In vivo characterization of connective tissue remodeling using infrared photoacoustic spectra

Premature cervical remodeling is a critical precursor of spontaneous preterm birth, and the remodeling process is characterized by an increase in tissue hydration. Nevertheless, current clinical measurements of cervical remodeling are subjective and detect only late events, such as cervical effacement and dilation. Here, we present a photoacoustic endoscope that can quantify tissue hydration by measuring near-infrared cervical spectra. We quantify the water contents of tissue-mimicking hydrogel phantoms as an analog of cervical connective tissue. Applying this method to pregnant women in vivo, we observed an increase in the water content of the cervix throughout pregnancy. The application of this technique in maternal healthcare may advance our understanding of cervical remodeling and provide a sensitive method for predicting preterm birth

Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the R6/2 Mouse Model of HD

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6/2 mouse model of HD expresses a mutant version of exon 1 HTT and develops motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Despite the vast number of studies that have been performed on this model, the association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood. In an attempt to link these factors, we have performed longitudinal assessments of behavior (rotarod, open field, passive avoidance) and of regional brain abnormalities determined through magnetic resonance imaging (MRI) (whole brain, striatum, cortex, hippocampus, corpus callosum), as well as an end-stage histological assessment. Detailed correlative analyses of these three measures were then performed. We found a gender-dependent emergence of motor impairments that was associated with an age-related loss of regional brain volumes. MRI measurements further indicated that there was no striatal atrophy, but rather a lack of striatal growth beyond 8 weeks of age. T2 relaxivity further indicated tissue-level changes within brain regions. Despite these dramatic motor and neuroanatomical abnormalities, R6/2 mice did not exhibit neuronal loss in the striatum or motor cortex, although there was a significant increase in neuronal density due to tissue atrophy. The deposition of the mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the brain. End-stage histopathological assessments were not found to be as robustly correlated with the longitudinal measures of brain atrophy or motor impairments. In conclusion, modeling pre-manifest and early progression of the disease in more slowly progressing animal models will be key to establishing which changes are causally related. © 2013 Rattray et al

Modelling the cost-effectiveness of public awareness campaigns for the early detection of non-small-cell lung cancer

Background: Survival rates in lung cancer in England are significantly lower than in many similar countries. A range of Be Clear on Cancer (BCOC) campaigns have been conducted targeting lung cancer and found to improve the proportion of diagnoses at the early stage of disease. This paper considers the cost-effectiveness of such campaigns, evaluating the effect of both the regional and national BCOC campaigns on the stage distribution of non-small-cell lung cancer (NSCLC) at diagnosis. Methods: A natural history model of NSCLC was developed using incidence data, data elicited from clinical experts and model calibration techniques. This structure is used to consider the lifetime cost and quality-adjusted survival implications of the early awareness campaigns. Incremental cost-effectiveness ratios (ICERs) in terms of additional costs per quality-adjusted life-years (QALYs) gained are presented. Two scenario analyses were conducted to investigate the role of changes in the ‘worried-well’ population and the route of diagnosis that might occur as a result of the campaigns. Results: The base-case theoretical model found the regional and national early awareness campaigns to be associated with QALY gains of 289 and 178 QALYs and ICERs of d13 660 and d18 173 per QALY gained, respectively. The scenarios found that increases in the ‘worried-well’ population may impact the cost-effectiveness conclusions. Conclusions: Subject to the available evidence, the analysis suggests that early awareness campaigns in lung cancer have the potential to be cost-effective. However, significant additional research is required to address many of the limitations of this study. In addition, the estimated natural history model presents previously unavailable estimates of the prevalence and rate of disease progression in the undiagnosed population

EMS Systems: Foundations for the Future

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73462/1/j.1553-2712.1999.tb00094.x.pd

The functional brain networks that underlie Early Stone Age tool manufacture

After 800,000 years of making simple Oldowan tools, early humans began manufacturing Acheulian handaxes around 1.75 million years ago. This advance is hypothesized to reflect an evolutionary change in hominin cognition and language abilities. We used a neuroarchaeology approach to investigate this hypothesis, recording brain activity using functional near-infrared spectroscopy as modern human participants learned to make Oldowan and Acheulian stone tools in either a verbal or nonverbal training context. Here we show that Acheulian tool production requires the integration of visual, auditory and sensorimotor information in the middle and superior temporal cortex, the guidance of visual working memory representations in the ventral precentral gyrus, and higher-order action planning via the supplementary motor area, activating a brain network that is also involved in modern piano playing. The right analogue to Broca’s area—which has linked tool manufacture and language in prior work1,2—was only engaged during verbal training. Acheulian toolmaking, therefore, may have more evolutionary ties to playing Mozart than quoting Shakespeare

Infection of Cultured Human Endothelial Cells by Legionella pneumophila

Legionella pneumophila is a gram-negative pathogen that causes a severe pneumonia known as Legionnaires' disease. Here, we demonstrate for the first time that L. pneumophila infects and grows within cultured human endothelial cells. Endothelial infection may contribute to lung damage observed during Legionnaires' disease and to systemic spread of this organism

Nanotubes Impregnated Human Olfactory Bulb Neural Stem Cells Promote Neuronal Differentiation in Trimethyltin-induced Neurodegeneration Rat Model

Neural stem cells (NSCs) are multipotent self-renewing cells that could be used in cellular-based therapy for a wide variety of neurodegenerative diseases including Alzheimer's diseases (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Being multipotent in nature, they are practically capable of giving rise to major cell types of the nervous tissue including neurons, astrocytes and oligodendrocytes. This is in marked contrast to neural progenitor cells which are committed to a specific lineage fate. In previous studies, we have demonstrated the ability of NSCs isolated from human olfactory bulb (OB) to survive, proliferate, differentiate, and restore cognitive and motor deficits associated with AD, and PD rat models, respectively. The use of carbon nanotubes (CNTs) to enhance the survivability and differentiation potential of NSCs following their in vivo engraftment have been recently suggested. Here, in order to assess the ability of CNTs to enhance the therapeutic potential of human OBNSCs for restoring cognitive deficits and neurodegenerative lesions, we co-engrafted CNTs and human OBNSCs in TMT-neurodegeneration rat model. The present study revealed that engrafted human OBNSCS-CNTs restored cognitive deficits, and neurodegenerative changes associated with TMT-induced rat neurodegeneration model. Moreover, the CNTs seemed to provide a support for engrafted OBNSCs, with increasing their tendency to differentiate into neurons rather than into glia cells. The present study indicate the marked ability of CNTs to enhance the therapeutic potential of human OBNSCs which qualify this novel therapeutic paradigm as a promising candidate for cell-based therapy of different neurodegenerative diseases

Aggressive fibromatosis of the head and neck: a new classification based on a literature review over 40 years (1968-2008)

BACKGROUND: Fibromatosis is an aggressive fibrous tumor of unknown etiology that is, in some cases, lethal. Until now, there has been no particular classification for the head and neck. Therefore, the aim of the present study was to review the current literature in order to propose a new classification for future studies. METHODS: An evidence-based literature review was conducted from the last 40 years regarding aggressive fibromatosis in the head and neck. Studies that summarized patients' data without including individual data were excluded. RESULTS: Between 1968 and 2008, 179 cases with aggressive fibromatosis of the head and neck were published. The male to female ratio was 91 to 82 with a mean age of 16.87 years, and 57.32% of the described cases that involved the head and neck were found in patients under 11 years. The most common localization was the mandible, followed by the neck. All together, 143 patients were followed up, and in 43 (30.07%), a recurrence was seen. CONCLUSION: No clear prognostic factors for recurrence (age, sex, or localization) were observed. A new classification with regard to hormone receptors and bone involvement could improve the understanding of risk factors and thereby assist in future studies

The read-across hypothesis and environmental risk assessment of pharmaceuticals

This article is made available through the Brunel Open Access Publishing Fund. Copyright © 2013 American Chemical Society.Pharmaceuticals in the environment have received increased attention over the past decade, as they are ubiquitous in rivers and waterways. Concentrations are in sub-ng to low μg/L, well below acute toxic levels, but there are uncertainties regarding the effects of chronic exposures and there is a need to prioritise which pharmaceuticals may be of concern. The read-across hypothesis stipulates that a drug will have an effect in non-target organisms only if the molecular targets such as receptors and enzymes have been conserved, resulting in a (specific) pharmacological effect only if plasma concentrations are similar to human therapeutic concentrations. If this holds true for different classes of pharmaceuticals, it should be possible to predict the potential environmental impact from information obtained during the drug development process. This paper critically reviews the evidence for read-across, and finds that few studies include plasma concentrations and mode of action based effects. Thus, despite a large number of apparently relevant papers and a general acceptance of the hypothesis, there is an absence of documented evidence. There is a need for large-scale studies to generate robust data for testing the read-across hypothesis and developing predictive models, the only feasible approach to protecting the environment.BBSRC Industrial Partnership Award BB/ I00646X/1 and BBSRC Industrial CASE Partnership Studentship BB/I53257X/1 with AstraZeneca Safety Health and Environment Research Programme

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation