Study of the effect of HFE gene mutations on iron overload in Egyptian thalassemia patients

Background: HFE gene mutations have been shown to be responsible for hereditaryhemochromatosis. Their effect on iron load in β-thalassemia patients and carriers remains controversial.Objectives: We aimed to determine the prevalence of HFE gene mutations (C282Y and H63D) in β-thalassemia patients and carriers and to investigate its effect on their serum ferritin levels.Patients and methods: A total of 100 β-thalassemia subjects; 75 patients and 25 carriers were screened for HFE gene mutations by PCR-RFLP. Serum ferritin measured by ELISA was evaluated in relation to HFE mutations.Results: Twenty-eight β-thalassemia patients (37.3%) were heterozygotes for H63D mutation (H/D), 8 (10.7%) were D/D and 39 (52%) were negative (H/H). Among carriers, 4 (16%) were D/D and 21 (84%) were H/H homozygotes. C282Y mutant allele was not detected in any of the subjects. Serum ferritin levels were significantly higher in β-thalassemia patients heterozygotes or homozygotes for H63D mutation compared to those without mutation (p= 0.000). Carriers homozygotes for H63D mutation showed significantly higher serum ferritin levels compared to those without mutation (p< 0.001).Conclusion: Homozygosity for H63D mutation tends to be associated with higher ferritin levels in beta-thalassemia patients and carriers suggesting its modulating effect on iron load in these cases

Self-assembled liquid crystalline nanotemplates and their incorporation in dye-sensitised solar cells

Liquid junction dye-sensitised solar cells (DSSCs) suffer from solvent evaporation and leakage which limit their large-scale production. Here, we have prepared DSSC using a simple and cheap fabrication process with improved photovoltaic parameters and stability. A binary mixture of Smectic A (SmA) and Nematic Liquid Crystal (NLC) was used to provide a self-assembled template for a polymerisable reactive mesogen LC. The layered structure of SmA combined with a low viscosity NLC forms a polygonal structure that provides an ordered and continuous template for reactive mesogens. Once the reactive mesogen is polymerised under UV light, the SmA:NLC mixture is washed away, resulting in a polymer network template containing nanochannels. We demonstrate the incorporation of these templates into DSSCs and find that DSSCs containing these nanochannels show improved open-circuit voltage (V$_{OC}$) (0.705 V) and short-circuit current (J$_{SC}$) (13.25 mA cm$^{-2}$) compared to that of the liquid electrolyte (V$_{OC}$ = 0.694 V and JSC = 10.46 mA cm$^{-2}$). The highest obtained power conversion efficiency with Sm-PE was 5.94% which is higher than that of the reference solar cell (5.51%). These can be attributed to the improved ionic conductivity and ionic diffusion of Sm-PE where the presence of the nanochannels aided the ionic conduction in the polymer electrolyte. In addition, it is hypothesized that the light scattering effect of the polymerised reactive mesogen also contributed to the improved performance of the photovoltaic devices. This finding is important because it is known fact that when a polymer is added to liquid electrolyte, the ionic conductivity will decrease although the stability is improved.A.A.K. and G.R. would like to thank the Cambridge Commonwealth Trust for financial support. A.A.K. would also like to thank the HEC (Pakistan) for financial support. C.W would like to thank EPSRC Integrated Photonics and Electronics Systems funding

Sustainable waste management of medical waste in African developing countries: A narrative review

This is the final version. Available on open access from SAGE Publications via the DOI in this recordAfrica is the second populous continent, and its population has the fastest growing rate. Some African countries are still plagued by poverty, poor sanitary conditions and limited resources, such as clean drinking water, food supply, electricity, and effective waste management systems. Underfunded healthcare systems, poor training and lack of awareness of policies and legislations on handling medical waste have led to increased improper handling of waste within hospitals, healthcare facilities and transportation and storage of medical waste. Some countries, including Ethiopia, Botswana, Nigeria and Algeria, do not have national guidelines in place to adhere to the correct disposal of such wastage. Incineration is often the favoured disposal method due to the rapid diminishment of up to 90% of waste, as well as production of heat for boilers or for energy production. This type of method – if not applying the right technologies – potentially creates hazardous risks of its own, such as harmful emissions and residuals. In this study, the sustainability aspects of medical waste management in Africa were reviewed to present resilient solutions for health and environment protection for the next generation in Africa. The findings of this research introduce policies, possible advices and solutions associated with sustainability and medical waste management that can support decision-makers in developing strategies for the sustainability by using the eco-friendly technologies for efficient medical waste treatment and disposal methods and also can serve as a link between the healthcare system, decision-makers, and stakeholders in developing health policies and programmes.University of Exete

The FLASSH study: protocol for a randomised controlled trial evaluating falls prevention after stroke and two sub-studies

This randomised controlled trial aims to evaluate the effectiveness of a multi-factorial falls prevention program for stroke survivors who are at high risk of falling when they return home after rehabilitation. Intervention will consist of a home exercise program as well as individualised falls prevention and injury minimisation strategies based on identified risk factors for falls. Additionally, two sub-studies will be implemented in order to explore other key areas related to falls in this population. The first of these is a longitudinal study evaluating the relationship between fear of falling, falls and function over twelve months, and the second evaluates residual impairment in gait stability and obstacle crossing twelve months after discharge from rehabilitation

The influence of bisphosphonates on human osteoblast migration and integrin aVb3/tenascin C gene expression in vitro

<p>Abstract</p> <p>Background</p> <p>Bisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jaw (BONJ) often requires surgical treatment and is accompanied with a disturbed wound healing.</p> <p>Therefore, the influence on adhesion and migration of human osteoblasts (hOB) after bisphosphonate therapy has been investigated by morphologic as well as gene expression methods.</p> <p>Methods</p> <p>By a scratch wound experiment, which measures the reduction of defined cell layer gap, the morphology and migration ability of hOB was evaluated. A test group of hOB, which was stimulated by zoledronate 5 × 10^-5M, and a control group of unstimulated hOB were applied. Furthermore the gene expression of integrin aVb3 and tenascin C was quantified by Real-Time rtPCR at 5data points over an experimental period of 14 days. The bisphosphonates zoledronate, ibandronate and clodronate have been compared with an unstimulated hOB control.</p> <p>Results</p> <p>After initially identical migration and adhesion characteristics, zoledronate inhibited hOB migration after 50 h of stimulation. The integrinavb3 and tenascin C gene expression was effected by bisphosphonates in a cell line dependent manner with decreased, respectively inconsistent gene expression levels over time. The non-nitrogen containing bisphosphonates clodronate led to decreased gene expression levels.</p> <p>Conclusion</p> <p>Bisphosphonates seem to inhibit hOB adhesion and migration. The integrin aVb3 and tenascin C gene expression seem to be dependent on the cell line. BONJ could be enhanced by an inhibition of osteoblast adhesion and migration. The gene expression results, however, suggest a cell line dependent effect of bisphosphonates, which could explain the interindividual differences of BONJ incidences.</p

Tissue eosinophilia: a morphologic marker for assessing stromal invasion in laryngeal squamous neoplasms

BACKGROUND: The assessment of tumor invasion of underlying benign stroma in neoplastic squamous proliferation of the larynx may pose a diagnostic challenge, particularly in small biopsy specimens that are frequently tangentially sectioned. We studied whether thresholds of an eosinophilic response to laryngeal squamous neoplasms provides an adjunctive histologic criterion for determining the presence of invasion. METHODS: Eighty-seven(n = 87) cases of invasive squamous cell carcinoma and preinvasive squamous neoplasia were evaluated. In each case, the number of eosinophils per high power field(eosinophils/hpf), and per 10 hpf in the tissue adjacent to the neoplastic epithelium, were counted and tabulated. For statistical purposes, the elevated eosinophils were defined and categorized as: focally and moderately elevated (5–9 eos/hpf), focally and markedly increased(>10/hpf), diffusely and moderately elevated(5–19 eos/10hpf), and diffusely and markedly increased (>20/10hpf). RESULTS: In the invasive carcinoma, eosinophil counts were elevated focally and /or diffusely, more frequently seen than in non-invasive neoplastic lesions. The increased eosinophil counts, specifically >10hpf, and >20/10hpf, were all statistically significantly associated with stromal invasion. Greater than 10 eosinophils/hpf and/or >20 eosinophils/10hpf had highest predictive power, with a sensitivity, specificity and positive predictive value of 82%, 93%, 96% and 80%, 100% and 100%, respectively. Virtually, greater than 20 eosinophils/10 hpf was diagnostic for tumor invasion in our series. CONCLUSION: Our study suggests for the first time that the elevated eosinophil count in squamous neoplasia of the larynx is a morphologic feature associated with tumor invasion. When the number of infiltrating eosinophils exceeds 10/hpf and or >20/10 hpf in a laryngeal biopsy with squamous neoplasia, it represents an indicator for the possibility of tumor invasion. Similarly, the presence of eosinophils meeting these thresholds in an excisional specimen should prompt a thorough evaluation for invasiveness, when evidence of invasion is absent, or when invasion is suspected by conventional criteria in the initial sections

Targeting Mitochondrial Cell Death Pathway to Overcome Drug Resistance with a Newly Developed Iron Chelate

Background: Multi drug resistance (MDR) or cross-resistance to multiple classes of chemotherapeutic agents is a major obstacle to successful application of chemotherapy and a basic problem in cancer biology. The multidrug resistance gene, MDR1, and its gene product P-glycoprotein (P-gp) are an important determinant of MDR. Therefore, there is an urgent need for development of novel compounds that are not substrates of P-glycoprotein and are effective against drug-resistant cancer. Methodology/Principal Findings: In this present study, we have synthesized a novel, redox active Fe (II) complex (chelate), iron N- (2-hydroxy acetophenone) glycinate (FeNG). The structure of the complex has been determined by spectroscopic means. To evaluate the cytotoxic effect of FeNG we used doxorubicin resistant and/or sensitive T lymphoblastic leukemia cells and show that FeNG kills both the cell types irrespective of their MDR phenotype. Moreover, FeNG induces apoptosis in doxorubicin resistance T lymphoblastic leukemia cell through mitochondrial pathway via generation reactive oxygen species (ROS). This is substantiated by the fact that the antioxidant N-acetyle-cysteine (NAC) could completely block ROS generation and, subsequently, abrogated FeNG induced apoptosis. Therefore, FeNG induces the doxorubicin resistant T lymphoblastic leukemia cells to undergo apoptosis and thus overcome MDR. Conclusion/Significance: Our study provides evidence that FeNG, a redox active metal chelate may be a promising ne