The evidence for better health from health assessments: A large clustered randomised controlled trial

Aim: To test the efficacy of a comprehensive health assessment using the CHAP tool in adults with an intellectual disability (ID). Method: A cluster randomised control design was used. The intervention group received the CHAP, while the control group received usual care. This tool directed carers to gather a health history, which was reviewed by the person’s general practitioner (GP) who completed a medical examination and a healthcare plan. The tool acted as an advocacy tool, a ticket-of-entry to the GPs surgery and educated the GP and the caregiver about the deficits in the healthcare of adults with ID. The healthcare of the participants was followed for one-year after intervention by the collection of data from GP and service providers’ notes. Also interviews were performed with all those involved. Results: We obtained a representative sample of  adults with ID (RR%). We found the intervention group received a significant increase in many health promotion/disease prevention activities e.g. hearing screening was  times and a Pap smear was  times more likely to have occurred in the intervention groups.We also found a trend towards earlier detection of disease. Conclusions: The CHAP process improves the provision of health screening/promotion activities and should be implemented.

A spectral clustering algorithm for manufacturing cell formation

A graph clustering algorithm constructs groups of closely related parts and machines separately. After they are matched for the least intercell moves, a refining process runs on the initial cell formation to decrease the number of intercell moves. A simple modification of this main approach can deal with some practical constraints, such as the popular constraint of bounding the maximum number of machines in a cell. Our approach makes a big improvement in the computational time. More importantly, improvement is seen in the number of intercell moves when the computational results were compared with best known solutions from the literature. (C) 2009 Elsevier Ltd. All rights reserved.

Esmodil: An acetylcholine mimetic resurfaces in a southern australian marine sponge Raspailia (Raspailia) sp.

Bioassay directed fractionation of a Raspailia (Raspailia) sp. (Order Poecilosclerida; Family Raspailiidae) collected during scientific trawling operations off the Northern Rottnest Shelf yielded as nematocidal agents the known metabolites, phorboxazoles A (1) and B (2). Further examination revealed the new natural product but known synthetic compound, esmodil (3). The structure for 3 was confirmed by spectroscopic analysis and total synthesis.

An insight into the thermostability of a pair of xylanases: the role of hydrogen bonds

Xylanases are enzymes that are very tolerant to temperature. Their potential use in several biotechnological applications, such as animal food manufacture and pulp bleaching, is due to their intrinsic thermostability. The present report deals with two xylanases, the mesophilic xylanase from Bacillus circulans, BCX, and the thermophilic xylanase from Thermomyces lanuginosus,TLX. These enzymes belong to family 11, and they are the most structurally similar mesophilic-thermophilic pair. Molecular dynamics simulations were employed to investigate the factors responsible for the different thermostabilities exhibited by these structurally similar enzymes. Their active site is their most rigid region, and it is equally rigid at all temperatures. Inter and intramolecular interactions, hydrogen bonds in particular, are the key to the main differences between BCX and TLX. The intramolecular hydrogen bonds and salt bridges are important for maintenance of the backbone rigidity even at high temperature, and the highly solvated surface is a clear optimization in TLX compared with BCX. The main differences between these two enzymes can be found on the fingers domain, which indicates that this domain must be the target for the site-directed mutagenesis responsible for improving the temperature tolerance of this family of enzymes.

Permeabilization of E-coli K12 inner and outer membranes by bothropstoxin-I, A LYS49 phospholipase A2 from Bothrops jararacussu

Although lacking catalytic activity, the Lys49-PLA(2)s damage artificial membranes by a Ca2+-independent mechanism, and demonstrate a potent bactericidal effect. The relationship between the membrane-damaging activity and bactericidal effect of bothropstoxin-I (BthTx-1), a Lys49-PLA(2) from the venom of Bothrops jararacussu, was evaluated for the wildtype protein and a series of site-directed mutants in the active site and C-terminal regions of the protein. The membrane permeabilization effect against the inner and outer membranes of Escherichia coli K12 was evaluated by fluorescence changes of Sytox Green and N-phenyl-N-naphthylamine, respectively. With the exception of H48Q, all mutants reduced the bactericidal activity, which correlated with a reduction of the permeabilization effect both against the inner bacterial membrane. No significant differences in the permeabilization of the bacterial outer membrane were observed between the native, wild-type recombinant and mutant proteins. These results suggest different permeabilization mechanisms against the inner and outer bacterial membranes. Furthermore, the structural determinants of bacterial inner membrane damage identified in this study correlate with those previously observed for artificial membrane permeabilization, suggesting that a common mechanism of membrane damage underlies the two effects. (C) 2007 Elsevier Ltd. All rights reserved.

Retrograde delivery of photosensitizer (TPPp-O-beta-GluOH)(3) selectively potentiates its photodynamic activity

Photodynamic therapy involves administration of a photosensitizing drug and its subsequent activation by visible light of the appropriate wavelength. Several approaches to increasing the specificity of photosensitizers for cancerous tissues and, in particular, through their conjugation to ligands that are directed against tumor-associated antigens have been investigated. Here, we have studied the delivery of the photocytotoxic porphyrin compound TPP(p-O-beta-D-GluOH)(3) into tumor cells that overexpress the glycosphingolipid Gb3, using the Gb3-binding nontoxic B-subunit of Shiga toxin (STxB) as a vector. To allow for site-directed chemical coupling, an STxB variant carrying a free sulfhydryl moiety at its C-terminal end has been used. Binding affinity, cellular uptake, singlet oxygen quantum yield, and phototoxicity of the conjugate have been examined. Despite some effect of coupling on both the photophysical properties of TPP(p-O-beta-D-GluOH)(3) and the affinity of STxB for its receptor, the conjugate exhibited a higher photocytotoxic activity than the photosensitizer alone and was exquisitely selective for Gb3-expressing tumor cells. Furthermore, our data strongly suggest that STxB-mediated retrograde delivery of the photosensitizer to the biosynthetic/secretory pathway is critical for optimal cytotoxic activity. In conclusion, a strong rationale for using retrograde delivery tools such as STxB in combination with photosensitizing agents for the photodynamic therapy of tumors is presented.

Shared structural determinants for the calcium-independent liposome membrane permeabilization and sarcolemma depolarization in Bothropstoxin-I, a LYS49-PLA(2) from the venom of Bothrops jararacussu

The structural determinants of myotoxicity of bothropstoxin-I (BthTX-I), a Lys49 phospholipase A(2) from Bothrops jararacussu venom, were studied by measuring the resting membrane potential in the mouse phrenic nerve-diaphragm preparation. This method proved to be around 100-fold more sensitive than the creatine kinase release assay, and was used to evaluate a total of 31 site-directed BthTX-I alanine scanning mutants. Mutants that reduced the resting membrane potential were located in a surface patch defined by residues in the C-terminal loop (residues 115-129), positions 37-39 in the membrane interfacial recognition surface (Y46 and K54), and residue K93. These results expand the known structural determinants of the biological activity as evaluated by previous creatine kinase release experiments. Furthermore, a strong correlation is observed between the structural determinants of sarcolemma depolarization and calcium-independent disruption of liposome membranes, suggesting that a common mechanism of action underlies the permeabilization of the biological and model membranes. (C) 2009 Elsevier Ltd. All rights reserved.

Refolding and purification of the human secreted group IID phospholipase A(2) expressed as inclusion bodies in Escherichia coli

The secreted phospholipases A(2) (sPLA(2)s) are water-soluble enzymes that bind to the surface of both artificial and biological lipid bilayers and hydrolyze the membrane phospholipids. The tissue expression pattern of the human group IID secretory phospholipase A(2) (hsPLA(2)-IID) suggests that the enzyme is involved in the regulation of the immune and inflammatory responses. With an aim to establish an expression system for the hsPLA(2)-IID in Escherichia coli, the DNA-coding sequence for hsPLA(2)-IID was subcloned into the vector pET3a, and expressed as inclusion bodies in E. coli (BL21). A protocol has been developed to refold the recombinant protein in the presence of guanidinium hydrochloride, using a size-exclusion chromatography matrix followed by dilution and dialysis to remove the excess denaturant. After purification by cation-exchange chromatography, far ultraviolet circular dichroism spectra of the recombinant hsPLA(2)-IID indicated protein secondary structure content similar to the homologous human group IIA secretory phospholipase A(2). The refolded recombinant hsPLA(2)-IID demonstrated Ca(2+)-dependent hydrolytic activity, as measuring the release free fatty acid from phospholipid liposomes. This protein expression and purification system may be useful for site-directed mutagenesis experiments of the hsPLA(2)-IID which will advance our understanding of the structure-function relationship and biological effects of the protein. (C) 2009 Elsevier Inc. All rights reserved.

A Delphi study of district nursing research priorities in Australia

This study, using a Delphi approach, sought the opinion of a self-selected panel of 320 district nurses regarding research priorities for district nursing in Australia. Over three rounds of questionnaires, the 419 research clinical problem areas requiring research as suggested by the panel were each rated in importance by the panel and then ranked through analysis from high to low average rating scores, thereby, whittling down the list to the top 15% (68) research questions and to a final list of the top 10 research priorities overall. Research questions focusing on discharge planning are dominant in these top 10 priorities, with documentation issues the second most common focus. Other foci in the top 10 priorities are staffing, aged care, palliative care, and assessment. The organization-specific top 10 research priorities focus on wound care, funding, education, and communication issues. Additionally, the top 68 priorities, which are either finitely practice-based or contextual-issues research questions, were categorized into 20 themes. The results will hopefully lead to scarce human and financial resources being directed to practice-relevant research programs that will facilitate improved health for district nursing (primarily home-nursing) clients in Australia and elsewhere. (c) 2005 Elsevier Inc. All rights reserved.

Interferon-gamma is required for killing keratinocytes in vitro and in vivo

Epithelial malignancies are common in immunosuppressed individuals and the general population. However the mechanisms by which the adaptive immune system can eliminate immunogenic epithelial cells remain undefined. The aim of this project was to determine the effector molecules required for induction of apoptosis in murine epidermal keratinocytes (MEKs) in vitro and in vivo. HPV16E7-specific CTL lines and T cell receptor transgenic (E7TCRtg) effector cells were obtained from wild type (wt)-C57 and syngeneic mice rendered functionally inactive for perforin (Pfp), interferon-g (IFN-g) or FasL. CTLs or E7TCRtg spleen cells were co-cultured with primary MEKs in vitro or transferred into skin graft recipients. Inhibition of colony formation and skin graft rejection were used as indicators of T cell:KC interaction. Wt E7-specific CTLs and CTLs deficient in perforin, FasL or IFN-g produced mean reductions in colony formation of 67% (62.4–71.3%), 72% (71.1–72%), 76% (73–78%) and 21.5% (14– 34%) respectively. Wt, perforin deficient or FasL deficient CTLs all induced rejection of skin grafts (wt: 6/12; Pfp: 9/15; FasL: 3/13 survival). Transfer and immunisation of wt E7TCRtg spleen cells induces rejection of 50% of grafts (4/8 survival). In contrast, perforin or IFN-g deficient E7TCRtg failed to induce graft rejection (5/6; 4/4 survival). FasL deficient E7TCRtg induced nonspecific rejection of grafts (E7- 2/6 survival; C57- 4/7 survival). Therefore IFN-g production by CTL is necessary and sufficient in vitro and in vivo to kill epithelial cells which express a nonself antigen. Assessment of immunotherapies directed against epithelial tissues may be more effectively achieved by assaying the amount of IFN-g production by CD8 T cells, and the number and affinity of those cells, in conjunction with quantitation of perforin mediated effects in short term assays.

Insights into the organization of dorsal spinal cord pathways from an evolutionarily conserved raldh2 intronic enhancer

Comparative studies of the tetrapod raldh2 (aldh1a2) gene, which encodes a retinoic acid (RA) synthesis enzyme, have led to the identification of a dorsal spinal cord enhancer. Enhancer activity is directed dorsally to the roof plate and dorsal-most (dl1) interneurons through predicted Tcf- and Cdx-homeodomain binding sites and is repressed ventrally via predicted Tgif homeobox and ventral Lim-homeodomain binding sites. Raldh2 and Math1/Cath1 expression in mouse and chicken highlights a novel, transient, endogenous Raldh2 expression domain in dl1 interneurons, which give rise to ascending circuits and intraspinal commissural interneurons, suggesting roles for RA in the ontogeny of spinocerebellar and intraspinal proprioceptive circuits. Consistent with expression of raldh2 in the dorsal interneurons of tetrapods, we also found that raldh2 is expressed in dorsal interneurons throughout the agnathan spinal cord, suggesting ancestral roles for RA signaling in the ontogenesis of intraspinal proprioception.

Extra-curricular involvement and self-regulation in children

The research investigated the relationship between extra-curricular involvement (ECI) and self-regulated behaviours in 8 to 9 year old children, and identified sex, location, and socio-economic status (SES) differences in their ECI and self-regulatory behaviours. 550 children from 44 schools in Queensland and New South Wales completed the Child Self-Regulatory Process Inventory and questions about their ECI. Nearly 90 percent of students were involved in at least one extra-curricular activity with the mean number of activities being 1.27. Girls and urban children were significantly more involved in school-based extra- curricular activities than their male and rural counterparts; there were no significant differences among SES groups. Urban children and children in the high SES group reported significantly greater involvement for non-school based activities. For the three self- regulation strategies, girls scored significantly higher than boys. Moreover, children in the high ECI group reported significantly greater use of self-regulation strategies than children in both the low and medium ECI groups. Implications of findings are discussed in light of the need for quality extra-curricular programs, especially in terms of emotional climate and self-directed activities.

Trade spectrum of K4-e

A K-4 - e trade consists of two disjoint decompositions of some simple graph H into copies of K-4 - e. The number of vertices of H is referred to as the foundation of the trade, while the number of copies of K-4 - e in each of the decompositions is called the volume of the trade. We determine the values of v and s for which there exists a K-4 - e trade of volume s and foundation v.

Bernard Michael Bindon - reproductive physiologist, animal scientist, research leader

This paper is a foreword to a series of papers commissioned on 'the impact of science on the beef industry', where the Beef CRC-related collaborative scientific work of Professor Bernard Michael Bindon will be reviewed. These papers will be presented in March 2006, as part of a 'festschrift' to recognise his wider contributions to the Australian livestock industries for over 40 years. Bindon's career involved basic and applied research in many areas of reproductive physiology, genetics, immunology, nutrition, meat science and more recently genomics, in both sheep and cattle. Together with his collaborators, he made large contributions to animal science by improving the knowledge of mechanisms regulating reproductive functions and in elucidating the physiology and genetics of high fecundity livestock. His collaborative studies with many colleagues of the reproductive biology and genetics of the Booroola Merino were amongst the most extensive ever conducted on domestic livestock. He was instrumental in the development of immunological techniques to control ovulation rate and in examining the application of these and other techniques to increase beef cattle reproductive output. This paper tracks his investigations and achievements both within Australia and internationally. In the later stages of his career he was the major influence in attracting a large investment in Cooperative Research Centres for the Australian cattle industry, in which he directed a multi-disciplinary approach to investigate, develop and disseminate science and technology to improve commercial cattle productivity.

Idiopathic spinal epidural hematoma in patients with sudden paraplegia: A case report

Introduction. Spontaneous spinal epidural hematoma (SEH) represents 0.3-0.9% of spinal epidural space-occupying lesions, and most surgeons advocate aggressive and early surgical intervention. In. this paper we describe a patient with SEH with sudden paraplegia. Case report. This 30-year-old man had experienced one prior episode of sudden dorsal pain two days before the current admission and while he waited medical attendance, his legs suddenly became weak, and immediately afterwards, he became completely paraplegic in minutes. The patient had complete paraplegia, analgesia below the T4 level and urinary retention. He had no anticoagulant agent and no coagulopathic disease. He was submitted to computerized tomography that demonstrated a dorsally located epidural hematoma extending from the T3 to the T6 level with spinal cord compression. A laminectomy from T3 to T7 was performed four hours after the onset of the symptom. In postoperative time the patient presented the partial sensorial recovery and motor force grade II. The patient was directed to a neurorehabilitation program and in the last medical evaluation he presented recovery for motor grade III-IV without pain. Conclusion. The SHE is rare, with severe neurological consequences for patients and early surgical treatment persist as essential for motor recovery.