179 research outputs found
Working to Make Philadelphians Healthier
This session is a roundup of current and recent public health policy initiatives in Philadelphia related to the prevention of chronic conditions.
Learning objectives: Describe the structure and projected impact of Philadelphia’s tax on sweetened drinks. Discuss Philadelphia’s new retail tobacco regulations and the background behind their implementation. Explain the impact of flavored tobacco and its relationship to health disparities in Philadelphia.
Presentation: 47:2
The WIC program: background, trends and factors associated with participation among WIC eligible families
Introduction
The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides access to supplemental foods, nutrition education etc. to low-income pregnant women, infants and children under 5. Despite being a safety net for nutritionally at-risk individuals, the coverage rates for WIC eligible individuals are far lower than the eligibility rates. This study seeks to understand the history of the WIC program, analyze current trends and discuss factors affecting participation in the WIC program.
Methods
The target population are populations that are eligible for the WIC program. A narrative review of journal articles was conducted. Databases searched were EBSCO host, PubMed and Google Scholar. The main predictor examined in this study was factors that affect participation in WIC programs, and the Outcome variable was WIC coverage rates. A thematic analysis was done to categorize results from studies that were reviewed
Results
Reviewed for this study were 30 studies that met the inclusion criteria. Trends from the studies reviewed showed that a significant percentage of children who were not participating in the WIC program were still at risk for food insufficiency. Themes like structural barriers, bureaucratic complications, specific WIC program characteristics and income status were identified. Findings were then explored under these themes.
Conclusion
The main results of this study showed that the WIC programs has had a great impact on the nutrition and health outcomes of low-income individuals or families. This study identified factors that may negatively impact enrollment and retention in WIC programs. Furthermore, this study shows that there may be direct implications like increased nutritional risk for populations who do not participate in or withdraw from the WIC program. Thus, further research on this topic specific to particular geographical locations need to be undertaken in this area
Changing The Playbook For Immigrant Health
Philadelphia’s response to welcoming Afghan evacuees during the COVID-19 pandemic suggests the need for a new approach to immigrant health care
Oleate but not stearate induces the regulatory phenotype of myeloid suppressor cells
Tumor infiltrating myeloid cells play contradictory roles in the tumor
development. Dendritic cells and classical activated macrophages support anti-
tumor immune activity via antigen presentation and induction of pro-
inflammatory immune responses. Myeloid suppressor cells (MSCs), for instance
myeloid derived suppressor cells (MDSCs) or tumor associated macrophages play
a critical role in tumor growth. Here, treatment with sodium oleate, an
unsaturated fatty acid, induced a regulatory phenotype in the myeloid
suppressor cell line MSC-2 and resulted in an increased suppression of
activated T cells, paralleled by increased intracellular lipid droplets
formation. Furthermore, sodium oleate potentiated nitric oxide (NO) production
in MSC-2, thereby increasing their suppressive capacity. In primary polarized
bone marrow cells, sodium oleate (C18:1) and linoleate (C18:2), but not
stearate (C18:0) were identified as potent FFA to induce a regulatory
phenotype. This effect was abrogated in MSC-2 as well as primary cells by
specific inhibition of droplets formation while the inhibition of de novo FFA
synthesis proved ineffective, suggesting a critical role for exogenous FFA in
the functional induction of MSCs. Taken together our data introduce a new
unsaturated fatty acid-dependent pathway shaping the functional phenotype of
MSCs, facilitating the tumor escape from the immune system
Self-healing capability of large-scale engineered cementitious composites beams
YesEngineered Cementitious Composites (ECC) is a material which possesses advanced self-healing properties. Although the self-healing performance of ECC has been revealed in numerous studies, only small-scale, laboratory-size specimens have been used to assess it under fixed laboratory conditions and curing techniques. In order to evaluate the effect of intrinsic self-healing ability of ECC on the properties of structural-size, large-scale reinforced-beam members, specimens with four different shear span to effective depth (a/d) ratios, ranging from 1 to 4, were prepared to evaluate the effects of shear and flexural deformation. To ensure a realistic assessment, beams were cured using wet burlap, similar to on-site curing. Each beam was tested for mechanical properties including load-carrying capacity, deflection capacity, ductility ratio, yield stiffness, energy absorption capacity, and the influence of self-healing, by comparing types of failure and cracking. Self-healed test beams showed higher strength, energy absorption capacity and ductility ratio than damaged test beams. In test beams with an a/d ratio of 4 in which flexural behavior was prominent, self-healing application was highly successful; the strength, energy absorption capacity and ductility ratios of these beams achieved the level of undamaged beams. In addition, flexural cracks healed better, helping recover the properties of beams with predominantly flexural cracks rather than shear cracks.The authors gratefully acknowledge the financial assistance of the Scientific and Technical Research Council (TUBITAK) of Turkey provided under Project: MAG-112M876 and the Turkish Academy of Sciences, Young Scientist Award program. The second author would also like to acknowledge the financial support of TĂśBITAK for the 2219 Scholarship
IRE1α–XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity
Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function 1?4 . However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals. Here we report that ovarian cancer?an aggressive malignancy that is refractory to standard treatments and current immunotherapies 5?8 ?induces endoplasmic reticulum stress and activates the IRE1α?XBP1 arm of the unfolded protein response 9,10 in T cells to control their mitochondrial respiration and anti-tumour function. In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression. Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α?XBP1 activation that suppressed mitochondrial activity and IFNÎł production. Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions. Restoring N-linked protein glycosylation, abrogating IRE1α?XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites. XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity. Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival. Controlling endoplasmic reticulum stress or targeting IRE1α?XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.Fil: Song, Minkyung. Weill Cornell Medicine; Estados UnidosFil: Sandoval, Tito A.. Weill Cornell Medicine; Estados UnidosFil: Chae, Chang-Suk. Weill Cornell Medicine; Estados UnidosFil: Chopra, Sahil. Weill Cornell Medicine; Estados UnidosFil: Tan, Chen. Weill Cornell Medicine; Estados UnidosFil: Rutkowski, Melanie R.. University of Virginia; Estados UnidosFil: Raundhal, Mahesh. Dana Farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados UnidosFil: Chaurio, Ricardo A.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Payne, Kyle K.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Konrad, Csaba. Weill Cornell Medicine; Estados UnidosFil: Bettigole, Sarah E.. Quentis Therapeutics Inc.; Estados UnidosFil: Shin, Hee Rae. Quentis Therapeutics Inc.; Estados UnidosFil: Crowley, Michael J. P.. Weill Cornell Graduate School of Medical Sciences; Estados UnidosFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental. FundaciĂłn de Instituto de BiologĂa y Medicina Experimental. Instituto de BiologĂa y Medicina Experimental; ArgentinaFil: Kossenkov, Andrew V.. The Wistar Institute; Estados UnidosFil: Motorykin, Ievgen. Weill Cornell Medicine,; Estados UnidosFil: Zhang, Sheng. Weill Cornell Medicine,; Estados UnidosFil: Manfredi, Giovanni. Weill Cornell Medicine,; Estados UnidosFil: Zamarin, Dmitriy. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Holcomb, Kevin. Weill Cornell Medicine,; Estados UnidosFil: Rodriguez, Paulo C.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental. FundaciĂłn de Instituto de BiologĂa y Medicina Experimental. Instituto de BiologĂa y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de QuĂmica BiolĂłgica; ArgentinaFil: Conejo Garcia, Jose R.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Glimcher, Laurie H.. Dana Farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados UnidosFil: Cubillos-Ruiz, Juan R.. Weill Graduate School Of Medical Sciences; Estados Unidos. Weill Graduate School Of Medical Sciences; Estados Unido
The unfolded protein response in immunity and inflammation.
The unfolded protein response (UPR) is a highly conserved pathway that allows the cell to manage endoplasmic reticulum (ER) stress that is imposed by the secretory demands associated with environmental forces. In this role, the UPR has increasingly been shown to have crucial functions in immunity and inflammation. In this Review, we discuss the importance of the UPR in the development, differentiation, function and survival of immune cells in meeting the needs of an immune response. In addition, we review current insights into how the UPR is involved in complex chronic inflammatory diseases and, through its role in immune regulation, antitumour responses.This work was supported by the Netherlands Organization for Scientific Research Rubicon grant 825.13.012 (J.G.); US National Institutes of Health (NIH) grants DK044319, DK051362, DK053056 and DK088199, and the Harvard Digestive Diseases Center (HDDC) grant DK034854 (R.S.B.); National Institutes of Health grants DK042394, DK088227, DK103183 and CA128814 (R.J.K.); and European Research Council (ERC) Starting Grant 260961, ERC Consolidator Grant 648889, and the Wellcome Trust Investigator award 106260/Z/14/Z (A.K.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nri.2016.6
ER stress arm XBP1s plays a pivotal role in proteasome inhibition-induced bone formation
Background
Bone destruction is a hallmark of multiple myeloma (MM). It has been reported that proteasome inhibitors (PIs) can reduce bone resorption and increase bone formation in MM patients, but the underlying mechanisms remain unclear.
Methods
Mesenchymal stem cells (MSCs) were treated with various doses of PIs, and the effects of bortezomib or carfilzomib on endoplasmic reticulum (ER) stress signaling pathways were analyzed by western blotting and real-time PCR. Alizarin red S (ARS) and alkaline phosphatase (ALP) staining were used to determine the osteogenic differentiation in vitro. Specific inhibitors targeting different ER stress signaling and a Tet-on inducible overexpressing system were used to validate the roles of key ER stress components in regulating osteogenic differentiation of MSCs. Chromatin immunoprecipitation (ChIP) assay was used to evaluate transcription factor-promoter interaction. MicroCT was applied to measure the microarchitecture of bone in model mice in vivo.
Results
We found that both PERK-ATF4 and IRE1α-XBP1s ER stress branches are activated during PI-induced osteogenic differentiation. Inhibition of ATF4 or XBP1s signaling can significantly impair PI-induced osteogenic differentiation. Furthermore, we demonstrated that XBP1s can transcriptionally upregulate ATF4 expression and overexpressing XBP1s can induce the expression of ATF4 and other osteogenic differentiation-related genes and therefore drive osteoblast differentiation. MicroCT analysis further demonstrated that inhibition of XBP1s can strikingly abolish bortezomib-induced bone formation in mouse.
Conclusions
These results demonstrated that XBP1s is a master regulator of PI-induced osteoblast differentiation. Activation of IRE1α-XBP1s ER stress signaling can promote osteogenesis, thus providing a novel strategy for the treatment of myeloma bone disease
- …