Ethnicity classification systems for public health surveys: experiences from HIV behavioural surveillance among men who have sex with men.

BACKGROUND: Race and ethnicity classification systems have considerable implications for public health, including the potential to reveal or mask inequities. Given increasing "super-diversity" and multiple racial/ethnic identities in many global settings, especially among younger generations, different ethnicity classification systems can underrepresent population heterogeneity and can misallocate and render invisible Indigenous people and ethnic minorities. We investigated three ethnicity classification methods and their relationship to sample size, socio-demographics and sexual health indicators. METHODS: We examined data from New Zealand's HIV behavioural surveillance programme for men who have sex with men (MSM) in 2006, 2008, 2011, and 2014. Participation was voluntary, anonymous and self-completed; recruitment was via community venues and online. Ethnicity allowed for multiple responses; we investigated three methods of dealing with these: Prioritisation, Single/Combination, and Total Response. Major ethnic groups included Asian, European, indigenous Maori, and Pacific. For each classification method, statistically significant associations with ethnicity for demographic and eight sexual health indicators were assessed using multivariable logistic regression. RESULTS: Overall, 10,525 MSM provided ethnicity data. Classification methods produced different sample sizes, and there were ethnic disparities for every sexual health indicator. In multivariable analysis, when compared with European MSM, ethnic differences were inconsistent across classification systems for two of the eight sexual health outcomes: Maori MSM were less likely to report regular partner condomless anal intercourse using Prioritisation or Total Response but not Single/Combination, and Pacific MSM were more likely to report an STI diagnosis when using Total Response but not Prioritisation or Single/Combination. CONCLUSIONS: Different classification approaches alter sample sizes and identification of health inequities. Future research should strive for equal explanatory power of Indigenous and ethnic minority groups and examine additional measures such as socially-assigned ethnicity and experiences of discrimination and racism. These findings have broad implications for surveillance and research that is used to inform public health responses.

Targeting the relaxin hormonal pathway in prostate cancer.

Targeting the androgen signalling pathway has long been the hallmark of anti-hormonal therapy for prostate cancer. However, development of androgen-independent prostate cancer is an inevitable outcome to therapies targeting this pathway, in part, owing to the shift from cancer dependence on androgen signalling for growth in favor of augmentation of other cellular pathways that provide proliferation-, survival- and angiogenesis-promoting signals. This review focuses on the role of the hormone relaxin in the development and progression of prostate cancer, prior to and after the onset of androgen independence, as well as its role in cancers of other reproductive tissues. As the body of literature expands, examining relaxin expression in cancerous tissues and its role in a growing number of in vitro and in vivo cancer models, our understanding of the important involvement of this hormone in cancer biology is becoming clearer. Specifically, the pleiotropic functions of relaxin affecting cell growth, angiogenesis, blood flow, cell migration and extracellular matrix remodeling are examined in the context of cancer progression. The interactions and intercepts of the intracellular signalling pathways of relaxin with the androgen pathway are explored in the context of progression of castration-resistant and androgen-independent prostate cancers. We provide an overview of current anti-hormonal therapeutic treatment options for prostate cancer and delve into therapeutic approaches and development of agents aimed at specifically antagonizing relaxin signalling to curb tumor growth. We also discuss the rationale and challenges utilizing such agents as novel anti-hormonals in the clinic, and their potential to supplement current therapeutic modalities.

Factors associated with recent HIV testing among younger gay and bisexual men in New Zealand, 2006-2011.

BACKGROUND: Understanding HIV testing behaviour is vital to developing evidence-based policy and programming that supports optimal HIV care, support, and prevention. This has not been investigated among younger gay, bisexual, and other men who have sex with men (YMSM, aged 16-29) in New Zealand. METHODS: National HIV sociobehavioural surveillance data from 2006, 2008, and 2011 was pooled to determine the prevalence of recent HIV testing (in the last 12 months) among YMSM. Factors associated with recent testing were determined using manual backward stepwise multivariate logistic regression. RESULTS: Of 3,352 eligible YMSM, 1,338 (39.9%) reported a recent HIV test. In the final adjusted model, the odds of having a recent HIV test were higher for YMSM who were older, spent more time with other gay men, reported multiple sex partners, had a regular partner for 6-12 months, reported high condom use with casual partners, and disagreed that HIV is a less serious threat nowadays and that an HIV-positive man would disclose before sex. The odds of having a recent HIV test were lower for YMSM who were bisexual, recruited online, reported Pacific Islander or Asian ethnicities, reported no regular partner or one for >3 years, were insertive-only during anal intercourse with a regular partner, and who had less HIV-related knowledge. CONCLUSION: A priority for HIV management should be connecting YMSM at risk of infection, but unlikely to test with appropriate testing services. New generations of YMSM require targeted, culturally relevant health promotion that provides accurate understandings about HIV transmission and prevention.

Iron content of Cambodian foods when prepared in cooking pots containing an iron ingot.

OBJECTIVES: To investigate the effect of cooking with an iron ingot on the iron content of several water and Cambodian food preparations. METHODS: Various food and water samples were prepared, in replicate, in glass and aluminium pots with and without an iron ingot. The samples were subjected to iron content analysis using standard ICP-OES procedures. RESULTS: Prepared with an ingot, the iron content was 76.3 µg iron/g higher in lemon water, 32.6 µg iron/g higher in pork soup and 3.3 µg iron/g higher in fish soup, than in the same foods prepared without an ingot. Acidity of the food samples was positively associated with iron leaching. CONCLUSIONS: Even when taking into account the low bioavailability of contaminant iron, approximately 75% of the daily iron requirement can be met by consuming 1L of lemon water prepared with an iron ingot. Its use may be a cheap and sustainable means of improving iron intake for those with iron-deficient diets.

Iron-deficiency anaemia in rural Cambodia: community trial of a novel iron supplementation technique.

BACKGROUND: More than 3.5 billion people are affected by iron-deficiency anaemia (IDA). Previous studies have shown that the use of iron pots in daily cooking ameliorates IDA. We report a study on the use of a novel treatment to address IDA in rural women in Cambodia, where the use of iron pots is not common. METHODS: A community-wide randomized controlled trial was conducted in the village of Preak Ruessei, Kandal Province, Cambodia. Rural women (n = 189) were enrolled and randomly assigned by household to one of three groups: (i) control, (ii) iron treatment with no follow-up and (iii) iron treatment with follow-up visits to provide IDA education. Haemoglobin, serum iron and C-reactive protein concentrations were measured at baseline, 3 and 6 months. A reusable fish-shaped iron ingot was distributed to the two treatment groups and participants were directed to use them daily for cooking. We hypothesized that iron from the ingot would leach iron into food providing an effective iron source. RESULTS: Blood iron levels were higher in women in the iron fish plus follow-up at 3 months compared with controls, but this was not maintained. At 6 months, haemoglobin and serum iron had fallen in all groups and the proportion of anaemic women had increased. CONCLUSIONS: This study shows that the iron ingot was effective in the short but not longer-term against IDA. Though a novel treatment option, further research is warranted to determine bioavailability of leached iron and whether or not the surface area is large enough for sufficient iron leaching.

Gazing into the crystal ball: where should the veterinary profession go next?

The Foresight Report, published in 2007, provided a vision for the future of the veterinary profession. Many of the directions set in the report have already been remarkably accurate, but fiscal constraints stemming from the global recession that began in 2008 will have a significant impact on academia and on the future of the veterinary profession. Three primary forces will shape veterinary education in the coming decade: (1) the urgent need to lead an integrated approach to animal, human, and environmental health; (2) the continued information explosion; and (3) the challenge of delivering high-quality veterinary clinical training at a time of fiscal restraint. Despite economic woes and financial pressure, this is the time to rethink veterinary medical education. This article outlines these challenges and suggests ways to continue to evolve veterinary education.

National trends in sexual health indicators among gay and bisexual men disaggregated by ethnicity: repeated cross-sectional behavioural surveillance in New Zealand.

OBJECTIVES: To assess trends in sexual health outcomes among men who have sex with men (MSM) disaggregated by ethnicity. DESIGN: Repeated cross-sectional. SETTING: Behavioural surveillance data from 2006, 2008, 2011 and 2014 were collected in-person and online across Aotearoa New Zealand. PARTICIPANTS: Eligible participants were self-identified men aged 16 years or older who reported sex with another man in the past 5 years. We classified 10 525 participants' ethnicities: Asian (n=1003, 9.8%), Maori (Indigenous people of Aotearoa New Zealand, n=1058, 10.3%), Pacific (n=424, 4.1%) and European (n=7867, 76.8%). OUTCOME MEASURES: The sexual health outcomes examined were >20 recent (past 6 months) male sexual partners, past-year sexually transmitted infection (STI) testing, past-year STI diagnosis, lifetime and past-year HIV testing, lifetime HIV-positive diagnosis and any recent (past 6 months) condomless anal intercourse with casual or regular partners. RESULTS: When disaggregated, Indigenous and ethnic minority groups reported sexual health trends that diverged from the European MSM and each other. For example, Asian MSM increased lifetime HIV testing (adjusted OR, AOR=1.31 per survey cycle, 95% CI 1.17 to 1.47) and recent HIV testing (AOR=1.14, 95% CI 1.02 to 1.28) with no changes among Maori MSM or Pacific MSM. Condomless anal intercourse with casual partners increased among Maori MSM (AOR=1.13, 95% CI 1.01 to 1.28) with no changes for Asian or Pacific MSM. Condomless anal intercourse with regular partners decreased among Pacific MSM (AOR=0.83, 95% CI 0.69 to 0.99) with no changes for Asian or Maori MSM. CONCLUSIONS: Population-level trends were driven by European MSM, masking important differences for Indigenous and ethnic minority sub-groups. Surveillance data disaggregated by ethnicity highlight inequities in sexual health service access and prevention uptake. Future research should collect, analyse and report disaggregated data by ethnicity to advance health equity.

Relaxin alters cardiac myofilament function through a PKC-dependent pathway.

The pregnancy hormone relaxin (RLX) is a powerful cardiostimulatory peptide. Despite its well-characterized effects on the heart, the intracellular mechanisms responsible for RLX's positive inotropic effects are unknown. Cardiac myofilaments are the central contractile elements of the heart, and changes in the phosphorylation status of myofilament proteins are known to mediate changes in function. The first objective of this study was to determine whether RLX stimulates myofilament activation and alters the phosphorylation of one or more myofilament proteins. RLX works through a variety of intracellular signaling cascades in different tissue types. Protein kinases A (PKA) and C (PKC) are two common molecules implicated in RLX signaling and are known to affect myofilament function. Thus the second objective of this study was to determine whether RLX mediates its myocardial effects through PKA or PKC activation. Murine myocardium was treated with recombinant H2-RLX, and cardiac myofilaments were isolated. RLX increased cardiac myofilament force development at physiological levels of intracellular Ca(2+) without altering myofilament ATP consumption. Myosin binding protein C, troponin T, and troponin I phosphorylation levels were increased with RLX treatment. Immunoblot analysis revealed an increase in myofilament-associated PKC-delta, decreases in PKC-alpha and -beta(II), but no effect on PKC-epsilon. Inhibition of PKC with chelerythrine chloride or PKC-delta with rottlerin prevented the RLX-dependent changes in myofilament function and protein phosphorylation. PKA antagonism with H-89 had no effect on the myofilament effects of RLX. This study is the first to show that RLX-dependent changes in myofilament-associated PKC alters myofilament activation in a manner consistent with its cardiostimulatory effects.

Analog of H2 relaxin exhibits antagonistic properties and impairs prostate tumor growth.

Hormone antagonists can be effective tools to delineate receptor signaling pathways and their resulting downstream physiological actions. Mutation of the receptor binding domain (RBD) of human H2 relaxin (deltaH2) impaired its biological function as measured by cAMP signaling. In a competition assay, deltaH2 exhibited antagonistic activity by blocking recombinant H2 relaxin from binding to receptors on THP-1 cells. In a flow cytometry-based binding assay, deltaH2 demonstrated weak binding to 293T cells expressing the LGR7 receptor in the presence of biotinylated H2 relaxin. When human prostate cancer cell lines (PC-3 and LNCaP) were engineered to overexpress eGFP, wild-type (WT) H2, or deltaH2, and subsequently implanted into NOD/SCID mice, tumor xenografts overexpressing deltaH2 displayed smaller volumes compared to H2 and eGFP controls. Plasma osmolality readings and microvessel density and area assessment suggest that deltaH2 modulates physiological parameters in vivo. In a second murine model, intratumoral injections of lentivectors engineered to express deltaH2/eGFP led to suppressed tumor growth compared to controls. This study provides further evidence supporting a role for H2 relaxin in prostate tumor growth. More importantly, we report how mutation of the H2 relaxin RBD confers the hormone derivative with antagonistic properties, offering a novel reagent for relaxin research.

Randomized controlled trial assessing the efficacy of a reusable fish-shaped iron ingot to increase hemoglobin concentration in anemic, rural Cambodian women.

Background: Anemia affects 45% of women of childbearing age in Cambodia. Iron supplementation is recommended in populations in which anemia prevalence is high. However, there are issues of cost, distribution, and adherence. A potential alternative is a reusable fish-shaped iron ingot, which, when added to the cooking pot, leaches iron into the fluid in which it is prepared.Objective: We sought to determine whether there was a difference in hemoglobin concentrations in rural Cambodian anemic women (aged 18-49 y) who cooked with the iron ingot or consumed a daily iron supplement compared with a control after 1 y.Design: In Preah Vihear, 340 women with mild or moderate anemia were randomly assigned to 1) an iron-ingot group, 2) an iron-supplement (18 mg/d) group, or 3) a nonplacebo control group. A venous blood sample was taken at baseline and at 6 and 12 mo. Blood was analyzed for hemoglobin, serum ferritin, and serum transferrin receptor. Hemoglobin electrophoresis was used to detect structural hemoglobin variants.Results: Anemia prevalence was 44% with the use of a portable hemoglobinometer during screening. At baseline, prevalence of iron deficiency was 9% on the basis of a low serum ferritin concentration. There was no significant difference in mean hemoglobin concentrations between the iron-ingot group (115 g/L; 95% CI: 113, 118 g/L; P = 0.850) or iron-supplement group (115 g/L; 95% CI: 113, 117 g/L; P = 0.998) compared with the control group (115 g/L; 95% CI: 113, 117 g/L) at 12 mo. Serum ferritin was significantly higher in the iron-supplement group (73 µg/L; 95% CI: 64, 82 µg/L; P = 0.002) than in the control group at 6 mo; however, this significance was not maintained at 12 mo (73 µg/L; 95% CI: 58, 91 µg/L; P = 0.176).Conclusions: Neither the iron ingot nor iron supplements increased hemoglobin concentrations in this population at 6 or 12 mo. We do not recommend the use of the fish-shaped iron ingot in Cambodia or in countries where the prevalence of iron deficiency is low and genetic hemoglobin disorders are high. This trial was registered at clinicaltrials.gov as NCT02341586.

Functional expression of mouse relaxin and mouse relaxin-3 in the lung from an Ebola virus glycoprotein-pseudotyped lentivirus via tracheal delivery.

The peptide hormone relaxin is a known modulator of connective tissue and the extracellular matrix by virtue of its ability to regulate matrix metalloproteinases (MMPs). Relaxin knockout mice exhibit age-related pulmonary fibrosis, and delivery of recombinant human H2 relaxin ameliorates fibrotic-like conditions in the mouse lung. We investigated whether lentiviral vectors (LVs) engineering the expression of murine relaxins could induce MMP activity in the mouse lung. Mouse relaxin and mouse relaxin-3 peptides engineered by recombinant LVs were biologically active as shown by stimulation of cAMP from both THP-1 and 293T cells stably expressing relaxin receptor LGR7 and by up-regulation of MMP-2 activity from primary C57BL/6 lung cell cultures. To provide the virions with enhanced tropism for the lung, LVs were pseudotyped with the Zaire strain of the Ebola virus glycoprotein (EboZ GP) and delivered by endotracheal intubation. LVs engineering luciferase pseudotyped with EboZ GP, but not with vesicular stomatitis virus glycoprotein resulted in successful LV transduction and transgene expression in C57BL/6 mouse lung by as early as d 4. Mice treated via tracheal delivery with EboZ GP pseudotyped LVs that engineered expression of mouse relaxins exhibited increased MMP-2 and MMP-9 activity in lung tissue up until the end of our study at d 21. Taken together, this study provides proof-of- principle that relaxin gene expression targeted to the mouse lungs can result in enhanced MMP activity offering potential for alleviating disease conditions characterized by dysregulation of extracellular matrix protein accumulation.

Frequent condom use with casual partners varies by sexual position among younger gay and bisexual men in New Zealand: national behavioural surveillance 2006-2011.

UNLABELLED: Background Condom promotion remains a cornerstone of HIV/STI control, but must be informed by evidence of uptake and address disparities in use. This study sought to determine the prevalence of, and demographic, behavioural and relational factors associated with, condom use during insertive and receptive anal intercourse with casual partners among younger gay, bisexual and other men who have sex with men (YMSM) in New Zealand. METHODS: The 2006-2011 national HIV behavioural surveillance data for YMSM aged 16-29 years was pooled. Separately for each sexual position, frequent (always/almost always) versus infrequent condom use was regressed onto explanatory variables using manual backward stepwise multivariable logistic regression analysis. RESULTS: Three-quarters of YMSM reported frequent condom use during insertive (76.0%) and receptive (73.8%) anal intercourse. YMSM who were exclusively insertive were more likely to report frequent condom use than versatile YMSM. Factors positively associated with frequent condom use, irrespective of sexual position were: in-person versus web-based recruitment, testing HIV negative versus never testing or testing HIV positive, having no recent sex with women, reporting two to five versus one male sexual partner in the past 6 months, reporting no current regular partner, but if in a regular relationship, reporting a boyfriend-type versus fuckbuddy-type partner, and frequent versus infrequent regular partner condom use. Pacific ethnicity and less formal education were negatively associated with frequent condom use only during receptive anal intercourse. CONCLUSIONS: The findings from this study demonstrate that condom norms can be actively established and maintained among YMSM. Condom promotion efforts must increase YMSM's capacity, agency and skills to negotiate condom use, especially for the receptive partner.

Central effects of long-term relaxin expression in the rat.

A recombinant adenovirus containing the human H2 preprorelaxin (hH2) cDNA and a reporter gene was coinjected with a transactivator virus (Ad-tTA) into the lateral cerebral ventricles of female rats. Cardiovascular effects were measured over a 21-day period. Circulating vasopressin in the periphery was significantly greater (P < .0001) in the relaxin-treated group throughout the experimental period, compared with controls. There was a significant decrease in plasma osmolality (P < .05) by approximately 10 mmol/L in the treated group by day 14. Immunofluorescence for hH2 present in cryosections showed rAd transduction and hH2 expression from ependymal cells of the ventricular system. Adenovirus-mediated delivery of hH2 to the brain is capable of producing bioactive relaxin that affects cardiovascular parameters.

Anemia in Cambodia: a cross-sectional study of anemia, socioeconomic status and other associated risk factors in rural women.

Iron deficiency and associated anemia are severe public health problems, which are prevalent in the developing world. We conducted a cross-sectional survey, comprised of written interview questions and laboratory analysis of blood biomarkers, in Kandal Province, Cambodia. The objective of this study is to examine possible factors that are associated with anemia in rural Cambodia. Data on socioeconomic status, water source/treatment practices, and meat consumption was also collected. Of the 297 women surveyed, 51.2% were anemic. Of those women found to be anemic, iron deficiency was implicated in 9.7% of cases (SF <15 ng/L), with an additional 18.5% reported to be borderline iron deficient (serum ferritin=15-30 ng/L). Meat consumption was very low, with nearly one-half of the women consuming meat one time per month or less. This study highlights the multi-faceted etiology of anemia in Cambodia and emphasizes the need for comprehensive nutrition surveying in order to better inform prevention and treatment programming and policy development.

Relaxin peptide hormones are protective during the early stages of ischemic stroke in male rats.

The pregnancy hormone relaxin protects tissue from ischemic damage. The ability of relaxin-3, a relaxin paralog, to do so has not been explored. The cerebral expression levels of these peptides and their receptors make them logical targets for study in the ischemic brain. We assessed relaxin peptide-mediated protection, relative relaxin family peptide receptor (RXFP) involvement, and protective mechanisms. Sprague-Dawley rats receiving permanent (pMCAO) or transient middle cerebral artery occlusions (tMCAO) were treated with relaxin peptides, and brains were collected for infarct analysis. Activation of the endothelial nitric oxide synthase pathway was evaluated as a potential protective mechanism. Primary cortical rat astrocytes were exposed to oxygen glucose deprivation and treated with relaxin peptides, and viability was examined. Receptor involvement was explored using RXFP3 antagonist or agonist treatment and real-time PCR. Relaxin and relaxin-3 reduced infarct size after pMCAO. Both peptides activated endothelial nitric oxide synthase. Because relaxin-3 has not previously been associated with this pathway and displays promiscuous RXFP binding, we explored the receptor contribution. Expression of rxfp1 was greater than that of rxfp3 in rat brain, although peptide binding at either receptor resulted in similar overall protection after pMCAO. Only RXFP3 activation reduced infarct size after tMCAO. In astrocytes, rxfp3 gene expression was greater than that of rxfp1. Selective activation of RXFP3 maintained astrocyte viability after oxygen glucose deprivation. Relaxin peptides are protective during the early stages of ischemic stroke. Differential responses among treatments and models suggest that RXFP1 and RXFP3 initiate different protective mechanisms. This preliminary work is a pivotal first step in identifying the clinical implications of relaxin peptides in ischemic stroke.

Younger Gay and Bisexual Men's Condom Use With Main Regular Sexual Partner in New Zealand.

Main partners are a common source of new HIV infections among men who have sex with men (MSM). National behavioral surveillance data (2006-2011) for younger MSM (YMSM, aged 16-29) in New Zealand were analyzed to investigate condom use during anal intercourse with a regular partner (boyfriend/fuckbuddy) by sexual position (insertive/receptive). Backward-stepwise multivariate multinomial logistic regression was used to identify demographic, relational, behavioral, and cognitive factors associated with condom use frequency (high, medium, low). Most YMSM who reported a current regular partner (n=1,221) classified them as a boyfriend (59.5%) versus fuckbuddy (40.5%), though condom use was higher with the latter partner type. Condom use or nonuse was habitual across partners, although insertive sexual position was positively associated with condom use. YMSM who believed condoms reduce sensitivity reported lower condom use. Condoms remain the leading HIV/STI prevention tool for YMSM; efforts to improve condom use must consider sexual position and relationship factors.

Adenovirus-mediated expression of human prorelaxin promotes the invasive potential of canine mammary cancer cells.

This study reports the characterization of a recombinant adenoviral vector containing a tetracycline-regulatable promoter, driving the bicistronic expression of the human H2 preprorelaxin (hH2) cDNA and enhanced green fluorescent protein, via an internal ribosomal entry site. An hH2 ELISA was used to measure the secreted levels of recombinant hH2 in transfected canine (CF33.Mt) and human (MDA-MB-435) mammary cancer cell lines over a 6-d period; secreted peptide peaked on d 2 and 4 for the canine and human cell types, respectively. An unprocessed hH2 immunoreactive form of approximately 18 kDa was identified by Western blotting analysis and confirmed by mass spectrometry, suggesting that prorelaxin remains unprocessed in these cell types. The biological activity of the adenovirally expressed human prorelaxin was measured in the established human monocytic cell line THP-1 cAMP ELISA and in an in vitro Transwell cell migration system. Exogenous recombinant hH2 and adenovirally-mediated delivery of prorelaxin to CF33.Mt cells conferred a significant migratory action in the cells, compared with controls. Cell proliferation assays were performed to discount the possibility that the effect of relaxin was mitogenic. Thus, we have demonstrated that prorelaxin has the ability to facilitate cell migration processes exclusive of its ability to stimulate cell proliferation. In validating this adenovirus-based system, we have created a potential tool for further exploration of the physiology of relaxin in mammalian systems.

Relaxin protects astrocytes from hypoxia in vitro.

The peptide relaxin has recently been shown to protect brain tissues from the detrimental effects of ischemia. To date, the mechanisms for this remain unclear. In order to investigate the neuroprotective mechanisms by which relaxin may protect the brain, we investigated the possibility that relaxin protects astrocytes from hypoxia or oxygen/glucose deprivation (OGD). Cultured astrocytes were pre-treated with either relaxin-2 or relaxin-3 and exposed to OGD for 24 or 48 hours. Following OGD exposure, viability assays showed that relaxin-treated cells exhibited a higher viability when compared to astrocytes that experienced OGD-alone. Next, to test whether relaxin reduced the production of reactive oxygen species (ROS) astrocytes were exposed to the same conditions as the previous experiment and a commercially available ROS detection kit was used to detect ROS production. Astrocytes that were treated with relaxin-2 and relaxin-3 showed a marked decrease in ROS production when compared to control astrocytes that were exposed only to OGD. Finally, experiments were performed to determine whether or not the mitochondrial membrane potential was affected by relaxin treatment during 24 hour OGD. Mitochondrial membrane potential was higher in astrocytes that were treated with relaxin-2 and relaxin-3 compared to untreated OGD-alone astrocytes. Taken together, these data present novel findings that show relaxin protects astrocytes from ischemic conditions through the reduction of ROS production and the maintenance of mitochondrial membrane potential.

Women's nutrient intakes and food-related knowledge in rural Kandal province, Cambodia.

In Cambodia, both anaemia and vitamin A deficiency are serious health problems. Despite this, few comprehensive nutritional surveys have been completed to date. This study evaluates the adequacy of iron and vitamin A intakes, as well as women's nutritional knowledge in rural Kandal province. Twenty-four hour recalls, pile sort activities, socioeconomic surveys, focus groups, and market surveys were carried out with 67 women from 5 villages in rural Kandal Province. Ninety seven percent of women did not meet their daily-recommended intake of iron, while 70% did not meet their daily-recommended intake of vitamin A. Although many women consume vitamin A-rich and iron rich-foods daily, they do not consume large enough quantities of these foods. Results suggest that both the cost of foods as well as the extent of health knowledge is linked to nutritional practice. Most animal-source iron and vitamin A-rich foods are considered expensive; however, small fish, and several plant-source vitamin A-rich foods are inexpensive and easy to access. Despite health education, food restrictions lead some healthy foods to be considered to be harmful to women. Ultimately, this study demonstrates the importance of developing comprehensive nutritional interventions in Cambodia. Health programming must provide women with not only suggestions to include low-cost nutrient-rich foods, but also advise them about the quantities that are likely to have an impact on nutritional status. Programs should take a community-based, inter-sectoral approach that simultaneously combines culturally informed health education with initiatives that combat poverty and increase access to nutrient rich foods.

Relaxin receptor antagonist AT-001 synergizes with docetaxel in androgen-independent prostate xenografts.

Androgen hormones and the androgen receptor (AR) pathway are the main targets of anti-hormonal therapies for prostate cancer. However, resistance inevitably develops to treatments aimed at the AR pathway resulting in androgen-independent or hormone-refractory prostate cancer (HRPC). Therefore, there is a significant unmet need for new, non-androgen anti-hormonal strategies for the management of prostate cancer. We demonstrate that a relaxin hormone receptor antagonist, AT-001, an analog of human H2 relaxin, represents a first-in-class anti-hormonal candidate treatment designed to significantly curtail the growth of androgen-independent human prostate tumor xenografts. Chemically synthesized AT-001, administered subcutaneously, suppressed PC3 xenograft growth by up to 60%. AT-001 also synergized with docetaxel, standard first-line chemotherapy for HRPC, to suppress tumor growth by more than 98% in PC3 xenografts via a mechanism involving the downregulation of hypoxia-inducible factor 1 alpha and the hypoxia-induced response. Our data support developing AT-001 for clinical use as an anti-relaxin hormonal therapy for advanced prostate cancer.