Atovaquone and Berberine Chloride Reduce SARS-CoV-2 Replication In Vitro.

Epidemic RNA viruses seem to arise year after year leading to countless infections and devastating disease. SARS-CoV-2 is the most recent of these viruses, but there will undoubtedly be more to come. While effective SARS-CoV-2 vaccines are being deployed, one approach that is still missing is effective antivirals that can be used at the onset of infections and therefore prevent pandemics. Here, we screened FDA-approved compounds against SARS-CoV-2. We found that atovaquone, a pyrimidine biosynthesis inhibitor, is able to reduce SARS-CoV-2 infection in human lung cells. In addition, we found that berberine chloride, a plant-based compound used in holistic medicine, was able to inhibit SARS-CoV-2 infection in cells through direct interaction with the virion. Taken together, these studies highlight potential avenues of antiviral development to block emerging viruses. Such proactive approaches, conducted well before the next pandemic, will be essential to have drugs ready for when the next emerging virus hits.

Cervical transcutaneous vagal nerve stimulation (ctVNS) improves human cognitive performance under sleep deprivation stress.

Fatigue is a pervasive public health and safety issue. Common fatigue countermeasures include caffeine or other chemical stimulants. These can be effective in limited circumstances but other non-pharmacological fatigue countermeasures such as non-invasive electrical neuromodulation have shown promise. It is reasonable to suspect that other types of non-invasive neuromodulation may be similarly effective or perhaps even superior. The objective of this research was to evaluate the efficacy of cervical transcutaneous vagal nerve stimulation (ctVNS) to mitigate the negative effects of fatigue on cognition and mood. Two groups (active or sham stimulation) of twenty participants in each group completed 34 h of sustained wakefulness. The ctVNS group performed significantly better on arousal, multi-tasking, and reported significantly lower fatigue ratings compared to sham for the duration of the study. CtVNS could be a powerful fatigue countermeasure tool that is easy to administer, long-lasting, and has fewer side-effects compared to common pharmacological interventions.

Periaqueductal gray inputs to the paraventricular nucleus of the thalamus: Columnar topography and glucocorticoid (in)sensitivity.

The ability to cope with a novel acute stressor in the context of ongoing chronic stress is of critical adaptive value. The hypothalamic-pituitary-adrenal (HPA) axis contributes to the integrated physiological and behavioural responses to stressors. Under conditions of chronic stress, the posterior portion of the paraventricular thalamic nucleus (pPVT) mediates the 'habituation' of HPA-axis responses, and also facilitates HPA-axis reactivation to novel acute stressors amidst this habituation. Since pPVT neurons are sensitive to the inhibitory effects of circulating glucocorticoids, a glucocorticoid-insensitive neural pathway to the pPVT is likely essential for this reactivation process. The pPVT receives substantial inputs from neurons of the periaqueductal gray (PAG) region, which is organised into longitudinal columns critical for processing acute and/or chronic stressors. We investigated the columnar organisation of PAG â†’ pPVT projections and for the first time determined their glucocorticoid sensitivity. Retrograde tracer injections were made into different rostro-caudal regions of the pPVT, and their PAG columnar inputs compared. Glucocorticoid receptor immunoreactivity (GR-ir) was quantified in these projection neurons. We found that the dorsolateral PAG projected most strongly to rostral pPVT and the ventrolateral PAG most strongly to the caudal pPVT. Despite abundant GR-ir in the PAG, we report a striking absence of GR-ir in PAG â†’ pPVT neurons. Our data suggests that these pathways, which are insensitive to the direct actions of circulating glucocorticoids, likely play an important role in both the habituation of HPA-axis to chronic stressors and its facilitation to acute stressors in chronically stressed rats.

"The More They Know, the Better Care They Can Give": Patient Perspectives on Measuring Functional Status in Primary Care.

BACKGROUND: Despite its importance to care and outcomes for older adults, functional status is seldom routinely measured in primary care. Understanding patient perspectives is necessary to develop effective, patient-centered approaches for measuring function, yet we know little about patient views on this topic. OBJECTIVE: To examine patient and caregiver perspectives on measuring activities of daily living (ADLs) and instrumental ADLs (IADLs). DESIGN: Qualitative study using semi-structured interviews. PARTICIPANTS: Twenty-eight patients aged 65 or older and five caregivers in primary care clinics at one Veterans Affairs Medical Center. APPROACH: We conducted interviews to elicit patient and caregiver perspectives on the importance of measuring function, including preferences for method of screening and assessment, wording of questions, and provider communication style. We analyzed interviews using qualitative thematic analysis. KEY RESULTS: We identified several themes related to measuring function in primary care. First, most participants reported that measuring function is part of quality, holistic care. However, a minority of participants noted that discussing function, especially IADLs, was not medically relevant. Second, in terms of preferences for measuring function, participants noted that interdisciplinary approaches to measuring function are optimal and that face-to-face assessment is most "intimate" and can prompt reflection on one's limitations. However, some participants indicated that self-assessment is less invasive than in-person assessment. Third, participants had varied preferences regarding communicating about function. Participants noted that asking about difficulty with activities versus need for help are distinct and complementary concepts and that providing context is essential when discussing sensitive topics such as functional decline. CONCLUSIONS: Most patients and caregivers reported that measuring function was important, preferred face-to-face assessment, and emphasized the importance of providing context when asking about function. These findings suggest that incorporating patient and caregiver preferences for measuring function can improve satisfaction and experience with functional assessment in primary care.

The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Very low birthweight or preterm infants are at increased risk of adverse outcomes including sepsis, necrotising enterocolitis, and death. We assessed whether supplementing the enteral diet of very low-birthweight infants with lactoferrin, an antimicrobial protein, reduces all-cause mortality or major morbidity. METHODS: We did a multicentre, double-blind, pragmatic, randomised superiority trial in 14 Australian and two New Zealand neonatal intensive care units. Infants born weighing less than 1500 g and aged less than 8 days, were eligible and randomly assigned (1:1) using minimising web-based randomisation to receive once daily 200 mg/kg pasteurised bovine lactoferrin supplements or no lactoferrin supplement added to breast or formula milk until 34 weeks' post-menstrual age (or for 2 weeks, if longer), or until discharge from the study hospital if that occurred first. Designated nurses preparing the daily feeds were not masked to group assignment, but other nurses, doctors, parents, caregivers, and investigators were unaware. The primary outcome was survival to hospital discharge or major morbidity (defined as brain injury, necrotising enterocolitis, late-onset sepsis at 36 weeks' post-menstrual age, or retinopathy treated before discharge) assessed in the intention-to-treat population. Safety analyses were by treatment received. We also did a prespecified, PRISMA-compliant meta-analysis, which included this study and other relevant randomised controlled trials, to estimate more precisely the effects of lactoferrin supplementation on late-onset sepsis, necrotising enterocolitis, and survival. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12611000247976. FINDINGS: Between June 27, 2014, and Sept 1, 2017, we recruited 1542 infants; 771 were assigned to the intervention group and 771 to the control group. One infant who had consent withdrawn before beginning lactoferrin treatment was excluded from analysis. In-hospital death or major morbidity occurred in 162 (21%) of 770 infants in the intervention group and in 170 (22%) of 771 infants in the control group (relative risk [RR] 0·95, 95% CI 0·79-1·14; p=0·60). Three suspected unexpected serious adverse reactions occurred; two in the lactoferrin group, namely unexplained late jaundice and inspissated milk syndrome, but were not attributed to the intervention and one in the control group had fatal inspissated milk syndrome. Our meta-analysis identified 13 trials completed before Feb 18, 2020, including this Article, in 5609 preterm infants. Lactoferrin supplements significantly reduced late-onset sepsis (RR 0·79, 95% CI 0·71-0·88; p<0·0001; I2=58%), but not necrotising enterocolitis or all-cause mortality. INTERPRETATION: Lactoferrin supplementation did not improve death or major morbidity in this trial, but might reduce late-onset sepsis, as found in our meta-analysis of over 5000 infants. Future collaborative studies should use products with demonstrated biological activity, be large enough to detect moderate and clinically important effects reliably, and assess greater doses of lactoferrin in infants at increased risk, such as those not exclusively receiving breastmilk or infants of extremely low birthweight. FUNDING: Australian National Health and Medical Research Council.

In vitro screening of 51 birdsfoot trefoil (Lotus corniculatus L.; Fabaceae) strains for anti-parasitic effects against Haemonchus contortus.

Secondary plant compounds have shown bioactivity against multi-drug resistant Haemonchus contortus in small ruminants. This study screened 51 strains of birdsfoot trefoil (BFT, Lotus corniculatus) crude aqueous extracts (BFT-AqE) for anti-parasitic activity in vitro against egg hatching, and of those 51 strains, 13 were selected for further testing of motility of first (L1) and third stage (L3) larvae, and exsheathment of L3. Proanthocyanidin content ranged between 1.4 and 63.8 mg PAC g-1 powder across the 51 BFT strains. When tested against egg hatching, 21 of the 51 aqueous extracts had an EC50 of 1-2 mg powder mL-1, 70% of the strains were >90% efficacious at 6 mg powder mL-1 and 11 of the strains were 100% efficacious at 3 mg powder mL-1 BFT-AqE. Across the 13 strains tested against L3, efficacy ranged from 0 to 75% exsheathment inhibition, and 17 to 92% L3 motility inhibition at a concentration of 25 mg powder mL-1 BFT-AqE. There was no correlation between the PAC content of BFT powders and the anti-parasitic activity of aqueous extracts, therefore other secondary compounds may have contributed to the observed anti-parasitic effects. Further testing of BFT using bioactivity-driven fractionation and screening of BFT populations for the identified anti-parasitic compounds is needed.

Limited evidence for a beneficial effect of vitamin C supplementation on biomarkers of cardiovascular diseases: an umbrella review of systematic reviews and meta-analyses.

Vitamin C is an essential nutrient with important antioxidant properties. Higher vitamin C intake appears to be associated with positive effects on cardiovascular risk factors in cohort studies, whereas large randomized controlled clinical trials did not confirm the benefits of supplemental vitamin C on cardiovascular disease (CVD) outcomes. In this overview of systematic reviews and meta-analyses, an "umbrella review," we investigated the effects of vitamin C supplementation on biomarkers of cardiovascular risk, that is, arterial stiffness, blood pressure, endothelial function, glycemic control, and lipid profile. In addition, we assessed the strength of the evidence and the methodological qualities of available studies. Two independent investigators searched 4 databases (Medline, Embase, Scopus, and The Cochrane Library databases) from inception until February 2018. After full text examination, 10 systematic reviews and meta-analyses were included in the umbrella review which included 6409 participants. Three systematic reviews investigated the effects of vitamin C on endothelial function with contrasting results (2 reviews reported a significant effect, and all 3 showed a high heterogeneity [I2> 50%]); 1 systematic review reported significant improvement for each of the following risk factors: blood pressure, and blood concentrations of glucose, low-density lipoprotein cholesterol, and triglycerides. There were no overall effects of vitamin C on arterial stiffness and blood concentration of insulin, total cholesterol, and high-density lipoprotein cholesterol, but subgroup analyses revealed some evidence for significant improvements in subpopulations with higher body mass index, higher plasma concentrations of glucose or cholesterol, and low plasma concentration of vitamin C. Results from this umbrella review emphasize the weakness of the current evidence base about effects of vitamin C supplementation on markers of CVD risk. There is limited evidence that some population subgroups (older people, the obese, those with lower vitamin C status at baseline, and those at higher CVD risk) may be more responsive to vitamin C supplementation and offer opportunities for tailored nutritional interventions to improve cardiometabolic health. Future studies should implement a selective recruitment strategy that is informed by evidence-based literature synthesis.

Making Function Part of the Conversation: Clinician Perspectives on Measuring Functional Status in Primary Care.

OBJECTIVES: Although there is increasing interest in using functional status to guide clinical decision making, function is seldom routinely assessed in primary care. We explored clinician perspectives on barriers and facilitators to routine measurement of older adults' functional status in primary care settings. DESIGN: Qualitative study using semistructured interviews. SETTING: Primary care and geriatrics clinics at six Veterans Affairs Medical Centers. PARTICIPANTS: Twenty-four primary care providers, including 17 from primary care clinics and 7 from geriatrics clinics. MEASUREMENTS: We conducted interviews to elicit clinician perspectives about functional status measurement, including barriers and facilitators to routine assessment. We analyzed transcripts iteratively using a hybrid inductive and deductive thematic approach. RESULTS: Interviews revealed three distinct aspects to measuring function: screening and assessment, documentation, and use of data to inform care. Barriers and facilitators to screening and assessment included time availability, clinic processes, and degree of interdisciplinary environment. Barriers and facilitators to documentation included the usability and integration of electronic instruments into workflows and the availability of a standardized location to document function in the electronic medical record. Barriers and facilitators to use of data included the availability of a standardized location to retrieve data on function, the availability of appropriate referrals and services, and provider knowledge of available resources to address functional impairments. To address these barriers, providers emphasized the critical importance of connecting measurement of function directly to improved patient care. CONCLUSION: Although clinicians emphasized the importance of measuring function, they also cautioned against additional workload burdens, cumbersome electronic documentation, and measurement of function without ensuring that these data are used to improve care. Approaches to functional status measurement must address these barriers to improve care and outcomes for older adults. J Am Geriatr Soc 67:493-502, 2019.

Effect of Ultrasonography on Student Learning of Shoulder Anatomy and Landmarks.

CONTEXT: Ultrasonography is becoming more common in clinical use, and it has been shown to have promising results when introduced into medical school curricula. OBJECTIVE: To determine whether the use of ultrasonography as an educational supplement can improve osteopathic medical students' confidence and ability to locate 4 specific shoulder anatomical landmarks: the coracoid process, the transverse process of T1, the long head of the biceps within the bicipital groove, and the supraspinatus tendon. METHODS: In this randomized controlled study, first-year osteopathic medical students aged 18 years or older were recruited and randomly assigned to a group with exposure (ultrasonography group) or without exposure (control group) to an ultrasonography machine. First, a survey was administered to measure students' baseline knowledge of shoulder anatomy, confidence in palpation skills, and opinion on anatomical landmark identification teaching methods. Next, students were shown presentations on shoulder anatomy and allowed to practice locating and palpating the specified landmarks. Students in the ultrasonography group were also given instruction on the use of ultrasonography. All students were asked to locate each of the 4 specified anatomical landmarks and then given a follow-up survey. A Mann Whitney U test was used to compare the confidence of the students before and after the intervention. A secondary analysis was performed to compare the degree of deviance from the correct position of the specified anatomical landmark between the ultrasonography and control groups. P values less than .05 were considered statistically significant. RESULTS: Sixty-four students participated. Compared with the control group, students in the ultrasonography group had a greater increase in confidence after the session in their ability to locate the coracoid process, bicipital tendon, and supraspinatus tendon (P=.022, P=.029, P=.44, respectively). Students in the ultrasonography group were also able to more accurately palpate the landmarks than those in the control group, with a significant difference in accurate palpation of the bicipital tendon (P=.024). The ultrasonography group showed less deviation with palpation of the other 3 landmarks compared with the control group, but these results were not significant (P=.50, P=.82, P=.29, respectively). CONCLUSION: Ultrasonography in the preclinical curriculum may improve medical students' confidence in and accuracy of palpation.

Nonsuicidal Self-Injury in Adolescents.

BACKGROUND: 25-35% of adolescents in random samples drawn from German schools have been found to have manifested at least one episode of nonsuicidal self-injury (NSSI). The prevalence in samples from child and adolescent psychiatric clinics is approximately 50%. NSSI can arise as a symptom in the setting of various types of mental illness. METHODS: This review is based on a selective literature search carried out in the PubMed, PsycINFO, and Cochrane Library databases, with special consideration of regional study samples. RESULTS: NSSI is usually resorted to as a dysfunctional coping strategy for emotional regulation. The main risk factors for NSSI include bullying, accompanying mental illnesses, and a history of abuse and neglect in childhood. Neurobiological studies have shown abnormal stress processing in persons with NSSI and an elevated pain threshold in persons with repetitive NSSI. Psychotherapeutic interventions of various kinds lessen the frequency of NSSI; to date, no particular type of psychotherapy has been found to be clearly superior to the others. Randomized controlled trials have revealed small to moderate effects from dialectic-behavioral therapy and mentalization-based therapy in adolescent patients. No psychoactive drug has yet been found to possess specific efficacy against NSSI in adolescents. CONCLUSION: The first ever German-language clinical guidelines for the treatment of NSSI have now been issued. Psychotherapy is the treatment of first choice. More research is needed so that subgroups with different disease courses can be more clearly defined.

Comparative systems pharmacology of HIF stabilization in the prevention of retinopathy of prematurity.

Retinopathy of prematurity (ROP) causes 100,000 new cases of childhood blindness each year. ROP is initiated by oxygen supplementation necessary to prevent neonatal death. We used organ systems pharmacology to define the transcriptomes of mice that were cured of oxygen-induced retinopathy (OIR, ROP model) by hypoxia-inducible factor (HIF) stabilization via HIF prolyl hydroxylase inhibition using the isoquinolone Roxadustat or the 2-oxoglutarate analog dimethyloxalylglycine (DMOG). Although both molecules conferred a protective phenotype, gene expression analysis by RNA sequencing found that Roxadustat can prevent OIR by two pathways: direct retinal HIF stabilization and induction of aerobic glycolysis or indirect hepatic HIF-1 stabilization and increased serum angiokines. As predicted by pathway analysis, Roxadustat rescued the hepatic HIF-1 knockout mouse from retinal oxygen toxicity, whereas DMOG could not. The simplicity of systemic treatment that targets both the liver and the eye provides a rationale for protecting the severely premature infant from oxygen toxicity.

Detection of macrolide resistant Mycoplasma pneumoniae in England, September 2014 to September 2015.

Mycoplasma pneumoniae infection can cause pneumonia, particularly in children. Global increase in macrolide-resistant M. pneumoniae is of concern due to limited therapeutic options. We describe the detection of macrolide resistance-conferring mutations in 9.3% of 43 clinical specimens where M. pneumoniae was detected in England and Wales from September 2014‒September 2015. This study aims to impact by highlighting the presence of macrolide resistance in M. pneumoniae positive patients, promoting increased clinical vigilance.

Setting the scene: an overview of issues related to policies and programs for moderate and severe acute malnutrition.

BACKGROUND: Moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) continue to exist at unacceptably high levels. There is a renewed momentum to dramatically improve nutritional status and decrease rates of malnutrition of all kinds. Although much focus is on the first 1,000 days, the period from conception to age 2 years, in relation to growth retardation (or stunting), it is just as important to pay adequate attention to wasting as a major contributor to both morbidity and mortality. OBJECTIVE: This paper reviews what is known about effective approaches for treatment and prevention of MAM and SAM, highlights nutrition blind spots in our strategies, and identifies programmatic and research gaps that, if addressed, will enhance our understanding of the menu of cost-effective approaches to alleviate acute forms of malnutrition. METHODS: The paper synthesizes presentations from the opening session of a May 2014 International Atomic Energy Agency symposium on Moderate Acute Malnutrition held in Vienna, Austria. RESULTS: Although understanding of efficacious approaches to the treatment and prevention of MAM and SAM has recently improved, the evidence base for informed policies and programs remains limited. CONCLUSIONS: If priority evidence gaps can be urgently addressed, our understanding of the menu of cost-effective interventions to alleviate acute forms of malnutrition will be considerably enhanced and the potential for impact at global scale significantly increased.

Prevention of acute malnutrition: distribution of special nutritious foods and cash, and addressing underlying causes--what to recommend when, where, for whom, and how.

Acute malnutrition is associated with increased morbidity and mortality risk. When episodes are prolonged or frequent, acute malnutrition is also associated with poor growth and development, which contributes to stunting Nutrition-specific and nutrition-sensitive strategies to prevent undernutrition during the first 1,000 days from conception to 24 months of age can reduce the risks of wasting, stunting, and micronutrient deficiencies. Under circumstances that exacerbate the underlying causes of undernutrition and increase the incidence of wasting, such as food insecurity related to lean seasons or emergencies, or increased incidence of illness, such as diarrhea or measles, additional efforts are required to prevent and treat wasting. Special nutritious foods directly meet the increased nutrient requirements of children at risk for wasting; assistance to vulnerable households, in the form of cash or food, enables households to better meet the food, health, and other needs of household members and may increase resilience; water, sanitation, and hygiene (WASH) and health interventions help prevent and address illness and hence reduce wasting risk. The contributions of specific interventions to reducing the incidence of wasting are difficult to assess under emergency conditions, due to ethical constraints and to the fact that multiple strategies are implemented at the same time. However, pragmatic studies under real-life circumstances, using different designs, e.g., including a group receiving "best possible" treatment, can provide evidence about what works, to what extent, at what cost, and under which circumstances. Programs should address the most important causes in given contexts, be feasible to implement at scale, and assess implementation, coverage, and outcomes.

The effect of adding ready-to-use supplementary food to a general food distribution on child nutritional status and morbidity: a cluster-randomized controlled trial.

BACKGROUND: Recently, operational organizations active in child nutrition in developing countries have suggested that blanket feeding strategies be adopted to enable the prevention of child wasting. A new range of nutritional supplements is now available, with claims that they can prevent wasting in populations at risk of periodic food shortages. Evidence is lacking as to the effectiveness of such preventive interventions. This study examined the effect of a ready-to-use supplementary food (RUSF) on the prevention of wasting in 6- to 36-mo-old children within the framework of a general food distribution program. METHODS AND FINDINGS: We conducted a two-arm cluster-randomized controlled pragmatic intervention study in a sample of 1,038 children aged 6 to 36 mo in the city of Abeche, Chad. Both arms were included in a general food distribution program providing staple foods. The intervention group was given a daily 46 g of RUSF for 4 mo. Anthropometric measurements and morbidity were recorded monthly. Adding RUSF to a package of monthly household food rations for households containing a child assigned to the intervention group did not result in a reduction in cumulative incidence of wasting (incidence risk ratio: 0.86; 95% CI: 0.67, 1.11; p = 0.25). However, the intervention group had a modestly higher gain in height-for-age (+0.03 Z-score/mo; 95% CI: 0.01, 0.04; p<0.001). In addition, children in the intervention group had a significantly higher hemoglobin concentration at the end of the study than children in the control group (+3.8 g/l; 95% CI: 0.6, 7.0; p = 0.02), thereby reducing the odds of anemia (odds ratio: 0.52; 95% CI: 0.34, 0.82; p = 0.004). Adding RUSF also resulted in a significantly lower risk of self-reported diarrhea (-29.3%; 95% CI: 20.5, 37.2; p<0.001) and fever episodes (-22.5%; 95% CI: 14.0, 30.2; p<0.001). Limitations of this study include that the projected sample size was not fully attained and that significantly fewer children from the control group were present at follow-up sessions. CONCLUSIONS: Providing RUSF as part of a general food distribution resulted in improvements in hemoglobin status and small improvements in linear growth, accompanied by an apparent reduction in morbidity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01154595 Please see later in the article for the Editors' Summary.

A genetic linkage map for hazelnut (Corylus avellana L.) based on RAPD and SSR markers.

A linkage map for European hazelnut (Corylus avellana L.) was constructed using random amplified polymorphic DNA (RAPD) and simple sequence repeat (SSR) markers and the 2-way pseudotestcross approach. A full-sib population of 144 seedlings from the cross OSU 252.146 x OSU 414.062 was used. RAPD markers in testcross configuration, segregating 1:1, were used to construct separate maps for each parent. Fifty additional RAPD loci were assigned to linkage groups as accessory markers whose exact location could not be determined. Markers in intercross configuration, segregating 3:1, were used to pair groups in one parent with their homologues in the other. Eleven groups were identified for each parent, corresponding to the haploid chromosome number of hazelnut (n = x = 11). Thirty of the 31 SSR loci were able to be assigned to a linkage group. The maternal map included 249 RAPD and 20 SSR markers and spanned a distance of 661 cM. The paternal map included 271 RAPD and 28 SSR markers and spanned a distance of 812 cM. The maps are quite dense, with an average of 2.6 cM between adjacent markers. The S-locus, which controls pollen-stigma incompatibility, was placed on chromosome 5S where 6 markers linked within a distance of 10 cM were identified. A locus for resistance to eastern filbert blight, caused by Anisogramma anomala, was placed on chromosome 6R for which two additional markers tightly linked to the dominant allele were identified and sequenced. These maps will serve as a starting point for future studies of the hazelnut genome, including map-based cloning of important genes. The inclusion of SSR loci on the map will make it useful in other populations.

The ECOMAN project: A novel approach to defining sustainable ecosystem function.

The ECOMAN was initiated in 2001 by the University of Plymouth, UK, Plymouth Marine Laboratory and the Department of the Environment, Fisheries and Rural Affairs (DEFRA) to address the need for more pragmatic assessment techniques linking environmental degradation with its causes. The primary aim of the project was to develop an evidence-based approach in which suites of easy-to-use, cost-effective and environmentally valid biological responses (biomarkers) could be used together to assess the health of coastal systems through the general condition of individuals. A range of sub-lethal endpoints, chosen to reflect successive levels of biological organisation (molecular, cellular, physiological), was evaluated in common coastal organisms showing different feeding types (filter feeding, grazing, predation) and habitat requirements (estuary, rocky shore). Initially, the suite of biomarkers was used in laboratory studies to determine the relative sensitivities of key species within different functional groups to common contaminants. These results were then validated in field studies performed in a range of ecosystems exhibiting different degrees/signatures of contamination. Here, an example is provided of a field study in the Humber Estuary, UK, which illustrates how multivariate statistical analysis can be used to identify patterns of response to discriminate between contaminated and clean sites. The use of a holistic, integrated approach of this kind is advocated as a practical means of assessing the impact of chemical contamination on organismal health and of ranking the status of marine ecosystems.

Ecosystem management bioindicators: the ECOMAN project--a multi-biomarker approach to ecosystem management.

The ECOMAN project was initiated from an awareness of the complexity of the functioning of coastal marine systems and the clear need for more pragmatic environmental assessment techniques linking environmental degradation with its causes. The aim of the project is to develop a suite of easy to use, cost effective and environmentally valid biological responses (biomarkers) to assess the general health of coastal systems, including estuaries. To achieve this aim, various sublethal endpoints are being measured and evaluated from a range of common coastal organisms showing different feeding types (filter feeding, grazing and predation) and habitat requirements (estuary and rocky shore) and at different levels of biological response (cellular, physiological and behavioural). This holistic integrated approach is essential to identify the full impact of chemical contamination on organisms, and enables the sensitivity of organisms to be ranked and key sentinel species for specific habitats to be identified.

A multibiomarker approach to environmental assessment.

Incorporation of ecologically relevant biomarkers into routine environmental management programs has been advocated as a pragmatic means of linking environmental degradation with its causes. Here, suites of biomarkers, devised to measure molecular damage, developmental abnormality and physiological impairment, were combined with chemical analysis to determine exposure to and the effects of pollution at sites within Southampton Water (UK). Test species included a filter feeder, a grazer, and an omnivore to determine the sensitivity of organisms occupying different trophic levels. Linear regression confirmed a significant association between incidence of intersex in Littorina littorea and tributyltin (TBT) concentrations (R2 = 0.954) and between PAH metabolites in Carcinus maenas urine and PAHs in sediments (R2 = 0.754). Principal component analysis revealed a gradient of detrimental impact to biota from the head to the mouth of the estuary, coincident with high sediment concentrations of heavy metals, PAHs, and biocides. Multidimensional scaling identified C. maenas as the organism most sensitive to contamination. Carboxylesterase activity, metallothionein and total haemolymph protein were the most discriminating biomarkers among sites. This holistic approach to environmental assessment is encouraged as it helps to identify the integrated impact of chemical contamination on organisms and to provide a realistic measure of environmental quality.

Dance and reducing television viewing to prevent weight gain in African-American girls: the Stanford GEMS pilot study.

OBJECTIVE: To test the feasibility, acceptability, and potential efficacy of after-school dance classes and a family-based intervention to reduce television viewing, thereby reducing weight gain, among African-American girls. DESIGN: Twelve-week, 2-arm parallel group, randomized controlled trial. SETTING: Low-income neighborhoods. PARTICIPANTS: Sixty-one 8-10-year-old African-American girls and their parents/guardians. INTERVENTIONS: The treatment intervention consisted of after-school dance classes at 3 community centers, and a 5-lesson intervention, delivered in participants' homes, and designed to reduce television, videotape, and video game use. The active control intervention consisted of disseminating newsletters and delivering health education lectures. MAIN OUTCOME MEASURES: Implementation and process measures, body mass index, waist circumference, physical activity measured by accelerometry, self-reported media use, and meals eaten with TV. RESULTS: Recruitment and retention goals were exceeded. High rates of participation were achieved for assessments and intervention activities, except where transportation was lacking. All interventions received high satisfaction ratings. At follow up, girls in the treatment group, as compared to the control group, exhibited trends toward lower body mass index (adjusted difference = -.32 kg/m2, 95% confidence interval [CI] -.77, .12; Cohen's d = .38 standard deviation units) and waist circumference (adjusted difference = -.63 cm, 95% CI -1.92, .67; d = .25); increased after-school physical activity (adjusted difference = 55.1 counts/minute, 95% CI -115.6, 225.8; d = .21); and reduced television, videotape, and video game use (adjusted difference = -4.96 hours/week, 95% CI -11.41, 1.49; d = .40). The treatment group reported significantly reduced household television viewing (d = .73, P = .007) and fewer dinners eaten while watching TV (adjusted difference = -1.60 meals/week, 95% CI -2.99, -.21; d = .59; P = .03). Treatment group girls also reported less concern about weight (d = .60; P = .03), and a trend toward improved school grades (d = .51; P = .07). CONCLUSIONS: This study confirmed the feasibility, acceptability, and potential efficacy of using dance classes and a family-based intervention to reduce television viewing, thereby reducing weight gain, in African-American girls.