Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo.

Epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in squamous cell carcinoma of the head and neck (SCCHN). In addition to EGFR, other ErbB family members are expressed and activated in SCCHN. Afatinib is an ErbB family blocker that has been approved for treating patients with EGFR-mutated nonsmall cell lung cancer. We sought to determine the efficacy of afatinib in preclinical models and compare this to other EGFR-targeted agents. Afatinib efficacy was characterized in a panel of ten SCCHN cell lines and found to be most effective against cell lines amplified for EGFR. Afatinib had lower IC(50) values than did gefitinib against the same panel. Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib. Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo. Both afatinib and cetuximab were effective in tumor xenograft model. Afatinib is an effective agent in SCCHN especially in models with EGFR amplification

Development of a questionnaire to assess maternal attitudes towards infant growth and milk feeding practices.

BACKGROUND: There is increasing recognition that public health strategies to prevent childhood obesity need to start early in life. Any behavioural interventions need to target maternal attitudes and infant feeding practices, This paper describes the development and preliminary validation of a questionnaire to assess maternal attitudes towards infant growth and milk feeding practices. METHODS: We designed a 57-item (19 questions), self-administered questionnaire to measure the following four domains- 1) type of milk feeding, decision making and sources of advice; 2) frequency and quantity of milk feeds; 3) attitudes to infant feeding and growth; and 4) theory-based beliefs about following infant feeding recommendations. Forty mothers completed the questionnaire on two occasions six days apart (to assess test-retest reliability) and then participated in a semi-structured, open-ended telephone interview covering the same domains (to assess criterion validity). Percentage agreement, Cohen's Kappas (for categorical variables) and Spearman's correlation coefficients (for continuous variables) were used to quantify reliability and validity. Internal consistency between theory-based constructs (self-efficacy, outcome expectancy and intention) was quantified by Chronbach's alpha. RESULTS: Of the 57 questionnaire items 51 (89%) had percentage agreement above 70% indicating good test-retest reliability, and the remaining 6 items had moderate or substantial levels of agreement (kappa 0.41-0.68). Comparing questionnaire with interview coding (validity), percentage agreement was above 66% for 39/57 items (68%). Of the 16 items with percentage agreement below 66%, only five had kappa values below 0.20 (two items had insufficient interview responses). Internal consistency was 0.51, 0.79 and 0.90 for self-efficacy, outcome expectancy and intention respectively. CONCLUSIONS: This questionnaire could be a useful tool in understanding the determinants of infant feeding and the 'causal mechanism' of interventions that target infant feeding practices to prevent early obesity.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Range of motion and between-measurement variation of spinal kinematics in sound horses at trot on the straight line and on the lunge

Clinical assessment of spinal motion in horses is part of many routine clinical exams but remains highly subjective. A prerequisite for the quantification of spinal motion is the assessment of the expected normal range of motion and variability of back kinematics. The aim of this study was to objectively quantify spinal kinematics and between-measurement,-surface and-day variation in owner-sound horses. In an observational study, twelve ownersound horses were trotted 12 times on four different paths (hard/soft straight line, soft lunge left and right). Measurements were divided over three days, with five repetitions on day one and two, and two repetitions on day three (recheck) which occurred 28-55 days later. Optical motion capture was used to collect kinematic data. Elements of the outcome were: 1) Ranges of Motion (ROM) with confidence intervals per path and surface, 2) a variability model to calculate between-measurement variation and test the effect of time, surface and path, 3) intraclass correlation coefficients (ICC) to determine repeatability. ROM was lowest on the hard straight line. Cervical lateral bending was doubled on the left compared to the right lunge. Mean variation for the flexion-extension and lateral bending of the whole back were 0.8 and 1 degrees. Pelvic motion showed a variation of 1.0 (pitch), 0.7 (yaw) and 1.3 (roll) degrees. For these five parameters, a tendency for more variation on the hard surface and reduced variation with increased repetitions was observed. More variation was seen on the recheck (p<0.001). ICC values for pelvic rotations were between 0.76 and 0.93, for the whole back flexion-extension and lateral bending between 0.51 and 0.91. Between-horse variation was substantially higher than within-horse variation. In conclusion, ROM and variation in spinal biomechanics are horse-specific and small, necessitating individual analysis and making subjective and objective clinical assessment of spinal kinematics challenging

Designing theoretically-informed implementation interventions

Clinical and health services research is continually producing new findings that may contribute to effective and efficient patient care. However, the transfer of research findings into practice is unpredictable and can be a slow and haphazard process. Ideally, the choice of implementation strategies would be based upon evidence from randomised controlled trials or systematic reviews of a given implementation strategy. Unfortunately, reviews of implementation strategies consistently report effectiveness some, but not all of the time; possible causes of this variation are seldom reported or measured by the investigators in the original studies. Thus, any attempts to extrapolate from study settings to the real world are hampered by a lack of understanding of the effects of key elements of individuals, interventions, and the settings in which they were trialled. The explicit use of theory offers a way of addressing these issues and has a number of advantages, such as providing: a generalisable framework within which to represent the dimensions that implementation studies address, a process by which to inform the development and delivery of interventions, a guide when evaluating, and a way to allow for an exploration of potential causal mechanisms. However, the use of theory in designing implementation interventions is methodologically challenging for a number of reasons, including choosing between theories and faithfully translating theoretical constructs into interventions. The explicit use of theory offers potential advantages in terms of facilitating a better understanding of the generalisability and replicability of implementation interventions. However, this is a relatively unexplored methodological area

Засади та історія становлення соціального вчення Українського католицизму

In equine medicine the use of Botox® is experimental. Dosages are determined from human treatment-protocols and limited numbers of equine studies. Determination of target-muscle volume can be helpful to extrapolate human dosages. The aim of the study was to calculate a formula enabling the estimation of the deep digital flexor muscle (DDFM) volume based on distances between anatomical landmarks. Nineteen cadaveric limbs were collected and distance A (top of olecranon to Os carpi accessorium) and B (circumference of limb) were measured. Converting mathematical formulas, C was calculated: π × (((0.5B)/π)(2)) × A. DDFM volume was determined by water displacement. Linear Regression Analysis was used to analyse data. The line best fitting the observed points was: Ln(volume[ml]) = -1.89 + 0.98 × Ln(value C[cm(3)]). Correlation was highest when natural logarithm was applied to both variables and was 0.97. The calculated formula enables estimating DDFM volume of a living horse. This estimated volume can be useful to apply human Botox® treatment-protocols

Human red blood cell behaviour under homogeneous extensional flow in a hyperbolic-shaped microchannel

It is well known that certain pathological conditions result in a decrease of red blood cells (RBCs) deformability and subsequently can significantly alter the blood flow in microcirculation, which may block capillaries and cause ischemia in the tissues. Microfluidic systems able to obtain reliable quantitative measurements of RBC deformability hold the key to understand and diagnose RBC related diseases. In this work, a microfluidic system composed of a microchannel with a hyperbolic-shaped contraction followed by a sudden expansion is presented. We provide a detailed quantitative description of the degree of deformation of human RBCs under a controlled homogeneous extensional flow field. We measured the deformation index (DI) as well as the velocity of the RBCs travelling along the center line of the channel for four different flow rates and analyze the impact of the particle Reynolds number. The results show that human RBC deformation tends to reach a plateau value in the region of constant extensional rate, the value of which depends on the extension rate. Additionally, we observe that the presence of a sudden expansion downstream of the hyperbolic contraction modifies the spatial distribution of cells and substantially increases the cell free layer (CFL) downstream of the expansion plane similarly to what is seen in other expansion flows. Beyond a certain value of flow rate, there is only a weak effect of inlet flow rates on the enhancement of the downstream CFL. These in vitro experiments show the potential of using microfluidic systems with hyperbolic-shaped microchannels both for the separation of the RBCs from plasma and to assess changes in RBC deformability in physiological and pathological situations for clinical purposes. However, the selection of the geometry and the identification of the most suitable region to evaluate the changes on the RBC deformability under extensional flows are crucial if microfluidics is to be used as an in vitro clinical methodology to detect circulatory diseases

Flow of red blood cells suspensions through hyperbolic microcontractions

The present study uses a hyperbolic microchannel with a low aspect ratio (AR) to investigate how the red blood cells (RBCs) deform under conditions of both extensional and shear induced flows. The deformability is presented by the degree of the deformation index (DI) of the flowing RBCs throughout the microchannel at its centerline. A suitable image analysis technique is used for semi-automatic measurements of average DIs, velocity and strain rate of the RBCs travelling in the regions of interest. The results reveal a strong deformation of RBCs under both extensional and shear stress dominated flow conditions

Cloning and characterization of a novel gene, striamin, that interacts with the tumor suppressor protein p53

Expression analysis of a novel cDNA isolated from immortal murine fibroblasts revealed a single transcript of 3.0 kilobase pairs that was highly expressed in mouse and human striated muscle and in mouse heart. The gene has therefore been named striamin. Its expression was confined to skeletal muscle types with a fast glycolytic (2B) contractile phenotype. It was also detected in C2C12 mouse myoblasts and was down-regulated during in vitro myogenesis. The cDNA has a single open reading frame encoding a predicted 16.8-kDa protein of 149 amino acids with no homology to known proteins. Microinjection and transfection of green fluorescence protein-tagged striamin demonstrated that it localizes to the nucleus. Coimmunoprecipitations revealed that it can interact with p53 (a positive marker for myoblast differentiation) in vivo and in vitro. Furthermore, it repressed p53 activity in p53-mediated reporter assays. Fluorescence in situ hybridization with a mouse P1 genomic clone localized the gene to chromosome 12C3, which is syntenic to human chromosome 14q21-22