Effect of Vegetable Based Lubricants on Equal Channel Angular Extrusion Pressure

This research aimed at investigating vegetable based lubricant as a replacement for chemical based lubricants on extrusion pressure of equal channel angular extrusion of Aluminum. In the process, aluminum alloy (Al 6063) was heated at 350°C for one hour, machined and cut to billets size of 11.95 m x 11.95 m x 40 m (l × b × h). The billets were extruded through die of 12 mm x 12 mm channel cross-section area, the channel angle was 60°. Four vegetable based lubricants namely jatropha, neem, castor and cotton seed oils were used. The die was centrally located on the bed of vertical hydraulic testing machine and the billet was inserted into the entrance channel. Lubrication was applied to the billet to decrease its friction and with the channel inner wall. The ram displacement per plunger speed was 1 mm per 1 second respectively. For each lubricant, four samples were extruded through ECAE die to confirm the repeatability of the results and the average values of the extrusion pressure were computed. The results were compared to the sample extruded via conventional lubricants. It was discovered of all the extruded samples, jatropha oil gave the least extrusion pressure of 83 kN, cottonseed oil extruded at 104 kN and castor oil at 151.4 kN while neem oil require the highest pressure at 220.9 kN. The chemical based lubricants that serve as the control from the literature gave the extrusion pressure of 81 kN. It can be concluded that the oil from jatropha seed is the best in terms of extrusion pressure and can effectively replace the chemical based lubricants

Efficacy of DOPE/DC-cholesterol liposomes and GCPQ micelles as AZD6244 nanocarriers in a 3D colorectal cancer in vitro model

Aim: In this work, we use cationic organic nanocarriers as chemotherapy delivery platforms and test them in a colorectal cancer 3D in vitro model. Materials & methods: We used 3beta-(N-[N′,N′-dimethylaminoethane]carbamoyl])cholesterol (DC-chol) and dioleoylphosphatidylethanolamine (DOPE) liposomes and N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) micelles, to deliver AZD6244, a MEK inhibitor, to HCT116 cells cultured as monolayers and in 3D in vitro cancer models (tumoroids). Results: Nanoparticle-mediated drug delivery was superior to the free drug in monolayer experiments and despite their therapeutic effect being hindered by poor diffusion through the cancer mass, GCPQ micelles were also superior in tumoroids. Conclusion: These results support the role of nanoparticles in improving drug delivery and highlight the need to include 3D cancer models in early phases of drug development

Efficacy of DOPE/DC-cholesterol liposomes and GCPQ micelles as AZD6244 nanocarriers in a 3D colorectal cancer in vitro model

AIM: In this work, we use cationic organic nanocarriers as chemotherapy delivery platforms and test them in a colorectal cancer 3D in vitro model. MATERIALS & METHODS: We used 3beta-(N-[N',N'-dimethylaminoethane]carbamoyl])cholesterol (DC-chol) and dioleoylphosphatidylethanolamine (DOPE) liposomes and N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) micelles, to deliver AZD6244, a MEK inhibitor, to HCT116 cells cultured as monolayers and in 3D in vitro cancer models (tumoroids). RESULTS: Nanoparticle-mediated drug delivery was superior to the free drug in monolayer experiments and despite their therapeutic effect being hindered by poor diffusion through the cancer mass, GCPQ micelles were also superior in tumoroids. CONCLUSION: These results support the role of nanoparticles in improving drug delivery and highlight the need to include 3D cancer models in early phases of drug development

Health economic burden that wounds impose on the National Health Service in the UK

OBJECTIVE: To estimate the prevalence of wounds managed by the UK's National Health Service (NHS) in 2012/2013 and the annual levels of healthcare resource use attributable to their management and corresponding costs. METHODS: This was a retrospective cohort analysis of the records of patients in The Health Improvement Network (THIN) Database. Records of 1000 adult patients who had a wound in 2012/2013 (cases) were randomly selected and matched with 1000 patients with no history of a wound (controls). Patients' characteristics, wound-related health outcomes and all healthcare resource use were quantified and the total NHS cost of patient management was estimated at 2013/2014 prices. RESULTS: Patients' mean age was 69.0 years and 45% were male. 76% of patients presented with a new wound in the study year and 61% of wounds healed during the study year. Nutritional deficiency (OR 0.53; p<0.001) and diabetes (OR 0.65; p<0.001) were independent risk factors for non-healing. There were an estimated 2.2 million wounds managed by the NHS in 2012/2013. Annual levels of resource use attributable to managing these wounds and associated comorbidities included 18.6 million practice nurse visits, 10.9 million community nurse visits, 7.7 million GP visits and 3.4 million hospital outpatient visits. The annual NHS cost of managing these wounds and associated comorbidities was pound5.3 billion. This was reduced to between pound5.1 and pound4.5 billion after adjusting for comorbidities. CONCLUSIONS: Real world evidence highlights wound management is predominantly a nurse-led discipline. Approximately 30% of wounds lacked a differential diagnosis, indicative of practical difficulties experienced by non-specialist clinicians. Wounds impose a substantial health economic burden on the UK's NHS, comparable to that of managing obesity ( pound5.0 billion). Clinical and economic benefits could accrue from improved systems of care and an increased awareness of the impact that wounds impose on patients and the NHS.Ye

PHYTOCHEMICAL EVALUATION BY GC-MS ANALYSIS OF THE SEEDS OF MUCUNA FLAGELLIPES EXTRACT.

Mucuna flagellipes seeds were analyzed for essential oil composition. The ethanol extract of the seeds was subjected for GC-MS studies. Ten phyto-constituents were identified from M. flagellipes comprising 60 % of esters and 30 % of carboxylic acids and 10 % hydrocarbon. 9-octadecenoic acid, ethyl ester constitutes the bulk of the oil (18.66 %), followed by linoleic acid, ethyl ester (16.99 %) and a carboxylic acid, 9-octadecanoic acid (16.71%).  Other Compounds identified in the seeds were hexadecanoic acid (11.14 %), ethyl hexadecanoate (14.76 %), ethyl octadecanoate (4.18 %), Eicosanoic acid (1.39 %), ethyl icosanoate (0.84%), 3-hydroxypropyl-9-octadecenoate (1.11 %) and 9-methylbicyclo (3,3,1) nonane (14.21%). The presence of many esters  in the seeds may be the reason the seeds enhance the aroma of  soup. These compounds present in the plant made it possible for the use of M. flagellipes seed extract in phytomedicine in Nigeria for the treatment of different ailments. Key words : Mucuna, ester, phytomedicine, ailment

A nano-enabled cancer-specific ITCH RNAi chemotherapy booster for pancreatic cancer

UNLABELLED: Gemcitabine is currently the standard therapy for pancreatic cancer. However, growing concerns over gemcitabine resistance mean that new combinatory therapies are required to prevent loss of efficacy with prolonged treatment. Here, we suggest that this could be achieved through co-administration of RNA interference agents targeting the ubiquitin ligase ITCH. Stable anti-ITCH siRNA and shRNA dendriplexes with a desirable safety profile were prepared using generation 3 poly(propylenimine) dendrimers (DAB-Am16). The complexes were efficiently taken up by human pancreatic cancer cells and produced a 40-60% decrease in ITCH RNA and protein expression in vitro (si/shRNA) and in a xenograft model of pancreatic cancer (shRNA). When co-administered with gemcitabine (100 mg/kg/week) at a subtherapeutic dose, treatment with ITCH-shRNA (3x 50 mg/week) was able to fully suppress tumour growth for 17 days, suggesting that downregulation of ITCH mediated by DAB-Am16/shRNA sensitizes pancreatic cancer to gemcitabine in an efficient and specific manner. FROM THE CLINICAL EDITOR: Gemcitabine delivery to pancreatic cancer often results in the common problem of drug resistance. This team overcame the problem through co-administration of siRNA and shRNA dendriplexes targeting the ubiquitin ligase ITCH

Experimental analytical design of CNC machine tool SCFC based on electro-pneumatic system simulation

AbstractA Smart Clamping Force Control (SCFC) is adapted to hold sensitive workpiece using magnetic proximity switch during a machining operation on the CNC machine tool. It has been ascertained that work-holding of different workpiece materials and shapes during machining operation is one of the problems encountered during CNC milling machining operations. This work proposes a novel clamping strategy for workpieces with the aid of SCFC. The purpose of the study is to adjust the forward movement of the clamp and reduce the damage caused by the clamp on the workpiece, this depends on the material of the work-piece. The speed of the clamp is reduced using the inlet flow control throttle valve and a magnetic proximity switch (MPS). It provides careful handling of workpiece and prevent it from damage and as well optimizes the forward movement of the cylinder. The proposed strategy is based on dynamic machine loading in which the impact of applied forces were monitored to optimize the clamping control system of the machine tool. The mode of operation and performance of the SCFC were simulated in the FluidSIM® software, and the validated results was presented on Festo workstation. This work therefore further elucidate the fundamental design criterion for machine tool clamping forces and the sustainable manufacture of its components

Surface enhanced deep Raman detection of cancer tumour through 71 mm of heterogeneous tissue

Detection of solid tumours through tissue− from depths relevant to humans− has been a significant challenge for biomedical Raman spectroscopy. The combined use of surface enhanced Raman scattering (SERS) imaging agents with deep Raman spectroscopy (DRS), i.e., surface enhanced deep Raman spectroscopy (SEDRS), offer prospects for overcoming such obstacles. In this study, we investigated the maximum detection depth through which the retrieval of SERS signal of a passively targeted biphenyl-4-thiol tagged gold nanoparticle (NP) imaging agent, injected subcutaneously into a mouse bearing breast cancer tumour, was possible. A compact 830 nm set-up with a hand-held probe and the flexibility of switching between offset, transmission and conventional Raman modalities was developed for this study. In vivo injection of the above SERS NP primary dose allowed surface tumour detection, whereas additional post mortem NP booster dose was required for detection of deeply seated tumours through heterogeneous animal tissue (comprising of proteins, fat, bone, organs, blood, and skin). The highest detection depth of 71 mm was probed using transmission, translating into a ∼40% increase in detection depth compared to earlier reports. Such improvements in detection depth along with the inherent Raman chemical sensitivity brings SEDRS one step closer to future clinical cancer imaging technology

Lomustine Nanoparticles Enable Both Bone Marrow Sparing and High Brain Drug Levels – A Strategy for Brain Cancer Treatments

Purpose The blood brain barrier compromises glioblastoma chemotherapy. However high blood concentrations of lipophilic, alkylating drugs result in brain uptake, but cause myelosuppression. We hypothesised that nanoparticles could achieve therapeutic brain concentrations without dose-limiting myelosuppression. Methods Mice were dosed with either intravenous lomustine Molecular Envelope Technology (MET) nanoparticles (13 mg kg-1) or ethanolic lomustine (6.5 mg kg-1) and tissues analysed. Efficacy was assessed in an orthotopic U-87 MG glioblastoma model, following intravenous MET lomustine (daily 13 mg kg-1) or ethanolic lomustine (daily 1.2 mg kg-1 - the highest repeated dose possible). Myelosuppression and MET particle macrophage uptake were also investigated. Results The MET formulation resulted in modest brain targeting (brain/ bone AUC0-4h ratios for MET and ethanolic lomustine = 0.90 and 0.53 respectively and brain/ liver AUC0-4h ratios for MET and ethanolic lomustine = 0.24 and 0.15 respectively). The MET formulation significantly increased mice (U-87 MG tumours) survival times; with MET lomustine, ethanolic lomustine and untreated mean survival times of 33.2, 22.5 and 21.3 days respectively and there were no material treatment-related differences in blood and femoral cell counts. Macrophage uptake is slower for MET nanoparticles than for liposomes. Conclusions Particulate drug formulations improved brain tumour therapy without major bone marrow toxicity

Early Economic Evaluation of Diagnostic Technologies: Experiences of the NIHR Diagnostic Evidence Co-operatives

Diagnostic tests are expensive and time-consuming to develop. Early economic evaluation using decision modeling can reduce commercial risk by providing early evidence on cost-effectiveness. The National Institute for Health Research Diagnostic Evidence Co-operatives (DECs) was established to catalyze evidence generation for diagnostic tests by collaborating with commercial developers; DEC researchers have consequently made extensive use of early modeling. The aim of this article is to summarize the experiences of the DECs using early modeling for diagnostics. We draw on 8 case studies to illustrate the methods, highlight methodological strengths and weaknesses particular to diagnostics, and provide advice. The case studies covered diagnosis, screening, and treatment stratification. Treatment effectiveness was a crucial determinant of cost-effectiveness in all cases, but robust evidence to inform this parameter was sparse. This risked limiting the usability of the results, although characterization of this uncertainty in turn highlighted the value of further evidence generation. Researchers evaluating early models must be aware of the importance of treatment effect evidence when reviewing the cost-effectiveness of diagnostics. Researchers planning to develop an early model of a test should also 1) consult widely with clinicians to ensure the model reflects real-world patient care; 2) develop comprehensive models that can be updated as the technology develops, rather than taking a “quick and dirty” approach that may risk producing misleading results; and 3) use flexible methods of reviewing evidence and evaluating model results, to fit the needs of multiple decision makers. Decision models can provide vital information for developers at an early stage, although limited evidence mean researchers should proceed with caution