Preliminary Evaluation of the Sural Nerve Using 22-MHz Ultrasound: A New Approach for Evaluation of Diabetic Cutaneous Neuropathy

Background: The application of 22-MHz high-frequency ultrasound allows for visualization of the inner part of the sural nerve. The aim of this study was to evaluate the morphological changes of sural nerves in patients with type 2 diabetes mellitus using ultrasound. Materials and Methods: The thickness/width (T/W) ratio, the cross-sectional area (CSA) of the sural nerves and the maximum thickness (MT) of the nerve fascicles were measured in 100 patients with type 2 diabetes mellitus and 50 healthy volunteers using 22-MHz ultrasound. Receiver operating characteristic (ROC) curves were plotted to determine the optimal cut-off values as well as the sensitivities and specificities. All parameters were significantly different between the subject and control groups. The ROC curves demonstrated that the MT was the most predictive of diabetic cutaneous neuropathy, with an optimal cut-off value of 0.365 mm that yielded a sensitivity of 90.3 % and a specificity of 87.7%. Conclusions: The results of this study suggest that 22-MHz ultrasound may be a valuable tool for evaluating diabeti

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Ca2+ Cycling in Heart Cells from Ground Squirrels: Adaptive Strategies for Intracellular Ca2+ Homeostasis

Heart tissues from hibernating mammals, such as ground squirrels, are able to endure hypothermia, hypoxia and other extreme insulting factors that are fatal for human and nonhibernating mammals. This study was designed to understand adaptive mechanisms involved in intracellular Ca2+ homeostasis in cardiomyocytes from the mammalian hibernator, ground squirrel, compared to rat. Electrophysiological and confocal imaging experiments showed that the voltage-dependence of L-type Ca2+ current (ICa) was shifted to higher potentials in ventricular myocytes from ground squirrels vs. rats. The elevated threshold of ICa did not compromise the Ca2+-induced Ca2+ release, because a higher depolarization rate and a longer duration of action potential compensated the voltage shift of ICa. Both the caffeine-sensitive and caffeine-resistant components of cytosolic Ca2+ removal were more rapid in ground squirrels. Ca2+ sparks in ground squirrels exhibited larger amplitude/size and much lower frequency than in rats. Due to the high ICa threshold, low SR Ca2+ leak and rapid cytosolic Ca2+ clearance, heart cells from ground squirrels exhibited better capability in maintaining intracellular Ca2+ homeostasis than those from rats and other nonhibernating mammals. These findings not only reveal adaptive mechanisms of hibernation, but also provide novel strategies against Ca2+ overload-related heart diseases

Ensemble Analysis of Angiogenic Growth in Three-Dimensional Microfluidic Cell Cultures

We demonstrate ensemble three-dimensional cell cultures and quantitative analysis of angiogenic growth from uniform endothelial monolayers. Our approach combines two key elements: a micro-fluidic assay that enables parallelized angiogenic growth instances subject to common extracellular conditions, and an automated image acquisition and processing scheme enabling high-throughput, unbiased quantification of angiogenic growth. Because of the increased throughput of the assay in comparison to existing three-dimensional morphogenic assays, statistical properties of angiogenic growth can be reliably estimated. We used the assay to evaluate the combined effects of vascular endothelial growth factor (VEGF) and the signaling lipid sphingoshine-1-phosphate (S1P). Our results show the importance of S1P in amplifying the angiogenic response in the presence of VEGF gradients. Furthermore, the application of S1P with VEGF gradients resulted in angiogenic sprouts with higher aspect ratio than S1P with background levels of VEGF, despite reduced total migratory activity. This implies a synergistic effect between the growth factors in promoting angiogenic activity. Finally, the variance in the computed angiogenic metrics (as measured by ensemble standard deviation) was found to increase linearly with the ensemble mean. This finding is consistent with stochastic agent-based mathematical models of angiogenesis that represent angiogenic growth as a series of independent stochastic cell-level decisions

Corticospinal output during muscular fatigue differs in multiple sclerosis patients compared to healthy controls

In multiple sclerosis (MS), fatigue is a common and often disabling symptom. It has multiple causes with central motor fatigue playing an important role

A COMPREHENSIVE, TWO-MONTH CIRCUIT TRAINING IN PEOPLE WITH MULTIPLE SCLEROSIS - ADHERENCE AND SATISFACTION WITH THE STUDY INTERVENTION

Background: Exercise therapy in people with multiple sclerosis (MS) can improve strength, aerobic capacity, fatigue, balance and manual dexterity. Circuit training has been shown to be an effective exercise intervention in several neurological diseases, though it has been poorly investigated in people with MS. So far, a few small trials reported promising results, but exercise adherence and patient satisfaction have not yet been investigated. Purpose: As part of a larger randomized controlled trial this study aimed to investigate the adherence of people with MS to a structured, two-month ambulatory circuit training (MS-Fit) and to determine their overall satisfaction with the program. Methods: People with MS-related disability affecting activities of daily living (ADL) and/or quality of life (QoL) were included. The participants attended the circuit training for 2x2 hours weekly over 2 months. The circuit training was conducted in two rehabilitation centres in Switzerland and supervised by experienced physiotherapists. The program consisted of six workstations, where endurance, strength, flexibility, balance, dexterity and reaction were exercised individually. Physiotherapists evaluated and adapted quality and intensity according to the participants' performance. A training group consisted of two to six participants. Program satisfaction and adherence were evaluated using a face-validated questionnaire and attendance rate. Results: From totally 51 people with MS eligible, 37 (10 men, 27 women, mean age 52.7±10.3, median Expanded Disability Status Scale (EDSS) 3.5 (min 2.0, max 6.5) participated in the MS-fit program. Main reasons not to participate were lack of time, or family issues. All 37 participants achieved >80% (mean 90.5%±8.2) of attendance rate and sent the evaluation questionnaire back. Participants rated the program quality as good with an overall median score of 39/50 (min 26, max 50). Overall program satisfaction was median 8 (min4, max10) on a Likert scale from 0-10. 95% of participants would recommend the program to others. Moreover, participants highlighted the positive impact on social participation, peer learning opportunities and reported an increase in exercise management competences. Expectations concerning further program availability was high. Conclusion(s): The MS-Fit training program seems to be a highly appreciated form of exercise therapy with a high rate of attendance. The two-month program intensity and duration was practicable and acceptable. Furthermore, the program positively affected social participation and stimulated participants' exercise competences and learning aspects. Further research is needed to evaluate the functional, mental and physical effects of the program. Implications: The MS-Fit training program might motivate people with MS that are usually involved in one-to-one therapy settings. After analysis of the effectiveness of the circuit training program, implementation and national dispersion might be proposed to offer MS-fit access to people with MS close to their domicile

Responsive biomimetic networks from polyisocyanopeptide hydrogels

Contains fulltext : 111406.pdf (preprint version ) (Open Access) Contains fulltext : 111406_suppl.pdf (preprint version ) (Open Access