Bacterial Effector Binding to Ribosomal Protein S3 Subverts NF-κB Function

Enteric bacterial pathogens cause food borne disease, which constitutes an enormous economic and health burden. Enterohemorrhagic Escherichia coli (EHEC) causes a severe bloody diarrhea following transmission to humans through various means, including contaminated beef and vegetable products, water, or through contact with animals. EHEC also causes a potentially fatal kidney disease (hemolytic uremic syndrome) for which there is no effective treatment or prophylaxis. EHEC and other enteric pathogens (e.g., enteropathogenic E. coli (EPEC), Salmonella, Shigella, Yersinia) utilize a type III secretion system (T3SS) to inject virulence proteins (effectors) into host cells. While it is known that T3SS effectors subvert host cell function to promote diarrheal disease and bacterial transmission, in many cases, the mechanisms by which these effectors bind to host proteins and disrupt the normal function of intestinal epithelial cells have not been completely characterized. In this study, we present evidence that the E. coli O157:H7 nleH1 and nleH2 genes encode T3SS effectors that bind to the human ribosomal protein S3 (RPS3), a subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcriptional complexes. NleH1 and NleH2 co-localized with RPS3 in the cytoplasm, but not in cell nuclei. The N-terminal region of both NleH1 and NleH2 was required for binding to the N-terminus of RPS3. NleH1 and NleH2 are autophosphorylated Ser/Thr protein kinases, but their binding to RPS3 is independent of kinase activity. NleH1, but not NleH2, reduced the nuclear abundance of RPS3 without altering the p50 or p65 NF-κB subunits or affecting the phosphorylation state or abundance of the inhibitory NF-κB chaperone IκBα NleH1 repressed the transcription of a RPS3/NF-κB-dependent reporter plasmid, but did not inhibit the transcription of RPS3-independent reporters. In contrast, NleH2 stimulated RPS3-dependent transcription, as well as an AP-1-dependent reporter. We identified a region of NleH1 (N40-K45) that is at least partially responsible for the inhibitory activity of NleH1 toward RPS3. Deleting nleH1 from E. coli O157:H7 produced a hypervirulent phenotype in a gnotobiotic piglet model of Shiga toxin-producing E. coli infection. We suggest that NleH may disrupt host innate immune responses by binding to a cofactor of host transcriptional complexes

Incorporation of lipid nanosystems containing omega‑3 fatty acids and resveratrol in textile substrates for wound healing and anti‑inflammatory applications

In the present work, lipid nanosystems containing omega-3 fatty acid (nanostructured lipid carriers, NLCs) or omega-3 fatty acid and resveratrol (liposomes) were developed to improve cotton textile substrates as dressings with anti-inflammatory properties for wound healing applications. Lipid nanosystems were incorporated into woven, non-woven and knitted cotton substrates by exhaustion and impregnation. Based on physical–chemical characterization of the textile substrates, the textile structure and type of lipid nanosystems dictated the adsorption efficiency. In the case of NLCs, the woven substrate functionalized by exhaustion had a higher omega-3 release being the most promising for wound dressing application. Whereas for liposomes, the most adequate textile was the cationized knitted fabric functionalized by impregnation, that showed a more prolonged release profile of resveratrol.This work is financed by Project UID/CTM/00264/2019 of 2C2T - Centro de Ciencia e Tecnologia Textil, funded by National Founds through FCT/MCTES. The authors also acknowledge the Portuguese Foundation for Science and Technology (FCT) for financial support in the framework of the Strategic Funding UID/Multi/04546/2013 and UID/FIS/04650/2019 in the ambit of the project POCI-01-0145-FEDER-032651, co-financed by the European Regional Development Fund (ERDF), through COMPETE 2020, under Portugal 2020

Phylogeny and Biogeography of the Carnivorous Plant Family Sarraceniaceae

The carnivorous plant family Sarraceniaceae comprises three genera of wetland-inhabiting pitcher plants: Darlingtonia in the northwestern United States, Sarracenia in eastern North America, and Heliamphora in northern South America. Hypotheses concerning the biogeographic history leading to this unusual disjunct distribution are controversial, in part because genus- and species-level phylogenies have not been clearly resolved. Here, we present a robust, species-rich phylogeny of Sarraceniaceae based on seven mitochondrial, nuclear, and plastid loci, which we use to illuminate this family's phylogenetic and biogeographic history. The family and genera are monophyletic: Darlingtonia is sister to a clade consisting of Heliamphora+Sarracenia. Within Sarracenia, two clades were strongly supported: one consisting of S. purpurea, its subspecies, and S. rosea; the other consisting of nine species endemic to the southeastern United States. Divergence time estimates revealed that stem group Sarraceniaceae likely originated in South America 44–53 million years ago (Mya) (highest posterior density [HPD] estimate = 47 Mya). By 25–44 (HPD = 35) Mya, crown-group Sarraceniaceae appears to have been widespread across North and South America, and Darlingtonia (western North America) had diverged from Heliamphora+Sarracenia (eastern North America+South America). This disjunction and apparent range contraction is consistent with late Eocene cooling and aridification, which may have severed the continuity of Sarraceniaceae across much of North America. Sarracenia and Heliamphora subsequently diverged in the late Oligocene, 14–32 (HPD = 23) Mya, perhaps when direct overland continuity between North and South America became reduced. Initial diversification of South American Heliamphora began at least 8 Mya, but diversification of Sarracenia was more recent (2–7, HPD = 4 Mya); the bulk of southeastern United States Sarracenia originated co-incident with Pleistocene glaciation, <3 Mya. Overall, these results suggest climatic change at different temporal and spatial scales in part shaped the distribution and diversity of this carnivorous plant clade

Implementation of the CALM intervention for anxiety disorders: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Investigators recently tested the effectiveness of a collaborative-care intervention for anxiety disorders: Coordinated Anxiety Learning and Management(CALM) []) in 17 primary care clinics around the United States. Investigators also conducted a qualitative process evaluation. Key research questions were as follows: (1) What were the facilitators/barriers to implementing CALM? (2) What were the facilitators/barriers to sustaining CALM after the study was completed?</p> <p>Methods</p> <p>Key informant interviews were conducted with 47 clinic staff members (18 primary care providers, 13 nurses, 8 clinic administrators, and 8 clinic staff) and 14 study-trained anxiety clinical specialists (ACSs) who coordinated the collaborative care and provided cognitive behavioral therapy. The interviews were semistructured and conducted by phone. Data were content analyzed with line-by-line analyses leading to the development and refinement of themes.</p> <p>Results</p> <p>Similar themes emerged across stakeholders. Important facilitators to implementation included the perception of "low burden" to implement, provider satisfaction with the intervention, and frequent provider interaction with ACSs. Barriers to implementation included variable provider interest in mental health, high rates of part-time providers in clinics, and high social stressors of lower socioeconomic-status patients interfering with adherence. Key sustainability facilitators were if a clinic had already incorporated collaborative care for another disorder and presence of onsite mental health staff. The main barrier to sustainability was funding for the ACS.</p> <p>Conclusions</p> <p>The CALM intervention was relatively easy to incorporate during the effectiveness trial, and satisfaction was generally high. Numerous implementation and sustainability barriers could limit the reach and impact of widespread adoption. Findings should be interpreted with the knowledge that the ACSs in this study were provided and trained by the study. Future research should explore uptake of CALM and similar interventions without the aid of an effectiveness trial.</p

A group randomized trial of a complexity-based organizational intervention to improve risk factors for diabetes complications in primary care settings: study protocol

<p>Abstract</p> <p>Background</p> <p>Most patients with type 2 diabetes have suboptimal control of their glucose, blood pressure (BP), and lipids – three risk factors for diabetes complications. Although the chronic care model (CCM) provides a roadmap for improving these outcomes, developing theoretically sound implementation strategies that will work across diverse primary care settings has been challenging. One explanation for this difficulty may be that most strategies do not account for the complex adaptive system (CAS) characteristics of the primary care setting. A CAS is comprised of individuals who can learn, interconnect, self-organize, and interact with their environment in a way that demonstrates non-linear dynamic behavior. One implementation strategy that may be used to leverage these properties is practice facilitation (PF). PF creates time for learning and reflection by members of the team in each clinic, improves their communication, and promotes an individualized approach to implement a strategy to improve patient outcomes.</p> <p>Specific objectives</p> <p>The specific objectives of this protocol are to: evaluate the effectiveness and sustainability of PF to improve risk factor control in patients with type 2 diabetes across a variety of primary care settings; assess the implementation of the CCM in response to the intervention; examine the relationship between communication within the practice team and the implementation of the CCM; and determine the cost of the intervention both from the perspective of the organization conducting the PF intervention and from the perspective of the primary care practice.</p> <p>Intervention</p> <p>The study will be a group randomized trial conducted in 40 primary care clinics. Data will be collected on all clinics, with 60 patients in each clinic, using a multi-method assessment process at baseline, 12, and 24 months. The intervention, PF, will consist of a series of practice improvement team meetings led by trained facilitators over 12 months. Primary hypotheses will be tested with 12-month outcome data. Sustainability of the intervention will be tested using 24 month data. Insights gained will be included in a delayed intervention conducted in control practices and evaluated in a pre-post design.</p> <p>Primary and secondary outcomes</p> <p>To test hypotheses, the unit of randomization will be the clinic. The unit of analysis will be the repeated measure of each risk factor for each patient, nested within the clinic. The repeated measure of glycosylated hemoglobin A1c will be the primary outcome, with BP and Low Density Lipoprotein (LDL) cholesterol as secondary outcomes. To study change in risk factor level, a hierarchical or random effect model will be used to account for the nesting of repeated measurement of risk factor within patients and patients within clinics.</p> <p>This protocol follows the CONSORT guidelines and is registered per ICMJE guidelines:</p> <p>Clinical Trial Registration Number</p> <p>NCT00482768</p

Advancing the application of systems thinking in health: managing rural China health system development in complex and dynamic contexts

Background: This paper explores the evolution of schemes for rural finance in China as a case study of the long and complex process of health system development. It argues that the evolution of these schemes has been the outcome of the response of a large number of agents to a rapidly changing context and of efforts by the government to influence this adaptation process and achieve public health goals. Methods:The study draws on several sources of data including a review of official policy documents and academic papers and in-depth interviews with key policy actors at national level and at a sample of localities. Results: The study identifies three major transition points associated with changes in broad development strategy and demonstrates how the adaptation of large numbers of actors to these contextual changes had a major impact on the performance of the health system. Further, it documents how the Ministry of Health viewed its role as both an advocate for the interests of health facilities and health workers and as the agency responsible for ensuring that government health system objectives were met. It is argued that a major reason for the resilience of the health system and its ability to adapt to rapid economic and institutional change was the ability of the Ministry to provide overall strategy leadership. Additionally, it postulates that a number of interest groups have emerged, which now also seek to influence the pathway of health system development. Conclusions: This history illustrates the complex and political nature of the management of health system development and reform. The paper concludes that governments will need to increase their capacity to analyze the health sector as a complex system and to manage change processes.UKaid: DFI

Organizational interventions employing principles of complexity science have improved outcomes for patients with Type II diabetes

<p>Abstract</p> <p>Background</p> <p>Despite the development of several models of care delivery for patients with chronic illness, consistent improvements in outcomes have not been achieved. These inconsistent results may be less related to the content of the models themselves, but to their underlying conceptualization of clinical settings as linear, predictable systems. The science of complex adaptive systems (CAS), suggests that clinical settings are non-linear, and increasingly has been used as a framework for describing and understanding clinical systems. The purpose of this study is to broaden the conceptualization by examining the relationship between interventions that leverage CAS characteristics in intervention design and implementation, and effectiveness of reported outcomes for patients with Type II diabetes.</p> <p>Methods</p> <p>We conducted a systematic review of the literature on organizational interventions to improve care of Type II diabetes. For each study we recorded measured process and clinical outcomes of diabetic patients. Two independent reviewers gave each study a score that reflected whether organizational interventions reflected one or more characteristics of a complex adaptive system. The effectiveness of the intervention was assessed by standardizing the scoring of the results of each study as 0 (no effect), 0.5 (mixed effect), or 1.0 (effective).</p> <p>Results</p> <p>Out of 157 potentially eligible studies, 32 met our eligibility criteria. Most studies were felt to utilize at least one CAS characteristic in their intervention designs, and ninety-one percent were scored as either "mixed effect" or "effective." The number of CAS characteristics present in each intervention was associated with effectiveness (p = 0.002). Two individual CAS characteristics were associated with effectiveness: interconnections between participants and co-evolution.</p> <p>Conclusion</p> <p>The significant association between CAS characteristics and effectiveness of reported outcomes for patients with Type II diabetes suggests that complexity science may provide an effective framework for designing and implementing interventions that lead to improved patient outcomes.</p

Characteristics of the Mesophotic Megabenthic Assemblages of the Vercelli Seamount (North Tyrrhenian Sea)

The biodiversity of the megabenthic assemblages of the mesophotic zone of a Tyrrhenian seamount (Vercelli Seamount) is described using Remotely Operated Vehicle (ROV) video imaging from 100 m depth to the top of the mount around 61 m depth. This pinnacle hosts a rich coralligenous community characterized by three different assemblages: (i) the top shows a dense covering of the kelp Laminaria rodriguezii; (ii) the southern side biocoenosis is mainly dominated by the octocorals Paramuricea clavata and Eunicella cavolinii; while (iii) the northern side of the seamount assemblage is colonized by active filter-feeding organisms such as sponges (sometimes covering 100% of the surface) with numerous colonies of the ascidian Diazona violacea, and the polychaete Sabella pavonina. This study highlights, also for a Mediterranean seamount, the potential role of an isolated rocky peak penetrating the euphotic zone, to work as an aggregating structure, hosting abundant benthic communities dominated by suspension feeders, whose distribution may vary in accordance to the geomorphology of the area and the different local hydrodynamic conditions

The limits of corporate social responsibility : Techniques of neutralization, stakeholder management and political CSR

Since scholarly interest in corporate social responsibility (CSR) has primarily focused on the synergies between social and economic performance, our understanding of how (and the conditions under which) companies use CSR to produce policy outcomes that work against public welfare has remained comparatively underdeveloped. In particular, little is known about how corporate decision-makers privately reconcile the conflicts between public and private interests, even though this is likely to be relevant to understanding the limitations of CSR as a means of aligning business activity with the broader public interest. This study addresses this issue using internal tobacco industry documents to explore British-American Tobacco’s (BAT) thinking on CSR and its effects on the company’s CSR Programme. The article presents a three-stage model of CSR development, based on Sykes and Matza’s theory of techniques of neutralization, which links together: how BAT managers made sense of the company’s declining political authority in the mid-1990s; how they subsequently justified the use of CSR as a tool of stakeholder management aimed at diffusing the political impact of public health advocates by breaking up political constituencies working towards evidence-based tobacco regulation; and how CSR works ideologically to shape stakeholders’ perceptions of the relative merits of competing approaches to tobacco control. Our analysis has three implications for research and practice. First, it underlines the importance of approaching corporate managers’ public comments on CSR critically and situating them in their economic, political and historical contexts. Second, it illustrates the importance of focusing on the political aims and effects of CSR. Third, by showing how CSR practices are used to stymie evidence-based government regulation, the article underlines the importance of highlighting and developing matrices to assess the negative social impacts of CSR