Clostridium difficile-associated diarrhea outbreaks: the name of the game is isolation and cleaning.
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Anti-Bacterial Agents↗
Biomedical subjects
David Williamson
Publications and source records attributed to David Williamson.
A framework for mental health consumers to evaluate service provision.
OBJECTIVES: This paper outlines a proposed framework including values, principles and steps, developed by consumers, to evaluate mental health services from a consumer's perspective. METHOD: A research team consisting of consumer researchers, established academics and students developed the framework. The team had already conducted qualitative research with consumers of mental health services. Using these experiences and the evaluation literature, the proposed framework was developed over a series of 13 meetings. RESULTS: An evaluation framework, which describes the values underpinning consumer-directed evaluation of mental health services and the principles and steps to follow in conducting this type of evaluation, is presented. CONCLUSIONS: The evaluation framework will guide consumers and services in conducting consumer-directed evaluation of mental health services, and assist in developing more genuine consumer participation in services.
Australia↗
Major endocrinology meetings.
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Endocrinology↗
Fractionation of Aloe vera L. inner gel, purification and molecular profiling of activity.
Products derived from the inner gel of the Aloe vera L. plant have demonstrated multiple clinical activities, and are used routinely to accelerate wound healing. However, typical of natural products, the complex nature of Aloe vera gels may contribute to diverse pharmacologic activities. Our focus on the hematopoietic activities of Aloe vera extracts is extended by these functional studies, which used purified fractions from Aloe vera gel and included a preliminary organ-specific in vitro molecular profile. Studies using a >99% pure carbohydrate fraction from Aloe vera extracts revealed increased hematopoietic and hematologic activity compared to the starting material. In addition, this fraction differentially regulated liver and lung cytokine mRNA levels, resulting in significant increases in message for hematopoietic cytokines [granulocyte colony stimulating factor (G-CSF) and stem cell factor (SCF)]. This profile of activity differed from another fraction obtained from Aloe vera, suggesting the potential for diverse pharmacologic activity. The molecular studies were undertaken using co-cultures of organ slices to limit the amount of purified material required. In summary, these studies revealed significant hematopoietic activity by both pharmacologic and molecular analysis using a >99% pure carbohydrate fraction from Aloe vera gels.
Aloe↗
Absolute assessment of adsorption-based porous solid characterization methods: comparison methods.
The design and use of microporous solids depends on having access to characteristics such as the pore volume and surface area. Comparison methods such as the alpha(s) method are one of the most widely used means of determining these parameters. An assessment of this group of methods was undertaken by comparing estimates obtained from them using adsorption isotherms generated by grand canonical Monte Carlo simulation on a selection of model nanoporous solids with exactly known surface areas and pore volumes. Conclusions are drawn from this absolute assessment in regard to the validity of the alpha(s) method for determining the micropore volume, the mesopore surface area, and the separation of pore groups based on the concept of primary and cooperative filling, the subtracting pore effect (SPE) method, and the required character of the reference surface.
Journal Article↗
Molecular simulation evidence for solidlike adsorbate in complex carbonaceous micropore structures.
Adsorption of a model nitrogen vapor on a range of complex nanoporous carbon structures is simulated by grand canonical Monte Carlo simulation for a single subcritical temperature above the bulk freezing point. Adsorption and desorption isotherms, heats of adsorption, and three-dimensional singlet distribution functions (SDFs) were generated. Inspection of the SDFs reveals significant levels of solidlike adsorbate at saturation even in the most complex of the microporous solids considered. This strongly suggests that solidlike adsorbate will also occur for simple subcritical vapors adsorbed on real noncrystalline solids such as microporous carbons at temperatures above the bulk freezing point, supporting indirect experimental observations. The presence of significant levels of solidlike adsorbate has implications for characterization of microporous solids where adsorbate density is used (e.g., determination of pore volume from loading). Detailed consideration of the SDF at different loadings for a model microporous solid indicates solidlike adsorbate forms at distributed points throughout the pore space at pressures dependent on the nature of the local porosity. The nature of the local porosity also dictates the freezing mechanism. A local freezing/ melting/refreezing process is also observed. Introduction of mesoporosity into the model causes hysteresis between the adsorption and desorption isotherms. Adsorption in the hysteresis loop occurs by a series of local condensation events. It appears as if the presence of adjacent microporosity and/or adsorbate within it affects the pressure at which these events occur. Reversal of the condensation during desorption occurs throughout the mesoporosity at a single pressure; this pressure is unaffected by the presence of adjacent microporosity or the adsorbate within it. It is also shown that the empirical concept of "pore size" is not consistent for describing adsorption in the complex solids considered here. A new concept is, therefore, proposed that seeks to account for the factors that affect local adsorption energy: local geometry, microtexture, surface atom density, and surface chemistry.
Journal Article↗
Polymorphisms at positions -22 and -348 in the promoter of the BAT1 gene affect transcription and the binding of nuclear factors.
BAT1 (D6S81E, UAP56) lies in the central MHC between TNF and HLA-B, a region containing genes that affect susceptibility to immunopathologic disorders. BAT1 protein may be directly responsible for the genetic association, as antisense studies show it can down-regulate inflammatory cytokines. Here we investigate polymorphisms at positions -22 and -348 relative to the BAT1 transcription start site. DNA samples from healthy donors were used to confirm haplotypic associations with the type 1 diabetes-susceptible 8.1 ancestral haplotype (AH; HLA-A1,B8,BAT1-22*C,BAT1-348*C,DR3 ) and the diabetes-resistant 7.1 AH (HLA-A3,B7,BAT1-22*G,BAT1-348*T,DR15). Alleles carried at BAT1-22 and -348 were in linkage disequilibrium. Electrophoretic mobility shift assays using nuclear proteins from T-cells (Jurkat and HT2), monocytes (THP1, U937) and epithelial cells (HeLa and MDA468) demonstrated DNA : protein complexes binding oligonucleotides spanning positions -22 and -348 on the 7.1 AH only. Competition assays, supershifts and molecular weight determinations suggest the complexes include the transcription factors YY1 (at -348) and Oct1 (at -22). Promoter activity was demonstrated using 520 bp and 336 bp fragments cloned from immediately upstream of the transcription start site and carrying all combinations of -22 and -348 alleles, suggesting an unidentified non-polymorphic sequence within 336 bp of the start site drives transcription. The 520 bp fragment of the BAT1 promoter cloned from the 8.1 AH was slightly less efficient than the equivalent from the 7.1 AH, whilst the reverse was observed with 336 bp fragments. This suggests BAT1 transcription on the 7.1 AH is modified by interactions involving DNA flanking positions -22 and -348.
Cells, Cultured↗
A promoter polymorphism in the central MHC gene, IKBL, influences the binding of transcription factors USF1 and E47 on disease-associated haplotypes.
The human major histocompatibility complex (MHC) contains genes that affect susceptibility to numerous immunopathological diseases. We propose that genes in the central MHC between TNFA and HLA-B explain associations between the 8.1 haplotype (HLA-A1, B8, DR3) and disease. IKBL encodes a protein resembling members of the IkappaB protein family that regulate bioavailability of NFkappaB. We have identified two polymorphisms in the 500 bp upstream of the transcription start site of IKBL that distinguish the 8.1 haplotype from the resistant 7.1 haplotype (HLA-A3, B7, DR15). A single nucleotide polymorphism at -62 disrupts a putative E-box binding sequence. To investigate binding of transcription factors in vitro, we exposed 32P-labeled DNA fragments carrying both alleles to nuclear extracts, showing allele-specific binding of nuclear proteins from Jurkat cells but not from other lineages. Supershift studies using Jurkat nuclear extract showed that the E-box protein, E47, and ubiquitously expressed transcription factor USF1 bind to the E-box element of the 7.1 haplotype. Transient transfections of luciferase reporter constructs carrying promoter alleles of IKBL into Jurkat cells showed an effect of IKBL-62 alleles. In contrast, alleles at -421 did not affect transcription factor binding or transcription. IKBL was expressed at low levels in Jurkat cells but not in blood mononuclear cells, and expression declined following mitogenic stimulation. The restriction of IKBL expression to Jurkat cells is consistent with evidence that E47 is expressed in thymocytes and suggests IKBL may affect autoimmunity through an effect on T-cell selection.
Adaptor Proteins, Signal Transducing↗
Role of the intracellular domains of GPIb in controlling the adhesive properties of the platelet GPIb/V/IX complex.
Glycoprotein (GP) Ib/V/IX complex-dependent platelet adhesion to von Willebrand factor (VWF) is supported by the 45-kd N-terminal extracellular domain of the GPIb alpha subunit. Recent results with an adhesion blocking antibody (RAM.1) against GPIb beta, which is disulfide linked to GPIb alpha, have suggested a novel function of this subunit in regulating VWF-mediated platelet adhesion, possibly involving its intracellular face. A putative cooperation between the GPIb alpha and GPIb beta cytoplasmic domains was investigated by measuring the adhesion under flow to immobilized VWF of K562 and Chinese hamster ovary (CHO) cells transfected with GPIb/(V)/IX containing mutations in this region. Adhesion of cells carrying a glycine substitution of the GPIb beta Ser166 phosphorylation site was 50% lower than normal and became insensitive to inhibition by RAM.1. In contrast, forskolin or PGE(1) treatment increased both the phosphorylation of GPIb beta and adhesion of control cells, both effects being reversed by RAM.1, but had no influence on cells expressing the Ser166Gly mutation. A role of the GPIb alpha intracellular domain was also apparent as the VWF-dependent adhesion of cells containing deletions of the entire (Delta 518-610) or portions (Delta 535-568, Delta 569-610) of the GPIb alpha cytoplasmic tail was insensitive to RAM.1 inhibition. Cells carrying progressive 11 amino acid deletions spanning the GPIb alpha 535-590 region were equally unresponsive to RAM.1, with the exception of those containing GPIb alpha Delta 569-579, which behaved like control cells. These findings support a role of the GPIb beta intracellular domain in controlling the adhesive properties of the GPIb/V/IX complex through phosphorylation of GPIb beta Ser166 and point to the existence of cross-talk between the GPIb beta and GPIb alpha intracellular domains.
Alprostadil↗
Maintenance of whole muscle strength and size following resistance training in older men.
Following a progressive resistance training (PRT) program of 3 days per week, we sought to examine how effective a resistance training maintenance program of 1 day per week would be to preserve muscle strength and size in older men. Each subject's whole muscle strength (1 repetition maximum, or 1RM) and whole muscle size (determined by computed tomography scan) were measured before (T1) and after (T2) 12 weeks of PRT and again following 6 months (T3) of training (TR) or detraining (DT). During the 12-week PRT, older men (N = 10; age 70 +/- 4 years) trained their knee extensors 3 days per week at 80% of their 1RM. The maintenance program consisted of older men (n = 5; TR; 75 +/- 1 years) who completed 3 sets of 10 repetitions at 80% of their 1RM 1 day per week (this was equivalent to a single training session that was performed 3 days per week during the 12-week PRT). The other group of older men (n = 5; DT; 69 +/- 1 years) resumed their normal lifestyle (no regular physical activity) following the 12-week PRT. From T1 to T2, muscle strength increased (p <.05) 45% (66 +/- 10 to 94 +/- 10 kg) in the TR group and 53% (50 +/- 6 to 74 +/- 7 kg) in the DT group. From T2 to T3, whole muscle strength of the TR group was unchanged (96 +/- 11 kg), whereas strength decreased (p <.05) in the DT group by 11% (66 +/- 6 kg). Muscle size demonstrated a similar pattern with a 7% increase (p <.05) in both groups from T1 to T2. No change in muscle size was found in the TR group from T2 to T3, whereas the DT group had a 5% reduction (p <.05). These data indicate that resistance training 1 day per week was sufficient to maintain muscle strength and size in these older men following a 12-week PRT program. Furthermore, the men who resumed their normal lifestyle (no regular physical activity) experienced significant losses in muscle strength and size.
Aged↗
Judgments about length, weight, and width covariation as a function of intelligence and depth of processing in elementary school children: a preliminary study.
28 elementary school students were assessed for intelligence, then blindfolded and asked to explore objects manually before rendering judgments about how weight and width were related to length. Exploration time for each object was hypothesized to reflect the level of processing engaged in by the participants. It was also predicted that more intelligent children would produce the most accurate judgments. Inconsistent with the predictions, analysis indicated that children of higher intelligence did not produce the most accurate judgments. However, longer exploration times reflected a tendency to refrain from endorsing a negative correlation between length and width. Depth of processing is, therefore, presumed to aid in reasoning about covariation.
Child↗
Interaction between platelet glycoprotein Ibalpha and filamin-1 is essential for glycoprotein Ib/IX receptor anchorage at high shear.
The interaction of the glycoprotein (GP) Ib-V-IX receptor complex with the membrane skeleton of platelets is dependent on a specific interaction between the cytoplasmic tail of GPIbalpha and filamin-1. This interaction has been proposed to regulate key aspects of platelet function, including the ligand binding of GPIb-V-IX and the ability of the cells to sustain adhesion to von Willebrand factor (vWf) under high shear. In this study we have examined sequences in the GPIbalpha intracellular domain necessary for interaction of the receptor with filamin-1. We have identified two adjacent sequences involving amino acids 557-568 and 569-579 of the GPIbalpha cytoplasmic domain that are critical for normal association between the receptor complex and filamin-1. Under flow conditions, Chinese hamster ovary (CHO) cells expressing these two mutant receptors exhibited an increase in translocation velocity that was associated with increased cell detachment from the vWf matrix at high shear. The shear-dependent acceleration in velocity of mutant Delta557-568 and Delta569-579 CHO cells was associated with a critical defect in receptor anchorage, evident from significant extraction of GPIb-IX from the CHO cell membrane at high shear. These studies define a critical role for amino acids within the 557-579 sequence of GPIbalpha for interaction with filamin-1.
Amino Acid Sequence↗
A richer tapestry of many identities.
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Australia↗
[Epidemiology of falls among the elderly].
INTRODUCTION: Falls among the elderly have important physical and psychological consequences. Interventions of proven effectiveness exist at individual and population level for their prevention. Studies conducted in other countries have estimated the prevalence and identified the health and environmental risk factors associated with falls, while in Italy, the information available is limited to elderly living in protected residences. To estimate therefore the prevalence of falls and to estimate the association between these events and different risk factors, a series of questions on falls and their possible determinants were included in Studio Argento, a cross-sectional survey of the state of health of the non-institutionalized population > or = 65 years of age that was conducted in 2002 in 11 Italian Regions. METHODS: In each region, two-stage cluster sampling was used to sample 210 individuals. In the first phase, 30 communes were selected, with the probability of selection proportionate to their population; in the second phase, simple random sampling using the communal population register to select the persons to be interviewed. Interviews were conducted in the homes of the study subjects using a standardized questionnaire. Data from the 11 regions were merged for purposes of the analysis, and the C-sample routine of Epi-Info version 2002 was used to conduct the analysis, taking into account of the survey design and the size of the total population > or = 65 years in the various Regions. SUDAAN, an application of SAS was used for the calculation of the rate ratios (R.R.) and 95% confidence intervals (95% CI) and the population-attributable fractions, taking into account potentially confounding variables. RESULTS: A total of 2,273 persons were included in the study. During the previous 12 months, 651 (28.6%; 95% CI = 26.4%-30.7%) had fallen; of these 43.1% (95% IC = 38.6%-47.7%) had fallen 2 or more times. Sixty percent (95% CI = 55,6%-64,2%) of those who had fallen reported having fallen at home. Risk factors for falls included stroke (adjusted RR = 1.4 (95% CI = 1.03-1.8)). diabetes (adjusted RR = 1.7 (95% CI = 1.2-2.1)). visual difficulties (adjusted RR = 1.3 (95% CI = 1.02-1.6)). urinary incontinence (adjusted RR = 1.3 (95%CI= 1.1-1.5) and physical inactivity (adjusted RR = 1.3 (95% CI = 1.03-1.5)). In addition, the consumption of anti-anxiety drugs was also associated with a greater risk of falls. The highest population-attributable fractions were seen for urinary incontinence (9.4%) and lack of physical activity (10.0%). CONCLUSIONS: Falls are common in Italian elderly and are linked with the fragility of aging. To prevent falls, it is necessary to intervene on factors associated with fragility. Methods include encouraging regular physical activity to improve equilibrium and muscle strength and the continuous monitoring of health status to prevent further deterioration. Moreover studies carried out in other countries have demonstrated that the multidisciplinary interventions targeted at persons who have already experienced a fall reduces their risk of further falls. These interventions consist of evaluations of visual acuity, balance, and gait and a review of clinical history with eventual modifications of drug therapy and the environmental risks in the home.
Accidental Falls↗