Alcohol and other drug use disorders among older-aged people

In Australia people aged 65 years or older currently comprise 12.1% of the population. This has been estimated to rise to 24.2% by 2051. Until recently there has been relatively little research on alcohol and other drug use disorders among these individuals but, given the ageing population, this issue is likely to become of increasing importance and prominence. Epidemiological research shows a strong age-related decline in the prevalence of alcohol and other drug use disorders with age. Possible reasons for this include: age-related declines in the use and misuse of alcohol and other drugs; increased mortality among those with a lifetime history of alcohol and other drug use disorders; historical differences in exposure to and use of alcohol and other drugs. Despite the age-related decline in the prevalence of these disorders, they do still occur among those aged 65 years or older and, given historical changes in exposure to and use of illicit drugs, it likely that the prevalence of these disorders among older-aged individuals will rise. Specific issues faced by older-aged individuals with alcohol and other drug use problems are discussed. These include: interactions with prescribed medications, under-recognition and treatment of alcohol and drug problems, unintentional injury and social isolation. Finally, a brief discussion of treatment issues is provided.

Will chymase inhibitors be the next major development for the treatment of cardiovascular disorders?

Chymase is contained in the secretory granules of mast cells. In addition to the synthesis of angiotensin II, chymase is involved in transforming growth factor-beta activation and cleaves Type I procollagen to produce collagen. NK301 and BCEAB are orally-active inhibitors of chymase. NK301 was tested in a dog model of vascular intimal hyperplasia after balloon injury and shown to reduce the increased chymase activity in the injured arteries and prevent intimal thickening. In a hamster model of cardiac fibrosis associated with cardiomyopathy, BCEAB reduced the increased cardiac chymase activity in cardiomyopathy and reduced fibrosis. Chymase inhibitors may be an important development for the treatment of cardiovascular injury associated with mast cell degranulation.

A longitudinal analysis of sex differences in bone mineral accrual in healthy 8-19-year-old boys and girls

Background: Although early in life there is little discernible difference in bone mass between boys and girls, at puberty sex differences are observed. It is uncertain if these differences represent differences in bone mass or just differences in anthropometric dimensions. Aim: The study aimed to identify whether sex independently affects bone mineral content (BMC) accrual in growing boys and girls. Three sites are investigated: total body (TB), femoral neck (FN) and lumbar spine (LS). Subjects and methods: 85 boys and 67 girls were assessed annually for seven consecutive years. BMC was assessed by dual energy X-ray absorptiometry (DXA). Biological age was defined as years from age at peak height velocity (PHV). Data were analysed using a hierarchical (random effects) modelling approach. Results: When biological age, body size and body composition were controlled, boys had statistically significantly higher TB and FN BMC at all maturity levels (p < 0.05). No independent sex differences were found at the LS (p > 0.05). Conclusion: Although a statistical significant sex effect is observed, it is less than the error of the measurement, and thus sex difference are debatable. In general, sex difference are explained by anthropometric difference

Physical Activity and Bone Mineral Accrual During Childhood and Adolescence

The epidemic that is osteoporosis has led to an increasing interest in bone mineral, and the factors that influence the levels of bone mineral, in recent years. While it is unrealistic to try and turn back the clock, a return to an increased level of physical activity may be an important consideration in terms of skeletal health. Peak bone mass is largely determined by heredity, but lifestyle and dietary patterns also influence the level of bone mineral accrued during the growing years. In this review, we summarize the evidence that vigorous weight-bearing physical activity and adequate calcium intake represent the best possibility for enhancing the attainment of an optimal level of bone mineral, within genetic limits.

The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells

Lipid homeostasis is controlled by the peroxisome proliferator-activated receptors (PPARalpha, -beta/delta, and -gamma) that function as fatty acid-dependent DNA-binding proteins that regulate lipid metabolism. In vitro and in vivo genetic and pharmacological studies have demonstrated PPARalpha regulates lipid catabolism. In contrast, PPARgamma regulates the conflicting process of lipid storage. However, relatively little is known about PPARbeta/delta in the context of target tissues, target genes, lipid homeostasis, and functional overlap with PPARalpha and -gamma. PPARbeta/delta, a very low-density lipoprotein sensor, is abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for approximately 40% of total body weight. Skeletal muscle is a metabolically active tissue, and a primary site of glucose metabolism, fatty acid oxidation, and cholesterol efflux. Consequently, it has a significant role in insulin sensitivity, the blood-lipid profile, and lipid homeostasis. Surprisingly, the role of PPARbeta/delta in skeletal muscle has not been investigated. We utilize selective PPARalpha, -beta/delta, -gamma, and liver X receptor agonists in skeletal muscle cells to understand the functional role of PPARbeta/delta, and the complementary and/or contrasting roles of PPARs in this major mass peripheral tissue. Activation of PPARbeta/delta by GW501516 in skeletal muscle cells induces the expression of genes involved in preferential lipid utilization, beta-oxidation, cholesterol efflux, and energy uncoupling. Furthermore, we show that treatment of muscle cells with GW501516 increases apolipoprotein-A1 specific efflux of intracellular cholesterol, thus identifying this tissue as an important target of PPARbeta/delta agonists. Interestingly, fenofibrate induces genes involved in fructose uptake, and glycogen formation. In contrast, rosiglitazone-mediated activation of PPARgamma induces gene expression associated with glucose uptake, fatty acid synthesis, and lipid storage. Furthermore, we show that the PPAR-dependent reporter in the muscle carnitine palmitoyltransferase-1 promoter is directly regulated by PPARbeta/delta, and not PPARalpha in skeletal muscle cells in a PPARgamma coactivator-1-dependent manner. This study demonstrates that PPARs have distinct roles in skeletal muscle cells with respect to the regulation of lipid, carbohydrate, and energy homeostasis. Moreover, we surmise that PPARgamma/delta agonists would increase fatty acid catabolism, cholesterol efflux, and energy expenditure in muscle, and speculate selective activators of PPARbeta/delta may have therapeutic utility in the treatment of hyperlipidemia, atherosclerosis, and obesity.

Role of HuR in skeletal myogenesis through coordinate regulation of muscle differentiation genes

In this report, we investigate the role of the RNA-binding protein HuR during skeletal myogenesis. At the onset of myogenesis in differentiating C2C12 myocytes and in vivo in regenerating mouse muscle, HuR cytoplasmic abundance increased dramatically, returning to a predominantly nuclear presence upon completion of myogenesis. mRNAs encoding key regulators of myogenesis-specific transcription (myogenin and MyoD) and cell cycle withdrawal (p21), bearing AU-rich regions, were found to be targets of HuR in a differentiation-dependent manner. Accordingly, mRNA half-lives were highest during differentiation, declining when differentiation was completed. Importantly, HuR-overexpressing C2C12 cells displayed increased target mRNA expression and half-life and underwent precocious differentiation. Our findings underscore a critical function for HuR during skeletal myogenesis linked to HuR's coordinate regulation of muscle differentiation genes.

3: Rehabilitation principles for treating chronic musculoskeletal injuries

Evaluation of patients for rehabilitation after musculoskeletal injury involves identifying, grading and assessing the injury and its impact on the patient's normal activities. Management is guided by a multidisciplinary team, comprising the patient, doctor and physical therapist, with other health professionals recruited as required. Parallel interventions involving the various team members are specified in a customised management plan. The key component of the plan is active mobilisation utilising strengthening, flexibility and endurance exercise programs. Passive physical treatments (heat, ice, and manual therapy), as well as drug therapy and psychological interventions, are used as adjunctive therapy. Biomechanical devices or techniques (eg, orthotic devices) may also be helpful. Coexisting conditions such as depression and drug dependence are treated at the same time as the injury. Effective team communication, simulated environmental testing and, for those employed, contact with the employer facilitate a staged return to normal living, sports and occupational activities.

Effect of poling state and morphology of piezoelectric poly(vinylidene fluoride) membranes for skeletal muscle tissue engineering

This work reports on the influence of polarization and morphology of electroactive poly(vinylidene fluoride), PVDF, on the biological response of myoblast cells. Non-poled, ‘‘poled +’’ and “poled-“ -PVDF were prepared in the form of films. Further, random and aligned electrospun -PVDF fiber mats were also prepared. It is demonstrated that negatively charged surfaces improve cell adhesion and proliferation and that the directional growth of the myoblast cells can be achieved by the cell culture on oriented fibers. Therefore, the potential application of electroative materials for muscle regeneration is demonstrated.

Analysis of the return on preventive measures in musculoskeletal disorders through the benefitecost ratio: A case study in a hospital

Work-related musculoskeletal disorders (WMSDs) are among the most costly health problems that society is facing today. Prevention involves investments and it is important for organizations to make a cost ebenefit analysis of ergonomic projects. Return on prevention is a recent concern in the domain of occupational safety and health (OSH). There are many studies concerning the return on the prevention of WMSDs, in terms of the benefits for the organization in which the preventive measures are implemented. However, it is also important to perform an analysis of the impact of each measure on society (externalities). A model to perform a financial and economic costebenefit analysis related to OSH projects was developed and it was applied in the case of the prevention of WMSDs in a Portuguese hospital. An analysis of the accidents and corresponding costs has been made in six of the services of the hospital. Financial and an economic costebenefit analysis have been made and the benefitecost ratio (B/C) has been calculated. While the B/C financial ratio, considering only the benefits to the hospital, is around 2, the economic B/C ratio, taking into account all the external benefits that have been quantified, is higher than 14. Relevance to industry: Both the economic and the financial B/C ratio are important support tools for decision makers in public and private organizations, helping them to define which preventive measures should be implemented, taking into account the costs involved and the resulting quantified benefits, for the organization, for the workers and for the society.