Individual characteristics and psychosocial factors may play a larger role than disease-related variables in determining how an individual responds to the stress of cancer diagnosis and treatment. Given the rates of reported cancer-related PTSS in this sample, and other non-veteran samples, clinicians should consider screening these following diagnosis and treatment, particularly in younger adults and those with previous trauma histories.
BackgroundWhen patients have multiple chronic illnesses, it is not feasible to provide disease‐based care when treatments for one condition adversely affect another. Instead, health‐care delivery requires a broader person‐centred treatment plan based on collaborative, patient‐oriented values and goals.ObjectiveWe examined the individual variability, thematic content, and sociodemographic correlates of valued life abilities and activities among multimorbid veterans diagnosed with life‐altering cancer.Setting and participantsParticipants were 144 veterans in the ‘Vet‐Cares’ study who completed a health‐care values and goals scale 12 months after diagnosis of head and neck, gastro‐oesophageal, or colorectal cancer. They had mean age of 65 years and one quarter identified as Hispanic and/or African American.DesignAt twelve months post‐diagnosis, participants rated 16 life abilities/activities in their importance to quality of life on a 10‐point Likert scale, during an in‐person interview. Scale themes were validated via exploratory factor analysis and examining associations with sociodemographic variables.ResultsParticipants rated most life abilities/activities as extremely important. Variability in responses was sufficient to identify three underlying values themes in exploratory factor analysis: self‐sufficiency, enjoyment/comfort, and connection to family, friends and spirituality. Veterans with a spouse/partner rated self‐sufficiency as less important. African American veterans rated connection as more important than did White veterans.ConclusionsIt is feasible yet challenging to ask older, multimorbid patients to rate relative importance of values associated with life abilities/activities. Themes related to self‐sufficiency, enjoyment/comfort in daily life and connection are salient and logically consistent with sociodemographic traits. Future studies should explore their role in goal‐directed health care.
PSA-N 100 or more is a new, independent molecular staging criterion for localized PC that identifies high-risk group patients with clinically relevant occult micrometastases in N0-PLN, who may benefit from additional therapy to prevent BCR.
Expression strains of Escherichia coli BL21(DE3) overproducing the E. coli m 5 C McrA restriction protein were produced by cloning the mcrA coding sequence behind a T7 promoter. The recombinant mcrA minus BL21 (DE3) host produces active McrA as evidenced by its acquired ability to selectively restrict the growth of T7 phage containing DNA methylated in vitro by HpaII methylase. The mcrA coding region contains several non-optimal E. coli triplets. Addition of the pACYC-RIL tRNA encoding plasmid to the BL21(DE3) host increased the yield of recombinant McrA (rMcrA) upon induction about 5-to 10-fold. McrA protein expressed at 37 °C is insoluble but a significant fraction is recovered as soluble protein after autoinduction at 20 °C. rMcrA protein, which is predicted to contain a Cys 4 -Zn 2+ finger and a catalytically important histidine triad in its putative nuclease domain, binds to several metal chelate resins without addition of a poly-histidine affinity tag. This feature was used to develop an efficient protocol for the rapid purification of nearly homogeneous rMcrA. The native protein is a dimer with a high α-helical content as measured by circular dichroism analysis. Under all conditions tested purified rMcrA does not have measurable nuclease activity on HpaII methylated (Cm 5 CGG) DNA, although the purified protein does specifically bind HpaII methylated DNA. These results have implications for understanding the in vivo activity of McrA in "restricting" m 5 C-containing DNA and suggest that rMcrA may have utility as a reagent for affinity purification of DNA fragments containing m 5 C residues. KeywordsMcrA; Zn 2+ finger; DNA methylation; C 5 -methylcytosine (m 5 C); DNA binding; CpG island affinity purification Epigenetic factors, and in particular methylation at the 5-position in cytosine residues in CpG dinucleotides to form m 5 CpG 1 , regulate the function of vertebrate genomes by controlling gene expression and chromatin folding. Aberrant hypermethylation of CpG islands near promoters of human tumor suppressor and other genes is now recognized as an important contributing factor in cancer, aging and several other pathological states. Detecting these aberrantly methylated regions and accurately determining their methylation profile is an area of considerable interest primarily because of their potential use as diagnostic and prognostic biomarkers for cancer [1][2][3][4]. Reagents, such as m 5 CpG binding proteins, which preferentially * Corresponding author. Fax: +1 631 344 3407. Jdunn@BNL.gov (J.J. Dunn). 1 Abbreviations used: m 5 C, C 5 -methylcytosine; CD, CpG, cytosine-guanosine dinucleotide; circular dichroism; SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; RT, room temperature; ORF, open reading frame; YT, yeast-tryptone medium; PBS, phosphate buffered saline; Kan, kanamycin; EMSA, electrophoretic mobility shift assay. NIH Public Access Author ManuscriptProtein Expr Purif. Author manuscript; available in PMC 2010 July 9. -3,5-8]. In this study we set out to characteri...
BackgroundCancer survivors are a rapidly growing and aging population in the U.S., but there are many challenges associated with the survivorship experience such as functional disabilities and psychosocial distress. When viewed next to the general population, Veterans are especially at risk for these challenges as they are older and have a high incidence of co-morbid conditions. While the Institute of Medicine (IOM) has called for further cancer survivorship research to address these challenges, we still know little about this experience from the perspective of aging Veterans.Methods/designWe conducted a longitudinal, mixed-methods study over the course of three and a half years at the Boston and Houston VA Medical Centers. We recruited 170 Veterans diagnosed with head and neck, colorectal and esophageal/gastric cancers that were identified from the VA tumor registry. Veterans completed three in-depth interviews, conducted at 6, 12 and 18 months after pathology confirmation, measuring the physical, social and psychological factors related to cancer survivorship. The longitudinal design allowed us to assess any changes in cancer related disability and distress over time.DiscussionWeekly teleconference study team meetings were a key aspect to the research process. Issues related to recruitment, data management and analysis, and the dissemination of research results was discussed. Interviewers presented detailed case reports of completed interviews that allowed us to refine our interview protocols. We also discussed issues relevant to the Veteran population of which we were previously unaware and some of the challenges of the research process itself. This novel study produced a robust data set that documents the functional and psychosocial cancer survivorship experiences of aging Veterans. The longitudinal design will help us more fully understand the recovery patterns for this specific population, and identify the unique needs and gaps in health services.
The Escherichia coli McrA protein, a putative C5-methylcytosine/C5-hydroxyl methylcytosine-specific nuclease, binds DNA with symmetrically methylated HpaII sequences (Cm5CGG), but its precise recognition sequence remains undefined. To determine McrA’s binding specificity, we cloned and expressed recombinant McrA with a C-terminal StrepII tag (rMcrA-S) to facilitate protein purification and affinity capture of human DNA fragments with m5C residues. Sequence analysis of a subset of these fragments and electrophoretic mobility shift assays with model methylated and unmethylated oligonucleotides suggest that N(Y > R) m5CGR is the canonical binding site for rMcrA-S. In addition to binding HpaII-methylated double-stranded DNA, rMcrA-S binds DNA containing a single, hemimethylated HpaII site; however, it does not bind if A, C, T or U is placed across from the m5C residue, but does if I is opposite the m5C. These results provide the first systematic analysis of McrA’s in vitro binding specificity.
Development of multi-method adherence measures across all treatment components will be important to understand the influence of adherence on treatment outcomes as monitoring adherence to time in bed and time out of bed had limited utility for understanding treatment outcomes in our sample.
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