ATP-gated ionotropic P2X7 receptor controls follicular T helper cell numbers in Peyer's patches to promote host-microbiota mutualism.

Microbial colonization of the gut induces the development of gut-associated lymphoid tissue (GALT). The molecular mechanisms that regulate GALT function and result in gut-commensal homeostasis are poorly defined. T follicular helper (Tfh) cells in Peyer's patches (PPs) promote high-affinity IgA responses. Here we found that the ATP-gated ionotropic P2X7 receptor controls Tfh cell numbers in PPs. Lack of P2X7 in Tfh cells enhanced germinal center reactions and high-affinity IgA secretion and binding to commensals. The ensuing depletion of mucosal bacteria resulted in reduced systemic translocation of microbial components, lowering B1 cell stimulation and serum IgM concentrations. Mice lacking P2X7 had increased susceptibility to polymicrobial sepsis, which was rescued by Tfh cell depletion or administration of purified IgM. Thus, regulation of Tfh cells by P2X7 activity is important for mucosal colonization, which in turn results in IgM serum concentrations necessary to protect the host from bacteremia.

VEGFR2 Signaling Prevents Colorectal Cancer Cell Senescence to Promote Tumorigenesis in Mice With Colitis.

BACKGROUND & AIMS Senescence prevents cellular transformation. We investigated whether vascular endothelial growth factor (VEGF) signaling via its receptor, VEGFR2, regulates senescence and proliferation of tumor cells in mice with colitis-associated cancer (CAC). METHODS CAC was induced in VEGFR2(ΔIEC) mice, which do not express VEGFR2 in the intestinal epithelium, and VEGFR2(fl/fl) mice (controls) by administration of azoxymethane followed by dextran sodium sulfate. Tumor development and inflammation were determined by endoscopy. Colorectal tissues were collected for immunoblot, immunohistochemical, and quantitative polymerase chain reaction analyses. Findings from mouse tissues were confirmed in human HCT116 colorectal cancer cells. We analyzed colorectal tumor samples from patients before and after treatment with bevacizumab. RESULTS After colitis induction, VEGFR2(ΔIEC) mice developed significantly fewer tumors than control mice. A greater number of intestinal tumor cells from VEGFR2(ΔIEC) mice were in senescence than tumor cells from control mice. We found VEGFR2 to activate phosphatidylinositol-4,5-bisphosphate-3-kinase and AKT, resulting in inactivation of p21 in HCT116 cells. Inhibitors of VEGFR2 and AKT induced senescence in HCT116 cells. Tumor cell senescence promoted an anti-tumor immune response by CD8(+) T cells in mice. Patients whose tumor samples showed an increase in the proportion of senescent cells after treatment with bevacizumab had longer progression-free survival than patients in which the proportion of senescent tumor cells did not change before and after treatment. CONCLUSIONS Inhibition of VEGFR2 signaling leads to senescence of human and mouse colorectal cancer cells. VEGFR2 interacts with phosphatidylinositol-4,5-bisphosphate-3-kinase and AKT to inactivate p21. Colorectal tumor senescence and p21 level correlate with patient survival during treatment with bevacizumab.

The Phosphoinositide 3-Kinase p110α Isoform Regulates Leukemia Inhibitory Factor Receptor Expression via c-Myc and miR-125b to Promote Cell Proliferation in Medulloblastoma.

Medulloblastoma (MB) is the most common malignant brain tumor in childhood and represents the main cause of cancer-related death in this age group. The phosphoinositide 3-kinase (PI3K) pathway has been shown to play an important role in the regulation of medulloblastoma cell survival and proliferation, but the molecular mechanisms and downstream effectors underlying PI3K signaling still remain elusive. The impact of RNA interference (RNAi)-mediated silencing of PI3K isoforms p110α and p110δ on global gene expression was investigated by DNA microarray analysis in medulloblastoma cell lines. A subset of genes with selectively altered expression upon p110α silencing in comparison to silencing of the closely related p110δ isoform was revealed. Among these genes, the leukemia inhibitory factor receptor α (LIFR α) was validated as a novel p110α target in medulloblastoma. A network involving c-Myc and miR-125b was shown to be involved in the control of LIFRα expression downstream of p110α. Targeting the LIFRα by RNAi, or by using neutralizing reagents impaired medulloblastoma cell proliferation in vitro and induced a tumor volume reduction in vivo. An analysis of primary tumors revealed that LIFRα and p110α expression were elevated in the sonic hedgehog (SHH) subgroup of medulloblastoma, indicating its clinical relevance. Together, these data reveal a novel molecular signaling network, in which PI3K isoform p110α controls the expression of LIFRα via c-Myc and miR-125b to promote MB cell proliferation.

Uncertainty analysis of cost effectiveness in a tailored intervention to promote screening for colorectal cancer

Background. Screening for colorectal cancer (CRC) is considered cost effective but screening compliance in the US remains low. There have been very few studies on economic analyses of screening promotion strategies for colorectal cancer. The main aim of the current study is to conduct a cost effectiveness analysis (CEA) and examine the uncertainty involved in the results of the CEA of a tailored intervention to promote screening for CRC among patients of a multispeciality clinic in Houston, TX. ^ Methods. The two intervention arms received a PC based tailored program and web based educational information to promote CRC screening. The incremental cost of implementing a tailored PC based program was compared to the website based education and the status quo of no intervention for each unit of effect after 12 months of delivering the intervention. Uncertainty analysis in the point estimates of cost and effect was conducted using nonparametric bootstrapping. ^ Results. The cost of implementing a web based educational intervention was $36.00 per person and the cost of the tailored PC based interactive intervention was $43.00 per person. The additional cost per person screened for the web-based strategy was $2374 and the effect of the tailored intervention was negative. ^

Community health workers: The critical link to sustainable, healthy societies in low-resource settings---A model for the Baylor Shoulder to Shoulder Foundation

Community health workers (CHWs) can serve as a bridge between healthcare providers and communities to positively impact social determinants of health and, thus, the overall health of the population. The potential to effect lasting change is particularly significant within resource-poor settings with limited access to formally trained health care providers such as the small, rural village of Santa Ana Intibucá, Honduras and surrounding areas—located on the geographically and politically isolated border of Honduras and El Salvador. The Baylor Shoulder to Shoulder Foundation (BSTS) works in conjunction with Santa Ana's volunteer health committee to bring a health brigade that has provided health care and public health projects to the area at least twice a year since 2001. They have also hired a full-time Honduran physician, a Honduran in-country administrative director, and built a clinic; yet, no community health worker program exists. This CHW program model is the response to a clear need for a CHW program within the area served by BSTS and presents a CHW program model specific to Santa Ana Intibucá and surrounding areas to be implemented by BSTS. Methods used to develop this model include reviewing the literature for recommendations from leading authorities as well as successfully implemented CHW programs in comparable regions. This information was incorporated into existing knowledge and materials currently being used in the area. Using the CHW model proposed here, each brigade, in conjunction with the communities served, can help develop new modules to respond to the specific health priorities of the region at that time, incorporating consistent modes of contact with the local physician and the CHWs to provide refresher courses, training in new topics of interest, and to be reminded of the importance of community health workers' role as the critical link to healthy societies. With cooperation, effort, and support, the brigade can continue to help integrate a sustainable CHW system in which communities may be able to maximize the care they receive while also learning to care for their own health and the future of their communities.^

Use of empowerment evaluation to determine a sustainability plan for a community-based preconception care program

Women With IMPACT (WWI) is a community-based preconception care educational intervention. WWI is being implemented by the Impacting Maternal and Prenatal Care Together (IMPACT) Collaborative and targets zip codes in Harris County, Texas at high risk for infant mortality, low birthweight, and preterm birth. WWI started March 2012 and continues through August 2013. Three workshop series are planned. This study was conducted with participants and facilitators from the first workshop series. This study aimed to 1) evaluate the WWI program using empowerment evaluation, 2) engage all WWI stakeholders in an empowerment evaluation so the method could be adopted as a participatory evaluation process for future IMPACT activities, and 3) develop recommendations for sustainability of the WWI intervention, based on empowerment evaluation findings and results from the pre/post program evaluation completed by WWI participants. Study participants included WWI participants and facilitators and IMPACT Collaborative Steering Committee members. WWI participants were female, 18-35 year-old, non-pregnant residents of zip codes at high risk of adverse birth outcomes. All other study participants were 18 years or older. A two-phased empowerment evaluation (EE) was utilized in this study. Sessions 1-4 were conducted independently of one another – 3 with participants at different sites and one with the facilitators. The fifth session included WWI participant and facilitator representatives, and IMPACT Steering Committee members. Session 5 built upon the work of the other sessions. Observation notes were recorded during each session. Thematic content analysis was conducted on all EE tables and observation notes. Mission statements drafted by each group focused on improvement of physical and mental health through behavior change and empowerment of all participants. The top 5 overall program components were: physical activity, nutrition, self-worth, in-class communication, and stress. Goals for program improvement were set by EE participants for each of these components. Through thematic content analysis of the tables and observation notes, social support emerged as an important theme of the program among all participant groups. Change to a healthy lifestyle emerged as an important theme in terms of program improvement. Two-phased EE provided an opportunity for all program stakeholders to provide feedback regarding important program components and provide suggestions for program improvement. EE, thematic content analysis, pre/post evaluation results, and inherent program knowledge were triangulated to make recommendations to sustain the program once the initial funding ends. ^

Educational orientation regarding vocabulary and literacy access : Evaluating the impact of an intervention program designed to promote early learning at home

El estudio evalúa el impacto de un programa de promoción del desarrollo lingüístico y cognitivo para niños de 5 años implementado según dos modalidades: una que implicó acciones de alfabetización familiar en los hogares de los niños (modalidad intensiva) y otra que incluyó la participación de los niños en las salas de jardín de infantes (modalidad extensiva). La evaluación del impacto se realizó por medio de un diseño pre-test ? post-test. Se tomaron pruebas de vocabulario receptivo (VR), producción de categorías (PC) y escritura a una muestra de 214 niños participantes de la modalidad intensiva, 69 participantes de la modalidad extensiva y un grupo control de no participó del programa (49 niños). Los resultados mostraron que la participación en la modalidad intensiva implicó un mayor incremento en las habilidades infantiles de VR, PC que en la modalidad extensiva. A su vez ambas modalidades experimentales mostraron un mayor incremento en las variables examinadas respecto de las observadas en el grupo control. No se detectaron efectos de la escolaridad de la madre y la asistencia previa al jardín. Los resultados mostraron correlaciones significativas entre todas las variables analizadas y el valor predictivo de los puntajes en VR a principio de año respecto de los puntajes en VR y escritura a fin de año.

Educational orientation regarding vocabulary and literacy access : Evaluating the impact of an intervention program designed to promote early learning at home

El estudio evalúa el impacto de un programa de promoción del desarrollo lingüístico y cognitivo para niños de 5 años implementado según dos modalidades: una que implicó acciones de alfabetización familiar en los hogares de los niños (modalidad intensiva) y otra que incluyó la participación de los niños en las salas de jardín de infantes (modalidad extensiva). La evaluación del impacto se realizó por medio de un diseño pre-test ? post-test. Se tomaron pruebas de vocabulario receptivo (VR), producción de categorías (PC) y escritura a una muestra de 214 niños participantes de la modalidad intensiva, 69 participantes de la modalidad extensiva y un grupo control de no participó del programa (49 niños). Los resultados mostraron que la participación en la modalidad intensiva implicó un mayor incremento en las habilidades infantiles de VR, PC que en la modalidad extensiva. A su vez ambas modalidades experimentales mostraron un mayor incremento en las variables examinadas respecto de las observadas en el grupo control. No se detectaron efectos de la escolaridad de la madre y la asistencia previa al jardín. Los resultados mostraron correlaciones significativas entre todas las variables analizadas y el valor predictivo de los puntajes en VR a principio de año respecto de los puntajes en VR y escritura a fin de año.

Educational orientation regarding vocabulary and literacy access : Evaluating the impact of an intervention program designed to promote early learning at home

El estudio evalúa el impacto de un programa de promoción del desarrollo lingüístico y cognitivo para niños de 5 años implementado según dos modalidades: una que implicó acciones de alfabetización familiar en los hogares de los niños (modalidad intensiva) y otra que incluyó la participación de los niños en las salas de jardín de infantes (modalidad extensiva). La evaluación del impacto se realizó por medio de un diseño pre-test ? post-test. Se tomaron pruebas de vocabulario receptivo (VR), producción de categorías (PC) y escritura a una muestra de 214 niños participantes de la modalidad intensiva, 69 participantes de la modalidad extensiva y un grupo control de no participó del programa (49 niños). Los resultados mostraron que la participación en la modalidad intensiva implicó un mayor incremento en las habilidades infantiles de VR, PC que en la modalidad extensiva. A su vez ambas modalidades experimentales mostraron un mayor incremento en las variables examinadas respecto de las observadas en el grupo control. No se detectaron efectos de la escolaridad de la madre y la asistencia previa al jardín. Los resultados mostraron correlaciones significativas entre todas las variables analizadas y el valor predictivo de los puntajes en VR a principio de año respecto de los puntajes en VR y escritura a fin de año.

The voices and protests of China's labour NGOs and their effort to promote migrant worker rights

Labour NGOs in China are relatively new organizations that emerged in the 1990s and have spread during the 2000s. Migrant workers in China are weak both socially and economically and have been lacking ways of voicing grievances and protesting. Grassroots labour NGOs for migrant workers seem to be an efficient channel for their voices. This paper examines how labour NGOs emerged and how they function in the context of current Chinese society. This paper adopts the case study method to describe three NGOs in Beijing and Shenzhen. The paper shows that these NGOs are using different methods to resolve migrant worker problems. At the same time, they are voicing the migrants' grievances and protesting in their own ways.

Is prohibiting land reallocation enough to promote development of farmland rental markets in China?

Prohibiting land reallocation improves tenure security, but it remains unclear whether this sufficiently facilitates the development of farmland rental markets in China. To fill this gap, we investigate how farmland rental activities are influenced by full-scale land reallocation (FSLR) and partial land reallocation (PLR), which differ in scale and imposition. Employing the instrumental-variables and the difference-in-differences approaches, we find that PLR substitutes relation-specific contracting in the markets, while FSLR complements arms-length contracting. The different impacts are attributable to the difference in imposition rather than scale. These findings suggest the need for further reforms.

Is the concept of a green economy a useful way of framing Policy Discussions and policymaking to promote sustainable development?

In the Viewpoints section, academics, practitioners and experts share their perspectives on policy questions relevant to sustainable development. In this issue, experts address the question: “Is the concept of a green economy a useful way of framing policy discussions and policymaking to promote sustainable development?