Regulation of phosphoinositide dynamics in cell signalling by ADP-ribosylation factor and phosphatidylinositol transfer protein

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is an important source of second messengers and can act as a signalling molecule in its own right. This study has investigated the mechanism of ADP-ribosylation factor (ARF)-stimulated PI(4,5)P2 synthesis. ARF proteins can directly activate type I phosphatidylinositol 4-phosphate 5-kinase (PIP 5-kinase) and phospholipase D (PLD) in vitro. The role of PLD in the regulation of PI(4,5)P2 synthesis was examined in cytosol-depleted HL60 cells using butan- l-ol to diminish the PLD-derived phosphatidic acid (PA), and an ARFl point mutant, N52R-ARF1, that can selectively activate type I PIP 5-kinase but not PLD activity. This work concluded that both PA derived from the PLD pathway, and ARF proteins by directly stimulating type I PIP 5-kinase activity, contribute to the regulation of PI(4,5)P2 synthesis at the plasma membrane in HL60 cells. The PI(4,5)P2 synthesized upon ARF addition was available for hydrolysis by phospholipase C (PLC) only in the presence of a phosphatidylinositol transfer protein a (PITPa). PITP[alpha] was previously identified as a cytosolic factor which can reconstitute agonist-stimulated PLC signalling in cytosol-depleted cells. This study has examined the importance of PITP[alpha] to bind and transfer PI or PC, as well as interact with a membrane surface, for PI delivery required for PLC signalling. Using structural information obtained from the recently elucidated crystal structure of human PITP[alpha] bound to PI, amino acid residues were identified that were predicted to be important for PITPa to bind to PI, and to interact with a membrane surface. Residues T59, K61, E86, and N90 were responsible for interacting with the inositol ring of PI and single point mutants at these residues were sufficient to cause a selective loss in PI but not PC binding and transfer. These mutants were also unable to restore PLC signalling. These amino acid residues were conserved in all proteins with a PITP domain identified in many organisms including mammals, flies, worms, amphibian, fish, and several unicellular organisms. Two tryptophan residues (W203 and W204) were required to dock at the membrane, allowing a model to be described for how PITP[alpha] may undergo lipid exchange at a membrane surface

Self-Care as a Pedagogical Ontology in the Professional Care Practice of Others and with Others: A Hermeneutic Phenomenology of Self-Care in Nursing Education

Healthcare practitioners work in reciprocally dynamic roles in which their health and well-being directly impact their professional competence. This interplay is often understated in ways that regulatory colleges influence training and education programs. In Ontario, for example, we see this in nursing. Although the College of Nurses of Ontario stipulates nursing professional competencies, it does not provide explicit performance expectations related to nursing self-care (i.e., the intentional way one takes care of one’s self). Accordingly, not all Ontario nursing education programs teach self-care. Different from research that deliberates nursing as a discipline or body of knowledge, this research examined how self-care is articulated, prioritized, taught, and assessed in nursing education. As such, the scholarly contribution it offers in the context of education is a pedagogy supporting self-care as a professional competency. Eight nursing faculty shared their lived experiences (through one-on-one interviews) surrounding the notion and phenomenon of self-care in nursing. Through a reiterative hermeneutic interchange that focused on whose voice is missing, an art-informed method that paralleled knowledge creation metaphorically according to the depth and breadth of “delving beneath the surface,” transformed participants spoken words into interpretive texts. Study conclusions suggest that self-care in nursing may be understood and taught through emotionally engaged self-reflection, not as a prescribed set of behaviours or individual task-based activities, but instead, as a pedagogical ontology in the professional care practice of others and with others. To foster successful self-care practice in nursing, educators should consider using arts-based methods to help learners enter and navigate spaces for emotionally engaged self-reflection. Given the urgent need for innovative and rigorous curriculum to support successful self-care practices as part of a healthcare practitioner’s professional role, this research is both timely and relevant

Duoethnography as a dialogic and collaborative form of curriculum inquiry for resident professionalism and self-care education

Medical residency is an important time in the development of physician professionalism, as residents’ identities and medical responsibilities shift from student-learners to practitioner-leaders. During this transition time, many residents struggle with stress due to the unique pressures of their post-graduate training. This, in turn, can potentially hinder successful professional identity development. In response, the Royal College of Physicians and Surgeons of Canada (RCPSC) has incorporated physician health into its CanMEDS professional competency framework.Although this framework identifies enabling self-care professional competencies (e.g., capacity for self-regulation and resilience for sustainable practice), it does not specify the types of educational strategies best suited to teach and assess these competencies. To support the prevention and rehabilitation of resident health issues, residency training programs are faced with the complex challenge of developing socially accountable curricula that successfully foster self-care competencies. Duoethnography, a dialogic and collaborative form of curriculum inquiry, is presented as a pedagogical model for resident professionalism and self-care education. Merits of duoethnography centers on its: 1) capability to foster self-reflexive and transformative learning; 2) versatility to accommodate learner diversity; and 3) adaptability for use in different social, situational, and ethical contexts

Effect of hyperventilation on regional cerebral blood flow in head-injured children

Journal ArticleObjectives: To study cerebral blood flow and cerebral oxygen consumption in severe head-injured children and also to assess the effect of hyperventilation on regional cerebral blood flow. Design: Prospective cohort study. Setting: Pediatric intensive care unit at a tertiary-level university children's hospital. Patients: Twenty-three children with isolated severe brain injury, whose admission Glasgow Coma Scores were 35,25 to 35, and 4.7,3.3 to 4.7, and <3.3 kPa]) after allowing 15 mins for equilibrium. Measurements and Main Results: Thirty-eight studies (each study consisting of three sets of measurements at different levels of Paco2) were performed on 23 patients. At each level of Paco2, the following measurements were made: xenon-enhanced computed tomography scans; cerebral blood flow; intracranial pressure; jugular venous bulb oxygen saturation; mean arterial pressure; and arterial oxygen saturation. Derived variables included: cerebral oxygen consumption; cerebral perfusion pressure; and oxygen extraction ratio. Cerebral blood flow decreased below normal after head injury (mean 49.6 + 14.6 mL/min/100 g). Cerebral oxygen consumption decreased out of proportion to the decrease in cerebral blood flow; cerebral oxygen consumption was only a third of the normal range (mean 1.02 ? 0.59 mL/min/100 g). Neither cerebral blood flow nor cerebral oxygen consumption showed any relationship to time after injury, Glasgow Coma Score at the time of presentation, or intracranial pressure. The frequency of one or more regions of ischemia (defined as cerebral blood flow of <18 mL/min/ 100 g) was 28.9% during normocapnia. This value increased to 73.1% for Paco2 at <25 torr. Conclusions: Severe head injury in children produced a modest decrease in cerebral blood flow but a much larger decrease in cerebral oxygen consumption. Absolute hyperemia was uncommon at any time, but measured cerebral blood flow rates were still above the metabolic requirements of most children. The clear relationship between the frequency of cerebral ischemia and hypocarbia, combined with the rarity of hyperemia, suggests that hyperventilation should be used with caution and monitored carefully in children with severe head injuries. (Crit Care Med 1997; 25:1402-1409)

Challenging the Status Quo: The Evolution of the Supervisor-Student Relationship in the Process of Potentially Stigmatizing and Emotionally Complex Autoethnographic Research

Writing and reliving autoethnographic research is a complex process, both emotionally and intellectually. This is especially true when the focus of the autoethnographer’s research involves experiences with stigma, discrimination, and marginalization in the presence of mental illness. Supervising this process, where students may find themselves feeling vulnerable and confused, presents a unique academic and ethical challenge. How far can a supervisor “push” the student to unearth personal experiences that draw meaning to the larger socio-cultural context to which those experiences took place? How do students confront emotionally painful issues to describe and systematically analyze as part of the academic process? By engaging in a duoethnographic process that pushed beyond surface learning to exploring depths of unconscious biases and hidden assumptions, this paper unveils how the academic relationship between a supervisor and student evolved in terms of understanding, influence, and inspiration, as part of the student’s autoethnographic research. It serves to guide others in the academic supervisor-student relationship when students find themselves confronting emotionally painful issues in their learning. Specifically, the dialogic process of duoethnographic research, where sensitive lived experiences are brought to light and examined, has the potential for students and supervisors to reconceptualize their ways of knowing and being in relation to one another. If successful, this pedagogical framework may be used to support students in their scholarly growth

The donkey skin trade: a growing global problem

A crescente demanda por ejiao – uma gelatina produzida a partir da pele de jumento e usada na medicina tradicional chinesa – está colocando em risco as populações globais de jumentos e ameaçando a subsistência de milhões de pessoas que dependem delas em países de renda média e baixa. Centenas de milhares de jumentos são abatidos para obter suas peles e exportados anualmente, principalmente da África para a China. No entanto, o comércio está se espalhando pelo globo, inclusive para o Brasil. Este artigo destaca as péssimas condições de bem-estar para os jumentos apanhados no comércio legal e ilegal, bem como os efeitos sobre as pessoas vulneráveis e o potencial de propagação de doenças e riscos para a saúde humana.Growing demand for ejiao – gelatin produced from donkey skin and used in Traditional Chinese Medicine – is putting global donkey populations at risk and threatening the livelihoods of millions of people that depend on them in lower and middle-income countries. Hundreds of thousands of donkeys are slaughtered for their skins and exported annually, mostly from Africa to China. However, the trade is spreading across the globe, including Brazil. This article highlights the appalling welfare conditions for donkeys caught up in both the legal and illegal trade, as well as the effects on vulnerable people and the potential for disease spread and hazards to human health

Obstetric practice and cephalopelvic disproportion in Glasgow between 1840 and 1900

This thesis examines obstetric practice associated with cephalopelvic disproportion in Glasgow between 1840 and 1900. Disproportion is a complication of labour, which occurs when there is a physical disparity between the size of the fetus and the size of the birth canal. The majority of these cases involved women who had suffered from rickets as a child, and had a deformed pelvis as a result. During this period the number of children affected by rickets appeared to increase, and as a consequence more cases of disproportion were encountered towards the end of the century. Descriptions of these cases found in a wide-range of published and unpublished materials have been used to analyse changes to obstetric practice in Glasgow. The complex nature of medical decision-making in cases of disproportion is shown. Methods available for the treatment of disproportion included caesarean section, craniotomy, forceps, induction of premature labour, symphysiotomy, and turning. Medical practitioners’ decisions were subject to social, medical and scientific factors. Practitioners’ choices were influenced by their experience, reports of successful cases both abroad and at home, the severity of the pelvic deformity, innovations in medical technique, perceptions of the value of the mother compared to her unborn child, location, and the decisions of the women and their friends and family. After the 1870s there was an increase in the number of women who were delivered by one of these forms of intervention at the Glasgow Maternity Hospital. This change can be attributed to an increase in the prevalence of this condition, but it also reflected a shift from women being admitted on social grounds to medical reasons. This change was in response to an acknowledgement that selecting cases earlier improved the chances of a successful outcome, as evidenced by Murdoch Cameron’s work with caesarean section. In addition, as obstetrics emerged as a specialism, obstetric practitioners claimed these difficult cases for themselves. It was stressed that general practitioners and midwives should send women to obstetric physicians as soon as they were aware of complications, and that obstetric specialists were to replace general surgeons as the operator in severe cases of disproportion when caesarean section was required

Living in the Skin That I Am: An Organizational Autoethnography of an Adult Educator's Plight to Survive the Stigma of Invisible and Episodic Disability in an Academy of Administritiva

Through the reflective lens of an adult educator with invisible and episodic disabilities, this paper has been written as an organizational autoethnography. Through a process of autoethnographical sensemaking, it is intended to illuminate important gaps in organizational theory. Feminist/relational care ethics, critical reflection, and transformative learning serve as the educational theories that comprise its framework. In telling my story, embodied writing and performance narrative are used to convey the felt existence of a body exposed through words—where my “abled” and “disabled” professional teaching and learning identities may be studied against the backdrop of organizational policies and procedures. Words used to describe unfamiliar experiences and situations shape meaning for which new meaning may emerge. At the conclusion of this paper, an alternative frame of reference—a view from the margins—may be offered to articulate authenticity in the expectancy of workplace equity for adult educators with disabilities. Taken collectively on a larger level, it is hoped that this research may provide a source of inspiration for systemic organizational change in adult learning environments