Is The Financial Burden Of Cancer Impacting Survivors\u27 Quality Of Life?

ABSTRACT: Purpose: Little is known about the relationship between the financial burden of cancer and the physical and emotional health of cancer survivors. We examined the association between financial problems caused by cancer and reported quality of life in two samples of cancer patients. Patients and Methods: Data from the 2010 National Health Interview Survey (NHIS) were analyzed. A multivariate regression model was used to examine the relationship between the degree to which cancer caused financial problems and the patients\u27 reported quality of life. In a separate study, a cross-sectional survey was administered at a large academic breast center. Patients who had received a diagnosis of breast cancer between 6 and 18 months prior were eligible. Patients who qualified were invited to complete a survey including sociodemographic factors, and questions pertaining to their perceived quality of life and the financial burden of their cancer treatment. These data were correlated with tumor and treatment factors. Non-parametric statistical analyses were conducted using SPSS. Results: In the NHIS data, of 2108 cancer patients who answered the survey question, To what degree has cancer caused financial problems for you and your family? , 8.6% reported a lot , while 69.6% reported not at all . Patients reporting a lot of financial problems due to cancer were more likely to rate their physical health (18.6% vs. 4.3%, p\u3c0.001), mental health (8.3% vs. 1.8%, p\u3c0.001), and satisfaction with social activities and relationships (11.8% vs. 3.6%, p\u3c0.001) to be poor compared to those with no financial hardship. On multivariate analysis controlling for all of the significant covariates on bivariate analysis, the degree to which cancer caused financial problems was the strongest independent predictor of quality of life. Patients who reported that cancer caused a lot of financial problems were four times less likely to rate their quality of life as excellent , very good , or good (OR=0.24; 95% CI: 0.14-0.40, p\u3c0.001). In the Yale Breast Center study, a total of 72 patients completed the survey. The mean age was 60 and mean tumor size was 2.3cm. When asked to what degree cancer caused financial problems, 18.1% responded a lot , 12.5% some , 18.1% a little , and 44.4% not at all . The majority (84.7%) self-reported their QOL to be excellent , very good , or good , while 8.4% answered fair or poor . On bivariate analysis, insurance status (p=0.029), education (p=0.013), family income (p=0.029), treatment history (chemotherapy, endocrine therapy, neither, or both) (p\u3c0.001), and ER receptor status (p=0.037) were all significantly associated with the degree to which cancer caused financial problems. Conclusion: Increased financial burden due to cancer was the strongest independent predictor of poor quality of life among cancer survivors in a nationwide population-based survey. We studied this relationship in a population of breast cancer patients at an academic center. Patients with hormone receptor-negative disease were more likely to report a large degree of financial problems. These patients represent a subset of patients with a poorer prognosis requiring more intensive therapy, These data support the need for increased clinician awareness of financial distress due to cancer, which may preferentially impact subsets of breast cancer patients

Sequence-Specific Biosensors Report Drug-Induced Changes in Epigenetic Silencing in Living Cells

Treatment with demethylating drugs can induce demethylation and reactivation of abnormally silenced tumor suppressor genes in cancer cells, but it can also induce potentially deleterious loss of methylation of repetitive elements. To enable the observation of unwanted drug effects related to loss of methylation of repetitive DNA, we have developed a novel biosensor capable of reporting changes in DNA accessibility via luminescence, in living cells. The biosensor design comprises two independent modules, each with a polydactyl zinc finger domain fused to a half intein and to a split-luciferase domain that can be joined by conditional protein splicing after binding to adjacent DNA targets. We show that an artificial zinc finger design specifically targeting DNA sequences near the promoter region of the L1PA2 subfamily of Line-1 retroelements is able to generate luminescent signals, reporting loss of epigenetic silencing and increased DNA accessibility of retroelements in human cells treated with the demethylating drugs decitabine or 5-azacytidine

Synthesis

Human activity in the last century has led to a substantial increase in nitrogen (N) emissions and deposition. This N deposition has reached a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. One approach for quantifying the level of pollution that would be harmful to ecosystems is the critical loads approach. The critical load is dei ned as the level of a pollutant below which no detrimental ecological effect occurs over the long term according to present knowledge. The objective of this project was to synthesize current research relating atmospheric N deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The receptors that we evaluated included freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical, and (2) individual species, population, and community responses. This report synthesizes current research relating atmospheric nitrogen (N) deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The report evaluates the following receptors: freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical; and (2) individual species, population, and community responses. The range of critical loads for nutrient N reported for U.S. ecoregions, inland surface waters, and freshwater wetlands is 1 to 39 kg N ha-1 y-1. This range spans the range of N deposition observed over most of the country. The empirical critical loads for N tend to increase in the following sequence for different life forms: diatoms, lichens and bryophytes, mycorrhizal fungi, herbaceous plants and shrubs, trees

Synthesis

Human activity in the last century has led to a substantial increase in nitrogen (N) emissions and deposition. This N deposition has reached a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. One approach for quantifying the level of pollution that would be harmful to ecosystems is the critical loads approach. The critical load is dei ned as the level of a pollutant below which no detrimental ecological effect occurs over the long term according to present knowledge. The objective of this project was to synthesize current research relating atmospheric N deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The receptors that we evaluated included freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical, and (2) individual species, population, and community responses. This report synthesizes current research relating atmospheric nitrogen (N) deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The report evaluates the following receptors: freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical; and (2) individual species, population, and community responses. The range of critical loads for nutrient N reported for U.S. ecoregions, inland surface waters, and freshwater wetlands is 1 to 39 kg N ha-1 y-1. This range spans the range of N deposition observed over most of the country. The empirical critical loads for N tend to increase in the following sequence for different life forms: diatoms, lichens and bryophytes, mycorrhizal fungi, herbaceous plants and shrubs, trees

Bioactive Endophytes Warrant Intensified Exploration and Conservation

A key argument in favor of conserving biodiversity is that as yet undiscovered biodiversity will yield products of great use to humans. However, the link between undiscovered biodiversity and useful products is largely conjectural. Here we provide direct evidence from bioassays of endophytes isolated from tropical plants and bioinformatic analyses that novel biology will indeed yield novel chemistry of potential value.We isolated and cultured 135 endophytic fungi and bacteria from plants collected in Peru. nrDNAs were compared to samples deposited in GenBank to ascertain the genetic novelty of cultured specimens. Ten endophytes were found to be as much as 15–30% different than any sequence in GenBank. Phylogenetic trees, using the most similar sequences in GenBank, were constructed for each endophyte to measure phylogenetic distance. Assays were also conducted on each cultured endophyte to record bioactivity, of which 65 were found to be bioactive.The novelty of our contribution is that we have combined bioinformatic analyses that document the diversity found in environmental samples with culturing and bioassays. These results highlight the hidden hyperdiversity of endophytic fungi and the urgent need to explore and conserve hidden microbial diversity. This study also showcases how undergraduate students can obtain data of great scientific significance

Dilated cardiomyopathy myosin mutants have reduced force-generating capacity

Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) can cause arrhythmias, heart failure, and cardiac death. Here, we functionally characterized the motor domains of five DCM-causing mutations in human ?-cardiac myosin. Kinetic analyses of the individual events in the ATPase cycle revealed that each mutation alters different steps in this cycle. For example, different mutations gave enhanced or reduced rate constants of ATP binding, ATP hydrolysis, or ADP release or exhibited altered ATP, ADP, or actin affinity. Local effects dominated, no common pattern accounted for the similar mutant phenotype, and there was no distinct set of changes that distinguished DCM mutations from previously analyzed HCM myosin mutations. That said, using our data to model the complete ATPase contraction cycle revealed additional critical insights. Four of the DCM mutations lowered the duty ratio (the ATPase cycle portion when myosin strongly binds actin) because of reduced occupancy of the force-holding A·M.D complex in the steady-state. Under load, the A·M·D state is predicted to increase owing to a reduced rate constant for ADP release, and this effect was blunted for all five DCM mutations. We observed the opposite effects for two HCM mutations, namely R403Q and R453C. Moreover, the analysis predicted more economical use of ATP by the DCM mutants than by WT and the HCM mutants. Our findings indicate that DCM mutants have a deficit in force generation and force holding capacity due to the reduced occupancy of the force-holding state

Microglial brain region−dependent diversity and selective regional sensitivities to aging

Microglia play critical roles in neural development, homeostasis and neuroinflammation and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration often occurs in disease-specific spatially-restricted patterns, the origins of which are unknown. We performed the first genome-wide analysis of microglia from discrete brain regions across the adult lifespan of the mouse and reveal that microglia have distinct region-dependent transcriptional identities and age in a regionally variable manner. In the young adult brain, differences in bioenergetic and immunoregulatory pathways were the major sources of heterogeneity and suggested that cerebellar and hippocampal microglia exist in a more immune vigilant state. Immune function correlated with regional transcriptional patterns. Augmentation of the distinct cerebellar immunophenotype and a contrasting loss in distinction of the hippocampal phenotype among forebrain regions were key features during ageing. Microglial diversity may enable regionally localised homeostatic functions but could also underlie region-specific sensitivities to microglial dysregulation and involvement in age-related neurodegeneration