Nucleotide sequence analyses of genomic RNAs of Peanut stunt virus Mi,the type strain representative of a novel PSV subgroup from China

Summary. The complete nucleotide sequence of Peanut stunt virus strain Mi (PSV-Mi) from China was determined and compared to other viruses of the genus Cucumovirus. The tripartite genome of PSV-Mi encoded five open reading frames (ORFs) typical of cucumoviruses. Distance analyses of four ORFs indicated that PSV-Mi differed sufficiently in nucleotide sequence from other PSV strains of subgroups I and II to warrant establishment of a third subgroup of PSV.     

Effect of choice of measles-mumps-rubella vaccine on immediate vaccination pain in infants

OBJECTIVE: To compare acute pain response to 2 measles-mumps-rubella vaccines. DESIGN: Double-blind clinical trial. SETTING: Hospital for Sick Children, Toronto, Ontario.Patients Forty-nine infants 12 months of age receiving their first measles-mumps-rubella vaccination. INTERVENTIONS: Random allocation to receive Priorix or M-M-R II. MAIN OUTCOME MEASURES: Pain responses before (baseline) and after (within 15 seconds) vaccination were quantified by visual analog scale (VAS; range, 0-100), completed by the parent and independently by the pediatrician, and the Modified Behavioral Pain Scale (range, 0-10), scored by a coder blinded to the vaccine allocation. Crying (yes or no) and latency to the first cry after injection were also measured. RESULTS: Twenty-six infants received Priorix and 23 received M-M-R II. There were no differences between the 2 groups in baseline characteristics or prevaccination baseline pain scores. Median pain scores after vaccination (Priorix vs M-M-R II) were as follows: pediatrician VAS, 15 vs 58 (P =.001); parent VAS, 22 vs 53 (P =.007); and Modified Behavioral Pain Scale, 6 vs 8 (P =.02). Median difference in pain scores (after minus before) for Priorix vs M-M-R II were as follows: pediatrician VAS, 15 vs 53 (P =.003); parent VAS, 22 vs 47 (P =.008); and Modified Behavioral Pain Scale, 3 vs 5 (P =.03). The median latency to first cry was 1.5 seconds in the Priorix group compared with 1 second in the M-M-R II group (P =.26). CONCLUSIONS: Priorix vaccine causes significantly less pain than M-M-R II at the time of injection for 12-month-old infants receiving their first measles-mumps-rubella vaccination.     

No need for outpatient physiotherapy following total knee arthroplasty: a randomized trial of 120 patients

BACKGROUND: We have not found any reports on the effect of physiotherapy after knee replacement. PATIENTS AND METHODS: In a prospective randomized controlled trial, we randomized two groups to receive or not receive outpatient physiotherapy following total knee arthroplasty. 120 patients were recruited over 2 years, each followed up for 1 year. Inclusion criteria were age between 55-90 years, less than 40 degrees of fixed flexion contracture and the ability to walk at least 10 meters unaided preoperatively with monoarticular arthrosis. RESULTS: We found no statistically significant benefit of outpatient physiotherapy at any of the three times measured. After adjusting for baseline differences between the two treatment groups, the mean difference in knee flexion 1 year postoperatively was only 2.9 degrees. This mean difference is of no clinical significance. INTERPRETATION: We concluded that in a preselected group of patients following primary total knee arthroplasty, inpatient physiotherapy with good instructions and a well-structured home exercise regime can dispense with the need for outpatient physiotherapy.     

Actin-related myopathy without any missense mutation in the ACTA1 gene

Actinopathies are defined by missense mutations in the ACTA1 gene coding for sarcomeric actin, of which some 70 families have, so far, been identified. Often, but not always, muscle fibers carry large patches of actin filaments. Many such patients also have nemaline myopathy, qualifying actinopathies as a subgroup of nemaline myopathies. This article concerns a then newborn, now 2 1/2-year-old boy, the first and single child of nonconsanguineous parents, who was born floppy, requiring immediate postnatal assisted ventilation. A quadriceps muscle biopsy revealed large patches of thin myofilaments reacting at light and electron microscopic levels with antibodies against actin but only a few sarcoplasmic rods and no intranuclear rods. DNA analysis of the patient's and both parents' blood did not reveal any missense mutation in the ACTA1 gene. Thus, this congenital myopathy can be caused by a new type of ACTA1 gene mutation, a new non-ACTA1 gene mutation, or no mutation at all, designating it as an actin-related myopathy, perhaps a new type of congenital myopathy and a new member of protein aggregate myopathies marked by aggregation of proteins within muscle fibers, among them desminopathies, alpha-beta crystallinopathies, other desmin-related myopathies (also termed myofibrillar myopathies), actinopathies and, now, actin-related myopathies.     

BRAF mutations are detectable in conjunctival but not uveal melanomas

Activating mutations in exon 15 of BRAF have been detected in a high proportion of cutaneous melanomas. To determine whether such mutations are a feature of conjunctival or uveal melanomas, we screened DNA from these tumours. Twenty-one conjunctival and 88 uveal tumours were included in the study. Mutation analysis of BRAF exons 11 and 15 was undertaken using a combination of conformationally sensitive gel electrophoresis and direct sequencing. Mutations in exon 15 were detected in three of the conjunctival tumours (two V599E and one E585 K). None of the uveal tumours possessed a BRAF mutation in either exon 15 or 11. We conclude that uveal melanomas arise independently of oncogenic BRAF mutations, but the development of a proportion of conjunctival tumours involves mutation of this gene.     

HLA associations with occupational sensitization to rat lipocalin allergens: a model for other animal allergies?

BACKGROUND: Laboratory animal allergy is a common occupational health problem affecting between 11% and 44% of exposed researchers. Allergy to rats and mice is most common, probably because these are the animals most frequently used. OBJECTIVE: We hypothesized that HLA class II molecules, involved in the presentation of allergen to the T cell and likely candidates for controlling the immune response, might be associated with sensitization to rat urinary proteins among laboratory animal handlers. METHODS: We undertook a cross-sectional study of 741 employees at 6 pharmaceutical sites across the United Kingdom who had contact at work with laboratory rats. In all, 109 cases with specific sensitization to rat proteins and 397 referents were HLA-typed for DRB1 and DQB1 loci. Amino acid analyses of significantly associated HLA molecules were carried out. RESULTS: HLA-DR7 was associated with sensitization (odds ratio [OR], 1.82; CI, 1.12-2.97), respiratory symptoms at work (OR, 2.96; CI, 1.64-5.37) and, most strongly, sensitization with symptoms (OR, 3.81; CI, 1.90-7.65). HLA-DR3 was protective against sensitization (OR, 0.55; CI, 0.31-0.97). Amino acid analyses of these 2 molecules indicated a biologically plausible explanation for the associations. CONCLUSION: HLA phenotype is an important determinant of individual susceptibility to sensitization and asthma among laboratory animal workers. Similar mechanisms might apply in other animal allergies.     

Genetic organisation of <Emphasis Type="Italic">Iris yellow spot virus</Emphasis> M RNA: indications for functional homology between the G<Subscript>(C)</Subscript> glycoproteins of tospoviruses and animal-infecting bunyaviruses

Summary.  The complete nucleotide sequence (4838 nucleotides) of Iris yellow spot virus (IYSV) M RNA indicates, typical for tospoviruses, the presence of two genes in ambisense arrangement. The vRNA ORF codes for the potential cell-to-cell movement (NSm) protein (34.8 kDa) and the vcRNA ORF for the viral glycoprotein (G1/G2) precursor (128.6 kDa). Multiple sequence alignment of the NSm and G1/G2 precursor proteins of IYSV with those of other tospoviruses, showed highest homologies to Peanut bud necrosis virus (PBNV) and Watermelon silver mottle virus (WSMV). The potential cell-to-cell movement protein of tospoviruses is highly conserved (40–70% identity), with the exception of the first 60 N terminal amino acids, a domain that clearly diverged. For the G1 and G2 viral glycoproteins, blast searches revealed a significant homology between the C-terminally located tospoviral G1 (G_(C)) protein with the counterpart of the animal-infecting bunyaviruses, suggesting a functional homology for these proteins. Received January 15, 2002; accepted July 10, 2002     

A 6-year study of cognition and spatial function in the demented and non-demented elderly: the Sydney Older Persons Study

BACKGROUND: Spatial function has been suggested to be disproportionately worse in people with dementia with Lewy bodies (DLB) than other dementia groups, and poor performance on the Mini-Mental State Examination pentagon copying (PC) task has been proposed as adequate for assessing this. We aimed to establish the prevalence of poor PC in the non-demented elderly; determine the validity of the use of PC as a spatial function test, and determine if poor PC is more common in DLB than non-DLB dementias. METHODS: In a population-based sample of 299 participants, 126 were rated as being cognitively normal (clinical rating scale [CDR] = 0), 95 mildly cognitively impaired (CDR = 0.5), and 78 met criteria for dementia, 19 of whom met criteria for probable DLB (pDLB) and 25 with none of the core features of DLB (non-DLB). The accuracy of PC performance was determined across CDR groups, and the relationship of PC to performance on a broad range of cognitive tests was evaluated. The dementia groups were compared cross-sectionally to determine differences in PC and other cognitive test performance, as well as 3 and 6 years earlier to determine cognitive differences at initial stages of cognitive decline. RESULTS: Poor PC was common in the non-demented elderly (39% CDR = 0; 43% CDR = 0.5). In this non-demented group, PC was selectively related to tests of spatial function. Poor PC was not significantly different in the pDLB and non-DLB groups at any assessment time, however it became more prevalent as dementia severity increased. Memory function and verbal fluency were more impaired in the pDLB group in the early stages of the disorder. COMMENT: PC appears to be a good measure of spatial function in the elderly. However, in contrast to other findings of poor spatial skills in DLB when dementia is in the mild to moderate stages, poor PC performance has not been shown to be a good early marker of DLB and its clinical correlates are yet to be determined.     

Estimating the marginal value of 'better' research output: 'designed' versus 'routine' data in randomised controlled trials

We recently completed a study which demonstrated that the costs of health technology assessment (HTA) by randomised controlled trial (RCT) can be reduced by substituting routine datasets for data designed and collected specifically for a trial. This cost reduction, however, had the effect of reducing the quality of the research output. In the present study we attempted to tease out the values attached to the 'better' information provided by designed data RCTs using a mock grants committee. Two valuation techniques, implied values and willingness to pay, were used. Ex ante valuations were determined by comparing alternative research proposals - a more costly version using designed data and a cheaper version using routine data. Ex post valuations were determined by comparing results of both versions. The exercise was performed on four exemplar studies. Overall, the committee expressed a general lack of trust towards routine data both ex ante and ex post and placed high values on the better information from the designed data studies - particularly information on preferences. This suggests that currently available routine datasets are not perceived to be able to provide efficient alternatives to designed data for RCTs.