Differentiating between heat pain intensities: the combined effect of multiple autonomic parameters

Although it is well known that pain induces changes in autonomic parameters, the extent to which these changes correlate with the experience of pain is under debate. The aim of the present study was to compare a combination of multiple autonomic parameters and each parameter alone in their ability to differentiate among 4 categories of pain intensity. Tonic heat stimuli (1minute) were individually adjusted to induce no pain, low, medium, and high pain in 45 healthy volunteers. Electrocardiogram, photoplethysmogram, and galvanic skin response were recorded, and the following parameters were calculated: heart rate; heart rate variability-high frequency (0.15 to 0.4Hz) spectral power; skin conductance level; number of skin conduction fluctuations; and photoplethysmographic pulse wave amplitude. A combination of parameters was created by fitting an ordinal cumulative logit model to the data and using linear coefficients of the model. Friedman test with post-hoc Wilcoxon test were used to compare between pain intensity categories for every parameter alone and for their linear combination. All of the parameters successfully differentiated between no pain and all other pain categories. However, none of the parameters differentiated between all 3 pain categories (i.e., low and medium; medium and high; low and high). In contrast, the linear combination of parameters significantly differentiated not only between pain and no pain, but also between all pain categories (P<.001 to .02). These results suggest that multiparameter approaches should be further investigated to make progress toward reliable autonomic-based pain assessment.     

In vitro assembly of physiological cohesin/DNA complexes

Cohesin is a member of the Smc family of protein complexes that mediates higher-order chromosome structure by tethering different regions of chromatin. We present a new in vitro system that assembles cohesin-DNA complexes with in vivo properties. The assembly of these physiological salt-resistant complexes requires the cohesin holo-complex, its ability to bind ATP, the cohesin loader Scc2p and a closed DNA topology. Both the number of cohesin molecules bound to the DNA substrate and their distribution on the DNA substrate are limited. Cohesin and Scc2p bind preferentially to cohesin associated regions (CARs), DNA sequences with enriched cohesin binding in vivo. A subsequence of CARC1 promotes cohesin binding to neighboring sequences within CARC1. The enhancer-like function of this sequence is validated by in vivo deletion analysis. By demonstrating the physiological relevance of these in vitro assembled cohesin-DNA complexes, we establish our in vitro system as a powerful tool to elucidate the mechanism of cohesin and other Smc complexes.     

The impact of acute moderate intensity exercise on arterial regional stiffness, lipid peroxidation, and antioxidant status in healthy males

There is a paucity of research examining the influence of acute exercise on pulse wave velocity (PWV) and oxidative stress. The purpose of this study was to examine the effects of acute moderate aerobic exercise on PWV and oxidative stress in healthy males. Eight apparently healthy males (age 23.6 ± 2.8 yrs; stature 181.4 ± 8.1 cm; weight 83.4 ± 16.2 kg; all data mean ±SD) participated in a randomized crossover design consisting of (i) a one hour bout of moderate aerobic exercise and (ii) a control trial of one hour rest. Pre- and post-exercise blood samples were drawn for the determination of lipid hydroperoxides (LOOHs) and lipid-soluble antioxidants (lycopene, retinol, and β-carotene). Exercise had no effect on stiffness and LOOHs (P > 0.05). Retinol and lycopene were increased following exercise (P < 0.05). These findings suggest that acute moderate exercise has no effect on PWV and LOOHs, but it can increase systemic antioxidants, which may be of benefit to health.     

Students with visual impairments in Israel: quality of life as a subjective experience

The present paper is based on research that investigated the quality of life of students with visual impairments, included in the regular education system, according to their own perceptions as reported in individual open interviews. The research comprised 19 students between the ages of 14 and 19 years. The main findings revealed three major themes: life in school with a focus on teachers' behavior towards the pupil; peers' reactions and the impact of stigma; family coping with the disability. Mixed feelings appeared in the first two themes. Regarding their teachers, the students reported support while at the same time they also felt a lack of sincere respect. Concerning peers, students felt that stigma affected their friendship behavior. Finally, most reports indicated satisfaction with the family bonds. Yet, there is almost no direct reference to the visual problem.     

Sonodynamic Therapy for Malignant Glioma Using 220-kHz Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound and 5-Aminolevulinic acid

Sonodynamic therapy (SDT) is used to treat various malignancies and can be applied to brain tumors using a transcranial magnetic resonance imaging-guided focused ultrasound (TcMRgFUS) device. This study investigated the efficacy of 220-kHz TcMRgFUS combined with 5-aminolevulinic acid (5-ALA) on malignant glioma in vitro and in vivo. F98 cells were irradiated with focused ultrasound (FUS) (4000 J, 20 W, 240 s, 100% duty cycle, target medium temperature <40°C) after treatment with 200 µg/mL 5-ALA, and cell viability and apoptosis were evaluated with the water-soluble tetrazolium-1 assay, triple fluorescent staining and Western blot analysis 20 h later. The anti-tumor effects of 5-ALA combined with FUS (500 J, 18 W, 30 s, 100% duty cycle, 10 repeats, target tissue temperature ≤42°C) were assessed on the basis of changes in tumor volume determined by MRI and histopathological analysis before and after treatment. The FUS/5-ALA combination reduced cell viability by inducing apoptosis and suppressed tumor proliferation and invasion as well as angiogenesis in vivo, while causing minimal damage to normal brain tissue. SDT with 220-kHz TcMRgFUS and 5-ALA can be safely used for the treatment of malignant glioma.     

Microsecond atomic force sensing of protein conformational dynamics: Implications for the primary light-induced events in bacteriorhodopsin

In this paper a new atomic force sensing technique is presented for dynamically probing conformational changes in proteins. The method is applied to the light-induced changes in the membrane-bound proton pump bacteriorhodopsin (bR). The microsecond time-resolution of the method, as presently implemented, covers many of the intermediates of the bR photocycle which is well characterized by spectroscopical methods. In addition to the native pigment, we have studied bR proteins substituted with chemically modified retinal chromophores. These synthetic chromophores were designed to restrict their ability to isomerize, while maintaining the basic characteristic of a large light-induced charge redistribution in the vertically excited Franck–Condon state. An analysis of the atomic force sensing signals lead us to conclude that protein conformational changes in bR can be initiated as a result of a light-triggered redistribution of electronic charge in the retinal chromophore, even when isomerization cannot take place. Although the coupling mechanism of such changes to the light-induced proton pump is still not established, our data question the current working hypothesis which attributes all primary events in retinal proteins to an initial transcis isomerization.     

Anti-IL-6 Therapies for Neuromyelitis Optica Spectrum Disorders: A Systematic Review of Safety and Efficacy

Background Neuromyelitis Optica Spectrum Disorder (NMOSD) is a chronic autoimmune disease of the central nervous system that causes recurrent attacks of optic neuritis, myelitis, and brainstem symptoms, resulting in severe neurological disability. Preventive treatment with immunosuppressive agents reduces relapse rate and improves long-term prognosis. In recent years, the potential therapeutical effect of new agents has been investigated. Two of these, the anti-interleukin 6 (IL-6) agents tocilizumab and satralizumab, have been studied in active NMOSD.Objective To systematically review the current data regarding the efficacy and safety of anti-IL-6 agents in NMOSD.Results Fourteen case reports and 5 case series of intravenous tocilizumab have shown beneficial clinical and paraclinical effects compared to commonly used therapies, and another case series of subcutaneous tocilizumab has shown it is as effective as the IV formulation. A phase 2 comparative trial has shown tocilizumab IV to be more effective than azathioprine for relapse prevention. A phase 3 trial of subcutaneous satralizumab versus placebo, has shown a lower risk of relapse in the sartralizumab-treated group, both as add-on therapy to stable immunosuppressant and as monotherapy. Tocilizumab also reduced pain severity in two trials and fatigue scores in one trial, but satralizumab did not significantly improve pain and fatigue. Adverse events with both agents were relatively mild and comparable to placebo and azathioprine.Conclusion The anti-Il-6 agents tocilizumab and satralizumab show promising results in active NMOSD.Further randomized, larger-scale trials are needed to better define the role of these agents in the growing arsenal of NMOSD treatments.