Audit and comprehensive health assessment programme in the primary healthcare of adults with intellectual disability: a pilot study

International research has demonstrated significant shortcomings in the health of adults with intellectual disability (ID). Because general practitioners (GPs) are the main providers of primary healthcare for this population, strategies to improve general practice care are an important aspect of rectifying these shortcomings. The present pilot study aimed to determine the effect of various interventions on health maintenance activities and to assess their acceptability to GPs, with a view to informing larger scale studies. The GPs were recruited through an earlier questionnaire-based postal survey. The GPs identified all their adult patients with ID, then obtained consent for participation from three patients randomly selected by the investigators. The GPs completed two self-evaluation forms and case note audits 12 months apart, read a synopsis of the relevant literature provided by the researchers, and completed a comprehensive health assessment (CHA) of their three patients. Forty-five GPs agreed to participate in the CHA programme (CHAP), and 15 completed the project. Thirty-eight patients completed the project. The number of patient-GP dyads who completed the project was too small to demonstrate statistically significant changes in health issues over time. The GPs found that the synopsis of the literature was the best intervention for increasing knowledge and was also the most practical to use in general practice. The CHAP was the intervention that prompted the most action from the GP which would not have been undertaken otherwise. The CHAP appeared to provide a superior review process compared to the other interventions used in the present study. The numbers of health maintenance activities found to be overdue and the number of health issues detected as a result of the process were considerable. The CHAP served as a communication tool and an educative instrument, providing a basis for future studies and strategies to improve the general practice care of adults with ID.

Kinase-dependent and kinase-independent functions of EphA4 receptors in major axon tract formation in vivo

The EphA4 receptor tyrosine kinase regulates the formation of the corticospinal tract (CST), a pathway controlling voluntary movements, and of the anterior commissure (AC), connecting the neocortical temporal robes. To study EphA4 kinase signaling in these processes, we generated mice expressing mutant EphA4 receptors either lacking kinase activity or with severely downregulated kinase activity. We demonstrate that EphA4 is required for CST formation as a receptor for which it requires an active kinase domain. In contrast, the formation of the AC is rescued by kinase-dead EphA4, suggesting that in this structure EphA4 acts as a ligand for which its kinase activity is not required. Unexpectedly, the cytoplasmic sterile-alpha motif (SAM) domain is not required for EphA4 functions. Our findings establish both kinase-dependent and kinase-independent functions of EphA4 in the formation of major axon tracts.

Vps45p stabilizes the syntaxin homologue Tlg2p and positively regulates SNARE complex formation

Sec1p-like/Munc-18 (SM) proteins bind to t-SNAREs and inhibit ternary complex formation. Paradoxically, the absence of SM proteins does not result in constitutive membrane fusion, Here, we show that in yeast cells lacking the SM protein Vps45p, the t-SNARE Tlg2p is down-regulated, to undetectable levels, by rapid proteasomal degradation. In the absence of Vps45p, Tlg2p can be stabilized through abolition of proteasome activity. Surprisingly, the stabilized Tlg2p was targeted to the correct intracellular location. However, the stabilized Tlg2p is non-functional and unable to bind its cognate SNARE binding partners, Tlg1p and Vti1p, in the absence of Vps45p, A truncation mutant lacking the first 230 residues of Tlg2p no longer bound Vps45p but was able to form complexes with Tlg1p and Vti1p in the absence of the SM protein. These data provide us with two valuable insights into the function of SM proteins. First, SM proteins act as chaperone-like molecules for their cognate t-SNAREs, Secondly, SM proteins play an essential role in the activation process allowing their cognate t-SNARE to participate in ternary complex formation.

Cost of malaria control in China: Henan's consolidation programme from community and government perspectives

Objective To assist with strategic planning for the eradication,of malaria in Henan Province, China, which reached the consolidation phase of malaria control in 1992, when only 318 malaria cases were reported, Methods We conducted a prospective two-year study of the costs for Henan's malaria control programme. We used a cost model that could also be applied to other malaria programmes in-mainland China, and analysed the cost of the three components of Henan's malaria programme. suspected malaria case management,, vector surveillance,,and population blood surveys. Primary cost data were collected from the government, and data on suspected malaria patient's were collected in two malaria counties (population 2 093 100). We enlisted the help of 260 village doctors. in six-townships or former communities (population 247 762), and studied all 12 315 reported cases of suspected malaria in catchment areas in 1994 and 1995. Findings The average-annual government investment in malaria control was estimated to be US$ 111 516 (case-management 59%; active blood surveys 25%;vector surveillance 12%; and contingencies and special projects 4%). The average cost (direct and indirect) for-patients seeking-treatment for suspected malaria was US$ 3.48, equivalent,to 10 days' income for rural residents. Each suspected malaria case cost the government an, average of US$ 0.78. Conclusion Further cuts in government funding will increase future costs, when epidemic malaria returns; investment in malaria control should therefore continue at least at current levels,of US$ 0.03 per person a risk.

Complementation analysis of the flavivirus Kunjin NS3 and NS5 proteins defines the minimal regions essential for formation of a replication complex and shows a requirement of NS3 in cis for virus assembly

We have previously reported successful trans-complementation of defective Kunjin virus genomic RNAs with a range of large lethal deletions in the nonstructural genes NSI, NS3, and NS5 (A. A. Khromykh et al., J. Virol. 74:3253-3263, 2000). In this study we have mapped further the minimal region in the NS5 gene essential for efficient trans-complementation of genome-length RNAs in repBHK cells to the first 316 of the 905 codons. To allow amplification and easy detection of complemented defective RNAs with deletions apparently affecting virus assembly, we have developed a dual replicon complementation system. In this system defective replicon RNAs with a deletion(s) in the nonstructural genes also encoded the puromycin resistance gene (PAC gene) and the reporter gene for beta-galactosidase (beta-Gal). Complementation of these defective replicon RNAs in repBHK cells resulted in expression of PAC and beta-Gal which allowed establishment of cell lines stably producing replicating defective RNAs by selection with puromycin and comparison of replication efficiencies of complemented defective RNAs by beta-Gal assay. Using this system we demonstrated that deletions in the C-terminal 434 codons of NS3 (codons 178 to 611) were complemented for RNA replication, while any deletions in the first 178 codons were not. None of the genome-length RNAs containing deletions in NS3 shown to be complementable for RNA replication produced secreted defective viruses during complementation in repBHK cells. In contrast, structural proteins produced from these complemented defective RNAs were able to package helper replicon RNA. The results define minimal regions in the NS3 and NS5 genes essential for the formation of complementable replication complex and show a requirement of NS3 in cis for virus assembly.

Shoot control of hypernodulation and aberrant root formation in the har1-1 mutant of Lotus japonicus

The har1-1 mutant of Lotus japonicus B-129-S9 Gifu is characterized by two phenotypes: greater than normal nodulation (hypernodulation) and significantly inhibited root growth in the presence of its microsymbiont Mesorhizobium loti strain NZP2235. We demonstrate that the two traits co-segregate, suggesting a single genetic alteration involving developmental pleiotropy. A cross between the mutant and genotype Funakura (with wild-type root and nodule morphology) demonstrated Mendelian recessive segregation of both phenotypes (root and nodule) in 216 F2 individuals. Using DNA-amplification fingerprinting polymorphisms in Gifu har1-1 and Funakura, the mutant locus was positioned between two markers at about 7 and 13 cM distance. Reciprocal hypocotyl grafting of shoots and roots showed that the hypernodulation and reduced root phenotypes are both predominantly controlled by the shoot.

Differential requirements for COPI coats in formation of replication complexes among three genera of Picornaviridae

Picornavirus RNA replication requires the formation of replication complexes (RCs). consisting of virus-induced vesicles associated with viral nonstructural proteins and RNA. Brefeldin A (BFA) has been shown to strongly inhibit RNA replication of poliovirus but not of encephalomyocarditis virus (EMCV). Here, we demonstrate that the replication of parechovirus 1 (ParV1) is partly resistant to BFA, whereas echovirus 11 (EV11) replication is strongly inhibited. Since BFA inhibits COPI-dependent steps in endoplasmic reticulum (ER)-Golgi transport, we tested a hypothesis that different picornaviruses may have differential requirements for COPI in the formation of their RCs. Using immunofluorescence and cryo-immunoelectron microscopy we examined the association of a COPI component, beta-COP, with the RCs of EMCV, ParV1, and EV11 EMCV RCs did not contain beta-COP. In contrast, beta-COP appeared to be specifically distributed to the RCs of EV11 In ParV1-infected cells beta-COP was largely dispersed throughout the cytoplasm, with some being present in the RCs. These results suggest that there are differences in the involvement of COPI in the formation of the RCs of various picornaviruses, corresponding to their differential sensitivity to BFA. EMCV RCs are likely to be formed immediately after vesicle budding from the ER, prior to COPI association with membranes. ParV1 RCs are formed from COPI-containing membranes but COPI is unlikely to be directly involved in their formation, whereas formation of EV11 RCs appears to be dependent on COPI association with membranes.

Petrology and geochemistry of the Bandas del Sur Formation, Las Canadas Edifice, Tenerife (Canary Islands)

The Bandas del Sur Formation preserves a Quaternary extra-caldera record of central phonolitic explosive volcanism of the Las Canadas volcano at Tenerife. Volcanic rocks are bimodal in composition, being predominantly phonolitic pyroclastic deposits, several eruptions of which resulted in summit caldera collapse, alkali basaltic lavas erupted from many fissures around the flanks. For the pyroclastic deposits, there is a broad range of pumice glass compositions from phonotephrite to phonolite. The phonolite pyroclastic deposits are also characterized by a diverse, 7-8-phase phenocryst assemblage (alkali feldspar + biotite + sodian diopside + titanomagnetite + ilmenite + nosean-hauyne + titanite + apatite) with alkali feldspar dominant, in contrast to interbedded phonolite lavas that typically have lower phenocryst contents and lack hydrous phases. Petrological and geochemical data are consistent with fractional crystallization (involving the observed phenocryst assemblages) as the dominant process in the development of phonolite magmas. New stratigraphically constrained data indicate that petrological and geochemical differences exist between pyroclastic deposits of the last two explosive cycles of phonolitic volcanism. Cycle 2 (0.85-0.57 Ma) pyroclastic fall deposits commonly show a cryptic compositional zonation indicating that several eruptions tapped chemically, and probably thermally stratified magma systems. Evidence for magma mixing is most widespread in the pyroclastic deposits of Cycle 3 (0.37-0.17 Ma), which includes the presence of reversely and normally zoned phenocrysts, quenched mafic glass blebs in pumice, banded pumice, and bimodal to polymodal phenocryst compositional populations. Syn-eruptive mixing events involved mostly phonolite and tephriphonolite magmas, whereas a pre-eruptive mixing event involving basaltic magma is recorded in several banded pumice-bearing ignimbrites of Cycle 3. The periodic addition and mixing of basaltic magma ultimately may have triggered several eruptions. Recharge and underplating by basaltic magma is interpreted to have elevated sulphur contents (occurring as an exsolved gas phase) in the capping phonolitic magma reservoir. This promoted nosean-hauyne crystallization over nepheline, elevated SO3 contents in apatite, and possibly resulted in large, climatologically important SO2 emissions.

Attitudes of paediatric medical ward staff to a dog visitation programme

No previous studies regarding either structured, strictly controlled pet visitation programmes in paediatric hospital wards or hospital staff attitudes towards them have been conducted in Australia. Information regarding these is essential in order to minimize problems during implementation of such programmes. The aim of the study was to analyse hospital staff perceptions regarding the introduction of a pet visitation programme in an acute paediatric medical ward prior to and following implementation of the programme and to compare attitudes between the various professional groups. The study consisted of two cross-sectional surveys. A total of 224 anonymous questionnaires were distributed to administrators, doctors, nursing staff and therapists 6 weeks before and 195 were distributed 12 weeks after the introduction of a pet visitation programme. Responses were received from 115 respondents (before the programme introduction) and 45 respondents (after the programme introduction). Prior to the introduction of the dog visitation programme, there were high staff expectations that the programme would distract children from their illness, relax children and that it was a worthwhile project for the hospital to undertake. Following implementation of the programme these expectations were strongly endorsed, in addition to the perception that the ward was a happier place, the work environment was more interesting and that nurses accepted the dogs. After implementation staff were less concerned about the possibility of dog bites and dogs doing damage to equipment. Allied health staff and non-clinical staff were more positive about the programme with respect to ward climate and acceptance than were doctors and nurses. We conclude that well-planned dog visitation programmes result in positive anticipation among staff and high levels of satisfaction following programme impact.

Multiple shoot formation in lentil (Lens culinaris) seeds

A protocol based on seed culture was developed for efficient in vitro propagation of lentil (Lens culinaris Medik). Benzyladenine (BA), thidiazuron (TDZ), and kinetin all induced multiple shoot formation. In terms of the number of long shoots (>2.0 cm) produced per seed, BA and TDZ at optimum concentrations (0.2-0.4 and 0.1 mg/litre, respectively) had similar efficiency, whereas kinetin produced less shoots. Murashige and Skoog (MS) salt composition was better than that of Gamborge (B5) for shoot induction. Increasing calcium (Ca) concentration was necessary to overcome shoot-tip necrosis. For shoot elongation, fresh medium of the same composition of shoot induction medium could be used for stumps from medium with low BA (

Hepatic covalent adduct formation with zomepirac in the CD26-deficient mouse

Background and Aims: Zomepirac (ZP), a non-steroidal anti-inflammatory drug (NSAID), has been reported to cause immune-mediated liver injury. In vivo, ZP is metabolized to a chemically reactive acyl glucuronide conjugate (ZAG) which can undergo covalent adduct formation with proteins. Such acyl glucuronide-derived drug-protein adducts may be important in the development of immune and toxic responses caused by NSAID. We have shown using immunoabsorptions that the 110 kDa CD26 (dipeptidyl peptidase IV) is one of the hepatic target proteins for covalent modification by ZAG. In the present study, a CD26-deficient mouse strain was used to examine protein targets for covalent modification by ZP/metabolites in the liver. Methods and Results: The CD26-deficient phenotype was confirmed by immunohistochemistry, flow cytometry analysis, RT-PCR, enzyme assay and immunoblotting. Moreover, by using monoclonal antibody immunoblots, CD26 was not detected in the livers of ZP-treated CD26-deficient mice. Immunoblots using a polyclonal antiserum to ZP on liver from ZP-treated mice showed three major sizes of protein bands, in the 70, 110 and 140 kDa regions. Most, but not all, of the anti-ZP immunoreactivity in the 110 kDa region was absent from ZP-treated CD26-deficient mice. Conclusion: These data definitively showed that CD26 was a component of ZP-modified proteins in vivo. In addition, the data suggested that at least one other protein of approximately 110 kDa was modified by covalent adduct formation with ZAG. (C) 2002 Blackwell Science Asia Pty Ltd.