Lower limb strength training in children with cerebral palsy – a randomized controlled trial protocol for functional strength training based on progressive resistance exercise principles

<p>Abstract</p> <p>Background</p> <p>Until recently, strength training in children with cerebral palsy (CP) was considered to be inappropriate, because it could lead to increased spasticity or abnormal movement patterns. However, the results of recent studies suggest that progressive strength training can lead to increased strength and improved function, but low methodological quality and incomplete reporting on the training protocols hampers adequate interpretation of the results. This paper describes the design and training protocol of a randomized controlled trial to assess the effects of a school-based progressive functional strength training program for children with CP.</p> <p>Methods/Results</p> <p>Fifty-one children with Gross Motor Function Classification Systems levels I to III, aged of 6 to 13 years, were recruited. Using stratified randomization, each child was assigned to an intervention group (strength training) or a control group (usual care). The strength training was given in groups of 4–5 children, 3 times a week, for a period of 12 weeks. Each training session focussed on four exercises out of a 5-exercise circuit. The training load was gradually increased based on the child's maximum level of strength, as determined by the 8 Repetition Maximum (8 RM). To evaluate the effectiveness of the training, all children were evaluated before, during, directly after, and 6 weeks after the intervention period. Primary outcomes in this study were gross motor function (measured with the Gross Motor Function Measure and functional muscle strength tests) and walking ability (measured with the 10-meter, the 1-minute and the timed stair test). Secondary outcomes were lower limb muscle strength (measured with a 6 RM test, isometric strength tests, and a sprint capacity test), mobility (measured with a mobility questionnaire), and sport activities (measured with the Children's Assessment of Participation and Enjoyment). Spasticity and range of motion were assessed to evaluate any adverse events.</p> <p>Conclusion</p> <p>Randomized clinical trials are considered to present the highest level of evidence. Nevertheless, it is of utmost importance to report on the design, the applied evaluation methods, and all elements of the intervention, to ensure adequate interpretation of the results and to facilitate implementation of the intervention in clinical practice if the results are positive.</p> <p>Trial Registration</p> <p>Trial Register NTR1403</p

Open Problems on Central Simple Algebras

We provide a survey of past research and a list of open problems regarding central simple algebras and the Brauer group over a field, intended both for experts and for beginners.Comment: v2 has some small revisions to the text. Some items are re-numbered, compared to v

Removal and Reconstitution of the Carotenoid Antenna of Xanthorhodopsin

Salinixanthin, a C40-carotenoid acyl glycoside, serves as a light-harvesting antenna in the retinal-based proton pump xanthorhodopsin of Salinibacter ruber. In the crystallographic structure of this protein, the conjugated chain of salinixanthin is located at the protein–lipid boundary and interacts with residues of helices E and F. Its ring, with a 4-keto group, is rotated relative to the plane of the π-system of the carotenoid polyene chain and immobilized in a binding site near the β-ionone retinal ring. We show here that the carotenoid can be removed by oxidation with ammonium persulfate, with little effect on the other chromophore, retinal. The characteristic CD bands attributed to bound salinixanthin are now absent. The kinetics of the photocycle is only slightly perturbed, showing a 1.5-fold decrease in the overall turnover rate. The carotenoid-free protein can be reconstituted with salinixanthin extracted from the cell membrane of S. ruber. Reconstitution is accompanied by restoration of the characteristic vibronic structure of the absorption spectrum of the antenna carotenoid, its chirality, and the excited-state energy transfer to the retinal. Minor modification of salinixanthin, by reducing the carbonyl C=O double bond in the ring to a C-OH, suppresses its binding to the protein and eliminates the antenna function. This indicates that the presence of the 4-keto group is critical for carotenoid binding and efficient energy transfer

Association between Proximity to a Health Center and Early Childhood Mortality in Madagascar

Objective: To evaluate the association between proximity to a health center and early childhood mortality in Madagascar, and to assess the influence of household wealth, maternal educational attainment, and maternal health on the effects of distance. Methods: From birth records of subjects in the Demographic and Health Survey, we identified 12565 singleton births from January 2004 to August 2009. After excluding 220 births that lacked global positioning system information for exposure assessment, odds ratios (ORs) and their 95% confidence intervals (CIs) for neonatal mortality and infant mortality were estimated using multilevel logistic regression models, with 12345 subjects (level 1), nested within 584 village locations (level 2), and in turn nested within 22 regions (level 3). We additionally stratified the subjects by the birth order. We estimated predicted probabilities of each outcome by a three-level model including cross-level interactions between proximity to a health center and household wealth, maternal educational attainment, and maternal anemia. Results: Compared with those who lived >1.5–3.0 km from a health center, the risks for neonatal mortality and infant mortality tended to increase among those who lived further than 5.0 km from a health center; the adjusted ORs for neonatal mortality and infant mortality for those who lived >5.0–10.0 km away from a health center were 1.36 (95% CI: 0.92–2.01) and 1.42 (95% CI: 1.06–1.90), respectively. The positive associations were more pronounced among the second or later child. The distance effects were not modified by household wealth status, maternal educational attainment, or maternal health status. Conclusions: Our study suggests that distance from a health center is a risk factor for early childhood mortality (primarily, infant mortality) in Madagascar by using a large-scale nationally representative dataset. The accessibility to health care in remote areas would be a key factor to achieve better infant health

Ethnicity and incidence of Hodgkin lymphoma in Canadian population

<p>Abstract</p> <p>Background</p> <p>Research has shown that ethnicity is a significant predictor of Hodgkin lymphoma (HL). Variations in cancer incidence among ethnic groups in the same country can lead to important information in the search for etiological factors. Other risk factors important in the etiology of HL are medical history and exposure to pesticides. In this report we investigated the association between ethnicity and HL in the presence of medical history, and exposure to pesticides.</p> <p>Methods</p> <p>The data resulting from a matched population-based case-control study conducted in six provinces of Canada (Ontario, Quebec, Manitoba, Saskatchewan, Alberta, and British Columbia) was analyzed to determine whether or not there was any association between ethnicity and incidence of HL when adjusted for personal medical history and pesticide exposure. Information on ethnicity, personal medical history, and pesticide exposure was collected by questionnaires via mail on 316 men diagnosed with HL; and on 1506 controls. A conditional logistic regression was utilized and results were presented as odds ratios and 95% confidence intervals.</p> <p>Results</p> <p>In our study population, the distribution of ethnic groups was: 38.5% North American, 15% British, 8.4% Western European, 8.2% Eastern European, 1.7% Asian, 1.4% Scandinavian and 27% of other ethnic origin. Compared to North Americans (i) the risk of HL was greater among the Eastern European descendents (Odds Ratio (OR_adj): 1.82; 95% confidence interval (CI): 1.02, 3.25) and Western European (OR_adj: 1.62; 95% CI: 0.95–2.76) descent population (borderline significance at 5% level); and (ii) the risk of HL was lower in Asian descents. Diagnosis with measles (OR_adj: 0.72, 95% C.I.: 0.53–0.98) and/or positive history of allergy desensitization shots (OR_adj: 0.55, 95% C.I.: 0.30–0.99) were negatively associated with the incidence of HL, while diagnosis with acne (OR_adj: 2.12, 95% C.I.: 1.19–3.78), shingles (OR_adj: 2.41, 95% C.I.: 1.38–4.22) and positive family history of cancer (OR_adj: 1.93, 95% C.I.: 1.40–2.65) increased the risk of HL. Exposure to individual herbicide dichlorprop showed an increased risk of HL (OR_adj: 6.35, 95% C.I.: 1.56–25.92).</p> <p>Conclusion</p> <p>In Canada, compared to North Americans descendents, the risk of HL was significantly greater among the Eastern European and Western European descent population. Our results related to association between ethnicity and HL support the findings reported by other researchers. Our data showed that subjects who were diagnosed with measles or had allergy desensitization shots negatively associated with the incidence of HL; and other medical conditions, ever diagnosed with acne, and positive family history of cancer were positively associated with the incidence of HL.</p

FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa

Pseudomonas aeruginosa, a ubiquitous bacteria found in diverse ecological niches, is an important cause of acute infections in immunocompromised individuals and chronic infections in patients with Cystic Fibrosis. One signaling molecule required for the coordinate regulation of virulence factors associated with acute infections is 3′, 5′-cyclic adenosine monophosphate, (cAMP), which binds to and activates a catabolite repressor homolog, Vfr. Vfr controls the transcription of many virulence factors, including those associated with Type IV pili (TFP), the Type III secretion system (T3SS), the Type II secretion system, flagellar-mediated motility, and quorum sensing systems. We previously identified FimL, a protein with histidine phosphotransfer-like domains, as a regulator of Vfr-dependent processes, including TFP-dependent motility and T3SS function. In this study, we carried out genetic and physiologic studies to further define the mechanism of action of FimL. Through a genetic screen designed to identify suppressors of FimL, we found a putative cAMP-specific phosphodiesterase (CpdA), suggesting that FimL regulates cAMP levels. Inactivation of CpdA increases cAMP levels and restores TFP-dependent motility and T3SS function to fimL mutants, consistent with in vivo phosphodiesterase activity. By constructing combinations of double and triple mutants in the two adenylate cyclase genes (cyaA and cyaB), fimL, and cpdA, we show that ΔfimL mutants resemble ΔcyaB mutants in TM defects, decreased T3SS transcription, and decreased cAMP levels. Similar to some of the virulence factors that they regulate, we demonstrate that CyaB and FimL are polarly localized. These results reveal new complexities in the regulation of diverse virulence pathways associated with acute P. aeruginosa infections

Effect of Cytoskeletal Disruption on Mechanotransduction of Hydrostatic Pressure by C3H10T1/2 Murine Fibroblasts

Cyclic hydrostatic pressure of physiological magnitude (< 10 MPa) stimulates chondrogenic differentiation of mesenchymal stem cells, but mechanotransduction mechanisms are not well understood. It was hypothesized that an intact cytoskeleton would be required for uninhibited mechanotransduction of hydrostatic pressure. Therefore we examined the effects of drugs which selectively interfere with actin and tubulin polymerization on pressure-induced upregulation of aggrecan and col2a1 (type II collagen) mRNA expression. C3H10T1/2 cells were cultured as pellets in either 4µM cytochalasin D or 4µM nocodazole and subjected to 3 days of cyclic hydrostatic compression (1 Hz, 5 MPa, 2 h per day). Phalloidin staining and indirect immunostaining with anti α-tubulin antibody confirmed disruption of microfilament and microtubule assemblies, respectively. Real time RT-PCR revealed that both drugs substantially lowered the basal level of aggrecan and col2a1 mRNA, but that neither drug prevented a pressure-stimulated increase in gene expression relative to the altered basal state. Thus upregulation of macromolecular gene expression by cyclic hydrostatic pressure did not require a completely intact cytoskeleton

MexEF-OprN Efflux Pump Exports the Pseudomonas Quinolone Signal (PQS) Precursor HHQ (4-hydroxy-2-heptylquinoline)

Bacterial cells have evolved the capacity to communicate between each other via small diffusible chemical signals termed autoinducers. Pseudomonas aeruginosa is an opportunistic pathogen involved, among others, in cystic fibrosis complications. Virulence of P. aeruginosa relies on its ability to produce a number of autoinducers, including 4-hydroxy-2-alkylquinolines (HAQ). In a cell density-dependent manner, accumulated signals induce the expression of multiple targets, especially virulence factors. This phenomenon, called quorum sensing, promotes bacterial capacity to cause disease. Furthermore, P. aeruginosa possesses many multidrug efflux pumps conferring adaptive resistance to antibiotics. Activity of some of these efflux pumps also influences quorum sensing. The present study demonstrates that the MexEF-OprN efflux pump modulates quorum sensing through secretion of a signalling molecule belonging to the HAQ family. Moreover, activation of MexEF-OprN reduces virulence factor expression and swarming motility. Since MexEF-OprN can be activated in infected hosts even in the absence of antibiotic selective pressure, it could promote establishment of chronic infections in the lungs of people suffering from cystic fibrosis, thus diminishing the immune response to virulence factors. Therapeutic drugs that affect multidrug efflux pumps and HAQ-mediated quorum sensing would be valuable tools to shut down bacterial virulence

Isolated patellofemoral osteoarthritis: A systematic review of treatment options using the GRADE approach

Background and purpose The optimal treatment for isolated patellofemoral osteoarthritis is unclear at present. We systematically reviewed the highest level of available evidence on the nonoperative and operative treatment of isolated patellofemoral osteoarthritis to develop an evidenced-based discussion of treatment options