Development of Graphene Nanostructures for Use in Anti-cancer Nanomedicine

Nanomedicine utilises biocompatible nanomaterials for therapeutic as well as imaging purposes, for the treatment of various diseases including cancer, neurological disorders and wound infections. Graphene, a material composed of a single layer of carbon atoms, has recently shown great potential to improve diagnostics and therapeutics, owing to its small size, large surface-area-to-volume ratio and unique physicochemical properties. However, the limited fabrication, in vitro and in vivo functionalities published in the literature indicate inconsistencies regarding the factors affecting metabolic fate, biodistribution as well as toxicity patterns of graphene. This thesis focuses on the biological effects of graphene-based materials, including graphene oxide (GO), reduced graphene oxide (rGO), graphene nanopores (GNPs), graphene quantum dots (GQDs) and three-dimensional graphene foam (GF). These can be used to closely mimic therapeutic functions and thereby open up new pathways to anticancer nanomedicine. In this work, a biocompatible GO-based anti-metastatic enzyme cancer therapy approach has been introduced for the first time to target the extracellular pro-metastatic and pro- tumourigenic enzymes of cathepsin D and cathepsin L, which are typically overexpressed in ovarian and breast cancers. Definitive binding and modulation of cathepsin- D and -L with GO has revealed that both of the enzymes were adsorbed onto the surface of GO through its cationic and hydrophilic residues under the biologically relevant condition of acidic pH. It has been demonstrated that low concentrations of rGO were shown to significantly produce late apoptosis and necrosis rather than early apoptotic events in lung cancer cells (A549 and SKMES-1), suggesting that it was able to disintegrate the cellular membranes in a dose-dependent manner. GNPs at lower concentrations (250µg/ml) induce upregulation of phosphatidylserine on cell surface membrane (i.e. early apoptotic event), which does not significantly disintegrate the cell membrane in the aforementioned lung cancer cells, while higher concentrations of GNPs (5 and 15 mg/kg) in rats (when intraperitoneally injected) exhibited sub-chronic toxicity in a period of 27 days. The interaction of GQDs and trypsin has revealed the strong bonding capacity of GQDs with trypsin, owing to their surface charge and surface functionalities evidencing the high bioavailability of GQDs in enzyme engineering. Finally, 3D GF was developed to probe the role of graphene-based scaffold cues in the field of regenerative medicine revealing their cell attachment to in vitro cell cultures. Furthermore, GF was shown to maintain remarkable biocompatibility with in vitro and in vivo toxicity screening models when exposed for 7 days at doses of 5, 10 and 15 mg/l. Taken together, graphene and its modified structures developed in this thesis promise to revolutionise clinical settings across the board in nanomedicine which include, but are not limited to, ultra-high sensitive enzyme adsorbents, high throughput biosensors, enzyme modulators and smart scaffolds for tissue regeneration.EPSRC Centre for Doctoral Training in Metamaterials, XM2 (Grant no. EP/L015331/1) the University Of Exeter EX4, United Kingdom

Corrosion trends of Ti based Shape Memory Alloys having biomedical applications: A perspective study

Ti-based shape memory alloys (SMAs) have been investigated as materials for medical devices and as a biomaterial that can be implanted in a living system as an alternative of any part. The behavior of such materials is evaluated by its activity, corrosion resistance, stability and compatibility with the living body. The direction of this paper is to deliver a brief description of the trends of corrosion in these materials. Titanium (Ti) shows satisfactory resistance to corrosion in natural and acidic environment but it has a trend toward corrosion in reducing acids. The shape memory alloys based on Ti are much favorable corrosion resistant materials to use in reducing acids. Normally human body fluid is analogous to a solution of about 0.9% NaCl which has a pH value 7.4. During surgery this value can be changed, with an increase of 7.8 and then dropping it to 5.5. Later some days the standard pH value of 7.4 can be re-gained. To evaluate corrosion rate of Ti based shape memory alloys in human body fluid, 0.9% NaCl solution was used as a medium. The basics of the shape memory material i.e. the mechanisms for shape memory, the shape memory effect and characterization of the evaluation of corrosion in systems based on Ti shape memory alloy is also reviewed in this article

Autologous whole blood injection in chronic plantar fasciitis: a prospective clinical study

Background: Plantar fasciitis represents painful inflammatory process of plantar fascia with pain beneath the heel. The disease is frustrating for both the patient and the physician as the etiology is unknown. Conservative management is the mainstay of treatment. Patients with resistant pain can be treated with local injections. In this study we evaluated the effectiveness of autologous whole blood injection for treatment of chronic plantar fasciitis.Methods: The study was conducted on 55 patients (males=25, females=30) with chronic heel pain for more than 6 months and failed conservative treatment. After proper clinical evaluation and diagnosis, autologous whole blood was injected on medial aspect of heel at the most tender point. Visual analog score was noted before injection and at 3 and 6 months of follow-up.Results: Mean preprocedure visual analog score was 8.2 (range=4-10), which reduced to a mean of 4.5 (range=0-9) at 3 month follow-up and 3.3 (range 0-9) at 6 month follow-up. The reduction in VAS score was statistically significant (p<0.001). No complications occurred in our series.Conclusions: Autologous whole blood injections appear to be cost-effective for treatment of resistant plantar fasciitis with no serious side effects.

Treatment of Complex Fistula in Ano with Cable-Tie Seton: A Prospective Case Series

Objective. To determine the fecal incontinence and recurrence rate in patients with complex fistula in ano managed with cable tie seton at a tertiary care teaching hospital. Methods. This is a prospective case series of patients with complex anal fistula i.e. recurrent fistula or encircling >30% of external anal sphincter, managed with cable tie seton from March 2003 to March 2009. Patients were seen in the clinic after 72 hours of seton insertion under anesthesia and then every other week. Each time the cable-tie was tightened if found loose without anesthesia and incontinence was inquired according to wexner's score. Results. Seventy nine patients were treated during the study period with the age (mean ± standard deviation) of 41 ± 10.6 years and. The seton was tightened with a median of six times (3–15 times range). Complete healing was achieved in 11.2 ± 5.7 weeks. All the patients were followed for a minimum period of one year and none of the patients had any incontinence. Recurrence was found in 4 (5%) patients. Conclusion. The cable tie seton is safe, cost effective and low morbidity option for the treatment of complex fistulae-in-ano. It can, therefore, be recommended as the standard of treatment for complex fistulae-in-ano requiring the placement of a seton

Biocompatibility behavior and biomedical applications of Ti-Ni based shape memory alloys: a brief review

Shape memory alloys provide new areas for the design of biomaterials in biomedical engineering and also for the design of artificial hard tissues and surgical instruments, since they have definite distinctiveness and remarkable characteristics. This study will look at the biocompatibility behavior of Ti-Ni based shape memory alloys and its medical applications with high possible for improving the present and future quality of bioengineering. In particular, the biocompatibility behavior, vivo and vitro corrosion analysis, histological studies of tissues, vitro and vivo cytotoxicity and applications of Ti-Ni based shape memory alloys in the fields of Cardiovascular, Gastroenterology and Urology, Orthopedics and bone-related purposes have been discussed in this paper

Measuring Coverage in MNCH: Challenges in Monitoring the Proportion of Young Children with Pneumonia Who Receive Antibiotic Treatment

Pneumonia remains a major cause of child death globally, and improving antibiotic treatment rates is a key control strategy. Progress in improving the global coverage of antibiotic treatment is monitored through large household surveys such as the Demographic and Health Surveys (DHS) and the Multiple Indicator Cluster Surveys (MICS), which estimate antibiotic treatment rates of pneumonia based on two-week recall of pneumonia by caregivers. However, these survey tools identify children with reported symptoms of pneumonia, and because the prevalence of pneumonia over a two-week period in community settings is low, the majority of these children do not have true pneumonia and so do not provide an accurate denominator of pneumonia cases for monitoring antibiotic treatment rates. In this review, we show that the performance of survey tools could be improved by increasing the survey recall period or by improving either overall discriminative power or specificity. However, even at a test specificity of 95% (and a test sensitivity of 80%), the proportion of children with reported symptoms of pneumonia who truly have pneumonia is only 22% (the positive predictive value of the survey tool). Thus, although DHS and MICS survey data on rates of care seeking for children with reported symptoms of pneumonia and other childhood illnesses remain valid and important, DHS and MICS data are not able to give valid estimates of antibiotic treatment rates in children with pneumonia

A COMPARATIVE STUDY OF MECHANICAL PROPERTIES AND MICROSTRUCTURES OF DEFORMED BARS (GRADE-60) LOCALLY MANUFACTURED IN PAKISTAN

The MS deformed bars are widely used in construction, housing, bridges, flyovers, dams etc. And often the properties claimed by the industries may or may not be compatible with ASTM Standards. In order to check their compatibility with ASTM standards, MS deformed bar samples of Grade 60 of one inch (25 mm) diameter of five different companies were taken from open market. As One of Pakistan's popular examples of consistent business success has been the stainless steel and mild steel production. The hypothesis explored in this paper is that meeting such standards requires greater properties, both among producers as well as mechanical properties obtained by Tensometer and Universal Hydralic Tensile Machine. The study draws on qualitative data to examine either how much difference or similarity is drawn within samples of various industries. And these samples were coded as S-1, S-2, S-3, S-4 and S-5. First of all composition was determined by using Optical Spectrometer then Tensile performed at universal hydraulic Testing Machine and time load graphs were taken as this test is commercially used, and also Tensile was performed on Tensometer at laboratory level and Stress-Strain graph was obtained and calculated. It was concluded that the experimental results of most of the industries were in good agreement with ASTM but only a few did not show compatibility with ASTM standards

Explaining the diffusion of energy-efficient lighting in India : a technology innovation systems approach

Electricity consumption from lighting accounts for about 15% of total power demand and 5−6% of greenhouse gas emissions in developing countries. It is therefore a promising avenue to achieve considerable energy savings through technological innovation and upgrading. India has been very successful in recent years with a nationwide roll-out of modern light-emitting diode (LED) applications. This study uses the framework of technology innovation systems to identify the actors, institutions, and processes behind the diffusion of this technology. Our findings indicate that national innovation strategies, along with low-carbon technology (LCT) transfer policies, helped to bring down the cost of LED lamps in a rapidly expanding domestic market. Based on the findings, we further explore lessons for broader issues of low-carbon technology transfer and suggest an emerging intermediate step between north−south and south−south technology transfer

Iatrogenic trauma following percutaneous and minimally invasive surgical interventions

Technological progress has changed the landscape of surgical practice. Minimally invasive surgery (MIS) and percutaneous interventions (PC) are constantly replacing open procedures. This reduces hospital stay and allows quicker recovery. The application of MIS should follow the good medical practice dictum by Hippocrates i.e. First do no harm . To remain abreast with new procedures, the medical personnel are required to update and enhance their knowledge and skill. To ensure safety, the innovations are rigorously tested and tried. The learning curve of MIS is shortened by simulator training and proctorship. Credentialing processes are in place to enhance safe delivery of care. Despite of all these measures MIS and PCI are associated with adverse effects. The purpose of this article is to overview the iatrogenic trauma associated with MIS and PCI in major surgical subspecialties