Transformation of Major Peanut (Arachis hypogaea) Stilbenoid Phytoalexins Caused by Selected Microorganisms

The peanut plant accumulates defensive stilbenoid phytoalexins in response to the presence of soil fungi, which in turn produce phytoalexin-detoxifying enzymes for successfully invading the plant host. Aspergillus spp. are opportunistic pathogens that invade peanut seeds; most common fungal species often produce highly carcinogenic aflatoxins. The purpose of the present research was to evaluate the in vitro dynamics of peanut phytoalexin transformation/detoxification by important fungal species. This work revealed that in feeding experiments, Aspergillus spp. from section Flavi were capable of degrading the major peanut phytoalexin, arachidin-3, into its hydroxylated homolog, arachidin-1, and a benzenoid, SB-1. However, Aspergillus niger from section Nigri as well as other fungal and bacterial species tested, which are not known to be involved in the infection of the peanut plant, were incapable of changing the structure of arachidin-3. The results of feeding experiments with arachidin-1 and resveratrol are also reported. The research provided new knowledge on the dynamics of peanut stilbenoid transformations by essential fungi. These findings may contribute to the elucidation of the phytoalexin detoxification mechanism involved in the infection of peanut by important toxigenic Aspergillus spp

Community first responders and responder schemes in the United Kingdom: systematic scoping review

Background: Community First Responder (CFR) schemes support lay people to respond to medical emergencies, working closely with ambulance services. They operate widely in the UK. There has been no previous review of UK literature on these schemes. This is the first systematic scoping review of UK literature on CFR schemes, which identifies the reasons for becoming a CFR, requirements for training and feedback and confusion between the CFR role and that of ambulance service staff. This study also reveals gaps in the evidence base for CFR schemes. Methods: We conducted a systematic scoping review of the published literature, in the English language from 2000 onwards using specific search terms in six databases. Narrative synthesis was used to analyse article content. Results: Nine articles remained from the initial search of 15,969 articles after removing duplicates, title and abstract and then full text review. People were motivated to become CFRs through an altruistic desire to help others. They generally felt rewarded by their work but recognised that the help they provided was limited by their training compared with ambulance staff. There were concerns about the possible emotional impact on CFRs responding to incidents. CFRs felt that better feedback would enhance their learning. Ongoing training and support were viewed as essential to enable CFRs to progress. They perceived that public recognition of the CFR role was low, patients sometimes confusing them with ambulance staff. Relationships with the ambulance service were sometimes ambivalent due to confusion over roles. There was support for local autonomy of CFR schemes but with greater sharing of best practice. Discussion: Most studies dated from 2005 and were descriptive rather than analytical. In the UK and Australia CFRs are usually lay volunteers equipped with basic skills for responding to medical emergencies, whereas in the US they include other emergency staff as well as lay people. Conclusion: Opportunities for future research include exploring experiences and perceptions of patients who have been treated by CFRs and other stakeholders, while also evaluating the effectiveness and costs of CFR schemes

Delays in seeking an abortion until the second trimester: a qualitative study in South Africa

<p>Abstract</p> <p>Background</p> <p>Despite changes to the South African abortion legislation in 1996, barriers to women accessing abortions still exist. Second trimester abortions, an inherently more risky procedure, continue to be 20% of all abortions. Understanding the reasons why women delay seeking an abortion until the second trimester is important for informing interventions to reduce the proportion of second trimester abortions in South Africa.</p> <p>Methods</p> <p>Qualitative research methods were used to collect data. Twenty-seven in-depth interviews were conducted in 2006 with women seeking a second trimester abortion at one public sector tertiary hospital and two NGO health care facilities in the greater Cape Town area, South Africa. Data were analysed using a grounded theory approach.</p> <p>Results</p> <p>Almost all women described multiple and interrelated factors that influenced the timing of seeking an abortion. Reasons why women delayed seeking an abortion were complex and were linked to changes in personal circumstances often leading to indecision, delays in detecting a pregnancy and health service related barriers that hindered access to abortion services.</p> <p>Conclusion</p> <p>Understanding the complex reasons why women delay seeking an abortion until the second trimester can inform health care interventions aimed at reducing the proportion of second trimester abortions in South Africa.</p

How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men

Tumours in rodent and human colon share many histological and genetic features. To know if rodent models of colon carcinogenesis are good predictors of chemopreventive efficacy in humans, we made a meta-analysis of aspirin, beta-carotene, calcium, and wheat bran studies. Controlled intervention studies of adenoma recurrence in human volunteers were compared with chemoprevention studies of carcinogen-induced tumours in rats, and of polyps in Min (Apc(+/-)) mice: 6714 volunteers, 3911 rats and 458 mice were included in the meta-analyses. Difference between models was small since most global relative risks were between 0.76 and 1.00. A closer look showed that carcinogen-induced rat studies matched human trials for aspirin, calcium, carotene, and were compatible for wheat bran. Min mice results were compatible with human results for aspirin, but discordant for calcium and wheat bran (no carotene study). These few results suggest that rodent models roughly predict effect in humans, but the prediction is not accurate for all agents. Based on three cases only, the carcinogen-induced rat model seems better than the Min mouse model. However, rodent studies are useful to screen potential chemopreventive agents, and to study mechanisms of carcinogenesis and chemoprevention

Nonlinear Cancer Response at Ultralow Dose: A 40800-Animal ED 001 Tumor and Biomarker Study

Assessment of human cancer risk from animal carcinogen studies is severely limited by inadequate experimental data at environmentally relevant exposures, and procedures requiring modeled extrapolations many orders of magnitude below observable data. We used rainbow trout, an animal model well suited to ultra low-dose carcinogenesis research, to explore dose-response down to a targeted 10 excess liver tumors per 10,000 animals (ED001). A total of 40,800 trout were fed 0–225 ppm dibenzo[a,l]pyrene (DBP) for four weeks, sampled for biomarker analyses, and returned to control diet for nine months prior to gross and histologic examination. Suspect tumors were confirmed by pathology, and resulting incidences were modeled and compared to the default EPA LED10 linear extrapolation method. The study provided observed incidence data down to two above-background liver tumors per 10,000 animals at lowest dose (that is, an un-modeled ED0002 measurement). Among nine statistical models explored, three were determined to fit the liver data well - linear probit, quadratic logit, and Ryzin-Rai. None of these fitted models is compatible with the LED10 default assumption, and all fell increasingly below the default extrapolation with decreasing DBP dose. Low-dose tumor response was also not predictable from hepatic DBP-DNA adduct biomarkers, which accumulated as a power function of dose (adducts = 100 * DBP1.31). Two-order extrapolations below the modeled tumor data predicted DBP doses producing one excess cancer per million individuals (ED10−6) that were 500–1500-fold higher than that predicted by the five-order LED10 extrapolation. These results are considered specific to the animal model, carcinogen, and protocol used. They provide the first experimental estimation in any model of the degree of conservatism that may exist for the EPA default linear assumption for a genotoxic carcinogen

The Impact of a Community-based Pilot Health Education Intervention for Older People as Caregivers of Orphaned and Sick Children as a Result of HIV and AIDS in South Africa

The increasing HIV and AIDS epidemic in South Africa poses a substantial burden to older people, in particular older women who mainly provide care for sick adult children and their grandchildren who have become orphaned and rendered vulnerable by the death or illness of their parents. In this study, 202 isiXhosa speaking older caregivers from Motherwell in the Eastern Cape Province of South Africa were trained to provide care for grandchildren and adult children living with HIV or AIDS. Based on a community needs assessment, a health education intervention comprising four modules was designed to improve skills and knowledge which would be used to assist older people in their care-giving tasks. Some topics were HIV and AIDS knowledge, effective intergenerational communication, providing home-based basic nursing care, accessing social services and grants, and relaxation techniques. Structured one-on-one interviews measured differences between pre-intervention and post-intervention scores among those who attended all four modules vs. those that missed one or more of the sessions. The results demonstrated that older people who participated in all four workshops perceived themselves more able and in control to provide nursing care. The participants also showed a more positive attitude towards people living with HIV or AIDS and reported an increased level of HIV and AIDS knowledge. The results provided valuable information upon which the development of future interventions may be based and psychosocial and structural needs of the older caregivers may be addressed by relevant stakeholders

Multizone Paper Platform for 3D Cell Cultures

In vitro 3D culture is an important model for tissues in vivo. Cells in different locations of 3D tissues are physiologically different, because they are exposed to different concentrations of oxygen, nutrients, and signaling molecules, and to other environmental factors (temperature, mechanical stress, etc). The majority of high-throughput assays based on 3D cultures, however, can only detect the average behavior of cells in the whole 3D construct. Isolation of cells from specific regions of 3D cultures is possible, but relies on low-throughput techniques such as tissue sectioning and micromanipulation. Based on a procedure reported previously (“cells-in-gels-in-paper” or CiGiP), this paper describes a simple method for culture of arrays of thin planar sections of tissues, either alone or stacked to create more complex 3D tissue structures. This procedure starts with sheets of paper patterned with hydrophobic regions that form 96 hydrophilic zones. Serial spotting of cells suspended in extracellular matrix (ECM) gel onto the patterned paper creates an array of 200 micron-thick slabs of ECM gel (supported mechanically by cellulose fibers) containing cells. Stacking the sheets with zones aligned on top of one another assembles 96 3D multilayer constructs. De-stacking the layers of the 3D culture, by peeling apart the sheets of paper, “sections” all 96 cultures at once. It is, thus, simple to isolate 200-micron-thick cell-containing slabs from each 3D culture in the 96-zone array. Because the 3D cultures are assembled from multiple layers, the number of cells plated initially in each layer determines the spatial distribution of cells in the stacked 3D cultures. This capability made it possible to compare the growth of 3D tumor models of different spatial composition, and to examine the migration of cells in these structures

Who is accessing public-sector anti-retroviral treatment in the Free State, South Africa? An exploratory study of the first three years of programme implementation

<p>Abstract</p> <p>Background</p> <p>Although South Africa has the largest public-sector anti-retroviral treatment (ART) programme in the world, anti-retroviral coverage in adults was only 40.2% in 2008. However, longitudinal studies of who is accessing the South African public-sector ART programme are scarce. This study therefore had one main research question: who is accessing public-sector ART in the Free State Province, South Africa? The study aimed to extend the current literature by investigating, in a quantitative manner and using a longitudinal study design, the participants enrolled in the public-sector ART programme in the period 2004-2006 in the Free State Province of South Africa.</p> <p>Methods</p> <p>Differences in the demographic (age, sex, population group and marital status) socio-economic (education, income, neo-material indicators), geographic (travel costs, relocation for ART), and medical characteristics (CD4, viral load, time since first diagnosis, treatment status) among 912 patients enrolled in the Free State public-sector ART programme between 2004 and 2006 were assessed with one-way analysis of variance, Bonferroni post-hoc analysis, and cross tabulations with the chi square test.</p> <p>Results</p> <p>The patients accessing treatment tended to be female (71.1%) and unemployed (83.4%). However, although relatively poor, those most likely to access ART services were not the most impoverished patients. The proportion of female patients increased (<it>P </it>< 0.05) and their socio-economic situation improved between 2004 and 2006 (<it>P </it>< 0.05). The increasing mean transport cost (<it>P </it>< 0.05) to visit the facility is worrying, because this cost is an important barrier to ART uptake and adherence. Encouragingly, the study results revealed that the interval between the first HIV-positive diagnosis and ART initiation decreased steadily over time (<it>P </it>< 0.05). This was also reflected in the increasing baseline CD4 cell count at ART initiation (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>Our analysis showed significant changes in the demographic, socio-economic, geographic, and medical characteristics of the patients during the first three years of the programme. Knowledge of the characteristics of these patients can assist policy makers in developing measures to retain them in care. The information reported here can also be usefully applied to target patient groups that are currently not reached in the implementation of the ART programme.</p

Generational distribution of a Candida glabrata population: Resilient old cells prevail, while younger cells dominate in the vulnerable host.

Similar to other yeasts, the human pathogen Candida glabrata ages when it undergoes asymmetric, finite cell divisions, which determines its replicative lifespan. We sought to investigate if and how aging changes resilience of C. glabrata populations in the host environment. Our data demonstrate that old C. glabrata are more resistant to hydrogen peroxide and neutrophil killing, whereas young cells adhere better to epithelial cell layers. Consequently, virulence of old compared to younger C. glabrata cells is enhanced in the Galleria mellonella infection model. Electron microscopy images of old C. glabrata cells indicate a marked increase in cell wall thickness. Comparison of transcriptomes of old and young C. glabrata cells reveals differential regulation of ergosterol and Hog pathway associated genes as well as adhesion proteins, and suggests that aging is accompanied by remodeling of the fungal cell wall. Biochemical analysis supports this conclusion as older cells exhibit a qualitatively different lipid composition, leading to the observed increased emergence of fluconazole resistance when grown in the presence of fluconazole selection pressure. Older C. glabrata cells accumulate during murine and human infection, which is statistically unlikely without very strong selection. Therefore, we tested the hypothesis that neutrophils constitute the predominant selection pressure in vivo. When we altered experimentally the selection pressure by antibody-mediated removal of neutrophils, we observed a significantly younger pathogen population in mice. Mathematical modeling confirmed that differential selection of older cells is sufficient to cause the observed demographic shift in the fungal population. Hence our data support the concept that pathogenesis is affected by the generational age distribution of the infecting C. glabrata population in a host. We conclude that replicative aging constitutes an emerging trait, which is selected by the host and may even play an unanticipated role in the transition from a commensal to a pathogen state.post-print10768 K