both are very new concepts for the population of Dhaka, public acceptability would be a principal issue driving their success or failure. This paper explores the travel behaviour of workers in Dhaka and public perception toward Road Pricing with regards to work trips- based on worker’s travel behaviour. A revealed preference and stated preference survey has been conducted on sample of workers in Dhaka. They were asked limited demographic questions, their current travel behaviour and at the end they had been given several hypothetical choices of integrated BRT and road pricing to choose from. Key finding from the survey is the objective of integrated road pricing; subsidies Bus rapid Transit by road pricing to get reduced BRT fare; cannot be achieved in Dhaka. This is because most of the respondent stated that they would choose the cheapest option Walk-BRT-Walk, even though this would be more time consuming and uncomfortable as they have to walk from home to BRT station and also from BRT station to home. Proper economic analysis has to be carried out to find out the appropriate fare of BRT and road charge with some incentive for the low income people.

Patriarchy reasserted : fathers' rights and anti-VAWA activism

The backlash against gender-sensitive responses to women's victimization, offending, and imprisonment is inseparable from contemporary reaction against feminism and other progressive movements. The backlash against the American Violence Against Women Act (VAWA) provides a prime example of this resistance. Despite widespread support for VAWA and other policies designed to address violence against women, some constituencies object to their existence. The author investigates fathers' rights rhetoric on VAWA as an example of antifeminist backlash.

How males and females define speeding and how they’d feel getting caught for it : some implications for anti-speeding message development

Speeding represents a major contributor to road trauma, increasing crash frequency and severity. Antispeeding campaigns represent a key strategy aimed at discouraging individuals from speeding. This paper investigated salient beliefs underpinning male and female drivers’ travel speed behaviour, with the view to use such insight to, ultimately, inform the content of targeted anti-speeding messages. A survey of N = 751 (579 males, 16-79 years) drivers assessed what they regarded as speeding in 60km/hr and 100km/hr zones and their beliefs about how they would respond to receiving a speeding infringement. Participants responded to scales which extended up to 20km/hr above each respective speed limit, the lowest speed that they considered was speeding and the speed at which they would be willing to drive and still feel in control. For analyses, to enable greater scrutiny of potential gender differences regarding the speeds identified, participants’ responses to these items were categorised into 5km/hr increments and chi-square analyses conducted. For their responses to (beliefs about) the possibility of being caught speeding, drivers were asked how applicable various beliefs were to them (e.g., feeling unlucky). These beliefs were analysed via MANOVA. The results revealed that there was considerable variability in the speeds identified, thus supporting the value of categorising speeds. Within the 100km/hr zone, based on the categories, a significant difference was found regarding the speed that males would be willing to drive (and still feel in control) relative to females. Specifically, the greatest proportion of males (30.4%) identified speeds within the 106-110km/hr category whereas the greatest proportion of females (38.1%) identified a lower speed, within the 101-105km/hr category, as the speed they would be willing to drive. No other significant differences emerged, however, either in relation to the definition of speeding reported for 100km/hr zones (i.e., males and females tended to identify a similar speed as indicative of speeding) nor for these same items as assessed in relation to the 60km/hr zones. For their responses to the possibility of being caught, males were significantly more likely than females to report that, if caught, a likely response they would have would be to think that they had still been driving safely. In contrast, females were significantly more likely than males to report thinking that their speeding had been unsafe and that they should not have been speeding. Females were also significantly more likely to report feeling embarrassed to tell important others about having received a speeding infringement than males. The findings are discussed in terms of their implications for developing well-targeted advertising messages aimed at discouraging drivers’ from speeding.

Anti-infectives

18.1 Antibiotics 18.1.1 Introduction to bacteria 18.1.2 Introduction to antibiotics 18.1.3 Inhibitors of bacterial cell wall synthesis 18.1.3.1 β-Lactams 18.1.3.2 Glycopeptides 18.1.4 Inhibitors of bacterial protein synthesis 18.1.4.1 Tetracyclines 18.1.4.2 Aminoglycosides 18.1.4.3 Chloramphenicol 18.1.4.4 Macrolides 18.1.4.5 Lincosamides 18.1.4.6 Oxalazidones 18.1.5 Inhibitors of DNA synthesis 18.2. Anti-tuberculotic drugs 18.2.1 Introduction 18.2.2 Isoniazid 18.2.3 Ethambutol 18.2.4 Rifamycin 18.2.5 Pyrazinamide 18.3. Anti-viral drugs 18.3.1 Introduction to viruses 18.3.2 Drugs used to treat herpesviruses 18.3.3 Drugs used to treat the flu 18.3.4 Drugs used to treat HIV/AIDS 18.4. Antifungal drugs 18.4.1 Introduction to Fungi 18.4.2 Antifungal drugs

Plant made anti-HIV microbicides-A field of opportunity

HIV remains a significant global burden and without an effective vaccine, it is crucial to develop microbicides to halt the initial transmission of the virus. Several microbicides have been researched with various levels of success. Amongst these, the broadly neutralising antibodies and peptide lectins are promising in that they can immediately act on the virus and have proven efficacious in in vitro and in vivo protection studies. For the purpose of development and access by the relevant population groups, it is crucial that these microbicides be produced at low cost. For the promising protein and peptide candidate molecules, it appears that current production systems are overburdened and expensive to establish and maintain. With recent developments in vector systems for protein expression coupled with downstream protein purification technologies, plants are rapidly gaining credibility as alternative production systems. Here we evaluate the advances made in host and vector system development for plant expression as well as the progress made in expressing HIV neutralising antibodies and peptide lectins using plant-based platforms. © 2012 Elsevier Inc.

Effect of Australia's walk to work day campaign on adults' active commuting and physical activity behavior

Purpose. To determine whether Australia's Walk to Work Day media campaign resulted in behavioural change among targeted groups. Methods. Pre- and postcampaign telephone surveys of a cohort of adults aged 18 to 65 years (n = 1100, 55% response rate) were randomly sampled from Australian major melropolitan areas. Tests for dependent samples were applied (McNemax chi(2) or paired t-test). Results. Among participants who did not usually actively commute to work was a significant decrease in car only use an increase in walking combined with public transport. Among those who were employed was a significant increase in total time walking (+16 min/wk; t [780] = 2.04, p < .05) and in other moderate physical activity (+120 min/wk; t [1087] = 4.76, p < .005), resulting in a significant decrease in the proportion who were inactive (chi(2) (1) = 6.1, p < .05). Conclusion. Although nonexperimental, the Walk to Work Day initiative elicited short-term changes in targeted behaviors among target groups. Reinforcement by integrating worksite health promotion strategies may be required for sustained effects.

The relationship between unsafe working conditions and workers’ behavior and their impacts on injury severity in the U.S.

Unsafe acts of workers (e.g. misjudgment, inappropriate operation) become the major root causes of construction accidents when they are combined with unsafe working conditions (e.g. working surface conditions, weather) on a construction site. The overarching goal of the research presented in this paper is to explore ways to prevent unsafe acts of workers and reduce the likelihood of construction accidents occurring. The study specifically aims to (1) understand the relationships between human behavior related and working condition related risk factors, (2) identify the significant behavior and condition factors and their impacts on accident types (e.g. struck by/against, caught in/between, falling, shock, inhalation/ingestion/absorption, respiratory failure) and injury severity (e.g. fatality, hospitalized, non-hospitalized), and (3) analyze the fundamental accident-injury relationship on how each accident type contributes to the injury severity. The study reviewed 9,358 accidents which occurred in the U.S. construction industry between 2002 and 2011. The large number of accident samples supported reliable statistical analyses. The analysis identified a total of 17 significant correlations between behavior and condition factors and distinguished key risk factors that highly impacted on the determination of accident types and injury severity. The research outcomes will assist safety managers to control specific unsafe acts of workers by eliminating the associated unsafe working conditions and vice versa. They also can prioritize risk factors and pay more attention to controlling them in order to achieve a safer working environment.

Biology or behavior : which is the strongest contributor to weight gain?

Combating unhealthy weight gain is a major public health and clinical management issue. The extent of research into the etiology and pathophysiology of obesity has produced a wealth of evidence regarding the contributing factors. While aspects of the environment are ‘obesogenic’, weight gain is not inevitable for every individual. What then explains potentially unhealthy weight gain in individuals living within an environment where others remain lean? In this paper we explore the biological compensation that acts in response to a reduced energy intake by reducing energy needs, in order to defend against weight loss. We then examine the evidence that there is only a weak biological compensation to surplus energy supply, and that this allows behavior to drive weight gain. The extent to which biology impacts behavior is also considered.

Variation in risk seeking behavior in a natural experiment following a large negative wealth shock induced by a natural disaster

An ongoing challenge in behavioral economics is to understand the variations observed in risk attitudes as a function of their environmental context. Of particular interest is the effect of wealth on risk attitudes. The research in this area has however faced two constraints: the difficulty to study the causal effects of large changes in wealth, and the causal effects of losses on risk behavior. The present paper address this double limitation by providing evidence of the variation of risk attitude after large losses using a natural disaster (Brisbane floods) as the setting for a natural experiment.

An extended theory of planned behavior intervention for older adults With Type 2 diabetes and cardiovascular disease

A randomized controlled trial evaluated the effectiveness of a 4-wk extended theory of planned behavior (TPB) intervention to promote regular physical activity and healthy eating among older adults diagnosed with Type 2 diabetes or cardiovascular disease (N = 183). Participants completed TPB measures of attitude, subjective norm, perceived behavioral control, and intention, as well as planning and behavior, at preintervention and 1 wk and 6 wk postintervention for each behavior. No significant time-by-condition effects emerged for healthy eating. For physical activity, significant time-by-condition effects were found for behavior, intention, planning, perceived behavioral control, and subjective norm. In particular, compared with control participants, the intervention group showed short-term improvements in physical activity and planning, with further analyses indicating that the effect of the intervention on behavior was mediated by planning. The results indicate that TPB-based interventions including planning strategies may encourage physical activity among older people with diabetes and cardiovascular disease.

Experimental studies of the shear behavior and strength of LiteSteel beams with stiffened web openings

Abstract: LiteSteel beam (LSB) is a new cold-formed steel hollow flange channel section produced using a patented manufacturing process. It is commonly used as flexural members in residential, industrial and commercial buildings. Current practice in flooring systems is to include openings in the web element of floor joists or bearers so that building services can be located within them. Test results have shown that the shear capacity of LSBs can be reduced considerably by the inclusion of web openings. A cost effective method of eliminating the detrimental effects of a large web opening is to attach suitable stiffeners around the web openings of LSBs. A detailed experimental study consisting of 17 shear tests was therefore undertaken to investigate the shear behaviour and strength of LSBs with stiffened circular web openings. Both plate and stud stiffeners with varying sizes and thicknesses were attached to the web elements of LSBs using a number of screw-fastening arrangements in order to develop a suitable stiffening arrangement for LSBs. Simply supported test specimens of LSBs with an aspect ratio of 1.5 were loaded at mid-span until failure. This paper presents the details of this experimental study of LSBs with stiffened web openings, and the results of their shear capacities and associated behavioural characteristics. Suitable screw-fastened plate stiffener arrangements have been recommended in order to restore the original shear capacity of LSBs.

Concurrent and longitudinal links between children’s and their friends’ antisocial and prosocial behavior in preschool

Concurrent and longitudinal links between children’s own and their nominated best friends’ antisocial and prosocial behavior were studied in a normative sample of 3–5-year-olds (N = 203). Moderating effects of age and gender were also explored. Subscales of the Strength and Difficulties Questionnaire (SDQ) were used to obtain teacher ratings of behavior for each target child and his/her nominated best friends. Nomination of best friends with higher levels of antisocial behavior and lower levels of prosocial behavior was concurrently linked to more antisocial behavior in boys. Nomination of highly prosocial best friends was concurrently linked to more prosocial behavior in both boys and girls. However, the study found no longitudinal effects of best friends’ behavior on target child’s behavior over a one-year period. A group of children who nominated no best friends at T1 were generally perceived as less prosocial, but not more antisocial, than other children. © 2011 Elsevier Inc. All rights reserved.