Gonadotropin-induced ovarian cancer cell migration and proliferation require extracellular signal-regulated kinase 1/2 activation regulated by calcium and protein kinase Cδ

The gonadotropin hypothesis proposes that elevated serum gonadotropin levels may increase the risk of epithelial ovarian cancer (EOC). We have studied the effect of treating EOC cell lines (OV207 and OVCAR-3) with FSH or LH. Both gonadotropins activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and increased cell migration that was inhibited by the MAPK 1 inhibitor PD98059. Both extra- and intracellular calcium ion signalling were implicated in gonadotropin-induced ERK1/2 activation as treatment with either the calcium chelator EGTA or an inhibitor of intracellular calcium release, dantrolene, inhibited gonadotropin-induced ERK1/2 activation. Verapamil was also inhibitory, indicating that gonadotropins activate calcium influx via L-type voltage-dependent calcium channels. The cAMP/protein kinase A (PKA) pathway was not involved in the mediation of gonadotropin action in these cells as gonadotropins did not increase intracellular cAMP formation and inhibition of PKA did not affect gonadotropin-induced phosphorylation of ERK1/2. Activation of ERK1/2 was inhibited by the protein kinase C (PKC) inhibitor GF 109203X as well as by the PKCδ inhibitor rottlerin, and downregulation of PKCδ was inhibited by small interfering RNA (siRNA), highlighting the importance of PKCδ in the gonadotropin signalling cascade. Furthermore, in addition to inhibition by PD98059, gonadotropin-induced ovarian cancer cell migration was also inhibited by verapamil, GF 109203X and rottlerin. Similarly, gonadotropin-induced proliferation was inhibited by PD98059, verapamil, GF 109203X and PKCδ siRNA. Taken together, these results demonstrate that gonadotropins induce both ovarian cancer cell migration and proliferation by activation of ERK1/2 signalling in a calcium- and PKCδ-dependent manner.

Nitrone [2]rotaxanes: Simultaneous chemical protection and electrochemical activation of a functional group

We report on the use of the hydrogen bond accepting properties of neutral nitrone moieties to prepare benzylic-amide-macrocycle-containing [2]rotaxanes in yields as high as 70 %. X-Ray crystallography shows the presence of up to four intercomponent hydrogen bonds between the amide groups of the macrocycle and the two nitrone groups of the thread. Dynamic 1H NMR studies of the rates of macrocycle pirouetting in nonpolar solutions indicate that amide-nitrone hydrogen bonds are particularly strong, ~1.3 and ~0.2 kcal mol-1 stronger than similar amide-ester and amide-amide interactions, respectively. In addition to polarizing the N-O bond through hydrogen bonding, the rotaxane structure affects the chemistry of the nitrone groups in two significant ways: The intercomponent hydrogen bonding activates the nitrone groups to electrochemical reduction, a one electron reduction of the rotaxane being stablized by a remarkable 400 mV (8.1 kcal mol-1) with respect to the same process in the thread; encapsulation, however, protects the same functional groups from chemical reduction with an external reagent (and slows down electron transfer to and from the electroactive groups in cyclicvoltammetry experiments). Mechanical interlocking with a hydrogen bonding molecular sheath thus provides a route to an encapsulated polarized functional group and radical anions of significant kinetic and thermodynamic stability.

Patient influences on satisfaction and loyalty for GP services

Little is known about the influence that patients themselves have on their loyalty to a general practitioner (GP). Consequently, a theoretical framework that draws on diverse literature is proposed to suggest that along with satisfaction, patient loyalty is an important outcome for GPs. Comprising 174 Australian patients, this study identified that knowledgeable patients reported lower levels of loyalty while older patients and patients visiting a GP more frequently reported higher levels of loyalty. The results suggest that extending patient-centred care practices to encompass all patients may be warranted in order to improve patient satisfaction and loyalty. Further, future research opportunities abound, with intervention and dyadic research methodologies recommended.

Modelling the activation of words in human memory : the spreading activation, spooky-activation-at-a-distance and the entanglement models compared

Modelling how a word is activated in human memory is an important requirement for determining the probability of recall of a word in an extra-list cueing experiment. The spreading activation, spooky-action-at-a-distance and entanglement models have all been used to model the activation of a word. Recently a hypothesis was put forward that the mean activation levels of the respective models are as follows: Spreading � Entanglment � Spooking-action-at-a-distance This article investigates this hypothesis by means of a substantial empirical analysis of each model using the University of South Florida word association, rhyme and word norms.

Under the carpet : the politics and trauma of patient harm

Few studies have investigated iatrogenic outcomes from the viewpoint of patient experience. To address this anomaly, the broad aim of this research is to explore the lived experience of patient harm. Patient harm is defined as major harm to the patient, either psychosocial or physical in nature, resulting from any aspect of health care. Utilising the method of Consensual Qualitative Research (CQR), in-depth interviews are conducted with twenty-four volunteer research participants who self-report having been severely harmed by an invasive medical procedure. A standardised measure of emotional distress, the Impact of Event Scale (IES), is additionally employed for purposes of triangulation. Thematic analysis of transcript data indicate numerous findings including: (i) difficulties regarding patients‘ prior understanding of risks involved with their medical procedure; (ii) the problematic response of the health system post-procedure; (iii) multiple adverse effects upon life functioning; (iv) limited recourse options for patients; and (v) the approach desired in terms of how patient harm should be systemically handled. In addition, IES results indicate a clinically significant level of distress in the sample as a whole. To discuss findings, a cross-disciplinary approach is adopted that draws upon sociology, medicine, medical anthropology, psychology, philosophy, history, ethics, law, and political theory. Furthermore, an overall explanatory framework is proposed in terms of the master themes of power and trauma. In terms of the theme of power, a postmodernist analysis explores the politics of patient harm, particularly the dynamics surrounding the politics of knowledge (e.g., notions of subjective versus objective knowledge, informed consent, and open disclosure). This analysis suggests that patient care is not the prime function of the health system, which appears more focussed upon serving the interests of those in the upper levels of its hierarchy. In terms of the master theme of trauma, current understandings of posttraumatic stress disorder (PTSD) are critiqued, and based on data from this research as well as the international literature, a new model of trauma is proposed. This model is based upon the principle of homeostasis observed in biology, whereby within every cell or organism a state of equilibrium is sought and maintained. The proposed model identifies several bio-psychosocial markers of trauma across its three main phases. These trauma markers include: (i) a profound sense of loss; (ii) a lack of perceived control; (iii) passive trauma processing responses; (iv) an identity crisis; (v) a quest to fully understand the trauma event; (vi) a need for social validation of the traumatic experience; and (vii) posttraumatic adaption with the possibility of positive change. To further explore the master themes of power and trauma, a natural group interview is carried out at a meeting of a patient support group for arachnoiditis. Observations at this meeting and members‘ stories in general support the homeostatic model of trauma, particularly the quest to find answers in the face of distressing experience, as well as the need for social recognition of that experience. In addition, the sociopolitical response to arachnoiditis highlights how public domains of knowledge are largely constructed and controlled by vested interests. Implications of the data overall are discussed in terms of a cultural revolution being needed in health care to position core values around a prime focus upon patients as human beings.

A Cochrane review on the effects of end-of-life care pathways : do they improve patient outcomes?

Clinical pathways for end-of-life care management are used widely around the world and have been regarded as the gold standard. The aim of this review was to assess the effects of end-of-life care pathways (EOLCP), compared with usual care (no pathway) or with care guided by a different end-of-life care pathway, across all healthcare settings (e.g. hospitals, residential aged care facilities, community). We searched the Cochrane Register of Controlled Trials (CENTRAL), the Pain, Palliative and Supportive Care Review group specialised register, MEDLINE, EMBASE, review articles and reference lists of relevant articles. The search was carried out in September 2009. All randomised controlled trials (RCTs), quasi-randomised trials or high quality controlled before and after studies comparing use versus non-use of an EOLCP in caring for the dying were considered for inclusion. The search identified 920 potentially relevant titles, but no studies met criteria for inclusion in the review. Without further available evidence, recommendations for the use of end-of-life pathways in caring for the dying cannot be made. There are now recent concerns regarding the big scale roll-out of EOLCP despite the lack of evidence, nurses should report any safety concerns or adverse effects associated with such pathways.

Planning volunteer responses to low-volume mass gatherings: do event characteristics predict patient workload?

INTRODUCTION: Workforce planning for first aid and medical coverage of mass gatherings is hampered by limited research. In particular, the characteristics and likely presentation patterns of low-volume mass gatherings of between several hundred to several thousand people are poorly described in the existing literature. OBJECTIVES: This study was conducted to: 1. Describe key patient and event characteristics of medical presentations at a series of mass gatherings, including events smaller than those previously described in the literature; 2. Determine whether event type and event size affect the mean number of patients presenting for treatment per event, and specifically, whether the 1:2,000 deployment rule used by St John Ambulance Australia is appropriate; and 3. Identify factors that are predictive of injury at mass gatherings. METHODS: A retrospective, observational, case-series design was used to examine all cases treated by two Divisions of St John Ambulance (Queensland) in the greater metropolitan Brisbane region over a three-year period (01 January 2002-31 December 2004). Data were obtained from routinely collected patient treatment forms completed by St John officers at the time of treatment. Event-related data (e.g., weather, event size) were obtained from event forms designed for this study. Outcome measures include: total and average number of patient presentations for each event; event type; and event size category. Descriptive analyses were conducted using chi-square tests, and mean presentations per event and event type were investigated using Kruskal-Wallis tests. Logistic regression analyses were used to identify variables independently associated with injury presentation (compared with non-injury presentations). RESULTS: Over the three-year study period, St John Ambulance officers treated 705 patients over 156 separate events. The mean number of patients who presented with any medical condition at small events (less than or equal to 2,000 attendees) did not differ significantly from that of large (>2,000 attendees) events (4.44 vs. 4.67, F = 0.72, df = 1, 154, p = 0.79). Logistic regression analyses indicated that presentation with an injury compared with non-injury was independently associated with male gender, winter season, and sporting events, even after adjusting for relevant variables. CONCLUSIONS: In this study of low-volume mass gatherings, a similar number of patients sought medical treatment at small (<2,000 patrons) and large (>2,000 patrons) events. This demonstrates that for low-volume mass gatherings, planning based solely on anticipated event size may be flawed, and could lead to inappropriate levels of first-aid coverage. This study also highlights the importance of considering other factors, such as event type and patient characteristics, when determining appropriate first-aid resourcing for low-volume events. Additionally, identification of factors predictive of injury presentations at mass gatherings has the potential to significantly enhance the ability of event coordinators to plan effective prevention strategies and response capability for these events.

Improving patient privacy and confidentiality in one regional Emergency Department – a quality project

Background: Patient privacy and confidentiality (PPaC) is an important consideration for nurses and other members of the health care team. Can a patient expect to have confidentiality and in particular privacy in the current climate of emergency health care? Do staff who work in the Emergency Department (ED) see confidentiality as an important factor when providing emergency care? These questions are important to consider. Methods: This is a two phased quality improvement project, developed and implemented over a six month period in a busy regional, tertiary referral ED. Results: Issues identified for this department included department design and layout, overcrowding due to patient flow and access block, staff practices and department policies which were also impacted upon by culture of the team, and use of space. Conclusions: Changes successful in improving this issue include increased staff awareness about PPaC, intercom paging prior to nursing handover to remove visitors during handover, one visitor per patient policy, designated places for handover, allocated bed space for patient reviews/assessment and a strategy to temporarily move the patient if procedures would have been undertaken in shared bed space. These are important issues when considering policy, practice and department design in the ED.

Patient-Specific Modeling of Scoliosis

Current complication rates for adolescent spinal deformity surgery are unacceptably high and in order to improve patient outcomes, the development of a simulation tool which enables the surgical strategy for an individual patient to be optimized is necessary. In this chapter we will present our work to date in developing and validating patient-specific modeling techniques to simulate and predict patient outcomes for surgery to correct adolescent scoliosis deformity. While these simulation tools are currently being developed to simulate adolescent idiopathic scoliosis patients, they will have broader applications in simulating spinal disorders and optimizing surgical planning for other types of spine surgery. Our studies to date have highlighted the need for not only patient-specific anatomical data, but also patient-specific tissue parameters and biomechanical loading data, in order to accurately predict the physiological behaviour of the spine. Even so, patient-specific computational models are the state-of-the art in computational biomechanics and offer much potential as a pre-operative surgical planning tool.