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Effects of low-frequency stimulation on soluble and structure-bound activities of hexokinase and phosphofructokinase in rat fast-twitch muscle.

Several glycolytic enzymes exist in muscle as free and structure-bound forms. A fraction of hexokinase (HK) is associated with the outer mitochondrial membrane. Phosphofructokinase (PFK) and aldolase (ALD) bind to F-actin, and AMP deaminase (AMPase) interacts with myosin. Using low-frequency stimulation (10 Hz, 24 h/d), we studied in rat fast-twitch muscle effects of contractile activity on soluble and structure-bound forms of these enzymes. Phosphoglucose isomerase (PGI), a soluble enzyme, was also examined. Fractional extraction was applied to study the intracellular distribution of soluble and bound enzyme activities 5 min, 1 h, 3 h, 1 d, and 7 d after the onset of stimulation. Confirming previous findings, total HK activity increased 7-fold in 7-d-stimulated muscles, whereas PFK, ALD, and PGI were reduced, ranging between 55% and 80% of their normal activities. AMPase activity was unaltered. At the time points studied, no changes were found in the extraction behavior of PGI and AMPase. The fraction of bound ALD increased slightly (12%). However, the distribution of HK and PFK was markedly altered. Bound PFK increased from 50% in the control to 85% in 7-d-stimulated muscles. Bound HK rose from 52% to 83% during the same time period. The increase in PFK binding was steep and occurred mainly within the first minutes and hours. The increase in HK binding occurred with some delay, but was significant in muscles stimulated for more than 1 h. In view of the altered kinetic properties of F-actin-bound PFK (alleviated allosteric inhibition by ATP) and bound HK (elevated catalytic activity), these changes are interpreted as early responses to match the metabolic demands during maximal contractile activity imposed on a muscle not programmed for sustained activity: Enhanced binding of PFK serves to accelerate glycolytic flux immediately after the onset of stimulation, whereas mitochondrial binding of HK facilitates the phosphorylation of exogenous glucose when glycogen stores have been depleted.

Animals↗

International conferences on environmental mutagens in human populations-opportunities, accomplishments and challenges.

A major mission for organizing the series of International Conferences on Environmental Mutagens in Human Populations is to bring science and scientists to the sites where the field of environmental health is in developmental stages and environmental health is a serious concern. The mission has been fulfilled in each of the previous conferences that were held in Egypt, Czech Republic, Thailand and Brazil. These conferences have led to significant enhancement of regional scientific expertise from the acquisition of scientific knowledge and from the generation of sustainable collaborative programs.

Environment↗

Local inflammation as a possible mechanism of resistance to gastrointestinal nematodes in Angus heifers.

Understanding mechanisms of resistance to gastrointestinal nematodes is important in developing effective and sustainable control programs. A resource population of Angus cattle consisting of approximately 600 animals with complete pedigree records has been developed. The majority of these animals were completely characterized for their resistance to natural challenge by gastrointestinal nematodes. As the first step towards understanding the molecular basis of disease resistance, we investigated expression profiles of 17 cytokines, cytokine receptors, and chemokines using real-time RT-PCR in animals demonstrating resistance or susceptibility to pasture challenge. The animals exposed to natural infection for approximately 6 months were treated to remove existing parasites and then experimentally challenged with both Ostertagia ostertagi and Cooperia oncophora. The mRNA expression profiles of these genes in abomasal and mesenteric lymph nodes (ALN, MLN), fundic and pyloric abomasa (FA, PA), and small intestine (SI) were compared between resistant and susceptible animals. Resistant heifers exhibited elevated expression of inflammatory cytokines such as TNFalpha, IL-1beta, and MIP-1alpha in fundic and pyloric abomasa 7 days post infection. Expression levels of IL-10, polymeric immunoglobullin receptor gene (PIGR), and WSX-1 were also 2.7-19.9-folds higher in resistant than susceptible heifers in these tissues. No difference in expression of CXCL6, CXCL10, IFN-gamma, IL-2, IL-4, IL-6, IL-8, IL-12 p40, IL-13, IL-15 and IL-18 was observed between the two groups. The expression of MIP-1alpha, IL-6, and IL-10 was also elevated in small intestines in resistant animals. In contrast, little difference in expression of these genes was detected between resistant and susceptible groups in the draining lymph nodes. These data indicate that resistant animals can better maintain inflammatory responses at the site of infection, suggesting a possible novel mechanism of resistance.

Animals↗

Telehealth: 'real life' implementation issues.

This paper addresses the practical issues specific to the successful integration of telehealth into the Canadian health system at national, regional, provincial and territorial levels. Five key issues for optimal implementation were readiness of the environment; needs analysis/strategic business plans/diverse partnerships; equipment and Information Technology (IT) vendors; staged implementation; and evaluation. Strong professional, as well as technical policy standards, were also required. Recognizing the importance of human factors and workforce implications, the change process, and the changing culture were also viewed as critical to successful implementation. The importance of 'best practices', 'lessons learned', 'buy-in', inter-connectivity, inter-operability, and sustainability issues was noted. Lastly, ongoing systemic evaluation was seen to be key to sustained telehealth programs.

Canada↗

Enhancing school-based prevention and youth development through coordinated social, emotional, and academic learning.

A comprehensive mission for schools is to educate students to be knowledgeable, responsible, socially skilled, healthy, caring, and contributing citizens. This mission is supported by the growing number of school-based prevention and youth development programs. Yet, the current impact of these programs is limited because of insufficient coordination with other components of school operations and inattention to implementation and evaluation factors necessary for strong program impact and sustainability. Widespread implementation of beneficial prevention programming requires further development of research-based, comprehensive school reform models that improve social, health, and academic outcomes; educational policies that demand accountability for fostering children's full development; professional development that prepares and supports educators to implement programs effectively; and systematic monitoring and evaluation to guide school improvement.

Adolescent↗

Quantifying genetic and genotypic gain gaps in Eucalyptus: the hidden cost of ignoring inbreeding and dominance.

Understanding the mating system of Eucalyptus species is necessary to accurately estimate genetic parameters and improve breeding programs. Eucalyptus species often exhibit mixed mating systems, leading to complex relationships among progenies. Traditional tree breeding programs that assume a half-sibling relationship for open-pollinated (OP) trials may overestimate genetic gains by neglecting the effects of inbreeding and dominance. This study focuses on Eucalyptus pellita, a species with a mixed mating system, to quantify the impact of selfing and dominance on breeding strategies. We simulated OP trial growth data for 100 randomly selected families in a randomized complete block design, using published estimated parameters for diameter at breast height (DBH). Our analysis indicated that marker-based models, particularly those incorporating dominance effects, provide more accurate genetic parameter estimates and larger predicted genetic gains than pedigree-based models. These results reveal pronounced genetic and genotypic gain gaps when traditional models are employed, underscoring the imperative for integrating dominance-informed genomic selection strategies. Thus, our study provides essential guidance for optimizing breeding programs to sustainably enhance productivity and genetic quality in Eucalyptus plantations.

Eucalyptus↗

Evaluating a suicide prevention program: a question of impact.

ISSUE ADDRESSED: This paper explores the evaluation objectives of a suicide prevention program known as the Regional Trainers Sustainability Plan. The program aims to train practitioners to intervene appropriately where they come into contact with individuals who show suicide risk. As evaluators we argue for the critical role of impact evaluation in determining how well programs achieve their ultimate objectives, however, in this case our ability to know that suicide prevention has taken place is limited. METHODS: As a suicide prevention program, performance information about the effect of the program activity was difficult to define and obtain because of cautions about the interpretation and use of measures such as 'how many lives were saved'. As a second-best option, we defined the program in terms of a set of goals that ranged from lower order to higher order. This helped to avoid unrealistic and unfounded conclusions being drawn from the data collected. CONCLUSIONS: Organising performance information into a series of levels clarified what the information collected could prove and what it could not prove. This layout also helped to demonstrate links between activities and suicide prevention and, despite an impact evaluation being unobtainable, a level of confidence in the program's worth was gained. However, our paper maintains that this does not replace the value and importance of thorough impact evaluation, given that very little is known about what works in the suicide prevention area.

Evidence-Based Medicine↗

Cocaine abuse in methadone maintenance programs: integrating pharmacotherapy with psychosocial interventions.

Cocaine abuse by methadone-maintained patients threatens to undermine the success of methadone programs by sustaining a drug-abusing lifestyle as well as contributing to the spread of HIV. The search for a pharmacotherapeutic agent for the treatment of cocaine has met with limited success. The most promising results emerge when specific agents, such as desipramine, are matched appropriately to specific patient characteristics, such as depression or antisocial personality disorder. For some patients, abstinence from cocaine may also require the addition of intensive psychosocial treatments that target the considerable problems faced by inner-city opioid-addicted individuals. This article discusses ways in which future research could be directed toward investigating the interaction between psychosocial services and pharmacologic treatments, while at the same time developing and testing hypotheses concerning appropriate patient-treatment matching variables.

Cocaine↗

CHOICES: promoting early access to end-of-life care through home-based transition management.

CHOICES is a comprehensive home-based care coordination program designed to bridge the gap between home health and hospice for Medicare + Choice enrollees with advanced chronic illness in San Francisco's East Bay region. Key elements of the program include physician education, enrollment of patients with high disease burden who may not be terminally ill, co-management of care with the primary physician, and an advanced practice clinical team that provides comprehensive in-home assessments, a flexible mix of life-prolonging and palliative care that evolves with disease progression, focused education and advance planning, and caregiver support. During a 42-month demonstration, 208 patients were enrolled in the program. Eighty percent had a non-cancer diagnosis; 40% were people of color. After an 8-month follow-up, 44% of the study cohort had died in the program or after transfer to hospice, 51% had been discharged, and 5% remained active. Median length of stay for decedents was 260 days. Preliminary evidence supports the program's feasibility and acceptability to patients, families, physicians, and agency partners. However, the uncertain future of Medicare + Choice and of managed care may jeopardize the program's sustainability. Policymakers and taxpayers will need to determine how to care for the growing number of chronically ill elderly who wish to remain at home as illness advances. The care needs of these patients and their families may overwhelm a health system organized around hospital treatment of acute illness.

Advance Care Planning↗

Long-term effects of exercise on blood pressure and lipids in healthy women aged 40-65 years: The Sedentary Women Exercise Adherence Trial (SWEAT).

OBJECTIVES: To evaluate the long-term effects of regular moderate or vigorous intensity exercise on blood pressure and blood lipids in previously sedentary older women. DESIGN: Subjects were randomly assigned to either a supervised centre-based (CB) or a minimally supervised home-based (HB) exercise program, initially for 6 months. Within each program, subjects were further randomized to exercise either at moderate (40-55% heart rate reserve, HRres) or vigorous intensity (65-80% HRres). After 6 months, all groups continued a HB moderate or vigorous exercise program for another 12 months. METHODS: Healthy, sedentary women (aged 40-65 years) (n = 126) were recruited from the community. Subjects exercised three times per week for 30 min. They were evaluated at baseline, 6, 12 and 18 months. RESULTS: There was a significant fall of 2.81 mmHg in systolic blood pressure (P = 0.049) and 2.70 mmHg in diastolic blood pressure (P = 0.004) after correction for age and baseline values with moderate exercise, but not with vigorous-intensity exercise. When this analysis was repeated with the change in body mass included, the results were unchanged. After correction for potential confounding factors, there was a significant fall in total cholesterol and low density lipoprotein cholesterol with vigorous but not moderate exercise at 6 months (P < 0.05) but not at 18 months. CONCLUSIONS: In this largely normotensive population of older women, a moderate, but not vigorous exercise program, achieved sustained falls in resting systolic and diastolic blood pressure over 18 months. The study demonstrates that, in older women, moderate intensity exercise is well accepted, sustainable long-term and has the health benefit of reduced blood pressure.

Adult↗

Exercise in chronic pulmonary disease: aerobic exercise prescription.

Endurance exercise training (EXT) is singly the most important aspect of rehabilitation for patients with chronic pulmonary disease. When effective, this modality of physical reconditioning leads to improved functional exercise capacity and reduced breathlessness. Early implementation is desirable to obtain more meaningful responses (e.g., when FEV1 falls below 50% of the predicted value in patients with chronic obstructive disease). Preparation for effective EXT requires optimization of respiratory system mechanics (e.g., using bronchodilator therapy), prevention of gas exchange failure (i.e., using supplemental oxygen), nutritional guidance, and psychological support (e.g., to overcome stigmata of disability, fear, and inclination to panic). EXT should be applied using a rigorous, scientifically based aerobic exercise prescription (AXRx) that recognizes basic principles of the human response to exercise prescription while considering individual pathophysiological limitations and identifying safety thresholds for exercise participation. The mode of aerobic exercise should use large muscle groups of the legs (e.g., treadmill or cycle ergometer). The recommended duration is an accumulation of 30 min of exercise per session at the target intensity, achieved by continuous or interval training. EXT should be supervised with a recommended frequency of at least three times per week for 6--8 wk. Target exercise intensity can be monitored by oxygen uptake, work rate, heart rate, or perceived exertion. Target intensity can be determined initially on the basis of 40% of a reference value for maximum oxygen uptake and linked to other variables through predictable interrelationships. All aspects of the AXRx must be reviewed with regard to progression during training. Pulmonary rehabilitation must recognize the importance of achieving clinically meaningful responses (e.g., increased 6-min walking distance of 54 m) as well as the need for maintenance exercise program to sustain the benefits.

Exercise↗

Continuing education in neuroscience nursing.

Since its inception in 1968 the American Association of Neuroscience Nurses (AANN) has devoted the majority of its energy and resources to establishing and maintaining excellence in continuing education (CE). Building and sustaining a program for CE is both challenging and rewarding. AANN, accredited as a provider and approver of CE in nursing by the American Nurses' Association, has awarded hundreds of contact hours to individuals and AANN chapters. It now has the authority to approve CE for any organization or individual meeting specific criteria. In order to promote ongoing growth of its CE program, and thus the knowledge of nurses caring for neuroscience patients, AANN encourages groups and individuals to provide CE and offers this article as assistance. The article defines terms, addresses components of development of CE and offers the opportunity to earn contact hours.

Budgets↗

Determining the optimal developmental route of Strongyloides ratti: an evolutionarily stable strategy approach.

Understanding the processes that drive parasite evolution is crucial to the development of management programs that sustain long-term, effective control of infectious disease in the face of parasite adaptation. Here we present a novel evolutionarily stable strategy (ESS) model of the developmental decisions of a nematode parasite, Strongyloides ratti. The genus Strongyloides exhibits an unusual developmental plasticity such that progeny from an individual may either develop via a direct (homogonic) route, where the developing larvae are infective to new hosts, or an indirect (heterogonic) route, where the larvae develop into free-living, dioecious adults that undergo at least one bout of sexual reproduction outside the host, before producing offspring that develop into infective larvae. The model correctly predicts a number of observed features of the parasite's behavior and shows that this plasticity may be adaptive such that pure homogonic development, pure heterogonic development, or a mixed strategy may be optimal depending on the prevailing environmental conditions, both within and outside the host. Importantly, our results depend only on the benefits of an extra round of reproduction in the environment external to the host and not on benefits to sexual reproduction through the purging of deleterious mutation or the generation of novel, favorable genotypes. The ESS framework presented here provides a powerful, general approach to predict how macroparasites, the agents of many of the world's most important infectious diseases, will evolve in response to the various selection pressures imposed by different control regimes in the future.

Adaptation, Biological↗

Sedentary behaviours among Australian adolescents.

OBJECTIVE: To describe the prevalence and distribution (by demographic characteristics and body mass index [BMI] category) of sedentary behaviour among Australian adolescents aged 11-15 years. METHOD: Cross-sectional representative population survey of school students (n = 2,750) in New South Wales, conducted in 2004. Students' self-reported time spent during a usual week in five categories of sedentary behaviour (small screen recreation [SSR], education, cultural, social and non-active travel). Height and weight were measured. RESULTS: Grade 6, 8 and 10 students spent approximately 34 hours, 41 hours and 45 hours/week of their discretionary time, respectively, engaged in sedentary behaviour. Urban students and students from Asian-speaking backgrounds spent significantly more time sedentary than students from rural areas or other cultural backgrounds. SSR accounted for 60% and 54% of sedentary behaviour among primary and high school students, respectively. Overweight and obese students spent more time in SSR than healthy weight students. Out-of-school hours educational activities accounted for approximately 20% of sedentary behaviour and increased with age. Girls spent twice the time in social activities compared with boys. Time spent in cultural activities declined with age. CONCLUSION: Sedentary behaviours among young people differ according to sex, age and cultural background. At least half of all time spent in sedentary behaviours was spent engaged in SSR. BMI was significantly associated with sedentary behaviour among some children, but not consistently across age groups. IMPLICATIONS: A clear understanding of young people's patterns of sedentary behaviour is required to develop effective and sustainable intervention programs to promote healthy living.

Adolescent↗

Iatrogenic and nurisgenic effects of prolonged immobilization of the ill aged.

The kinesio, phychopathologic and psychosocial effects of prolonged immobilization of the ill aged are outlined. The iatrogenic (physician-induced) and nurisgenic (nurse-induced) factors related to such functional disabilities are described. Illustrative case histories are given. The syndrome is reversible. Thus physicians and nurses have a continued responsibility to support a sustained rehabilitation program for these patients. The biochemical effects of prolonged inactivity indicate that immobilization of the elderly patient results in adverse physical and psychologic phenomena.

17-Ketosteroids↗

Supervised toothbrushing and oral health education program in Kuwait for children and young adults with Down syndrome.

The authors report on the effectiveness of a school-based, supervised toothbrushing program among a group of 112 children with Down syndrome in Kuwait. The study involved 45 boys and 67 girls, who ranged in age from 11-22 years (mean, 14.8 years). The participants had moderate mental retardation and attended one of two special needs schools. Plaque was scored according to the Silness and Löe plaque index and gingivitis according to the Löe and Silness gingival index. Supervised toothbrushing and dental health education sessions were conducted twice a week. The program was evaluated at the end of three months. The mean plaque score decreased from 1.93 to 0.95 (p < 0.001), and the mean gingival score from 2.00 to 0.83 (p < 0.001). This three-month supervised toothbrushing program was effective in reducing plaque and gingivitis scores, but the key to long-term success of the program is sustaining the children's motivation to make oral hygiene a part of their daily life.

Adolescent↗

Challenges to implementing and sustaining comprehensive mental health service programs.

The President's New Freedom Commission recently concluded that the nation's mental health service delivery system is ill equipped to meet the complex needs of persons with mental illness. A major contributor to this service quality crisis has been the longstanding divergence of research efforts and clinical programs. In this article, the authors begin by describing the unique needs of persons with serious and persisting psychiatric disorders and the evolution of the mental health service system that has attempted to meet these needs. They then discuss recent efforts to upgrade services by emphasizing the use of evidence-based practices (EBPs) and the research underlying their development. Next, they describe the difficulties of using traditional research methods to develop and test interventions for persons receiving services at public mental health agencies. Finally, they outline the challenges confronted when trying to disseminate these EBPs to the wider clinical community.

Advisory Committees↗