Smoking mull: a grounded theory model on the dynamics of combined tobacco and cannabis use among adult men.

ISSUE ADDRESSED: Australians' use of cannabis has been increasing. Over a third of Australians (35.4%) have used cannabis at some time in their lives and 10.3% are recent users. Almost two-thirds of cannabis users combine cannabis with tobacco. The aim of this study was to understand the process of mulling - smoking tobacco and cannabis together - using a grounded theory approach. METHODS: Twenty-one in-depth semistructured interviews were conducted with men aged 25-34 and living on the North Coast of New South Wales. Interviews explored participants' smoking practices, histories and cessation attempts. RESULTS: A model describing mulling behaviour and the dynamics of smoking cannabis and tobacco was developed. It provides an explanatory framework that demonstrates the flexibility in smoking practices, including substance substitution - participants changed the type of cannabis they smoked, the amount of tobacco they mixed with it and the devices they used to smoke according to the situations they were in and the effects sought. CONCLUSION: Understanding these dynamic smoking practices and the importance of situations and effects, as well as the specific role of tobacco in mulling, may allow health workers to design more relevant and appropriate interventions. SO WHAT? Combining tobacco with cannabis is the most common way of smoking cannabis in Australia. However, tobacco cessation programmes rarely address cannabis use. Further research to develop evidence-based approaches for mull use would improve cessation outcomes.

Acetylenic TACE inhibitors. Part 2: SAR of six-membered cyclic sulfonamide hydroxamates.

The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a butynyloxy P1' group was explored. In particular, compound 5k has excellent in vitro potency against TACE enzyme and in cells, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model.

Acetylenic TACE inhibitors. Part 1. SAR of the acyclic sulfonamide hydroxamates.

The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors, all bearing a butynyloxy P1' group, was explored. In particular, compound 5j has excellent in vitro potency against isolated TACE enzyme and in cells, good selectivity over MMP-1 and MMP-9, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model.

Synthesis and SAR of bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors.

Potent and selective bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors were synthesized by a novel convergent route. Selectivity and efficacy versus MMPs and TACE could be controlled by appropriate substitution on the scaffolds and by variation of the P1' group. Select compounds were found to be effective in in vivo models of arthritis.

Can we skill and activate children through primary school physical education lessons? "Move it Groove it"--a collaborative health promotion intervention.

BACKGROUND: Physical education (PE) lessons are an ideal setting to improve child fundamental movement skills (FMSs) and increase physical activity (PA) for optimal health. Despite this, few studies have assessed the potential to do both simultaneously. The "Move It Groove It" primary school intervention in New South Wales, Australia, had this opportunity. METHODS: A whole school approach to implementation included establishment of school project teams, a teacher "buddy" system, project Web site, teacher training workshops, and small grants for equipment. The quasi-experimental evaluation involved 1,045 year 3 and 4 children (aged 7 to 10 years) in nine intervention and nine control rural primary schools (53% boys/47% girls). It utilised pre- and postobservational surveys of (1) mastery or near mastery levels for each of eight FMSs, (2) proportion of PE lesson time spent in moderate to vigorous PA (MVPA) and vigorous PA (VPA), and (3) teacher- and lesson-related contextual covariates. Data were analysed by hierarchical logistic multiple regression. RESULTS: For FMSs, overall mastery or near mastery level at baseline was 47% ranging from 22.7% for the overarm throw among girls to 75.4% for the static balance among boys. The intervention delivered substantial improvements in every FMS for both genders ranging from 7.2% to 25.7% (13 of 16 comparisons were significant). For PA level, mean MVPA at baseline was 34.7%. Baseline MVPA for boys was 38.7% and for girls was 33.2%. The intervention was associated with a nonsignificant 4.5% increase in MVPA and a significant 3.0% increase in VPA. This translates to a gain of <1 minute of MVPA per average 21-minute lesson. CONCLUSIONS: This is the first study to show that by modifying existing PE lessons, significant improvements in FMS mastery can be gained without adversely affecting children's MVPA and VPA. To increase PA levels, we recommend increasing the number of PE lessons per week.

How active are rural children in Australian physical education?

Physical education lessons offer a venue for children to accrue valuable and health-conferring time being physically active. The first Australian direct observational data are presented on activity of year 3 and 4 children during physical education. Analysis accounts for the nested nature of the data through multi level logistic regression using 13,080 records within 231 lessons within 18 randomly selected schools. Activity was analysed in relation to lesson context (focus of lesson), child gender, school year of child, teacher gender, lesson duration and start time. Children spent 36.7% of a lesson in moderate to vigorous and 12.9% in vigorous activity. Most of the lesson was spent in the context of management/instruction (37.4%), followed by games (25.0%), skill (21.4%), and fitness (14.7%). The highest level of moderate to vigorous activity was observed in the fitness lesson context (61.9%). followed by skill (46.4%), games (42.6%) and management/instruction (17.1%). Moderate to vigorous activity was significantly higher for boys than girls. There was no significant difference in moderate to vigorous activity in lessons led by male or female teachers. However vigorous activity was significantly higher for female led lessons. Children participated in less physical activity during physical education lessons timetabled in the afternoon, compared to physical education lessons time-tabled in the morning. Physical activity levels were not related to lesson duration. Physical education lessons can potentially be more active. However improvement rests on school capacity and may require a health promoting schools approach to implement curricular policy.

Fundamental movement skills--how do primary school children perform? The 'Move it Groove it' program in rural Australia.

Child Fundamental Movement Skills (FMS) underpin active lifestyles yet little is known of their distribution and mastery. 'Move it Groove it' project rated proficiency of primary school children (n = 1045, 18 schools) in skills of balance, throw, catch, sprint, hop, kick, side gallop and jump. Rating categories were 'mastery', 'near mastery' or 'poor' (ie mastered all, all but one, or less of the five to six components of an FMS). Less than half of all child tests were rated at mastery (21.3%) or near mastery (25.7%) level. In grade three, 75.4% of children achieved mastery or near mastery (MNM) in static balance but less than half did so for any other FMS. In grade four, 59.0% achieved MNM in the side gallop and 56.0% in the catch but less than half did so for any other FMS. Although the highest percent mastery for both genders was for the balance, the skills best performed thereafter by boys (throw and kick) rated poorest for girls. Conversely the hop and side gallop which rated, after balance, as the skills best mastered by girls, were among the more poorly performed skills for boys. The low prevalence of FMS mastery found in this survey suggests that there may be great potential to improve fundamental movement skills of primary aged children in many parts of rural Australia. Even if the aim were for children to achieve near mastery levels, the improvement could be substantial in every skill category. Where appropriate, gender differences in mastery might easily be addressed by tailored physical education programs and modification of social and physical environments.

Active school playgrounds-myth or reality? Results of the "move it groove it" project.

BACKGROUND: School playgrounds during break times provide potential opportunities for children to be active during the school day. However, there is limited research on how active children really are during these breaks. METHODS: The CAST (Children's Activity Scanning Tool) instrument was developed, validated, and used to assess the percentages of children engaged in moderate to vigorous physical activity (MVPA) and vigorous physical activity (VPA-a subset of MVPA) in 18 primary schools (children ages 5-12) in rural Australia. Related environmental factors were also measured. RESULTS: For a school of median size (200 students), 51.4% of boys and 41.6% of girls were engaged in MVPA while 14.7% of boys and 9.4% of girls were engaged in VPA. Levels of engagement in MVPA and VPA were significantly higher during lunch periods than during recess. MVPA and VPA engagement in smaller schools was significantly higher than in larger schools. CONCLUSIONS: With growing concern about children's physical activity (PA), school playgrounds offer an opportunity to increase children's MVPA engagement especially among girls. Consideration may be given to the lengthening of recess periods in order to increase PA levels. More research is needed to investigate factors affecting PA levels in larger schools.

The discovery of anthranilic acid-based MMP inhibitors. Part 2: SAR of the 5-position and P1(1) groups.

A novel series of anthranilic acid-based inhibitors of MMP-1, MMP-9, MMP-13, and TACE was prepared and evaluated. Selective inhibitors of MMP-9, MMP-13, and TACE were identified, including the potent, orally active MMP-13 inhibitor 4p.

Heteroaryl and cycloalkyl sulfonamide hydroxamic acid inhibitors of matrix metalloproteinases.

Heteroaryl and cycloalkyl sulfonamide-hydroxamic acid MMP inhibitors were investigated. Of these, the pyridyl analogue 2 is the most potent and selective inhibitor of MMP-9 and MMP-13 in vitro.

Design and synthetic considerations of matrix metalloproteinase inhibitors.

Experimental evidence confirms that the matrix metalloproteinases (MMPs) play a fundamental role in a wide variety of pathologic conditions that involve connective tissue destruction including osteoarthritis and rheumatoid arthritis, tumor metastasis and angiogenesis, corneal ulceration, multiple sclerosis, periodontal disease, and atherosclerosis. Modulation of MMP regulation is possible at several biochemical sites, but direct inhibition of enzyme action provides a particularly attractive target for therapeutic intervention. Hypotheses concerning inhibition of specific MMP(s) with respect to disease target and/or side-effect profile have emerged. Examples are presented of recent advances in medicinal chemistry approaches to the design of matrix metalloproteinase inhibitors (MMPIs), approaches that address structural requirements and that influence potency, selectivity, and bioavailability. Two important approaches to the design, synthesis, and biological evaluation of MMPIs are highlighted: (1) the invention of alternatives to hydroxamic acid zinc chelators and (2) the construction of nonpeptide scaffolds. One current example in each of these two approaches from our own work is described.

Synthesis and antihyperglycemic activity of novel 5-(naphthalenylsulfonyl)-2,4-thiazolidinediones.

A series of 5-(naphthalenylsulfonyl)-2,4-thiazolidinediones were synthesized and evaluated for antihyperglycemic activity in an insulin-resistant, genetically diabetic db/db mouse model of non-insulin-dependent diabetes mellitus (NIDDM). The sulfones could be synthesized by a novel, selective C-5 sulfonylation of dilithio-2,4-thiazolidinedione with appropriate sulfonyl chlorides. Within this series, naphthalene was found to be superior to other groups for eliciting antihyperglycemic activity, including the p-alkoxyphenyl group found in ciglitazone, a prototypical agent for this activity. Attachment of the 5-sulfonyl-2,4-thiazolidinedione moiety to the 2-naphthalene position led to optimum activity. Other linkers between the naphthalene and 2,4-thiazolidinedione rings, such as thio, methylene, oxy, and sulfinyl led to decreased antihyperglycemic activity. The best analogue, 5-(2-naphthalenylsulfonyl)-2,4-thiazolidinedione (AY-31,637) was equipotent to ciglitazone in two animal models of NIDDM.