Background All health researchers in South Africa (SA) are explicitly encouraged by the ethicolegal framework to engage stakeholders meaningfully in their research. Research ethics committees (RECs) ...have a role to play in shaping researchers' practices in this regard, but very little research has explored how RECs might best achieve this.Objectives To explore whether SA REC documents are prompting researchers to plan sound stakeholder engagement in health research.Methods We reviewed publicly available documents of RECs registered with the SA National Health Research Ethics Council. Of the 46 registered RECs as of November 2019, the documents of 37 were publicly accessible. These comprised 72 documents (e.g. standard operating procedures and application forms). We coded these according to ethical reasons mentioned for engagement, stakeholders and strategies highlighted for engagement. We used semantic coding, staying close to the actual wording of REC documents. We utilised thematic analysis to identify key themes.Results We found that many REC documents encouraged researchers to plan engagement in a way that resonates with ethics guidance (theme 1: 'encouraging sound engagement'). However, we found many wasted opportunities in this regard (theme 2: 'missing opportunities'). For some RECs, there was little harmonisation across their key documents regarding this important issue (theme 3: 'moving towards harmonisation').Conclusion In the short term, we recommend that RECs should amend their application forms in particular to better 'trigger' researchers to thoughtfully plan sound stakeholder engagement. In the longer term, we recommend that RECs' documents be better harmonised internally regarding their stance on stakeholder engagement.
Background: Between 2013 and 2018 the PopART study, a randomized study evaluating community level impact of a package of HIV prevention interventions on HIV incidence, was conducted in South Africa ...and Zambia. Community Advisory Boards (CABs), a common mechanism of community engagement, were established early in the research process and served as a main form of communication. In Zambia, CAB engagement included quarterly meetings, protocol review, and participation in national HIV events. At community level, however, the CAB had limited spaces to provide feedback to community health structures, civil society organizations (CSOs) and the general population. To help address this gap, seven CSOs formed the Community Partnership Platform (CPP). This "outside-in'' or CSO led model of engagement built broader support for the study intervention. Methods: The CPP partnered with the PopART trial team to build capacity of stakeholders on the Good Participatory Practice guidelines (GPP). The CPP used a mixed method approach to identify the impact of the trial sites' stakeholder engagement programs. Score cards were created to anonymously evaluate perceived stakeholder engagement quality by the community in line with GPP. Focus groups were conducted with a range of stakeholders to provide a robust picture of community involvement throughout the research process. Findings were reported back to the trial in real-time. Results: Through community trainings, the CPP identified treatment iteracy needs and supported development of effective training tools and evaluation measures. Through networking, the CPP held meetings with at-risk populations to create demand, increase awareness, and ensure meaningful engagement with the study team. At the nationa level, the CPP represented community groups and CSOs in the National Steering Committee of the PopART study. This helped amplify the community voice during Pop ART study forums. Conclusions: The use of CSOs as a community engagement mechanism is critical to optimizing the research process. The CPP initiative provided a parallel opportunity for engaging broader stakeholders in research and ensures the wider viewpoints of a community are included. This approach has the potential to improve transparency and accountability at a range of stakeholder levels from trial staff to policy makers.
Background. All health researchers in South Africa (SA) are explicitly encouraged by the ethicolegal framework to engage stakeholders meaningfully in their research. Research ethics committees (RECs) ...have a role to play in shaping researchers' practices in this regard, but very little research has explored how RECs might best achieve this. Objectives. To explore whether SA REC documents are prompting researchers to plan sound stakeholder engagement in health research. Methods. We reviewed publicly available documents of RECs registered with the SA National Health Research Ethics Council. Of the 46 registered RECs as of November 2019, the documents of 37 were publicly accessible. These comprised 72 documents (e.g. standard operating procedures and application forms). We coded these according to ethical reasons mentioned for engagement, stakeholders and strategies highlighted for engagement. We used semantic coding, staying close to the actual wording of REC documents. We utilised thematic analysis to identify key themes. Results. We found that many REC documents encouraged researchers to plan engagement in a way that resonates with ethics guidance (theme 1: 'encouraging sound engagement'). However, we found many wasted opportunities in this regard (theme 2: 'missing opportunities'). For some RECs, there was little harmonisation across their key documents regarding this important issue (theme 3: 'moving towards harmonisation'). Conclusion. In the short term, we recommend that RECs should amend their application forms in particular to better 'trigger' researchers to thoughtfully plan sound stakeholder engagement. In the longer term, we recommend that RECs' documents be better harmonised internally regarding their stance on stakeholder engagement.
The interaction between Rhizobium lipopolysaccharide (LPS) and white clover roots was examined. The Limulus lysate assay indicated that Rhizobium leguminosarum bv. trifolii (hereafter called R. ...trifolii) released LPS into the external root environment of slide cultures. Immunofluorescence and immunoelectron microscopy showed that purified LPS from R. trifolii 0403 bound rapidly to root hair tips and infiltrated across the root hair wall. Infection thread formation in root hairs was promoted by preinoculation treatment of roots with R. trifolii LPS at a low dose (up to 5 micrograms per plant) but inhibited at a higher dose. This biological activity of LPS was restricted to the region of the root present at the time of exposure to LPS, higher with LPS from cells in the early stationary phase than in the mid-exponential phase, incubation time dependent, incapable of reversing inhibition of infection by NO3(-) or NH4(+), and conserved among serologically distinct LPSs from several wild-type R. trifolii strains (0403, 2S-2, and ANU843). In contrast, infections were not increased by preinoculation treatment of roots with LPSs from R. leguminosarum bv. viciae strain 300, R. meliloti 102F28, or members of the family Enterobacteriaceae. Most infection threads developed successfully in root hairs pretreated with R. trifolii LPS, whereas many infections aborted near their origins and accumulated brown deposits if pretreated with LPS from R. meliloti 102F28. LPS front R. leguminosarum 300 also caused most infection threads to abort. Other specific responses of root hairs to infection-stimulating LPS from R. trifolii included acceleration of cytoplasmic streaming and production of novel proteins. Combined gas chromatography-mass spectroscopy and proton nuclear magnetic resonance analyses indicated that biologically active LPS from R. trifolii 0403 in the early stationary phase had less fucose but more 2-O-methylfucose, quinovosamine, 3,6-dideoxy-3-(methylamino)galactose, and noncarbohydrate substituents (O-methyl, N-methyl, and acetyl groups) on glycosyl components than did inactive LPS in the mid-exponential phase. We conclude that LPS-root hair interactions trigger metabolic events that have a significant impact on successful development of infection threads in this Rhizobium-legume symbiosis.
The activities of salt-elutable peroxidases from roots of white clover and pea were examined during the early interaction of these legume hosts with strains of Rhizobium leguminosarum in homologous ...and heterologous combination. Peroxidase-specific activity from clover root hairs began to increase 6 hr after inoculation with R. l. bv. viciae RL300 and was localized over the entire area of their deformations. In contrast, the onset of elicitation of peroxidase activity from root hairs was delayed after inoculation with R. l. bv. trifolii ANU843 and was localized only at the site of infection thread initiation. Three wild-type strains (R. l. bv. trifolii ANU843, R. l. bv. viciae RL300 and 1003) and one hybrid transconjugant strain of R. leguminosarum containing pSym from R. l. bv. viciae 248 (RBL5715) elicited increased specific activity of peroxidases eluted from pea and clover roots in heterologous combination. A comparison of peroxidase activity eluted from pea roots inoculated with ANU843 or its pSym-cured derivative indicated that pSym is required for elicitation of peroxidase on this heterologous host. The level of peroxidase activity elicited by nodE mutants (which have extended host range) is decreased on their new host. An extracellular fraction of RL300 contained flavonoid-dependent, heat-stable, and ethanol-soluble elicitor(s) of peroxidase activity. Treatment of clover seedlings with this cell-free fraction decreased the number of root hairs infected by ANU843. We propose that elicitation of root hair peroxidase may contribute to the infection process in this Rhizobium-legume symbiosis by altering root hair wall structure at sites of incipient penetration.
We used bright-field, time-lapse video, cross-polarized, phase-contrast, and fluorescence microscopies to examine the influence of isolated chitolipooligosaccharides (CLOSs) from wild-type Rhizobium ...leguminosarum bv. trifolii on development of white clover root hairs, and the role of these bioactive glycolipids in primary host infection. CLOS action caused a threefold increase in the differentiation of root epidermal cells into root hairs. At maturity, root hairs were significantly longer because of an extended period of active elongation without a change in the elongation rate itself. Time-series image analysis showed that the morphological basis of CLOS-induced root hair deformation is a redirection of tip growth displaced from the medial axis as previously predicted. Further studies showed several newly described infection-related root hair responses to CLOSs, including the localized disruption of the normal crystallinity in cell wall architecture and the induction of new infection sites. The application of CLOS also enabled a NodC- mutant of R. leguminosarum bv. trifolii to progress further in the infection process by inducing bright refractile spot modifications of the deformed root hair walls. However, CLOSs did not rescue the ability of the NodC- mutant to induce marked curlings or infection threads within root hairs. These results indicate that CLOS Nod factors elicit several host responses that modulate the growth dynamics and symbiont infectibility of white clover root hairs but that CLOSs alone are not sufficient to permit successful entry of the bacteria into root hairs during primary host infection in the Rhizobium-clover symbiosis.
Suspension cell cultures of Nicotiana tabacum L. inoculated with the incompatible pathogen Pseudomonas syringae pv pisi undergo a hypersensitive reaction. Addition of the singlet oxygen quencher ...bixin to cell suspensions had no effect on hypersensitive cell death. Addition of the singlet oxygen quencher 1,4-diazabicyclo octane (DABCO) increased the medium pH and delayed the onset of cell death. This delay was eliminated when cell suspensions were buffered, and could also be induced by increasing medium pH with KOH. Bixin and DABCO also did not suppress the hypersensitive reaction in tobacco leaves. These data do not support a role for singlet oxygen in the hypersensitive reaction. Medium pH, however, appears to be a critical factor in cell suspension cultures
Recent clinical trials utilizing Interferon-alpha (IFN) in combination with chemoradiation have demonstrated significant improvements in the survival of patients with pancreatic cancer. However, ...efficacy was limited by the systemic toxicity of IFN and low intratumoral levels of the cytokine. We sought to address these drawbacks by using an Oncolytic Adenovirus expressing IFN (OAd-hamIFN) in combination with chemotherapy and/or radiation in regimens mimicking the IFN-based therapies used in clinical trials. IFN expressed from OAd-hamIFN potentiated the cytotoxicity of radiation and chemotherapy (5-FU, Gemcitabine, and Cisplatin), and enhanced pancreatic cancer cell death in both
and
experimental settings. Notably, synergism was demonstrated in therapeutic groups that combined the interferon-expressing oncolytic virus with chemotherapy and radiation. In an
immunocompetent hamster model, treatment regimens combining oncolytic virus therapy with 5-FU and radiation demonstrated significant tumor growth inhibition and enhanced survival. This is the first study to report synergism between an IFN-expressing oncolytic adenovirus and chemoradiation-based therapies. When combined with an IFN-expressing OAd, there is a significant enhancement of radiation and especially chemoradiation, which may broaden the application of this new therapeutic approach to the pancreatic cancer patients who cannot tolerate existing chemotherapy regimens.
Exposure to maternal anxiety symptoms during infancy has been associated with difficulties in development and greater risk for developing anxiety later in life. Although previous studies have ...examined associations between prenatal maternal distress, infant brain development, and developmental outcomes, it is still largely unclear if there are associations between postnatal anxiety, infant brain development, and cognitive development in infancy. In this study, we used resting‐state functional magnetic resonance imaging to examine the association between maternal anxiety symptoms and resting‐state functional connectivity in the first year of life. We also examine the association between frontolimbic functional connectivity and infant cognitive development. The sample consisted of 21 infants (mean age = 24.15 months, SD = 4.17) that were scanned during their natural sleep using. We test the associations between maternal trait anxiety symptoms and amygdala–anterior cingulate cortex (ACC) functional connectivity, a neural circuit implicated in early life stress exposure. We also test the associations between amygdala–ACC connectivity and cognitive development. We found a significant negative association between maternal trait anxiety symptoms and left amygdala–right ACC functional connectivity (p < .05, false discovery rate corrected). We found a significant negative association between left amygdala–right ACC functional connectivity and infant cognitive development (p < .05). These findings have potential implications for understanding the role of postpartum maternal anxiety symptoms in functional brain and cognitive development in infancy.
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