Enhanced depth-independent chondrocyte proliferation and phenotype maintenance in an ultrasound bioreactor and an assessment of ultrasound dampening in the scaffold

Chondrocyte-seeded scaffolds were cultured in an ultrasound (US)-assisted bioreactor, which supplied the cells with acoustic energy around resonance frequencies (∼5.0 MHz). Polyurethane-polycarbonate (BM), chitosan (CS) and chitosan–n-butanol (CSB) based scaffolds with varying porosities were chosen and the following US regimen was employed: 15 kPa and 60 kPa, 5 min per application and 6 applications per day for 21 days. Non-stimulated scaffolds served as control. For BM scaffolds, US stimulation significantly impacted cell proliferation and depth-independent cell population density compared to controls. The highest COL2A1/COL1A1 ratios and ACAN mRNA were noted on US-treated BM scaffolds compared to controls. A similar trend was noted on US-treated cell-seeded CS and CSB scaffolds, though COL2A1/COL1A1 ratios were significantly lower compared to BM scaffolds. Expression of Sox-9 was also elevated under US and paralleled the COL2A1/COL1A1 ratio. As an original contribution, a simplified mathematical model based on Biot theory was developed to understand the propagation of the incident US wave through the scaffolds and the model analysis was connected to cellular responses. Scaffold architecture influenced the distribution of US field, with the US field being the least attenuated in BM scaffolds, thus coupling more mechanical energy into cells, and leading to increased cellular activity.     

Curcumin- and natural extract-loaded nanofibres for potential treatment of lung and breast cancer: in vitro efficacy evaluation

Drug-eluting medical implants are more common, particularly for fighting against cancers. FDA and other drug regulatory bodies have approved many nanoformulated devices eluting active pharmaceutical ingredients and thus there is growing demand for further value- added devices. Nanofibre membranes are known for its versatility of drug incorporation and sustained drug release. We intend to fabricate natural ingredient or extract, and their combination loaded polycaprolactone (PCL) nanofibre for usage as drug-eluting stents or implants for anticancer activity against lung and breast cancers. The fabricated nanofibre membranes were characterised by scanning electron microscope for morphology, FT-IR for chemical nature and tensile testing for mechanical strengths. Release of curcumin was studied with time to find the applicability of the device as drug-eluting implant. The activity of the nanofibre membranes was tested against human breast cancer (MCF7) and lung cancer (A459) cell lines in vitro. In both the cell lines tested, 1% aloe vera and 5% curcumin-loaded PCL nanofibre exhibited 15% more cytotoxicity in comparison with the commercial drug 1% cis-Platin-loaded PCL nanofibre after 24?h incubation.     

Microcytosis and possible early iron deficiency in paediatric inpatients: a retrospective audit

Background  

Iron deficiency anaemia is a common paediatric problem worldwide, with significant neurodevelopmental morbidity if left untreated. A decrease in the mean corpuscular volume (MCV) can be used as a surrogate marker for detecting early iron deficiency prior to definitive investigation and treatment. An audit cycle was therefore undertaken to evaluate and improve the identification, follow-up and treatment of abnormally low MCV results amongst the paediatric inpatients in an English district general hospital.     

Type III restriction enzymes cleave DNA by long-range interaction between sites in both head-to-head and tail-to-tail inverted repeat

Cleavage of viral DNA by the bacterial Type III Restriction-Modification enzymes requires the ATP-dependent long-range communication between a distant pair of DNA recognition sequences. The classical view is that Type III endonuclease activity is only activated by a pair of asymmetric sites in a specific head-to-head inverted repeat. Based on this assumption and due to the presence of helicase domains in Type III enzymes, various motor-driven DNA translocation models for communication have been suggested. Using both single-molecule and ensemble assays we demonstrate that Type III enzymes can also cleave DNA with sites in tail-to-tail repeat with high efficiency. The ability to distinguish both inverted repeat substrates from direct repeat substrates in a manner independent of DNA topology or accessory proteins can only be reconciled with an alternative sliding mode of communication.     

Primary cardiac lymphoma masquerading as right atrial myxoma causing complete heart block—a case report

Secondary involvement of the heart and pericardium by systemic lymphoma is well documented. Primary Cardiac lymphomas (PCL) are extremely rare. Incidence of PCL is increasing in immunocompromised patients. However PCL in immunocompetent is much rarer. We report such a case of PCL in an immunocompetent elderly female masquerading as right atrial myxoma causing complete heart block which was surgically debulked successfully. Her rhythm resumed to Sinus rhythm following surgical debulking. Immunohistochemistry of the excised tumour revealed Diffuse Large B cell lymphoma. With combination chemotherapy, she is symptom free on six months follow up.     

Prevalence and correlates of tobacco use among Russian cancer patients: Implications for the development of smoking cessation interventions at a cancer center in Russia

This study examined the rate of smoking among 399 cancer patients in Russia and assessed correlates of tobacco use and readiness to quit smoking. The results indicated that (a) 41.6% of patients were smokers; and (b) smokers were likely to be male, have lung or colorectal cancer, exhibit low levels of knowledge concerning the negative effects of smoking, report a low level of advantages to quitting smoking and a high level of disadvantages to quitting smoking, show low perceived risk for the adverse effects of smoking, and exhibit high fatalistic beliefs. Though certain findings converge well with data collected from U.S. samples of cancer patients, these results can guide the development of smoking interventions that address the specific needs of Russian cancer patients. In sum, this study fills a critical gap in knowledge concerning the epidemic of tobacco use in Russia and broadens research regarding tobacco use by cancer patients from the United States to the Russian Federation. Support for this study was provided by National Institutes of Health grant CA95678 (R. Schnoll) and by a U.S. federal appropriation to the American-Russian Cancer Alliance.     

Subject Specific Optimisation of the Stiffness of Footwear Material for Maximum Plantar Pressure Reduction

Current selection of cushioning materials for therapeutic footwear and orthoses is based on empirical and anecdotal evidence. The aim of this investigation is to assess the biomechanical properties of carefully selected cushioning materials and to establish the basis for patient-specific material optimisation. For this purpose, bespoke cushioning materials with qualitatively similar mechanical behaviour but different stiffness were produced. Healthy volunteers were asked to stand and walk on materials with varying stiffness and their capacity for pressure reduction was assessed. Mechanical testing using a surrogate heel model was employed to investigate the effect of loading on optimum stiffness. Results indicated that optimising the stiffness of cushioning materials improved pressure reduction during standing and walking by at least 16 and 19% respectively. Moreover, the optimum stiffness was strongly correlated to body mass (BM) and body mass index (BMI), with stiffer materials needed in the case of people with higher BM or BMI. Mechanical testing confirmed that optimum stiffness increases with the magnitude of compressive loading. For the first time, this study provides quantitative data to support the importance of stiffness optimisation in cushioning materials and sets the basis for methods to inform optimum material selection in the clinic.     

Ethinyl estradiol treats collagen-induced arthritis in DBA/1LacJ mice by inhibiting the production of TNF-alpha and IL-1beta

We previously demonstrated the therapeutic effects of ethinyl estradiol (EE), an orally active estrogen and a component of birth control pills, in encephalitogenic autoimmune encephalomyelitis (EAE). In this study, we report the effectiveness of EE in treating collagen-induced arthritis (CIA) induced with bovine type II collagen (bCII) in DBA/1LacJ mice, a CIA susceptible strain. Both low and high doses of EE notably suppressed clinical and histological signs of CIA in a dose-dependent manner compared to vehicle-treated controls. Oral treatment with EE decreased proliferation and secretion of pro-inflammatory factors, TNF-alpha IFN-gamma, MCP-1 and IL-6 by bCII peptide-specific T cells, production of bCII-specific IgG2a antibodies, and mRNA for cytokines, chemokines and chemokine receptors in joint tissue. This is the first report demonstrating effective treatment of joint inflammation and clinical signs of CIA with orally administered ethinyl estradiol, thus supporting its possible clinical use for treating rheumatoid arthritis in humans.     

Crosslinked chitosan: its physical properties and the effects of matrix stiffness on chondrocyte cell morphology and proliferation

Chitosan [beta(1-4)-2 amino-2-deoxy-D-glucose], the natural polyaminosaccharide derived from N-deacetylation of chitin [beta(1-4)-2 acetamide-2-deoxy-D-glucose], has been shown to possess attractive biological and cell interactive properties. Recently chitosan and chitosan analogs have also been shown to support the growth and continued function of chondrocytes. In the present study, chitosan substrates are crosslinked with a functional diepoxide (1,4 butanediol diglycidyl ether) to alter its mechanical property, and the viability and proliferation of the canine articular chondrocytes seeded on the crosslinked surface are further assayed. Of interest is the impact of substrate stiffness on the growth and proliferation of articular canine chondrocytes. Crosslinked scaffolds were also subjected to degradation by chitosanase to examine the impact of crosslinking on enzyme-assisted degradation. The hydrophilicity and compression modulus of the crosslinked surfaces were measured via contact-angle measurements and compression tests, respectively. Scanning electron microscopy (SEM) and fluorescent staining were used to observe the proliferation and morphology of chondrocyte cells on noncrosslinked and crosslinked surfaces. The crosslinked chitosan was found to be nontoxic to chondrocytes and more hydrophilic. Its compression modulus and stiffness increased, which may improve the scaffold resistance to wear and in vivo shrinkage once implanted. The increased stiffness also seemed to serve as an additional mechanical stimulus to promote chondrocyte growth and proliferation. The cell morphology on crosslinked scaffolds seen by SEM and fluorescent stain was the typical chondrocytic rounded shape. The method proposed provides a nontoxic way to increase the mechanical strength of the chitosan scaffolds.     

Replication timing properties, of the humanHPRT locus on active, inactive and reactivated X chromosomes

X chromosome inactivation is associated with a highly asynchronous pattern of DNA replication at most X-linked loci in females. We studied the human HPRT locus, which is subject to X inactivation and expressed from only the active homolog, with the goal of comparing replication properties between the active and inactive homologs in this region using a fluorescence in situ hybridization approach. We found that in normal female lymphoblasts this locus is replicated in a highly asynchronous manner across a broad, discrete 500–600 kb zone with earliest replication appearing at the gene coding sequence. This general timing profile is maintained in normal male lymphoblasts, as well as in hamster x human hybrid cells containing the active human X chromosome. However, the inactive human X chromosome in the hamster cell background does not appear to function in a fully equivalent manner to the normal inactive X chromosome in female cells. Furthermore, reactivation of the inactive human X chromosome in a hamster x human hybrid system by 5-azacytidine treatment and HAT selection restores early replication at the HPRT gene itself, but does not change the overall domain behavior.