308 research outputs found

    Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up

    Get PDF
    To use a unique longitudinal data set to assess the association between e-cigarette use while smoking with smoking cessation attempts, cessation and substantial reduction, taking into account frequency of use and key potential confounders

    Cell Death of Melanophores in Zebrafish trpm7 Mutant Embryos Depends on Melanin Synthesis

    Get PDF
    Transient receptor potential melastatin 7 (TRPM7) is a broadly expressed, non-selective cation channel. Studies in cultured cells implicate TRPM7 in regulation of cell growth, spreading, and survival. However, zebrafish trpm7 homozygous mutants display death of melanophores and temporary paralysis, but no gross morphological defects during embryonic stages. This phenotype implies that melanophores are unusually sensitive to decreases in Trpm7 levels, a hypothesis we investigate here. We find that pharmacological inhibition of caspases does not rescue melanophore viability in trpm7 mutants, implying that melanophores die by a mechanism other than apoptosis. Consistent with this possibility, ultrastructural analysis of dying melanophores in trpm7 mutants reveals abnormal melanosomes and evidence of a ruptured plasma membrane, indicating that cell death occurs by necrosis. Interestingly, inhibition of melanin synthesis largely prevents melanophore cell death in trpm7 mutants. These results suggest that melanophores require Trpm7 in order to detoxify intermediates of melanin synthesis. We find that unlike TRPM1, TRPM7 is expressed in human melanoma cell lines, indicating that these cells may also be sensitized to reduction of TRPM7 levels

    Contemporary murine models in preclinical astrocytoma drug development

    Get PDF
    Despite 6 decades of research, only 3 drugs have been approved for astrocytomas, the most common malignant primary brain tumors. However, clinical drug development is accelerating with the transition from empirical, cytotoxic therapy to precision, targeted medicine. Preclinical animal model studies are critical for prioritizing drug candidates for clinical development and, ultimately, for their regulatory approval. For decades, only murine models with established tumor cell lines were available for such studies. However, these poorly represent the genomic and biological properties of human astrocytomas, and their preclinical use fails to accurately predict efficacy in clinical trials. Newer models developed over the last 2 decades, including patient-derived xenografts, genetically engineered mice, and genetically engineered cells purified from human brains, more faithfully phenocopy the genomics and biology of human astrocytomas. Harnessing the unique benefits of these models will be required to identify drug targets, define combination therapies that circumvent inherent and acquired resistance mechanisms, and develop molecular biomarkers predictive of drug response and resistance. With increasing recognition of the molecular heterogeneity of astrocytomas, employing multiple, contemporary models in preclinical drug studies promises to increase the efficiency of drug development for specific, molecularly defined subsets of tumors

    Corn Stover Availability and Collection Efficiency Using Typical Hay Equipment

    Get PDF
    Corn stover has been identified as a potential feedstock for the production of fermentable sugars and thermochemical processes. The availability and efficiency of typical hay equipment for collecting corn stover has not been well quantified. Corn stover was collected for two years on a central Kentucky farm near Louisville. Six different harvesting treatments, using traditional hay equipment, were used to harvest corn stover. A rotary mower, rotary scythe (flail-type mower with windrow-forming shields), parallel bar rake, and a round baler were utilized. The average stover moisture content prior to grain harvest was above 40%, and field drying was required before baling. All treatments were analyzed for collection efficiency and corn stover yield. The stover collection yields varied from 1.93 to 5.34 dry t/ha, with collection efficiencies (ratio of stover collected to the total above-ground stover excluding grain) between 32.1% and 94.5%. The most promising collection strategy was disengaging the straw chopper and spreader to produce a windrow behind the combine. This windrow could then be baled in a separate operation that resulted in a collection efficiency of 74.1%

    Evidence review of e-cigarettes and heated tobacco products 2018: a report commissioned by Public Health England.

    Get PDF
    The report covers e-cigarette use among young people and adults, public attitudes, the impact on quitting smoking, an update on risks to health and the role of nicotine. It also reviews heated tobacco products. The main findings of PHE’s evidence review are that: • vaping poses only a small fraction of the risks of smoking and switching completely from smoking to vaping conveys substantial health benefits • e-cigarettes could be contributing to at least 20,000 successful new quits per year and possibly many more • e-cigarette use is associated with improved quit success rates over the last year and an accelerated drop in smoking rates across the country • many thousands of smokers incorrectly believe that vaping is as harmful as smoking; around 40% of smokers have not even tried an e-cigarette • there is much public misunderstanding about nicotine (less than 10% of adults understand that most of the harms to health from smoking are not caused by nicotine) • the use of e-cigarettes in the UK has plateaued over the last few years at just under 3 million • the evidence does not support the concern that e-cigarettes are a route into smoking among young people (youth smoking rates in the UK continue to decline, regular use is rare and is almost entirely confined to those who have smoked

    Patient specific modeling of palpation-based prostate cancer diagnosis: effects of pelvic cavity anatomy and intrabladder pressure.

    Get PDF
    Computational modeling has become a successful tool for scientific advances including understanding the behavior of biological and biomedical systems as well as improving clinical practice. In most cases, only general models are used without taking into account patient-specific features. However, patient specificity has proven to be crucial in guiding clinical practice because of disastrous consequences that can arise should the model be inaccurate. This paper proposes a framework for the computational modeling applied to the example of the male pelvic cavity for the purpose of prostate cancer diagnostics using palpation. The effects of patient specific structural features on palpation response are studied in three selected patients with very different pathophysiological conditions whose pelvic cavities are reconstructed from MRI scans. In particular, the role of intrabladder pressure in the outcome of digital rectal examination is investigated with the objective of providing guidelines to practitioners to enhance the effectiveness of diagnosis. Furthermore, the presence of the pelvic bone in the model is assessed to determine the pathophysiological conditions in which it has to be modeled. The conclusions and suggestions of this work have potential use not only in clinical practice and also for biomechanical modeling where structural patient-specificity needs to be considered. © 2015 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd

    Tissue quality assessment using a novel direct elasticity assessment device (the E-finger): a cadaveric study of prostatectomy dissection.

    Get PDF
    INTRODUCTION: Minimally invasive radical prostatectomy (RP) (robotic and laparoscopic), have brought improvements in the outcomes of RP due to improved views and increased degrees of freedom of surgical devices. Robotic and laparoscopic surgeries do not incorporate haptic feedback, which may result in complications secondary to inadequate tissue dissection (causing positive surgical margins, rhabdosphincter damage, etc). We developed a micro-engineered device (6 mm2 sized) [E-finger]) capable of quantitative elasticity assessment, with amplitude ratio, mean ratio and phase lag representing this. The aim was to assess the utility of the device in differentiating peri-prostatic tissue types in order to guide prostate dissection. MATERIAL AND METHODS: Two embalmed and 2 fresh frozen cadavers were used in the study. Baseline elasticity values were assessed in bladder, prostate and rhabdosphincter of pre-dissected embalmed cadavers using the micro-engineered device. A measurement grid was created to span from the bladder, across the prostate and onto the rhabdosphincter of fresh frozen cadavers to enable a systematic quantitative elasticity assessment of the entire area by 2 independent assessors. Tissue was sectioned along each row of elasticity measurement points, and stained with haematoxylin and eosin (H&E). Image analysis was performed with Image Pro Premier to determine the histology at each measurement point. RESULTS: Statistically significant differences in elasticity were identified between bladder, prostate and sphincter in both embalmed and fresh frozen cadavers (p = < 0.001). Intra-class correlation (ICC) reliability tests showed good reliability (average ICC = 0.851). Sensitivity and specificity for tissue identification was 77% and 70% respectively to a resolution of 6 mm2. CONCLUSIONS: This cadaveric study has evaluated the ability of our elasticity assessment device to differentiate bladder, prostate and rhabdosphincter to a resolution of 6 mm2. The results provide useful data for which to continue to examine the use of elasticity assessment devices for tissue quality assessment with the aim of giving haptic feedback to surgeons performing complex surgery

    Quantitative mechanical assessment of the whole prostate gland ex vivo using dynamic instrumented palpation

    Get PDF
    An instrumented palpation sensor, designed for measuring the dynamic modulus of tissue in vivo, has been developed and trialled on ex vivo whole prostate glands. The sensor consists of a flexible membrane sensor/actuator with an embedded strain gauge and is actuated using a dynamically varying airflow at frequencies of 1 and 5 Hz. The device was calibrated using an indentation stiffness measurement rig and gelatine samples with a range of static modulus similar to that reported in the literature for prostate tissue. The glands were removed from patients with diagnosed prostate cancer scheduled for radical prostatectomy, and the stiffness was measured within 30 min of surgical removal. Each prostate was later examined histologically in a column immediately below each indentation point and graded into one of the four groups; normal, benign prostatic hyperplasia, cancerous and mixed cancer and benign prostatic hyperplasia. In total, 11 prostates were assessed using multiple point probing, and the complex modulus at 1 and 5 Hz was calculated on a point-by-point basis. The device yielded values of quasi-static modulus of 15 ± 0.5 kPa and dynamic modulus of 20 ± 0.5 kPa for whole prostates, and a sensitivity of up to 80% with slightly lower specificity was achieved on diagnosis of prostate cancer using a combination of mechanical measures. This assessment did not take into account some obvious factors such as edge effects, overlap and clinical significance of the cancer, all of which would improve performance. The device, as currently configured, is immediately deployable in vivo. A number of improvements are also identified which could improve the sensitivity and specificity in future embodiments of the probe
    corecore