Innovative playgrounds: use, physical activity, and implications for health.

OBJECTIVES: The aim of the study is to assess the use and levels of moderate-to-vigorous physical activity (MVPA) occurring in innovative playgrounds in London vs. traditional playgrounds in the US in neighborhoods with a similar population density. STUDY DESIGN: This is a cross-sectional observational study. METHODS: We selected a sample of London playgrounds based on their innovative design. One group of eight playgrounds was matched to the US playgrounds by size and population density; a second group of very large London playgrounds was matched only by population density. Playground use and person-hours of MVPA were measured using direct observation at similar times of the day and days of the week in all locations. RESULTS: The number of playground visit hours was 58% higher in London than in the US (394 vs 249). The matched London playgrounds had 37.8% more children and 129% more adults who were, respectively, engaging in 90% and 116% more MVPA. While the London playgrounds were nearly 8.5 times larger than the US ones, they attracted a total of 5.8 times more visitors (1399 vs 243, P < .0001), and this included 10 times as many adults (679 vs. 66, P < .0001) and 7.5 times more seniors (23 vs. 3). The London playgrounds included more amenities targeting adults. CONCLUSIONS: The design of an innovative playground was associated with the amount of MVPA in similar-sized playgrounds, but the size of the playground was more strongly associated with the number of visitors. It is as important to design playgrounds for adults as it is for children to increase visit hours.

Development of an autologous canine cancer vaccine system for resectable malignant tumors in dogs.

While conventional therapies exist for canine cancer, immunotherapies need to be further explored and applied to the canine setting. We have developed an autologous cancer vaccine (K9-ACV), which is available for all dogs with resectable disease. K9-ACV was evaluated for safety and immunogenicity for a variety of cancer types in a cohort of companion dogs under veterinary care. The autologous vaccine was prepared by enzymatic digestion of solid tumor biopsies. The resultant single cell suspensions were then UV-irradiated resulting in immunogenic cell death of the tumor cells. Following sterility and endotoxin testing, the tumor cells were admixed with CpG ODN adjuvant and shipped to the participating veterinary clinics. The treating veterinarians then vaccinated each patient with three intradermal injections (10 million cells per dose) at 30-day intervals (one prime and two boost injections). In a cohort of 20 dogs completing the study, 17 dogs (85%) developed an augmented IgG response to autologous tumor antigens as demonstrated using western blot analysis of pre- and post-peripheral blood samples. We also report several dogs have lived beyond expected survival time based on previously published data. In summary, K9-ACV is an additional option to be considered for the treatment of dogs with resectable cancer.

Obesity prevention at the point of purchase.

The point of purchase is when people may make poor and impulsive decisions about what and how much to buy and consume. Because point of purchase strategies frequently work through non-cognitive processes, people are often unable to recognize and resist them. Because people lack insight into how marketing practices interfere with their ability to routinely eat healthy, balanced diets, public health entities should protect consumers from potentially harmful point of purchase strategies. We describe four point of purchase policy options including standardized portion sizes; standards for meals that are sold as a bundle, e.g. 'combo meals'; placement and marketing restrictions on highly processed low-nutrient foods; and explicit warning labels. Adoption of such policies could contribute significantly to the prevention of obesity and diet-related chronic diseases. We also discuss how the policies could be implemented, along with who might favour or oppose them. Many of the policies can be implemented locally, while preserving consumer choice.

Appropriate antimicrobial therapy in the era of multidrug-resistant human pathogens.

The past decade has brought a significant rise in antimicrobial resistance, and the ESKAPE pathogens have become a significant threat to public health. Three epidemiological features that negatively impact patients, which are consistently seen with the ESKAPE pathogens, are the following: 1) there has been a rise in incidence of these organisms as causative human pathogens, 2) there has been a significant increase in antimicrobial resistance in these bacterial species, and 3) the infections caused by these resistant strains are associated with worse outcomes when compared with infections caused by their susceptible counterparts. Significant delays in time to appropriate antimicrobial therapy of up to 5 days have been reported in infections due to these organisms and this is the strongest predictor of mortality with ESKAPE pathogens, particular in critically ill patients, where every hour delay has an incremental survival disadvantage for patients. Strategies to decrease these delays are urgently needed. Although routine broad-spectrum empiric coverage for these organisms would ideally limit this delay, agents with activity against these organisms are sometimes less effective, have significant toxicity risk, and their use can result in the development of resistance. Therefore, strategies to optimize therapy, although limiting unnecessary use of broad-spectrum antimicrobials, are urgently needed. This review will discuss potential strategies to optimize empiric therapy in the age of multi-drug resistance, the limitations of these strategies, and will discuss future directions and opportunities.

Use of neighbourhood parks: does socio-economic status matter? A four-city study.

OBJECTIVES: To determine if neighbourhood socio-economic status (SES) is associated with park use and park-based physical activity. STUDY DESIGN: Cross-sectional study. METHODS: The use and characteristics of 24 neighbourhood parks in Albuquerque, Chapel Hill/Durham, Columbus and Philadelphia were observed systematically in three seasons (spring, summer and autumn), with nearly 36,000 park users observed. Twelve parks were in high-poverty neighbourhoods and 12 parks were in low-poverty neighbourhoods. In total, 3559 park users and 3815 local residents were surveyed. Park incivilities were assessed and park administrators were interviewed about management practices. RESULTS: The size and number of facilities in parks in high-poverty neighbourhoods were similar to those in parks in low-poverty neighbourhoods, but the former had more hours of programming. Neighbourhood poverty level, perception of safety and the presence of incivilities were not associated with the number of park users observed. However, programmed activities and the number of activity facilities were strongly correlated with park use and energy expended in the park. CONCLUSIONS: The finding that park programming is the most important correlate of park use and park-based physical activity suggests that there are considerable opportunities for facilitating physical activity among populations of both high- and low-poverty areas.

Impact of two pulmonary enteral formulations on nutritional indices and outcomes.

BACKGROUND: Enteral nutrition formulas enriched with eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) may modulate inflammatory processes and improve outcomes in mechanically-ventilated patients with respiratory failure. The present study aimed to determine whether there were differences in nutritional indices (protein intake, energy intake, fat intake) and outcomes [days on mechanical ventilation, days in the intensive care unit (ICU)] between mechanically-ventilated subjects who received a standard pulmonary enteral formula compared to those who received an EPA/GLA enriched pulmonary enteral formula. METHODS: Data on 50 adult subjects who were admitted to an ICU in a community hospital who required both mechanical ventilation and enteral nutrition support were collected (n = 19 in the standard enteral formula group; n = 31 in the EPA/GLA-enriched enteral formula group). The present study involved both retrospective and prospective data. RESULTS: Subjects who were provided the EPA/GLA enriched enteral formula received significantly more enteral formula volume (P = 0.011), total fat (P < 0.0005) and total energy (P = 0.017) than subjects who were provided the standard enteral formula. When controlling for the effects of enteral formula volume, total fat intake and total energy intake as confounding variables, there were no significant differences between the enteral formula groups in ICU days (P = 0.440) or hours spent on mechanical ventilation (P = 0.410). CONCLUSIONS: The use of a specialised pulmonary enteral formulation did not result in any statistically significant effects on ICU days and hours on mechanical ventilation. Subjects who were on the specialised formula did receive more enteral formula volume and more total energy intake, which may be clinically important. Further clinical studies are needed to address the impact that a specialised pulmonary enteral formula has on ICU stay and ventilator hours.

Contextual influences on eating behaviours: heuristic processing and dietary choices.

This paper reviews some of the evidence that dietary behaviours are, in large part, the consequence of automatic responses to contextual food cues, many of which lead to increased caloric consumption and poor dietary choices. We describe studies that illustrate how these automatic mechanisms underlie eating behaviours, as well as evidence that individuals are subject to inherent cognitive limitations, and mostly lack the capacity to consistently recognize, ignore or resist contextual cues that encourage eating. Restaurants and grocery stores are the primary settings from which people obtain food. These settings are often designed to maximize sales of food by strategically placing and promoting items to encourage impulse purchases. Although a great deal of marketing research is proprietary, this paper describes some of the published studies that indicate that changes in superficial characteristics of food products, including packaging and portion sizes, design, salience, health claims and labelling, strongly influence food choices and consumption in ways for which people generally lack insight. We discuss whether contextual influences might be considered environmental risk factors from which individuals may need the kinds of protections that fall under the mission of public health.

Targeted deletion of MyD88 in intestinal epithelial cells results in compromised antibacterial immunity associated with downregulation of polymeric immunoglobulin receptor, mucin-2, and antibacterial peptides.

Intestinal epithelial cells (IECs) form a physical and immunological barrier that separates the vast gut microbiota from host tissues. MyD88-dependent Toll-like receptor signaling is a key mediator of microbial-host cross-talk. We examined the role of epithelial MyD88 expression by generating mice with an IEC-targeted deletion of the Myd88 gene (MyD88(ΔIEC)). Loss of epithelial MyD88 signaling resulted in increased numbers of mucus-associated bacteria; translocation of bacteria, including the opportunistic pathogen Klebsiella pneumoniae, to mesenteric lymph nodes; reduced transmucosal electrical resistance; impaired mucus-associated antimicrobial activity; and downregulated expression of polymeric immunoglobulin receptor (the epithelial IgA transporter), mucin-2 (the major protein of intestinal mucus), and the antimicrobial peptides RegIIIγ and Defa-rs1. We further observed significant differences in the composition of the gut microbiota between MyD88(ΔIEC) mice and wild-type littermates. These physical, immunological, and microbial defects resulted in increased susceptibility of MyD88(ΔIEC) mice to experimental colitis. We conclude that MyD88 signaling in IECs is crucial for maintenance of gut homeostasis.

Nutrition standards for away-from-home foods in the USA.

Away-from-home foods are regulated with respect to the prevention of food-borne diseases and potential contaminants, but not for their contribution to dietary-related chronic diseases. Away-from-home foods have more calories, salt, sugar and fat, and include fewer fruits and vegetables than recommended by national nutrition guidelines. Thus, frequent consumption of away-from-home foods contributes to obesity, hypertension, diabetes, heart disease, and cancer. In light of this, many localities are already adopting regulations or sponsoring programs to improve the quality of away-from-home foods. We review the rationale for developing nutritional performance standards for away-from-home foods in light of limited human capacity to regulate intake or physiologically compensate for a poor diet. We offer a set of model performance standards to be considered as a new area of environmental regulation. Models for voluntary implementation of consumer standards exist in the environmental domain and may be useful templates for implementation. Implementing such standards, whether voluntarily or via regulations, will require addressing a number of practical and ideological challenges. Politically, regulatory standards contradict the belief that adults should be able to navigate dietary risks in away-from-home settings unaided.

Granzyme B-mRNA expression by equine lymphokine activated killer (LAK) cells is associated with the induction of apoptosis in target cells.

Lymphokine-activated killer (LAK) cells are a subset of cytotoxic cells capable of lysing freshly isolated tumor cells. While LAK activity is typically measured using the (51)Cr-release assay, here we used a non-radioactive flow cytometric method to demonstrate equine LAK activity. Equine peripheral blood mononuclear cells (PBMC) were stimulated in vitro with recombinant human interleukin 2 (hIL-2) to generate LAK cells. An equine tumor cell line, EqT8888, labeled with carboxyfluorescein succinimidyl ester (CFSE) was used as target cells. Following incubation of the targets with different concentrations of LAK cells, Annexin V was added to identify the early apoptotic cells. With increasing effector to target cell ratios, EqT8888 apoptosis was increased. We also measured interferon-gamma, granzyme B and perforin mRNA expression in the LAK cell cultures as possible surrogate markers for cytotoxic cell activity and found granzyme B mRNA expression correlated best with LAK activity. Also, we found that the reduced LAK activity of young horses was associated with decreased granzyme B mRNA expression. Our results indicate that fluorescence-based detection of LAK cell activity provides a suitable non-radioactive alternative to (51)Cr-release assays and mRNA expression of granzyme B can be used as surrogate marker for these cytotoxic cells.

Inside the fitness for work consultation: a qualitative study.

BACKGROUND: Evidence now suggests that work is generally good for physical and mental health and well-being. Worklessness for whatever reason can lead to poorer physical and mental health. The role of the general practitioner (GP) in the management of fitness for work is pivotal. AIMS: To understand the interaction between GP and patient in the fitness for work consultation. This study forms part of a larger research project to develop a learning programme for GPs around the fitness for work consultation based on behaviour change methodology. METHODS: A qualitative study set in South Wales. Structured discussion groups with seven GPs. Two sessions each lasting 3 h were conducted to explore the GP and patient interaction around the fitness for work consultation. Multiple methods were used to enhance engagement. Thematic analysis was used to analyse the data. RESULTS: Four major themes emerged from the meetings: role legitimacy, negotiation, managing the patient and managing the systems. Within these, subthemes emerged around role legitimacy. 'It's not my job', 'It's not what I trained for' and the 'shifting agenda' Negotiation was likened to 'A polite tug of war' and subthemes around decision making, managing the agenda and dealing with uncertainty emerged. CONCLUSIONS: This study starts to unravel the complexity of the fitness for work consultation. It illustrates how GPs struggle with the 'importance' of their role and 'confidence' in managing the fitness for work consultation. It addresses the skillful negotiation that is required to manage the consultation effectively.

Obesity and the built environment: changes in environmental cues cause energy imbalances.

The past 30 years have seen dramatic changes in the food and physical activity environments, both of which contribute to the changes in human behavior that could explain obesity. This paper reviews documented changes in the food environment, changes in the physical activity environment and the mechanisms through which people respond to these environments, often without conscious awareness or control. The most important environmental changes have been increases in food accessibility, food salience and decreases in the cost of food. The increases in food marketing and advertising create food cues that artificially stimulate people to feel hungry. The existence of a metabolic pathway that allows excess energy to be stored as fat suggests that people were designed to overeat. Many internal mechanisms favor neurophysiologic responses to food cues that result in overconsumption. External cues, such as food abundance, food variety and food novelty, cause people to override internal signals of satiety. Other factors, such as conditioning and priming, tie food to other desirable outcomes, and thus increase the frequency that hunger is stimulated by environmental cues. People's natural response to the environmental cues are colored by framing, and judgments are flawed and biased depending on how information is presented. People lack insight into how the food environment affects them, and subsequently are unable to change the factors that are responsible for excessive energy consumption. Understanding the causal pathway for overconsumption will be necessary to interrupt the mechanisms that lead to obesity.

Macrophage-mediated neuroprotection and neurogenesis in the olfactory epithelium.

Resident and recruited olfactory epithelial macrophages participate in the regulation of the survival, degeneration, and replacement of olfactory sensory neurons (OSNs). We have reported that liposome-encapsulated clodronate (Lip-C) induced selective and statistically significant depletion of macrophages in the OE of sham and 48 h OBX mice (38 and 35%, respectively) that resulted in increased OSN apoptosis and decreased numbers of mature OSNs and proliferating basal cells compared to controls (Lip-O). The aim of this study was to identify molecular mechanisms by which the selective depletion of macrophages in the OE resulted in these cellular changes by using a microarray expression pattern analysis. A 2x2 ANOVA identified 4,085 overall significantly (P < 0.01) regulated genes in the OE of Lip-O and Lip-C sham and 48 h OBX mice, and further statistical analysis using pairwise comparisons identified 4,024 genes that had either a significant (P < 0.01) treatment main effect (n = 2,680), group main effect (n = 778), or interaction effect (n = 980). The mean hybridization signals of immune response genes, e.g., Cxcr4, and genes encoding growth factors and neurogenesis regulators, e.g., Hdgf and Neurod1, respectively, were primarily lower in Lip-C mice compared with Lip-O mice. Apoptosis genes, e.g., Bak1, were also differentially regulated in Lip-C and/or OBX mice. Expression patterns of selected genes were validated with real-time RT-PCR; immunohistochemistry was used to localize selected gene products. These results identified the differential regulation of several novel genes through which alternatively activated macrophages regulate OSN progenitor cell proliferation, differentiation, and maturation, and the survival of OSNs.

The collectivity of sexual behaviour.

Human behaviour can be viewed as a collective phenomenon, determined partly by the group to which individuals belong. Collectivities of health behaviour have been found in alcohol consumption, hypertension, obesity, mental illness, and sodium intake in that the average level of risk is associated with the percentage of individuals at extremely high risk.The goal was to investigate whether sexual behaviour may be collectively determined. A cross-sectional US survey was conducted. Across 45 states, the mean number of lifetime sex partners excluding persons with >10, >20, and >40 lifetime partners was strongly associated with the proportion with >10, > 20 and > 40 lifetime sex partners, respectively, among men and women. Sexual activity may represent collectively determined behaviour. If so, interventions to reduce high-risk sexual behaviour to prevent HIV or sexually transmitted diseases (STDs) may be more effective if they address the entire population, rather than target only those at the extremes of risk.

Suburban sprawl and physical and mental health.

OBJECTIVE: To study the association between objective measures of suburban sprawl and chronic medical conditions and mental health disorders in the USA. METHODS: Cross-sectional analysis of survey data merged with objective measures of suburban sprawl. Outcomes are self-reported medical conditions, mental health disorders and health-related quality of life. RESULTS: Sprawl significantly predicts chronic medical conditions and health-related quality of life, but not mental health disorders. An increase in sprawl from one standard deviation less to one standard deviation more than average implies 96 more chronic medical problems per 1000 residents, which is approximately similar to an aging of the population of 4 years. CONCLUSIONS: A robust association between sprawl and physical (but not mental) health suggests that suburban design may be an important new avenue for health promotion and disease prevention.

Idiopathic pneumonia syndrome after bone marrow transplantation: the role of pre-transplant radiation conditioning and local cytokine dysregulation in promoting lung inflammation and fibrosis.

Pulmonary complications and graft-vs.-host disease (GVHD) remain severe threats to survival after bone marrow transplantation (BMT). Idiopathic pneumonia syndrome (IPS) accounts for nearly 50% of all the cases of interstitial pneumonitis after BMT. IPS is characterized by an early inflammatory phase followed by chronic inflammation and fibrosis of lung tissue; however, the immunopathogenesis of this disease is not yet clearly understood. This biphasic syndrome has been reported to be associated with pre-transplant radiation conditioning in some studies while others have suggested that GVHD or autoimmune phenomena may be responsible for its development. The early post-BMT phase is characterized by the presence of inflammatory cytokines whose net effect is to promote lymphocyte influx into lungs with minimal fibrosis, that leads to an acute form of graft-vs.-host reaction-mediated pulmonary tissue damage. Gradual changes over time in leucocyte influx and activation lead to dysregulated wound repair mechanisms resulting from the shift in the balance of cytokines that promote fibrosis. Using data from new animal models of IPS and information from studies of human IPS, we hypothesize that cytokine-modulated immunological mechanisms which occur during the acute and chronic phases after bone marrow transplantation lead to the development of the progressive, inflammatory, and fibrotic lung disease typical of idiopathic pneumonia syndrome.

Bleomycin-induced pulmonary fibrosis is independent of eosinophils.

Eosinophils have been shown to increase in tissues during many fibrotic conditions and consequently have been suggested to contribute to the development of fibrosis. This study tested the hypothesis that eosinophils are essential in the development of lung fibrosis in mice in response to bleomycin (BLM). Anti-IL-5 antibody was administered intraperitoneally into mice 2 h prior to endotracheal BLM inoculation and thereafter, every other day. Lung eosinophilia was evaluated by measurement of eosinophil peroxidase activity and confirmed by eosinophil counts in histologic sections. Lung fibrosis was evaluated by hydroxyproline content and confirmed by collagen staining in histological sections. Results demonstrated that BLM induced pronounced lung eosinophilia, which was maximal 7 days after BLM treatment and remained elevated through day 14, in C57B1/6 SCID mice and CBA/J mice. In contrast, eosinophilia was a minor component in the lungs of wildtype C57B1/6 mice after BLM treatment, although lung fibrosis developed similarly in all three strains of mice. Treatment with anti-IL-5 completely abrogated eosinophilia but failed to block pulmonary fibrosis induced by BLM in all mouse strains, including C57B1/6 SCID, wildtype C57B1/6 mice, and CBA/J mice. Analysis of cytokine mRNA by RNase-protection assay in C57B1/6 SCID mice indicated that BLM treatment caused enhanced expression of the cytokines, TNF-alpha, and IL-6 at days 3, 7, and 14 post-BLM inoculation, regardless of whether eosinophils were depleted by anti-IL-5. Finally, the importance of eosinophils in lung fibrosis was examined in IL-5 gene knockout mice (IL-5tm1Kopf). BLM treatment induced significant lung fibrosis in IL-5 knockout mice in the absence of eosinophilia. These findings indicate that eosinophils are not an absolute requirement for BLM-induced pulmonary fibrosis in the mouse.

Participation in a school-based sexually transmitted disease screening program.

BACKGROUND: A school-based chlamydia screening program was offered repeatedly in three Louisiana public high schools in an effort to expand sexually transmitted disease screening services for adolescents. GOAL: To describe participation of a fixed cohort of students to elucidate the impact of screening on chlamydia prevalence. STUDY DESIGN: Five opportunities for chlamydia testing were offered in 3 schools during 3 school years (1995-1996, 1996-1997, 1997-1998). Only students with parental consent could be tested. Students consistently enrolled during the 3 years (n = 1475) were included in this analysis. RESULTS: During the 3 school years, parental consent was cumulatively obtained for 1443 students (97.8%), and 1305 students (88.5%) were tested at least once. Of those tested, 81.1% tested more than once. The prevalence of Chlamydia trachomatis infection at first test among students who tested more than once was 1.8% for males and 7.7% for females. Among students tested only once, 6.2% of males and 12.7% of females had chlamydial infection. Among students tested more than once, no significant difference in C. trachomatis prevalence was associated with repeat screenings. Incidence rates per 1000 person-months were 4.3 (2.2, males; 7.1, females; P < 0.0001). Reinfections explained only 5.6% of all incident cases. CONCLUSION: The documented high response from both parents and students to this school-based chlamydia screening program offers great promise for sexually transmitted disease control among adolescents. Overall, C. trachomatis prevalence was two times higher among students testing only once than among those testing more than once. Routine and continued availability of school-based chlamydia screening programs can potentially reduce the burden of disease among adolescents.