Estimating uninsured and underinsured women eligible for Minnesota's Breast Cancer Screening Program.

Since its inception in 1991, the mission of the National Breast and Cervical Cancer Early Detection Program's (NBCCEDP) mission is to improve access to mammography. This program has demonstrated evidence showing that it has improved breast cancer screening rates for women who are uninsured and underinsured. However, the literature has shown that NBCCEDP screenings are decreasing, and only reach a portion of eligible women. Reliable estimates at the sub-county level are needed to identify and reach eligible women. Our work builds upon previous estimates by integrating uninsured and insurance status into spatially adaptive filters. We use spatially adaptive filters to create small area estimates of standardized incidence ratios describing the utilization rate of NBCCEDP services in Minnesota. We integrate the American Community Survey (2010-2014) insurance status data to account for the percentage that an individual is uninsured. We test five models that integrate insurance status by age, sex, and race/ethnicity. Our composite model, which adjusts for age, sex, and race/ethnicity insurance statuses, reduces 95% of the estimation error. We estimate that there approximately 49,913.7 women eligible to receive services for Minnesota. We also create small geography (i.e., county and sub-county) estimates for Minnesota. The integration of the insurance data improved our utilization estimate. The development of these methods will allow state programs to more efficiently use their resources and understand their reach.

Oral Supplementation with Algal Sulphated Polysaccharide in Subjects with Inflammatory Skin Conditions: A Randomised Double-Blind Placebo-Controlled Trial and Baseline Dietary Differences.

We examined the effect of a dietary seaweed extract-sulfated xylorhamnoglucuronan (SXRG84)-on individuals with inflammatory skin conditions. A subgroup analysis of a larger trial was undertaken, where 44 participants with skin conditions were enrolled in a double-blind placebo-controlled crossover design. Subjects ingested either SXRG84 extract (2 g/day) for six weeks and placebo for six weeks, or vice versa. At baseline, six- and twelve-weeks inflammatory markers and the gut microbiota were assessed, as well as skin assessments using the dermatology quality of life index (DQLI), psoriasis area severity index (PASI) and visual analogue scales (VAS). There were significant differences at weeks six and twelve for pro-inflammatory cytokines IFN-γ (p = 0.041), IL-1ß (p = 0.030), TNF-α (p = 0.008) and the anti-inflammatory cytokine IL-10 (p = 0.026), determined by ANCOVA. These cytokines were all significantly higher at six weeks post placebo compared to twelve weeks post placebo followed by SXRG84 treatment. A total of 23% of participants reported skin improvements, as measured by VAS (mean difference 3.1, p = 0.0005) and the DQLI score (mean difference -2.0, p = 0.049), compared to the 'non-responders'. Thus, the ingestion of SXRG84 for 6 weeks reduced inflammatory cytokines, and a subset of participants saw improvements.

Estimating Uninsured and Underinsured Women Eligible for Minnesota's Breast Cancer Screening Program.

The mission of the National Breast and Cervical Cancer Early Detection Program's (NBCCEDP) mission is to improve access to mammography and other health services for underserved women. Since its inception in 1991, this national program has improved breast cancer screening rates for women who are uninsured and underinsured. However, the literature has shown that NBCCEDP screenings are decreasing, and only reach a portion of eligible women. Reliable estimates at the sub-county level are needed to identify and reach eligible women. Our work builds upon previous estimates by integrating uninsured and insurance status into spatially adaptive filters. We use spatially adaptive filters to create small area estimates of standardized incidence ratios describing the utilization rate of NBCCEDP services in Minnesota. We integrate the American Community Survey (2010-2014) insurance status data to account for the percentage that an individual is uninsured. We test five models that integrate insurance status by age, sex, and race/ethnicity. Our composite model, which adjusts for age, sex, and race/ethnicity insurance statuses, reduces 95% of the estimation error. We estimate that there approximately 49,913.7 women eligible to receive services for Minnesota. We also create small geography (i.e., county and sub-county) estimates for Minnesota. The integration of the insurance data improved our utilization estimate. The development of these methods will allow state programs to more efficiently use their resources and understand their reach.

Impact of whole-body resistance exercise timing on mitigating hyperglycaemia-induced vascular dysfunction.

NEW FINDINGS: What is the central question of this study? Is the estrous cycle affected during disuse atrophies and if so, how do estrous cycle changes relate to musculoskeletal outcomes? What is the main finding and its importance? Rodent estrous cycles are altered during disuse atrophy, which corresponds to musculoskeletal outcomes. However, the estrous cycle does not appear changed in Lewis Lung Carcinoma, which corresponded to no differences in muscle size compared to healthy controls. These findings suggest a relationship between estrous cycle and muscle size during atrophic pathologies. ABSTRACT: Hyperglycemia can cause disruptions in vascular function, whereas exercise has been shown to restore vascular function. The primary aim of this study is to investigate the effect of performing whole-body resistance exercise, 30-min before, immediately following, or 30- or 60-min after a high carbohydrate meal, on endothelial function, measured by flow-mediated dilation (FMD). Healthy adults will be recruited to this randomized crossover trial to compare the postprandial glycaemic and vascular responses to four different exercise timing conditions and a control: i) C- control, high carbohydrate meal/no exercise, ii) 30Pre- 30 min of resistance exercises (~30% of 1RM [Repetition Maximum]), 30 min before a high carbohydrate meal, iii) IP- 30 min of resistance exercises (~30% of 1RM), immediately following a high carbohydrate meal, iv) 30Post- 30 min of resistance exercises, 30 min after a high carbohydrate meal and v) 60Post- 30 min of resistance exercises, 60 min after a high carbohydrate meal. Measures of metabolic and vascular function will be assessed at baseline and for two hours following the carbohydrate-based breakfast meal.

Loss of BIM in T cells results in BCL-2 family BH3-member compensation but incomplete cell death sensitivity normalization.

BIM is the master BH3-only BCL-2 family regulator of lymphocyte survival. To understand how long-term loss of BIM affects apoptotic resistance in T cells we studied animals with T cell-specific deletion of Bim. Unlike CD19CREBimfl/fl animals, LCKCREBimfl/fl mice have pronounced early lymphocytosis followed by normalization of lymphocyte counts over time. This normalization occurred in mature T cells, as thymocyte development and apoptotic sensitivity remained abnormal in LCKCREBimfl/fl mice. T cells from aged mice experienced normalization of their absolute cell numbers and responses against various apoptotic stimuli. mRNA expression levels of BCL-2 family proteins in CD4+ and CD8+ T cells from young and old mice revealed upregulation of several BH3-only proteins, including Puma, Noxa, and Bmf. Despite upregulation of various BH3 proteins, there were no differences in anti-apoptotic BCL-2 protein dependency in these cells. However, T cells had continued resistance to direct BIM BH3-induced mitochondrial depolarization. This study further highlights the importance of BIM in cell death maintenance in T cells and provides new insight into the dynamism underlying BH3-only regulation of T cell homeostasis versus induced cell death and suggests that CD4+ and CD8+ T cells compensate differently in response to loss of Bim.

Preferential targeting of MCL-1 by a hydrocarbon-stapled BIM BH3 peptide.

BCL-2 family proteins are central regulators of apoptosis and represent prime therapeutic targets for overcoming cell death resistance in malignancies. However, plasticity of anti-apoptotic members, such as MCL-1, often allows for a switch in cell death dependency patterns that lie outside the binding profile of targeted BH3-mimetics. Therefore discovery of therapeutics that effectively inactivate all anti-apoptotic members is a high priority. To address this we tested the potency of a hydrocarbon stapled BIM BH3 peptide (BIM SAHB A ) to overcome both BCL-2 and MCL-1 apoptotic resistance given BIM's naturally wide ranging affinity for all BCL-2 family multidomain members. BIM SAHB A effectively killed diffuse large B-cell lymphoma (DLBCL) cell lines regardless of their anti-apoptotic dependence. Despite BIM BH3's ability to bind all BCL-2 anti-apoptotic proteins, BIM SAHB A 's dominant intracellular target was MCL-1 and this specificity was exploited in sequenced combination BH3-mimetic treatments targeting BCL-2, BCL-XL, and BCL-W. Extending this MCL-1 functional dependence, mouse embryonic fibroblasts (MEFs) deficient in MCL-1 were resistant to mitochondrial changes induced by BIM SAHB A . This study demonstrates the importance of understanding BH3 mimetic functional intracellular affinities for optimized use and highlights the diagnostic and therapeutic promise of a BIM BH3 peptide mimetic as a potential MCL-1 inhibitor.

p19Arf represses platelet-derived growth factor receptor ß by transcriptional and posttranscriptional mechanisms.

In addition to cancer surveillance, p19(Arf) plays an essential role in blocking signals stemming from platelet-derived growth factor receptor ß (Pdgfrß) during eye development, but the underlying mechanisms have not been clear. We now show that without Arf, pericyte hyperplasia in the eye results from enhanced Pdgfrß-dependent proliferation from embryonic day 13.5 (E13.5) of mouse development. Loss of Arf in the eye increases Pdgfrß expression. In cultured fibroblasts and pericyte-like cells, ectopic p19(Arf) represses and Arf knockdown enhances the expression of Pdgfrß mRNA and protein. Ectopic Arf also represses primary Pdgfrß transcripts and a plasmid driven by a minimal promoter, including one missing the CCAAT element required for high-level expression. p19(Arf) uses both p53-dependent and -independent mechanisms to control Pdgfrß. In vivo, without p53, Pdgfrß mRNA is elevated and eye development abnormalities resemble the Arf (-/-) phenotype. However, effects of p53 on Pdgfrß mRNA do not appear to be due to direct p53 or RNA polymerase II recruitment to the promoter. Although p19(Arf) controls Pdgfrß mRNA in a p53-dependent manner, it also blunts Pdgfrß protein expression by blocking new protein synthesis in the absence of p53. Thus, our findings demonstrate a novel capacity for p19(Arf) to control Pdgfrß expression by p53-dependent and -independent mechanisms involving RNA transcription and protein synthesis, respectively, to promote the vascular remodeling needed for normal vision.