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Background: By 1990, 94 percent of the acquired immunodeficiency syndrome (AIDS) cases in Romania were in children less than 13 years of age. The majority of the cases were identified in the city of Constanta. The purpose of this paper was to describe the current burden of pediatric human immunodeficiency virus (HIV) infection in the Constanta county.Methods: A cross-sectional study was designed to address the primary objective. Between April 1999 and March 2000, all living cases of pediatric HIV infection in the Constanta county were identified from records at the HIV hospital clinic which serves the Constanta county. Standard demographic, social, clinical, treatment and hospitalization data were collected for each study subject. Data were analyzed according to cross-sectional study design methodology.Results: Of the 762 subjects, the majority were seven to 11 years of age, lived with their parents and attended school. Only 70% of the fathers and 13% of the mothers were employed. Horizontal transmission accounted for 90% of the cases. Most of the children had moderate to severe disease as indicated by their AIDS-defining signs; 40% had AIDS. Less than half of the children were receiving antiretroviral therapy (ART). ART and children of mothers with a high school or greater education were independent predictors of long-term non-progression of HIV disease.Conclusions: This cross-sectional study demonstrated that ten years after the HIV epidemic was identified in Romania, it remains a health and economic burden. The infected children are very ill, but ART is not available for all. The proportion with vertical transmission has increased from an estimated four % to nine %. Our findings support the need to get HIV therapy to economically challenged countries such as Romania. [ABSTRACT FROM AUTHOR]

Background: Chemical methods of transfection that have proven successful with cell lines often do not work with primary cultures of neurons. Recent data, however, suggest that linear polymers of the cation polyethyleneimine (PEI) can facilitate the uptake of nucleic acids by neurons. Consequently, we examined the ability of a commercial PEI preparation to allow the introduction of foreign genes into postmitotic mammalian neurons. Sympathetic neurons were obtained from perinatal rat pups and maintained for 5 days in vitro in the absence of nonneuronal cells. Cultures were then transfected with varying amounts of a plasmid encoding either E. coli beta-galactosidase or enhanced green fluorescence protein (EGFP) using PEI.Results: Optimal transfection efficiency was observed with 1 microg/ml of plasmid DNA and 5 microg/ml PEI. Expression of beta-galactosidase was both rapid and stable, beginning within 6 hours and lasting for at least 21 days. A maximum yield was obtained within 72 hours with approximately 9% of the neurons expressing beta-galactosidase, as assessed by both histochemistry and antibody staining. Cotransfection of two plasmids encoding reporter genes was achieved. Postmitotic neurons from adult human retinal cultures also demonstrated an ability to take up and express foreign DNA using PEI as a vector.Conclusions: These data suggest that PEI is a useful agent for the stable expression of plasmid-encoded genes in neuronal cultures. [ABSTRACT FROM AUTHOR]

Background: The mammalian homologue of Seven in Absentia (Siah) can act in the ubiquitin/proteasome pathway. Recent work has shown that Siah can bind group I metabotropic glutamate receptors (mGluRs), but the functional consequences of this interaction are unknown.Results: The effects of coexpression of Siah on group I mGluR signaling were examined using heterologous expression in rat sympathetic, superior cervical ganglion neurons. Siah1a attenuated heterologously expressed group I mGluR-mediated calcium current inhibition, but was without effect on group II mGluR- or NE-mediated calcium current modulation via heterologously expressed mGluR2 or native a2 adrenergic receptors, respectively, indicating that the effect of Siah was specific for group I mGluRs. Surface expression and subcellular distribution of group I mGluRs were not detectably altered in the presence of Siah1a as assessed by immunoflourescence experiments with epitope tagged receptors and imaging of a GFP/mGluR fusion construct. In addition, an N-terminal Siah deletion construct, which cannot function in the proteolysis pathway, displayed effects similar to the wild type Siah1a. Finally, coexpression of calmodulin, which competes with Siah1a for binding to the C-terminal tail of group I mGluRs, reversed the effect of Siah1a on mGluR-mediated signaling.Conclusions: These data supported the conclusion that the attenuation of mGluR signaling induced by Siah1a expression was likely a direct consequence of Siah/mGluR association rather than a result of targeting of the receptors to the proteosome. In addition, the data suggest that the binding of CaM and Siah may play an important role in the regulation of group I mGluR function. [ABSTRACT FROM AUTHOR]

Background: One mechanism that directs the action of the second messengers, cAMP and diacylglycerol, is the compartmentalization of protein kinase A (PKA) and protein kinase C (PKC). A-kinase anchoring proteins (AKAPs) can recruit both enzymes to specific subcellular locations via interactions with the various isoforms of each family of kinases. We found previously that a new class of AKAPs, dual-specific AKAPs, denoted D-AKAP1 and D-AKAP2, bind to RIalpha in addition to the RII subunits.Results: Immunohistochemistry and confocal microscopy were used here to determine that D-AKAP1 colocalizes with RIalpha at the postsynaptic membrane of the vertebrate neuromuscular junction (NMJ) and the adjacent muscle, but not in the presynaptic region. The labeling pattern for RIalpha and D-AKAP1 overlapped with mitochondrial staining in the muscle fibers, consistent with our previous work showing D-AKAP1 association with mitochondria in cultured cells. The immunoreactivity of D-AKAP2 was distinct from that of D-AKAP1. We also report here that even though the PKA type II subunits (RIIalpha and RIIbeta) are localized at the NMJ, their patterns are distinctive and differ from the other R and D-AKAP patterns examined. PKCbeta appeared to colocalize with the AKAP, gravin, at the postsynaptic membrane.Conclusions: The kinases and AKAPs investigated have distinct patterns of colocalization, which suggest a complex arrangement of signaling micro-environments. Because the labeling patterns for RIalpha and D-AKAP 1 are similar in the muscle fibers and at the postsynaptic membrane, it may be that this AKAP anchors RIalpha in these regions. Likewise, gravin may be an anchor of PKCbeta at the NMJ. [ABSTRACT FROM AUTHOR]

Introduction: Clustered within the nomenclature of Asian American are numerous subgroups, each with their own ethnic heritage, cultural, and linguistic characteristics. An understanding of the prevailing health knowledge, attitudes, and screening behaviors of these subgroups is essential for creating population-specific health promotion programs.Methods: Korean American women (123) completed baseline surveys of breast cancer knowledge, attitudes, and screening behaviors as part of an Asian grocery store-based breast cancer education program evaluation. Follow-up telephone surveys, initiated two weeks later, were completed by 93 women.Results: Low adherence to the American Cancer Society's breast cancer screening guidelines and insufficient breast cancer knowledge were reported. Participants' receptiveness to the grocery store-based breast cancer education program underscores the importance of finding ways to reach Korean women with breast cancer early detection information and repeated cues for screening. The data also suggest that the Asian grocery store-based cancer education program being tested may have been effective in motivating a proportion of the women to schedule a breast cancer screening between the baseline and follow-up surveys.Conclusion: The program offers a viable strategy to reach Korean women that addresses the language, cultural, transportation, and time barriers they face in accessing breast cancer early detection information. [ABSTRACT FROM AUTHOR]

Background: Gaps in disease surveillance capacity, particularly for emerging infections and bioterrorist attack, highlight a need for efficient, real time identification of diseases.Methods: We studied automated records from 1996 through 1999 of approximately 250,000 health plan members in greater Boston.Results: We identified 152,435 lower respiratory infection illness visits, comprising 106,670 episodes during 1,143,208 person-years. Three diagnoses, cough (ICD9CM 786.2), pneumonia not otherwise specified (ICD9CM 486) and acute bronchitis (ICD9CM 466.0) accounted for 91% of these visits, with expected age and sex distributions. Variation of weekly occurrences corresponded closely to national pneumonia and influenza mortality data. There was substantial variation in geographic location of the cases.Conclusion: This information complements existing surveillance programs by assessing the large majority of episodes of illness for which no etiologic agents are identified. Additional advantages include: a) sensitivity, uniformity and efficiency, since detection of events does not depend on clinicians' to actively report diagnoses, b) timeliness, the data are available within a day of the clinical event; and c) ease of integration into automated surveillance systems. These features facilitate early detection of conditions of public health importance, including regularly occurring events like seasonal respiratory illness, as well as unusual occurrences, such as a bioterrorist attack that first manifests as respiratory symptoms. These methods should also be applicable to other infectious and non-infectious conditions. Knowledge of disease patterns in real time may also help clinicians to manage patients, and assist health plan administrators in allocating resources efficiently. [ABSTRACT FROM AUTHOR]

Asthma is the most common chronic childhood disease in the developed nations, and is a complex disease that has high social and economic costs. Studies of the genetic etiology of asthma offer a way of improving our understanding of its pathogenesis, with the goal of improving preventive strategies, diagnostic tools, and therapies. Considerable effort and expense have been expended in attempts to detect specific polymorphisms in genetic loci contributing to asthma susceptibility. Concomitantly, the technology for detecting single nucleotide polymorphisms (SNPs) has undergone rapid development, extensive catalogues of SNPs across the genome have been constructed, and SNPs have been increasingly used as a method of investigating the genetic etiology of complex human diseases. This paper reviews both current and potential future contributions of SNPs to our understanding of asthma pathophysiology. [ABSTRACT FROM AUTHOR]

Background: There has been increasing concern regarding the potential effects of the commercialization of research. Methods: In order to examine the relationships between funding source, trial outcome and reporting quality, recent issues of five peer-reviewed, high impact factor, general medical journals were hand-searched to identify a sample of 100 randomized controlled trials (20 trials/journal). Relevant data, including funding source (industry/not-for-profit/mixed/not reported) and statistical significance of primary outcome (favouring new treatment/favouring conventional treatment/ neutral/unclear), were abstracted. Quality scores were assigned using the Jadad scale and the adequacy of allocation concealment. Results: Sixty-six percent of trials received some industry funding. Trial outcome was not associated with funding source (p= .461). There was a preponderance of favourable statistical conclusions among published trials with 67% reporting results that favored a new treatment whereas 6% favoured the conventional treatment. Quality scores were not associated with funding source or trial outcome. Conclusions: It is not known whether the absence of significant associations between funding source, trial outcome and reporting quality reflects a true absence of an association or is an artefact of inadequate statistical power, reliance on voluntary disclosure of funding information, a focus on trials recently published in the top medical journals, or some combination thereof. Continued and expanded monitoring of potential conflicts is recommended, particularly in light of new guidelines for disclosure that have been endorsed by the ICMJE. [ABSTRACT FROM AUTHOR]

Background: It has been proposed that high insulin levels may cause delayed lung development in the fetuses of diabetic mothers. A key event in lung development is the production of adequate amounts of pulmonary surfactant. Insulin inhibits the expression of surfactant protein A (SP-A), the major surfactant-associated protein, in lung epithelial cells. In the present study, we investigated the signal transduction pathways involved in insulin inhibition of SP-A gene expression.Methods: H441 cells, a human lung adenocarcinoma cell line, or human fetal lung explants were incubated with or without insulin. Transcription run-on assays were used to determine SP-A gene transcription rates. Northern blot analysis was used to examine the effect of various signal transduction inhibitors on SP-A gene expression. Immunoblot analysis was used to evaluate the levels and phosphorylation states of signal transduction protein kinases.Results: Insulin decreased SP-A gene transcription in human lung epithelial cells within 1 hour. Insulin did not affect p44/42 mitogen-activated protein kinase (MAPK) phosphorylation and the insulin inhibition of SP-A mRNA levels was not affected by PD98059, an inhibitor of the p44/42 MAPK pathway. In contrast, insulin increased p70 S6 kinase Thr389 phosphorylation within 15 minutes. Wortmannin or LY294002, both inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase), or rapamycin, an inhibitor of the activation of p70 S6 kinase, a downstream effector in the PI 3-kinase pathway, abolished or attenuated the insulin-induced inhibition of SP-A mRNA levels.Conclusion: Insulin inhibition of SP-A gene expression in lung epithelial cells probably occurs via the rapamycin-sensitive PI 3-kinase signaling pathway. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine the effect of stress reduction via the Transcendental Meditation program on school rule infractions in adolescents.Methods: Forty-five African American adolescents (ages 15-18 years) with high normal systolic blood pressure were randomly assigned to either Transcendental Meditation (n = 25) or health education control (n = 20) groups. The meditation group engaged in 15-min sessions at home and at school each day for 4 months. The control group was presented 15-min sessions of health education at school each day for 4 months. Primary outcome measures were changes in absenteeism, school rule infractions and suspension days during the four-month pretest period prior to randomization compared with the four-month intervention period.Results: Comparing the pretest and intervention periods, the meditation group exhibited a mean decrease of 6.4 absentee periods compared to an increase of 4.8 in the control group (p <.05). The meditation group exhibited a mean decrease of 0.1 infractions over the four months compared to an increase of 0.3 in the control group (p <.03). There was a mean reduction of 0.3 suspension days due to behavior-related problems in the meditation group compared to an increase of 1.2 in the control group (p <.04).Conclusion: These findings demonstrate that the Transcendental Meditation program conducted in the school setting has a beneficial impact upon absenteeism, rule infractions, and suspension rates in African American adolescents. [ABSTRACT FROM AUTHOR]

Background: In 2002 the Australian National Competitive Grants System was opened to the Institute of Advanced Studies at the Australian National University as part of a commitment to transparency, competitiveness, and collaboration in national research funding. Results: The block grant to the John Curtin School of Medical Research had progressively eroded over many years. Access to the National Competitive Grants Schemes and associated infrastructure (through an agreed 'buy-in' price of 20% of block funding) has succeeded in its aims and in reversing this progressive effective decrease in funding. Conclusion: Access to the National Competitive Grant Scheme has allowed the John Curtin School of Medical Research to contribute more broadly to Australia's health and medical research effort through increased collaboration, in a transparent and competitive funding environment. [ABSTRACT FROM AUTHOR]

Background: Nicotinic acetylcholine receptors (nAChRs) are pentameric proteins that are important drug targets for a variety of diseases including Alzheimer's, schizophrenia and various forms of epilepsy. One of the most intensively studied nAChR subunits in recent years has been alpha7. This subunit can form functional homomeric pentamers (alpha7)5, which can make interpretation of physiological and structural data much simpler. The growing amount of structural, pharmacological and physiological data for these receptors indicates the need for a dedicated and accurate database to provide a means to access this information in a coherent manner.Description: A7DB http://www.lgics.org/a7db/ is a new relational database of manually curated experimental physiological data associated with the alpha7 nAChR. It aims to store as much of the pharmacology, physiology and structural data pertaining to the alpha7 nAChR. The data is accessed via web interface that allows a user to search the data in multiple ways: 1) a simple text query 2) an incremental query builder 3) an interactive query builder and 4) a file-based uploadable query. It currently holds more than 460 separately reported experiments on over 85 mutations.Conclusions: A7DB will be a useful tool to molecular biologists and bioinformaticians not only working on the alpha7 receptor family of proteins but also in the more general context of nicotinic receptor modelling. Furthermore it sets a precedent for expansion with the inclusion of all nicotinic receptor families and eventually all cys-loop receptor families. [ABSTRACT FROM AUTHOR]

Background: Nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) all play important roles in the development of the peripheral sensory nervous system. Additionally, these growth factors are proposed to modulate the properties of the sensory system in the adult under pathological conditions brought about by nerve injury or inflammation. We have examined the effects of NGF, GDNF and BDNF on adult rat trigeminal ganglion (TG) neurons in culture to gain a better understanding of how these growth factors alter the cytochemical and functional phenotype of these neurons, with special attention to properties associated with nociception.Results: Compared with no growth factor controls, GDNF, at 1 and 100 ng/ml, significantly increased by nearly 100% the number of neurons in culture at 5 days post-plating. A significant, positive, linear trend of increasing neuron number as a function of BDNF concentration was observed, also peaking at nearly 100%. NGF treatment was without effect. Chronic treatment with NGF and GDNF significantly and concentration-dependently increased 100 nM capsaicin (CAP)-evoked calcitonin gene-related peptide (CGRP) release, reaching approximately 300% at the highest concentration tested (100 ng/ml). Also, NGF and GDNF each augmented anandamide (AEA)- and arachidonyl-2-chloroethylamide (ACEA)-evoked CGRP release, while BDNF was without effect. Utilizing immunohistochemistry to account for the proportions of TRPV1- or CGRP-positive neurons under each growth factor treatment condition and then standardizing evoked CGRP release to these proportions, we observed that NGF was much more effective in enhancing CAP- and 50 mM K+-evoked CGRP release than was GDNF. Furthermore, NGF and GDNF each altered the concentration-response function for CAP- and AEA-evoked CGRP release, increasing the Emax without altering the EC50 for either compound.Conclusions: Taken together, our results illustrate that NGF, GDNF and BDNF differentially alter TG sensory neuron survival, neurochemical properties and TRPV1-mediated neuropeptide release in culture. In particular, our findings suggest that GDNF and NGF differentially modulate TRPV1-mediated neuropeptide secretion sensitivity, with NGF having a much greater effect on a per neuron basis than GDNF. These findings are discussed in relation to possible therapeutic roles for growth factors or their modulators in pathological pain states, especially as these relate to the trigeminal system. [ABSTRACT FROM AUTHOR]

Background: Disparities in health status among ethnic groups favor the Caucasian population in the United States on almost all major indicators. Disparities in exposure to health-related mass media messages may be among the environmental factors contributing to the racial and ethnic imbalance in health outcomes. This study evaluated whether variations exist in health-related advertisements and health promotion cues among lay magazines catering to Hispanic, African American and Caucasian women.Methods: Relative and absolute assessments of all health-related advertising in 12 women's magazines over a three-month period were compared. The four highest circulating, general interest magazines oriented to Black women and to Hispanic women were compared to the four highest-circulating magazines aimed at a mainstream, predominantly White readership. Data were collected and analyzed in 2002 and 2003.Results: Compared to readers of mainstream magazines, readers of African American and Hispanic magazines were exposed to proportionally fewer health-promoting advertisements and more health-diminishing advertisements. Photographs of African American role models were more often used to advertise products with negative health impact than positive health impact, while the reverse was true of Caucasian role models in the mainstream magazines.Conclusion: To the extent that individual levels of health education and awareness can be influenced by advertising, variations in the quantity and content of health-related information among magazines read by different ethnic groups may contribute to racial disparities in health behaviors and health status. [ABSTRACT FROM AUTHOR]

Background: There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA.Methods: To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis.Results: We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth.Conclusion: We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype. [ABSTRACT FROM AUTHOR]

Background: Changing immigration trends pose new challenges for the UK's open access health service and there is considerable speculation that migrants from resource-poor countries place a disproportionate burden on services. Data are needed to inform provision of services to migrant groups and to ensure their access to appropriate health care. We compared sociodemographic characteristics and impact of migrant groups and UK-born patients presenting to a hospital A&E/Walk-In Centre and prior use of community-based General Practitioner (GP) services.Methods: We administered an anonymous questionnaire survey of all presenting patients at an A&E/Walk-In Centre at an inner-city London hospital during a 1 month period. Questions related to nationality, immigration status, time in the UK, registration and use of GP services. We compared differences between groups using two-way tables by Chi-Square and Fisher's exact test. We used logistic regression modelling to quantify associations of explanatory variables and outcomes.Results: 1611 of 3262 patients completed the survey (response rate 49.4%). 720 (44.7%) were overseas born, representing 87 nationalities, of whom 532 (73.9%) were new migrants to the UK (< or =10 years). Overseas born were over-represented in comparison to local estimates (44.7% vs 33.6%; p < 0.001; proportional difference 0.111 [95% CI 0.087-0.136]). Dominant immigration status' were: work permit (24.4%), EU citizens (21.5%), with only 21 (1.3%) political asylum seekers/refugees. 178 (11%) reported nationalities from refugee-generating countries (RGCs), eg, Somalia, who were less likely to speak English. Compared with RGCs, and after adjusting for age and sex, the Australians, New Zealanders, and South Africans (ANS group; OR 0.28 [95% CI 0.11 to 0.71]; p = 0.008) and the Other Migrant (OM) group comprising mainly Europeans (0.13 [0.06 to 0.30]; p = 0.000) were less likely to have GP registration and to have made prior contact with GPs, yet this did not affect mode of access to hospital services across groups nor delay access to care.Conclusion: Recently arrived migrants are a diverse and substantial group, of whom migrants from refugee-generating countries and asylum seekers comprise only a minority group. Service reorganisation to ensure improved access to community-based GPs and delivery of more appropriate care may lessen their impact on acute services. [ABSTRACT FROM AUTHOR]

Background: New HIV diagnoses related to injection drug use (IDU) have declined in the United States. Access to clean syringes and decreasing HIV transmission among injection drug users have been HIV prevention priorities of the Rhode Island (RI) HIV community. To examine trends in IDU-related new HIV diagnoses in RI, we performed a retrospective analysis of new HIV diagnoses according to HIV risk factor from 1990-2003.Results: There has been an 80% absolute reduction in IDU-related new HIV diagnoses in RI coincident with IDU-specific prevention efforts.Conclusion: There has been a greater decline in IDU-related new HIV diagnoses in Rhode Island compared to national data reported by the Centers for Disease Control and Prevention. We hypothesize that this dramatic decline in Rhode Island is related to extensive HIV prevention efforts targeting IDUs. Further research is needed to examine the impact of specific HIV prevention interventions for injection drug users. [ABSTRACT FROM AUTHOR]

Background: Retinoids are used to treat several types of cancer; however, their effects on liver cancer have not been fully characterized. To investigate the therapeutic potential of retinoids on hepatocellular carcinoma (HCC), the present study evaluates the apoptotic effect of a panel of natural and synthetic retinoids in three human HCC cell lines as well as explores the underlying mechanisms.Methods: Apoptosis was determined by caspase-3 cleavage using western blot, DNA double-strand breaks using TUNEL assay, and phosphatidylserine translocation using flow cytometry analysis. Gene expression of nuclear receptors was assessed by real-time PCR. Transactivation assay and chromatin immunoprecipitation (ChIP) were conducted to evaluate the activation of RXRalpha/RARbeta pathway by fenretinide. Knockdown of RARbeta mRNA expression was achieved by siRNA transfection.Results: Our data revealed that fenretinide effectively induces apoptosis in Huh-7 and Hep3B cells. Gene expression analysis of nuclear receptors revealed that the basal and inducibility of retinoic acid receptor beta (RARbeta) expression positively correlate with the susceptibility of HCC cells to fenretinide treatment. Furthermore, fenretinide transactivates the RXRalpha/RARbeta-mediated pathway and directly increases the transcriptional activity of RARbeta. Knockdown of RARbeta mRNA expression significantly impairs fenretinide-induced apoptosis in Huh-7 cells.Conclusion: Our findings reveal that endogenous expression of retinoids receptor RARbeta gene determines the susceptibility of HCC cells to fenretinide-induced apoptosis. Our results also demonstrate fenretinide directly activates RARbeta and induces apoptosis in Huh-7 cells in a RARbeta-dependent manner. These findings suggest a novel role of RARbeta as a tumor suppressor by mediating the signals of certain chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of Cimicifuga dahurica showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of C. dahurica and therefore might eventually be useful in the prevention or treatment of Hepatoma.Methods: The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H22 hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA in vivo.Results: The IC50 values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 mug/ml, respectively. TGA induced G0/G1 cell cycle arrest at lower concentration (25 mug/ml), and triggered G2/M arrest and apoptosis at higher concentrations (50 and 100 mug/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H22 tumor in a dose-dependent manner.Conclusion: TGA may potentially find use as a new therapy for the treatment of hepatoma. [ABSTRACT FROM AUTHOR]

Background: We investigated if personal socioeconomic position (SEP) factors and neighborhood characteristics were associated with incident mobility impairment in the elderly.Methods: We used data from the Cardiovascular Health Study, a longitudinal, population-based examination of coronary heart disease and stroke among persons aged 65 and older in the United States.Results: Among 3,684 persons without baseline mobility impairment, lower baseline SEP was associated with increased risk of incident mobility disability during the 10-year follow-up period, although the strengths of these associations varied by socioeconomic indicator and race/sex group.Conclusion: Among independent-living elderly, SEP affected development of mobility impairment into later life. Particular effort should be made to prevent or delay its onset among the elderly with low income, education, and/or who live in economically disadvantaged neighborhoods. [ABSTRACT FROM AUTHOR]

Background: The UK, like other developed countries, is experiencing a marked change in the age structure of its population characterised by increasing life expectancy and continuing growth in the older fraction of the population. There is remarkably little up-to-date information about the health of the oldest old (over 85 years), demographically the fastest growing section of the population. There is a need, from both a policy and scientific perspective, to describe in detail the health status of this population and the factors that influence individual health trajectories. For a very large proportion of medical conditions, age is the single largest risk factor. Gaining new knowledge about why aged cells and tissues are more vulnerable to pathology is likely to catalyse radical new insights and opportunities to intervene. The aims of the Newcastle 85+ Study are to expose the spectrum of health within an inception cohort of 800 85 year-olds; to examine health trajectories and outcomes as the cohort ages and their associations with underlying biological, medical and social factors; and to advance understanding of the biological nature of ageing.Methods: A cohort of 800 85 year olds from Newcastle and North Tyneside will be recruited at baseline and followed until the last participant has died. Eligible individuals will be all those who turn 85 during the year 2006 (i.e. born in 1921) and who are registered with a Newcastle or North Tyneside general practice. Participants will be visited in their current residence (own home or institution) by a research nurse at baseline, 18 months and 36 months. The assessment protocol entails a detailed multi-dimensional health assessment together with review of general practice medical records. Participants will be flagged with the NHS Central Register to provide details of the date and cause of death.Discussion: The Newcastle 85+ Study will address key questions about health and health-maintenance in the 85+ population, with a particular focus on quantitative assessment of factors underlying variability in health, and on the relationships between health, nutrition and biological markers of the fundamental processes of ageing. [ABSTRACT FROM AUTHOR]

Background: Health policy in the UK has rapidly diverged since devolution in 1999. However, there is relatively little comparative data available to examine the impact of this natural experiment in the four UK countries. The Quality and Outcomes Framework of the 2004 General Medical Services Contract provides a new and potentially rich source of comparable clinical quality data through which we compare quality of primary medical care for coronary heart disease (CHD), stroke, hypertension and diabetes across the four UK countries.Methods: A cross-sectional analysis was undertaken involving 10,064 general practices in England, Scotland, Wales and Northern Ireland. The main outcome measures were prevalence rates for CHD, stroke, hypertension and diabetes. Achievement on 14 simple process, 3 complex process, 9 intermediate outcome and 5 treatment indicators for the four clinical areas.Results: Prevalence varies by up to 28% between the four UK countries, which is not reflected in resource distribution between countries, and penalises practices in the high prevalence countries (Wales and Scotland). Differences in simple process measures across countries are small. Larger differences are found for complex process, intermediate outcome and treatment measures, most notably for Wales, which has consistently lower quality of care. Scotland has generally higher quality than England and Northern Ireland is most consistently the highest quality.Conclusion: Previously identified weaknesses in Wales related to waiting times appear to reflect a more general quality problem within NHS Wales. Identifying explanations for the observed differences is limited by the lack of comparable data on practice resources and organisation. Maximising the value of cross-jurisdictional comparisons of the ongoing natural experiment of health policy divergence within the UK requires more detailed examination of resource and organisational differences. [ABSTRACT FROM AUTHOR]

Background: Low vitamin E levels are often found in HIV-1 infection, and studies have suggested that higher levels may decrease the risk of disease progression. However, vitamin E supplementation has also been reported to increase CCR5 expression, which could increase HIV-1 replication. We hypothesized that vitamin E levels at HIV-1 acquisition may influence disease progression.Methods: Vitamin E status was measured in stored samples from the last pre-infection visit for 67 Kenyan women with reliably estimated dates of HIV-1 acquisition. Regression analyses were used to estimate associations between pre-infection vitamin E and plasma viral load, time to CD4 count <200 cells/muL, and mortality.Results: After controlling for potential confounding factors, each 1 mg/L increase in pre-infection vitamin E was associated with 0.08 log10 copies/mL (95% CI -0.01 to +0.17) higher set point viral load and 1.58-fold higher risk of mortality (95% CI 1.15-2.16). The association between higher pre-infection vitamin E and mortality persisted after adjustment for set point viral load (HR 1.55, 95% CI 1.13-2.13).Conclusion: Higher pre-infection vitamin E levels were associated with increased mortality. Further research is needed to elucidate the role vitamin E plays in HIV-1 pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Impaired proprioception in the lumbar spine has often been reported in people with low back pain. However, no prospective studies exist to assert the cause and effect of this association. We hypothesized that athletes with a history of low back injury (LBI) would demonstrate poorer lumbar position sense (PS) than athletes without a history of LBI, and that this deficit would be a risk factor for future LBI.Methods: This was a prospective cohort study with 2-3 year follow-up. Lumbar spine PS in the transverse plane was evaluated in 292 athletes using three tests: 1) passive and 2) active trunk repositioning, and 3) motion perception threshold. Mean absolute (accuracy) and variable (precision) errors were computed.Results: There were no significant differences in the repositioning errors or motion perception threshold between athletes with and without a history of LBI or between those who did and did not get injured during the follow-up. Active trunk repositioning resulted in smaller errors than passive repositioning (1.6 degrees +/- 0.8 degrees ) versus 2.1 degrees +/- 1.0 degrees ) and 1.7 degrees +/- 0.8 degrees ) versus 2.3 degrees +/- 1.1 degrees ) for the absolute and relative errors, respectively).Conclusion: Poor trunk PS in transverse plane is not associated with LBI in athletes, nor does it appear that poor trunk PS predisposes athletes to LBI. [ABSTRACT FROM AUTHOR]

Background: Law and policy in several countries require health services to demonstrate that they are promoting racial/ethnic equality. However, suitable and accurate data are usually not available. We demonstrated, using acute myocardial infarction, that linkage techniques can be ethical and potentially useful for this purpose.Methods: The linkage was based on probability matching. Encryption of a unique national health identifier (the Community Health Index (CHI)) ensured that information about health status and census-based ethnicity could not be ascribed to an identified individual. We linked information on individual ethnic group from the 2001 Census to Scottish hospital discharge and mortality data.Results: Overall, 94% of the 4.9 million census records were matched to a CHI record with an estimated false positive rate of less than 0.1 %, with 84.9 - 87.6% of South Asians being successfully linked. Between April 2001 and December 2003 there were 126 first episodes of acute myocardial infarction (AMI) among South Asians and 30,978 among non-South Asians. The incidence rate ratio was 1.45 (95% CI 1.17, 1.78) for South Asian compared to non-South Asian men and 1.80 (95% CI 1.31, 2.48) for South Asian women. After adjustment for age, sex and any previous admission for diabetes the hazard ratio for death following AMI was 0.59 (95% CI 0.43, 0.81), reflecting better survival among South Asians.Conclusion: The technique met ethical, professional and legal concerns about the linkage of census and health data and is transferable internationally wherever the census (or population register) contains ethnic group or race data. The outcome is a retrospective cohort study. Our results point to increased incidence rather than increased case fatality in explaining high CHD mortality rate. The findings open up new methods for researchers and health planners. [ABSTRACT FROM AUTHOR]

The article reflects on how national health research systems should be organised. Researchers say that they are most likely to succeed when they are funded to explore issues in science and medicine. They suggest that there should be a detailed analysis and action both at the national and international levels that adopt a systems approach to meet various needs. They applaud the health research systems in Great Britain and Canada.

By nature, scientists contribute to our understanding of nature and ourselves. As communities undergo significant changes, new challenges are presented. Here, we offer alternative views on recent changes in society. [ABSTRACT FROM AUTHOR]

Many western industrialized countries are currently suffering from a crisis in health human resources, one that involves a debate over the recruitment and licensing of foreign-trained doctors and nurses. The intense public policy interest in foreign-trained medical personnel, however, is not new. During the 1960s, western countries revised their immigration policies to focus on highly-trained professionals. During the following decade, hundreds of thousands of health care practitioners migrated from poorer jurisdictions to western industrialized countries to solve what were then deemed to be national doctor and nursing 'shortages' in the developed world. Migration plummeted in the 1980s and 1990s only to re-emerge in the last decade as an important debate in global health care policy and ethics. This paper will examine the historical antecedents to this ethical debate. It will trace the early articulation of the idea of a 'brain drain', one that emerged from the loss of NHS doctors to other western jurisdictions in the 1950s and 1960s. Only over time did the discussion turn to the 'manpower' losses of 'third world countries', but the inability to track physician migration, amongst other variables, muted any concerted ethical debate. By contrast, the last decade's literature has witnessed a dramatically different ethical framework, informed by globalization, the rise of South Africa as a source donor country, and the ongoing catastrophe of the AIDS epidemic. Unlike the literature of the early 1970s, recent scholarship has focussed on a new framework of global ethics. [ABSTRACT FROM AUTHOR]

Background: There is considerable potential for health research to contribute to improved health services, programs, and outcomes; the policies of health research funding agencies are critical to achieving health gains from research. The need for research to better address health disparities in Indigenous people has been widely recognised. This paper: (i) describes the policy changes made by the National Health and Medical Research Council (NHMRC) from 1997 to 2002 to improve funding of Aboriginal health research (ii) examines catalysts for the policy changes (iii) describes the extent to which policy changes were followed by new models of research and (iv) outlines issues for Indigenous health policy in the future. Methods: This study had two parts: (i) semi-structured interviews were conducted over a four - month period with seven individuals who played a leading role in the policy changes at NHMRC during the period 1997-2002, to describe policy changes and to examine the catalysts for the changes; (ii) a case study was undertaken to evaluate projects by recipients of NHMRC People Support awards and NHMRC Capacity Building Grants in Population Health Research to examine the types of research being undertaken five years after the policy changes were implemented. The proposals of these researchers were assessed in terms of whether they reported intending to: evaluate interventions; engage Indigenous community members and organisations; and build research capacity among Indigenous people. Results: Seven policy changes over a period of five years were identified, including those to: establish an ethical approach to working with Indigenous people; increase the influence of Indigenous people within NHMRC; encourage priority research directed at improving Indigenous health; and recognise Aboriginal and Torres Strait Islander health research as a priority area including a commitment to an expenditure target of 5% of annual funds. Seven catalysts for this change were identified. These included: a perceived lack of effective response to the health needs of Indigenous people; a changed perception of the role of NHMRC in encouraging research to maximise health gains; and leadership within the organisation. The case study analysis demonstrated that 45% of all People Support recipients intend to engage Indigenous community members and organisations in consultation, 26% included an evaluation of an intervention and two (6.5%) were granted to an individual from an Indigenous background. Six of seven Population Health Capacity Building Grants that were awarded to study Indigenous health between 2004 and 2006 included an intervention component; these grants supported 34 researchers from Indigenous backgrounds. Conclusion: NHMRC made significant policy changes from 1997 to 2002 to better support Indigenous health as a result of external pressure and internal commitment. The policy changes have made some progress in supporting better research models particularly in improving engagement with Indigenous communities. However, there remains a need for further reform to optimise research outcomes for Indigenous people from research. [ABSTRACT FROM AUTHOR]

Background: Lung cancer remains the leading cause of cancer-related mortality despite continuous efforts to find effective treatments. Data from the American Cancer Society indicate that while the overall incidence of lung cancer is declining, it continues to rise in women. Stem cell-based therapy has been an emerging strategy to treat various diseases. The purpose of this paper is to determine the efficacy of an intrinsic anti-cancer effect of rat umbilical cord matrix stem cells (UCMSCs) on lung cancer.Methods: A mouse syngeneic lung carcinoma model was used to test the basic ability of UCMSCs to control the growth of lung cancer. Lung tumors were experimentally induced by tail vein administration of Lewis lung carcinoma (LLC) cells derived from the lung of C57BL/6 mouse. Rat UCMSCs were then administered intratracheally five days later or intravenously on days 5 and 7. The tumor burdens were determined by measuring lung weight three weeks after the treatment.Results: Co-culture of rat UCMSCs with LLC significantly attenuated the proliferation of LLC cells as monitored by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), a tetrazole cell proliferation assay, thymidine uptake, and direct cell counts. In vitro colony assays with rat UCMSCs as feeder layers markedly reduced LLC colony size and number. Co-culture of rat UCMSCs with LLCs causes G0/G1 arrest of cancer cells. This is evident in the decrease of cyclin A and CDK2 expression. The in vivo studies showed that rat UCMSC treatment significantly decreased tumor weight and the total tumor mass. Histological study revealed that intratracheally or systemically administered rat UCMSCs homed to tumor areas and survived for at least 3 weeks without any evidence of differentiation or adverse effects.Conclusions: These results indicate that rat UCMSCs alone remarkably attenuate the growth of lung carcinoma cells in vitro and in a mouse syngeneic lung carcinoma graft model and could be used for targeted cytotherapy for lung cancer. [ABSTRACT FROM AUTHOR]

Background: The Boston Puerto Rican Health Study is an ongoing longitudinal cohort study designed to examine the role of psychosocial stress on presence and development of allostatic load and health outcomes in Puerto Ricans, and potential modification by nutritional status, genetic variation, and social support.Methods: Self-identified Puerto Ricans, aged 45-75 years and residing in the Boston, MA metro area, were recruited through door-to-door enumeration and community approaches. Participants completed a comprehensive set of questionnaires and tests. Blood, urine and salivary samples were extracted for biomarker and genetic analysis. Measurements are repeated at a two-year follow-up.Results: A total of 1500 eligible participants completed baseline measurements, with nearly 80% two-year follow-up retention. The majority of the cohort is female (70%), and many have less than 8th grade education (48%), and fall below the poverty level (59%). Baseline prevalence of health conditions is high for this age range: considerable physical (26%) and cognitive (7%) impairment, obesity (57%), type 2 diabetes (40%), hypertension (69%), arthritis (50%) and depressive symptomatology (60%).Conclusions: The enrollment of minority groups presents unique challenges. This report highlights approaches to working with difficult to reach populations, and describes some of the health issues and needs of Puerto Rican older adults. These results may inform future studies and interventions aiming to improve the health of this and similar communities. [ABSTRACT FROM AUTHOR]

Background: In Ontario, local public health inspectors play an important frontline role in protecting the public from foodborne illness. This study was an in-depth exploration of public health inspectors' perceptions of the key food safety issues in public health, and their opinions and needs with regards to food safety information resources.Methods: Four focus group discussions were conducted with public health inspectors from the Central West region of Ontario, Canada during June and July, 2008. A questioning route was used to standardize qualitative data collection. Audio recordings of sessions were transcribed verbatim and data-driven content analysis was performed.Results: A total of 23 public health inspectors participated in four focus group discussions. Five themes emerged as key food safety issues: time-temperature abuse, inadequate handwashing, cross-contamination, the lack of food safety knowledge by food handlers and food premise operators, and the lack of food safety information and knowledge about specialty foods (i.e., foods from different cultures). In general, participants reported confidence with their current knowledge of food safety issues and foodborne pathogens. Participants highlighted the need for a central source for food safety information, access to up-to-date food safety information, resources in different languages, and additional food safety information on specialty foods.Conclusions: The information gathered from these focus groups can provide a basis for the development of resources that will meet the specific needs of public health inspectors involved in protecting and promoting food safety. [ABSTRACT FROM AUTHOR]

Background: There has been limited research on the impact of research funding for small, institutional grants. The IWK Health Centre, a children and women's hospital in Maritime Canada, provides small amounts (up to $15,000) of research funding for staff and trainees at all levels of experience through its Research Operating Grants. These grants are rigorously peer-reviewed. To evaluate the impact of these grants, an assessment was completed of several different areas of impact. Findings: An online questionnaire was sent to 64 Principal Investigators and Co-Investigators from Research Operating Grants awarded from 2004 to 2006. The questionnaire was designed to assess five areas of potential impact: (1) research, (2) policy, (3) practice, (4) society and (5) personal. Research impact reported by participants included publications (72%), presentations (82%) and knowledge transfer beyond the traditional formats (51%). Practice impact was reported by 67% of participants, policy impact by 15% and societal impact by 18%. All participants reported personal impact. Conclusions: Small research grants yield similar impacts to relatively large research grants. Regardless of the total amount of research funds awarded, rigorously peer-reviewed research projects have the potential for significant impact at the level of knowledge transfer and changes in clinical practice and policy. Additional findings in the present research indicate that small awards have the potential to have significant impact on the individual grant holder across a variety of capacity building variables. These personal impacts are particularly noteworthy in the context of developing the research programs of novice researchers. [ABSTRACT FROM AUTHOR]

Background: In the UK, most funding bodies now expect a commitment or effort on the part of grant holders to disseminate the findings of their research. The emphasis is on ensuring that publicly funded research is made available, can be used to support decision making, and ultimately improve the quality and delivery of healthcare provided. In this study, we aimed to describe the dissemination practices and impacts of applied and public health researchers working across the UK.Methods: We conducted a survey of 485 UK-based principal investigators of publicly funded applied and public health research. Participants were contacted by email and invited to complete an online questionnaire via an embedded URL. Gift vouchers were given to all participants who completed the questionnaire. Four reminder emails were sent out to non-respondents at one, two, three, and four weeks; a fifth postal reminder was also undertaken.Results: A total of 243/485 (50%) questionnaires were returned (232 completed, 11 declining to participate). Most researchers recognise the importance of and appear committed to research dissemination. However, most dissemination activity beyond the publishing of academic papers appears to be undertaken an ad hoc fashion. There is some evidence that access to dissemination advice and support may facilitate more policy interactions; though access to such resources is lacking at an institutional level, and advice from funders can be variable. Although a minority of respondents routinely record details about the impact of their research, when asked about impact in relation to specific research projects most were able to provide simple narrative descriptions.Conclusions: Researchers recognise the importance of and appear committed to disseminating the findings of their work. Although researchers are focussed on academic publication, a range of dissemination activities are being applied albeit in an ad hoc fashion. However, what constitutes effective dissemination (in terms of impact and return on investment) remains unclear. Researchers need greater and clearer guidance on how best to plan, resource, and facilitate their dissemination activities. [ABSTRACT FROM AUTHOR]

Mammalian lung development is a complex biological process, which is temporally and spatially regulated by growth factors, hormones, and extracellular matrix proteins. Abnormal changes of these molecules often lead to impaired lung development, and thus pulmonary diseases. Epithelial-mesenchymal interactions are crucial for fetal lung development. This paper reviews two interconnected pathways, pleiotrophin and Wnt/beta-catenin, which are involved in fibroblast and epithelial cell communication during fetal lung development. [ABSTRACT FROM AUTHOR]

A COST Action is a consortium of -mainly- European scientists (but open to international cooperation) working on a common research area, with the same subject; COST provides funding to the Actions for networking and dissemination activities, thus the participating scientists must have secured research funding from other national or European sources. COST funding is in the scale of approximately 100 kEuros per year and in this vein, it is often criticized both in that it does not fund research and the core science and in that its funding is 'limited'. However, COST with its instruments is an integral pillar of the European Research Area, and it is through its mission that a variety of aspects of the research environment, fundamental to the success of the research, are catered for; these include scientific networking, collaboration/exchange/training and dissemination activities. Through fast procedures, proposals are evaluated and approved for funding in less than one year from submission date and Actions become operational immediately, managed on flexible management. In this way, COST contributes to reducing the fragmentation in European research investments, while opening the European Research Area to cooperation worldwide. COST Actions have an excellent record of building the critical mass for follow up activities in the EU FP or other similarly competitive programmes. [ABSTRACT FROM AUTHOR]

Background: Research has identified women in rural and remote areas as higher users of complementary and alternative medicine (CAM) practitioners than their urban counterparts. However, we currently know little about what influences women's CAM consumption across the urban/rural divide. This paper analyses 10,638 women's CAM use across urban and rural Australia. Methods: Data for this research comes from Survey 5 of the Australian Longitudinal Study on Women's Health conducted in 2007. The participants were aged 56-61years. The health status and health service use of CAM users and non-users were compared using chi-square tests for categorical variables and t-tests for continuous variables. Results: Women who consulted a CAM practitioner varied significantly by place of residence: 28%, 32% and 30% for urban, rural and remote areas respectively (P < .005). CAM users tended to be more dissatisfied with conventional care than CAM non-users, but this was consistent across the 3 areas of residence. CAM users have higher percentages of most symptoms but the only rural/urban differences were for severe tiredness, night sweats, depression and anxiety. For diagnosed diseases, CAM users have higher percentages of most diagnoses but only hypertension and skin cancer were statistically significantly higher for rural and remote but not urban women (P < .005). Conclusions: In contrast to some recent claims, our analysis suggests the lack of access to and/or patient dissatisfaction with conventional health practitioners may not play a central role in explaining higher use of CAM by women in rural and remote areas when compared to women in urban areas. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that the barks and roots of some Apocynaceae species have anticancer and antimalarial properties. In this study, leaf extracts of five selected species of Apocynaceae used in traditional medicine (Alstonia angustiloba, Calotropis gigantea, Dyera costulata, Kopsia fruticosa and Vallaris glabra) were assessed for antiproliferative (APF) and antiplasmodial (APM) activities, and analysed for total alkaloid content (TAC), total phenolic content (TPC) and radical-scavenging activity (RSA). As V. glabra leaf extracts showed wide spectrum APF and APM activities, they were further screened for saponins, tannins, cardenolides and terpenoids. Methods: APF and APM activities were assessed using the sulphorhodamine B and lactate dehydrogenase assays, respectively. TAC, TPC and RSA were analysed using Dragendorff precipitation, Folin-Ciocalteu and DPPH assays, respectively. Screening for saponins, tannins, cardenolides and terpenoids were conducted using the frothing, ferric chloride, Kedde and vanillin-H2SO4 tests, respectively. Results: Leaf extracts of A. angustiloba, C. gigantea and V. glabra displayed positive APF activity. Dichloromethane (DCM) extract of C. gigantea, and DCM and DCM:MeOH extracts of V. glabra showed strong APF activity against all six human cancer cell lines tested. DCM extract of A. angustiloba was effective against three cancer cell lines. Against MCF-7 and MDA-MB-231 cell lines, DCM extract of C. gigantea was stronger than standard drugs of xanthorrhizol, curcumin and tamoxifen. All five species were effective against K1 strain of Plasmodium falciparum and three species (C. gigantea, D. costulata and K. fruticosa) were effective against 3D7 strain. Against K1 strain, all four extracts of V. glabra displayed effective APM activity. Extracts of D. costulata were effective against 3D7 strain. Selectivity index values of extracts of A. angustiloba, C. gigantea and V. glabra suggested that they are potentially safe for use to treat malaria. Extracts of K. fruticosa had the highest TAC while D. costulata had the highest TPC and RSA. Phytochemical screening of extracts of V. glabra also showed the presence of terpenoids, tannins and saponins. Conclusions: Leaf extracts of C. gigantea and V. glabra showed great promise as potential candidates for anticancer drugs as they inhibited the growth of all six cancer cell lines. Against K1 strain of P. falciparum, all four extracts of V. glabra displayed effective APM activity. The wide spectrum APF and APM activities of V. glabra are reported for the first time and this warrants further investigation into its bioactive compounds. [ABSTRACT FROM AUTHOR]

Background: Both resveratrol and vitamin C (ascorbic acid) are frequently used in complementary and alternative medicine. However, little is known about the underlying mechanisms for potential health benefits of resveratrol and its interactions with ascorbic acid. Methods: The antioxidant enzymes heme oxygenase-1 and paraoxonase-1 were analysed for their mRNA and protein levels in HUH7 liver cells treated with 10 and 25 μmol/l resveratrol in the absence and presence of 100 and 1000 μmol/l ascorbic acid. Additionally the transactivation of the transcription factor Nrf2 and paraoxonase-1 were determined by reporter gene assays. Results: Here, we demonstrate that resveratrol induces the antioxidant enzymes heme oxygenase-1 and paraoxonase-1 in cultured hepatocytes. Heme oxygenase-1 induction by resveratrol was accompanied by an increase in Nrf2 transactivation. Resveratrol mediated Nrf2 transactivation as well as heme oxygenase-1 induction were partly antagonized by 1000 μmol/l ascorbic acid. Conclusions: Unlike heme oxygenase-1 (which is highly regulated by Nrf2) paraoxonase-1 (which exhibits fewer ARE/Nrf2 binding sites in its promoter) induction by resveratrol was not counteracted by ascorbic acid. Addition of resveratrol to the cell culture medium produced relatively low levels of hydrogen peroxide which may be a positive hormetic redox-signal for Nrf2 dependent gene expression thereby driving heme oxygenase-1 induction. However, high concentrations of ascorbic acid manifold increased hydrogen peroxide production in the cell culture medium which may be a stress signal thereby disrupting the Nrf2 signalling pathway. [ABSTRACT FROM AUTHOR]

Background: The 'Physical Activity Care Pathway' (a Pilot for the 'Let's Get Moving' policy) is a systematic approach to integrating physical activity promotion into the primary care setting. It combines several methods reported to support behavioural change, including brief interventions, motivational interviewing, goal setting, providing written resources, and follow-up support. This paper compares costs falling on the UK National Health Service (NHS) of implementing the care pathway using two different recruitment strategies and provides initial insights into the cost of changing physical activity behaviour.Methods: A combination of a time driven variant of activity based costing, audit data through EMIS and a survey of practice managers provided patient-level cost data for 411 screened individuals. Self reported physical activity data of 70 people completing the care pathway at three month was compared with baseline using a regression based 'difference in differences' approach. Deterministic and probabilistic sensitivity analyses in combination with hypothesis testing were used to judge how robust findings are to key assumptions and to assess the uncertainty around estimates of the cost of changing physical activity behaviour.Results: It cost £53 (SD 7.8) per patient completing the PACP in opportunistic centres and £191 (SD 39) at disease register sites. The completer rate was higher in disease register centres (27.3% vs. 16.2%) and the difference in differences in time spent on physical activity was 81.32 (SE 17.16) minutes/week in patients completing the PACP; so that the incremental cost of converting one sedentary adult to an 'active state' of 150 minutes of moderate intensity physical activity per week amounts to £ 886.50 in disease register practices, compared to opportunistic screening.Conclusions: Disease register screening is more costly than opportunistic patient recruitment. However, additional costs come with a higher completion rate and better outcomes in terms of behavioural change in patients completing the care pathway. Further research is needed to rigorously evaluate intervention efficiency and to assess the link between behavioural change and changes in quality adjusted life years (QALYs). [ABSTRACT FROM AUTHOR]

We prepared a consolidated list of edible and therapeutic insects used in Arunachal Pradesh (N.E. India) by two tribal societies (i.e., the Nyishi of East Kameng and the Galo of West Siang). The list is based on thorough, semi-structured field-interviews with 20 informants of each tribal group. At least 81 species of local insects, belonging to 26 families and five orders of insects, namely Coleoptera (24 species), Orthoptera (17 species), Hemiptera (16 species), Hymenoptera (15 species) and Odonata (9 species), are being used as food among members of these two indigenous societies. However, Nyishi use overall more species of insects as food than Galo people do and consume mostly Coleoptera and Hemiptera; amongst the Galo, on the other hand, Odonata and Orthoptera dominate. The selection of the food insects amongst the Nyishi and Galo is dictated by traditional tribal beliefs as well as the taste and availability of the insects. Depending on the species, only particular or all developmental stages are consumed. Some food insects may be included in the local diet throughout the year, others only when seasonally available. Commonly specimens are being prepared for consumption by roasting, frying or boiling. Twelve species of insects are deemed therapeutically valuable by the locals and are being used by the tribes investigated to treat a variety of disorders in humans and domestic animals. Members of the Galo use a greater number of insect species for remedial purposes than the Nyishi. With the degradation of natural resources, rapid population growth, and increasing influence of 'westernization', the traditional wisdom of entomophagy and entomotherapy is at risk of being lost. There is thus an urgent need to record the role insects play as components of local diets and folk remedies and to assess insect biodiversity in the light of these uses. [ABSTRACT FROM AUTHOR]

In this study, we sought to investigate the biology (diet and reproduction) and ethnobiology (fishers knowledge and fishing spots used to catch snappers) of five species of snappers (Lutjanidae), including Lutjanus analis, Lutjanus synagris, Lutjanus vivanus, Ocyurus chrysurus, and Romboplites saliens at five sites along the northeast (Riacho Doce, Maceió in Alagoas State, and Porto do Sauípe, Entre Rios at Bahia State) and the southeast (SE) Brazilian coast (Paraty and Rio de Janeiro cities at Rio de Janeiro State, and Bertioga, at São Paulo State.). We collected 288 snappers and interviewed 86 fishermen. The stomach contents of each fish were examined and macroscopic gonad analysis was performed. Snappers are very important for the fisheries of NE Brazil, and our results indicated that some populations, such as mutton snapper (L. analis) and lane snapper (L. synagris), are being caught when they are too young, at early juvenile stages. Local knowledge has been shown to be a powerful tool for determining appropriate policies regarding management of target species, and artisanal fishermen can be included in management processes. Other suggestions for managing the fisheries are discussed, including proposals that could provide motivation for artisanal fishermen to participate in programs to conserve resources, such as co-management approaches that utilize local knowledge, the establishment of fishing seasons, and compensation of fishermen, through 'payment for environmental services'. These suggestions may enhance the participation of local artisanal fishermen in moving to a more realistic and less top-down management approach of the fish population. [ABSTRACT FROM AUTHOR]

Arunachal Pradesh, the easternmost part of India, is endowed with diverse natural resources and inhabited by a variety of ethnic groups that have developed skills to exploit the biotic resources of the region for food and medicines. Information on animals and animal parts as components of folk remedies used by local healers and village headmen of the Nyishi and Galo tribes in their respective West Siang and Subansiri districts were obtained through interviews and structured questionnaires. Of a total of 36 vertebrate species used in treatments of ailments and diseases, mammals comprised 50%; they were followed by birds (22%), fishes (17%), reptiles (8%) and amphibians (3%). Approximately 20 common complaints of humans as well as foot and mouth disease of cattle were targets of zootherapies. Most commonly treated were fevers, body aches and pains, tuberculosis, malaria, wounds and burns, typhoid, smallpox, dysentery and diarrhoea, jaundice, and early pregnancy pains. Very few domestic animal species (e.g., goat and cattle) were used zootherapeutically. More frequently it was wild animals, including endangered or protective species like hornbill, pangolin, clouded leopard, tiger, bear, and wolf, whose various parts were either used in folk remedies or as food. Some of the animal-based traditional medicines or animal parts were sold at local markets, where they had to compete with modern, western pharmaceuticals. To record, document, analyze and test the animal-derived local medicines before they become replaced by western products is one challenge; to protect the already dwindling populations of certain wild animal species used as a resource for the traditional animal-derived remedies, is another. [ABSTRACT FROM AUTHOR]

Background: Ethnobotanical research was carried out with speakers of Iquito, a critically endangered Amazonian language of the Zaparoan family. The study focused on the concept of "dieting" (siyan++ni in Iquito), a practice involving prohibitions considered necessary to the healing process. These restrictions include: 1) foods and activities that can exacerbate illness, 2) environmental influences that conflict with some methods of healing (e.g. steam baths or enemas) and 3) foods and activities forbidden by the spirits of certain powerful medicinal plants. The study tested the following hypotheses: H1 - Each restriction will correlate with specific elements in illness explanatory models and H2 - Illnesses whose explanatory models have personalistic elements will show a greater number and variety of restrictions than those based on naturalistic reasoning. Methods: The work was carried out in 2009 and 2010 in the Alto Nanay region of Peru. In structured interviews, informants gave explanatory models for illness categories, including etiologies, pathophysiologies, treatments and dietary restrictions necessary for 49 illnesses. Seventeen botanical vouchers for species said to have powerful spirits that require diets were also collected. Results: All restrictions found correspond to some aspect of illness explanatory models. Thirty-five percent match up with specific illness etiologies, 53% correspond to particular pathophysiologies, 18% correspond with overall seriousness of the illness and 18% are only found with particular forms of treatment. Diets based on personalistic reasoning have a significantly higher average number of restrictions than those based on naturalistic reasoning. Conclusions: Dieting plays a central role in healing among Iquito speakers. Specific prohibitions can be explained in terms of specific aspects of illness etiologies, pathophysiologies and treatments. Although the Amazonian literature contains few studies focusing on dietary proscriptions over a wide range of illnesses, some specific restrictions reported here do correspond with trends seen in other Amazonian societies, particularly those related to sympathetic reasoning and for magical and spiritual uses of plants. [ABSTRACT FROM AUTHOR]

Background: Nogo-66 receptor NgR1 and its structural homologue NgR2 are binding proteins for a number of myelin-associated inhibitory factors. After neuronal injury, these inhibitory factors are responsible for preventing axonal outgrowth via their interactions with NgR1 and NgR2 expressed on neurons. In vitro, cells expressing NgR1/2 are inhibited from adhering to and spreading on a myelin substrate. Neuronal injury also results in the presence of dendritic cells (DCs) in the central nervous system, where they can come into contact with myelin debris. The exact mechanisms of interaction of immune cells with CNS myelin are, however, poorly understood.Methods: Human DCs were differentiated from peripheral blood monocytes and mouse DCs were differentiated from wild type and NgR1/NgR2 double knockout bone marrow precursors. NgR1 and NgR2 expression were determined with quantitative real time PCR and immunoblot, and adhesion of cells to myelin was quantified.Results: We demonstrate that human immature myeloid DCs express NgR1 and NgR2, which are then down-regulated upon maturation. Human mature DCs also adhere to a much higher extent to a myelin substrate than immature DCs. We observe the same effect when the cells are plated on Nogo-66-His (binding peptide for NgR1), but not on control proteins. Mature DCs taken from Ngr1/2 knockout mice adhere to a much higher extent to myelin compared to wild type mouse DCs. In addition, Ngr1/2 knockout had no effect on in vitro DC differentiation or phenotype.Conclusions: These results indicate that a lack of NgR1/2 expression promotes the adhesion of DCs to myelin. This interaction could be important in neuroinflammatory disorders such as multiple sclerosis in which peripheral immune cells come into contact with myelin debris. [ABSTRACT FROM AUTHOR]

Novel, exciting intervention strategies to prevent infection with HIV have been tested in the past year, and the field is rapidly evolving. EUROPRISE is a network of excellence sponsored by the European Commission and concerned with a wide range of activities including integrated developmental research on HIV vaccines and microbicides from discovery to early clinical trials. A central and timely theme of the network is the development of the unique concept of co-usage of vaccines and microbicides. This review, prepared by the PhD students of the network captures much of the research ongoing between the partners. The network is in its 5th year and involves over 50 institutions from 13 European countries together with 3 industrial partners; GSK, Novartis and Sanofi-Pasteur. EUROPRISE is involved in 31 separate world-wide trials of Vaccines and Microbicides including 6 in African countries (Tanzania, Mozambique, South Africa, Kenya, Malawi, Rwanda), and is directly supporting clinical trials including MABGEL, a gp140-hsp70 conjugate trial and HIVIS, vaccine trials in Europe and Africa. [ABSTRACT FROM AUTHOR]

Background: Heavy alcohol consumption during adolescence has many known harmful health and social consequences and is strongly associated with numerous health risk behaviours. The consequences of heavy alcohol use during adolescence on nutritional status, specifically growth and weight status are largely unknown at this time.Methods: Substance use, anthropometric indices of growth and weight, dietary energy intake and physical activity in heavy drinking adolescents (meeting DSM-IV criteria for alcohol use disorders) and matched light/non-drinking control adolescents were assessed.Results: Lifetime alcohol dose, measured in standard drinks of alcohol, was orders of magnitude higher in adolescents with alcohol use disorders (AUDs) compared to controls. The AUDs group was selected to represent relatively 'pure' AUDs, with minimal other drug use and no psychiatric diagnoses. The growth and weight status of adolescents with AUDs were generally comparable to that of controls, and is in line with the growth and weight status of the South African adolescent population. A greater proportion of overweight/obese females was found in both groups, with this percentage tending to be greater, although not significantly so, in the AUDs group. Adolescent females with AUDs had increased odds of being overweight/obese compared to controls, after adjustment for smoking, physical activity and energy intake.Conclusion: Anthropometric indices of growth and weight status of participants in the Control and AUD groups were generally comparable. Female adolescents with AUDs may have an increased risk of being overweight/obese compared to adolescent females without AUDs. The presence of an AUD in our adolescent sample was associated with higher energy intake. Longitudinal studies are needed to elucidate the effects of heavy alcohol use on energy balance, growth and weight status in adolescents as they age. Nonetheless, the current study contributes to our understanding of the impacts of heavy alcohol consumption on important aspects of adolescent development. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE) is a major health and financial burden. VTE impacts health outcomes in surgical and non-surgical patients. VTE prophylaxis is underutilized, particularly amongst high risk medical patients. We conducted a multicentre clinical audit to determine the extent to which appropriate VTE prophylaxis in acutely ill hospitalized medical patients could be improved via implementation of a multifaceted nurse facilitated educational program. Methods: This multicentre clinical audit of 15 Australian hospitals was conducted in 2007-208. The program incorporated a baseline audit to determine the proportion of patients receiving appropriate VTE prophylaxis according to best practice recommendations issued by the Australian and New Zealand Working Party on the Management and Prevention of Venous Thromboembolism (ANZ-WP recommendations), followed by a 4-month education intervention program and a post intervention audit. The primary endpoint was to compare the proportion of patients being appropriately managed based on their risk profile between the two audits. Results: A total of 8774 patients (audit 1; 4399 and audit 2; 4375) were included in the study, most (82.2% audit 1; and 81.0% audit 2) were high risk based on ANZ-WP recommendations. At baseline 37.9% of high risk patients were receiving appropriate thromboprophylaxis. This increased to 54.1% in the post intervention audit (absolute improvement 16%; 95% confidence interval [CI] 11.7%, 20.5%). As a result of the nurse educator program, the likelihood of high risk patients being treated according to ANZ-WP recommendations increased significantly (OR 1.96; 1.62, 2.37). Conclusion: Utilization of VTE prophylaxis amongst hospitalized medical patients can be significantly improved by implementation of a multifaceted educational program coordinated by a dedicated nurse practitioner. [ABSTRACT FROM AUTHOR]

Background: Elastin microfibril interface located protein 2 (EMILIN2) is an extracellular glycoprotein associated with cardiovascular development. While other EMILIN proteins are reported to play a role in elastogenesis and coagulation, little is known about EMILIN2 function in the cardiovascular system. The objective of this study was to determine whether EMILIN2 could play a role in thrombosis. Results: EMILIN2 mRNA was expressed in 8 wk old C57BL/6J mice in lung, heart, aorta and bone marrow, with the highest expression in bone marrow. In mouse cells, EMILIN2 mRNA expression in macrophages was higher than expression in endothelial cells and fibroblasts. EMILIN2 was identified with cells and extracellular matrix by immunohistochemistry in the carotid and aorta. After carotid ferric chloride injury, EMILIN2 was abundantly expressed in the thrombus and inhibition of EMILIN2 increased platelet de-aggregation after ADP-stimulated platelet aggregation. Conclusions: These results suggest EMILIN2 could play a role in thrombosis as a constituent of the vessel wall and/or a component of the thrombus. [ABSTRACT FROM AUTHOR]

Background: This protocol is for a study of a new program to improve outcomes in children suffering from chronic pain disorders, such as fibromyalgia, recurrent headache, or recurrent abdominal pain. Although teaching active pain self-management skills through cognitive-behavioral therapy (CBT) or a complementary program such as hypnotherapy or yoga has been shown to improve pain and functioning, children with low expectations of skill-building programs may lack motivation to comply with therapists' recommendations. This study will develop and test a new manualized peer-mentorship program which will provide modeling and reinforcement by peers to other adolescents with chronic pain (the mentored participants). The mentorship program will encourage mentored participants to engage in therapies that promote the learning of pain self-management skills and to support the mentored participants' practice of these skills. The study will examine the feasibility of this intervention for both mentors and mentored participants, and will assess the preliminary effectiveness of this program on mentored participants' pain and functional disability.Methods: This protocol will recruit adolescents ages 12-17 with chronic pain and randomly assign them to either peer mentorship or a treatment-as-usual control group. Mentored participants will be matched with peer mentors of similar age (ages 14-18) who have actively participated in various treatment modalities through the UCLA Pediatric Pain Program and have learned to function successfully with a chronic pain disorder. The mentors will present information to mentored participants in a supervised and monitored telephone interaction for 2 months to encourage participation in skill-building programs. The control group will receive usual care but without the mentorship intervention. Mentored and control subjects' pain and functioning will be assessed at 2 months (end of intervention for mentored participants) and at 4 month follow-up to see if improvements persist. Measures of treatment adherence, pain, disability, and anxiety and depression will be assessed throughout study participation. Qualitative interviews for mentors, mentored participants, and control subjects will also be administered.Trial Registration: ClinicalTrials.gov NCT01118988. [ABSTRACT FROM AUTHOR]