Can testosterone replacement decrease the memory problem of old age?

The world is rapidly ageing. It is against this backdrop that there are increasing incidences of dementia reported worldwide, with Alzheimer's disease (AD) being the most common form of dementia in the elderly. It is estimated that AD affects almost 4 million people in the US, and costs the US economy more than 65 million dollars annually. There is currently no cure for AD but various therapeutic agents have been employed in attempting to slow down the progression of the illness, one of which is oestrogen. Over the last decades, scientists have focused mainly on the roles of oestrogen in the prevention and treatment of AD. Newer evidences suggested that testosterone might also be involved in the pathogenesis of AD. Although the exact mechanisms on how androgen might affect AD are still largely unknown, it is known that testosterone can act directly via androgen receptor-dependent mechanisms or indirectly by converting to oestrogen to exert this effect. Clinical trials need to be conducted to ascertain the putative role of androgen replacement in Alzheimer's disease.

Metal ion levels post unilateral primary Exeter total hip replacement

There has been much discussion and controversy in the media recently regarding metal toxicity following large head metal on metal (MoM) total hip replacement (THR). Patients have been reported as having hugely elevated levels of metal ions with, at times, devastating systemic, neurolgical and/or orthopaedic sequelae. However, no direct correlation between metal ion level and severity of metallosis has yet been defined. Normative levels of metal ions in well functioning, non Cobalt-Chrome hips have also not been defined to date. The Exeter total hip replacement contains no Cobalt-Chrome (Co-Cr) as it is made entirely from stainless steel. However, small levels of these metals may be present in the modular head of the prosthesis, and their effect on metal ion levels in the well functioning patient has not been investigated. We proposed to define the “normal” levels of metal ions detected by blood test in 20 well functioning patients at a minimum 1 year post primary Exeter total hip replacement, where the patient had had only one joint replaced. Presently, accepted normal levels of blood Chromium are 10–100 nmol/L and plasma Cobalt are 0–20 nmol/L. The UK Modern Humanities Research Association (MHRA) has suggested that levels of either Cobalt or Chromium above 7 ppb (equivalent to 135 nmol/L for Chromium and 120 nmol/L for Cobalt) may be significant. Below this level it is indicated that significant soft tissue reaction and tissue damage is less likely and the risk of implant failure is reduced. Hips were a mixture of cemented and hybrid procedures performed by two experienced orthopaedic consultants. Seventy percent were female, with a mixture of head sizes used. In our cohort, there were no cases where the blood Chromium levels were above the normal range, and in more than 70% of cases, levels were below recordable levels. There were also no cases of elevated plasma Cobalt levels, and in 35% of cases, levels were negligible. We conclude that the implantation with an Exeter total hip replacement does not lead to elevation of blood metal ion levels.

Clinically-indicated replacement versus routine replacement of peripheral venous catheters

BACKGROUND: US Centers for Disease Control guidelines recommend replacement of peripheral intravenous (IV) catheters no more frequently than every 72 to 96 hours. Routine replacement is thought to reduce the risk of phlebitis and bloodstream infection. Catheter insertion is an unpleasant experience for patients and replacement may be unnecessary if the catheter remains functional and there are no signs of inflammation. Costs associated with routine replacement may be considerable. This is an update of a review first published in 2010. OBJECTIVES: To assess the effects of removing peripheral IV catheters when clinically indicated compared with removing and re-siting the catheter routinely. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases (PVD) Group Trials Search Co-ordinator searched the PVD Specialised Register (December 2012) and CENTRAL (2012, Issue 11). We also searched MEDLINE (last searched October 2012) and clinical trials registries. SELECTION CRITERIA: Randomised controlled trials that compared routine removal of peripheral IV catheters with removal only when clinically indicated in hospitalised or community dwelling patients receiving continuous or intermittent infusions. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Seven trials with a total of 4895 patients were included in the review. Catheter-related bloodstream infection (CRBSI) was assessed in five trials (4806 patients). There was no significant between group difference in the CRBSI rate (clinically-indicated 1/2365; routine change 2/2441). The risk ratio (RR) was 0.61 but the confidence interval (CI) was wide, creating uncertainty around the estimate (95% CI 0.08 to 4.68; P = 0.64). No difference in phlebitis rates was found whether catheters were changed according to clinical indications or routinely (clinically-indicated 186/2365; 3-day change 166/2441; RR 1.14, 95% CI 0.93 to 1.39). This result was unaffected by whether infusion through the catheter was continuous or intermittent. We also analysed the data by number of device days and again no differences between groups were observed (RR 1.03, 95% CI 0.84 to 1.27; P = 0.75). One trial assessed all-cause bloodstream infection. There was no difference in this outcome between the two groups (clinically-indicated 4/1593 (0.02%); routine change 9/1690 (0.05%); P = 0.21). Cannulation costs were lower by approximately AUD 7.00 in the clinically-indicated group (mean difference (MD) -6.96, 95% CI -9.05 to -4.86; P ≤ 0.00001). AUTHORS' CONCLUSIONS: The review found no evidence to support changing catheters every 72 to 96 hours. Consequently, healthcare organisations may consider changing to a policy whereby catheters are changed only if clinically indicated. This would provide significant cost savings and would spare patients the unnecessary pain of routine re-sites in the absence of clinical indications. To minimise peripheral catheter-related complications, the insertion site should be inspected at each shift change and the catheter removed if signs of inflammation, infiltration, or blockage are present. OBJECTIVES: To assess the effects of removing peripheral IV catheters when clinically indicated compared with removing and re-siting the catheter routinely. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases (PVD) Group Trials Search Co-ordinator searched the PVD Specialised Register (December 2012) and CENTRAL (2012, Issue 11). We also searched MEDLINE (last searched October 2012) and clinical trials registries. SELECTION CRITERIA: Randomised controlled trials that compared routine removal of peripheral IV catheters with removal only when clinically indicated in hospitalised or community dwelling patients receiving continuous or intermittent infusions. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Seven trials with a total of 4895 patients were included in the review. Catheter-related bloodstream infection (CRBSI) was assessed in five trials (4806 patients). There was no significant between group difference in the CRBSI rate (clinically-indicated 1/2365; routine change 2/2441). The risk ratio (RR) was 0.61 but the confidence interval (CI) was wide, creating uncertainty around the estimate (95% CI 0.08 to 4.68; P = 0.64). No difference in phlebitis rates was found whether catheters were changed according to clinical indications or routinely (clinically-indicated 186/2365; 3-day change 166/2441; RR 1.14, 95% CI 0.93 to 1.39). This result was unaffected by whether infusion through the catheter was continuous or intermittent. We also analysed the data by number of device days and again no differences between groups were observed (RR 1.03, 95% CI 0.84 to 1.27; P = 0.75). One trial assessed all-cause bloodstream infection. There was no difference in this outcome between the two groups (clinically-indicated 4/1593 (0.02%); routine change 9/1690 (0.05%); P = 0.21). Cannulation costs were lower by approximately AUD 7.00 in the clinically-indicated group (mean difference (MD) -6.96, 95% CI -9.05 to -4.86; P ≤ 0.00001). AUTHORS' CONCLUSIONS: The review found no evidence to support changing catheters every 72 to 96 hours. Consequently, healthcare organisations may consider changing to a policy whereby catheters are changed only if clinically indicated. This would provide significant cost savings and would spare patients the unnecessary pain of routine re-sites in the absence of clinical indications. To minimise peripheral catheter-related complications, the insertion site should be inspected at each shift change and the catheter removed if signs of inflammation, infiltration, or blockage are present.

Isoenergetic replacement of dietary saturated with monounsaturated fat via macadamia nuts enhances endothelial function in overweight subjects

Background & aims: - Excess adiposity (overweight) is one of numerous risk factors for cardiometabolic disease. Most risk reduction strategies for overweight rely on weight loss through dietary energy restriction. However, since the evidence base for long-term successful weight loss interventions is scant, it is important to identify strategies for risk reduction independent of weight loss. The aim of this study was to compare the effects of isoenergetic substitution of dietary saturated fat (SFA) with monounsaturated fat (MUFA) via macadamia nuts on coronary risk compared to usual diet in overweight adults. Methods: - A randomised controlled trial design, maintaining usual energy intake, but manipulating dietary lipid profile in a group of 64 (54 female, 10 male) overweight (BMI > 25), otherwise healthy, subjects. For the intervention group, energy intakes of usual (baseline) diets were calculated from multiple 3 day diet diaries, and SFA was replaced with MUFA (target: 50%E from fat as MUFA) by altering dietary SFA sources and adding macadamia nuts to the diet. Both control and intervention groups received advice on national guidelines for physical activity and adhered to the same protocol for diet diary record keeping and trial consultations. Anthropometric and clinical measures were taken at baseline and at 10 weeks. Results: A significant increase in brachial artery flow-mediated dilation (p < 0.05) was seen in the monounsaturated diet group at week 10 compared to baseline. This corresponded to significant decreases in waist circumference, total cholesterol (p < 0.05), plasma leptin and ICAM-1 (p < 0.01). Conclusions: - In patient subgroups where adherence to dietary energy-reduction is poor, isoenergetic interventions may improve endothelial function and other coronary risk factors without changes in body weight. This trial was registered with the Australia New Zealand Clinical Trial Registry (ACTRN12607000106437).

Galvanic replacement mediated synthesis of hollow Pt nanocatalysts : significance of residual Ag for the H2 evolution reaction

With the increasing popularity of the galvanic replacement approach towards the development of bimetallic nanocatalysts, special emphasis has been focused on minimizing the use of expensive metal (e.g. Pt), in the finally formed nanomaterials (e.g. Ag/Pt system as a possible catalyst for fuel cells). However, the complete removal of the less active sacrificial template is generally not achieved during galvanic replacement, and its residual presence may significantly impact on the electrocatalytic properties of the final material. Here, we investigate the hydrogen evolution reaction (HER) activity of Ag nanocubes replaced with different amounts of Pt, and demonstrate how the bimetallic composition significantly affects the activity of the alloyed nanomaterial.

Galvanic replacement mediated transformation of Ag nanospheres into dendritic Au--Ag nanostructures in the ionic liquid [BMIM][BF4]

We demonstrate an unusual shape transformation of Ag nanospheres into {111}-oriented Au–Ag dendritic nanostructures by a galvanic replacement reaction in the ionic liquid (IL) 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]).

A study of localised galvanic replacement of copper and silver films with gold using scanning electrochemical microscopy

Galvanic replacement represents a highly significant process for the fabrication of bimetallic materials, but to date its application has been limited to either modification of large area metal surfaces or nanoparticles in solution. Here, the localised surface modification of copper and silver substrates with gold through the galvanic replacement process is reported. This was achieved by generation of a localised flux of AuCl4− ions from a gold ultramicroelectrode tip which interacts with the unbiased substrate of interest. The extent of modification with gold can be controlled through the tip–substrate distance and electrolysis time.

Galvanic Replacement of Semiconductor Phase I CuTCNQ Microrods with KAuBr4 to Fabricate CuTCNQ/Au Nanocomposites with Photocatalytic Properties

In this study, the reaction of semiconductor microrods of phase I copper 7,7,8,8-tetracyanoquinodimethane (CuTCNQ) with KAuBr4 in acetonitrile is reported. It was found that the reaction is redox in nature and proceeds via a galvanic replacement mechanism in which the surface of CuTCNQ is replaced with metallic gold nanoparticles. Given the slight solubility of CuTCNQ in acetonitrile, two competing reactions, namely CuTCNQ dissolution and the redox reaction with KAuBr4, were found to operate in parallel. An increase in the surface coverage of CuTCNQ microrods with gold nanoparticles occurred with an increased KAuBr4 concentration in acetonitrile, which also inhibited CuTCNQ dissolution. The reaction progress with time was monitored using UV−visible, FT-IR, and Raman spectroscopy as well as XRD and EDX analysis, and SEM imaging. The CuTCNQ/Au nanocomposites were investigated for their photocatalytic properties, wherein the destruction of Congo red, an organic dye, by simulated solar light was found dependent on the surface coverage of gold nanoparticles on the CuTCNQ microrods. This method of decorating CuTCNQ may open the possibility of modifying this and other metal-TCNQ charge transfer complexes with a host of other metals which may have significant applications.

Synthesis of CuTCNQ/Au microrods by galvanic replacement of semiconducting phase I CuTCNQ with KAuBr4 in aqueous medium

The spontaneous reaction between microrods of an organic semiconductor molecule, copper 7,7,8,8-tetracyanoquinodimethane (CuTCNQ) with [AuBr4]− ions in an aqueous environment is reported. The reaction is found to be redox in nature which proceeds via a complex galvanic replacement mechanism, wherein the surface of the CuTCNQ microrods is replaced with metallic gold nanoparticles. Unlike previous reactions reported in acetonitrile, the galvanic replacement reaction in aqueous solution proceeds via an entirely different reaction mechanism, wherein a cyclical reaction mechanism involving continuous regeneration of CuTCNQ consumed during the galvanic replacement reaction occurs in parallel with the galvanic replacement reaction. This results in the driving force of the galvanic replacement reaction in aqueous medium being largely dependent on the availability of [AuBr4]− ions during the reaction. Therefore, this study highlights the importance of the choice of an appropriate solvent during galvanic replacement reactions, which can significantly impact upon the reaction mechanism. The reaction progress with respect to different gold salt concentration was monitored using Fourier transform infrared (FT-IR), Raman, and X-ray photoelectron spectroscopy (XPS), as well as XRD and EDX analysis, and SEM imaging. The CuTCNQ/Au nanocomposites were also investigated for their potential photocatalytic properties, wherein the destruction of the organic dye, Congo red, in a simulated solar light environment was found to be largely dependent on the degree of gold nanoparticle surface coverage. The approach reported here opens up new possibilities of decorating metal–organic charge transfer complexes with a host of metals, leading to potentially novel applications in catalysis and sensing.

A study of the galvanic replacement reaction at surfaces and the role of lateral charge propagation

The galvanic replacement of isolated nanostructures of copper and silver on conducting supports as well as continuous films of copper with gold is reported. The surface morphology was characterized by scanning electron microscopy and the replacement with gold was confirmed by EDX analysis. It was found that lateral charge propagation during the replacement reaction had a significant effect in all cases. For the isolated nanostructures the deposition of gold was observed not only at the sacrificial template but also at the surrounding unmodified areas of the conducting substrate. In the case of copper films the role of lateral charge propagation was also confirmed by connecting it to an ITO electrode through an external circuit upon which gold deposition was also observed to occur. Interestingly, by inhibiting the rate of charge propagation, through the introduction of a series resistor, the morphology of gold on the copper substrate could be changed from discrete surface decoration with cube like nanoparticles to a more porous rough surface.

Lateral charge propagation effects during the galvanic replacement of electrodeposited MTCNQ (M= Cu, Ag) microstructures with gold and its influence on catalysed electron transfer reactions

The galvanic replacement of isolated electrodeposited semiconducting CuTCNQ microstructures on a glassy carbon (GC) substrate with gold is investigated. It is found that anisotropic metal nanoparticles are formed which are not solely confined to the redox active sites on the semiconducting materials but are also observed on the GC substrate which occurs via a lateral charge propagation mechanism. We also demonstrate that this galvanic replacement approach can be used for the formation of isolated AgTCNQ/Au microwire composites which occurs via an analogous mechanism. The resultant MTCNQ/Au (M = Cu, Ag) composite materials are characterized by Raman, spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and investigated for their catalytic properties for the reduction of ferricyanide ions with thiosulphate ions in aqueous solution. Significantly it is demonstrated that gold loading, nanoparticle shape and in particular the MTCNQ–Au interface are important factors that influence the reaction rate. It is shown that there is a synergistic effect at the CuTCNQ/Au composite when compared to AgTCNQ/Au at similar gold loadings.

Multi-criteria optimization of group replacement schedules for distributed water pipeline assets

This thesis presents a multi-criteria optimisation study of group replacement schedules for water pipelines, which is a capital-intensive and service critical decision. A new mathematical model was developed, which minimises total replacement costs while maintaining a satisfactory level of services. The research outcomes are expected to enrich the body of knowledge of multi-criteria decision optimisation, where group scheduling is required. The model has the potential to optimise replacement planning for other types of linear asset networks resulting in bottom-line benefits for end users and communities. The results of a real case study show that the new model can effectively reduced the total costs and service interruptions.

Clinical and radiographic outcomes of acetabular impaction grafting without cage reinforcement for revision hip replacement : a minimum ten-year follow-up study

Impaction bone grafting for reconstitution of bone stock in revision hip surgery has been used for nearly 30 years. We used this technique, in combination with a cemented acetabular component, in the acetabula of 304 hips in 292 patients revised for aseptic loosening between 1995 and 2001. The only additional supports used were stainless steel meshes placed against the medial wall or laterally around the acetabular rim to contain the graft. All Paprosky grades of defect were included. Clinical and radiographic outcomes were collected in surviving patients at a minimum of 10 years following the index operation. Mean follow-up was 12.4 years (SD 1.5; range 10.0-16.0). Kaplan-Meier survivorship with revision for aseptic loosening as the endpoint was 85.9% (95% CI 81.0 to 90.8%) at 13.5 years. Clinical scores for pain relief remained satisfactory, and there was no difference in clinical scores between cups that appeared stable and those that appeared loose radiographically.

Replacement of healthcare-associated MRSA by community-associated MRSA in Queensland : confirmation by genotyping

Objective To describe the changing prevalence of healthcare- and community-associated MRSA. Methods Susceptibility phenotypes of MRSA were observed from 2000 to 2012 using routine susceptibility data. Phenotypic definitions of major clones were validated by genotyping isolates from a nested period prevalence survey in 2011. Results The predominant healthcare-associated (AUS-2/3 like) MRSA phenotype decreased from 42 to 14 isolates per million occasions of service in outpatients (P < 0.0001) and from 650 to 75 isolates per million accrued patient days in inpatients (P 0.0005), while the respective rates of the healthcare-related EMRSA-15 like phenotype increased from 1 to 19 in outpatients (P < 0.0001) and from 11 to 83 in inpatients (P < 0.0001) and those of the community-associated MRSA phenotype increased from 17 to 296 in outpatients (P < 0.0001) and from 71 to 486 in inpatients (P < 0.0001). When compared with single nucleotide polymorphism genotyping the AUS-2/3 like phenotype had a sensitivity and positive predictive value (PPV) for CC239 of 1 and 0.791 respectively, while the EMRSA-15 like phenotype had a sensitivity and PPV for CC22 of 0.903 and 0.774. PVL-positive CA-MRSA, predominantly ST93 and CC30, accounted for 60.8% of MRSA, while PVL-negative CA-MRSA, mainly CC5 and CC1, accounted for 21.4%. Conclusions The initially dominant healthcare-associated MRSA clone has been progressively replaced, mainly by four community-associated lineages.