Barcoding human physical activity to assess chronic pain conditions

Background

Modern theories define chronic pain as a multidimensional experience – the result of complex interplay between physiological and psychological factors with significant impact on patients'' physical, emotional and social functioning. The development of reliable assessment tools capable of capturing the multidimensional impact of chronic pain has challenged the medical community for decades. A number of validated tools are currently used in clinical practice however they all rely on self-reporting and are therefore inherently subjective. In this study we show that a comprehensive analysis of physical activity (PA) under real life conditions may capture behavioral aspects that may reflect physical and emotional functioning.

Methodology

PA was monitored during five consecutive days in 60 chronic pain patients and 15 pain-free healthy subjects. To analyze the various aspects of pain-related activity behaviors we defined the concept of PA ‘barcoding’. The main idea was to combine different features of PA (type, intensity, duration) to define various PA states. The temporal sequence of different states was visualized as a ‘barcode’ which indicated that significant information about daily activity can be contained in the amount and variety of PA states, and in the temporal structure of sequence. This information was quantified using complementary measures such as structural complexity metrics (information and sample entropy, Lempel-Ziv complexity), time spent in PA states, and two composite scores, which integrate all measures. The reliability of these measures to characterize chronic pain conditions was assessed by comparing groups of subjects with clinically different pain intensity.

Conclusion

The defined measures of PA showed good discriminative features. The results suggest that significant information about pain-related functional limitations is captured by the structural complexity of PA barcodes, which decreases when the intensity of pain increases. We conclude that a comprehensive analysis of daily-life PA can provide an objective appraisal of the intensity of pain.     

A brief history of angiogenesis assays

The major problem with angiogenesis research is the choice of an appropriate assay. Currently, many in vitro and in vivo techniques are available for research into the functions of endothelial cells during angiogenesis. In this historical review article, we describe and evaluate the methodology and specific features of some of the most frequently used of these assays.     

Comparative Effects of Boric Acid and Calcium Fructoborate on Breast Cancer Cells

Recent studies suggested that boron has a chemo-preventive role in prostate cancer. In the present report, we investigated the effects of calcium fructoborate (CF) and boric acid (BA) on activation of the apoptotic pathway in MDA-MB-231 human breast cancer cells. Exposure to BA and CF inhibited the proliferation of breast cancer cells in a dose-dependent manner. Treatment with CF but not BA resulted in a decrease in p53 and bcl-2 protein levels. Furthermore, after the treatment with CF, augmentation of pro-caspase-3 protein expression, cytosolic cytochrome c level, and caspase-3 activity were observed, indicating apoptotic cell death induction. This was also demonstrated by terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate nick-end-labeling assay. In conclusion, our data provide arguments to the fact that both BA and CF inhibited the growth of breast cancer cells, while only CF induced apoptosis. Additional studies will be needed to identify the underlying mechanism responsible for the observed cellular responses to these compounds and to determine if BA and CF may be further evaluated as chemotherapeutic agents for human cancer.     

In Vitro Effects of Calcium Fructoborate upon Production of Inflammatory Mediators by LPS-stimulated RAW 264.7 Macrophages

The present study is supported by our previous findings suggesting that calcium fructoborate (CF) has anti-inflammatory and antioxidant properties. Thus, we investigated the effects of CF on a model for studying inflammatory disorders in vitro represented by lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. This investigation was performed by analyzing the levels of some mediators released during the inflammatory process: cytokines such as tumor necrosis factor-α (TNF-α), interleukins IL-1β and IL-6 as well as cyclooxygenase-2 (COX-2), the main enzyme responsible for endotoxin/LPS-induced prostaglandin synthesis by macrophages. We also measured production of nitric oxide (NO) that plays an important role in the cytotoxicity activity of macrophages towards microbial pathogens. After CF treatment of LPS-stimulated macrophages we found an up-regulation of TNF-α protein level in culture medium, no significant changes in the level of COX-2 protein expression and a decrease in NO production as well as in IL-1β and IL-6 release. Collectively, this series of experiments indicate that CF affect macrophage production of inflammatory mediators. However, further research is required in order to establish whether CF treatment can be beneficial in suppression of pro-inflammatory cytokine production and against progression of endotoxin-related diseases.     

In Vitro Effects of Calcium Fructoborate on fMLP-stimulated Human Neutrophil Granulocytes

Discovery of naturally occurring boron complexes with organic compounds containing hydroxyl groups, sugars, and polysaccharides, adenosine-5-phosphate, pyridoxine, riboflavin, dehydroascorbic acid, and pyridine nucleotides led to the reassessment of the biochemical role of boron. Boron’s anti-inflammatory actions were claimed but not yet demonstrated. This study investigated the effects of calcium fructoborate (CF) on the human polymorphonuclear neutrophils (PMN) that play a central role in the inflammatory response. Our results demonstrated that CF exposure induced a dose-dependent decrease in cell viability. Treatment of PMN cells, for 24 h, with 22,500 μM CF led to a decrease in cell viability by 61.1%, an inhibition of respiratory burst by 92.9% in the case of fMLP-stimulated cells, a diminution of intracellular level of superoxide anion with 59.3%, and a stimulation of superoxide dismutase activity by 72% in unstimulated PMN cells. Altogether, these results suggest the antioxidant and anti-inflammatory properties of CF.     

Validating the use of wrist-level light monitoring for in-hospital circadian studies

This clinical methods comparison study describes the difference between light levels measured at the wrist (Actiwatch-L) and at the eye (Daysimeter) in a postoperative in-patient population. The mean difference between the two devices was less than 10 lux at light levels less than 5000 lux. Agreement between the devices was found to decrease as eye-level light exposure increased. Measurements at eye level of 5000 lux or more corresponded to a difference between the devices of greater than 100 lux. Agreement between the eye- and wrist-level light measurements also appears to be influenced by time of day. During the day, the measurement differences were on average 50 lux higher at eye level, whereas at night they were on average 50 lux lower. Although the wrist-level monitor was found to underestimate light exposure at higher light levels, it was well tolerated by participants in the clinical setting. In contrast, the eye-level monitor was cumbersome and uncomfortable for the patients to wear. This study provides light-exposure data on patients in real conditions in the clinical environment. The results show that wrist-level monitoring provides an adequate estimate of light exposure for in-hospital circadian studies.     

Tyrenes: synthesis of new antiproliferative compounds with an extended conjugation

A series of substituted styryl-acrylonitriles was designed and synthesized. The new compounds, called tyrenes, were tested for the ability to inhibit acute lymphocytic leukemia (ALL) cancer cell growth, as well as on their toxicity to normal bone marrow (NBM) cells. The results showed that 3,4-dihydroxystyryl-acrylonitriles, in particular CR-4, revealed great potency as antitumor agents, and also exhibited low toxicity to normal cells. The effectiveness of these compounds with extended conjugation may be due to their possible functioning as reactive Michael acceptors.