Pragmatic application of a clinical prediction rule in primary care to identify patients with low back pain with a good prognosis following a brief spinal manipulation intervention

BACKGROUND: Patients with low back pain are frequently encountered in primary care. Although a specific diagnosis cannot be made for most patients, it is likely that sub-groups exist within the larger entity of nonspecific low back pain. One sub-group that has been identified is patients who respond rapidly to spinal manipulation. The purpose of this study was to examine the association between two factors (duration and distribution of symptoms) and prognosis following a spinal manipulation intervention. METHODS: Data were taken from two previously published studies. Patients with low back pain underwent a standardized examination, including assessment of duration of the current symptoms in days, and the distal-most distribution of symptoms. Based on prior research, patients with symptoms of <16 days duration and no symptoms distal to the knee were considered to have a good prognosis following manipulation. All patients underwent up to two sessions of spinal manipulation treatment and a range of motion exercise. Oswestry disability scores were recorded before and after treatment. If ≥ 50% improvement on the Oswestry was achieved, the intervention was considered a success. Sensitivity, specificity, and positive likelihood ratio were calculated for the association of the two criteria with the outcome of the treatment. RESULTS: 141 patients (49% female, mean age = 35.5 (± 11.1) years) participated. Mean pre- and post-treatment Oswestry scores were 41.9 (± 10.9) and 24.1 (± 14.2) respectively. Sixty-three subjects (45%) had successful treatment outcomes. The sensitivity of the two criteria was 0.56 (95% CI: 0.43, 0.67), specificity was 0.92 (95% CI: 0.84, 0.96), and the positive likelihood ratio was 7.2 (95% CI: 3.2, 16.1). CONCLUSION: The results of this study demonstrate that two factors; symptom duration of less than 16 days, and no symptoms extending distal to the knee, were associated with a good outcome with spinal manipulation

Locomotor changes in length and EMG activity of feline medial gastrocnemius muscle following paralysis of two synergists

The mechanism of the compensatory increase in electromyographic activity (EMG) of a cat ankle extensor during walking shortly after paralysis of its synergists is not fully understood. It is possible that due to greater ankle flexion in stance in this situation, muscle spindles are stretched to a greater extent and, thus, contribute to the EMG enhancement. However, also changes in force feedback and central drive may play a role. The aim of the present study was to investigate the short-term (1- to 2-week post-op) effects of lateral gastrocnemius (LG) and soleus (SO) denervation on muscle fascicle and muscle–tendon unit (MTU) length changes, as well as EMG activity of the intact medial gastrocnemius (MG) muscle in stance during overground walking on level (0%), downslope (−50%, presumably enhancing stretch of ankle extensors in stance) and upslope (+50%, enhancing load on ankle extensors) surfaces. Fascicle length was measured directly using sonomicrometry, and MTU length was calculated from joint kinematics. For each slope condition, LG-SO denervation resulted in an increase in MTU stretch and peak stretch velocity of the intact MG in early stance. MG muscle fascicle stretch and peak stretch velocity were also higher than before denervation in downslope walking. Denervation significantly decreased the magnitude of MG fascicle shortening and peak shortening velocity during early stance in level and upslope walking. MG EMG magnitude in the swing and stance phases was substantially greater after denervation, with a relatively greater increase during stance of level and upslope walking. These results suggest that the fascicle length patterns of MG muscle are significantly altered when two of its synergists are in a state of paralysis. Further, the compensatory increase in MG EMG is likely mediated by enhanced MG length feedback during downslope walking, enhanced feedback from load-sensitive receptors during upslope walking and enhanced central drive in all walking conditions

How portuguese and american teachers plan for literacy instruction

This study explored American and Portuguese elementary teachers' preferences in planning for literacy instruction using the Language Arts Activity Grid (LAAG; Cunningham, Zibulsky, Stanovich, & Stanovich, 2009), on which teachers described their preferred instructional activities for a hypothetical 2-h language arts block. Portuguese teachers (N = 186) completed Portuguese versions of a background questionnaire and LAAG electronically, in Survey Monkey; American teachers (N = 102) completed identical English measures using paper and pencil. Results showed that teachers in both groups usually addressed comprehension and reading fluency on their LAAGs and that they also allocated the most time to these two areas. However, American teachers were more likely to include teacher-directed fluency activities, whereas Portuguese teachers were more likely to include fluency activities that were not teacher directed. Significantly more American than Portuguese teachers addressed phonics in their planning, whereas significantly more Portuguese than American teachers addressed writing processes such as revision. Both groups of educators demonstrated large variability in planning, with many teachers omitting important components of literacy identified by researchers, for writing as well as reading. The study highlights the importance of providing teachers with comprehensive, research-based core literacy curricula as well as professional development on key components of literacy. Study findings also suggest significant relationships between orthographic transparency and teachers' instructional planning.This research was supported by a 2-year grant from the Foundation Francisco Manuel dos Santos in Portugal as well as by a Connecticut State University research grant in the U.S.A. We would like to express our sincere gratitude to these funding agencies as well as to the teachers and school districts who participated in the study and sent messages of interest about our research. In addition, warm thanks to our research assistants for their help with data collection, coding, and analysis, and to Anne Cunningham for providing us with inspiration as well as guidance in this work.info:eu-repo/semantics/publishedVersio

The Leukemia-Specific Fusion Gene ETV6/RUNX1 Perturbs Distinct Key Biological Functions Primarily by Gene Repression

-positive leukemic cell lines.-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories “stem cell properties”, “B-cell differentiation”, “immune response”, “cell adhesion” and “DNA damage” with RT-qPCR. fusion gene interferes with key regulatory functions that shape the biology of this leukemia subtype. E/R may thus indeed constitute the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets

Influenza Vaccine Effectiveness in the Elderly Based on Administrative Databases: Change in Immunization Habit as a Marker for Bias

Administrative databases provide efficient methods to estimate influenza vaccine effectiveness (IVE) against severe outcomes in the elderly but are prone to intractable bias. This study returns to one of the linked population databases by which IVE against hospitalization and death in the elderly was first assessed. We explore IVE across six more recent influenza seasons, including periods before, during, and after peak activity to identify potential markers for bias.Acute respiratory hospitalization and all-cause mortality were compared between immunized/non-immunized community-dwelling seniors ≥65 years through administrative databases in Manitoba, Canada between 2000-01 and 2005-06. IVE was compared during pre-season/influenza/post-season periods through logistic regression with multivariable adjustment (age/sex/income/residence/prior influenza or pneumococcal immunization/medical visits/comorbidity), stratification based on prior influenza immunization history, and propensity scores. Analysis during pre-season periods assessed baseline differences between immunized and unimmunized groups. The study population included ∼140,000 seniors, of whom 50-60% were immunized annually. Adjustment for key covariates and use of propensity scores consistently increased IVE. Estimates were paradoxically higher pre-season and for all-cause mortality vs. acute respiratory hospitalization. Stratified analysis showed that those twice consecutively and currently immunized were always at significantly lower hospitalization/mortality risk with odds ratios (OR) of 0.60 [95%CI0.48-0.75] and 0.58 [0.53-0.64] pre-season and 0.77 [0.69-0.86] and 0.71 [0.66-0.77] during influenza circulation, relative to the consistently unimmunized. Conversely, those forgoing immunization when twice previously immunized were always at significantly higher hospitalization/mortality risk with OR of 1.41 [1.14-1.73] and 2.45 [2.21-2.72] pre-season and 1.21 [1.03-1.43] and 1.78 [1.61-1.96] during influenza circulation.The most pronounced IVE estimates were paradoxically observed pre-season, indicating bias tending to over-estimate vaccine protection. Change in immunization habit from that of the prior two years may be a marker for this bias in administrative data sets; however, no analytic technique explored could adjust for its influence. Improved methods to achieve valid interpretation of protection in the elderly are needed

The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy

BACKGROUND: Filoviruses, including Ebola virus, are unusual in being filamentous animal viruses. Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment. The present study provides unique insights into the structure of this deadly pathogen. METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. We show that the helical Ebola virus inner nucleocapsid containing RNA and nucleoprotein is stabilized by an outer layer of VP24-VP35 bridges. Elucidation of the structure of the membrane-associated glycoprotein in its native state indicates that the putative receptor-binding site is occluded within the molecule, while a major neutralizing epitope is exposed on its surface proximal to the viral envelope. The matrix protein VP40 forms a regular lattice within the envelope, although its contacts with the nucleocapsid are irregular. CONCLUSIONS: The results of this study demonstrate a modular organization in Ebola virus that accommodates a well-ordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope

Patterns of democracy: Coalition governance and majoritarian modification in the United Kingdom, 2010–2015

The UK is often regarded as the archetype of Westminster democracy and as the empirical antithesis of the power-sharing coalitions of Western Europe. Yet, in recent years a different account has emerged that focuses on the subtler institutional dynamics which limit the executive. It is to this body of scholarship that this article responds, locating the recent chapter of coalition government within the wider context of the UK’s democratic evolution. To do so, the article draws Lijphart’s two-dimensional typology of democracies, developing a refined framework that enables systematic comparison over time. The article demonstrates that between over the course of the 2010-15 Parliament, the UK underwent another period of majoritarian modification, driven by factors including the long-term influence of the constitutional forces unleashed under Labour and the short-term impact of coalition management. The article makes several important contributions, salient in the UK and beyond. Theoretically, it offers a critical rejoinder to debates regarding the relationship between institutional design and democratic performance. Methodologically, it demonstrates that the tools of large-scale comparison can be effectively scaled-down to facilitate withincase analysis. Empirically, it provides a series of conclusions regarding the tenability of the UK’s extant democratic architecture under the weight of pressures to which it continues to be subject

Activation of Cell Cycle Arrest and Apoptosis by the Proto-Oncogene Pim-2

Potent survival effects have been ascribed to the serine/threonine kinase proto-oncogene PIM-2. Elevated levels of PIM-2 are associated with various malignancies. In human cells, a single Pim-2 transcript gives rise mainly to two protein isoforms (34, 41 kDa) that share an identical catalytic site but differ at their N-terminus, due to in-frame alternative translation initiation sites. In this study we observed that the 34 kDa PIM-2 isoform has differential nuclear and cytoplasmic forms in all tested cell lines, suggesting a possible role for the balance between these forms for PIM-2's function. To further study the cellular role of the 34 kDa isoform of PIM-2, an N-terminally HA-tagged form of this isoform was transiently expressed in HeLa cells. Surprisingly, this resulted in increased level of G1 arrested cells, as well as of apoptotic cells. These effects could not be obtained by a Flag-tagged form of the 41 kDa isoform. The G1 arrest and apoptotic effects were associated with an increase in T14/Y15 phosphorylation of CDK2 and proteasom-dependent down-regulation of CDC25A, as well as with up-regulation of p57, E2F-1, and p73. No such effects were obtained upon over-expression of a kinase-dead form of the HA-tagged 34 kDa PIM-2. By either using a dominant negative form of p73, or by over-expressing the 34 kDa PIM-2 in p73-silenced cells, we demonstrated that these effects were p73-dependent. These results demonstrate that while PIM-2 can function as a potent survival factor, it can, under certain circumstances, exhibit pro-apoptotic effects as well

Tandem E2F Binding Sites in the Promoter of the p107 Cell Cycle Regulator Control p107 Expression and Its Cellular Functions

The retinoblastoma tumor suppressor (Rb) is a potent and ubiquitously expressed cell cycle regulator, but patients with a germline Rb mutation develop a very specific tumor spectrum. This surprising observation raises the possibility that mechanisms that compensate for loss of Rb function are present or activated in many cell types. In particular, p107, a protein related to Rb, has been shown to functionally overlap for loss of Rb in several cellular contexts. To investigate the mechanisms underlying this functional redundancy between Rb and p107 in vivo, we used gene targeting in embryonic stem cells to engineer point mutations in two consensus E2F binding sites in the endogenous p107 promoter. Analysis of normal and mutant cells by gene expression and chromatin immunoprecipitation assays showed that members of the Rb and E2F families directly bound these two sites. Furthermore, we found that these two E2F sites controlled both the repression of p107 in quiescent cells and also its activation in cycling cells, as well as in Rb mutant cells. Cell cycle assays further indicated that activation of p107 transcription during S phase through the two E2F binding sites was critical for controlled cell cycle progression, uncovering a specific role for p107 to slow proliferation in mammalian cells. Direct transcriptional repression of p107 by Rb and E2F family members provides a molecular mechanism for a critical negative feedback loop during cell cycle progression and tumorigenesis. These experiments also suggest novel therapeutic strategies to increase the p107 levels in tumor cells