Genetic analyses of the parasitic nematode, Parelaphostrongylus tenuis, in Missouri and Kentucky reveal unexpected levels of diversity and population differentiation.

Wildlife translocations, which involve the introduction of naive hosts into new environments with novel pathogens, invariably pose an increased risk of disease. The meningeal worm Parelaphostrongylus tenuis is a nematode parasite of the white-tailed deer (Odocoileus virginianus), which serves as its primary host and rarely suffers adverse effects from infection. Attempts to restore elk (Cervus canadensis) to the eastern US have been hampered by disease caused by this parasite. Using DNA sequence data from mitochondrial and nuclear genes, we examined the hypothesis that elk translocated within the eastern US could be exposed to novel genetic variants of P. tenuis by detailing the genetic structure among P. tenuis taken from white-tailed deer and elk at a source (Kentucky) and a release site (Missouri). We found high levels of diversity at both mitochondrial and nuclear DNA in Missouri and Kentucky and a high level of differentiation between states. Our results highlight the importance of considering the potential for increased disease risk from exposure to novel strains of parasites in the decision-making process of a reintroduction or restoration.

The nucleosome DNA entry-exit site is important for transcription termination and prevention of pervasive transcription.

Compared to other stages in the RNA polymerase II transcription cycle, the role of chromatin in transcription termination is poorly understood. We performed a genetic screen in Saccharomyces cerevisiae to identify histone mutants that exhibit transcriptional readthrough of terminators. Amino acid substitutions identified by the screen map to the nucleosome DNA entry-exit site. The strongest H3 mutants revealed widespread genomic changes, including increased sense-strand transcription upstream and downstream of genes, increased antisense transcription overlapping gene bodies, and reduced nucleosome occupancy particularly at the 3' ends of genes. Replacement of the native sequence downstream of a gene with a sequence that increases nucleosome occupancy in vivo reduced readthrough transcription and suppressed the effect of a DNA entry-exit site substitution. Our results suggest that nucleosomes can facilitate termination by serving as a barrier to transcription and highlight the importance of the DNA entry-exit site in broadly maintaining the integrity of the transcriptome.

The nucleosome acidic patch directly interacts with subunits of the Paf1 and FACT complexes and controls chromatin architecture in vivo.

The nucleosome core regulates DNA-templated processes through the highly conserved nucleosome acidic patch. While structural and biochemical studies have shown that the acidic patch controls chromatin factor binding and activity, few studies have elucidated its functions in vivo. We employed site-specific crosslinking to identify proteins that directly bind the acidic patch in Saccharomyces cerevisiae and demonstrated crosslinking of histone H2A to Paf1 complex subunit Rtf1 and FACT subunit Spt16. Rtf1 bound to nucleosomes through its histone modification domain, supporting its role as a cofactor in H2B K123 ubiquitylation. An acidic patch mutant showed defects in nucleosome positioning and occupancy genome-wide. Our results provide new information on the chromatin engagement of two central players in transcription elongation and emphasize the importance of the nucleosome core as a hub for proteins that regulate chromatin during transcription.

A transcriptional switch controls meiosis.

A key protein involved in the segregation of meiotic chromosomes is produced 'just in time' by the regulated expression of two mRNA isoforms.

An evidence synthesis of qualitative and quantitative research on component intervention techniques, effectiveness, cost-effectiveness, equity and acceptability of different versions of health-related lifestyle advisor role in improving health.

BACKGROUND: There is a need to identify and analyse the range of models developed to date for delivering health-related lifestyle advice (HRLA), or training, for effectiveness and cost-effectiveness in improving the health and well-being of individuals and communities in the UK, with particular reference to the reduction of inequalities. OBJECTIVES: To identify the component intervention techniques of lifestyle advisors (LAs) in the UK and similar contexts, and the outcomes of HRLA interventions. DATA SOURCES: Stakeholder views, secondary analysis of the National Survey of Health Trainer Activity, telephone survey of health trainer leads/coordinators. A search of a range of electronic databases was undertaken [including the Applied Social Sciences Index and Abstracts (ASSIA), EMBASE, NHS Economic Evaluation Database (NHS EED), MEDLINE, Psyc INFO, etc.], as well searching relevant journals and reference lists, conducted from inception to September 2008. REVIEW METHODS: Identified studies were scanned by two reviewers and those meeting the following criteria were included: studies carrying out an evaluation of HRLA; those taking place in developed countries similar to the UK context; those looking at adult groups; interventions with the explicit aim of health improvement; interventions that involved paid or voluntary work with an individual or group of peers acting in an advisory role; advice delivered by post, online or electronically; training, support or counselling delivered to patients, communities or members of the public. After quality assessment, studies were selected for inclusion in the review. Data were abstracted from each study according to an agreed procedure and narrative, and realist and economic approaches were used to synthesise the data. Cost-effectiveness analysis of interventions was undertaken. RESULTS: In total, 269 studies were identified but 243 were excluded. The 26 included studies addressing chronic care, mental health, breastfeeding, smoking, diet and physical activity, screening and human immunodeficiency virus (HIV) infection prevention. Overall, there was insufficient evidence to either support or refute the use of LAs to promote health and improve quality of life (QoL), and thus uncertainty about the interventions' cost-effectiveness. However, the economic analysis showed that LA interventions were cost-effective in chronic care and smoking cessation, inconclusive for breastfeeding and mental health and not cost-effective for screening uptake and diet/physical activity. LA interventions for HIV prevention were cost-effective, but not in a UK context. LIMITATIONS: The wide variety of LA models, delivery settings and target populations prevented the reviewers from establishing firm causal relationships between intervention mode and study outcomes. CONCLUSIONS: Evidence was variable, giving only limited support to LAs having a positive impact on health knowledge, behaviours and outcomes. Levels of acceptability appeared to be high. LAs acted as translational agents, sometimes removing barriers to prescribed behaviour or helping to create facilitative social environments. Reporting of processes of accessing or capitalising on indigenous knowledge was limited. Ambiguity was apparent with respect to the role and impact of lay and peer characteristics of the interventions. A future programme of research on HRLA could benefit from further emphasis on identification of needs, the broadening of population focus and intervention aims, the measurement of outcomes and the reviewing of evidence. FUNDING: This study was funded by the Health Technology Assessment programme of the National Institute for Health Research.

Can we perceptually rate alaryngeal voice? Developing the Sunderland Tracheoesophageal Voice Perceptual Scale.

OBJECTIVE: To investigate the inter and intra reliability of raters (in relation to both profession and expertise) when judging two alaryngeal voice parameters: 'Overall Grade' and 'Neoglottal Tonicity'. Reliable perceptual assessment is essential for surgical and therapeutic outcome measurement but has been minimally researched to date. DESIGN: Test of inter and intra rater agreement from audio recordings of 55 tracheoesophageal speakers. SETTING: Cancer Unit. PARTICIPANTS: Twelve speech and language therapists and ten Ear, Nose and Throat surgeons. MAIN OUTCOME MEASURES: Perceptual voice parameters of 'Overall Grade' rated with a 0-3 equally appearing interval scale and 'Neoglottal Tonicity' with an 11-point bipolar semantic scale. RESULTS: All raters achieved 'good' agreement for 'Overall Grade' with mean weighted kappa coefficients of 0.78 for intra and 0.70 for inter-rater agreement. All raters achieved 'good' intra-rater agreement for 'Neoglottal Tonicity' (0.64) but inter-rater agreement was only 'moderate' (0.40). However, the expert speech and language therapists sub-group attained 'good' inter-rater agreement with this parameter (0.63). The effect of 'Neoglottal Tonicity' on 'Overall Grade' was examined utilising only expert speech and language therapists data. Linear regression analysis resulted in an r-squared coefficient of 0.67. Analysis of the perceptual impression of hypotonicity and hypertonicity in relation to mean 'Overall Grade' score demonstrated neither tone was linked to a more favourable grade (P = 0.42). CONCLUSIONS: Expert speech and language therapist raters may be the optimal judges for tracheoesophageal voice assessment. Tonicity appears to be a good predictor of 'Overall Grade'. These scales have clinical applicability to investigate techniques that facilitate optotonic neoglottal voice quality.

Swallowing problems in Parkinson disease: frequency and clinical correlates.

BACKGROUND: Changes to the efficiency and integrity of swallowing mechanisms are inevitable in Parkinson disease (PD); however, it remains unclear how many people with PD are at risk of dysphagia. The aim of this study was to establish the frequency of impaired swallowing in people with PD and the relationship between swallowing performance and indicators of disease progression. METHODS: A community-based and hospital-based cohort of 137 individuals with PD were asked to drink 150 ml of water as quickly as possible while in an 'off drug' state. RESULTS: Thirty-one (23%) patients could not completely drink the full 150 ml. Swallowing rate (ml/sec) fell to more than 1 SD below published norms for 115 (84%) patients and to more than 2SD below for 44 (32%) individuals. There were moderate correlations between rate of swallowing and disease severity, depression and cognition, but not between swallowing speed and disease duration. There was poor correlation between subjective reports of dysphagia and performance on the water swallow test. CONCLUSIONS: Swallowing problems are frequent in PD. Self-report of 'no difficulty' is not a reliable indicator of swallowing ability. Studies employing more-objective assessment of aspiration risk to compare with water swallow test performance are advocated.

A randomised controlled trial of early versus delayed oxytocin augmentation to treat primary dysfunctional labour in nulliparous women.

BACKGROUND: Oxytocin is widely used to speed up slow labour, especially in nulliparous women, but randomised trials, apart from one reported only in abstract, have been too small to exclude important effects. OBJECTIVE: To test the hypothesis that early use of oxytocin reduces the need for caesarean delivery. DESIGN: A randomised controlled trial. SETTING: Twelve obstetric units within the Northern and Yorkshire regions in the North East of England. PARTICIPANTS: A total of 412 low-risk nulliparous women in spontaneous labour at term, who had been diagnosed with primary dysfunctional labour were recruited from January 1999 to December 2001. INTERVENTION: Immediate oxytocin administration (active group) or oxytocin withheld for up to 8 hours (conservative group). MAIN OUTCOME MEASURES: Caesarean section and operative vaginal delivery rates. The length of labour measured from the time of randomisation to delivery. The rate of maternal Edinburgh Postnatal Depression Scale (EPDS) greater than 12 (major depression) within 48 hours of delivery. RESULTS: The caesarean section rates were 13.5% active versus 13.7% controls (OR 0.98, 95% CI 0.6-1.7). Operative delivery, 24.5% versus 30.9% (OR 0.73, 95% CI 0.5-1.1). The median (interquartile range) randomisation to delivery interval in the active group was 5 hours 52 minutes (3:57-8:28) and in the conservative group 9 hours 8 minutes (5:06-13:16) (P < 0.001). The rate of EPDS >12 was 20% in the active arm versus 15% among controls (OR 1.26, 95% CI 0.7-2.2). There was one perinatal death in each group and no major differences in perinatal outcomes. CONCLUSIONS: Among nulliparous women with primary dysfunctional labour, early use of oxytocin does not reduce caesarean section or short-term postnatal depression. However, it shortens labour considerably and may reduce operative vaginal deliveries.

Morbid obesity and intra-partum care.

Obesity is a major health problem in the developed world and is beginning to have an impact on pregnancy (CEMACH 2004). We aimed to examine the differences in the intra-partum care of morbidly obese women compared with those of normal weight women. Intra-partum variables of labour monitoring as well as anaesthetic and neonatal variables were compared between 50 morbidly obese and 50 normal weight women. The morbidly obese group was observed to be significantly more prone to invasive fetal monitoring (27% vs 0%, p

Entry site neovascularization and vitreous cavity hemorrhage after diabetic vitrectomy. The predictive value of inner sclerostomy site ultrasonography.

OBJECTIVE: To assess the incidence of neovascularization of the inner sclerostomy wound and occurrence of postoperative vitreous cavity hemorrhage (POVCH) after vitrectomy for proliferative diabetic retinopathy (PDR). DESIGN: Consecutive prospective longitudinal clinical study. PARTICIPANTS: Seventy-three eyes (58 patients) undergoing primary vitrectomy for PDR. METHODS: Twenty-megahertz (MHz) high-resolution anterior segment ultrasonography was performed on all sclerostomy sites 2 months postoperatively and repeated at the time of any POVCH. The appearance of the inner sclerostomy wound was divided into 4 classes (normal, spheroidal, tent, and trapezoidal, representing entry site neovascularization). The occurrence, degree, and duration of POVCH and need for revision surgery with vitreous cavity washout (VCW) were recorded. Postoperative vitreous cavity hemorrhage was divided into 3 groups-namely, mild, moderate, and major. MAIN OUTCOME MEASURES: Inner sclerostomy wound appearance on ultrasonography, degree and timing of POVCH, and need for VCW. RESULTS: There were 15 eyes in total with POVCH (20%): one patient had a persistent POVCH that required VCW. Fourteen other eyes (19%) had recurrent POVCH. Four (28%) of these 14 eyes with recurrent POVCH were classified as mild and 3 (21%) moderate: all cleared spontaneously with no further intervention needed. None of these had a trapezoidal image. Seven of the 14 eyes with recurrent POVCH were classified as major. Five of these 7 eyes had a trapezoidal image at 2 months postoperatively, and 4 required VCW (5.5% of total no. of eyes in study). All patients with a trapezoidal image experienced some degree of recurrent vitreous cavity hemorrhage (P = 0.0000024). The odds ratio was approximately 330:1. There was a significant correlation between the severity of POVCH and entry site appearance on ultrasound. In the first year of follow-up, all patients requiring VCW after recurrent POVCH had a trapezoidal image present at 2 months postoperatively (P = 0.009). CONCLUSION: The appearance of a trapezoidal image on 20-MHz high-resolution anterior segment ultrasonography at a sclerostomy site after vitrectomy for PDR was highly correlated with the occurrence of nonclearing POVCH and need for VCW. Conversely, the absence of a trapezoidal image in patients with POVCH was associated with spontaneous hemorrhage clearance.

Measuring symptom load in Idiopathic Parkinson's disease.

This study evaluated the symptom burden experienced by patients with Idiopathic Parkinson's Disease (IPD) by using a standard palliative care assessment tool (PACA) and comparing it with the Unified Parkinson's Disease Rating Scale (UPDRS). These tools together with the Mini-Mental State Examination, Beck Depression Inventory and the Schedule for the Evaluation of Individual Quality of Life were used in 123 IPD patients. The PACA demonstrated broad coverage of both motor and non motor symptoms (mean=14.3 symptoms per patient) whereas the UPDRS predominantly assessed motor symptoms. Implications for symptom assessment and palliative care provision in IPD are discussed.

Postkeratoplasty emergency visits--a review of 100 consecutive visits.

PURPOSE: Preoperative counselling for penetrating keratoplasty should include awareness of symptoms and signs of possible complications as early presentation can enhance long-term success. In our corneal transplantation service, all patients are routinely instructed to arrange a same day emergency visit through a dedicated telephone line if they experience any symptoms in eyes that have undergone keratoplasty. This study was designed to evaluate the reason for presentation, management outcome of each visit and the efficiency of the system in management of postkeratoplasty complications. METHODS: A review of 100 consecutive emergency visits by postpenetrating keratoplasty (PKP) patients in a tertiary eye care centre was included. RESULTS: Sixty-two patients with varied preoperative diagnoses presented during the review period. Sixteen visits were within the first month after surgery and 40 visits within the first year. Ten patients (16%) sought consultation more than twice during the study period with one patient presenting five times. Pain and grittiness were the main presenting symptoms (68%). Loose corneal suture (25%) necessitating removal was the most common diagnosis. Sixteen visits resulted in hospital admission for treatment. The graft survived in all patients and the visual acuity was preserved in 95% of our patients. CONCLUSION: Most corneal surgeons educate their patients to seek prompt treatment for symptoms such as redness, sensitivity to light, loss of vision, pain, or any other symptoms in eyes that have undergone keratoplasty. Early intervention of sight threatening complications increases the chance of graft survival and best-obtained vision. This review shows a simple open access system facilitates early presentation and successful management of postgraft complications.

A comparison of complications of pregnancy and delivery in morbidly obese and non-obese women.

Morbid obesity in pregnancy is a growing problem and is having an impact on morbidity, mortality as well as significantly increasing antenatal and intra-partum costs of pregnancy care. The incidence of morbid obesity in pregnancy in our unit was 7.5% during the study period and this was associated with statistically significant increased maternal and perinatal morbidity. It also led to increased costs because of multidisciplinary management of the pregnancies, increased investigations and hospital stay when compared with normal weight pregnant women. Looking after morbidly obese pregnant women is an expensive undertaking, as the cost of the care of one morbidly obese pregnant woman and her baby is several times that of the normal weight woman. Health planners need to factor in these costs which are set to escalate given the predicted increase in the obese population in the UK.

Reducing waiting times for GU medicine appointments: the impact of a new appointment system.

Our objective was to reduce the 'did not attend' (DNA) rates and waiting times by introducing a new confirmatory appointment system prior to their attendance at both Hartlepool and Middlesbrough genitourinary (GU) medicine departments. In Middlesbrough it was previous day appointment confirmation, whereas at Hartlepool it was 10 days. Both systems achieved significant attendance rates of 83.4% and 79.1% at Hartlepool and Middlesbrough, in comparison to 68.7% and 75.0% prior to the new system. The new system will improve the departmental capacity.

Double masked randomised controlled trial to assess the effectiveness of paracetamol in reducing pain in panretinal photocoagulation.

AIM: To assess the effectiveness of pre-emptive analgesia with paracetamol in reducing pain associated with panretinal photocoagulation (PRP) in a prospective, double masked, randomised controlled trial. METHOD: 60 patients undergoing PRP for the first time were enrolled and randomised to paracetamol or placebo, taken for 2 days starting 24 hours before the laser treatment. The laser treatment was performed following a standardised protocol. Pain during and after treatment was assessed using the McGill pain questionnaire (MPQ) and visual analogue scales (VAS). RESULTS: The statistical analysis looked for differences between the two study groups immediately after the laser surgery and 24 hours later. There was no statistically significant difference in the primary outcome measure of perception of pain during and 24 hours after PRP, between the paracetamol and placebo group. However, none of the patients in the paracetamol group reported increased total pain at 24 hours, whereas six patients in the placebo group reported increased pain; this difference (21%) was significant to p = 0.01. CONCLUSIONS: Pre-emptive analgesia with paracetamol did not significantly reduce pain associated with PRP. This study has described for the first time the type of pain associated with PRP, which is perceived mainly as a discomfort. The main attributes of the pain that patients described, were sharp, flashing, tiring, intense, piercing, intermittent, and brief.

A prospective, randomised controlled trial comparing the efficacy of pre-oxygenation in the 20 degrees head-up vs supine position.

We investigated whether positioning patients undergoing general anaesthesia for cholecystectomy in a 20 degrees head-up position, as opposed to supine, improved the efficacy of 3 min of standard pre-oxygenation via a circle breathing system. Following pre-oxygenation, patients received a standard induction of anaesthesia and the apnoea time (from administration of rocuronium to the arterial oxygen saturation to fall to 95%) was recorded. Mean (95% CI) apnoea time was 386 (343-429) s in the 20 degrees head-up position (n = 17) vs 283 (243-322) s in the supine position (n = 18; p = 0.002). Pre-oxygenation is significantly more efficacious and by inference more efficient in the 20 degrees head-up position than in the supine position.

A prospective, randomised, controlled study examining binaural beat audio and pre-operative anxiety in patients undergoing general anaesthesia for day case surgery.

Pre-operative anxiety is common and often significant. Ambulatory surgery challenges our pre-operative goal of an anxiety-free patient by requiring people to be 'street ready' within a brief period of time after surgery. Recently, it has been demonstrated that music can be used successfully to relieve patient anxiety before operations, and that audio embedded with tones that create binaural beats within the brain of the listener decreases subjective levels of anxiety in patients with chronic anxiety states. We measured anxiety with the State-Trait Anxiety Inventory questionnaire and compared binaural beat audio (Binaural Group) with an identical soundtrack but without these added tones (Audio Group) and with a third group who received no specific intervention (No Intervention Group). Mean [95% confidence intervals] decreases in anxiety scores were 26.3%[19-33%] in the Binaural Group (p = 0.001 vs. Audio Group, p < 0.0001 vs. No Intervention Group), 11.1%[6-16%] in the Audio Group (p = 0.15 vs. No Intervention Group) and 3.8%[0-7%] in the No Intervention Group. Binaural beat audio has the potential to decrease acute pre-operative anxiety significantly.

Beta blockers in older persons with heart failure: tolerability and impact on quality of life.

OBJECTIVE: To determine tolerability and symptom changes associated with the introduction of bisoprolol treatment in older patients with heart failure. DESIGN: Prospective observational cohort study. SETTING: Geriatric medicine outpatient department of a university hospital. PATIENTS: 51 patients (mean age 78 years, range 70-89 years) with stable symptomatic heart failure caused by left ventricular systolic dysfunction. INTERVENTIONS: Bisoprolol tablets, 1.25-10.0 mg. MAIN OUTCOME MEASURES: Tolerability; changes in symptoms and exercise tolerance. RESULTS: 69% of patients tolerated bisoprolol. Mean tolerated dose was 7.6 mg. There was no change in symptoms or exercise capacity in those who tolerated bisoprolol. Perceived health status and symptoms of anxiety and depression improved during the titration period. CONCLUSIONS: The rate of withdrawal from bisoprolol treatment in older patients with congestive heart failure was twice that previously reported in younger patients. The mean tolerated dose was similar to that found in trials reporting clinical efficacy. There was no evidence of a negative impact on symptoms or exercise capacity in patients who tolerated bisoprolol.

The development of a computerised equipment and drug calculator for use in resuscitation.

OBJECTIVES: To design a computerised system of calculating resuscitation requirements and to test this system to ensure that it gives accurate and fast results, so that it could potentially be used in the resuscitation of patients in a accident and emergency (A&E) department. METHODS: Using internet based technology we have developed a program that runs inside most web browsers and can be used to calculate several parameters (including endotracheal tube dimensions and drug doses). The only value that is required is the age of the patient. The weight is calculated and can be adjusted if known. The resuscitation requirement calculations are made from the weight. The program was then tested on staff members in the department to calculate theoretical resuscitation requirements for paediatric and adult patients. Accuracy and speed of the computerised calculator was compared with the conventional paper based calculation methods. RESULTS: Subjects performed better using the computerised calculator. On average they made significantly fewer errors (21.4% more accurate than using conventional methods) and were three times faster. CONCLUSION: The computerised calculator has proved, in a controlled setting, to be a more accurate and faster way of calculating resuscitation requirements than conventional methods.