Molecular profiling and characterization of luminal-like and basal-like in vivo breast cancer xenograft models

The number of relevant and well-characterized cell lines and xenograft models for studying human breast cancer are few, and may represent a limitation for this field of research. With the aim of developing new breast cancer model systems for in vivo studies of hormone dependent and independent tumor growth, progression and invasion, and for in vivo experimental therapy studies, we collected primary mammary tumor specimens from patients, and implanted them in immunodeficient mice. Primary tumor tissue from 29 patients with breast cancer was implanted subcutaneously with matrigel in SCID mice, in the presence of continuous release of estradiol. The tumors were transferred into new animals when reaching a diameter of 15 mm and engrafted tumors were harvested for morphological and molecular characterization from passage six. Further, gene expression profiling was performed using Agilent Human Whole Genome Oligo Microarrays, as well as DNA copy number analysis using Agilent Human Genome CGH 244K Microarrays. Of the 30 primary tumors implanted into mice (including two implants from the same patient), two gave rise to viable tumors beyond passage ten. One showed high expression levels of estrogen receptor-α protein (ER) while the other was negative. Histopathological evaluation of xenograft tumors was carried out at passage 10–12; both xenografts maintained the morphological characteristics of the original tumors (classified as invasive grade III ductal carcinomas). The genomic profile of the ER-positive xenograft tumor resembled the profile of the primary tumor, while the profile obtained from the ER-negative parental tumor was different from the xenograft. However, the ER-negative parental tumor and xenograft clustered on the same branch using unsupervised hierarchical clustering analysis on RNA microarray expression data of “intrinsic genes”. A significant variation was observed in the expression of extracellular matrix (ECM)-related genes, which were found downregulated in the engrafted tumors compared to the primary tumor. By IHC and qRT-PCR we found that the downregulation of stroma-related genes was compensated by the overexpression of such molecules by the mouse host tissue. The two established breast cancer xenograft models showed different histopathological characteristics and profound diversity in gene expression patterns that in part can be associated to their ER status and here described as basal-like and luminal-like phenotype, respectively. These two new breast cancer xenografts represent useful preclinical tools for developing and testing of new therapies and improving our knowledge on breast cancer biology.     

Respiratory syncytial virus infections in congenital heart defects--hospitalizations and costs

Aims: To register hospitalizations for respiratory syncytial virus (RSV) infections and estimate costs of prophylaxis with humanized monoclonal antibodies (palivizumab) against RSV, compared to hospital care, in cases with congenital heart defects (CHDs). Methods: Population based study with prospective registration of CHDs. Costs for hospital treatment of RSV-infections in CHD-patients calculated by means of the Norwegian Diagnosis Related Groups system. Results: In 43 470 infants live born in the population through the 18-year period 1987-2004 a structural CHD was diagnosed in 527 (1.2%). A total of 898 (2.1%) hospitalizations for RSV-infections occurred in the study population 1987-2005. The hospital admittance rate was significantly higher for CHD-cases (4.8%) than for children without CHD (2%) (P=0.002). Severe CHDs (need for surgery or catheter intervention) had a higher admittance rate (9.2%) compared to the group of remaining CHDs (3.3%) (P=0.01). Number needed to treat with palivizumab to avoid one hospitalization for RSV-infection in cases of severe CHDs was calculated to 24, at costs of US$ 195 000. The expenses for palivizuamab prophylaxis in severe CHDs were 31 times that of hospital treatment.

Conclusion: Prophylaxis with palivizumab in severe CHDs is not cost-effective.     

Mirau-based line-field confocal optical coherence tomography for three-dimensional high-resolution skin imaging

SignificanceLine-field confocal optical coherence tomography (LC-OCT) is a recently introduced high-resolution imaging modality based on a combination of low-coherence optical interferometry and reflectance confocal optical microscopy with line illumination and line detection. Capable of producing three-dimensional (3D) images of the skin with cellular resolution, in vivo, LC-OCT has been mainly applied in dermatology and dermo-cosmetology. The LC-OCT devices capable of acquiring 3D images reported so far are based on a Linnik interferometer using two identical microscope objectives. In this configuration, LC-OCT cannot be designed to be a very compact and light device, and the image acquisition speed is limited.AimThe objective of this work was to develop a more compact and lighter LC-OCT device that is capable of acquiring images faster without significant degradation of the resolution and with optimized detection sensitivity.ApproachWe developed an LC-OCT device based on a Mirau interferometer using a single objective. Dynamic adjustment of the camera frequency during the depth scan is implemented, using a faster camera and a more powerful light source. The reflectivity of the beam-splitter in the Mirau interferometer was optimized to maximize the detection sensitivity. A galvanometer scanner was incorporated into the device for scanning the illumination line laterally. A stack of adjacent B-scans, constituting a 3D image, can thus be acquired.ResultsThe device is able to acquire and display B-scans at 17 fps. 3D images with a quasi-isotropic resolution of ∼1.5μm (1.3, 1.9, and 1.1μm in the x,y, and z directions, respectively) over a field of 940μm×600μm×350μm (x×y×z) can be obtained. 3D imaging of human skin at cellular resolution, in vivo, is reported.ConclusionsThe acquisition rate of the B-scans, at 17 fps, is unprecedented in LC-OCT. Compared with the conventional LC-OCT devices based on a Linnik interferometer, the reported Mirau-based LC-OCT device can acquire B-scans ∼2 times faster. With potential advantages in terms of compactness and weight, a Mirau-based device could easily be integrated into a smaller and lighter handheld probe for use by dermatologists in their daily medical practice.     

Nuanced effects of music interventions on rehabilitation outcomes after stroke: a systematic review

Background: Music is affordable and easily integrated in rehabilitation exercises, and has demonstrated different effects on the brain. We hypothesized that music interventions could improve rehabilitation outcomes after stroke.

Objective: the aim of our review is to determine the effectiveness of different types of music interventions according to the rehabilitation objectives after stroke.

Method: A systematic review of randomized controlled trials, clinical controlled trials and cross-over design performed on PubMed and PEDro in May 2018. All of these studies focus on acute, sub-acute or chronic stroke rehabilitation with music or rhythmic auditory stimulation intervention in adults during clinical outcomes. Two independent reviewers extracted the data and assessed the risk of bias before bringing it together.

Results: Twenty-seven studies were included and analyzed. Our review found positive effects on physical status (upper-limb activity; gait parameters, balance), on cognition (neglect, attention, communication) and mood. The analysis of the quality of the evidence showed that a majority of the studies had a high risk of bias.

Conclusion: Focusing on high to moderate level evidence, our review highlighted that rhythmic auditory stimulation has a positive effect on gait and balance; that receptive music therapy improves mood as well as some cognitive functions; that there is not enough evidence to determine the effectiveness of active music therapy and melodic intonation therapy. High-quality trials with large samples would be necessary to further assess and/or recommend these interventions.