AN EVALUATION OF THE ADVANCE DIRECTIVES-LIVE ACTION SIMULATION TRAINING (AD-LAST) PROGRAM

Advance Care Planning (ACP) is a process that captures a patient’s wishes in the case of future circumstances in which they are unable to express them. Studies show that less than one third of the general population has completed some type of formal Advance Directive (AD). There are barriers to completing ADs, and these barriers operate on multiple levels, including, patient, provider and institutional. To improve providers’ capacity to help patients complete ACP, and overcome these barriers, a provider-focused intervention was conducted. The current study is an analysis of archival data collected from the Advance Directives-Live Action Simulation Training (AD-LAST) program developed and implemented at New York Presbyterian-Queens (NYP-Q). The AD-LAST workshop aimed to improve ACP and end-of-life (EOL) conversations by increasing clinician knowledge and self-efficacy in aspects of ACP and EOL. Although the intervention was independently successful in increasing clinicians’ knowledge and self-efficacy on ACP, we found that these two measures were unrelated to one another, and may represent distinct dimensions of improvements in ACP

Genome-wide analysis of the repertoire of TRIM genes in sea urchins

The eukaryotic TRIM (TRIpartite Motif) super-family represents one of the largest classes of putative E3 ubiquitin ligases involved in several processes, including epigenetic control of development and disease. In the post-genomic era, new approaches allow genome-wide studies of gene family. In particular, we performed a comprehensive analysis of the TRIM repertoire in selected sea urchin species. By combining iterations of ab initio predictions and pairwise comparative methods, we first retrieved the full complement of TRIM genes in Strongylocentrotus purpuratus, whose full genome sequence was available. Interestingly, such a DNA sequence set includes not previously classified, echinoderm-specific, TRIM genes as well as multiple copies of known ones. We also retrieved a landscape of cDNA sequences from staged EST libraries, indicating that most of these genes are actively transcribed during development. Phylogenetic analysis of the deduced proteins, using set of TRIMs from various species, revealed a degree of genetic variation between species. Worth of mention, we predicted the occurrence of transposition events involving some of these genes, according with the documented rapid evolution of this family. Next, we adopted heuristic algorithms and post-processing steps to investigate the evolutionarily distant Paracentrotus lividus, Allocentrotus fragilis and Lytechinus variegatus genomes, whose sequencing projects are actually in progress. We assembled partial pools of TRIM genes and specifically associated them to EST-derived cDNA sequences. Such a collection of data should provide a framework for unravel gene regulatory networks involving TRIM genes from an evolutionary perspective. Indeed, in the Pl species, we have previously isolated and functionally characterized the cDNA sequence encoding the first echinoderm TRIM factor, Strim1. Here, we identified five strim1 genes, all sharing a intronless organization, and roughly located their cis-regulatory apparatus

Specific expression of a TRIM-containing factor in ectoderm cells affects the skeletal morphogenetic program of the sea urchin embryo

In the indirect developing sea urchin embryo, the primary mesenchyme cells (PMCs) acquire most of the positional and temporal information from the overlying ectoderm for skeletal initiation and growth. In this study, we characterize the function of the novel gene strim1, which encodes a tripartite motif-containing (TRIM) protein, that adds to the list of genes constituting the epithelial-mesenchymal signaling network. We report that strim1 is expressed in ectoderm regions adjacent to the bilateral clusters of PMCs and that its misexpression leads to severe skeletal abnormalities. Reciprocally, knock down of strim1 function abrogates PMC positioning and blocks skeletogenesis. Blastomere transplantation experiments establish that the defects in PMC patterning, number and skeletal growth depend upon strim1 misexpression in ectoderm cells. Furthermore, clonal expression of strim1 into knocked down embryos locally restores skeletogenesis. We also provide evidence that the Otp and Pax2/5/8 regulators, as well as FGFA, but not VEGF, ligand act downstream to strim1 in ectoderm cells, and that strim1 triggers the expression of the PMC marker sm30, an ectoderm-signaling dependent gene. We conclude that the strim1 function elicits specific gene expression both in ectoderm cells and PMCs to guide the skeletal biomineralization during morphogenesis

Epigenetic Silencing of Ankrd26 Gene Contributes to Adipose Tissue Inflammation in Obesity

Environmental factors interact with the genome to influence gene expression, tissue function and also disease risk. External stimuli may affect the phenotype through epigenetic mechanisms that provide an interface with the genome. Indeed, epigenetic modifications represent a mechanism through which both genetic and environmental cues, including dietary factors, are integrated at specific genomic loci and affect individual phenotypes, contributing to susceptibility to obesity and type 2 diabetes. Recently, alterations of Ankyrin repeat domain 26 (Ankrd26) gene expression and function have been associated with the onset of these metabolic disorders. However, whether external cues can affect its expression remains unclear. Therefore, the aim of this study is to evaluate whether the administration of a high fat diet (HFD) in mice could affect Ankrd26 expression and function, and whether chromatin remodeling and epigenetic modifications take part in this regulation. Particularly, I examined the correlation between obesity and inflammation with defective regulation of Ankrd26 gene in visceral adipose tissue (VAT) depots, aiming at identifying epigenetic mechanism that might underpin the development of VAT dysfunctions induced by overnutrition. Using the HFD-induced obesity mouse model, I reported evidence of detailed epigenetic changes of Ankrd26 promoter. Indeed, I demonstrated that the HFD-induced Ankrd26 down-regulation in VAT was directly caused by specific hyper-methylation of -436 and -431 cytosine residues at its promoter region, that was followed by chromatin reorganization. Indeed, DNA methylation of these specific CpG sites impaired binding of the histone acetyltransferase/transcriptional coactivator p300 to this region, both in vitro and in vivo, causing hypo-acetylation of histone H4 at the Ankrd26 promoter and loss of binding of RNA Pol II at the Ankrd26 Transcription Start Site in obese mice. Furthermore, the HFD treatment increased binding of DNA methyl-transferases 3a and 3b and methyl-CpG-binding domain protein 2 to the Ankrd26 promoter. To evaluate the functional consequences of these changes, the HFD-induced Ankrd26 down-regulation was mimicked by silencing Ankrd26 gene expression in vitro in 3T3-L1 adipocytes. This silencing caused enhanced secretion of the pro-inflammatory chemokines KC/IL-8, Eotaxin, MCP1 and Rantes. The relevance of these observations to humans is supported by other findings in obese individuals, revealing that the reduction of ANKRD26 expression in VAT negatively correlates with serum concentrations of inflammatory markers. Taken together, my data provide evidence for environmentally induced DNA changes at Ankrd26 promoter and, for the first time, highlight a role for Ankrd26 epigenetic silencing in raising and/or sustaining VAT inflammation following unhealthy dieting and in development of obesity-related insulin resistance. Since direct evidence linking specific environmental cues and metabolic disorders are still limited, addressing this issue will provide new insight into the molecular basis of obesity as well as create novel translational perspective

Physiopathology of Spine Metastasis

The metastasis is the spread of cancer from one part of the body to another. Two-thirds of patients with cancer will develop bone metastasis. Breast, prostate and lung cancer are responsible for more than 80% of cases of metastatic bone disease. The spine is the most common site of bone metastasis. A spinal metastasis may cause pain, instability and neurological injuries. The diffusion through Batson venous system is the principal process of spinal metastasis, but the dissemination is possible also through arterial and lymphatic system or by contiguity. Once cancer cells have invaded the bone, they produce growth factors that stimulate osteoblastic or osteolytic activity resulting in bone remodeling with release of other growth factors that lead to a vicious cycle of bone destruction and growth of local tumour

Infection following bone tumor resection and reconstruction with tumoral prostheses: a literature review.

Bone resection is the choice treatment of malignant bone tumors. Tumor prosthesis is one of the most common solutions of reconstruction following resection of bone tumor located to the metaphysis of long bones. Periprosthetic infections are a frequent complication of limb-salvage surgery which is largely due to prolonged and repeated surgeries, as well as to the immunocompromised condition of these patients due to neoplastic treatment. Furthermore, the large exposure of tissues during this type of surgery and the dissection across vascular distributions also contributes to the high risk of infection. The authors reviewed the literature discussing the incidence of infections of tumor prosthesis implanted following resection of bone tumors, taking into account the different sites of implantation. In the English literature, the highest risk of infection which led to limb amputation was observed after proximal tibia resection and this difference was considered to be due to the poor condition of soft tissue and also after pelvic resection due to huge dead space after sarcoma resection not filled by implant. Independent of the location, the management of infected prosthesis is similar. That is, after one or more attempts at debridement and antibiotic therapy, it consists of implant removal and insertion of a new implant in a one- or two-stage procedure, with a decreased risk of failure with the two-stage procedure

Local adjuvants in surgical management of bone metastases.

Curettage is one of the most common method for surgical treatment of bone metastasis. Local adjuvant improve most commonly used for improving the effect of curettage in local cancer surgery may exerted their effects either chemically either physically; in Orthopedic Oncology the most common are phenol, liquid nitrogen, laser, and cement. This article reviewed the main characteristics of the most common chemical and physical agents used in bone oncology, emphasizing the toxic effects of some of them, especially phenol and liquid nitrogen

Development of a database for cervical cytology reports

Background Cervical cancer is an important cause of female mortality. Its incidence, however, has been drastically reduced by early detection using the Papanicolaou screening method. As a result of the widespread use of this method, a large amount of cytological information has to be stored, printed and handled efficiently. This paper describes a database system designed to manage information from studies of cervical cytology, which was developed at the Faculty of Medical Sciences, National University of La Plata, Argentina. Methods Information needs were assessed by interviews with physicians and analysis of cytology reports. The database was developed using MS Access 2007. Results The database is designed to collect, display, sort and print patient demographics, clinical data and cytological studies. Diagnoses can be stored either as international classifications or as free text. The database contains 45 tables and 50 forms for data entry, editing and display. This information can be exported to spreadsheets and statistical packages. Conclusion This database gives users easy access to patients' cytological diagnoses and provides a useful tool for physicians and public health researchers

Angiogenesis in hand chondroma: an immunohistochemical study.

Hand chondroma is a particular cartilagineous tumour, being clinically benign, but morphologically malignant. This study investigates the expression of VEGF together with other growth factors and proliferation markers such as TGF&bT2, Ki-67, TNF, FGF1, P53 in 8 cases of hand chondroma treated with courettage, in order to define the ethiopathogenesis of this tumour and the clinical significance of the resulting immunohistochemical profile, with particular respect to angiogenesis. VEGF was expressed in all cases; 5 cases were positive for TFGβ2 and 3 for PDGF. None of the other factors was expressed. On the basis of histologic results a specific model of tumour progression based on the indicators of angiogenesis could be related to hand tumours, in which VEGF expression should be the first stadium of the tumour aggressiveness, and the following PDGF, TGF 2 expression should be accompanied with a morphological outline worsening. Nevertheless the non constant expression of these indicators and the absent expression of proliferated indicators can explain the scant tendency to the relapse in presence of accurate curettage. It is important to remember that the cellular polymorphism typical of the cartilaginous tumours does not allow the application of an only oncogenesis model

Hypoxia inducible factor-1β regulates a pro-invasive phenotype in acute monocytic leukemia

Hypoxia inducible transcription factors (HIFs) are the main regulators of adaptive responses to hypoxia and are often activated in solid tumors, but their role in leukemia is less clear. In acute myeloid leukemia (AML), in particular, controversial new findings indicate that HIF-1β can act either as an oncogene or a tumor suppressor gene, and this may depend on the stage of leukemia development and/or the AML sub-type. In this study, we find that HIF-1β promotes leukemia progression in the acute monocytic leukemia sub-type of AML through activation of an invasive phenotype. By applying a list of validated HIF-1β-target genes to different AML sub-types, we identified a HIF-1β signature that typifies acute monocytic leukemia when compared with all other AML sub-types. We validated expression of this signature in cell lines and primary cells from AML patients. Interestingly, this signature is enriched for genes that control cell motility at different levels. As a consequence, inhibiting HIF- 1β impaired leukemia cell migration, chemotaxis, invasion and transendothelial migration in vitro, and this resulted in impaired bone marrow homing and leukemia progression in vivo. Our data suggest that in acute monocytic leukemia an active HIF-1β-dependent pro-invasive pathway mediates the ability of leukemic cells to migrate and invade extramedullary sites and may be targeted to reduce leukemia dissemination