Effect of an attentional strategy on movement-related potentials recorded from subjects with Huntington's disease

Huntington's disease patients perform automatic movements in a bradykinetic manner, somewhat similar to patients with Parkinson's disease. Cortical activity relating to the preparation of movement in Parkinson's disease is significantly improved when a cognitive strategy is used. It is unknown whether patients with Huntington's disease can utilise an attentional strategy, and what effect this strategy would have on the premovement cortical activity. Movement-related potentials were recorded from 12 Huntington's disease patients and controls performing externally cued finger tapping movement, allowing an examination of cortical activity related to movement performance and bradykinesia in this disease. All subjects were tested in two conditions, which differed only by the presence or absence of the cognitive strategy. The Huntington's disease group, unlike controls, did not produce a rising premovement potential in the absence of the strategy. The Huntington's disease group did produce a rising premovement potential for the strategy condition, but the early slope of the potential was significantly reduced compared with the control group's early slope. These results are similar to those found previously with Parkinson's disease patients. The strategy may have put the task, which previously might have been under deficient automatic control, under attentional control. (C) 2002 Movement Disorder Society.

Dysregulation in retinal para-inflammation and age-related retinal degeneration in CCL2 or CCR2 deficient mice

We have shown previously that a para-inflammatory response exists at the retinal/choroidal interface in the aging eye; and this response plays an important role in maintaining retinal homeostasis under chronic stress conditions. We hypothesized that dysregulation of the para-inflammatory response may result in an overt pro-inflammatory response inducing retinal degeneration. In this study, we examined this hypothesis in mice deficient in chemokine CCL2 or its cognate receptor CCR2. CCL2- or CCR2-deficient mice developed retinal degenerative changes with age, characterized as retinal pigment epithelial (RPE) cell and photoreceptor cell death. Retinal cell death was associated with significantly more subretinal microglial accumulation and increased complement activation. In addition, monocytes from CCL2- or CCR2-deficient mice had reduced capacity for phagocytosis and chemotaxis, expressed less IL-10 but more iNOS, IL-12 and TNF-a when compared to monocytes from WT mice. Complement activation at the site of RPE cell death resulted in C3b/C3d but not C5b-9 deposition, indicating only partial activation of the complement pathway. Our results suggest that altered monocyte functions may convert the protective para-inflammatory response into an overtly harmful inflammation at the retina/choroidal interface in CCL2- or CCR2-deficient mice, leading to RPE and photoreceptor degeneration. These data support a concept whereby a protective para-inflammatory response relies upon a normally functioning innate immune system. If the innate immune system is deficient chronic stress may tip the balance towards an overt inflammatory response causing cell/tissue damage.

Characterization of 14 polymorphic microsatellite loci for the facultatively eusocial sweat bee Halictus rubicundus (Hymenoptera, Halictidae) and their variability in related species

Sweat bees display considerable variation in social organization and a few species, such as Halictus rubicundus, are even facultatively eusocial. Fourteen polymorphic, unlinked microsatellite loci were isolated from H. rubicundus and characterized in 45 females. The number of alleles per locus ranged from two to 18 (mean 10.1), observed heterozygosity ranged from 0.24 to 0.98 (mean 0.71) and expected heterozygosity ranged from 0.24 to 0.98 (mean 0.70). Six or more loci cross-amplified in four other sweat bees. These loci will be useful for the study of social evolution and population genetic structure in H. rubicundus and many other sweat bees.

Isolation, pharmacology and gene organization of KPSFVRFamide: A neuropeptide from Caenorhabditis elegans

To date, 53 peptides with C-terminal RFamides have been identified by the genome sequencing project in the nematode, Caenorhabditis elegans. In this study the FMRFamide-related peptide (FaRP) KPSFVRFamide (879.90 Da [MH](+)) was structurally characterized from extracts of the nematode, Caenorhabditis elegans. Two copies of KPSFVRFamide are encoded by a gene designated flp-9. RT-PCR identified a single cDNA product which was confirmed as flp-9 by sequence determination. Flp-9 cDNA was isolated from larval stages of C. elegans but was not detected-in adult worms, indicating that its expression is may be developmentally regulated. KPSFVRFamide displays sequence homology to the nematode peptide, KPNFIRFamide (PF4). The physiological effects of KPSFVRFamide, PF4 and the chimeras, KPNFVRFamide and KPSFIRFamide, were measured on body wall muscle and the vagina vera of the parasitic nematode, Ascaris suum. KPNFVRFamide and KPNFIRFamide had Cl--dependent inhibitory activity on innervated and denervated muscle-preparations, whereas KPSFVRFamide and KPSFIRFamide did not elicit a detectable physiological effect. Although all 4 peptides had inhibitory effects on the vagina vera, KPSFVRFamide and KPSFIRFamide (threshold, greater than or equal to 0.1 mu M) were less potent than KPNFVRFamide and KPNFIRFamide (threshold, greater than or equal to 10 nM). (C) 1999 Academic Press.

Vitamin D, calcium and dairy intake, and risk of oesophageal adenocarcinoma and its precursor conditions

Evidence is accumulating that vitamin D may be protective against carcinogenesis, although exceptions have been observed for some digestive tract neoplasms. The aim of the present study was to explore the association between dietary vitamin D and related nutrients and the risk of oesophageal adenocarcinoma and its precursor conditions, Barrett's oesophagus and reflux oesophagitis. In an all-Ireland case-control study conducted between March 2002 and July 2005, 218 oesophageal adenocarcinoma patients, 212 Barrett's oesophagus patients, 208 reflux oesophagitis patients and 252 population-based controls completed a 101-item FFQ, and provided lifestyle and demographic information. Multiple logistic regression analysis was applied to examine the association between dietary intake and disease risk. Oesophageal adenocarcinoma risk was significantly greater for individuals with the highest compared with the lowest tertile of vitamin D intake (OR 1·99, 95 % CI 1·03, 3·86; P for trend = 0·02). The direct association could not be attributed to a particular vitamin D food source. Vitamin D intake was unrelated to Barrett's oesophagus and reflux oesophagitis risk. No significant associations were observed for Ca or dairy intake and oesophageal adenocarcinoma, Barrett's oesophagus or reflux oesophagitis development. High vitamin D intake may increase oesophageal adenocarcinoma risk but is not related to reflux oesophagitis and Barrett's oesophagus. Ca and dairy product intake did not influence the development of these oesophageal lesions. These findings suggest that there may be population subgroups at an increased risk of oesophageal adenocarcinoma if advice to improve vitamin D intake from foods is implemented. Limited work has been conducted in this area, and further research is required.

Burkholderia cenocepacia requires RpoE for growth under stress conditions and delay of phagolysosomal fusion in macrophages

Burkholderia cenocepacia is an opportunistic pathogen causing serious infections in patients with cystic fibrosis. The widespread distribution of this bacterium in the environment suggests that it must adapt to stress to be able to survive. We identified in B. cenocepacia K56-2 a gene predicted to encode RpoE, the extra-cytoplasmic stress response regulator. The rpoE gene is the first gene of a predicted operon encoding proteins homologous to RseA, RseB, MucD and a protein of unknown function. The genomic organization and the co-transcription of these genes were confirmed by PCR and RT-PCR. The mucD and rpoE genes were mutated, giving rise to B. cenocepacia RSF24 and RSF25, respectively. While mutant RSF24 did not demonstrate any growth defects under the conditions tested, RSF25 was compromised for growth under temperature (44 degrees C) and osmotic stress (426 mM NaCl). Expression of RpoE in trans could complement the osmotic growth defect but exacerbated temperature sensitivity in both RSF25 and wild-type K56-2. Inactivation of rpoE altered the bacterial cell surface, as indicated by increased binding of the fluorescent dye calcofluor white and by an altered outer-membrane protein profile. These cell surface changes were restored by complementation with a plasmid encoding rpoE. Macrophage infections in which bacterial colocalization with fluorescent dextran was examined demonstrated that the rpoE mutant could not delay the fusion of B. cenocepacia-containing vacuoles with lysosomes, in contrast to the parental strain K56-2. These data show that B. cenocepacia rpoE is required for bacterial growth under certain stress conditions and for the ability of intracellular bacteria to delay phagolysosomal fusion in macrophages.

Micro-environmental conditions modulate protein secretion and infectivity of the Trichinella spiralis L1 larva

After digestion of infected meat the free L1 of Trichinella spp. penetrate the intestinal mucosa where they moult to the mature adult stage. We have used proteomics to identify changes in protein secretion during in vitro culture of free T. spiralis muscle larvae under different environmental conditions, and to correlate these changes with their infectivity in mice. Muscle larvae were cultured in different media (RPMI-1640, C-199 and HBSS) under conditions of anaerobiosis, microaerobiosis and in 5% CO(2) at 37 degrees C. Following incubation the larval excretory/secretory proteins were analysed by two-dimensional gel electrophoresis and the larvae were used to orally infect naïve CD1 mice. For all culture media tested, infectivity of the L1 was preserved following incubation in anaerobic conditions. In contrast, the infectivity of worms cultured in nutrient-rich media was almost completely abolished in both microaerobiosis and in the presence of 5% CO(2). Some infectivity was retained in poor or reduced culture media. Comparative analysis of larval infectivity and protein secretion showed that loss of infectivity correlated with the appearance of non-tyvelosylated proteins that in turn may be related to the onset of moulting.

Low temperature conditions in building sandstone: the role of extreme events in temperate environments

Data on rock temperatures has previously been collected to characterise typical diurnal regimes, and more recently to describe short-term variability in extreme locations. However, there is also the case that little is understood concerning the impact of extreme events in otherwise temperate environments. Internal stone temperatures (5?cm) collected during the atypical cold extreme experienced, throughout the UK, in December 2010 show a difference between ambient air temperatures and aspect-related thermal differences, particularly concerning temperature lows and the influence of radiative heating. In this case, debris release was not visible; however, laboratory simulations have shown that under such conditions, surface loss does not necessarily negate the occurrence of internal stone modifications. This preparatory sequence of change demonstrates that surface loss is not the result of one process, but rather many operating over time to sufficiently decrease stone strength to facilitate obvious damage.

Palaeoglacial and palaeoclimatic conditions in the NW Pacific, as revealed by a morphometric analysis of cirques upon the Kamchatka Peninsula

The distribution of glacial cirques upon the Kamchatka peninsula, Far Eastern Russia, is systematically mapped from satellite images and digital elevation model data. A total of 3,758 cirques are identified, 238 of which are occupied by active glaciers. The morphometry of the remaining 3,520 cirques is analysed. These cirques are found to show a very strong N bias in their azimuth (orientation), likely resulting from aspect-related variations in insolation. The strength of this N bias is considered to indicate that former glaciation upon the peninsula was often ‘marginal’, and mainly of cirque-type, with peaks extending little above regional equilibrium-line altitudes. This is supported by the fact that S and SE-facing cirques are the highest in the dataset, suggesting that glacier-cover was rarely sufficient to allow S and SE-facing glaciers to develop at low altitudes. The strength of these azimuth-related variations in cirque altitude is thought to reflect comparatively cloud-free conditions during former periods of glaciation. It is suggested that these characteristics, of marginal glaciation and comparatively cloud-free conditions, reflect the region’s former aridity, which was likely intensified at the global Last Glacial Maximum, and during earlier periods of ice advance, as a result of the development of negative pressure anomalies over the North Pacific (driven by the growth of the Laurentide Ice Sheet), combined with other factors, including an increase in the extent and duration of sea ice, a reduction in global sea levels, cooler sea surface temperatures, and the localised growth of mountain glaciers. There is published evidence to suggest extensive glaciation of the Kamchatka Peninsula at times during the Late Quaternary, yet the data presented here appears to suggest that such phases were comparatively short-lived, and that smaller cirque-type glaciers were generally more characteristic of the period.

A qualitative study of the relationship between clinician attributes, organization, and patient characteristics on implementation of a disease management program

The purpose of this study was to examine the challenges of integrating an asthma disease management (DM) program into a primary care setting from the perspective of primary care practitioners. A second goal was to examine whether barriers differed between urban-based and nonurban-based practices. Using a qualitative design, data were gathered using focus groups in primary care pediatric practices. A purposeful sample included an equal number of urban and nonurban practices. Participants represented all levels in the practice setting. Important themes that emerged from the data were coded and categorized. A total of 151 individuals, including physicians, advanced practice clinicians, registered nurses, other medical staff, and nonmedical staff participated in 16 focus groups that included 8 urban and 8 nonurban practices. Content analyses identified 4 primary factors influencing the implementation of a DM program in a primary care setting. They were related to providers, the organization, patients, and characteristics of the DM program. This study illustrates the complexity of the primary care environment and the challenge of changing practice in these settings. The results of this study identified areas in a primary care setting that influence the adoption of a DM program. These findings can assist in identifying effective strategies to change clinical behavior in primary care practices. © 2008 Mary Ann Liebert, Inc.

ALCOHOL-RELATED KNOWLEDGE AND ATTITUDES IN PEOPLE WITH A MILD LEARNING-DISABILITY - THE EFFECTS OF A SENSIBLE DRINKING GROUP

Alcohol-related knowledge and attitudes in people with a mild learning disability, who were either living, or being prepared to live, in relatively independent conditions in the community, were assessed through a structured interview format. Compared with non-learning-disabled teenagers, adults and a hospitalized patient sample, alcohol-related knowledge in the people with a learning disability was found to be significantly poorer, alcohol was reported as having particularly negative effects and susceptibility to social pressure to drink alcohol was greater. A 'sensible drinking' group, taking a social skills and influences approach to alcohol education, was conducted with a subgroup of the individuals with a learning disability. The group format and methods, including in vivo sessions in a public house, are described. Follow-up evaluations suggested some significant positive changes in knowledge, attitudes and sensible drinking skills. It is concluded that this population, which is increasingly living, or being moved into, independent conditions in the community, is at least as vulnerable to social influences on alcohol use and abuse as are young people. As with young people, the usefulness of making available such alcohol-education programmes as described in this study, is discussed.

Peer tutoring in reading: The effects of role and organization on two dimensions of self-esteem

Background. Paired reading (PR) is an application of peer tutoring. It has been extensively researched, and its efficacy across a range of outcomes has been established. Benefits include improvements in key reading skills, and also in affective aspects of learning. Several studies have shown gains in self-esteem, although measurement methods have varied, and the model of self-esteem has rarely been clearly articulated.
Aims. To investigate the changes in self-esteem of children participating in a randomized trial of PR over a 15-week treatment period. To investigate the relative contribution of self-worth and self-competence to any gains in self-esteem. To investigate whether the pattern of change differs in children who take on different roles in the PR process.
Participants. The participants comprised a subset of a large-scale randomized trial of peer learning (The Fife Peer Learning Project). Four schools were randomly selected from schools allocated to the same-age PR condition, and four schools from those allocated to the cross-age PR condition. The same-age group consisted of 87 primary 6 children (10–11 years old). The cross-age group consisted of 81 primary 6 children. The controls, from schools randomly selected from a neighbouring authority, consisted of 92 primary 6 children.
Method. A pre–post design employing self-report measures of self-esteem. Rosenberg’s Self-Esteem Scale was used, with scores analysed for worth and competence. The treatment period was 15 weeks, with the participants following a prescribed PR process.
Results. Significant pre–post gains were noted in self-esteem, driven predominantly by improved beliefs about competence, in both same-age and cross-age conditions, but not for controls. Gains were also seen in self-worth in the cross-age condition. Further analyses of the influence of organizational condition (same-age or cross-age) and role played (tutor vs. tutee) showed significant differences between same-age tutors and cross-age tutors in relation to self-worth. Effect sizes were generally small or moderate.
Conclusions. The findings provide further support for the belief that PR can enhance self-esteem. Importantly, the use of a two-dimensional model provides extra information about self-perceptions in PR contexts: first, the central role of self- competence; and second, the gains in self-worth which are associated with tutoring younger children (but not same-age peers). This new information has educational significance for schools considering the potential of peer tutoring and the benefits of different organizational conditions.

Molecular mapping the presence of druggable targets in preinvasive and precursor breast lesions:a comprehensive review of biomarkers related to therapeutic interventions

The analysis of clinical breast samples using biomarkers is integral to current breast cancer management. Currently, a limited number of targeted therapies are standard of care in breast cancer treatment. However, these targeted therapies are only suitable for a subset of patients and resistance may occur. Strategies to prevent the occurrence of invasive lesions are required to reduce the morbidity and mortality associated with the development of cancer. In theory, application of targeted therapies to pre-invasive lesions will prevent their progression to invasive lesions with full malignant potential. The diagnostic challenge for pathologists is to make interpretative decisions on early detected pre-invasive lesions. Overall, only a small proportion of these pre-invasive lesions will progress to invasive carcinoma and morphological assessment is an imprecise and subjective means to differentiate histologically identical lesions with varying malignant potential. Therefore differential biomarker analysis in pre-invasive lesions may prevent overtreatment with surgery and provide a predictive indicator of response to therapy. There follows a review of established and emerging potential druggable targets in pre-invasive lesions and correlation with lesion morphology.

Farmer perception of suitable conditions for slurry application compared with decision support system recommendations

The application of slurry nutrients to land can be associated with unintended losses to the environment depending on soil and weather conditions. Correct timing of slurry application, however, can increase plant nutrient uptake and reduce losses. A decision support system (DSS), which predicts optimum conditions for slurry spreading based on the Hybrid Soil Moisture Deficit (HSMD) model, was investigated for use as a policy tool. The DSS recommendations were compared to farmer perception of suitable conditions for slurry spreading for three soil drainage classes (well, moderate and poorly drained) to better understand on farm slurry management practices and to identify potential conflict with farmer opinion. Six farmers participated in a survey over two and a half years, during which they completed a daily diary, and their responses were compared to Soil Moisture Deficit (SMD) calculations and weather data recorded by on farm meteorological stations. The perception of land drainage quality differed between farmers and was related to their local knowledge and experience. It was found that the allocation of grass fields to HSMD drainage classes using a visual assessment method aligned farmer perception of drainage at the national scale. Farmer opinion corresponded to the theoretical understanding that slurry should not be applied when the soil is wetter than field capacity, i.e. when drainage can occur. While weather and soil conditions (especially trafficability) were the principal reasons given by farmers not to spread slurry, farm management practices (grazing and silage) and current Nitrates Directive policies (closed winter period for spreading) combined with limited storage capacities were obstacles to utilisation of slurry nutrients. Despite the slightly more restrictive advice of the DSS regarding the number of suitable spreading opportunities, the system has potential to address an information deficit that would help farmers to reduce nutrient losses and optimise plant nutrient uptake by improved slurry management. The DSS advice was in general agreement with the farmers and, therefore, they should not be resistant to adopting the tool for day to day management.

A review of patents relating to therapeutic angiogenesis using endothelial progenitors and other vasculogenesis-related cell types

Stem and progenitor cells have generated considerable scientific and commercial interest in recent years due to their potential for novel cell therapy for a variety of medical conditions. A highly active research area in the field of regenerative medicine is vascular biology. Blood vessel repair and angiogenesis are key processes with endothelial progenitor cells (EPCs) playing a central role. Clinical trials for ischemic conditions, such as myocardial infarction and peripheral arterial disease, have suggested cell therapies to be feasible, safe, and potentially beneficial. Development of efficient methodologies to deliver EPC-based cytotherapies offers new hope for millions of patients with ischemic conditions. Evidence indicates that EPCs, depending on the subtype, mediate angiogenesis through different mechanisms. Differentiation into endothelium and complete integration into damaged vasculature was the first EPC mechanism to be proposed. However, many studies have demonstrated that vasoregulatory paracrine factor secretion by transplanted cells is also important. Many EPC subsets enhance angiogenesis and promote tissue repair by cytokine release without incorporating into the damaged vasculature. Whatever the mechanism, vascular repair and therapeutic angiogenesis using EPCs represent a realistic treatment option and also provides many commercialization opportunities. This review discusses recent advances in the EPC field whilst recounting relevant patents.