Guillain-Barre Syndrome

Guillain-Barre Syndrome consists of a group of neuropathic conditions characterized by progressive weakness and diminished or absent myotatic reflexes. The estimated annual incidence in the United States is 1.65 to1.79 per 100,000 persons (Walling & Dickson, 2013). Understanding how this condition progresses and the affects it has on a patient will assistant in providing optimal patient care as a future nurse anesthetist. As stated by Turakhia, P., Barrick, B., and Berman, J. (2013) “the anesthetic implications for the various comorbidities are varied and can be profound” (p.1). An individual who suffers from Guillain-Barre is a patient who certainly requires critical care management in order to avoid complications associated with the disease. Being aware of the pathophysiology, risk factors, signs and symptoms, and treatment involved in caring for Guillain-Barre Syndrome can better prepare the advanced practicing nurse for patients suffering from this condition

Rural congestive heart failure mortality among US elderly, 1999–2013: Identifying counties with promising outcomes and opportunities for implementation research

Objective Describe modern trends in congestive heart failure (CHF) among elderly (\u3e65 years of age) in the United States, to identify potentially successful rural areas. Compare CHF mortality using multiple- (MCOD) versus underlying-(UCOD) cause of death data. Methods U.S. Centers for Disease Control and Prevention mortality files (WONDER internet site). Results Using MCOD data, overall mortality rates/100,000 population (and 95% confidence intervals) for CHF among persons \u3e65 years of age (1999–2013) were 482.0 (481.2–482.8) for large central and large fringe metropolitan (LCLF) counties, 549.6 (548.6–550.7) in small and medium metropolitan (SM) counties, and 652.6 (650.9–654.0) in micropolitan and non-core, non-metropolitan (MNCNM) counties. Twenty positive deviance NCNM counties (collectively including 198,581 residents \u3e65 years of age) had an overall CHF rate of 300.9 (275.0–326.9) in 2013. This was significantly lower than the LCLF rate for 2013 (482.0 [481.2–482.8]), and represented a reduction of 47% since 1999. Overall CHF occurrence as estimated with MCOD was 3.4-fold higher than that obtained with UCOD. Conclusion These data illustrate underestimation of CHF by UCOD data and the importance of correct death certification. Rural CHF mortality rates are higher than urban rates, but some positive deviance counties demonstrate that this is not inevitable. Further research is needed to understand the relative contribution of research innovation, medical care, and public health to rural-urban disparities and the relative success of positive deviance counties

Beyond the Binding Site: The Role of the β2 – β3 Loop and Extra-Domain Structures in PDZ Domains

A general paradigm to understand protein function is to look at properties of isolated well conserved domains, such as SH3 or PDZ domains. While common features of domain families are well understood, the role of subtle differences among members of these families is less clear. Here, molecular dynamics simulations indicate that the binding mechanism in PSD95-PDZ3 is critically regulated via interactions outside the canonical binding site, involving both the poorly conserved loop and an extra-domain helix. Using the CRIPT peptide as a prototypical ligand, our simulations suggest that a network of salt-bridges between the ligand and this loop is necessary for binding. These contacts interconvert between each other on a time scale of a few tens of nanoseconds, making them elusive to X-ray crystallography. The loop is stabilized by an extra-domain helix. The latter influences the global dynamics of the domain, considerably increasing binding affinity. We found that two key contacts between the helix and the domain, one involving the loop, provide an atomistic interpretation of the increased affinity. Our analysis indicates that both extra-domain segments and loosely conserved regions play critical roles in PDZ binding affinity and specificity

A mouse model of creatine transporter deficiency reveals impaired motor function and muscle energy metabolism

Creatine serves as fast energy buffer in organs of high-energy demand such as brain and skeletal muscle. L-Arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase are responsible for endogenous creatine synthesis. Subsequent uptake into target organs like skeletal muscle, heart and brain is mediated by the creatine transporter (CT1, SLC6A8). Creatine deficiency syndromes are caused by defects of endogenous creatine synthesis or transport and are mainly characterized by intellectual disability, behavioral abnormalities, poorly developed muscle mass, and in some cases also muscle weakness. CT1-deficiency is estimated to be among the most common causes of X-linked intellectual disability and therefore the brain phenotype was the main focus of recent research. Unfortunately, very limited data concerning muscle creatine levels and functions are available from patients with CT1 deficiency. Furthermore, different CT1-deficient mouse models yielded conflicting results and detailed analyses of their muscular phenotype are lacking. Here, we report the generation of a novel CT1-deficient mouse model and characterized the effects of creatine depletion in skeletal muscle. HPLC-analysis showed strongly reduced total creatine levels in skeletal muscle and heart. MR-spectroscopy revealed an almost complete absence of phosphocreatine in skeletal muscle. Increased AGAT expression in skeletal muscle was not sufficient to compensate for insufficient creatine transport. CT1-deficient mice displayed profound impairment of skeletal muscle function and morphology (i.e., reduced strength, reduced endurance, and muscle atrophy). Furthermore, severely altered energy homeostasis was evident on magnetic resonance spectroscopy. Strongly reduced phosphocreatine resulted in decreased ATP/Pi levels despite an increased inorganic phosphate to ATP flux. Concerning glucose metabolism, we show increased glucose transporter type 4 expression in muscle and improved glucose clearance in CT1-deficient mice. These metabolic changes were associated with activation of AMP-activated protein kinase - a central regulator of energy homeostasis. In summary, creatine transporter deficiency resulted in a severe muscle weakness and atrophy despite different compensatory mechanisms

Spatial dislocation and affective displacement: youth perspectives on gentrification in London

Analyses of contemporary processes of gentrification have been primarily produced from adult perspectives with little focus on how age affects or mediates urban change. However, in analysing young people’s responses to transformations in their neighbourhood we argue that there is evidence for a more complex relationship between ‘gentrifiers’ and residents than existing arguments of antagonism or tolerance would suggest. Using a participatory video methodology to document experiences of gentrification in the east London borough of Hackney, we found that young people involved in this study experienced their transforming city through processes of spatial dislocation and affective displacement. The former incorporated a sense of disorientation in the temporal disjunctions of the speed of change, while the latter invoked the embodiment of a sense of not belonging generated within classed and intercultural interactions. However, there are expressions of ambivalence rather than straightforward rejection. Benefits of gentrification were noted including conditions of alterity and the possibility to transcend normative behaviours that they found uncomfortable. Young people demonstrated the capacity to re-imagine their relationship with the complex spaces they call home. The findings suggest a need to reframe debates on gentrification to include a more nuanced understanding of its differential impact on young people

Service delivery and intervention intensity for phonology-based speech sound disorders

Background: When planning evidence-based intervention services for children with phonology-based speech sound disorders (SSD), speech and language therapists (SLTs) need to integrate research evidence regarding service delivery and intervention intensity within their clinical practice. However, relatively little is known about the optimal intensity of phonological interventions and whether SLTs’ services align with the research evidence.Aims: The aims are twofold. First, to review external evidence (i.e., empirical research evidence external to day-today clinical practice) regarding service delivery and intervention intensity for phonological interventions. Second,to investigate SLTs’ clinical practice with children with phonology-based SSD in Australia, focusing on service delivery and intensity. By considering these complementary sources of evidence, SLTs and researchers will be better placed to understand the state of the external evidence regarding the delivery of phonological interventions and appreciate the challenges facing SLTs in providing evidence-based services.Methods & Procedures: Two studies are presented. The first is a review of phonological intervention research published between 1979 and 2016. Details regarding service delivery and intervention intensity were extractedfrom the 199 papers that met inclusion criteria identified through a systematic search. The second study was an online survey of 288 SLTs working in Australia, focused on the service delivery and intensity of intervention provided in clinical practice.Main Contributions: There is a gap between the external evidence regarding service delivery and intervention intensity and the internal evidence from clinical practice. Most published intervention research has reported toprovide intervention two to three times per week in individual sessions delivered by an SLT in a university clinic, in sessions lasting 30–60 min comprising 100 production trials. SLTs reported providing services at intensities below that found in the literature. Further, they reported workplace, client and clinician factors that influenced the intensity of intervention they were able to provide to children with phonology-based SSD.Conclusions & Implications: Insufficient detail in the reporting of intervention intensity within published research coupled with service delivery constraints may affect the implementation of empirical evidence into everyday clinical practice. Research investigating innovative solutions to service delivery challenges is needed to provide SLTs with evidence that is relevant and feasible for clinical practice

Creating and curating an archive: Bury St Edmunds and its Anglo-Saxon past

This contribution explores the mechanisms by which the Benedictine foundation of Bury St Edmunds sought to legitimise and preserve their spurious pre-Conquest privileges and holdings throughout the Middle Ages. The archive is extraordinary in terms of the large number of surviving registers and cartularies which contain copies of Anglo-Saxon charters, many of which are wholly or partly in Old English. The essay charts the changing use to which these ancient documents were put in response to threats to the foundation's continued enjoyment of its liberties. The focus throughout the essay is to demonstrate how pragmatic considerations at every stage affects the development of the archive and the ways in which these linguistically challenging texts were presented, re-presented, and represented during the Abbey’s history

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Geospatial assessment of threats to freshwater mussel populations within the Upper Duck River watershed

Conservation of biodiversity is critical in maintaining healthy ecosystems. The Duck River of Tennessee is considered one of the most biologically diverse freshwater systems in North America. Mussel populations are particularly sensitive to pollution and are key indicators of water quality. A geospatial information system (GIS) was developed to identify the spatial location of stressors and the magnitude of stress in relation to mussels and mussel host fish occurrences. Threats assessed included non point source pollution from agriculture, point source pollution from Water Pollution Control (WPC) permits, and dams and their potential for mussel/host fish fragmentation and downstream effect on mussel populations. An assessment of population distribution of individual mussel species and their host fish identified the relationship between threat and mussel shoals. Stream reaches containing mussel and associated host fish habitat overlap were identified as productive reproduction sites, and mussel habitat lacking host fish overlap were located and prioritized as in need of field sampling to ensure the availability for population growth. The majority of mussel occurrences (12 to 440 observations per catchment) were found within eight catchments along 43 km of 139.7 km of the Upper Duck River. These eight catchments were consistently identified by the GIS as areas of medium to low threat risk regions, suggesting that the mussel communities were thriving in a clustered area with minimal threats. The small area, however, suggested that species richness and abundance may be low throughout the rest of the watershed. Mussel observation densities and species diversity were greatest within 0 to 15 km downstream of Lillard\u27s Mill Dam, while high observation densities and species diversity were not present until 100 km downstream of Normandy Dam, suggesting that the difference in type and operational characteristics of each dam had a vastly different effect on mussel populations downstream. The GIS developed in this project will be applied in the decision making process to identify threatened river reaches, and potential reintroduction sites for mussels, and areas where more study may be required