Paraganglioma of the cauda equina: a tertiary centre experience and scoping review of the current literature

Neurosurgical Review - Cauda equina paragangliomas are rare benign extra-adrenal neuroendocrine tumours arising from the neural crest cells associated with autonomic ganglia. These tumours are...     

Hemolytic Disease of the Newborn Apparently Caused by Anti-Lua

Report of the first example of pure anti-Lu^a associated with hemolytic disease of the newborn. Of special interest is the fact that this serum demonstrated a marked prozone reaction in saline, papain and indirect Coombs titrations, and is the first anti-Lu^a serum to react well by the indirect Coombs technic.     

Angiogenesis in myocardial laser "revascularization"

The clinical and experimental data relevant to the theoretical mechanisms and clinical results of laser myocardial "revascularization" are reviewed. Both transmyocardial (TMR) and percutaneous (PMR) approaches are considered. Special attention is paid to the issue of TMR-induced angiogenesis. Both TMR and PMR result in a reduction in angina symptoms in patients refractory to conventional therapy and are likely to act through common pathways. TMR-induced angiogenesis appears to result from the up-regulation of vascular growth factors. However, the available data suggest that the angiogenic response is not a unique consequence of laser revascularization. Rather, the angiogenesis associated with TMR is likely to be a non-specific response of the myocardium to injury.     

Septin assemblies form by diffusion-driven annealing on membranes

Septins assemble into filaments and higher-order structures that act as scaffolds for diverse cell functions including cytokinesis, cell polarity, and membrane remodeling. Despite their conserved role in cell organization, little is known about how septin filaments elongate and are knitted together into higher-order assemblies. Using fluorescence correlation spectroscopy, we determined that cytosolic septins are in small complexes, suggesting that septin filaments are not formed in the cytosol. When the plasma membrane of live cells is monitored by total internal reflection fluorescence microscopy, we see that septin complexes of variable size diffuse in two dimensions. Diffusing septin complexes collide and make end-on associations to form elongated filaments and higher-order structures, an assembly process we call annealing. Septin assembly by annealing can be reconstituted in vitro on supported lipid bilayers with purified septin complexes. Using the reconstitution assay, we show that septin filaments are highly flexible, grow only from free filament ends, and do not exchange subunits in the middle of filaments. This work shows that annealing is a previously unidentified intrinsic property of septins in the presence of membranes and demonstrates that cells exploit this mechanism to build large septin assemblies.Septin filaments form rings, bars, and gauzes that serve as a scaffold at cell division sites; act to retract blebbed regions of membrane; and restrict diffusion between cell compartments (1–4). Septin function is required for cell division and viability in many eukaryotes whereas misregulation is associated with cancers and neurodegenerative disorders (5–8). Furthermore, septins mediate entry of both bacterial and fungal pathogens into host cells (9–11). In vivo, septin assembly is restricted both in time and in space through local activation of small GTPases such as Cdc42. Localized signaling leads to higher-order septin structures forming closely apposed to the plasma membrane at the plane of division, sites of polarity, and curved membranes (10, 12–14). Notably, eukaryotic cells of different geometries build higher-order septin assemblies of various shapes, sizes, and functions (4, 15, 16). Although septins are critical for spatial organization of cell plasma membranes, their assembly and disassembly dynamics are not understood (15).Electron microscopy (EM) studies of recombinant and immunoprecipitated Saccharomyces cerevisiae septins have shown that septins form nonpolar hetero-octameric rod-shaped complexes in high-salt buffers (>300 mM) and elongated filaments when dialyzed into low-salt buffers (<100 mM) (17, 18). Structural analyses of worm and mammalian septins have revealed that the heteromeric, rod-shaped complex is conserved (19–21). Thus, septin rods characterized to date contain two copies of each septin subunit assembled into a nonpolar, heteromeric complex (Fig. S1). Association of purified septin proteins with phosphoinositide-containing membrane monolayers placed on EM grids can promote the assembly of septin filaments in otherwise nonpermissive conditions such as high salt or the presence of mutant septins in the complex (22). A polybasic region in the N terminus of septin proteins as well as other surfaces of the septin protein have been proposed to be the basis for septin association with phosphoinositides; however, the functional role of membranes in filament formation is not yet known (22–24).Previous work has defined a possible starting state of assembly (the rod) and endpoint (filaments and gauzes); however, there is nothing known about how filaments elongate either in vivo or in vitro. Do septin filaments extend by stepwise addition of rods? Does addition occur from both ends of the filament? Can subunits be added in the middle and/or sides of a filament? Do septin filaments grow in the cytosol or on plasma membranes? Thus, it is still not known where filaments form in vivo, how filaments elongate, and how filaments are brought together to construct higher-order assemblies.The goal of this study was to identify the locations and mechanism of septin filament polymerization. Using fluorescence correlation spectroscopy (FCS), we observed that cytosolic septins are likely rods, not monomers or filaments. Using total internal reflection fluorescence (TIRF) microscopy, we found septins form short filaments on the plasma membrane and then long filaments and higher-order assemblies grow when filaments merge. We have called the process of short filaments coming together “annealing” as this has previously been described for F-actin in vitro (25). We reconstituted septin assembly, using purified proteins and supported lipid bilayers, and found that annealing is an intrinsic property of septins that occurs at very low protein concentrations in the presence of a supported phospholipid bilayer. Our results suggest that the plasma membrane concentrates septins and provides a platform for 2D diffusion that promotes polymerization.     

Disparities in Influenza Vaccination Coverage Among Women with Live-Born Infants: PRAMS Surveillance During the 2009–2010 Influenza Season

Objectives

Vaccination during pregnancy significantly reduces the risk of influenza illness among pregnant women and their infants up to 6 months of age; however, many women do not get vaccinated. We examined disparities in vaccination coverage among women who delivered a live-born infant during the 2009–2010 influenza season, when two separate influenza vaccinations were recommended.

Methods

Pregnancy Risk Assessment Monitoring System (PRAMS) data from 29 states and New York City, collected during the 2009–2010 influenza season, were used to examine uptake of seasonal (unweighted n=27,153) and pandemic influenza A(H1N1)pdm09 (pH1N1) (n=27,372) vaccination by racially/ethnically diverse women who delivered a live-born infant from September 1, 2009, through May 31, 2010.

Results

PRAMS data showed variation in seasonal and pH1N1 influenza vaccination coverage among women with live-born infants by racial/ethnic group. For seasonal influenza vaccination, coverage was 50.5% for non-Hispanic white, 30.2% for non-Hispanic black, 42.1% for Hispanic, and 48.2% for non-Hispanic other women. For pH1N1, vaccination coverage was 41.4% for non-Hispanic white, 25.5% for non-Hispanic black, 41.1% for Hispanic, and 43.3% for non-Hispanic other women. Compared with non-Hispanic white women, non-Hispanic black women had lower seasonal (crude prevalence ratio [cPR] = 0.60, 95% confidence interval [CI] 0.55, 0.64) and pH1N1 (cPR=0.62, 95% CI 0.57, 0.67) vaccination coverage; these disparities diminished but remained after adjusting for provider recommendation or offer for influenza vaccination, insurance status, and demographic factors (seasonal vaccine: adjusted PR [aPR] = 0.80, 95% CI 0.74, 0.86; and pH1N1 vaccine: aPR=0.75, 95% CI 0.68, 0.82).

Conclusion

To reduce disparities in influenza vaccination uptake by pregnant women, targeted efforts toward providers and interventions focusing on pregnant and postpartum women may be needed.Pregnant women are at increased risk for complications from influenza and are more likely than the general population to be hospitalized due to respiratory illness during influenza season.^1–4 Seasonal vaccination can reduce morbidity and mortality associated with seasonal influenza.^1,2 While the influenza vaccine recommendations for pregnant women date back to the 1960s, it was in 2004 that the American College of Obstetricians and Gynecologists (ACOG) and the Advisory Committee on Immunization Practices (ACIP) recommended that women be vaccinated with the inactivated influenza vaccine any time during pregnancy.^5–7 Historically, the national estimates showed that, of the adult groups recommended to receive seasonal vaccination, pregnant women had the lowest coverage prior to the 2009–2010 influenza season.^7–9 Research has shown that there are racial/ethnic and economic disparities in vaccination coverage among adults. In general, vaccination coverage is lower among non-Hispanic black and Hispanic women than among non-Hispanic white women and women of lower socioeconomic status.^10–16 For pregnant women in particular, coverage prior to the 2009–2010 influenza season was less than 30%.^8,9Because influenza can be especially severe during pregnancy, pregnant women in particular were at increased risk of severe disease and mortality from pandemic influenza A(H1N1)pdm09 (pH1N1) virus infection.¹⁷ During the 2009–2010 influenza season, both the inactivated trivalent seasonal and monovalent pH1N1 vaccinations were recommended for pregnant women.^17,18 Pregnant women were deemed a priority group for the pH1N1 vaccine due to high morbidity and mortality associated with pH1N1 infection within this group. Monovalent pH1N1 vaccine was purchased by the federal government and made available to the public at no cost. Additionally, the monovalent vaccine was made available later than the trivalent seasonal influenza vaccine.Given the recommendation of vaccination for pregnant women and the importance of preventing morbidity and mortality from influenza, we examined disparities in vaccination uptake by pregnant women with recent live-born infants who participated in the Pregnancy Risk Assessment Monitoring System (PRAMS) survey. The rationale for examining data from the 2009–2010 influenza season was to learn about vaccination coverage of a vulnerable population (i.e., pregnant women) during the pandemic.^19,20 Research questions guiding the analysis included (1) What are the differences in vaccination coverage among racial/ethnic groups of pregnant women? and (2) Are there differences by race/ethnicity in the patterns of vaccination uptake for the two influenza vaccinations offered during the 2009–2010 influenza season?     

Rethinking Patient Engagement in Cancer Research

The Patient - Patient-Centered Outcomes Research -     

Problem-based learning (PBL) and speech-language pathology: A tutorial

The aim of this tutorial is to provide an introduction to problem-based learning (PBL), particularly as applied to speech-language pathology (SLP) programs. The tutorial is aimed at the reader who is less familiar with this learning approach. Additionally, it serves as a framework for the articles that follow in this special issue on PBL programs in SLP and other clinical education programs. A brief history of PBL is provided and the rationale and context for this approach are identified. PBL is defined and differentiated from related educational approaches. Different models and variations of PBL are outlined. The key components of PBL are further illustrated using the tutorial cycle. Finally, we present one specific case of a PBL-based SLP program in detail. This tutorial will provide a deeper understanding of PBL for many higher educators in SLP. The strengths of this approach are outlined and the challenges are identified, particularly for those contemplating converting an existing “traditional” course or curriculum.     

Educational Technologies in Problem-Based Learning in Health Sciences Education: A Systematic Review

BackgroundAs a modern pedagogical philosophy, problem-based learning (PBL) is increasingly being recognized as a major research area in student learning and pedagogical innovation in health sciences education. A new area of research interest has been the role of emerging educational technologies in PBL. Although this field is growing, no systematic reviews of studies of the usage and effects of educational technologies in PBL in health sciences education have been conducted to date.ObjectiveThe aim of this paper is to review new and emerging educational technologies in problem-based curricula, with a specific focus on 3 cognate clinical disciplines: medicine, dentistry, and speech and hearing sciences. Analysis of the studies reviewed focused on the effects of educational technologies in PBL contexts while addressing the particular issue of scaffolding of student learning.MethodsA comprehensive computerized database search of full-text articles published in English from 1996 to 2014 was carried out using 3 databases: ProQuest, Scopus, and EBSCOhost. Eligibility criteria for selection of studies for review were also determined in light of the population, intervention, comparison, and outcomes (PICO) guidelines. The population was limited to postsecondary education, specifically in dentistry, medicine, and speech and hearing sciences, in which PBL was the key educational pedagogy and curriculum design. Three types of educational technologies were identified as interventions used to support student inquiry: learning software and digital learning objects; interactive whiteboards (IWBs) and plasma screens; and learning management systems (LMSs).ResultsOf 470 studies, 28 were selected for analysis. Most studies examined the effects of learning software and digital learning objects (n=20) with integration of IWB (n=5) and LMS (n=3) for PBL receiving relatively less attention. The educational technologies examined in these studies were seen as potentially fit for problem-based health sciences education. Positive outcomes for student learning included providing rich, authentic problems and/or case contexts for learning; supporting student development of medical expertise through the accessing and structuring of expert knowledge and skills; making disciplinary thinking and strategies explicit; providing a platform to elicit articulation, collaboration, and reflection; and reducing perceived cognitive load. Limitations included cumbersome scenarios, infrastructure requirements, and the need for staff and student support in light of the technological demands of new affordances.ConclusionsThis literature review demonstrates the generally positive effect of educational technologies in PBL. Further research into the various applications of educational technology in PBL curricula is needed to fully realize its potential to enhance problem-based approaches in health sciences education.