Change in basic motor abilities, quality of movement and everyday activities following intensive, goal-directed, activity-focused physiotherapy in a group setting for children with cerebral palsy

Background: The effects of intensive training for children with cerebral palsy (CP) remain uncertain. The aim of the study was to investigate the impact on motor function, quality of movements and everyday activities of three hours of goal-directed activity-focused physiotherapy in a group setting, five days a week for a period of three weeks. Methods: A repeated measures design was applied with three baseline and two follow up assessments; immediately and three weeks after intervention. Twenty-two children with hemiplegia (n = 7), diplegia (n = 11), quadriplegia (n = 2) and ataxia (n = 2) participated, age ranging 3-9 y. All levels of Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) were represented. Parents and professionals participated in goal setting and training. ANOVA was used to analyse change over repeated measures. Results: A main effect of time was shown in the primary outcome measure; Gross Motor Function Measure-66 (GMFM- 66), mean change being 4.5 (p < 0.01) from last baseline to last follow up assessment. An interaction between time and GMFCS-levels was found, implying that children classified to GMFCS-levels I-II improved more than children classified to levels III-V. There were no main or interaction effects of age or anti-spastic medication. Change scores in the Pediatric Evaluation of Disability Inventory (PEDI) ranged 2.0-6.7, p < 0.01 in the Self-care domain of the Functional Skills dimension, and the Self-care and Mobility domains of the Caregiver Assistance dimension. The children's individual goals were on average attained, Mean Goal Attainment Scaling (GAS) T-score being 51.3. Non-significant improved scores on the Gross Motor Performance Measure (GMPM) and the Quality of Upper Extremities Skills Test (QUEST) were demonstrated. Significant improvement in GMPM scores were found in improved items of the GMFM, not in items that maintained the same score. Conclusions: Basic motor abilities and self-care improved in young children with CP after goal-directed activityfocused physiotherapy with involvement of their local environment, and their need for caregiver assistance in self-care and mobility decreased. The individualized training within a group context during a limited period of time was feasible and well-tolerated. The coherence between acquisition of basic motor abilities and quality of movement should be further examined

Utilizing the Luminex Magnetic Bead-Based Suspension Array for Rapid Multiplexed Phosphoprotein Quantification.

The study of protein phosphorylation is critical for the advancement of our understanding of cellular responses to external and internal stimuli. Phosphorylation, the addition of phosphate groups, most often occurs on serine, threonine, or tyrosine residues due to the action of protein kinases. This structural change causes the protein to become activated (or deactivated) and enables it in turn to initiate the phosphorylation of other proteins in a cascade, eventually causing cell-wide changes such as apoptosis, cell differentiation, and growth (among others). Cellular phosphoprotein pathway dysregulation by mutation or chromosomal instability can often give the cell a selective advantage and lead to cancer. Obviously the understanding of these systems is of huge importance to the field of oncology.This chapter aims to provide a "how to" manual for one such technology, the 96-well plate-based xMAP® platform from Luminex. The system utilizes antibody-bound free-floating magnetic spheres which can easily be removed from suspension via magnetization. There are 100 unique bead sets (moving up to 500 bead sets for the most recent system) identified by the ratio of two dyes coating the microsphere. Each bead set is conjugated to a specific antibody which allows targeted protein extraction from low-concentration lysate solution. Biotinylated secondary antibodies/streptavidin-R-phycoerythrin (SAPE) complexes provide the quantification mechanism for the phosphoprotein of interest

Dealing with heterogeneity of treatment effects: is the literature up to the challenge?

<p>Abstract</p> <p>Background</p> <p>Some patients will experience more or less benefit from treatment than the averages reported from clinical trials; such variation in therapeutic outcome is termed heterogeneity of treatment effects (HTE). Identifying HTE is necessary to individualize treatment. The degree to which heterogeneity is sought and analyzed correctly in the general medical literature is unknown. We undertook this literature sample to track the use of HTE analyses over time, examine the appropriateness of the statistical methods used, and explore the predictors of such analyses.</p> <p>Methods</p> <p>Articles were selected through a probability sample of randomized controlled trials (RCTs) published in <it>Annals of Internal Medicine</it>, <it>BMJ</it>, <it>JAMA</it>, <it>The Lancet</it>, and <it>NEJM </it>during odd numbered months of 1994, 1999, and 2004. RCTs were independently reviewed and coded by two abstractors, with adjudication by a third. Studies were classified as reporting: (1) HTE analysis, utilizing a formal test for heterogeneity or treatment-by-covariate interaction, (2) subgroup analysis only, involving no formal test for heterogeneity or interaction; or (3) neither. Chi-square tests and multiple logistic regression were used to identify variables associated with HTE reporting.</p> <p>Results</p> <p>319 studies were included. Ninety-two (29%) reported HTE analysis; another 88 (28%) reported subgroup analysis only, without examining HTE formally. Major covariates examined included individual risk factors associated with prognosis, responsiveness to treatment, or vulnerability to adverse effects of treatment (56%); gender (30%); age (29%); study site or center (29%); and race/ethnicity (7%). Journal of publication and sample size were significant independent predictors of HTE analysis (p < 0.05 and p < 0.001, respectively).</p> <p>Conclusion</p> <p>HTE is frequently ignored or incorrectly analyzed. An iterative process of exploratory analysis followed by confirmatory HTE analysis will generate the data needed to facilitate an individualized approach to evidence-based medicine.</p

Do People Taking Flu Vaccines Need Them the Most?

Background: A well targeted flu vaccine strategy can ensure that vaccines go to those who are at the highest risk of getting infected if unvaccinated. However, prior research has not explicitly examined the association between the risk of flu infection and vaccination rates. Purpose: This study examines the relationship between the risk of flu infection and the probability of getting vaccinated. Methods: Nationally representative data from the US and multivariate regression models were used to estimate what individual characteristics are associated with (1) the risk of flu infection when unvaccinated and (2) flu vaccination rates. These results were used to estimate the correlation between the probability of infection and the probability of getting vaccinated. Separate analyses were performed for the general population and the high priority population that is at increased risk of flu related complications. Results: We find that the high priority population was more likely to get vaccinated compared to the general population. However, within both the high priority and general populations the risk of flu infection when unvaccinated was negatively correlated with vaccination rates (r = 20.067, p,0.01). This negative association between the risk of infection when unvaccinated and the probability of vaccination was stronger for the high priority population (r = 20.361, p,0.01). Conclusions: There is a poor match between those who get flu vaccines and those who have a high risk of flu infectio

Burn Injury Reduces Neutrophil Directional Migration Speed in Microfluidic Devices

Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72–120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions

Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells

Patients with prolonged myelosuppression require frequent platelet and occasional granulocyte transfusions. Multi-donor transfusions induce alloimmunization, thereby increasing morbidity and mortality. Therefore, an autologous or HLA-matched allogeneic source of platelets and granulocytes is needed. To determine whether nonhematopoietic cells can be reprogrammed into hematopoietic cells, human mesenchymal stromal cells (MSCs) and skin fibroblasts were incubated with the demethylating agent 5-azacytidine (Aza) and the growth factors (GF) granulocyte-macrophage colony-stimulating factor and stem cell factor. This treatment transformed MSCs to round, non-adherent cells expressing T-, B-, myeloid-, or stem/progenitor-cell markers. The transformed cells engrafted as hematopoietic cells in bone marrow of immunodeficient mice. DNA methylation and mRNA array analysis suggested that Aza and GF treatment demethylated and activated HOXB genes. Indeed, transfection of MSCs or skin fibroblasts with HOXB4, HOXB5, and HOXB2 genes transformed them into hematopoietic cells. Further studies are needed to determine whether transformed MSCs or skin fibroblasts are suitable for therapy

Serotype-specific immunoglobulin G antibody responses to pneumococcal polysaccharide vaccine in children with sickle cell anemia:Effects of continued penicillin prophylaxis

Objectives: (1) To determine serotype-specific IgG antibody responses to reimmunization with pneumococcal polysaccharide vaccine at age 5 years ski children with sickle cell anemia and (2) to determine whether continued penicillin prophylaxis had any adverse effects on these responses. Study design: Children with sickle cell anemia, who had been treated with prophylactic penicillin for at least 2 years before their fifth birthday, were randomly selected at age 5 years to continue penicillin prophylaxis or to receive placebo treatment, These children had been immunized once or twice in early childhood with pneumococcal polysaccharide vaccine and were reimmunized at the time of randomization. Results: Serotype-specific IgG antibody responses to reimmunization varied according to pneumococcal serotype but in general were mediocre or poor; the poorest response was to serotype 6B. The antibody responses were similar in subjects with continued penicillin prophylaxis or placebo treatment, and in subjects who received one or two pneumococcal vaccinations before reimmunization. The occurrence of pneumococcal bacteremia was associated with low IgG antibody concentrations to the infecting serotype. Conclusions: Reimmunization of children with sickle cell anemia who received pneumococcal polysaccharide vaccine at age 5 years induces limited production of serotype-specific IgG antibodies, regardless of previous pneumococcal vaccine history, Continued penicillin prophylaxis does not interfere with serotype-specific IgG antibody responses to reimmunization