868 research outputs found
PI3Kδ Pathway Dysregulation and Unique Features of Its Inhibition by Leniolisib in Activated PI3Kδ Syndrome and Beyond
Communication skills for medical/dental students at the University of Pretoria: lessons learnt from a two-year study using a forum theatre method
Background: This study describes the lessons learnt from using a novel method for teaching communication skills to second-year medical/dental students.Methods: Medical and drama teachers designed this action research project to serve the educational interests of secondyear medical/dental and drama students. The drama students enacted problematic doctor-patient scenarios for their forum theatre course. The interactive enactment was done for groups of 60-70 medical/dental students. The latter interrupted the actors to suggest improved communication skills. The drama students then re-enacted the scenarios, incorporating the improvements. The medical/dental students\' knowledge of communication skills was assessed before the enactment, three weeks later, and again four months after that. Their semi-structured feedback was analysed thematically. In the next year, the feedback was used to improve the methodology for the new second-year students. Results: In both years, the medical/dental students\' knowledge showed a statistically significant improvement after the enactment, and this was sustained for four months. In year 1, the feedback revolved around language problems and disrespectful attitudes. In year 2, visual cue cards of the communication skills were displayed during the act, and the drama students emphasised these rather than attitudinal problems. However, feedback showed that caricaturing the doctors\' attitudes still detracted attention from the desired focus on communication skills. Conclusions: Although the forum theatre method can transfer knowledge of communication skills, the focus of the acting should be on the demonstration of inappropriate communication skills rather than inappropriate attitudes. One limitation of this study is that assessment was limited to knowledge and did not progress to skills. South African Family Practice Vol. 47(6) 2005: 60-6
WASp-dependent actin cytoskeleton stability at the dendritic cell immunological synapse is required for extensive, functional T cell contacts
The immunological synapse is a highly structured and molecularly dynamic interface between communicating immune cells. Although the immunological synapse promotes T cell activation by dendritic cells, the specific organization of the immunological synapse on the dendritic cell side in response to T cell engagement is largely unknown. In this study, confocal and electron microscopy techniques were used to investigate the role of dendritic cell actin regulation in immunological synapse formation, stabilization, and function. In the dendritic cell-restricted absence of the Wiskott-Aldrich syndrome protein, an important regulator of the actin cytoskeleton in hematopoietic cells, the immunological synapse contact with T cells occupied a significantly reduced surface area. At a molecular level, the actin network localized to the immunological synapse exhibited reduced stability, in particular, of the actin-related protein-2/3-dependent, short-filament network. This was associated with decreased polarization of dendritic cell-associated ICAM-1 and MHC class II, which was partially dependent on Wiskott-Aldrich syndrome protein phosphorylation. With the use of supported planar lipid bilayers incorporating anti-ICAM-1 and anti-MHC class II antibodies, the dendritic cell actin cytoskeleton organized into recognizable synaptic structures but interestingly, formed Wiskott-Aldrich syndrome protein-dependent podosomes within this area. These findings demonstrate that intrinsic dendritic cell cytoskeletal remodeling is a key regulatory component of normal immunological synapse formation, likely through consolidation of adhesive interaction and modulation of immunological synapse stability
Chlorination by-products in drinking water and menstrual cycle function.
We analyzed data from a prospective study of menstrual cycle function and early pregnancy loss to explore further the effects of trihalomethanes (THM) on reproductive end points. Premenopausal women ((italic)n(/italic) = 403) collected urine samples daily during an average of 5.6 cycles for measurement of steroid metabolites that were used to define menstrual parameters such as cycle and phase length. Women were asked about consumption of various types of water as well as other habits and demographics. A THM level was estimated for each cycle based on residence and quarterly measurements made by water utilities during a 90-day period beginning 60 days before the cycle start date. We found a monotonic decrease in mean cycle length with increasing total THM (TTHM) level; at > 60 microg/L, the adjusted decrement was 1.1 days [95% confidence interval (CI), -1.8 to -0.40], compared with less than or equal to 40 microg/L. This finding was also reflected as a reduced follicular phase length (difference -0.94 day; 95% CI, -1.6 to -0.24). A decrement in cycle and follicular phase length of 0.18 days (95% CI, -0.29 to -0.07) per 10 microg/L unit increase in TTHM concentration was found. There was little association with luteal phase length, menses length, or cycle variability. Examining the individual THMs by quartile, we found the greatest association with chlorodibromomethane or the sum of the brominated compounds. Incorporating tap water consumption showed a similar pattern of reduced cycle length with increasing TTHM exposure. These findings suggest that THM exposure may affect ovarian function and should be confirmed in other studies
Bone marrow transplantation in AML, and socioeconomic class: a UK population-based cohort study
<p>Abstract</p> <p>Background</p> <p>We have previously shown that in the UK mortality in people with Acute Myeloid Leukaemia (AML) was nearly 50% greater among the most socio-economically deprived. The aim of this study was to determine whether AML patients from lower socioeconomic classes had a lower chance of receiving a bone marrow transplant.</p> <p>Methods</p> <p>Using Hospital Episode Statistics (HES) data, we identified all incident cases of AML admitted to UK hospitals between 1998 and 2007. We calculated the number of bone marrow transplantations undertaken in AML patients, stratifying our results by gender, age at diagnosis, year of diagnosis, degree of socioeconomic deprivation and co-morbidity. We used logistic regression to calculate odds ratios for bone marrow transplantation, adjusting for gender, age at diagnosis, year of diagnosis, degree of socioeconomic deprivation and co-morbidity score.</p> <p>Results</p> <p>We identified a total of 23 910 incident cases of AML over this 10-year time period, of whom 1 140 (4.8%) underwent BMT. Bone marrow transplantation declined with increasing socioeconomic deprivation (p for trend < 0.001) such that people in the most deprived socioeconomic quintile were 40% less likely to have a transplant than those in the most advantaged group (Odds Ratio 0.60, 95% confidence interval 0.49, 0.73), even after adjusting for gender, age at diagnosis, year of diagnosis and co-morbidity.</p> <p>Conclusion</p> <p>This large cohort study demonstrates that AML patients from lower socioeconomic classes are less likely to undergo bone marrow transplantation than their better off counter-parts.</p
Bringing Social Science Into Critical Zone Science: Exploring Smallholder Farmers' Learning Preferences in Chinese Human‐Modified Critical Zones
There is a growing global emphasis on sustainable agriculture to reduce human impacts and improve delivery of Sustainable Development Goals (SDGs). With increasing investment in critical zone observatories (CZOs), it becomes important to understand how sustainable agricultural knowledge is produced, shared and used between different groups including farmers, scientists and government. To explore these issues, scientists leading the knowledge exchange (KE) component of a China‐UK CZO program studied three farming regions with contrasting geologies and varying economic levels, using a practice‐based research method. We demonstrate how additional funding for social science research allowed us to understand how farmers access and share farming knowledge through bonding, bridging and linking networks, and how this varies spatially, using interviews and survey questionnaires. Knowledge flows, barriers and opportunities for designing locally suited two‐way KE activities were identified. First, we highlight the need for a more locally, socially embedded and reflexive approach to build trust and better address pressing local environmental challenges. Second, we show how social science can usefully inform KE for collaborative, international development science, to draw on local knowledge, promote research impacts and capacity building while avoiding knowledge mismatches. Lastly, a blueprint for the design and funding of future CZOs, social‐ecological and planetary health research agendas that combine science, social science, local knowledge and KE is presented, including the need for substantive social science research to take place in addition to science research in human‐modified landscapes—enabling the CZ science to be better grounded in, informed by and useful to local communities
Regulation of cell protrusions by small GTPases during fusion of the neural folds.
Epithelial fusion is a crucial process in embryonic development, and its failure underlies several clinically important birth defects. For example, failure of neural fold fusion during neurulation leads to open neural tube defects including spina bifida. Using mouse embryos, we show that cell protrusions emanating from the apposed neural fold tips, at the interface between the neuroepithelium and the surface ectoderm, are required for completion of neural tube closure. By genetically ablating the cytoskeletal regulators Rac1 or Cdc42 in the dorsal neuroepithelium, or in the surface ectoderm, we show that these protrusions originate from surface ectodermal cells and that Rac1 is necessary for the formation of membrane ruffles which typify late closure stages, whereas Cdc42 is required for the predominance of filopodia in early neurulation. This study provides evidence for the essential role and molecular regulation of membrane protrusions prior to fusion of a key organ primordium in mammalian development
Australian radiation therapy - Part Two: Reflections of the past, the present, the future
INTRODUCTION: Documentation on the history of Australian radiotherapy is limited. This study provides radiation therapists' (RTs) perspectives of the people, workplace, and work practices in Australian radiotherapy centres from 1960 onwards. It provides a follow-up to our previous study: Australian radiation therapy: An overview – Part one, which outlines the history and development of radiotherapy from conception until present day. METHODS: Four focus groups were conducted on separate occasions in 2010, one in South Australia and three in Victoria, Australia. Participants who worked in radiotherapy were purposively selected to ensure a range of experience, age, and years of work. RESULTS: From a RT perspective, radiotherapy has evolved from a physically demanding ‘hands-on’ work environment, often with unpleasant sights and smells of disease, to a more technology-driven workplace. CONCLUSION: Understanding these changes and their subsequent effects on the role of Australian RTs will assist future directions in advanced role development
Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups
Leber congenital amaurosis (LCA) is an inherited retinal dystrophy that causes childhood blindness. Photoreceptors are especially sensitive to an intronic mutation in the cilia-related gene CEP290, which causes missplicing and premature termination, but the basis of this sensitivity is unclear. Here, we generated differentiated photoreceptors in three-dimensional optic cups and retinal pigment epithelium (RPE) from iPSCs with this common CEP290 mutation to investigate disease mechanisms and evaluate candidate therapies. iPSCs differentiated normally into RPE and optic cups, despite abnormal CEP290 splicing and cilia defects. The highest levels of aberrant splicing and cilia defects were observed in optic cups, explaining the retinal-specific manifestation of this CEP290 mutation. Treating optic cups with an antisense morpholino effectively blocked aberrant splicing and restored expression of full-length CEP290, restoring normal cilia-based protein trafficking. These results provide a mechanistic understanding of the retina-specific phenotypes in CEP290 LCA patients and potential strategies for therapeutic intervention
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