Novel scaffolds for tissue engineering of human skeletal muscles

Tissue engineering is a multidisciplinary approach aimed at producing new organs and tissues for implantation in order to circumvent the limitations imposed by current techniques such as surgical tissue transfer. Structure begets function and highly ordered skeletal muscle (SkM) consists of elongated, multinucleate muscle cells (fibres) that are arranged in bundles surrounded by connective tissue sheaths. It is therefore of no surprise that tissue engineered SkM complexes are often designed around fibre containing scaffolds. This work is the natural continuation of strategies introduced at TCES 200

Reduced Cost and Decreased Length of Stay Associated with Acute Ischemic Stroke Care Provided by Nurse Practitioners: A Single Primary Stroke Center Experience

Nurse practitioner (NP) have a wider role in modern stroke centers providing quality evidence based care to patients with both in and outpatient settings for acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients. We studies the outcome measures, length of stay (LOS) and cost before and after implementation of nurse practitioners as the primary medical provider in a community based stroke center.https://digitalcommons.centracare.com/nursing_posters/1075/thumbnail.jp

Microangiopathic Occlusion of a Perforating Prepontine Long Circumferential Artery Presenting with Lower Motor Neuron Facial Weakness: Clinical and Radiological Correlation

Case Description: A 79-year old male patient with myelodysplastic syndrome associated with severe neutropenia, thrombocytopenia, anemia, hypertension, and hyperlipidemia was admitted for pneumonia secondary to influenza A. Two weeks later he presented with new symptoms of acute dysarthria, and left facial weakness involving his upper and lower face; the following day he developed left arm weakness. Admission computed tomography (CT) and MRI scans revealed an acute ischemic stroke (AIS) in the right posterior frontal cortex. The initial MRI was reported negative for pontine lesions. Anatomically, the cortical infarct could not explain his left lower motor neuron cranial nerve VII (LMN CN VII) facial weakness distribution because in a cortical lesion the upper half of the face would be expected spared due to contralateral cortical innervation. Upon review of the MRI, the initial hyperintensity seen on Fluid-Attenuated Inversion Recovery (FLAIR) was overlooked and later identified as an acute stroke in the vicinity of the perforating prepontine long circumferential artery affecting the CN VII nucleus. Conclusion: In the absence of earache, active infection, and/or inflammation, a sudden onset facial palsy, lower motor neuron distribution, must poin

Engineered craniofacial muscle constructs express markers of muscle differentiation

Tissue engineering has the potential to serve as an alternative to surgical tissue transfer for the management of soft tissue defects. The perceived advantages include reduced donor site morbidity and restoration of function and aesthetics to ideal. Degradable scaffolds are utilised in the early stages of cell growth and development with the advantage of eventual elimination to leave space for the engineered tissue and a reduced chance of rejection

Donor ionization in size controlled silicon nanocrystals: The transition from defect passivation to free electron generation

We studied the photoluminescence spectra of silicon and phosphorus co-implanted silica thin films on (100) silicon substrates as a function of isothermal annealing time. The rapid phase segregation, formation, and growth dynamics of intrinsic silicon nanocrystals are observed, in the first 600 s of rapid thermal processing, using dark field mode X-TEM. For short annealing times, when the nanocrystal size distribution exhibits a relatively small mean diameter, formation in the presence of phosphorus yields an increase in the luminescence intensity and a blue shift in the emission peak compared with intrinsic nanocrystals. As the mean size increases with annealing time, this enhancement rapidly diminishes and the peak energy shifts further to the red than the intrinsic nanocrystals. These results indicate the existence of competing pathways for the donor electron, which depends strongly on the nanocrystal size. In samples containing a large density of relatively small nanocrystals, the tendency of phosphorus to accumulate at the nanocrystal-oxide interface means that ionization results in a passivation of dangling bond (Pb -centre) type defects, through a charge compensation mechanism. As the size distribution evolves with isothermal annealing, the density of large nanocrystals increases at the expense of smaller nanocrystals, through an Ostwald ripening mechanism, and the majority of phosphorus atoms occupy substitutional lattice sites within the nanocrystals. As a consequence of the smaller band-gap, ionization of phosphorus donors at these sites increases the free carrier concentration and opens up an efficient, non-radiative de-excitation route for photo-generated electrons via Auger recombination. This effect is exacerbated by an enhanced diffusion in phosphorus doped glasses, which accelerates silicon nanocrystal growth

A screen to identify drug resistant variants to target-directed anti-cancer agents

The discovery of oncogenes and signal transduction pathways important for mitogenesis has triggered the development of target-specific small molecule anti-cancer compounds. As exemplified by imatinib (Gleevec), a specific inhibitor of the Chronic Myeloid Leukemia (CML)-associated Bcr-Abl kinase, these agents promise impressive activity in clinical trials, with low levels of clinical toxicity. However, such therapy is susceptible to the emergence of drug resistance due to amino acid substitutions in the target protein. Defining the spectrum of such mutations is important for patient monitoring and the design of next-generation inhibitors. Using imatinib and BCR/ABL as a paradigm for a drug-target pair, we recently reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations. Here we provide a detailed methodology for the screen, which can be generally applied to any drug-target pair

P-loop mutations and novel therapeutic approaches for imatinib failures in chronic myeloid leukemia

Imatinib was the first BCR-ABL-targeted agent approved for the treatment of patients with chronic myeloid leukemia (CML) and confers significant benefit for most patients; however, a substantial number of patients are either initially refractory or develop resistance. Point mutations within the ABL kinase domain of the BCR-ABL fusion protein are a major underlying cause of resistance. Of the known imatinib-resistant mutations, the most frequently occurring involve the ATP-binding loop (P-loop). In vitro evidence has suggested that these mutations are more oncogenic with respect to other mutations and wild type BCR-ABL. Dasatinib and nilotinib have been approved for second-line treatment of patients with CML who demonstrate resistance (or intolerance) to imatinib. Both agents have marked activity in patients resistant to imatinib; however, they have differential activity against certain mutations, including those of the P-loop. Data from clinical trials suggest that dasatinib may be more effective vs. nilotinib for treating patients harboring P-loop mutations. Other mutations that are differentially sensitive to the second-line tyrosine kinase inhibitors (TKIs) include F317L and F359I/V, which are more sensitive to nilotinib and dasatinib, respectively. P-loop status in patients with CML and the potency of TKIs against P-loop mutations are key determinants for prognosis and response to treatment. This communication reviews the clinical importance of P-loop mutations and the efficacy of the currently available TKIs against them

Assessment of Yeasts as Potential Probiotics: A Review of Gastrointestinal Tract Conditions and Investigation Methods

Probiotics are microorganisms (including bacteria, yeasts and moulds) that confer various health benefits to the host, when consumed in sufficient amounts. Food products containing probiotics, called functional foods, have several health-promoting and therapeutic benefits. The significant role of yeasts in producing functional foods with promoted health benefits is well documented. Hence, there is considerable interest in isolating new yeasts as potential probiotics. Survival in the gastrointestinal tract (GIT), salt tolerance and adherence to epithelial cells are preconditions to classify such microorganisms as probiotics. Clear understanding of how yeasts can overcome GIT and salt stresses and the conditions that support yeasts to grow under such conditions is paramount for identifying, characterising and selecting probiotic yeast strains. This study elaborated the adaptations and mechanisms underlying the survival of probiotic yeasts under GIT and salt stresses. This study also discussed the capability of yeasts to adhere to epithelial cells (hydrophobicity and autoaggregation) and shed light on in vitro methods used to assess the probiotic characteristics of newly isolated yeasts

Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib

Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF), together with imatinib, has led to a significant reduction in leukemic stem cells in vitro. In this paper, we design a novel mathematical model of stem cell quiescence to investigate the treatment response to imatinib and G-CSF. We find that the addition of G-CSF to an imatinib treatment protocol leads to observable effects only if the majority of leukemic stem cells are quiescent; otherwise it does not modulate the leukemic cell burden. The latter scenario is in agreement with clinical findings in a pilot study administering imatinib continuously or intermittently, with or without G-CSF (GIMI trial). Furthermore, our model predicts that the addition of G-CSF leads to a higher risk of resistance since it increases the production of cycling leukemic stem cells. Although the pilot study did not include enough patients to draw any conclusion with statistical significance, there were more cases of progression in the experimental arms as compared to continuous imatinib. Our results suggest that the additional use of G-CSF may be detrimental to patients in the clinic