Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor.

Cellular senescence is acknowledged as a key contributor to organismal ageing and late-life disease. Though popular, the study of senescence in vitro can be complicated by the prolonged and asynchronous timing of cells committing to it and by its paracrine effects. To address these issues, we repurposed a small molecule inhibitor, inflachromene (ICM), to induce senescence to human primary cells. Within 6 days of treatment with ICM, senescence hallmarks, including the nuclear eviction of HMGB1 and -B2, are uniformly induced across IMR90 cell populations. By generating and comparing various high throughput datasets from ICM-induced and replicative senescence, we uncovered a high similarity of the two states. Notably though, ICM suppresses the pro-inflammatory secretome associated with senescence, thus alleviating most paracrine effects. In summary, ICM rapidly and synchronously induces a senescent-like phenotype thereby allowing the study of its core regulatory program without confounding heterogeneity.

Perfusion-CT analysis for assessment of hepatocellular carcinoma lesions: diagnostic value of different perfusion maps.

BACKGROUND: Computed tomography liver perfusion (CTLP) has been improved in recent years, offering a variety of perfusion-parametric maps. A map that better discriminates hepatocellular carcinoma (HCC) is still to be found. PURPOSE: To compare different CTLP maps, regarding their ability to differentiate cirrhotic or non-cirrhotic parenchyma from malignant HCC. MATERIAL AND METHODS: Twenty-six patients (11 cirrhotic) with 50 diagnosed HCC lesions, underwent CTLP on a 128-row dual-energy CT system. Nine different maps were generated. Regions of interest (ROIs) were positioned on non-tumorous parenchyma and on HCCs found on previous magnetic resonance imaging. Perfusion parameters for non-cirrhotic and cirrhotic livers were compared. Receiver operating characteristic (ROC) analysis was employed to evaluate each map's ability to discriminate HCCs from non-tumorous livers. Comparison of ROC curves was performed to evaluate statistical significance of differences in the discriminating efficiency of derived perfusion maps. RESULTS: Perfusion parameters for non-tumorous liver and HCCs recorded in cirrhotic patients did not significantly differ from corresponding values recorded in non-cirrhotic patients ( P > 0.05). The highest power for HCC discrimination was found for the maximum-slope-of-increase (MSI) parametric map, with estimated the area under ROC curve of 0.997. An MSI cut-off criterion of 2.2 HU/s was found to provide 96% sensitivity and 100% specificity. Time to peak, blood flow, and transit time to peak were also found to have high discriminating power. CONCLUSION: Among available CTLP-derived perfusion parameters, MSI was found to provide the highest diagnostic accuracy in discriminating HCCs from non-tumorous parenchyma. Perfusion parameters for non-tumorous livers and HCCs were not found to significantly differ between cirrhotic and non-cirrhotic patients.

Respiratory infections and gastrointestinal illness on a cruise ship: A three-year prospective study.

BACKGROUND: Cruise ships carry a large number of people in confined spaces providing an environment for transmission of infections. The aim of this study is to estimate the incidence of and describe the spectrum of respiratory infections and gastrointestinal illness among passengers and crew of cruise Ship A. MATERIAL AND METHODS: The study was carried out from January 2011 to December 2013 on cruise Ship A, including passengers and crew who presented with symptoms suggestive of acute respiratory infection (ARI), influenza-like illness (ILI) and gastrointestinal illness (GI). Advice about preventive measures of respiratory and gastrointestinal infections and influenza vaccination was given to passengers and crew. Data were collected by using one standardized form per patient. RESULTS: The most common destination was Northern Europe (90.7%). The mean duration of cruise was 10.6 days; 440 passengers and 421 crew members who sought medical attention were studied (mean age 72.6 ± 9.5 and 33 ± 7 years, respectively). ILI, ARI and GI were diagnosed in 32.7%, 15.9%, 17% and 10.9%, 80%, 0.2% of ill passengers and crew, respectively. The association of ARI, ILI and GI incidence in passengers was statistically significant with season, destination and duration of travel; the incidence for all illnesses was higher during winter, for travel to South America and for >14 days (p-value<0.001). CONCLUSION: ARI, ILI and GI continue to pose a burden on cruise travel; therefore pre-travel advice is crucial for passengers and crew regarding respiratory and gastrointestinal infections. Surveillance and implementation of control measures are important for outbreak prevention.

White matter and deep gray matter hemodynamic changes in multiple sclerosis patients with clinically isolated syndrome.

The dynamic susceptibility contrast magnetic resonance imaging perfusion technique was used to investigate possible hemodynamic changes in normal appearing white matter and deep gray matter (DGM) of 30 patients with clinically isolated syndrome (CIS) and 30 patients with relapsing-remitting multiple sclerosis. Thirty normal volunteers were studied as controls. Cerebral blood volume, cerebral blood flow (CBF), and mean transit time values were estimated. Normalization was achieved for each subject with respect to average values of CBF and mean transit time of the hippocampi's dentate gyrus. Measurements concerned three regions of normal white matter of normal volunteers, normal appearing white matter of CIS and patients with relapsing-remitting multiple sclerosis, and DGM regions, bilaterally. All measured normal appearing white matter and DGM regions of the patients with CIS had significantly higher cerebral blood volume and mean transit time values, while averaged DGM regions had significantly lower CBF values, compared to those of normal volunteers (P < 0.001). Regarding patients with relapsing-remitting multiple sclerosis, all measured normal appearing white matter and DGM regions showed lower CBF values than those of normal volunteers and lower cerebral blood volume and CBF values compared to patients with CIS (P < 0.001). These data provide strong evidence that hemodynamic changes--affecting both white and DGM--may occur even at the earliest stage of multiple sclerosis, with CIS patients being significantly different than relapsing-remitting multiple sclerosis patients.

A novel spectral microscope system: application in quantitative pathology.

In this paper, a novel spectral microscope system is presented together with a method for the quantitative assessment of the uptake by histologic samples of stains used in pathology to label tissue features of diagnostic importance. The critical component of the microscope is a variable interference filter-based monochromator. The system is capable of performing real-time spectral imaging in a plurality of spectral bands and micro-spectroscopy in any image pixel, in the spectral range 400-1000 nm. The wavelength-tuning step is 2.4-2.6 nm, while the full-width at half maximum in each step is about 1.5% of the operating central wavelength. The developed system integrates algorithms and calibration procedures for the calculation of the stain-uptake by the tissue. The acquired spectra from both stained tissue and calibration stain solutions enable the calculation of the concentration maps of the stains, even if the latter are multiple and overlap spatially and spectrally. The system was used for the quantitative mapping of the expression of estrogen and progesterone receptors in breast cancer cells. In this particular case, model validation shows that although two stains are employed, capturing of their transmittance at more than ten wavelengths is required in order to obtain an acceptable accuracy. These findings highlight the need for the development and implementation of spectral microscopy in pathology and its potential to introduce novel more reliable diagnostic criteria.