FLIM reveals alternative EV-mediated cellular up-take pathways of paclitaxel

In response to physiological and artificial stimuli, cells generate nano-scale extracellular vesicles (EVs) by encapsulating biomolecules in plasma membrane-derived phospholipid envelopes. These vesicles are released to bodily fluids, hence acting as powerful endogenous mediators in intercellular signaling. EVs provide a compelling alternative for biomarker discovery and targeted drug delivery, but their kinetics and dynamics while interacting with living cells are poorly understood. Here we introduce a novel method, fluorescence lifetime imaging microscopy (FLIM) to investigate these interaction attributes. By FLIM, we show distinct cellular uptake mechanisms of different EV subtypes, exosomes and microvesicles, loaded with anti-cancer agent, paclitaxel. We demonstrate differences in intracellular behavior and drug release profiles of paclitaxel-containing EVs. Exosomes seem to deliver the drug mostly by endocytosis while microvesicles enter the cells by both endocytosis and fusion with cell membrane. This research offers a new real-time method to investigate EV kinetics with living cells, and it is a potential advancement to complement the existing techniques. The findings of this study improve the current knowledge in exploiting EVs as next-generation targeted drug delivery systems.Peer reviewe

Greater levels of cardiorespiratory and muscular fitness are associated with low stress and high mental resources in normal but not overweight men

Background: The aim of the present study was to investigate how cardio respiratory (CRF) and muscular fitness (MF) together with leisure-time physical activity (LTPA) influence stress symptoms and mental resources among normal-weight and overweight men, because it is not known how body weight affects this association.Methods: In a cross-sectional study, 824 men (mean +/- SD: age 25 +/- 5 y, weight 81 +/- 13 kg, BMI 25 +/- 4 kg/m(2)) underwent CRF and MF tests and completed LTPA and stress questionnaires. For the analysis, the subjects were divided into BMI groups (normal vs. overweight) and CRF / MF / LTPA (low, moderate, high) tertiles.Results: Normal-weight men with low CRF reported 12 % (p = 0.001) more stress symptoms (SS) compared to normal-weight men with moderate CRF, and 13 % (p = 0.004) more SS compared to normal-weight men with high CRF. Normal-weight men with low MF reported 13 % (p = 0.001) higher SS compared to normal-weight men with moderate MF and 16 % (p = 0.002) more SS compared to men with high MF. Among overweight men, there were no significant differences in SS or mental resources (MR) between the low, moderate and high CRF and MF tertiles. Overweight men with high CRF experienced 8 % (p = 0.039) more SS compared to normal-weight participants with high CRF when age, tobacco and alcohol use, MF and LTPA were considered as covariates (p = 0.014).Conclusion: Higher CRF and MF are associated with lower stress and higher mental resources in normal-weight men, but in overweight men, these relationships may differ

Burden of childhood-onset arthritis

Juvenile arthritis comprises a variety of chronic inflammatory diseases causing erosive arthritis in children, often progressing to disability. These children experience functional impairment due to joint and back pain, heel pain, swelling of joints and morning stiffness, contractures, pain, and anterior uveitis leading to blindness. As children who have juvenile arthritis reach adulthood, they face possible continuing disease activity, medication-associated morbidity, and life-long disability and risk for emotional and social dysfunction. In this article we will review the burden of juvenile arthritis for the patient and society and focus on the following areas: patient disability; visual outcome; other medical complications; physical activity; impact on HRQOL; emotional impact; pain and coping; ambulatory visits, hospitalizations and mortality; economic impact; burden on caregivers; transition issues; educational occupational outcomes, and sexuality

Greater levels of cardiorespiratory and muscular fitness are associated with low stress and high mental resources in normal but not overweight men

Background: The aim of the present study was to investigate how cardio respiratory (CRF) and muscular fitness (MF) together with leisure-time physical activity (LTPA) influence stress symptoms and mental resources among normal-weight and overweight men, because it is not known how body weight affects this association. Methods: In a cross-sectional study, 824 men (mean ± SD: age 25 ± 5 y, weight 81 ± 13 kg, BMI 25 ± 4 kg/m2 ) underwent CRF and MF tests and completed LTPA and stress questionnaires. For the analysis, the subjects were divided into BMI groups (normal vs. overweight) and CRF / MF / LTPA (low, moderate, high) tertiles. Results: Normal-weight men with low CRF reported 12 % (p = 0.001) more stress symptoms (SS) compared to normal-weight men with moderate CRF, and 13 % (p = 0.004) more SS compared to normal-weight men with high CRF. Normal-weight men with low MF reported 13 % (p = 0.001) higher SS compared to normal-weight men with moderate MF and 16 % (p = 0.002) more SS compared to men with high MF. Among overweight men, there were no significant differences in SS or mental resources (MR) between the low, moderate and high CRF and MF tertiles. Overweight men with high CRF experienced 8 % (p = 0.039) more SS compared to normal-weight participants with high CRF when age, tobacco and alcohol use, MF and LTPA were considered as covariates (p = 0.014). Conclusion: Higher CRF and MF are associated with lower stress and higher mental resources in normal-weight men, but in overweight men, these relationships may differ.peerReviewe

A regression technique to analyze the second-order nonlinear optical response of thin films

We present a new technique, based on regression analysis, to determine the second-order nonlinear optical susceptibility tensor of thin films. The technique does not require the absolute levels or phases of measured signals to be mutually calibrated. In addition it yields indicators that address the quality of theoretical models describing the sample. We use the technique to determine the susceptibility tensor of samples of a nonracemic chiral material which have very low symmetry (both chiral and anisotropic) and have many independent tensor components. The results show the importance of using detailed theoretical models that account for the linear optical properties of the sample.Peer reviewe