Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment

We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal–curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments.     

Effect of Ag‐NPs synthesised by Chamaemelum nobile extract on the inflammation and oxidative stress induced by carrageenan in mice paw

An environmentally friendly and rapid procedure was developed to synthesise silver nanoparticles (Ag‐NPs) by Chamaemelum nobile extract and to evaluate its in vivo anti‐inflammatory and antioxidant activities. The ultraviolet–visible absorption spectrum of the synthesised Ag‐NPs showed an absorbance peak at 422. The average size of spherical nanoparticles was 24 nm as revealed by transmission electron microscopy. Fourier transform infra‐red spectroscopy analysis supported the presence of biological active compounds involved in the reduction of Ag ion and X‐ray diffraction confirmed the crystalline structure of the metallic Ag. The anti‐inflammatory and antioxidant activity of the Ag‐NPs was investigated against carrageenan‐induced paw oedema in mice. The levels of malondialdehyde (MDA) and antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase and inflammatory cytokines tumour necrosis factor (TNF‐α), interferon gamma and interleukin (IL)‐6, IL‐1β were assessed in this respect. The results demonstrated that anti‐inflammatory activity of the Ag‐NPs might be due to the ability of the nanoparticles to reduce IL‐1β, IL‐6 and TNF‐α. Moreover, reduction of antioxidant enzymes along with an increase in MDA level shows that the anti‐inflammatory activity of the synthesised Ag‐NPs by C. nobile is attributed to its ameliorating effect on the oxidative damage.Inspec keywords: silver, nanoparticles, nanofabrication, ultraviolet spectra, visible spectra, particle size, transmission electron microscopy, Fourier transform infrared spectra, X‐ray diffraction, crystal structure, enzymes, molecular biophysics, tumours, biomedical materials, nanomedicineOther keywords: Chamaemelum nobile extract, oxidative stress, mice paw, silver nanoparticles, antiinflammatory activity, antioxidant activity, ultraviolet‐visible absorption spectrum, spherical nanoparticle size, transmission electron microscopy, Fourier transform infrared spectroscopy, biological active compounds, X‐ray diffraction, crystalline structure, carrageenan‐induced paw oedema, malondialdehyde, antioxidant enzymes, superoxide dismutase, catalase, glutathione peroxidase, inflammatory cytokines, tumour necrosis factor, interferon gamma, interleukin, IL‐1β, IL‐6, TNF‐α, MDA level, Ag     

A Single Injection of NTG-101 Reduces the Expression of Pain-Related Neurotrophins in a Canine Model of Degenerative Disc Disease

Background: Tissue sources of pain emanating from degenerative discs remains incompletely understood. Canine intervertebral discs (IVDs) were needle puncture injured, 4-weeks later injected with either phosphate-buffered saline (PBS) or NTG-101, harvested after an additional fourteen weeks and then histologically evaluated for the expression of NGFr, BDNF, TrkB and CALCRL proteins. Quantification was performed using the HALO automated cell-counting scoring platform. Immunohistochemical analysis was also performed on human IVD tissue samples obtained from spinal surgery. Immunohistochemical analysis and quantification of neurotrophins and neuropeptides was performed using an in vivo canine model of degenerative disc disease and human degenerative disc tissue sections. Discs injected with NTG-101 showed significantly lower levels of Nerve Growth Factor receptor (NGFr/TrkA, p = 0.0001), BDNF (p = 0.009), TrkB (p = 0.002) and CALCRL (p = 0.008) relative to PBS injections. Human IVD tissue obtained from spinal surgery due to painful DDD show robust expression of NGFr, BDNF, TrkB and CALCRL proteins. A single intradiscal injection of NTG-101 significantly inhibits the expression of NGFr, BDNF, TrkB and CALCRL proteins in degenerative canine IVDs. These results strongly suggest that NTG-101 inhibits the development of neurotrophins that are strongly associated with painful degenerative disc disease and may have profound effects upon the management of patients living with discogenic pain.     

Deadlock-free scheduling in flexible manufacturing systems using Petri nets

This paper addresses the deadlock-free scheduling problem in Flexible Manufacturing Systems. An efficient deadlock-free scheduling algorithm was developed, using timed Petri nets, for a class of FMSs called Systems of Sequential Systems with Shared Resources (S 4 R). The algorithm generates a partial reachability graph to find the optimal or near-optimal deadlock-free schedule in terms of the firing sequence of the transitions of the Petri net model. The objective is to minimize the mean flow time (MFT). An efficient truncation technique, based on the siphon concept, has been developed and used to generate the minimum necessary portion of the reachability graph to be searched. It has been shown experimentally that the developed siphon truncation technique enhances the ability to develop deadlock-free schedules of systems with a high number of deadlocks, which cannot be achieved using standard Petri net scheduling approaches. It may be necessary, in some cases, to relax the optimality condition for large FMSs in order to make the search effort reasonable. Hence, a User Control Factor (UCF) was defined and used in the scheduling algorithm. The objective of using the UCF is to achieve an acceptable trade-off between the solution quality and the search effort. Its effect on the MFT and the CPU time has been investigated. Randomly generated examples are used for illustration and comparison. Although the effect of UCF did not affect the mean flow time, it was shown that increasing it reduces the search effort (CPU time) significantly.     

Controlled Creating of Cracks in Concrete for Non-destructive Testing

The non-destructive assessment of cracks in concrete is a common task for which non-destructive evaluation solutions have been published. Primarily, these tests have been carried out on artificial cracks that have been created by using notches instead of natural cracks. This study evaluates a procedure designed to create reproducible and controlled cracks in concrete. The procedure is based on using expanding mortar in a series of blind holes. This is done in combination with carefully aligned reinforcement to guide the direction of the crack development. The depth of the crack is also controlled by reinforcement. Crack depth varies statistically in the range of the maximum aggregate size (16 mm) used for concrete.     

Spray-dried pH-sensitive microparticles: effectual methodology to ameliorate the bioavailability of acid labile pravastatin

Pravastatin is a promising drug utilized in the treatment of hyperlipidemia, yet, its main clinical limitation is due to gastric liability which fractions its oral bioavailability to less than 18%. The purpose of the current study is to encapsulate pravastatin into Eudragit^®-based spray-dried microparticles aspiring to overcome its acid liability. With the aim to optimize the microparticles, formulation and process parameters were studied through acid resistance challenging test. Physicochemical characterization of the optimized spray-dried pH-sensitive microparticles namely; in-vitro dissolution, surface morphology, compatibility, and solid-state studies were performed. Moreover, in-vivo evaluation of the microparticles and accelerated stability studies were carried out. The results outlined that polymer to drug ratio at 5:1 and pravastatin concentration at 1%w/w in spray-drying feed solution showed 38.55% and 53.97% encapsulation efficiency, respectively. The significance of process parameters specifically; the flow rate and the inlet temperature on microparticles surface integrity were observed, and optimized until encapsulating efficiency reached 72.37%. The scanning electron microscopical examination of the optimized microparticles illustrate uniform smooth surface spheres entrapping the drug in an amorphous state as proved through Differential Scanning Calorimetry (DSC) and Fourier Transfer Infrared (FTIR) studies. The in-vivo evaluation demonstrated a 5-fold enhancement in pravastatin bioavailability compared to the marketed product. The results provided evidence for the significance of spray-dried pH-sensitive microparticles as a promising carrier for pravastatin, decreasing its acid liability, and improving its bioavailability.     

Assessing capacity scalability policies in RMS using system dynamics

This paper presents a model for assessing different capacity scalability policies in Reconfigurable Manufacturing System (RMS) for different changing demand scenarios. The novelty of this approach is two fold: (1) it is the first attempt to explore different capacity scalability policies in RMS based on multiple performance measures, mainly scaling rate, Work In Process level, inventory level and backlog level; and (2) the dynamic scalability process in RMS is modeled for the first time using System Dynamics. Different policies for capacity scalability for various demand scenarios were assessed. Numerical simulation results obtained using the developed capacity scalability model showed that the best capacity scalability policy to be adopted for RMS is dependent on the anticipated demand pattern as well as the various manufacturing objectives. The presented assessment results will help the capacity scalability planners better decide the different tradeoffs between the competing strategic and operational objectives of the manufacturing enterprise, before setting the suitable capacity scalability plan parameters.

Effects of relationship maintenance on psychological distress and dyadic adjustment among couples coping with lung cancer.

Objective: Relationship maintenance strategies help to ensure the continuation of valued relationships by keeping them at a certain level of intimacy. This study evaluated how lung cancer patients' and spouses' efforts to maintain their relationships affected their psychological and marital adjustment over time. Design: Psychosocial questionnaires were administered within 1 month of lung cancer treatment initiation (baseline) and 3 and 6 months later to 158 lung cancer patients and their spouses. Main Outcome Measures: Study outcomes were global severity index scores on the Brief Symptom Inventory, and total scores on the Dyadic Adjustment Scale. Results: Multilevel modeling analyses using the Actor-Partner Interdependence Model showed that, regardless of gender or social role (i.e., patient or spouse), individuals who engaged in the strategies of positivity, networks, and shared tasks reported less distress at baseline than other participants. Over time, the effects of providing more assurances and experiencing a partner's increased reliance on social networks differed: patient distress was exacerbated, and spouse distress was alleviated. Couples where both partners engaged in more frequent maintenance behaviors reported greater dyadic adjustment at baseline and over time. Conclusion: For couples coping with lung cancer, the initial treatment period may be an important time that sets the tone for future spousal interactions. Engaging in relationship maintenance during this stressful time may help mold more resilient relationships and facilitate adjustment as the disease progresses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)