Penta-block copolymer microspheres: Impact of polymer characteristics and process parameters on protein release

Here, we aimed to develop protein loaded microspheres (MSs) using penta-block PLGA-based copolymers to obtain sustained and complete protein release. We varied MS morphology and studied the control of protein release. Lysozyme was used as a model protein and MSs were prepared using the solid-in-oil-in-water emulsion solvent extraction method. We synthesized and studied various penta-block PLGA-based copolymers. Copolymer characteristics (LA/GA ratio and molecular weight of PLGA blocks) influenced MS morphology. MS porosity was influenced by process parameters (such as solvent type, polymer concentration, emulsifying speed), whereas the aqueous volume for extraction and stabilizer did not have a significant effect. MSs of the same size, but different morphologies, exhibited different protein release behavior, with porous structures being essential for the continuous and complete release of encapsulated protein. These findings suggest strategies to engineer the morphology of MSs produced from PLGA-based multi-block copolymers to achieve appropriate release rates for a protein delivery system.     

Parietal network underlying movement control: disturbances during subcortical electrostimulation

Our understanding of brain movement control has changed over the last two decades. Recent findings in the monkey and in humans have led to a parallel and interconnected network. Nevertheless, little is known about these networks. Here, we present two cases of patients with a parietal low-grade glioma. They underwent surgery under local anesthesia with cortical and subcortical mapping. For patient 1, subcortical electrostimulation immediately posterior to thalamocortical fibers induced movement disorders, with an inhibition of leg and arm movements medially and, more laterally, an acceleration of arm movement. For patient 2, electrostimulation of white matter immediately posterior to thalamocortical fibers induced an inhibition of both arm movement. It means that the detected fibers in the parietal lobe may be involved in the motor control modulation. They are distributed veil-like immediately posterior to thalamocortical pathways and could correspond to a fronto-parietal movement control subnetwork. These two cases highlight the major role of the subcortical connectivity in movement regulation, involving parietal lobe, thus the necessity to be identified and preserved during brain surgery.     

Parallel indirect solution of optimal control problems

This paper presents an algorithm for the indirect solution of optimal control problems that contain mixed state and control variable inequality constraints. The necessary conditions for optimality lead to an inequality constrained two‐point BVP with index‐1 differential‐algebraic equations (BVP‐DAEs). These BVP‐DAEs are solved using a multiple shooting method where the DAEs are approximated using a single‐step linearly implicit Runge–Kutta (Rosenbrock–Wanner) method. An interior‐point Newton method is used to solve the residual equations associated with the multiple shooting discretization. The elements of the residual equations, and the Jacobian of the residual equations, are constructed in parallel. The search direction for the interior‐point method is computed by solving a sparse bordered almost block diagonal (BABD) linear system. Here, a parallel‐structured orthogonal factorization algorithm is used to solve the BABD system. Examples are presented to illustrate the efficiency of the parallel algorithm. It is shown that an American National Standards Institute C implementation of the parallel algorithm achieves significant speedup with the increase in the number of processors used. Copyright © 2013 John Wiley & Sons, Ltd.     

Nephron-sparing surgery is superior to radical nephrectomy in preserving renal function benefit even when expanding indications beyond the traditional 4-cm cutoff

ObjectivesTo analyze to what extent partial nephrectomy (PN) is superior to radical nephrectomy (RN) in preserving renal function outcome in relation to tumor size indication.Methods and materialsClinical data from 973 patients operated at 9 academic institutions were retrospectively analyzed. Glomerular filtration rate (GFR) before and after surgery was calculated with the abbreviated Modification of the Diet in Renal Disease equation. For a fair comparison between the 2 techniques, all imperative indications for PN were excluded. A shift to a less favorable GFR group following surgery was considered clinically significant.ResultsMedian age at diagnosis was 60 years (19–91). Tumor size was smaller than 4 cm in 665 (68.3%) cases and larger than 4 cm in 308 (31.7%) cases. PN and RN were performed in 663 (68.1%) and 310 (31.9%) patients, respectively. In univariate analysis, patients undergoing PN had a smaller risk for developing significant GFR change following surgery than those undergoing RN did. This was true for tumors≤4 cm (P = 0.0001) and for tumors>4 cm (P = 0.0001). In multivariate analysis, the following criteria were independent predictive factors for developing significant postoperative GFR loss: the use of RN (P = 0.0001), preoperative GFR<60 ml/min (P = 0.0001), tumor size≥4 cm (P = 0.0001), and older age at diagnosis (P = 0.0001).ConclusionsThe renal function benefit carried out by elective PN over RN persists even when expanding nephron-sparing surgery indications beyond the traditional 4-cm cutoff.     

Knowledge of Repetitions Range Affects Force Production in Trained Females

Most studies have examined pacing strategies with cyclical activities (running and cycling). It has been demonstrated that males employ different pacing strategies during repeated maximal voluntary contractions (MVCs) dependent upon a known endpoint. Since different fatiguing mechanisms have been identified between the genders, it is not known if females use comparable pacing strategies. The purpose of this study was to examine if informing female subjects regarding the number of MVCs to perform would affect force and electromyography (EMG). Twenty well-trained females completed 3 fatiguing protocols in a randomized order. In the control condition participants were informed they would perform twelve MVCs and then actually completed twelve. In the unknown condition they were not told how many MVCs to perform but were stopped after twelve. In the deception condition they were initially informed to perform 6 MVCs, but after the 6^th MVC they were asked to perform a few more MVCs and were stopped after twelve. During the first 6 MVCs, forces in the deception condition were greater compared to the unknown (p = 0.021, ES = 0.65, 5%) and control (p = 0.022, ES = 0.42, 3%) conditions. No differences were found between conditions in the last 6 MVCs. A main effect for repetitions showed force deficits during the first 6 MVCs (p = 0.000, ES = 1.81, 13%) and last 6 MVCs (p = 0.05, ES = 0.34, 3%). No differences were found between conditions in biceps and triceps EMG. However, EMG decreased during the first 6 MVCs for biceps (p = 0.001, ES = 1.0, 14%) and triceps (p = 0.001, ES = 0.76, 14%) across conditions. No differences were found in the last 6 MVCs. The anticipation of performing fewer MVCs led to increased force, whereas no endpoint led to decreased force production.

Key points

• Pacing strategies occur during repeated (fatiguing) MVCs as a function of end point expectations.
• Females use similar pacing strategies as previously published results with males.
• Without a known end point, females will tend to pace themselves by decreasing force output even when asked to perform maximal contractions.

Key words: Fatigue, electromyography, deception, pacing