The therapeutic alliance is largely recognized as an important component of the therapeutic process. For clients of all ages, the therapeutic alliance has been associated with positive outcomes and increased engagement in therapy (Bachelor, 2013; Bhola, & Kapur, 2013; Liber et al., 2010). However, very few studies have explored the complex process of fostering the therapeutic alliance with adolescent clients, while also maintaining a positive therapeutic relationship with the adolescent’s caregivers. The present study attempted to fill the gap in the literature through qualitatively exploring therapists’ perspectives of the therapeutic alliance with adolescents and their caregivers. In order to discover the essence of therapists’ experiences of the therapeutic alliance with adolescents and their caregivers, a phenomenological research design was employed. Nine therapists were interviewed about their experiences of the therapeutic alliance with adolescents and their caregivers. The interviews were transcribed and analyzed, and various themes and subthemes were revealed. The themes were divided into three sections: (1) conceptualizing the therapeutic alliance, (2) therapeutic alliance with adolescents, and (3) therapeutic alliance with caregivers. Two themes emerged within the ‘conceptualizing the therapeutic alliance’ section: (1) trust, and (2) foundation of therapy. Two themes and various subthemes emerged within the ‘therapeutic alliance with adolescents’ section. The first theme describes the obstacles that therapists face when attempting to build the alliance with adolescent clients, and contained three subthemes: (1) viewed as an authority figure, (2) resistance to therapy, and (3) differences in SES. The second theme describes the strategies that therapists use to develop the therapeutic alliance and contains three subthemes: (1) discuss interests, (2) honor their voice, and (3) describe limits of confidentiality. Two themes were unveiled within the ‘therapeutic alliance with caregivers’ section: (1) obstacles, and (2) strategies. The ‘obstacles’ theme describes barriers that therapists face when constructing the alliance with caregivers of adolescent clients, and contains two subthemes: (1) fear of triangulation, and (2) caregivers’ expectations. The ‘strategies’ theme contains four subthemes: (1) empathy, (2) give caregivers an active role, (3) collaborative approach, and (4) establish clear boundaries. Clinical implications, recommendations for future research, and limitations of the study are discussed.

The effectiveness of estrogen replacement therapy in the prevention of postmenopausal osteoporosis has led to its current widespread use throughout the United States and much of Western Europe, and recently, clinical correlations between circulating androgen levels and structural bone integrity have been presented. Nevertheless, the biochemical mechanism through which estrogens and androgens act to protect and maintain bone has remained unclear. One possibility is that these hormones directly modulate the activity of cells responsible for bone formation. Therefore, studies were conducted to examine the effects of sex steroids on human osteoblast-like cells. In the first set of experiments, a finite human cell line was established from trabecular bone explants obtained from a 48 year-old woman. These cells, designated BG688, were characterized as osteoblast-like in phenotype using several independent criteria. In addition to classical osteoblast markers, BG688 cells also possess approximately 2400 high affinity (K(d) = 0.45nM) 17-β estradiol (E₂) binding sites per cell. The binding of E₂ to a subset of these sites was specific. BG688 cells were also shown to respond to a physiological concentration (10nM) of E₂, which elicits pleiotropic changes in several mRNA levels including a 2-fold increase in the steady state concentration of α₁(I)-procollagen mRNA. These results indicate that human osteoblast-like cells respond to E₂ via a receptor mediated mechanism, but that, unlike the reproductive tissues, osteoblasts are a less sensitive target. In the second series of experiments, the effects of androgenic hormones on the osteoblast-like, human osteosarcoma cell line, HOS TE85 were evaluated. Employing radiolabelled dihydrotestosterone (DHT), 2800 saturable, high-affinity (K(d) = 0.66nM) androgen binding sites were detected per HOS TE85 cell. Androgen binding was specific. The expression of androgen receptors in HOS TE85 cells was further substantiated by Northern analysis. Physiological concentrations of DHT and testosterone decreased HOS TE85 cell proliferation. This finding suggests that androgens may also play a role in osteoblast differentiation. In support of this hypothesis, treatment with testosterone enhanced the abundance of both α₁ (I)-procollagen mRNA and transforming growth factor- β mRNA. The non-aromatizable androgen DHT also elicited an increase in the steady state concentration of α₁(I)-procollagen mRNA. The findings presented herein are significant within the field of bone cell biology in that they demonstrate that osteoblasts are a target cell for the action of sex steroids, via their cognate, high-affinity receptors. These results also have important implications within the broader context of bone pathophysiology in that they suggest a direct modulation of bone forming and bone remodeling activity by sex steroids.

Vitamin A is known to have an important role in cellular differentiation and proliferation. In addition to regulating normal cellular processes vitamin A has also been shown to possess potent antineoplastic activity. The work in this dissertation characterizes the role of retinoic acid (RA) in cellular transformation and tumorigenesis with known oncogene involvement. These studies were initiated by examining the effects of RA on human carcinoma cell lines which express an activated c-ras gene. The bladder carcinoma, EJ/T24 (c-rasᴴ) and the two lung carcinoma cell lines, LXl (c-rasᴷ) and A2182 (c-rasᴷ), were not sensitive to RA. No inhibition of anchorage- or density-dependent growth was observed. Therefore, since these in vitro markers of transformation indicated a lack of effectiveness of RA on carcinomas containing a c-ras gene, retrovirally transformed cells were tested for RA sensitivity. Kirsten murine sarcoma, Balb/c murine sarcoma virus, and Simian sarcoma virus transformed NIH/3T3 and NRK cells were used in these studies. In contrast to the human carcinoma cell lines, anchorage-independent growth of some of the virally transformed cells was very sensitive to inhibition by RA. Anchorage-independent growth of KNRK and SSVNRK cells was sensitive to high concentrations (5 μM) of RA; whereas, Balb/cMSV3T3 and SSV3T3 were sensitive to 1-20 nM RA. BALB/cMSVNRK anchorage-independent growth was stimulated 3.5 fold by 1 μM RA. KNRK displayed a 60% reduction in anchorage-dependent growth at 10 μM RA while little inhibition was observed with the other retrovirally transformed cells. A high level of sensitivity to RA inhibition of anchorage-independent growth was correlated with the presence of cytoplasmic retinoic acid binding protein (CRABP). This indicated that CRABP may have some role in the inhibition of retrovirally induced cellular transformation. RA was shown to significantly reduce the incidence and size of Balb/cMSV3T3 cell tumors in nude mice. The inhibition of tumorigenesis in vivo therefore confirmed the results observed in vitro. To investigate the mechanism by which RA was acting to inhibit retroviral transformation, v-onc mRNA levels were examined. RA had no effect on v-onc mRNA levels in cell lines sensitive to the inhibition of transformation. The effect of RA on the relative rate of synthesis of p21, the transforming protein of KMSV and Balb/cMSV, was investigated. No effect of RA was observed in any of the cell lines. Also, GDP binding by p21 in KNRK cell was unchanged by RA treatment indicating that the functional activity of this transforming protein was not modified. RA does appear to be effective in inhibiting retrovirally induced cellular transformation and tumorigenesis. Evidence presented here indicates that this inhibition is not due to a direct effect of RA on the expression of the v-onc gene and/or gene product. Therefore, some other essential cooperating event(s) occurring within the cell are being acted upon by RA.

No description available.

A transient three-dimensional simulation program was developed to study the effects of scanning speed, scanning pattern, blood perfusion, transducer choice and multiple tilted transducers with overlapping foci during scanned focussed ultrasound hyperthermia. The results showed that (1) the temperature fluctuations increase linearly with decreasing scanning speed, (2) the temperature fluctuations are a weak, increasingly exponential function of the blood perfusion rate, and (3) that the largest temperature fluctuation is always located at the acoustical focal depth on the scan path independently of focal plane depth. Simulations using multiple scan paths showed that relatively uniform average temperature distributions can be achieved at the focal zone as long as the spacing between the concentric scans was not greater than the diameter of the focus of the power field. Finally, the results showed that using multiple tilted transducers with overlapping foci, increased focussing can be obtained at the focal depth.

A series of five, tetradentate Schiff-base ligands were synthesised and chelated to vanadyl to form oxovanadium(IV) complexes. The ligands, 4,4’-{benzene-1,2-diylbis[nitrilo(1E)phen-1-yl-1ylidene]}- dibenzene-1,3-diol (H2L1), 4,4’-{ethane-1,2-diylbis[nitrilo(1E)phenyl-1-yl-1-ylidene]}dibenzene-1,3-diol (H2L2), 4,4’-{propane-1,2-diylbis[nitrilo(1E)phen-1-yl-1-ylidene]}dibenzene-1,3-diol (H2L3), 4,4’-{(2- hydroxypropane-1,3-diyl)bis[nitrilo(1E)phen-1-yl-1-ylidene]}dibenzene-1,3-diol (H2L4) and 4,4’-{2,2- dimethylpropane-1,3-diyl)bis-[nitrilo(1E)phen-1-yl-1-ylidene]}-dibenzene-1,3-diol (H2L5), characterised by TOF-MS, IR, electronic absorption, 1H and 13C NMR spectroscopy. The ligand H2L5 was also characterised by XRD. The ligands were shown to have a bis-zwitterionic structure in the solid state, and possibly also in solution. Complexes were characterised by Elemental Analysis, TOF-MS, IR, electronic absorption spectra, EPR and 51V NMR spectroscopy. They form mononuclear complexes, with one ligand binding a single vanadyl ion. EPR spectroscopy was performed on both the powdered form and solutions of the complexes. All the complexes displayed axial symmetry, with increasing distortion from an ideal square pyramidal geometry as the size and bulk of the central chelate ring was increased. Isotropic g0 values suggest solvent interaction with the vanadium ion for the coordinating solvent DMSO. Additional distortion on the coordination geometry, presumably from the benzyl groups of the compounds, causes the isotropic hyperfine coupling constants to be greater than expected. Furthermore, the ability of the complexes to bind peroxide species was investigated by following the addition of H2O2 to the complexes using 51V NMR spectroscopy to observe shielding changes at the vanadium nucleus, and 1H NMR spectroscopy to monitor the bulk magnetic susceptibility, via a modified Evan’s NMR method. Similar experiments were done with sodium hydroxide for comparison. As expected, the oxoperoxovanadium(V) complexes were more stable than their progenitor oxovanadium(IV) complexes. Additionally, increasing the distortion from the ideal pseudo square-pyramidal coordination geometry for the vanadyl ion resulted in a greater increase in the apparent stability of the peroxocomplexes. This latter effect is further enhanced by the addition of a hydrogen-bonding group in close proximity to the vanadium nucleus. DFT calculations of the optimized geometries, natural bond orbitals, electronic absorption and infra-red frequencies were performed for both the ligands and the complexes; nuclear magnetic resonance calculations were performed for the ligands as well. The B3LYP/6-311G (d,p) and B3LYP/LANL2DZ level of theories were used for the ligands and complexes respectively, except for electronic transitions, which were calculated using TD-SCF methods for both ligands and complexes. Calculated and experimental results were compared where possible, and showed reasonable agreement for all calculations performed. The exception to this was for the NMR calculations for the ligands, which were poorly simulated. Finally, the in vitro biological activity of the complexes was evaluated for cytotoxicity against the human tumour cell lines: A549, U251, TK-10 and HT29, via an MTT assay. All complexes showed promising anticancer activity, as evidenced by their low IC50 values for the cell lines A549, U251 and TK-10, which are in general, lower than that observed for cisplatin. They did, however, express negligible activity against the HT29 colon adenocarcinoma cell line; showing an apparent selectivity for certain cell lines. These oxovanadium(IV) complexes, thus warrant further evaluation as chemotherapeutic agents. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.

This qualitative study aimed to identify how personnel working in a residential home in Sweden work withCognitive Behavioral Therapy (CBT) orientation within the organization. Semi-structured interviews were conducted with five personnel. The research questions were; How do the personnel describe the CBT orientation? How do the personnel describe the CBT tools and methods? How do the personnel describe and measure the implementation of CBT? The results were analyzed an Interpretive Phenomenological Analysis (IPA) tool in order to gain a greater understanding of the data. The theories used to analyze the results were the learning theory, attachment theory and New Public Management (NPM). The results of this study indicate that CBT was incorporated in the daily lives of the residents throughout the course of the day and the personnel described common methods such as Aggression Replacement Therapy (ART), Dialectal Behavioral Therapy (DBT), and Motivational Interviewing (MI).

A dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic, Durban Institute of Technology, 2002. / Plantar fasciitis (PF) is a syndrome that causes pain at the insertion of the plantar fascia to the medial calcaneal tubercle of the calcaneaus. This syndrome has been described as an overuse injury with subsequent inflammation at the insertion of the plantar fascia to the bone. The literature describes inflammatory changes that occur within the body and attachment of the plantar fascia, together with biomechanical aberrances that may be the result of the PF. The purpose of this study was to determine the relative effectiveness of pulsed ultrasound as an adjunct to foot manipulation in the treatment of plantar fasciitis. The foot manipulations are used to correct the biomechanical abnormalities, while the pulsed ultrasound is used for its anti-inflammatory properties. The combination of pulsed ultrasound and foot manipulation was compared to foot manipulation alone to determine if this ultrasound manipulation combination had any beneficial effect over and above foot manipulation alone. Thus determining whether it is of importance to o approach and treat both aspects of the syndrome described. This was a prospective, randomised, comparative controlled trial. Forty subjects were diagnosed with plantar fasciitis and chosen to participate in the study. They were subsequently divided into two groups (Group A and Group B) of twenty. Group A was the experimental group receiving foot manipulation and ultrasound as treatment, and Group B, the control group received foot manipulation alone as treatment. Each subject received six treatments within a period of three weeks, with a seventh follow-up within one week of the sixth treatment. There was no treatment at the seventh consultation; this was used for obtaining subjective and objective readings. Subjective assessment was by means of the Foot Function Index, and objective was by means of the manual algometer. Both the subjective. and objective readings were taken prior to the first, sixth and at the seventh (final) consultations. / M

<p>Anticoagulant agents are commonly used drugs to reduce blood coagulation in acute and chronic clinical settings. Many of these drugs target the common pathway of coagulation because it is critical for thrombin generation and disruption of this portion of the pathway has profound effects on the hemostatic process. Currently available drugs for these indications struggle with balancing desired activity with immunogenicity and poor reversibility or irreversibility in the event of hemorrhage. While improvements are being made with the current drugs, new drugs with better therapeutic indices are needed for surgical intervention and chronic indications to prevent thrombosis from occurring.</p><p> A class of therapeutics known as aptamers may be able to meet the need for safer anticoagulant agents. Aptamer are short single-stranded RNA oligonucleotides that adopt specific secondary and tertiary structures based upon their sequence. They can be generated to both enzymes and cofactors because they derive their inhibitory activity by blocking protein-protein interactions, rather than active site inhibition. They inhibit their target proteins with a high level of specificity and bind with high affinity to their target. Additionally, they can be reversed using two different antidote approaches, specific oligonucleotide antidotes, or with cationic, “universal” antidotes. The reversal of their activity is both rapid and durable.</p><p> The ability of aptamers to be generated to cofactors has been conclusively proven by generating an aptamer targeting the common pathway coagulation cofactor, Factor V (FV). We developed two aptamers with anticoagulant ability that bind to both FV and FVa, the active cofactor. Both aptamers were truncated to smaller functional sizes and had specific point mutant aptamers developed for use as controls. The anticoagulant activity of both aptamer-mutant pairs was characterized using plasma-based clotting assays and whole blood assays. The mechanism of action resulting in anticoagulant activity was assessed for one aptamer. The aptamer was found to block FVa docking to membrane surfaces, a mechanism not previously observed in any of our other anticoagulant aptamers.</p><p> To explore development of aptamers as anticoagulant agents targeting the common pathway for surgical interventions, we fused two anticoagulant aptamers targeting Factor X and prothrombin into a single molecule. The bivalent aptamer was truncated to a minimal size while maintaining robust anticoagulant activity. Characterization of the bivalent aptamer in plasma-based clotting assays indicated we had generated a very robust anticoagulant therapeutic. Furthermore, we were able to simultaneously reverse the activity of both aptamers with a single oligonucleotide antidote. This rapid and complete reversal of anticoagulant activity is not available in the antithrombotic agents currently used in surgery.</p> / Dissertation

A dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Durban University of Technology, 2008. / Conduct a randomised, double blind, placebo controlled study in order to determine the sphere of action of the imponderable remedy Pink 30CH on healthy volunteers who recorded the signs and symptoms produced in order to determine the substances potential usefulness in a future clinical setting according to the Law of Similars. Determine and highlight the commonalities shared between the symptoms and themes produced by remedy Pink 30CH and the other selected imponderable remedies. In the homoeopathic drug proving of remedy Pink 30CH, provers were uninformed to both the nature of the substance as well as to the potency selected and used for proving purposes. Neither the provers nor the research investigator had any knowledge of who received the verum or the placebo until the end of the proving. Thirty (30) provers were selected after meeting the inclusion criteria of which thirty percent (30%) of the subjects received placebo in a randomised fashion. Verum and placebo were dispensed to the proving body in a set of six (6) powders which were taken sublingually three (3) times daily or until any proving symptoms were experienced. All provers were examined and made to record in their journals before, during and after the administration of the proving substance so as to serve as their own intra-individual controls. At the end of the proving period all journals were then recalled and all proving data recorded was then collated and edited into a repertory and materia medica format, which was then used to formulate a homoeopathic drug picture of the remedy that could be used in future clinical settings. The homoeopathic drug picture thus derived was then analysed with the aim of highlighting the important themes that were elicited during the proving. These symptoms and themes were then related and compared to seven (7) other imponderable remedies: Luna (Moonlight); Magnetis Polus Arcticus (North pole of the magnet); Magnetis Polus Australis (South pole of the magnet); Positronium (Anti-matter); Radium bromatum (Radium bromide); Sol (Sunlight) and X-ray, in order to expand the overall understanding of the commonalities shared by the imponderabilia as an entirety. / M