A novel method to analyze leukocyte rolling behavior in vivo

Leukocyte endothelial cell interaction is a fundamentally important process in many disease states. Current methods to analyze such interactions include the parallel-plate flow chamber and intravital microscopy. Here, we present an improvement of the traditional intravital microscopy that allows leukocyte-endothelial cell interaction to be studied from the time the leukocyte makes its initial contact with the endothelium until it adheres to or detaches from the endothelium. The leukocyte is tracked throughout the venular tree with the aid of a motorized stage and the rolling and adhesive behavior is measured off-line. Because this method can involve human error, methods to automate the tracking procedure have been developed. This novel tracking method allows for a more detailed examination of leukocyte-endothelial cell interactions

Chemotherapy-Response Monitoring of Breast Cancer Patients Using Quantitative Ultrasound-Based Intra-Tumour Heterogeneities

© 2017 The Author(s). Anti-cancer therapies including chemotherapy aim to induce tumour cell death. Cell death introduces alterations in cell morphology and tissue micro-structures that cause measurable changes in tissue echogenicity. This study investigated the effectiveness of quantitative ultrasound (QUS) parametric imaging to characterize intra-tumour heterogeneity and monitor the pathological response of breast cancer to chemotherapy in a large cohort of patients (n = 100). Results demonstrated that QUS imaging can non-invasively monitor pathological response and outcome of breast cancer patients to chemotherapy early following treatment initiation. Specifically, QUS biomarkers quantifying spatial heterogeneities in size, concentration and spacing of acoustic scatterers could predict treatment responses of patients with cross-validated accuracies of 82 ± 0.7%, 86 ± 0.7% and 85 ± 0.9% and areas under the receiver operating characteristic (ROC) curve of 0.75 ± 0.1, 0.80 ± 0.1 and 0.89 ± 0.1 at 1, 4 and 8 weeks after the start of treatment, respectively. The patients classified as responders and non-responders using QUS biomarkers demonstrated significantly different survivals, in good agreement with clinical and pathological endpoints. The results form a basis for using early predictive information on survival-linked patient response to facilitate adapting standard anti-cancer treatments on an individual patient basis

Are autistic traits in the general population stable across development?

There is accumulating evidence that autistic traits (AT) are on a continuum in the general population, with clinical autism representing the extreme end of a quantitative distribution. While the nature and severity of symptoms in clinical autism are known to persist over time, no study has examined the long-term stability of AT among typically developing toddlers. The current investigation measured AT in 360 males and 400 males from the general population close to two decades apart, using the Pervasive Developmental Disorder subscale of the Child Behavior Checklist in early childhood (M = 2.14 years; SD = 0.15), and the Autism-Spectrum Quotient in early adulthood (M = 19.50 years; SD = 0.70). Items from each scale were further divided into social (difficulties with social interaction and communication) and non-social (restricted and repetitive behaviours and interests) AT. The association between child and adult measurements of AT as well the influence of potentially confounding sociodemographic, antenatal and obstetric variables were assessed using Pearson's correlations and linear regression. For males, Total AT in early childhood were positively correlated with total AT (r = .16, p = .002) and social AT (r = .16, p = .002) in adulthood. There was also a positive correlation for males between social AT measured in early childhood and Total (r = .17, p = .001) and social AT (r = .16, p = .002) measured in adulthood. Correlations for non-social AT did not achieve significance in males. Furthermore, there was no significant longitudinal association in AT observed for males or females. Despite the constraints of using different measures and different raters at the two ages, this study found modest developmental stability of social AT from early childhood to adulthood in boys

A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279

It is widely accepted that strong and variable radiation detected over all accessible energy bands in a number of active galaxies arises from a relativistic, Doppler-boosted jet pointing close to our line of sight. The size of the emitting zone and the location of this region relative to the central supermassive black hole are, however, poorly known, with estimates ranging from light-hours to a light-year or more. Here we report the coincidence of a gamma-ray flare with a dramatic change of optical polarization angle. This provides evidence for co-spatiality of optical and gamma-ray emission regions and indicates a highly ordered jet magnetic field. The results also require a non-axisymmetric structure of the emission zone, implying a curved trajectory for the emitting material within the jet, with the dissipation region located at a considerable distance from the black hole, at about 10^5 gravitational radii.Comment: Published in Nature issued on 18 February 2010. Corresponding authors: Masaaki Hayashida and Greg Madejsk

Differential expression of HSPA1 and HSPA2 proteins in human tissues; tissue microarray-based immunohistochemical study

In the present study we determined the expression pattern of HSPA1 and HSPA2 proteins in various normal human tissues by tissue-microarray based immunohistochemical analysis. Both proteins belong to the HSPA (HSP70) family of heat shock proteins. The HSPA2 is encoded by the gene originally defined as testis-specific, while HSPA1 is encoded by the stress-inducible genes (HSPA1A and HSPA1B). Our study revealed that both proteins are expressed only in some tissues from the 24 ones examined. HSPA2 was detected in adrenal gland, bronchus, cerebellum, cerebrum, colon, esophagus, kidney, skin, small intestine, stomach and testis, but not in adipose tissue, bladder, breast, cardiac muscle, diaphragm, liver, lung, lymph node, pancreas, prostate, skeletal muscle, spleen, thyroid. Expression of HSPA1 was detected in adrenal gland, bladder, breast, bronchus, cardiac muscle, esophagus, kidney, prostate, skin, but not in other tissues examined. Moreover, HSPA2 and HSPA1 proteins were found to be expressed in a cell-type-specific manner. The most pronounced cell-type expression pattern was found for HSPA2 protein. In the case of stratified squamous epithelia of the skin and esophagus, as well as in ciliated pseudostratified columnar epithelium lining respiratory tract, the HSPA2 positive cells were located in the basal layer. In the colon, small intestine and bronchus epithelia HSPA2 was detected in goblet cells. In adrenal gland cortex HSPA2 expression was limited to cells of zona reticularis. The presented results clearly show that certain human tissues constitutively express varying levels of HSPA1 and HSPA2 proteins in a highly differentiated way. Thus, our study can help designing experimental models suitable for cell- and tissue-type-specific functional differences between HSPA2 and HSPA1 proteins in human tissues

Work-life conflict and associations with work- and nonwork-related factors and with physical and mental health outcomes: a nationally representative cross-sectional study in Switzerland

BACKGROUND: The aim of the present cross-sectional study was to examine work- and nonwork-related factors and physical and mental health outcomes associated with combined time- and strain-based work-life conflict (WLC) among adult employees living and working in Switzerland as well as possible gender differences in this regard. METHODS: The data used for the study were taken from wave 6 of the nationally representative Swiss Household Panel (SHP) collected in 2004. The analysis was restricted to 4'371 employees aged 20 to 64 years. Trivariate crosstabulations and multivariate linear and logistic regression analyses stratified by gender were performed in order to calculate gender-specific prevalence rates (%), beta coefficients (SZ) and crude as well as multiple adjusted odds ratios (OR) as measures of association. RESULTS: Every eighth person (12.5%) within the study population has a high or very high WLC score. Prevalence rates are clearly above average in men and women with higher education, in executive positions or managerial functions, in full-time jobs, with variable work schedules, regular overtime, long commuting time to work and job insecurity. Working overtime regularly, having variable work schedules and being in a management position are most strongly associated with WLC in men, whereas in women the level of employment is the strongest explanatory variable by far, followed by variable work schedules and high job status (managerial position). In both men and women, WLC is associated with several physical and mental health problems. Employees with high or very high WLC show a comparatively high relative risk of self-reported poor health, anxiety and depression, lack of energy and optimism, serious backache, headaches, sleep disorders and fatigue. While overall prevalence rate of (very) high WLC is higher in men than in women, associations between degrees of WLC and most health outcomes are stronger in women than in men. CONCLUSIONS: This important issue which up to now has been largely neglected in public health research needs to be addressed in future public health research and, if the findings are confirmed by subsequent (longitudinal) studies, to be considered in workplace health promotion and interventions in Switzerland as elsewhere

HOXB13 is downregulated in colorectal cancer to confer TCF4-mediated transactivation

Mutations in the Wnt signalling cascade are believed to cause aberrant proliferation of colorectal cells through T-cell factor-4 (TCF4) and its downstream growth-modulating factors. HOXB13 is exclusively expressed in prostate and colorectum. In prostate cancers, HOXB13 negatively regulates β-catenin/TCF4-mediated transactivation and subsequently inhibits cell growth. To study the role of HOXB13 in colorectal tumorigenesis, we evaluated the expression of HOXB13 in 53 colorectal tumours originated from the distal left colon to rectum with their matching normal tissues using quantitative RT–PCR analysis. Expression of HOXB13 is either lost or diminished in 26 out of 42 valid tumours (62%), while expression of TCF4 RNA is not correlated with HOXB13 expression. TCF4 promoter analysis showed that HOXB13 does not regulate TCF4 at the transcriptional level. However, HOXB13 downregulated the expression of TCF4 and its target gene, c-myc, at the protein level and consequently inhibited β-catenin/TCF-mediated signalling. Functionally, forced expression of HOXB13 drove colorectal cancer (CRC) cells into growth suppression. This is the first description of the downregulation of HOXB13 in CRC and its mechanism of action is mediated through the regulation of TCF4 protein stability. Our results suggest that loss of HOXB13 may be an important event for colorectal cell transformation, considering that over 90% of colorectal tumours retain mutations in the APC/β-catenin pathway

Characterization techniques for studying the properties of nanocarriers for systemic delivery

Nanocarriers have attracted a huge interest in the last decade as efficient drug delivery systems and diagnostic tools. They enable effective, targeted, controlled delivery of therapeutic molecules while lowering the side effects caused during the treatment. The physicochemical properties of nanoparticles determine their in vivo pharmacokinetics, biodistribution and tolerability. The most analyzed among these physicochemical properties are shape, size, surface charge and porosity and several techniques have been used to characterize these specific properties. These different techniques assess the particles under varying conditions, such as physical state, solvents etc. and as such probe, in addition to the particles themselves, artifacts due to sample preparation or environment during measurement. Here, we discuss the different methods to precisely evaluate these properties, including their advantages or disadvantages. In several cases, there are physical properties that can be evaluated by more than one technique. Different strengths and limitations of each technique complicate the choice of the most suitable method, while often a combinatorial characterization approach is needed

Candida glabrata : a review of its features and resistance

Candida species belong to the normal microbiota of the oral cavity and gastrointestinal and vaginal tracts, and are responsible for several clinical manifestations, from mucocutaneous overgrowth to bloodstream infections. Once believed to be non-pathogenic, Candida glabrata was rapidly blamable for many human diseases. Year after year, these pathological circumstances are more recurrent and problematic to treat, especially when patients reveal any level of immunosuppression. These difficulties arise from the capacity of C. glabrata to form biofilms and also from its high resistance to traditional antifungal therapies. Thus, this review intends to present an excerpt of the biology, epidemiology, and pathology of C. glabrata, and detail an approach to its resistance mechanisms based on studies carried out up to the present.The authors are grateful to strategic project PTDC/SAU-MIC/119069/2010 for the financial support to the research center and for Celia F. Rodrigues' grant