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Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction. Results: At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012). Conclusion: Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.
The decrease in quality of Australian iron ore, coupled with the demand for more efficient energy use, means that closer monitoring and optimisation of process conditions for iron ore sinter production is required. Here, the suitability of using partial least-squares regression analysis of powder X-ray diffraction data, collected for iron ore sinter samples, for the prediction of iron ore sinter strength has been further assessed. In addition, a preliminary assessment of the effect of 2θ range on the quality of prediction has been made. For the purposes of process control, the level of correlation between predicted strength and actual sinter strength would inform an operator whether or not the process was operating within the acceptable limits, or whether there was a potential problem requiring further investigation or rapid intervention. Reducing the 2θ range was found to reduce the level of correlation between predicted and actual strength, to a point where the particular analysis may no longer be suitable for process control.
Background: Painful diabetic neuropathy (PDN) is a frequent complication of diabetes mellitus. Current treatment recommendations are based on short-term trials, generally of ≤3 months’ duration. Limited data are available on the long-term outcomes of this chronic disease. The objective of this study was to determine the long-term clinical effectiveness of the management of chronic PDN at tertiary pain centres. Methods: From a prospective observational cohort study of patients with chronic neuropathic non-cancer pain recruited from seven Canadian tertiary pain centres, 60 patients diagnosed with PDN were identified for analysis. Data were collected according to Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials guidelines including the Brief Pain Inventory. Results: At 12-month follow-up, 37.2% (95% confidence interval [CI], 23.0-53.3) of 43 patients with complete data achieved pain reduction of ≥30%, 51.2% (95% CI, 35.5-66.7) achieved functional improvement with a reduction of ≥1 on the Pain Interference Scale (0-10, Brief Pain Inventory) and 30.2% (95% CI, 17.2-46.1) had achieved both these measures. Symptom management included at least two medication classes in 55.3% and three medication classes in 25.5% (opioids, antidepressants, anticonvulsants). Conclusions: Almost one-third of patients being managed for PDN in a tertiary care setting achieve meaningful improvements in pain and function in the long term. Polypharmacy including analgesic antidepressants and anticonvulsants were the mainstays of effective symptom management.
In the United States alone, ∼14,000 children are hospitalised annually with acute heart failure. The science and art of caring for these patients continues to evolve. The International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was held on February 4 and 5, 2015. The 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was funded through the Andrews/Daicoff Cardiovascular Program Endowment, a philanthropic collaboration between All Children’s Hospital and the Morsani College of Medicine at the University of South Florida (USF). Sponsored by All Children’s Hospital Andrews/Daicoff Cardiovascular Program, the International Pediatric Heart Failure Summit assembled leaders in clinical and scientific disciplines related to paediatric heart failure and created a multi-disciplinary “think-tank”. The purpose of this manuscript is to summarise the lessons from the 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute, to describe the “state of the art” of the treatment of paediatric cardiac failure, and to discuss future directions for research in the domain of paediatric cardiac failure.
To determine whether real-time availability of rapid molecular results of Staphylococcus aureus would impact emergency department clinician antimicrobial selection for adults with cutaneous abscesses.
We performed a prospective, randomized controlled trial comparing a rapid molecular test with standard of care culture-based testing. Follow-up telephone calls were made at between 2 and 7 days, 1 month, and 3 months after discharge.
Two urban, academic emergency departments.
Patients at least 18 years old presenting with a chief complaint of abscess, cellulitis, or insect bite and receiving incision and drainage were eligible. Seven hundred seventy-eight people were assessed for eligibility and 252 met eligibility criteria.
Clinician antibiotic selection and clinical outcomes were evaluated. An ad hoc outcome of test performance was performed.
We enrolled 252 patients and 126 were randomized to receive the rapid test. Methicillin-susceptible S. aureus–positive patients receiving rapid test results were prescribed beta-lactams more often than controls (absolute difference, 14.5% [95% CI, 1.1%–30.1%]) whereas methicillin-resistant S. aureus–positive patients receiving rapid test results were more often prescribed anti–methicillin-resistant S. aureus antibiotics (absolute difference, 21.5% [95% CI, 10.1%–33.0%]). There were no significant differences between the 2 groups in 1-week or 3-month clinical outcomes.
Availability of rapid molecular test results after incision and drainage was associated with more-targeted antibiotic selection.
Neuropathic pain after spinal cord injury (SCI) is a type of central neuropathic pain and is a frequent complication of spinal injury which is often refractory. Studies in animal models describe a number of peripheral and central pathophysiological processes after nerve injury that would be the basis of underlying neuropathic pain mechanisms. A major inhibitory system related to pain is opioid receptor mediated analgesia. In neuropathic pain, N-methyl-d-aspartate (NMDA) receptor activation increases excitation in the pain transmitting systems. Recent advances in pain research indicate multiple mechanisms, including many components of peripheral and central sensitization mechanisms, underlying the initiation and maintenance of neuropathic pain. Neurosurgical interventions may be treatment options in patients with poor pain control despite pharmacotherapy. Besides the effectiveness of a treatment, the adverse event profiles of these analgesics have to be considered before starting therapy or combining different agents.
The rapid growth of educational technologies creates a broad spectrum of ways in which technology can be integrated into classroom instruction. These multiplying points of contact between technology and second language writing converge in the concept of electronic feedback.Writers who are linked to the screen are connected as well to the certainty of receiving some form of reply, whether that feedback comes as an e-mail note about favorite movies from a distant key pal, as an evaluation generated by an automated essay processing algorithm that performs high-stakes writing assessments, or as a compendium of comments from a class peer helping to make final revisions on an academic essay. Instructors can find it difficult, however, to choose from the variety of different pedagogical approaches and recommendations made by researchers. This chapter, by examining the latest developments in electronic feedback and the associated research, aims to help practitioners understand the issues and make a more focused and informed choice.
As we demonstrate, electronic feedback is a slippery term that covers a range of often dissimilar approaches to the teaching of writing. Just as the purposes of literacy take on different meanings and uses in a range of contexts, so do the uses of technology come to bear in a variety of ways depending on the research lens and pedagogical frame. For those who teach writing mainly as mastery of a compendium of subskills, electronic feedback often refers to automated feedback provided by a computer.
Research on networked language learning is now entering its second decade. While earlier research tended to focus on the linguistic and affective characteristics of computer-assisted discussion in single classrooms, more recent research has increasingly focused on long-distance collaboration. This type of learning environment is challenging to arrange, because it involves diverse learners who operate with different cultural backgrounds, communicative expectations, and rhetorical frameworks. These features, as well as the fact that the communication takes place both inside and outside of class and on students' own schedules, also pose special research challenges. This chapter summarizes what knowledge has been gained about learning and instruction in long-distance online exchanges, focusing on three key themes: (a) linguistic interaction and development, (b) intercultural awareness and learning, and (c) development of new multiliteracies and their relations to identity. In each area, research has indicated that there is no single effect of using online communication, but rather that processes and results vary widely depending on a range of logistical, pedagogical, and social factors.
The cerebroside-sulfate activator protein (CSAct
or Saposin B) is a small water-soluble glycoprotein that
plays an essential role in the metabolism of certain glycosphingolipids,
especially sulfatide. Deficiency of CSAct in humans leads
to sulfatide accumulation and neurodegenerative disease.
CSAct activity can be measured in vitro by assay of its
ability to activate sulfatide–sulfate hydrolysis
by arylsulfatase A. CSAct has seven methionine residues
and a mass of 8,845 Da when deglycosylated. Mildly oxidized,
deglycosylated CSAct (+16 Da), separated from nonoxidized
CSAct by reversed-phase high-performance liquid chromatography
(RP-HPLC), showed significant modulation of the in vitro
activity. Because oxidation partially protected against
CNBr cleavage and could largely be reversed by treatment
with dithiothreitol, it was concluded that the major modification
was conversion of a single methionine to its sulfoxide.
High-resolution RP-HPLC separated mildly oxidized CSAct
into seven or more different components with shorter retention
times than nonoxidized CSAct. Mass spectrometry showed
these components to have identical mass (+16 Da). The shorter
retention times are consistent with increased polarity
accompanying oxidation of surface-exposed methionyl side
chains, in general accordance with the existing molecular
model. A mass-spectrometric CNBr mapping protocol allowed
identification of five of the seven possible methionine–sulfoxide
CSAct oxoforms. The most dramatic suppression of activity
occurred upon oxidation of Met61 (26% of control) with
other residues in the Q60MMMHMQ66
motif falling in the 30–50% activity range. Under
conditions of oxidative stress, accumulation of minimally
oxidized CSAct protein in vivo could perturb metabolism
of sulfatide and other glycosphingolipids. This, in turn,
could contribute to the onset and progression of neurodegenerative
disease, especially in situations where the catabolism
of these materials is marginal.
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