Using qualitative system dynamics modeling to understand overdose bystander behavior in the context of Connecticut's Good Samaritan Laws and identify effective policy options.

BACKGROUND: Good Samaritan Laws are a harm reduction policy intended to facilitate a reduction in fatal opioid overdoses by enabling bystanders, first responders, and health care providers to assist individuals experiencing an overdose without facing civil or criminal liability. However, Good Samaritan Laws may not be reaching their full impact in many communities due to a lack of knowledge of protections under these laws, distrust in law enforcement, and fear of legal consequences among potential bystanders. The purpose of this study was to develop a systems-level understanding of the factors influencing bystander responses to opioid overdose in the context of Connecticut's Good Samaritan Laws and identify high-leverage policies for improving opioid-related outcomes and implementation of these laws in Connecticut (CT). METHODS: We conducted six group model building (GMB) workshops that engaged a diverse set of participants with medical and community expertise and lived bystander experience. Through an iterative, stakeholder-engaged process, we developed, refined, and validated a qualitative system dynamics (SD) model in the form of a causal loop diagram (CLD). RESULTS: Our resulting qualitative SD model captures our GMB participants' collective understanding of the dynamics driving bystander behavior and other factors influencing the effectiveness of Good Samaritan Laws in the state of CT. In this model, we identified seven balancing (B) and eight reinforcing (R) feedback loops within four narrative domains: Narrative 1 - Overdose, Calling 911, and First Responder Burnout; Narrative 2 - Naloxone Use, Acceptability, and Linking Patients to Services; Narrative 3 - Drug Arrests, Belief in Good Samaritan Laws, and Community Trust in Police; and Narrative 4 - Bystander Naloxone Use, Community Participation in Harm Reduction, and Cultural Change Towards Carrying Naloxone. CONCLUSIONS: Our qualitative SD model brings a nuanced systems perspective to the literature on bystander behavior in the context of Good Samaritan Laws. Our model, grounded in local knowledge and experience, shows how the hypothesized non-linear interdependencies of the social, structural, and policy determinants of bystander behavior collectively form endogenous feedback loops that can be leveraged to design policies to advance and sustain systems change.

Identifying opportunities for collective action around community nutrition programming through participatory systems science.

PURPOSE: To apply principles of group model building (GMB), a participatory systems science approach, to identify barriers and opportunities for collective impact around nutrition programming to reduce cancer risk for immigrant communities in an urban environment. METHODS: We convened four in-person workshops applying GMB with nine community partners to generate causal loop diagrams (CLDs)-a visual representation of hypothesized causal relationships between variables and feedback structures within a system. GMB workshops prompted participants to collaboratively identify programmatic goals and challenges related to (1) community gardening, (2) nutrition education, (3) food assistance programs, and (4) community-supported agriculture. Participants then attended a plenary session to integrate findings from all workshops and identify cross-cutting ideas for collective action. RESULTS: Several multilevel barriers to nutrition programming emerged: (1) food policies center the diets and practices of White Americans and inhibit culturally tailored food guidelines and funding for culturally appropriate nutrition education; (2) the lack of culturally tailored nutrition education in communities is a missed opportunity for fostering pride in immigrant food culture and sustainment of traditional food practices; and (3) the limited availability of traditional ethnic produce in food assistance programs serving historically marginalized immigrant communities increases food waste and worsens food insecurity. CONCLUSION: Emergent themes coalesced around the need to embed cultural tailoring into all levels of the food system, while also considering other characteristics of communities being reached (e.g., language needs). These efforts require coordinated actions related to food policy and advocacy, to better institutionalize these practices within the nutrition space.

Prenatal Consultation Outcomes for Infants With Cleft Lip With and Without Cleft Palate.

To assess the clinical impacts of prenatal consultation with a multidisciplinary cleft team on infants with cleft lip with or without cleft palate (CL ± P).Retrospective cases series.Tertiary pediatric hospital.Infants with CL ± P whose mothers received prenatal consultation with a pediatric otolaryngology team from June 2005 to December 2019 were identified. A random sample of infants with CL ± P without prenatal consultation from June 2005 to December 2019 was also identified.The primary outcomes were the length of hospitalization during the first 12 weeks of life, timing of surgical repair, length of postsurgical hospitalization, and number of unplanned clinic visits and phone calls for feeding evaluation.Time to cleft lip repair differed significantly between the 2 groups with repair performed at 13.4 (±0.9) weeks for the prenatal consultation group (n = 73) and 15.3 (±2.1) weeks for the control group (n = 80), (P < .05). If hospitalization was required for feeding difficulties during the first 12 weeks of life, length of stay was 4.9 (± 1.7) days for infants with prenatal consultation and 11.5 (± 7.2) days for control infants (P < .05). Unplanned clinic visits with a speech-language pathologist (SLP) for feeding difficulties were needed for 2.7% of prenatal consultation infants and 11.3% of control infants (P < .05).Prenatal consultation regarding CL ± P resulted in infants with decreased duration of early hospitalizations, earlier cleft lip repair, and decreased engagement with the SLP feeding clinic for feeding difficulties when compared with infants without prenatal consultation.

Associations of Park Use with Physical Activity in Renovated Parks Serving Low-Income Communities in New York City: Insights from the Community Parks Initiative.

Parks have the potential to encourage physical activity among urban communities. However, existing research on the link between park use and physical activity has produced inconsistent results. Mixed findings in the past may be due in part to differences in park quality across studies. The aim of this study was to explore the association between park use and physical activity among New York City adults in low-income communities that recently received city-sponsored park renovation as part of the Community Parks Initiative (CPI). Using population-weighted survey data from eight neighborhoods with recent park renovation (n = 2,000), we measured associations between park use frequency (≥ once/week vs. < once/week) and self-reported physical activity (high vs. low-moderate based on the International Physical Activity Questionnaire). We adjusted models for age, sex, education, race/ethnicity, income, study site, and use of other (non-CPI) parks, and conducted stratified analysis for demographic variables with significant interactions with park use. After adjusting for covariates, we observed a positive association between park use and physical activity (prevalence ratio [PR] = 1.30, 95% CI = 1.16-1.46). Greater frequency of park use was more strongly associated with high physical activity among adults ≤ 50 y (PR = 1.39, 95% CI = 1.14-1.69), individuals with annual household income < $25,000 (PR = 1.54, 95% CI = 1.13-2.08), and Latinos (PR = 1.77, 95% CI = 1.44-2.18). Our findings suggest that high-quality parks might be particularly beneficial for promoting physical activity among those with a lower socioeconomic background and in younger and Latino adults, emphasizing the importance of continued investment in park revitalization among urban communities of color.

Associations Between Serum Iron Biomarkers and Breast Cancer Tumor Size.

Excess iron has been shown to promote tumor growth in animals whereas iron deficiency has been associated with reduced or slowed tumor growth. The objective of this analysis was to estimate the associations between serum iron biomarkers and tumor size at diagnosis and metastatic status in a sample of breast cancer cases from the Sister Study.The analytic sample included 2,494 incident breast cancer cases with information on tumor size and iron biomarkers, including serum iron (mcg/dL), ferritin (mcg/dL), and percent transferrin saturation, measured in serum collected at baseline. We used Spearman rank correlation and linear regression models to assess the associations between one SD changes in serum iron biomarker levels and natural log of tumor size (cm) adjusting for body mass index and age at study entry.We did not find strong associations between any of the three serum iron biomarkers and tumor size. Adjusted regression slopes (95% confidence interval) were -0.016 (-0.048 to 0.016) for serum iron, -0.032 (-0.064 to <0.001) for ferritin, and -0.010 (-0.043 to 0.023) for transferrin saturation.This study did not provide evidence supporting the hypothesis of a positive association between breast cancer tumor size at diagnosis and prediagnostic serum iron levels. Conflicting evidence between this study and previous research in animal models suggests that iron in the human tumor microenvironment may operate independently of circulating iron or body iron stores.Iron has shown protumorigenic activity in animal models, but our data do not support a positive relationship between breast tumor growth and iron status. SIGNIFICANCE: Using a large sample of women from a U.S. prospective cohort, we assessed associations between several serum iron measures at baseline and breast cancer tumor size and metastatic status. All estimated associations were close to zero with no evidence to support our hypothesis of higher body iron levels associated with larger tumor size. These results suggest the human tumor microenvironment operates independently of circulating serum iron levels.

Universal reverse-transcriptase real-time PCR for infectious hematopoietic necrosis virus (IHNV).

Infectious hematopoietic necrosis virus (IHNV) is an acute pathogen of salmonid fishes in North America, Europe and Asia and is reportable to the World Organization for Animal Health (OIE). Phylogenetic analysis has identified 5 major virus genogroups of IHNV worldwide, designated U, M, L, E and J; multiple subtypes also exist within those genogroups. Here, we report the development and validation of a universal IHNV reverse-transcriptase real-time PCR (RT-rPCR) assay targeting the IHNV nucleocapsid (N) gene. Properties of diagnostic sensitivity (DSe) and specificity (DSp) were defined using laboratory-challenged steelhead trout Oncorhynchus mykiss, and the new assay was compared to the OIE-accepted conventional PCR test and virus isolation in cell culture. The IHNV N gene RT-rPCR had 100% DSp and DSe and a higher estimated diagnostic odds ratio (DOR) than virus culture or conventional PCR. The RT-rPCR assay was highly repeatable within a laboratory and highly reproducible between laboratories. Field testing of the assay was conducted on a random sample of juvenile steelhead collected from a hatchery raceway experiencing an IHN epizootic. The RT-rPCR detected a greater number of positive samples than cell culture and there was 40% agreement between the 2 tests. Overall, the RT-rPCR assay was highly sensitive, specific, repeatable and reproducible and is suitable for use in a diagnostic setting.

Effects of methylene blue photodynamic therapy on oral carcinoma and leukoplakia cells.

Objective: Methylene blue (MB) is a readily available and affordable substrate that can be used as a photosensitizer for photodynamic therapy (PDT). The objective of this study was to determine if PDT with MB can downregulate matrix metalloproteinases (MMPs) related to oral carcinoma. Methods: Cell cultures of oral squamous cell carcinoma (CA-9-22), oral leukoplakia (MSK-Leuk1), and immortalized keratinocytes (Rhek-1A) were photosensitized with MB and treated with PDT. MMP-9 gene expression was interrogated via qRT-PCR. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to confirm the efficacy of MB PDT. Results: MMP-9 gene expression was found to be significantly decreased in oral carcinoma, leukoplakia, and immortalized keratinocytes with use of MB PDT. Conclusion: This work demonstrates that MB-mediated PDT can downregulate MMPs which are critical to the invasion and metastasis of oral cancer. These results suggest that MB PDT could be a clinically significant and cost-effective treatment for oral leukoplakia and carcinoma. Level of Evidence: NA.

An outbreak of Salmonella enterica serotype Choleraesuis in goitered gazelle (Gazella subgutrosa subgutrosa) and a Malayan tapir (Tapirus indicus).

An outbreak of Salmonella enterica serotype Choleraesuis enteritis occurred in two juvenile goitered gazelles and an adult Malayan tapir over a period of 5 wk at the Minnesota Zoo. Diagnosis was made postmortem on one gazelle and one tapir, and a second gazelle was diagnosed via fecal culture. The death of the tapir was attributed to S. enterica serovar Choleraesuis septicemia, while salmonellosis was considered to be a contributing factor besides ostertagiasis for the death of one goitered gazelle and for the diarrhea of another goitered gazelle. A third gazelle became ill in the same time period, but Salmonella infection was not confirmed by culture. All exhibited the clinical signs of profuse, watery diarrhea. The gazelles developed a protein-losing enteropathy, and the tapir showed signs of sepsis and endotoxemia. Serotyping and pulsed-field gel electrophoresis revealed the Salmonella isolates to be indistinguishable from each other. One year prior to this outbreak, Salmonella sp. was cultured from a Visayan warty pig (Sus cebifrons) housed in the same building as the tapir. After further investigation into the outbreak, spread of this pathogen was speculated to be associated with human movement across animal areas.

Peanut sensitisation and allergy: influence of early life exposure to peanuts.

The aim of the present systematic review was to evaluate the influence of early life exposure (maternal and childhood) to peanuts and the subsequent development of sensitisation or allergy to peanuts during childhood. Studies were identified using electronic databases and bibliography searches. Studies that assessed the impact of non-avoidance compared with avoidance or reduced quantities of peanuts or peanut products on either sensitisation or allergy to peanuts, or both outcomes, were eligible. Six human studies were identified: two randomised controlled trials, two case-control studies and two cross-sectional studies. In addition, published animal and mechanistic studies, relevant to the question of whether early life exposure to peanuts affects the subsequent development of peanut sensitisation, were reviewed narratively. Overall, the evidence reviewed was heterogeneous, and was limited in quality, for example, through lack of adjustment for potentially confounding factors. The nature of the evidence has therefore hindered the development of definitive conclusions. The systematic review of human studies and narrative expert-led reviews of animal studies do not provide clear evidence to suggest that either maternal exposure, or early or delayed introduction of peanuts in the diets of children, has an impact upon subsequent development of sensitisation or allergy to peanuts. Results from some animal studies (and limited evidence from human subjects) suggest that the dose of peanuts is an important mediator of peanut sensitisation and tolerance; low doses tend to lead to sensitisation and higher doses tend to lead to tolerance.

Lower-limb joint reaction forces and moments during modified cycling in healthy controls and individuals with knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a clinical problem affecting an estimated 27 million adults in the United States, with the only clear treatment options being pain management. Cycling is an integral component of exercise for individuals with knee osteoarthritis, while the joint reaction forces during cycling remain unknown. METHODS: Thirteen subjects with medial compartment knee osteoarthritis and eleven healthy subjects performed a cycling protocol with a neutral pedal and four pedal modifications. Six hundred muscle-actuated inverse-dynamic simulations (24 subjects, 5 trials in each of 5 conditions) were performed to estimate joint reaction force differences between conditions. FINDINGS: Subjects with knee osteoarthritis had many significant changes among them was a reduction in knee adduction-abduction moment by 45% (5° lateral wedge), 77% (10° lateral wedge), 54% (5° toe-in) and 58% (10° toe-in). Conversely the healthy subjects had no significant changes in the knee adduction-abduction moment for the lateral wedge conditions and the 5° toe-in but did decrease by 18% for the 10° toe-in condition. When comparing the cohorts across the different pedal conditions, the data showed many significant differences among the groups. INTERPRETATION: This study showed that while cycling in different pedal modifications, the knee osteoarthritis subjects had more beneficial changes in their knee adduction-abduction moment compared to the healthy subjects with the lateral-wedge modification resulting in the greatest impact on the subjects with knee osteoarthritis. Both groups had greater contact forces at the hip and ankle across pedal modifications compared to neutral. For the knee, subjects with osteoarthritis mostly decreased their knee contact forces but the healthy subjects mostly increased these forces with all pedal modifications.

Acamprosate rescues neuronal defects in the Drosophila model of Fragile X Syndrome.

AIMS: Several off-label studies have shown that acamprosate can provide some clinical benefits in youth with Fragile X Syndrome (FXS), an autism spectrum disorder caused by loss of function of the highly conserved FMR1 gene. This study investigated the ability of acamprosate to rescue cellular, molecular and behavioral defects in the Drosophila model of FXS. MAIN METHODS: A high (100µM) and low (10µM) dose of acamprosate was fed to Drosophila FXS (dfmr1 null) or genetic control (w1118) larvae and then analyzed in multiple paradigms. A larval crawling assay was used to monitor aberrant FXS behavior, overgrowth of the neuromuscular junction (NMJ) was quantified to assess neuronal development, and quantitative RT-PCR was used to evaluate expression of deregulated cbp53E mRNA. KEY FINDINGS: Acamprosate treatment partially or completely rescued all of the FXS phenotypes analyzed, according to dose. High doses rescued cellular overgrowth and dysregulated cbp53E mRNA expression, but aberrant crawling behavior was not affected. Low doses of acamprosate, however, did not affect synapse number at the NMJ, but could rescue NMJ overgrowth, locomotor defects, and cbp53E mRNA expression. This dual nature of acamprosate suggests multiple molecular mechanisms may be involved in acamprosate function depending on the dosage used. SIGNIFICANCE: Acamprosate may be a useful therapy for FXS and potentially other autism spectrum disorders. However, understanding the molecular mechanisms involved with different doses of this drug will likely be necessary to obtain optimal results.

Identification of the major capsid protein of erythrocytic necrosis virus (ENV) and development of quantitative real-time PCR assays for quantification of ENV DNA.

Viral erythrocytic necrosis (VEN) is a disease of marine and anadromous fish that is caused by the erythrocytic necrosis virus (ENV), which was recently identified as a novel member of family Iridoviridae by next-generation sequencing. Phylogenetic analysis of the ENV DNA polymerase grouped ENV with other erythrocytic iridoviruses from snakes and lizards. In the present study, we identified the gene encoding the ENV major capsid protein (MCP) and developed a quantitative real-time PCR (qPCR) assay targeting this gene. Phylogenetic analysis of the MCP gene sequence supported the conclusion that ENV does not group with any of the currently described iridovirus genera. Because there is no information regarding genetic variation of the MCP gene across the reported host and geographic range for ENV, we also developed a second qPCR assay for a more conserved ATPase-like gene region. The MCP and ATPase qPCR assays demonstrated good analytical and diagnostic sensitivity and specificity based on samples from laboratory challenges of Pacific herring Clupea pallasii The qPCR assays had similar diagnostic sensitivity and specificity as light microscopy of stained blood smears for the presence of intraerythrocytic inclusion bodies. However, the qPCR assays may detect viral DNA early in infection prior to the formation of inclusion bodies. Both qPCR assays appear suitable for viral surveillance or as a confirmatory test for ENV in Pacific herring from the Salish Sea.

Relative efficacy of differential methods of dietary advice: a systematic review.

BACKGROUND: Dietary advice to lower blood cholesterol may be given by a variety of means. The relative efficacy of the different methods is unknown. OBJECTIVE: The objective was to assess the effects of dietary advice given by dietitians compared with advice from other health professionals, or self-help resources, in reducing blood cholesterol in adults. DESIGN: We performed a systematic review, identifying potential studies by searching the electronic databases of the Cochrane Library, MEDLINE, EMBASE, CINAHL, Human Nutrition, Science Citation Index, and Social Sciences Citation Index. We also hand-searched relevant conference proceedings, reference lists in trial reports, and review articles. Finally, we contacted experts in the field. The selection criteria included randomized trials of dietary advice given by dietitians compared with advice given by other health professionals or self-help resources. The main outcome was difference in blood cholesterol between the dietitian group compared with other intervention groups. Inclusion decisions and data extraction were duplicated. RESULTS: Eleven studies with 12 comparisons met the inclusion criteria. Four studies compared dietitians with doctors, 7 with self-help resources, and 1 with nurses. Participants receiving advice from dietitians experienced a greater reduction in blood total cholesterol than those receiving advice from doctors (-0.25 mmol/L, 95% CI -0.37, -0.12 mmol/L). There was no statistically significant difference in change in blood cholesterol between dietitians and self-help resources (-0.10 mmol/L, 95% CI -0.22, 0.03 mmol/L). CONCLUSIONS: Dietitians appeared to be better than doctors at lowering blood cholesterol in the short to medium term, though the difference was small (about 4%), but there was no evidence that they were better than self-help resources or nurses.

Validation of the ERS standard citric acid cough challenge in healthy adult volunteers.

UNLABELLED: Protocols measuring cough sensitivity can vary in terms of nebuliser, tussive agent, single and dose response. A definitive method for measuring cough sensitivity needs to be established.The ERS guidelines recommend the KoKo DigiDoser (KD) delivery system. Study aim, was to compare the reproducibility of this citric acid (CA) cough challenge and previously established Mefar dosimeter (MD) protocol.39 (female 26) volunteers mean age (40.4 yrs) were randomised to either KD or MD. Intra-day and inter-day reproducibility was compared.We calculated the concentration of citric acid evoking 2 coughs (C2).The geometric mean C2 (95%CI) was similar for both KD and MD, of 263 (200,339) mM and 209 (151,288) mM respectively.The mean KD C2 was not significantly different. (F = 0.807, p = 0.93) from baseline over 1, 2, and 4 hrs however, the MD demonstrated significant variability (F = 7.85, P < 0.001)Measuring mean log C2 at baseline and at 2 weeks, the KD demonstrated a stronger intraclass correlation of log C2 at baseline with 2 week log C2, ICC = 0.70 than was shown with the Mefar, ICC = 0.41Administering CA from KD offers a reproducible cough challenge in healthy volunteers. The results correlate well with the MD challenge but offer greater intra-day and inter-day reproducibility. TRIAL REGISTRATION: Current controlled trials ISRCTN98385033.

Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review.

OBJECTIVE: To review systematically the evidence for an effect of long chain and shorter chain omega 3 fatty acids on total mortality, cardiovascular events, and cancer. DATA SOURCES: Electronic databases searched to February 2002; authors contacted and bibliographies of randomised controlled trials (RCTs) checked to locate studies. REVIEW METHODS: Review of RCTs of omega 3 intake for (3) 6 months in adults (with or without risk factors for cardiovascular disease) with data on a relevant outcome. Cohort studies that estimated omega 3 intake and related this to clinical outcome during at least 6 months were also included. Application of inclusion criteria, data extraction, and quality assessments were performed independently in duplicate. RESULTS: Of 15,159 titles and abstracts assessed, 48 RCTs (36,913 participants) and 41 cohort studies were analysed. The trial results were inconsistent. The pooled estimate showed no strong evidence of reduced risk of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03) or combined cardiovascular events (0.95, 0.82 to 1.12) in participants taking additional omega 3 fats. The few studies at low risk of bias were more consistent, but they showed no effect of omega 3 on total mortality (0.98, 0.70 to 1.36) or cardiovascular events (1.09, 0.87 to 1.37). When data from the subgroup of studies of long chain omega 3 fats were analysed separately, total mortality (0.86, 0.70 to 1.04; 138 events) and cardiovascular events (0.93, 0.79 to 1.11) were not clearly reduced. Neither RCTs nor cohort studies suggested increased risk of cancer with a higher intake of omega 3 (trials: 1.07, 0.88 to 1.30; cohort studies: 1.02, 0.87 to 1.19), but clinically important harm could not be excluded. CONCLUSION: Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.

Dietary factors in the pathogenesis of asthma and chronic obstructive pulmonary disease.

This review focuses on the role of dietary factors in the pathogenesis of asthma and chronic obstructive pulmonary disease. Reduced pulmonary function and indicators of airway obstruction have been shown to be strong indicators of mortality; therefore, a link with diet in the pathogenesis of these diseases would have important public health implications. The results of the studies identified in the review suggest that people who have a diet rich in fruit and vegetables have a lower risk of poor respiratory health, and that this may be due to the antioxidant nutrients these foods contain. On the basis of the evidence, it seems justified to promote a healthy diet, high in fruits, vegetables, and whole grain foods and low in alcohol and fatty foods, as set out in existing guidelines for prevention of cardiovascular disease and cancer, to protect respiratory health in both children and adults.

Meta-analysis of the health effects of using the glycaemic index in meal-planning.

Diabetes mellitus and CVD are some of the leading causes of mortality and morbidity. Accumulating data indicate that a diet characterised by low-glycaemic index (GI) foods may improve the management of diabetes or lipid profiles. The objective of the present meta-analysis was to critically analyse the scientific evidence that low-GI diets have beneficial effects on carbohydrate and lipid metabolism compared with high-GI diets. We searched for randomised controlled trials with a crossover or parallel design published in English between 1981 and 2003, investigating the effect of low-GI v. high-GI diets on markers for carbohydrate and lipid metabolism. Unstandardised differences in mean values were examined using the random effects model. The main outcomes were fructosamine, glycated Hb (HbA1c), HDL-cholesterol, LDL-cholesterol, total cholesterol and triacylglycerol. Literature searches identified sixteen studies that met the strict inclusion criteria. Low-GI diets significantly reduced fructosamine by -0.1 (95 % CI -0.20, 0.00) mmol/l (P=0.05), HbA1c by 0.27 (95 % CI -0.5, -0.03) % (P=0.03), total cholesterol by -0.33 (95 % CI -0.47, -0.18) mmol/l (P<0.0001) and tended to reduce LDL-cholesterol in type 2 diabetic subjects by -0.15 (95 % CI -0.31, -0.00) mmol/l (P=0.06) compared with high-GI diets. No changes were observed in HDL-cholesterol and triacylglycerol concentrations. No substantial heterogeneity was detected, suggesting that the effects of low-GI diets in these studies were uniform. Results of the present meta-analysis support the use of the GI as a scientifically based tool to enable selection of carbohydrate-containing foods to reduce total cholesterol and to improve overall metabolic control of diabetes.

Defining the state of knowledge with respect to food, nutrition, physical activity, and the prevention of cancer.

The 1997 World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) report, Food, Nutrition and the Prevention of Cancer: a global perspective, has become the most authoritative statement on the topic. WCRF International has begun the process of producing its second global report on food, nutrition, physical activity, and the prevention of cancer. The process is in three stages. The first begins with the development of a suitable methodology as advised by a task force of experts. The second stage will involve the systematic collection and display of the evidence by independent review teams. The final stage will be the assessment and judgment of that evidence by an independent panel of experts responsible for the content of the report, including its conclusions and recommendations. Two major differences between this report and previous reports on the prevention of chronic diseases are that a portfolio approach to the evidence is being used in which all types of study are weighed and the process of collecting and displaying the evidence is being clearly separated from assessment and judgment. This paper outlines the methodological procedures and their development that will be applied for the second WCRF International report.

Inhibition of tumour necrosis factor-alpha and interleukin 6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation.

Increased dietary consumption of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (20 : 5n-3; EPA) and docosahexaenoic acid (22 : 6n-6; DHA) is associated with their incorporation into circulating phospholipid and increased production of lipid peroxide metabolites. The relationship between peripheral blood mononuclear cell (PBMC) function, n-3 PUFA intake and antioxidant co-supplementation is poorly defined. We therefore investigated tumour necrosis factor (TNF)-alpha and interleukin (IL) 6 production by PBMC and phospholipid fatty acid composition in plasma and erythrocytes of healthy male subjects (n 16) receiving supplemental intakes of 0.3, 1.0 and 2.0 g EPA+DHA/d, as consecutive 4-week courses. All subjects were randomised in a double-blind manner to receive a concurrent antioxidant supplement (200 microg Se, 3 mg Mn, 30 mg D-alpha-tocopheryl succinate, 90 mg ascorbic acid, 450 microg vitamin A (beta-carotene and retinol)) or placebo. There was a positive dose-dependent relationship between dietary n-3 PUFA intake and EPA and DHA incorporation into plasma phosphatidylcholine and erythrocyte phosphatidylethanolamine, with a tendency towards a plateau at higher levels of intake. Production of TNF-alpha and IL-6 by PBMC decreased with increasing n-3 PUFA intake but tended towards a 'U-shaped' dose response. Both responses appeared to be augmented by antioxidant co-supplementation at intermediate supplementary n-3 PUFA intakes. Thus, increased dietary n-3 PUFA consumption resulted in defined but contrasting patterns of modulation of phospholipid fatty acid composition and PBMC function, which were further influenced by antioxidant intake.