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Biomedical subjects

R Perera

Publications and source records attributed to R Perera.

At least 19 recordsLinked to original sources
PubMed2006

Statin treatment for children and adolescents with heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis.

AIMS: To assess efficacy and safety of HMG-CoA reductase inhibitor (statin) treatment in children and adolescents with heterozygous familial hypercholesterolaemia. METHODS: MEDLINE, EMBASE, COCHRANE and Current Controlled Trials databases were searched. Study design, efficacy, and safety outcome-measures were extracted. Results of parallel-group randomised placebo controlled trials with low density (LDL) and high density lipoprotein cholesterol (HDL), and triglycerides as outcomes were pooled using standard meta-analytical methods. RESULTS: One hundred and fifty seven of 1060 identified papers studied familial hypercholesterolaemia, and 18 papers reported 7 prospective case series, 1 non-randomised trial, 2 trials with active treatment control groups, and 8 parallel-group randomised placebo controlled trials (RCT). The RCTs randomised 947 children, aged 8-18 years, for periods of 6-96 weeks with an estimated 850 person-years follow-up. There were no differences in clinical or laboratory adverse reactions between placebo and active treatment. Statins lowered LDL 32.5% (95% CI 24.3, 40.7), increased HDL 3.4% (0.8, 6.0), lowered triglycerides 3.0% (-11.6, 17.6), attenuated progression of carotid medial thickness, and improved endothelial function. CONCLUSIONS: Statin monotherapy is efficacious, well tolerated and safe in the short-term, although long-term safety remains unclear. Current evidence supports treatment of children at highest cardiovascular risk, but results of on-going, longer-term studies may extend these indications.

Adolescent↗
PubMed2006

Autoinflation for hearing loss associated with otitis media with effusion.

BACKGROUND: Otitis media with effusion (OME) or 'glue ear' is an accumulation of fluid in the middle ear, in the absence of acute inflammation or infection. It is the commonest cause of acquired hearing loss in childhood and the usual reason for insertion of 'grommets'. Potential treatments include decongestants, mucolytics, steroids, antihistamines and antibiotics. Autoinflation devices have been proposed as a simple mechanical means of improving 'glue ear'. OBJECTIVES: To determine the effects of autoinflation in adults and children with otitis media with effusion. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, CENTRAL (The Cochrane Library Issue 1, 2006), MEDLINE (1951 to 2006), EMBASE (1974 to 2006) and twelve other databases, using the Cochrane Ear, Nose and Throat Disorders Group search strategy. SELECTION CRITERIA: We selected randomised controlled trials that compared any form of autoinflation to no autoinflation in individuals with 'glue ear'. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, assessed quality and extracted data from included studies. MAIN RESULTS: Six studies met the inclusion criteria. Improvement occurred for the composite measure of tympanogram or audiometry at less than one month (Relative Risk of Improvement (RRI) 2.47, 95% confidence interval (CI) 0.93 to 6.58) and at more than one month (RRI 2.20, 95% CI 1.71 to 2.82). Subgroup analysis based on the type of intervention showed a significant effect using a Politzer device under one month (RRI 7.07, 95% CI 3.70 to 13.51) and over one month (RRI 2.25, 95% CI 1.67 to 3.04). Pooled estimates showed non-significant change in tympanometry (type C2 and B) at less than one month (RRI 1.65, 95% CI 0.49 to 5.56) and non-significant improvement in tympanometry at greater than one month (RRI 1.89, 95% CI 0.77 to 4.67). Non-significant improvements occurred for discrete pure tone audiometry (RRI 0.80, 95% CI 0.22 to 2.88) and non-discrete audiometry (WMD 6.95 dB, 95% CI 21.03 to 7.13). None of the studies demonstrated a significant difference in the incidence of side effects between interventions. AUTHORS' CONCLUSIONS: All of the studies were small, of limited treatment duration and short follow up. However, because of the low cost and absence of adverse effects it is reasonable to consider autoinflation whilst awaiting natural resolution of otitis media with effusion. Further research should consider the duration of treatment and the long-term impact of autoinflation on developmental outcomes in children.

Adult↗
PubMed2006

School-based programmes for preventing smoking.

BACKGROUND: Smoking rates in adolescents are rising in some countries. Helping young people to avoid starting smoking is a widely endorsed goal of public health, but there is uncertainty about how to do this. Schools provide a route for communicating with a large proportion of young people, and school-based programmes for smoking prevention have been widely developed and evaluated. OBJECTIVES: To review all randomized controlled trials of behavioural interventions in schools to prevent children (aged 5 to12) and adolescents (aged 13 to18) starting smoking. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Tobacco Addiction Group's Specialized Register, MEDLINE, EMBASE, PsyclNFO, ERIC, CINAHL, Health Star, Dissertation Abstracts and studies identified in the bibliographies of articles. Individual MEDLINE searches were made for 133 authors who had undertaken randomized controlled trials in this area. SELECTION CRITERIA: Types of studies: those in which individual students, classes, schools, or school districts were randomized to the intervention or control groups and followed for at least six months. TYPES OF PARTICIPANTS: Children (aged 5 to12) or adolescents (aged 13 to18) in school settings. Types of interventions: Classroom programmes or curricula, including those with associated family and community interventions, intended to deter use of tobacco. We included programmes or curricula that provided information, those that used social influences approaches, those that taught generic social competence, and those that included interventions beyond the school into the community. We included programmes with a drug or alcohol focus if outcomes for tobacco use were reported. Types of outcome measures: Prevalence of non-smoking at follow up among those not smoking at baseline. We did not require biochemical validation of self-reported tobacco use for study inclusion. DATA COLLECTION AND ANALYSIS: We assessed whether identified citations were randomized controlled trials. We assessed the quality of design and execution, and abstracted outcome data. Because of the marked heterogeneity of design and outcomes, we computed pooled estimates only for those trials that could be analyzed together and for which statistical data were available. We predominantly synthesized the data using narrative systematic review. We grouped studies by intervention method (information; social competence; social influences; combined social influences/social competence; multi-modal programmes). Within each group, we placed them into three categories (low, medium and high risk of bias) according to validity using quality criteria for reported study design. MAIN RESULTS: Of the 94 randomized controlled trials identified, we classified 23 as category one (most valid). There was one category one study of information-giving and two of teaching social comeptence. There were thirteen category one studies of social influences interventions. Of these, nine found some positive effect of intervention on smoking prevalence, and four failed to detect an effect on smoking prevalence. The largest and most rigorous study, the Hutchinson Smoking Prevention Project, found no long-term effect of an intensive eight-year programme on smoking behaviour. There were three category one RCTs of combined social influences and social competence interventions: one provided significant results and one only for instruction by health educators compared to self-instruction. There was a lack of high quality evidence about the effectiveness of combinations of social influences and social competence approaches. There was one category one study providing data on social influences compared with information giving. There were four category one studies of multi-modal approaches but they provided limited evidence about the effectiveness of multi-modal approaches including community initiatives. AUTHORS' CONCLUSIONS: There is one rigorous test of the effects of information-giving about smoking. There are well-conducted randomized controlled trials to test the effects of social influences interventions: in half of the group of best quality studies those in the intervention group smoke less than those in the control, but many studies failed to detect an effect of the intervention. There are only three high quality RCTs which test the effectiveness of combinations of social influences and social competence interventions, and four which test multi-modal interventions; half showed significant positive results.

Adolescent↗
PubMed2006

Telephone counselling for smoking cessation.

BACKGROUND: Telephone services can provide information and support for smokers. Counselling may be provided proactively or offered reactively to callers to smoking cessation helplines. OBJECTIVES: To evaluate the effect of proactive and reactive telephone support to help smokers quit. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register for studies using free text term 'telephone*' or the keywords 'telephone counselling' or 'Hotlines' or 'Telephone' . Date of the most recent search: January 2006. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials in which proactive or reactive telephone counselling to assist smoking cessation was offered to smokers or recent quitters. DATA COLLECTION AND ANALYSIS: Trials were identified and data extracted by one person (LS) and checked by a second (TL). The main outcome measure was the odds ratio for abstinence from smoking after at least six months follow up. We selected the strictest measure of abstinence, using biochemically validated rates where available. We considered participants lost to follow-up to be continuing smokers. Where trials had more than one arm with a less intensive intervention we used only the most similar intervention without the telephone component as the control group in the primary analysis. We assessed statistical heterogeneity amongst sub groups of clinically comparable studies using the I(2) statistic. Where appropriate, we pooled studies using a fixed-effect model. A meta-regression was used to investigate the effect of differences in planned number of calls. MAIN RESULTS: Forty-eight trials met the inclusion criteria. Among smokers who contacted helplines, quit rates were higher for groups randomised to receive multiple sessions of call-back counselling (eight studies, >18,000 participants, odds ratio (OR) for long term cessation 1.41, 95% confidence interval (CI) 1.27 to 1.57). Two of these studies showed a significant benefit of more intensive compared to less intensive intervention. Telephone counselling not initiated by calls to helplines also increased quitting (29 studies, >17,000 participants, OR 1.33, 95% CI 1.21 to 1.47). A meta-regression detected a significant association between the maximum number of planned calls and the effect size. There was clearer evidence of benefit in the subgroup of trials recruiting smokers motivated to quit. Of two studies that provided access to a hotline one showed a significant benefit and one did not. Two studies comparing different counselling approaches during a single session did not detect significant differences. A further seven studies were too diverse to contribute to meta-analyses and are discussed separately. AUTHORS' CONCLUSIONS: Proactive telephone counselling helps smokers interested in quitting. There is evidence of a dose response; one or two brief calls are less likely to provide a measurable benefit. Three or more calls increases the odds of quitting compared to a minimal intervention such as providing standard self-help materials, brief advice, or compared to pharmacotherapy alone. Telephone quitlines provide an important route of access to support for smokers, and call-back counselling enhances their usefulness.

Counseling↗
PubMed2006

Self-monitoring of oral anticoagulation: a systematic review and meta-analysis.

BACKGROUND: Near-patient testing has made self-monitoring of anticoagulation with warfarin feasible, and several trials have suggested that such monitoring might be equal to or better than standard monitoring. We did a systematic review and meta-analysis of all randomised controlled trials that assessed the effects of self-monitoring or self-management (self-testing and self-dosage) of anticoagulation compared with standard monitoring. METHODS: We searched the Cochrane Register of Controlled Trials, MEDLINE, EMBASE to April 2005, and contacted manufacturers and authors of relevant studies. Outcomes analysed were: major haemorrhage, thromboembolic events, death, tests in range, minor haemorrhage, frequency of testing, and feasibility of self-monitoring. FINDINGS: We identified 14 randomised trials of self-monitoring: pooled estimates showed significant reductions in thromboembolic events (odds ratio 0.45, 95% CI 0.30-0.68), all-cause mortality (0.61, 0.38-0.98), and major haemorrhage (0.65, 0.42-0.99). Trials of combined self-monitoring and self-adjusted therapy showed significant reductions in thromboembolic events (0.27, 0.12-0.59) and death (0.37, 0.16-0.85), but not major haemorrhage (0.93, 0.42-2.05). No difference was noted in minor haemorrhage. 11 trials reported improvements in the mean proportion of international normalisation ratios in range. INTERPRETATION: Self-management improves the quality of oral anticoagulation. Patients capable of self-monitoring and self-adjusting therapy have fewer thromboembolic events and lower mortality than those who self-monitor alone. However, self-monitoring is not feasible for all patients, and requires identification and education of suitable candidates.

Adult↗
PubMed2006

Reminder packaging for improving adherence to self-administered long-term medications.

BACKGROUND: Current methods of improving medication adherence for health problems are mostly complex, labour-intensive, and not reliably effective. Medication 'reminder packaging' which incorporates a date or time for a medication to be taken in the packaging, can act as a reminder system to improve adherence. OBJECTIVES: The objective of this review was to determine the effects of reminder packaging to enhance patient adherence with self-administered medications taken for one month or more. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 3, 2004), MEDLINE, EMBASE, CINAHL and PsycINFO from the start of the databases to 1 September 2004. We also searched the internet, contacted packaging manufacturers, and checked abstracts from the Pharm-line database and reference lists from relevant articles. We did not apply any language restrictions. SELECTION CRITERIA: We selected randomised controlled trials with at least 80% follow up, comparing a reminder packaging device with no device in participants taking self-administered medications for a minimum of one month. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for inclusion, assessed quality, and extracted data from included studies. Where considered appropriate, data were combined for meta-analysis, or were reported and discussed in a narrative. MAIN RESULTS: Eight studies containing data on 1,137 participants were included. Six intervention groups in four trials provided data on the percentage of pills taken. Reminder packaging showed a significant increase in the percentage of pills taken, weighted mean difference 11% (95% confidence interval (CI) 6% to 17%). Notable heterogeneity occurred among these trials I(2 )= 96.3%. Two trials provided data for the proportion of self-reported adherent patients, reporting a reduction in the intervention group which was not statistically significant, odds ratio = 0.89 (95% CI 0.56 to 1.40). No appropriate data were available for meta-analysis of different clinical outcomes, the most common of these being blood pressure (three out of eight trials). Other clinical outcomes reported were glycated haemoglobin, serum Vitamin C and E levels, and self-reported psychological symptoms (one trial each). AUTHORS' CONCLUSIONS: Reminder packing may represent a simple method for improving adherence for patients with selected conditions examined to date. Further research is warranted to improve the design and targeting of these devices.

Drug Packaging↗
PubMed2006

Defining the dermatological content of the undergraduate medical curriculum: a modified Delphi study.

BACKGROUND: Dermatological problems are common, but in undergraduate medical courses time for learning dermatology and teaching dermatology is limited. The Delphi technique has been used in other specialties to define undergraduate and postgraduate curricula and to reach consensus on what is important. OBJECTIVES: To identify the core dermatological content of the undergraduate medical curriculum. METHODS: Modified Delphi technique. A questionnaire was designed after review of previous recommendations made by dermatologists. Items were written as explicit learning outcomes. A multidisciplinary panel of 66 individuals responded. Outcomes were rated using a Likert scale (1-5). RESULTS: Fifty-three learning outcomes were rated 'very important'. We recommend that these are included in the content of U.K. undergraduate medical core curricula. CONCLUSIONS: A multidisciplinary panel identified dermatological learning outcomes that should be achieved by all medical graduates. Undergraduate medical curricula must provide sufficient resources for learning, teaching and assessment of dermatology so that graduates achieve these outcomes.

Clinical Competence↗
PubMed2005

Competitions and incentives for smoking cessation.

BACKGROUND: Material or financial incentives may be used in an attempt to reinforce behaviour change, including smoking cessation. They have been widely used in workplace smoking cessation programmes, and to a lesser extent within community programmes. Quit and Win contests are the subject of a companion review. OBJECTIVES: To determine whether competitions and incentives lead to higher long-term quit rates. We also set out to examine the relationship between incentives and participation rates. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group Specialized Register, with additional searches of MEDLINE (January 1966 to September 2004), EMBASE (1980 to 2004/8), CINAHL (1982 to 2004/8) and PsycINFO (1872 to 2004/6). Search terms included incentive*, competition*, contest*, reward*, prize*, contingent payment*, deposit contract*. SELECTION CRITERIA: We considered randomized controlled trials, allocating individuals, workplaces, groups within workplaces, or communities to experimental or control conditions. We also considered controlled studies with baseline and post-intervention measures. DATA COLLECTION AND ANALYSIS: Data were extracted by one author and checked by the second. We contacted study authors for additional data where necessary. The main outcome measure was abstinence from smoking for at least six months from the start of the intervention. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates where available. Where possible we performed meta-analysis using a generic inverse variance model, grouped by timed endpoints, but not pooled across the subgroups. MAIN RESULTS: Fifteen studies met our inclusion criteria. None of the studies demonstrated significantly higher quit rates for the incentives group than for the control group beyond the six-month assessment. There was no clear evidence that participants who committed their own money to the programme did better than those who did not, or that different types of incentives were more or less effective. There is some evidence that although cessation rates have not been shown to differ significantly, recruitment rates can be improved by rewarding participation, which may be expected to deliver higher absolute numbers of successful quitters. Cost effectiveness analysis is not appropriate to this review, since the efficacy of the intervention has not been demonstrated. AUTHORS' CONCLUSIONS: Incentives and competitions do not appear to enhance long-term cessation rates, with early success tending to dissipate when the rewards are no longer offered. Rewarding participation and compliance in contests and cessation programmes may have more potential to deliver higher absolute numbers of quitters.

Health Promotion↗
PubMed2005

Quit and Win contests for smoking cessation.

BACKGROUND: Quit and Win contests were developed in the 1980s by the Minnesota Heart Health Program, and have been widely used since then as a population-based smoking cessation intervention at local, national and international level. Since 1994 an international contest has been held every two years in as many as 80 countries (2002). OBJECTIVES: To determine whether quit and win contests can deliver higher long-term quit rates than baseline community quit rates. To assess the impact of such programmes, we considered both the quit rates achieved by participants, and the population impact, which takes into account the proportion of the target population entering the contest. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group specialized register, with additional searches of MEDLINE (January 1966 to September 2004), EMBASE (180 to 2004/8), CINAHL (1982 to 2004/8) and PsycINFO (1872 to 2004/6). Search terms included competition*, quit and win, quit to win, contest*, prize*. SELECTION CRITERIA: We considered randomized controlled trials, allocating individuals or communities to experimental or control conditions. We also considered controlled studies with baseline and post-intervention measures. DATA COLLECTION AND ANALYSIS: Data were extracted by one author and checked by the second. We contacted study authors for additional data where necessary. The main outcome measure was abstinence from smoking for at least six months from the start of the intervention. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates where available. We decided against performing a meta-analysis, because of the heterogeneity of the included studies, and the small number of scientifically valid studies. MAIN RESULTS: Four studies met our inclusion criteria. Three demonstrated significantly higher quit rates (8% to 20%) for the quit and win group than for the control group at the 12-month assessment. However, the population impact measure, where available, suggests that the effect of contests on community prevalence of smoking is small, with fewer than one in 500 smokers quitting because of the contest. Levels of deception, where they could be quantified, were high. Although surveys suggest that international quit and win contests may be effective, especially in developing countries, the lack of controlled studies precludes any firm conclusions from this review. AUTHORS' CONCLUSIONS: Quit and win contests at local and regional level appear to deliver quit rates above baseline community rates, although the population impact of the contests seems to be relatively low. Contests may be subject to levels of deception which could compromise the validity of the intervention. International contests may prove to be an effective mechanism, particularly in developing countries, but a lack of well-designed comparative studies precludes any firm conclusions.

Awards and Prizes↗
PubMed2004

A children's acute respiratory illness scale (CARIFS) predicted functional severity and family burden.

OBJECTIVE: The Canadian Acute Respiratory Illness and Flu Scale (CARIFS) was developed to measure illness severity in children with acute respiratory infection. The objective of this study was to evaluate its performance in a European primary care setting. STUDY DESIGN AND SETTING: 178 children (median age 3 years) with cough and fever were recruited in UK general practice. Perceived severity of illness at recruitment was recorded by parents, doctors, and nurses. Parents also completed an illness diary, including the CARIF scale, until their child had recovered. In-depth interviews were conducted with 24 parents. RESULTS: Parents found CARIFS relatively easy and quick to complete (78% of parents returned a fully completed diary covering the duration of the illness), internal consistency was high (minimum item correlation with total score 0.22; overall Cronbach's alpha statistic 0.85), and responsiveness to improvement in health was good (observed effect size of 0.45 at 8 h). At presentation, however, neither the overall CARIFS score nor the clinical element of the score correlated with physician assessment of clinical severity. CONCLUSION: Of the three recognized domains of illness severity, CARIFS appears to be a good and valid measure of functional severity and burden of illness to the parent but it may not be a good measure of physiological severity.

Acute Disease↗
PubMed2001

Ultrasound to decontaminate heavy metals in dredged sediments.

Sediments contaminated with heavy metals due to past disposal practices threaten the environment and require remediation. This study was an attempt to develop a technology to decontaminate heavy metals in dredged sediments using ultrasound coupled with vacuum pressure. A set of laboratory scale experiments were conducted using dredged sediments obtained from New York/New Jersey harbor. This sediment sample is considered as category III, a material that failed to meet USEPA requirements for toxicity or bioaccumulation, and required secure disposal. Acoustic cavitation due to ultrasound energy coupled with vacuum pressure was used to facilitate the removal of chromium (the selected metal contaminant) from the sediments. Full factorial experimental designs were performed to evaluate the above treatment technique and to optimize the processes. Two coupled processes were used to separate and to treat both coarse (Process #1) and fine (Process #2) fractions of sediments. Selected variables for evaluation of Process #1 were ultrasound power, soil-to-water ratio, vacuum pressure and dwell time, and for Process #2 were ultrasound power, soil-to-water ratio and dwell time. Laboratory scale experiments were carried out with various combinations of these parameters according to the factorial design. The optimum removal was found to be 92% with the parameter levels at 1200W power, 1:15 soil-to-water ratio, 15 psi vacuum pressure and 15 min of dwell time. After the application of Process #2 for fine sediments it was found that the fines were separated into silt and clay. Only the silt faction had a considerable metal removal while the clay fraction was insensitive to the treatment. A maximum removal of 83% was obtained for silt fraction when factor levels were at 1200W power, 1:50 soil-to-water ratio and 90 min of dwell time. Further analysis of clay fraction showed that the chromium in clay is immobile and stable. The toxicity characteristic leaching procedure (TCLP) test on clay fraction confirmed that the treated clay fraction is safe to dispose. The study showed that the proposed treatment technique is effective and economical for sediments with lower clay contents.

Cost-Benefit Analysis↗
PubMed2001

Positive-negative selection for homologous recombination in Arabidopsis.

In plants gene knock-outs and targeted mutational analyses are hampered by the inefficiency of homologous recombination. We have developed a strategy to enrich for rare events of homologous recombination in Arabidopsis using combined positive and negative selection. The T-DNA targeting construct contained two flanking regions of the target alcohol dehydrogenase gene as homologous sequences, and neomycin phosphotransferase and cytosine deaminase as positive and negative markers, respectively. A root explant transformation procedure was used to obtain transgenic calli. Among 6250 transformants isolated by positive selection, 39 were found to be resistant to negative selection as well. Of these 39, at least one had undergone homologous recombination correlated with a unidirectional transfer of information. Although the ADH locus was not changed, our data demonstrate that a homologous recombination event can be selected by positive negative selection in plants.

Alcohol Dehydrogenase↗
PubMed2001

Telephone counselling for smoking cessation.

BACKGROUND: Telephone services can provide information and support for smokers. Counselling may be provided proactively or offered reactively to callers to smoking cessation helplines. OBJECTIVES: To evaluate the effect of proactive and reactive telephone support to help smokers quit. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register for studies using free text term 'telephone*' or the keywords 'telephone counselling' or 'Hotlines' or 'Telephone'. Date of the most recent search: August 2000. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in which proactive or reactive telephone counselling to assist smoking cessation was offered to smokers or recent quitters. DATA COLLECTION AND ANALYSIS: Trials were identified and data extracted by one person and checked by a second. The main outcome measure was abstinence from smoking after at least six months follow-up. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates where available. Participants lost to follow-up were considered to be continuing smokers. Where interventions were similar, we performed meta-analysis using a fixed effects model to give an odds ratio. MAIN RESULTS: Twenty three trials met inclusion criteria. Ten trials compared proactive counselling to a minimal intervention control. There was statistical heterogeneity, with three trials showing a significant benefit, and seven showing non significant differences. Four trials adding telephone support to a face to face intervention control failed to detect a significant effect on long term quit rates. Four trials failed to detect an additional effect of telephone support in users of nicotine replacement therapy. Providing access to a hotline showed a significant benefit in one trial and no significant difference in two. Varying the type of counselling provided has not been shown to affect outcome. REVIEWER'S CONCLUSIONS: Proactive telephone counselling can be effective compared to an intervention without personal contact. There was heterogeneity between trials so the size of effect is uncertain. The available evidence neither confirms nor rules out a benefit of telephone counselling as an adjunct to face to face counselling or pharmacotherapy. Further trials randomising access to helplines are unlikely to be done but indirect evidence suggests they can be a useful part of a smoking cessation service.

Counseling↗
PubMed2001

Alphavirus nucleocapsid protein contains a putative coiled coil alpha-helix important for core assembly.

The alphavirus nucleocapsid core is formed through the energetic contributions of multiple noncovalent interactions mediated by the capsid protein. This protein consists of a poorly conserved N-terminal region of unknown function and a C-terminal conserved autoprotease domain with a major role in virion formation. In this study, an 18-amino-acid conserved region, predicted to fold into an alpha-helix (helix I) and embedded in a low-complexity sequence enriched with basic and Pro residues, has been identified in the N-terminal region of the alphavirus capsid proteins. In Sindbis virus, helix I spans residues 38 to 55 and contains three conserved leucine residues, L38, L45, and L52, conforming to the heptad amino acid organization evident in leucine zipper proteins. Helix I consists of an N-terminally truncated heptad and two complete heptad repeats with beta-branched residues and conserved leucine residues occupying the a and d positions of the helix, respectively. Complete or partial deletion of helix I, or single-site substitutions at the conserved leucine residues (L45 and L52), caused a significant decrease in virus replication. The mutant viruses were more sensitive to elevated temperature than wild-type virus. These mutant viruses also failed to accumulate cores in the cytoplasm of infected cells, although they did not have defects in protein translation or processing. Analysis of these mutants using an in vitro assembly system indicated that the majority were defective in core particle assembly. Furthermore, mutant proteins showed a trans-dominant negative phenotype in in vitro assembly reactions involving mutant and wild-type proteins. We propose that helix I plays a central role in the assembly of nucleocapsid cores through coiled coil interactions. These interactions may stabilize subviral intermediates formed through the interactions of the C-terminal domain of the capsid protein and the genomic RNA and contribute to the stability of the virion.

Alphavirus↗
PubMed2001

In vitro assembly of Sindbis virus core-like particles from cross-linked dimers of truncated and mutant capsid proteins.

A nucleic acid-bound capsid protein dimer was previously identified using a Sindbis virus in vitro nucleocapsid assembly system and cross-linking reagents. Cross-link mapping, in combination with a model of the nucleocapsid core, suggested that this dimer contained one monomer from each of two adjacent capsomeres. This intercapsomere dimer is believed to be the initial intermediate in the nucleocapsid core assembly mechanism. This paper presents the purification of cross-linked dimers of a truncated capsid protein and the partial purification of cross-linked dimers of a full-length assembly-defective mutant. The assembly of core-like particles from these cross-linked capsid protein dimers is demonstrated. Core-like particles generated from cross-linked full-length mutant CP(19-264)L52D were examined by electron microscopy and appeared to have a morphology similar to that of wild-type in vitro-assembled core-like particles, although a slight size difference was often visible. Truncated cross-linked CP(81-264) dimers generated core-like particles as well. These core-like particles could subsequently be disassembled when reversible cross-linking reagents were used to form the dimers. The ability of the covalent intercapsomere cross-link to rescue capsid proteins with assembly defects or truncations in the amino-terminal region of the capsid protein supports the previous model of assembly and suggests a possible role for the amino-terminal region of the protein.

Blotting, Western↗