An item response analysis of the motor and behavioral subscales of the unified Huntington's disease rating scale in huntington disease gene expansion carriers

Although the Unified Huntington's Disease Rating Scale (UHDRS) is widely used in the assessment of Huntington disease (HD), the ability of individual items to discriminate individual differences in motor or behavioral manifestations has not been extensively studied in HD gene expansion carriers without a motor-defined clinical diagnosis (ie, prodromal-HD or prHD). To elucidate the relationship between scores on individual motor and behavioral UHDRS items and total score for each subscale, a nonparametric item response analysis was performed on retrospective data from 2 multicenter longitudinal studies. Motor and behavioral assessments were supplied for 737 prHD individuals with data from 2114 visits (PREDICT-HD) and 686 HD individuals with data from 1482 visits (REGISTRY). Option characteristic curves were generated for UHDRS subscale items in relation to their subscale score. In prHD, overall severity of motor signs was low, and participants had scores of 2 or above on very few items. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a lesser extent, saccade velocity, dysarthria, tongue protrusion, pronation/supination, Luria, bradykinesia, choreas, gait, and balance on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. In prHD, depressed mood, anxiety, and irritable behavior demonstrated good discriminative properties. In HD, depressed mood demonstrated a good relationship with the overall behavioral score. These data suggest that at least some UHDRS items appear to have utility across a broad range of severity, although many items demonstrate problematic features.

Rodents as carriers of disease: preliminary studies in the United Kingdom

The University of Reading has conducted some preliminary work on the prevalence of Campylobacter spp., Salmonella spp. and Arenavirus in Norway rats trapped from farms and semi-urban areas in central southern England. Campylobacter is the cause of a notificable disease in the UK, with 57,772 cases reported for England and Wales in 2009. Transmission to humans is believed to be primarily through undercooked meat, from contaminated water, and through contact with pets; and symptoms include a high temperature, severe diarrhoea, vomiting and abdominal pain. Ninety-seven per-cent of sporadic cases have been attributed to farm animals, and in particular the meat and poultry industry. There are eighteen species of Campylobacter, eleven of which can be pathogenic to humans; although the principal species that cause gastrointestinal disease in humans are C. jejuni and C. coli; although C. lari, C. helveticus and C. upsaliensis are also involved. Salmonella species also causes a gastrointestinal disease, and in the UK, is common in chicken and has been linked to egg production. Species are typed using antigen specific agglutination tests, or by their susceptibility to specific bacteriophage. Some strains are known to be linked with human disease (eg. S. enteritidis PT4).

The role of rodents as carriers of disease on UK farms: a preliminary investigation

In the UK, Campylobacter spp. and Lymphocytic Choriomeningitis Virus (LCMV), an Old World arenavirus, cause two zoonoses of concern that may be transmissible from rodents to humans and livestock. The aims of this preliminary investigation were to examine the occurrence of Campylobacter spp. and LCMV in Norway rats Rattus norvegicus on UK farms and to identify and characterise the Sequence Types of the Campylobacter isolates. Samples were collected from wild Norway rats and fresh Norway rat faeces. Multi Locus Sequence Typing (MLST) was performed on C. spp. isolates and samples were tested for arenavirus RNA by RT-PCR. Six C. spp. isolates were identified. One isolate was C. lari and five isolates were C. jejuni. Following MSLT profiling, three unique C. jejuni sequence types were identified. Two of which are novel and the third is typically associated with livestock and human infection. Nine positive results for LCMV were obtained giving an overall prevalence of 25% across four sites. This is higher than previously reported for this species.

Polysialic acid as a drug carrier: evaluation of a new polysialic acid–epirubicin conjugate and its comparison against established drug carriers

This paper explores the potential of polysialic acid (PSA) as a carrier for low molecular weight anticancer drugs. A PSA–epirubicin (Epi) conjugate was synthesized and compared against Epi conjugates containing established carriers, namely: N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers, poly(ethylene glycol) (PEG) and polyglutamic acid (PGA). Biological assessments in the breast cancer cell line MCF-7 and in the anthracycline resistant MCF-7/DX showed that the PSA–Epi conjugate had the highest activity (40% and 30% cell death in the two cell lines at 1 mM Epi equiv., respectively). FACS studies confirmed internalization of all conjugates by cholesterol-dependent endocytosis. PSA–Epi showed release of Epi (40% at 5 h) when incubated with lysosome extracts. In vivo evaluation showed that all conjugates had a significantly longer half-life compared to free Epi. This study also allowed an investigation on the effect of the polymeric carrier on the biological activity of a conjugate, with the biodegradability of the carrier emerging as an important feature.

Thr54 allele carriers of the Ala54Thr variant of FABP2 gene have associations with metabolic syndrome and hypertriglyceridemia in urban South Indians

The intestinal fatty acid-binding protein gene is proposed as a candidate gene for diabetes because the protein it codes is involved in fatty acid absorption and metabolism. This study investigates the association of the Ala54Thr variant of the intestinal fatty acid-binding protein gene on type 2 diabetes mellitus and other related metabolic traits in Asian Indians. Ala54Thr polymorphism was genotyped by using polymerase chain reaction-restriction fragment length polymorphism in unrelated 773 type 2 diabetic and 899 normal glucose-tolerant (NGT) subjects, randomly chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in South India. The Ala54Thr polymorphism was not associated with type 2 diabetes mellitus or obesity. However, genotype-phenotype study revealed that the NGT subjects carrying the Thr54 allele had significantly higher 2-hour plasma glucose (P = .007), glycated hemoglobin (P = .004), 2-hour insulin (P = .027), and fasting low-density lipoprotein cholesterol (P = .032) levels compared with those with the Ala54 allele. Normal glucose-tolerant subjects with Ala54Thr and Thr54Thr genotypes had significantly higher fasting serum triglyceride levels (P = .003) compared with those with Ala54Ala. The subjects were stratified into those with hypertriglyceridemia (serum triglyceride levels >or=150 mg/dL) and those without. The odds ratio for hypertriglyceridemia for the individuals carrying the Ala54Thr genotype was 1.491 (95% confidence interval [CI], 1.22-1.83, P < .0001), and for those carrying the Thr54Thr genotype, it was 1.888 (95% CI, 1.34-2.67; P < .0001). Subjects were also stratified into those with metabolic syndrome (MS) and those without, according to modified Adult Treatment Panel III guidelines. The odds ratio (adjusted for age and sex) for MS for the individuals carrying the Ala54Thr genotype was 1.240 (95% CI, 1.02-1.51; P = .03), whereas for those carrying the Thr54Thr genotype, it was 1.812 (95% CI, 1.28-2.57; P = .001). Carriers of the Thr54 allele have associations with MS and hypertriglyceridemia in this urban South Indian population.

Accounting information systems as institutional carriers: a case study of regulatory compliance in UK asset management houses

Previously, governments have responded to the impacts of economic failures and consequently have developed more regulations to protect employees, customers, shareholders and the economic wellbeing of the state. Our research addresses how Accounting Information Systems (AIS) may act as carriers for institutionalised practices associated with maintaining regulatory compliance within the context of UK Asset Management Houses. The AIS was found to be a strong conduit for institutionalized compliance related practices, utilising symbolic systems, relational systems, routines and artefacts to carry approaches relating to regulative, normative and cultural-cognitive strands of institutionalism. Thus, AIS are integral to the development and dissipation of best practice for the management of regulatory compliance. As institutional elements are clearly present we argue that AIS and regulatory compliance provide a rich context to further institutionalism. Since AIS may act as conduits for regulatory approaches, both systems adopters and clients may benefit from actively seeking to codify and abstract best practices into AIS. However, the application of generic institutionalized approaches, which may be applied across similar organizations, must be tempered with each firm’s business environment and associated regulatory exposure. A balance should be sought between approaches specific enough to be useful but generic enough to be universally applied.

Characterisation of dystrophin in carriers of Duchenne muscular dystrophy.

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, was studied in needle biopsy samples taken from the quadriceps muscle of 15 asymptomatic carriers of DMD (13 adults and 2 young girls) and one symptomatic adult carrier. Antibodies to N- and C-terminal regions of dystrophin were used for both Western blot analysis and immunocytochemistry and a monoclonal antibody to beta-spectrin used to assess membrane integrity. All asymptomatic adult carriers showed some abnormality in dystrophin immunostaining but very few negative fibres were present. A clear mosaic of dystrophin positive and negative fibres was seen only in the adult symptomatic carrier and the two young girls. On a Western blot, all carriers studied had dystrophin of normal molecular weight, but most had reduced abundance. In adult carriers, the amount of dystrophin relative to normal controls varied, but it was unrelated to age, serum creatine kinase (CK) levels or to the degree of pathology. Carriers with normal CK showed abnormalities in dystrophin expression. The dystrophin immunoblotting profile of the 2 young girls was very similar to that of their mothers, but the mosaic pattern of immunostaining was not apparent in the older carriers. In conclusion, dystrophin immunostaining and Western blot analysis of biopsy samples from asymptomatic carriers is often abnormal and they may be useful additional aids for establishing carrier status, particularly in younger girls.

Manifesting carriers of Xp21 muscular dystrophy; lack of correlation between dystrophin expression and clinical weakness.

Ten females presenting with muscle weakness and a raised serum creatine kinase revealed abnormalities in the expression of dystrophin in their muscle biopsies and were diagnosed as manifesting carriers of Xp21 Duchenne/Becker muscular dystrophy. Seven cases, aged 3-22 yr at the time of biopsy, had a variable proportion of dystrophin-deficient fibres and an abnormal expression on immunoblot. These were confidently diagnosed as manifesting carriers. Results in the remaining three cases, aged 8-10 yr, were less clear-cut. Dystrophin expression on immunoblots was slightly reduced and some unevenness and reduction of immunolabelling was seen on sections, but dystrophin-deficient fibres were not a feature of these cases. The weakness in the ten carriers ranged from minimal to severe and there was no correlation between the degree of weakness and the number of dystrophin-deficient fibres. Two minimally weak girls had a high proportion of dystrophin-deficient fibres. Our results show that analysis of dystrophin expression is useful for the differential diagnosis of carriers of Xp21 dystrophy and autosomal muscular dystrophy, but that dystrophin expression does not correlate directly with the degree of clinical weakness.