Community-onset Escherichia coli infection resistant to expanded- spectrum cephalosporins in low-prevalence countries

Background
By global standards the prevalence of community onset expanded-spectrum cephalosporin resistant Escherichia coli (ESC-R-EC) remains low in Australia and New Zealand. Of concern, our countries are in a unique position with high extramural resistance pressure from close population and trade links to Asia-Pacific neighbours with high ESC-R-EC rates. We aim to characterize the risks and dynamics of community onset ESC-R-EC in our low-prevalence region.

Methods
A case-control methodology was used. Patients with ESC-R-EC or susceptible E. coli isolated from blood or urine were recruited at six geographically dispersed tertiary hospitals in Australia and New Zealand. Epidemiological data was prospectively collected and bacteria were retained for analysis.

Results
In total, 182 patients (91 cases and 91 controls) were recruited. Multivariate logistic regression identified risk factors for ESC-R amongst E. coli including birth on the Indian subcontinent (OR=11.13, 2.17-56.98, p=0.003), urinary tract infection in the past year (per infection OR=1.430, 1.13-1.82, p=0.003), travel to South East Asia, China, Indian subcontinent, Africa and the Middle East (OR=3.089, 1.29-7.38, p=0.011), prior exposure to trimethoprim+/-sulfamethoxazole &/or an expanded-spectrum cephalosporin (OR=3.665, 1.30-10.35, p=0.014) and healthcare exposure in the previous six months (OR=3.16, 1.54-6.46, p=0.02).

Amongst our ESC-R-EC the blaCTX-M ESBLs was dominant (83% of ESC-R-EC), and the worldwide pandemic clone ST-131 was frequent (45% of ESC-R-EC).

Conclusion
In our low prevalence setting, ESC-R amongst community onset E. coli may be associated with both ‘export’ from healthcare facilities into the community and direct ‘import’ into the community from high-prevalence regions.

Improved fracture toughness of fire resistant composites through rapid curing

A study on the effect of material and fracture properties of phenolic composites cured with reduced thermal cycle times. These reductions were achieved using various techniques. The work highlights significant reductions in manufacturing times are possible for this group of materials and conveniently can also lead to improved properties.

Patient engagement strategies used for hypertension and their influence on self-management attributes

Background. Several effective methods to facilitate patient self-management of hypertension are available in primary care. These include direct support from community pharmacists and general practice, and the use of home blood pressure (BP) monitoring. The aim of this study is to establish the prevalence of use of key strategies and to determine their independent relationship with patient self-management attributes.

Methods. A survey of patients with treated hypertension was undertaken in 27 community pharmacies. This established recent use of BP monitoring and advice from health professionals. Patient awareness of BP and targets, appropriateness of BP targets and adherence to anti-hypertensive medications were assessed as indicative self-management outcomes. Predictors of outcomes were determined using binary logistic regression.

Results. Overall, 215 surveys were returned. Two-thirds of patients were aged >65 years, and 45% had conditions warranting tighter BP control (<130/80 mmHg). Almost all patients reported monitoring of their BP in the previous year and 63% could report their most recent BP reading. Just 36% reported knowing a target BP, and 78% of reported targets were within guidelines recommendations. One-fifth (22%) monitored their own BP, and 15% reported non-adherence to medication. Doctors provided the large majority of professional advice. Self-monitoring or documentation of BP readings was independently associated with increased likelihood of BP and target BP being known.

Conclusions. Regular monitoring of BP does not automatically translate to professional advice. Increased uptake of patient self-monitoring should be promoted as a means of enabling self-management.

ATP7A transgenic and nontransgenic mice are resistant to high copper exposure

The protein affected in Menkes disease, ATP7A, is a copper (Cu)-transporting P-type ATPase that plays an important role in Cu homeostasis, but the full extent of this role has not been defined at a systemic level. Transgenic mice that overexpress the human ATP7A from the chicken β-actin composite promoter (CAG) were used to further investigate the physiological function of ATP7A. Overexpression of ATP7A in the mice caused disturbances in Cu homeostasis, with depletion of Cu in some tissues, especially the heart. To investigate the effect of overexpression of ATP7A when dietary Cu intake was markedly increased, normal and transgenic mice were exposed to drinking water containing 300 mg/L of Cu as Cu acetate for 3 mo. Cu exposure resulted in partial restoration of heart Cu concentrations in male transgenic mice. Despite the extended period of Cu exposure, Cu concentrations in the liver remained relatively unaffected, with a significant increase in male nontransgenic mice. Liver pathology was unremarkable except for small areas of fibrosis that were detected only in livers of the Cu-exposed transgenic mice. Intracellular localization of ATP7A in various tissues was not affected by Cu exposure. Plasma Cu concentration and ceruloplasmin oxidase activity were reduced in both Cu-exposed transgenic and nontransgenic mice. The expression levels of other candidate Cu homeostatic proteins, endogenous Atp7b, ceruloplasmin, Ctr1, and transgenic ATP7A were not altered significantly by Cu exposure. Overall, mice are remarkably resistant to high Cu loads and the overexpression of ATP7A has only moderate effects on the response to Cu exposure. © 2008 American Society for Nutrition.

Studies of a wear resistant cast iron

 The objective of this investigation was to set down (on the base of the results obtained by the examination of white cast iron alloys with different content of the alloying elements) a correlation between chemical composition and microstructure, on one hand, and the properties relevant for this group of materials, i.e., abrasion wear resistance and fracture toughness, on the other. Experimental results indicate that the volume fracture of the carbide phase, carbide size and distribution, as well as the morphology of eutectic colonies, had an important influence on the wear resistance of white cast iron alloys under low-stress abrasion conditions, whereas fracture toughness was determined largely by the matrix microstructure.

Postexercise muscle glycogen resynthesis in obese insulin-resistant Zucker rats

We determined the effect of an acute bout of swimming (8 × 30 min) followed by either carbohydrate administration (0.5 mg/g glucose ip and ad libitum access to chow; CHO) or fasting (Fast) on postexercise glycogen resynthesis in soleus muscle and liver from female lean (ZL) and obese insulin-resistant (ZO) Zucker rats. Resting soleus muscle glycogen concentration ([glycogen]) was similar between genotypes and was reduced by 73 (ZL) and 63% (ZO) after exercise (P < 0.05). Liver [glycogen] at rest was greater in ZO than ZL (334 ± 31 vs. 247 ± 16 μmol/g wet wt; P < 0.01) and fell by 44 and 94% after exercise (P < 0.05). The fractional activity of glycogen synthase (active/total) increased immediately after exercise (from 0.22 ± 0.05 and 0.32 ± 0.04 to 0.63 ± 0.08 vs. 0.57 ± 0.05; P < 0.01 for ZL and ZO rats, respectively) and remained elevated above resting values after 30 min of recovery. During this time, muscle [glycogen] in ZO increased 68% with CHO (P < 0.05) but did not change in Fast. Muscle [glycogen] was unchanged in ZL from postexercise values after both treatments. After 6 h recovery, GLUT-4 protein concentration was increased above resting levels by a similar extent for both genotypes in both fasted (∼45%) and CHO-supplemented (∼115%) rats. Accordingly, during this time CHO refeeding resulted in supercompensation in both genotypes (68% vs. 44% for ZL and ZO). With CHO, liver [glycogen] was restored to resting levels in ZL but remained at postexercise values for ZO after both treatments. We conclude that the increased glucose availability with carbohydrate refeeding after glycogen-depleting exercise resulted in glycogen supercompensation, even in the face of muscle insulin-resistance.

Estradiol for treatment-resistant schizophrenia: a large-scale randomized-controlled trial in women of child-bearing age

Many women with schizophrenia remain symptomatic despite optimal use of current therapies. While previous studies suggest that adjunctive oestrogen therapy might be effective, large-scale clinical trials are required before clinical applications are possible. This study is the first large-scale randomized-controlled trial in women with treatment-resistant schizophrenia. This Definitive Oestrogen Patch Trial was an 8-week, three-arm, double-blind, randomized-controlled trial conducted between 2006 and 2011. The 183 female participants were aged between 18 and 45 (mean=35 years), with schizophrenia or schizoaffective disorder and ongoing symptoms of psychosis (Positive and Negative Syndrome Scale, PANSS score>60) despite a stable dose of antipsychotic medication for at least 4 weeks. Mean duration of illness was more than 10 years. Participants received transdermal estradiol 200 μg, transdermal estradiol 100 μg or an identical placebo patch. For the 180 women who completed the study, the a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56. Cognition was assessed at baseline and day 56 using the Repeatable Battery of Neuropsychological Status. Data were analysed using latent growth curve modelling. Both estradiol groups had greater decreases in PANSS positive, general and total symptoms compared with the placebo group (P<0.01), with a greater effect seen for 200 μg than 100 μg estradiol. The largest effect size was for the positive subscale of PANSS in the estradiol 200 μg treatment group (effect size 0.44, P<0.01). This study shows estradiol is an effective and clinically significant adjunctive therapy for women with treatment-resistant schizophrenia, particularly for positive symptoms.Molecular Psychiatry advance online publication, 15 April 2014; doi:10.1038/mp.2014.33.

The integrative management of treatment-resistant depression: a comprehensive review and perspectives.

Major depressive disorder is a prevalent and disabling illness. Notwithstanding numerous advances in the pharmacological treatment of depression, approximately 70% of patients do not remit after first-line antidepressant treatment.

Performance comparison of abrasion resistant textile motorcycle clothing

 Falling at speed onto a tarmac surface during cycling can cause abrasion and laceration of the skin and body tissue. Motorcycle clothing designed to reduce or avoid this type of injury has traditionally been made of animal leather as it has well known resistance to abrasion. In the last 20 years there has been an emergence of textile clothing reinforced with high performance/tenacity fibres such as those made from polyamides, aramids, ultra high molecular weight polyethylene and liquid crystal. Almost no comparative work has been undertaken to provide insight into the level of protection these clothing layers can provide.
This work has used a CE standard test method to evaluate a number of abrasion resistant textile pant products and compare them with a leather race product. It analysed the protective fabric layer structure for mass, thickness, construction method and resistance to abrasion.
Structures manufactured from high tenacity fibres performed better than those from lower tenacity ones. Fabric construction method and mass per unit area were the two key variables in providing an abrasion protective layer. Structures manufactured from knitted para-aramid fibres performed better than their woven counterparts due to the method of fabric failure. Several well designed protective layers performed at a similar level to that of leather; however, most garments tested failed to meet the lower level European standard of abrasion resistance (CE level 1), which may put their wearer at risk in the advent of a collision.

Towards integrated anti-microbial capabilities: Novel bio-fouling resistant membranes by high velocity embedment of silver particles

Biofilm formation on membranes during water desalination operation and pre-treatments limits performance and causes premature membrane degradation. Here, we apply a novel surface modification technique to incorporate anti-microbial metal particles into the outer layer of four types of commercial polymeric membranes by cold spray. The particles are anchored on the membrane surface by partial embedment within the polymer matrix. Although clear differences in particle surface loadings and response to the cold spray were shown by SEM, the hybrid micro-filtration and ultra-filtration membranes were found to exhibit excellent anti-bacterial properties. Poly(sulfone) ultra-filtration membranes were used as for cross-flow filtration of Escherichia coli bacteria solutions to investigate the impact of the cold spray on the material[U+05F3]s integrity. The membranes were characterized by SEM-EDS, FT-IR and TGA and challenged in filtration tests. No bacteria passed through the membrane and filtrate water quality was good, indicating the membranes remained intact. No intact bacteria were found on hybrid membranes, loaded with up to 15. wt% silver, indicating the treatment was lysing bacteria on contact. However, permeation of the hybrid membranes was found to be reduced compared to control non-modified poly(sulfone) membranes due to the presence of the particles across the membrane material. The implementation of cold spray technology for the modification of commercial membrane products could lead to significant operational savings in the field of desalination and water pre-treatments.

Community-associated methicillin-resistant Staphylococcus aureus transmission in households of infected cases : a pooled analysis of primary data from three studies across international settings

Diverse strain types of methicillin-resistant Staphylococcus aureus (MRSA) cause infections in community settings worldwide. To examine heterogeneity of spread within households and to identify common risk factors for household transmission across settings, primary data from studies conducted in New York (USA), Breda (The Netherlands), and Melbourne (Australia) were pooled. Following MRSA infection of the index patient, household members completed questionnaires and provided nasal swabs. Swabs positive for S. aureus were genotyped by spa sequencing. Poisson regression with robust error variance was used to estimate prevalence odds ratios for transmission of the clinical isolate to non-index household members. Great diversity of strain types existed across studies. Despite differences between studies, the index patient being colonized with the clinical isolate at the home visit (P < 0·01) and the percent of household members aged <18 years (P < 0·01) were independently associated with transmission. Targeted decolonization strategies could be used across geographical settings to limit household MRSA transmission.

Clinical aspects for survivin: a crucial molecule for targeting drug-resistant cancers

Drug resistance is frequently found in cancer patients who have prolonged chemotherapeutic treatments. Overcoming this phenomenon to make therapy available to these patients is one of the most important features in developing effective cancer therapeutic strategies. Identification of drug resistance causative molecules is one of the most focused areas of cancer research today. Many molecules have been identified in conferring cancer cells the property of drug resistance, and various small molecule inhibitors have been developed to target these molecules to restore the sensitivity of different traditional chemotherapeutic agents, which are frequently found to exhibit reduced potency during prolonged treatment, in cancer patients. Survivin, a member of the inhibitor of apoptosis proteins (IAP) family, has been identified as one of the most crucial biomarkers in the recognition of drug resistance. Survivin is overexpressed in tumor cells, helping in its proliferation and survival, and its overexpression is positively correlated with poor prognosis for cancer patients. Targeted therapeutic measures to inhibit survivin in cancers, particularly drug-resistant tumors, are the recent focus of research for cancer treatment.