A Heuristic Inquiry: The Narrative of a Beginning Dance/Movement Therapist\u27s Professional Identity Development

There are theories, models, and theses that explain what generally happens as people move through the identified phases of counselor and professional identity development. However, there is little literature that illustrates how this growth actually happens for clinicians. The purpose of this heuristic self-study was to identify and gain a deeper understanding of the narrative of how my clinical experiences have influenced my professional identity as a dance/movement therapist. This study utilized the six phases of heuristic inquiry as a structure to guide this discovery. My personal recollections of three identified cases were used as data, which was then analyzed through the use of Riessman’s Narrative Analysis. The analysis process included responding to structured journal questions and using movement to clarify responses. Unexpected factors that were influential in the development process were acknowledged. The final thesis product was my story, which consists of three mini-narratives that illustrate how my clinical experiences shaped my development as a dance/movement therapist. 115 pages

Pursuing Cardiac Progenitors: Regeneration Redux

Recent studies have questioned the accepted dogma that the regenerative capacity of the heart following injury is limited. Several apparently distinct populations of resident cardiac progenitor cells may have the potential to regenerate functional heart muscle. Despite this progress, the physiologic role and therapeutic potential of cardiac resident progenitor cells remain unclear

Alchemy and the New Age of Cardiac Muscle Cell Biology

Several studies have claimed to identify cardiac stem cells. But what criteria do such cells have to fulfil before we can be confident about their true potential

Prior Authorization Requirements for Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Across US Private and Public Payers

A comprehensive review of prior authorization (PA) requirements for a new class of expensive cholesterol-lowering drugs known as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has found unusually complex and burdensome demands across public and private insurance plans in the United States. These findings raise concerns that current policies may create undue barriers to care even in medically appropriate patients, particularly since requirements were just as stringent for patients with a genetic condition that creates more clear-cut eligibility for PCSK9 inhibitor treatment

Direct gene transfer into cardiac myocytes in vivo

Recent studies have demonstrated that cardiac and skeletal myocytes share the ability to take up and stably express plasmid DNA injected directly into myocardium or skeletal muscle in vivo. Although this is a relatively inefficient process, with less than 1% of the myocytes expressing the injected recombinant DNA, expression in these cells is stable for periods of at least 6 months. The majority of the injected DNA is maintained in myocytes as an episome and apparently does not undergo DNA replication. The direct DNA injection approach has been used to map cardiac-specific transcriptional regulatory elements in cellular promoter/enhancers. Expression of recombinant proteins in the heart following direct DNA injection also holds promise for the treatment of a variety of acquired and inherited cardiovascular diseases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29917/1/0000274.pd

Diabetes reduces bone marrow and circulating porcine endothelial progenitor cells, an effect ameliorated by atorvastatin and independent of cholesterol

Bone marrow derived endothelial progenitor cells (EPCs) are early precursors of mature endothelial cells which replenish aging and damaged endothelial cells. The authors studied a diabetic swine model to determine if induction of DM adversely affects either bone marrow or circulating EPCs and whether a HMG-CoA reductase inhibitor (statin) improves development and recruitment of EPCs in the absence of cholesterol lowering. Streptozotocin was administered to Yorkshire pigs to induce DM. One month after induction, diabetic pigs were treated with atorvastatin (statin, n = 10), ezetimibe (n = 10) or untreated (n = 10) and evaluated for number of bone marrow and circulating EPCs and femoral artery endothelial function. There was no effect of either medication on cholesterol level. One month after induction of DM prior to administration of drugs, the number of bone marrow and circulating EPCs significantly decreased (P < 0.0001) compared to baseline. Three months after DM induction, the mean proportion of circulating EPCs significantly increased in the atorvastatin group, but not in the control or ezetimibe groups. The control group showed progressive reduction in percentage of flow mediated vasodilatation (no dilatation at 3 months) whereas the atorvastatin group and ezetimibe exhibited vasodilatation, 6% and 4% respectively. DM results in significant impairment of bone marrow and circulating EPCs as well as endothelial function. The effect is ameliorated, in part, by atorvastatin independent of its cholesterol lowering effect. These data suggest a model wherein accelerated atherosclerosis seen with DM may, in part, result from reduction in EPCs which may be ameliorated by treatment with a statin

Protein synthesis and degradation during regression of thyroxine-induced cardiac hypertrophy

To characterize changes in rates of protein turnover during regression of thyroxine-induced left ventricular hypertrophy, New Zealand White rabbits received intravenous thyroxine (200 [mu]g/kg/d) for 9 days. Thyroxine was withheld, and in vivo protein turnover was evaluated on the 10th, 15th and 20th days. Animals not receiving thyroxine served as controls. Heart rate, blood pressure, and rate-pressure product were measured to correlate changes in cardiac work with protein turnover rates during the development and regression of hypertrophy. Thyroxine administration produced left ventricular hypertrophy by increasing the rate of protein synthesis (from 37.9 +/- 8.9 to 64.1 +/- 15.3 mg/day; P P &lt; 0.05). Cessation of thyroxine administration resulted in an eventual return of left ventricular mass to that of normally growing control animals. The major observation noted during thyroxine withdrawal was a return of protein synthetic rates to normal. Absolute rates of protein degradation remained elevated, whereas fractional protein degradative rates (i.e. the fraction of total protein degraded per day) were unchanged by the administration and withdrawal of thyroxine. These results indicate that suppression of both physiological and hormone-induced growth following cessation of thyroxine resulted from a decrease in cardiac protein synthetic rates and an increased rate of flux through the protein degradative pathway(s), while fractional rates of protein degradation (and thus average protein half-life) remained unchanged. The development and regression of thyroxine-induced hypertrophy correlated with thyroxine-mediated alterations in cardiac work.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27795/1/0000195.pd

Impaired Notch Signaling Promotes \u3cem\u3eDe novo\u3c/em\u3e Squamous Cell Carcinoma Formation

Signaling through Notch receptors in the skin has been implicated in the differentiation, proliferation, and survival of keratinocytes, as well as in the pathogenesis of basal cell carcinoma (BCC). To determine the composite function of Notch receptor–mediated signaling in the skin and overcome potential redundancies between receptors, conditional transgenic mice were generated that express the pan-Notch inhibitor, dominant-negative Mastermind Like 1 (DNMAML1), to repress all canonical [CBF-1/Suppressor of hairless/LAG-1 (CSL)–dependent] Notch signaling exclusively in the epidermis. Here, we report that DNMAML1 mice display hyperplastic epidermis and spontaneously develop cutaneous squamous cell carcinoma (SCC) as well as dysplastic precursor lesions, actinic keratoses. Mice expressing epidermal DNMAML1 display enhanced accumulation of nuclear ß-catenin and cyclin D1 in suprabasilar keratinocytes and in lesional cells from SCCs, which was also observed in human cutaneous SCC. These results suggest a model wherein CSL-dependent Notch signaling confers protection against cutaneous SCC. The demonstration that inhibition of canonical Notch signaling in mice leads to spontaneous formation of SCC and recapitulates the disease in humans yields fundamental insights into the pathogenesis of SCC and provides a unique in vivo animal model to examine the pathobiology of cutaneous SCC and for evaluating novel therapies

Perception of differentiation cues by GATA factors in primitive endoderm lineage determination of mouse embryonic stem cells

AbstractThe formation of the primitive endoderm covering the inner cell mass of early mouse embryos can be simulated in vitro by the differentiation of mouse embryonic stem (ES) cells in culture following either aggregation of suspended cells or stimulation of cell monolayers with retinoic acid. The developmentally regulated transcription factors GATA-4 and GATA-6 have determining role in mouse extraembryonic endoderm development. We analyzed the in vitro differentiation of mouse embryonic stem cells deficient of GATA factors and conclude that GATA-4 is required for ES cells to perceive a cell positioning (cell aggregation) signal and GATA-6 is required to sense morphogenic (retinoic acid) signal. The collaboration between GATA-6 and GATA-4, or GATA-6 and GATA-5 which can substitute for GATA-4, is involved in the perception of differentiation cues by embryonic stem cells in their determination of endoderm lineage. This study indicates that the lineage differentiation of ES cells can be manipulated by the expression of GATA factors

Simultaneous non-negative matrix factorization for multiple large scale gene expression datasets in toxicology

Non-negative matrix factorization is a useful tool for reducing the dimension of large datasets. This work considers simultaneous non-negative matrix factorization of multiple sources of data. In particular, we perform the first study that involves more than two datasets. We discuss the algorithmic issues required to convert the approach into a practical computational tool and apply the technique to new gene expression data quantifying the molecular changes in four tissue types due to different dosages of an experimental panPPAR agonist in mouse. This study is of interest in toxicology because, whilst PPARs form potential therapeutic targets for diabetes, it is known that they can induce serious side-effects. Our results show that the practical simultaneous non-negative matrix factorization developed here can add value to the data analysis. In particular, we find that factorizing the data as a single object allows us to distinguish between the four tissue types, but does not correctly reproduce the known dosage level groups. Applying our new approach, which treats the four tissue types as providing distinct, but related, datasets, we find that the dosage level groups are respected. The new algorithm then provides separate gene list orderings that can be studied for each tissue type, and compared with the ordering arising from the single factorization. We find that many of our conclusions can be corroborated with known biological behaviour, and others offer new insights into the toxicological effects. Overall, the algorithm shows promise for early detection of toxicity in the drug discovery process