Intermediaries in Bredon (Co)homology and Classifying Spaces

For certain contractible G-CW-complexes and F a family of subgroups of G, we construct a spectral sequence converging to the F-Bredon cohomology of G with E1-terms given by the F-Bredon cohomology of the stabilizer subgroups. As applications, we obtain several corollaries concerning the cohomological and geometric dimensions of the classifying space for the family F. We also introduce a hierarchically defined class of groups which contains all countable elementary amenable groups and countable linear groups of characteristic zero, and show that if a group G is in this class, then G has finite F-Bredon (co)homological dimension if and only if G has jump F-Bredon (co)homology.Comment: 18 page

Groups with twisted p-periodic cohomology

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Design of thermoresponsive polymeric gates with opposite controlled release behaviors

Stimuli-responsive devices are novel tools widely studied in the nanomedicine research field. In this work, magnetic-responsive mesoporous silica nanoparticles (MMSNs) were coated with an engineered thermoresponsive co-polymer. Magnetic cores are used as heating sources when they are exposed to an alternating magnetic field. The polymer structure suffers a change from hydrophilic to hydrophobic state when the temperature is raised above the lower critical solution temperature (LCST) or volume phase transition temperature (VPTT), acting as a gate-keeper of a model drug trapped inside the silica matrix. Fluorescein departure can be tuned employing two different polymer structures on the silica surface which exhibit the same transition temperature (42 degrees C) but a different grafting density: one of them being a dense crosslinked polymer network and the other one a hairy linear polymer layer. The release profile reveals to be the opposite between these two different coatings, allowing suitable drug release behavior for different clinical situations

Magnetic-Responsive Release Controlled by Hot Spot Effect

Magnetically triggered drug delivery nanodevices have attracted great attention in nanomedicine, as they can feature as smart carriers releasing their payload at clinician's will. The key principle of these devices is based on the properties of magnetic cores to generate thermal energy in the presence of an alternating magnetic field. Then, the temperature increase triggers the drug release. Despite this potential, the rapid heat dissipation in living tissues is a serious hindrance for their clinical application. It is hypothesized that magnetic cores could act as hot spots, this is, produce enough heat to trigger the release without the necessity to increase the global temperature. Herein, a nanocarrier has been designed to respond when the temperature reaches 43 degrees C. This material has been able to release its payload under an alternating magnetic field without the need of increasing the global temperature of the environment, proving the efficacy of the hot spot mechanism in magnetic-responsive drug delivery devices

A novel crosslinked hyaluronic Acid nanogel for drug delivery

An amphiphilic hyaluronic acid conjugate is successfully developed based on grafting a thiolated hydrophobic molecule to the polysaccharide backbone. The engineered conjugate is capable of assembling into nanostructures once dispersed in water, with average diameter of 80.2 ± 0.4 nm (n = 5), stable up to 6 months. The thiolated HyA conjugate is reticulated by dissulfide bond with a homofunctional crosslinker—1,4-Bis(3-[2-pyridyldithio]propionamido)butane (DPDPB). The drug loading efficiency of the reticulated and non-reticulated nanogel is accessed with two hydrophobic drugs, curcumin and simvastatin. Results suggest that crosslinked nanogel exhibit higher stability upon dilution and drug loading efficiency and proves to be a redox sensitive material. The nanogels hold great potential as stealth carriers of lipophilic drugs.The authors would like to acknowledge the support of FCT for the PhD grant reference SFRH/BD/61516/2009

Double sequential encrypted targeting sequence: A new concept for bone cancer treatment

The selective transportation of therapeutic agents to tumoral cells is usually achieved by their conjugation with targeting moieties able to recognize these cells. Unfortunately, simple and static targeting systems usually show selectivity lacks. Herein, double sequential encrypted targeting system is proposed as stimuliresponsive targeting analogue for selectivity enhancement. The system is able to recognize diseased bone tissue in first place, and once there, a hidden secondary targeting group is activated by the presence of an enzyme overproduced in the malignant tissue (cathepsin K), triggering the recognition of diseased cells. Transporting the cell targeting agent in a hidden conformation which contains a high selective tissular primary targeting, could avoid not only its binding to similar cell receptors but also the apparition of the binding-site barrier effect, which can enhance the penetration of the therapeutic agent within the affected zone. This strategy could be applied not only to conjugate drugs but also to drug loaded nanocarriers in order to improve the efficiency for bone cancer treatments

Prognostic value of cortically induced motor evoked activity by TMS in chronic stroke: caveats from a very revealing single clinical case

Background: We report the case of a chronic stroke patient (62 months after injury) showing total absence of motor activity evoked by transcranial magnetic stimulation (TMS) of spared regions of the left motor cortex, but near-to-complete recovery of motor abilities in the affected hand. Case presentation: Multimodal investigations included detailed TMS based motor mapping, motor evoked potentials (MEP), and Cortical Silent period (CSP) as well as functional magnetic resonance imaging (fMRI) of motor activity, MRI based lesion analysis and Diffusion Tensor Imaging (DTI) Tractography of corticospinal tract (CST). Anatomical analysis revealed a left hemisphere subinsular lesion interrupting the descending left CST at the level of the internal capsule. The absence of MEPs after intense TMS pulses to the ipsilesional M1, and the reversible suppression of ongoing electromyographic (EMG) activity (indexed by CSP) demonstrate a weak modulation of subcortical systems by the ipsilesional left frontal cortex, but an inability to induce efficient descending volleys from those cortical locations to right hand and forearm muscles. Functional MRI recordings under grasping and finger tapping patterns involving the affected hand showed slight signs of subcortical recruitment, as compared to the unaffected hand and hemisphere, as well as the expected cortical activations. Conclusions: The potential sources of motor voluntary activity for the affected hand in absence of MEPs are discussed. We conclude that multimodal analysis may contribute to a more accurate prognosis of stroke patients

Age-Specific Effects of Mirror-Muscle Activity on Cross-Limb Adaptations Under Mirror and Non-Mirror Visual Feedback Conditions

Cross-limb transfer (CLT) describes the observation of bilateral performance gains due to unilateral motor practice. Previous research has suggested that CLT may be reduced, or absent, in older adults, possibly due to age-related structural and functional brain changes. Based on research showing increases in CLT due to the provision of mirror visual feedback (MVF) during task execution in young adults, our study aimed to investigate whether MVF can facilitate CLT in older adults, who are known to be more reliant on visual feedback for accurate motor performance. Participants (N = 53) engaged in a short-term training regime (300 movements) involving a ballistic finger task using their dominant hand, while being provided with either visual feedback of their active limb, or a mirror reflection of their active limb (superimposed over the quiescent limb). Performance in both limbs was examined before, during and following the unilateral training. Furthermore, we measured corticospinal excitability (using TMS) at these time points, and assessed muscle activity bilaterally during the task via EMG; these parameters were used to investigate the mechanisms mediating and predicting CLT. Training resulted in significant bilateral performance gains that did not differ as a result of age or visual feedback (both p > 0.1). Training also elicited bilateral increases in corticospinal excitability (p < 0.05). For younger adults, CLT was significantly predicted by performance gains in the trained hand (β = 0.47), whereas for older adults it was significantly predicted by mirror activity in the untrained hand during training (β = 0.60). The present study suggests that older adults are capable of exhibiting CLT to a similar degree to younger adults. The prominent role of mirror activity in the untrained hand for CLT in older adults indicates that bilateral cortical activity during unilateral motor tasks is a compensatory mechanism. In this particular task, MVF did not facilitate the extent of CLT

Exploratory randomized double-blind placebo controlled trial of botulinum therapy on grasp release after Stroke (PrOMBiS)

Background. OnabotulinumtoxinA injections improve upper-limb spasticity after stroke, but their effect on arm function remains uncertain. Objective. To determine whether a single treatment with onabotulinumtoxinA injections combined with upper-limb physiotherapy improves grasp release compared with physiotherapy alone after stroke. Methods. A total of 28 patients, at least 1 month poststroke, were randomized to receive either onabotulinumtoxinA or placebo injections to the affected upper limb followed by standardized upper-limb physiotherapy (10 sessions over 4 weeks). The primary outcome was time to release grasp during a functionally relevant standardized task. Secondary outcomes included measures of wrist and finger spasticity and strength using a customized servomotor, clinical assessments of stiffness (modified Ashworth Scale), arm function (Action Research Arm Test [ARAT], Nine Hole Peg Test), arm use (Arm Measure of Activity), Goal Attainment Scale, and quality of life (EQ5D). Results. There was no significant difference between treatment groups in grasp release time 5 weeks post injection (placebo median = 3.0 s, treatment median = 2.0 s; t(24) = 1.20; P = .24; treatment effect = −0.44, 95% CI = −1.19 to 0.31). None of the secondary measures passed significance after correcting for multiple comparisons. Both groups achieved their treatment goals (placebo = 65%; treatment = 71%), and made improvements on the ARAT (placebo +3, treatment +5) and in active wrist extension (placebo +9°, treatment +11°). Conclusions. In this group of stroke patients with mild to moderate spastic hemiparesis, a single treatment with onabotulinumtoxinA did not augment the improvements seen in grasp release time after a standardized upper-limb physiotherapy program