Dense granule biogenesis, secretion, and function in Toxoplasma gondii.

Toxoplasma gondii is an obligate intracellular parasite and the causative agent of Toxoplasmosis. A key to understanding and treating the disease lies with determining how the parasite can survive and replicate within cells of its host. Proteins released from specialized secretory vesicles, named the dense granules (DGs), have diverse functions that are critical for adapting the intracellular environment, and are thus key to survival and pathogenicity. In this review, we describe the current understanding and outstanding questions regarding dense granule biogenesis, trafficking, and regulation of secretion. In addition, we provide an overview of dense granule protein ("GRA") function upon secretion, with a focus on proteins that have recently been identified.

Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial.

Importance: There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure. Objective: To compare low-dose digoxin with bisoprolol (a ß-blocker). Design, Setting, and Participants: Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019. Interventions: Digoxin (n = 80; dose range, 62.5-250 µg/d; mean dose, 161 µg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d). Main Outcomes and Measures: The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting. Results: Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, -1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, -2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P < .001). At 12 months, 8 of 20 outcomes were significantly different (all favoring digoxin), with a median NT-proBNP level of 960 pg/mL (interquartile range, 626 to 1531 pg/mL) in the digoxin group vs 1250 pg/mL (interquartile range, 847 to 1890 pg/mL) in the bisoprolol group (ratio of geometric means, 0.77 [95% CI, 0.64 to 0.92]; P = .005). Adverse events were less common with digoxin; 20 patients (25%) in the digoxin group had at least 1 AE vs 51 patients (64%) in the bisoprolol group (P < .001). There were 29 treatment-related AEs and 16 serious AEs in the digoxin group vs 142 and 37, respectively, in the bisoprolol group. Conclusions and Relevance: Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points. Trial Registration: ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13.

Quality of life benefits from arrhythmia ablation: A longitudinal study using the C-CAP questionnaire and EQ5D.

AIMS: To investigate long-term efficacy of cardiac ablation for symptomatic arrhythmia by gathering generic and arrhythmia-related quality of life data using patient-reported outcome measures before and after ablation. METHODS: Consecutive patients undergoing cardiac ablation procedures at three sites in the United Kingdom were enrolled (n = 561). Data were collected at baseline, at 8-16 weeks, and 12 months after the ablation with responses from 390 patients received at all three time points. Nonparametric tests were used to identify any changes in patient outcomes due to nonnormal data. RESULTS: There were significant improvements in symptom severity, impact on life scores, EQ-5D-5L indices, and visual analogue score (VAS) scores at pre- versus 3 months and at preablation versus 1 year. Impact on life score showed additional improvement at 1 year versus 3 months, while improvements in symptom severity, EQ-5D-5L indices, and VAS scores continued to be maintained between 3 months and 1 year. CONCLUSION: Cardiac ablation provides patients with arrhythmias relief from symptoms, and results in an improvement in quality of life. Improvements observed at 3 months are maintained at 1 year follow-up.

Questions remain regarding the long-term efficacy of cardiac ablation. We enrolled 561 consecutive patients undergoing ablation procedures at three UK sites. Data were collected at baseline, and at 3 and 12 months. Improvement in symptoms was reported following treatment, with patients continuing to maintain or show continued improvement at 1 year.

Haemodynamic effects of cardiac resynchronization therapy using single-vein, three-pole, multipoint left ventricular pacing in patients with ischaemic cardiomyopathy and a left ventricular free wall scar: the MAESTRO study.

AIMS: The clinical response to cardiac resynchronization therapy (CRT) is variable. Multipoint left ventricular (LV) pacing could achieve more effective haemodynamic response than single-point LV pacing. Deployment of an LV lead over myocardial scar is associated with a poor haemodynamic response to and clinical outcome of CRT. We sought to determine whether the acute haemodynamic response to CRT using three-pole LV multipoint pacing (CRT3P-MPP) is superior to that to conventional CRT using single-site LV pacing (CRTSP) in patients with ischaemic cardiomyopathy and an LV free wall scar. METHODS AND RESULTS: Sixteen patients with ischaemic cardiomyopathy [aged 72.6 ± 7.7 years (mean ± SD), 81.3% male, QRS: 146.0 ± 14.2 ms, LBBB in 14 (87.5%)] in whom the LV lead was intentionally deployed straddling an LV free wall scar (assessed using cardiac magnetic resonance), underwent assessment of LV + dP/dtmax during CRT3P-MPP and CRTSP. Interindividually, the ΔLV + dP/dtmax in relation to AAI pacing with CRT3P-MPP (6.2 ± 13.3%) was higher than with basal and mid CRTSP (both P < 0.001), but similar to apical CRTSP. Intraindividually, significant differences in the ΔLV + dP/dtmax to optimal and worst pacing configurations were observed in 10 (62.5%) patients. Of the 8 patients who responded to at least one configuration, CRT3P-MPP was optimal in 5 (62.5%) and apical CRTSP was optimal in 3 (37.5%) (P = 0.0047). CONCLUSIONS: In terms of acute haemodynamic response, CRT3P-MPP was comparable an apical CRTSP and superior to basal and distal CRTSP. In the absence of within-device haemodynamic optimization, CRT3P-MPP may offer a haemodynamic advantage over a fixed CRTSP configuration.

Cardiff cardiac ablation patient-reported outcome measure (C-CAP): validation of a new questionnaire set for patients undergoing catheter ablation for cardiac arrhythmias in the UK.

PURPOSE: To formally test and validate a patient-reported outcome measure (PROM) for patients with cardiac arrhythmias undergoing catheter ablation procedures in the UK [Cardiff Cardiac Ablation PROM (C-CAP)]. METHODS: A multicentre, prospective, observational cohort study with consecutive patient enrolment from three UK sites was conducted. Patients were sent C-CAP questionnaires before and after an ablation procedure. Pre-ablation C-CAP1 (17 items) comprised four domains: patient expectations; condition and symptoms; restricted activity and healthcare visits; medication and general health. Post-ablation C-CAP2 (19 items) comprised five domains including change in symptoms and procedural complications. Both questionnaires also included the generic EQ-5D-5L tool (EuroQol). Reliability, validity, and responsiveness measures were calculated. RESULTS: A total of 517 valid pre-ablation and 434 post-ablation responses were received; questionnaires showed good feasibility and item acceptability. Internal consistency was good (Cronbach's alpha >0.7) and test-retest reliability was acceptable for all scales. C-CAP scales showed high responsiveness (effect size >0.8). Patients improved significantly (p < 0.001) following ablation across all disease-specific and global scales. Minimal clinically important difference was calculated. Improvement beyond the smallest detectable change of 9 points (symptom severity scale), 3 points (frequency and duration of symptoms scale), and 8 points (impact on life scale) indicates an important change. Amendments to the C-CAP questionnaires were identified through the validation process and made to produce the final tools. CONCLUSIONS: The final C-CAP questionnaires are valid, reliable, and responsive tools for measuring symptom change, impact, and expectations in patients undergoing ablation for cardiac arrhythmias. C-CAP questionnaires provide a tool with disease-specific and generic domains to explore how cardiac ablation procedures in the UK impact upon patients' lives.

Living on a knife edge-the daily struggle of coping with symptomatic cardiac arrhythmias.

BACKGROUND: In 2010 a retrospective audit was undertaken to assess the viability of using PROMs in patients with symptomatic cardiac arrhythmias having undergone percutaneous arrhythmia ablation. A response rate of 74 % was achieved, with finding suggesting that arrhythmia patients reported a significant impact on their work, social and family life. AIMS: To conduct a qualitative cross sectional survey to understand patients' perspectives of how cardiac arrhythmias affect their daily lives, as part of a program to develop a Patient Reported Outcome Measure (PROM). METHOD: Twenty five patients aged 18 or over, diagnosed with a variety of symptomatic cardiac arrhythmias referred for a cardiac ablation procedure took part in cognitive interviews. These aimed to inform the development of a patient reported outcome measure and to determine factors important to this patient group. Common themes were identified using content analysis. RESULTS: Participants reported that symptoms of their arrhythmia caused them considerable problems and impacted adversely on their quality of life in many ways. This extended through daily routine, work and social activities and also to friends and family, with fear and anxiety being significant factors for most responders. Patients felt their illness was poorly understood, even by health professionals, and often reported that they felt isolated, lacking support and information. CONCLUSION: Symptomatic cardiac arrhythmias are a source of debilitating and life limiting symptoms, having a negative impact on quality of life. Symptoms and related complications are relevant across different arrhythmia substrates and patient groups. TRIAL REGISTRATION: The study is registered on the Clinical Trials website, Identifier NCT01672528.

Establishing content validity in a novel patient reported outcome measure for cardiac arrhythmia ablation patients.

AIM: Preliminary content validity testing of a UK Patient Reported Outcome Measure (PROM) for use in cardiac arrhythmia patients undergoing ablation treatment. METHODS: Twenty five patients diagnosed with symptomatic cardiac arrhythmias participated in qualitative interviews to obtain their perspective of a draft PROM. As part of the process to establish preliminary content validity, patients were asked to complete the questionnaires and to identify missing and redundant items within the PROM, while also reviewing the instructions and formatting. The questionnaires were updated iteratively to reflect patient feedback. RESULTS: Recurring themes were identified during qualitative interviews leading to improvements to the tool. Following modification of the PROM, based on patient feedback, subjects reported that the tool was fully inclusive and easy to comprehend. Patients found the instructions and layout of the tool acceptable and easy to use. CONCLUSION: Qualitative patient interviews are an important part of PROM tool development. In the case of this cardiac ablation PROM, it enabled end users to assess the tool for inclusivity and accessibility, and to ensure that it addressed concerns important to the patient. Cognitive interviews were able to obtain patients' perspectives to establish face validity and content validity of the PROM. This is part of a process which will ensure that this disease-specific PROM measures cardiac arrhythmia patient symptoms and impact on patients' lives accurately and sensitively. The next study will use the PROM prospectively in over 450 arrhythmia patients to prospectively validate the tool. CONDENSED ABSTRACT: Patients diagnosed with symptomatic cardiac arrhythmias provided feedback through cognitive interviews to facilitate improvements in a new disease specific PROM establishing preliminary face and content validity.

Patient reported outcome measures for cardiac ablation procedures: a multicentre pilot to develop a new questionnaire.

AIM: To assess the feasibility of administering Patient Reported Outcomes Measures (PROMs) in patients treated with ablation for cardiac arrhythmias, and to conduct the first stage of development and testing of a new PROM tool. METHODS AND RESULTS: A new tool was developed by a multidisciplinary team and tested alongside an adaptation of the patient perception of arrhythmia questionnaire (PPAQ) and EQ-5D-5L in a multicentre retrospective audit involving 791 consecutive cardiac arrhythmia patients treated with catheter ablation at three UK centres over 13 months. Data were recorded in the National Cardiac Rhythm Management Database, part of the National Institute for Cardiovascular Outcomes Research. The response rate was 71.9% (n = 569). Patients reported significant improvements across all outcomes and impacts, with reductions in symptoms of 51.7% (heart racing), 33.9% (fatigue) 31.8% (heart flutters), 43.5% (dizziness), 38.6% (breathlessness), 44.2% (chest pressure), 33.1% (trouble concentrating), 15.9% (headache), 28.3% (neck pressure), and 23.4% (fainting) (P < 0.001). The mean number of social days affected reduced by 7.49 days/month (P < 0.001); mean work/school days affected/month reduced by 6.26 (P < 0.001); mean GP/hospital visits reduced by 1.36 days/month (P < 0.001). The procedure met patient expectations in 72% of responders. CONCLUSIONS: The high response rate suggests that the use of PROMs in this patient group is feasible, with rates equalling those of the National PROMs Programme. The results showed that patients experienced significant improvements in their quality of life following ablation, while feedback allowed the tools to be improved. Further work is required to validate these tools; however, the findings suggest that PROMs could be useful in the audit of ablation techniques.

Development of national stressor-specific genus sensitivity values.

Effective water quality management is based on associations between at least two pieces of information: a stressor and a response. However, assessments are hindered by the lack of pre-developed stressor-response associations. To remedy this, I developed genus stressor-specific sensitivity values (SVs) for up to 704 genera to estimate a sensitive genera ratio (SGR) metric for as many as 34 common stream stressors. The SVs were estimated from a large, paired macroinvertebrate and environmental data set for the contiguous United States. Environmental variables measuring potential stressors were selected that were generally uncorrelated and usually had several thousand station observations. I calculated relative abundance weighted averages (WA) for each genus and environmental variable meeting data requirements in a calibration data set. Each environmental variable was split into 10 intervals along each stressor gradient. Genera were assigned an SV from 1 to 10 based on the interval consistent with the WA for each environmental parameter. Using the calibration derived SVs, SGRs were calculated for the calibration and a validation subsets. SGRs are the number of genera with SV ≤ 5 divided by the total number of genera in a sample. In general, as stress increased, the SGR (range: 0-1) decreased for many environmental variables, but for five environmental variables, the decrease was not consistent. The 95 % confidence intervals of the mean of the SGRs were greater for least disturbed stations compared to all other stations for 23 of the remaining 29 environmental variables. Regional performance of SGRs was evaluated by subdividing the calibration data set into West, Central, and East subsets and recalculating SVs. SGR mean absolute errors were smallest in the East and Central regions. These stressor-specific SVs expand the available tools for assessing stream biological impairments from commonly encountered environmental stressors.

Improving the diagnosis of heart failure in patients with atrial fibrillation.

OBJECTIVE: To improve the echocardiographic assessment of heart failure in patients with atrial fibrillation (AF) by comparing conventional averaging of consecutive beats with an index-beat approach, whereby measurements are taken after two cycles with similar R-R interval. METHODS: Transthoracic echocardiography was performed using a standardised and blinded protocol in patients enrolled in the RATE-AF (RAte control Therapy Evaluation in permanent Atrial Fibrillation) randomised trial. We compared reproducibility of the index-beat and conventional consecutive-beat methods to calculate left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and E/e' (mitral E wave max/average diastolic tissue Doppler velocity), and assessed intraoperator/interoperator variability, time efficiency and validity against natriuretic peptides. RESULTS: 160 patients were included, 46% of whom were women, with a median age of 75 years (IQR 69-82) and a median heart rate of 100 beats per minute (IQR 86-112). The index-beat had the lowest within-beat coefficient of variation for LVEF (32%, vs 51% for 5 consecutive beats and 53% for 10 consecutive beats), GLS (26%, vs 43% and 42%) and E/e' (25%, vs 41% and 41%). Intraoperator (n=50) and interoperator (n=18) reproducibility were both superior for index-beats and this method was quicker to perform (p<0.001): 35.4 s to measure E/e' (95% CI 33.1 to 37.8) compared with 44.7 s for 5-beat (95% CI 41.8 to 47.5) and 98.1 s for 10-beat (95% CI 91.7 to 104.4) analyses. Using a single index-beat did not compromise the association of LVEF, GLS or E/e' with natriuretic peptide levels. CONCLUSIONS: Compared with averaging of multiple beats in patients with AF, the index-beat approach improves reproducibility and saves time without a negative impact on validity, potentially improving the diagnosis and classification of heart failure in patients with AF.

Heart Rhythm UK position statement on clinical indications for implantable cardioverter defibrillators in adult patients with familial sudden cardiac death syndromes.

Whilst the decision regarding defibrillator implantation in a patient with a familial sudden cardiac death syndrome is likely to be most significant for any particular individual, the clinical decision-making process itself is complex and requires interpretation and extrapolation of information from a number of different sources. This document provides recommendations for adult patients with the congenital Long QT syndromes, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Although these specific conditions differ in terms of clinical features and prognosis, it is possible and logical to take an approach to determining a threshold for implantable cardioveter-defibrillator implantation that is common to all of the familial sudden cardiac death syndromes based on estimates of absolute risk of sudden death.

Influences of spatial scale and soil permeability on relationships between land cover and baseflow stream nutrient concentrations.

The Little Miami River (LMR) basin, dominated by agriculture, contains two geologically-distinct regions; a glaciated northern till plain with soils three times more permeable than a southern, pre-Wisconsinan drift plain. The influences of two landscape measures, percent row crop cover (%RCC, computed at three spatial scales), and soil permeability (PERM), on baseflow nutrient concentrations were modeled using linear regressions. Quarterly water samples collected for four years were analyzed for nitrate-N (NN), Kjeldahl-N (KN), total-N (TN), and total-P (TP). In till plain streams (n = 17), NN concentrations were 8.5-times greater than drift plain streams (n = 18), but KN and TP were 20-40% lower at comparable %RCC. These differences resulted in TN/TP molar ratios >80 in till plain streams, but <6 in drift plain streams. For till plain steams regression models based on %RCC accounted for 79% of the variance in NN concentrations but only 27% in drift plain streams. However, regressions on %RCC accounted for 68-75% of the KN and TP concentration variance in the drift plain streams but essentially none in the till plain. Catchment PERM influenced the regional NN/KN ratios which were 10-fold higher in the drift plain streams. For both till and drift streams the catchment scale %RCC gave the best predictions of NN, a water soluble anion, but the smaller spatial scales produced better models for insoluble nutrient species (e.g., KN and TP). Published literature on Ohio streams indicates that these inter-regional differences in nutrient ratios have potential implications for aquatic biota in the receiving streams.

Uptake of Sulfate from Ambient Water by Freshwater Animals.

To better understand how the sulfate (SO4 2-) anion may contribute to the adverse effects associated with elevated ionic strength or salinity in freshwaters, we measured the uptake and efflux of SO4 2- in four freshwater species: the fathead minnow (Pimephales promelas, Teleostei: Cyprinidae), paper pondshell (Utterbackia imbecillis, Bivalvia: Unionidae), red swamp crayfish (Procambarus clarkii, Crustacea: Cambaridae), and two-lined mayfly (Hexagenia bilineata, Insecta: Ephemeridae). Using δ( 34 S/ 32 S) stable isotope ratios and the concentrations of S and SO4 2-, we measured the SO4 2- influx rate (J in ), net flux (J net ), and efflux rate (Jout) during a 24 h exposure period. For all four species, the means of J in for SO4 2- were positive, and J in was significantly greater than 0 at both target SO4 2- concentrations in the fish and mollusk and at the lower SO4 2- concentration in the crayfish. The means of J out and J net were much more variable than those for J in , but several species by target SO4 2- concentration combinations for J out and J net , were negative, which suggests the net excretion of SO4 2- by the animals. The results of our experiments suggest a greater regulation of SO4 2- in freshwater animals than has been previously reported.

Consideration of spatial and temporal scales in stream restorations and biotic monitoring to assess restoration outcomes: A literature review, Part 2.

Stream and river restoration practices have become common in many parts of the world. To answer the question whether such restoration measures improve freshwater biotic assemblages or functions over time, and if not, can general reasons be identified for such outcomes, we conducted a literature survey and review of studies in which different types of stream restorations were conducted and outcomes assessed. In the first paper, we reviewed studies of culvert restorations, acid mine drainage or industrial pollution restoration; and urban stream restoration projects. Here, we review studies of restoration via dam removal, changes in dam operation or fish passage structures; instream habitat modification; riparian restoration or woody material addition; channel restoration and multiple restoration measures and develop some general conclusions from these reviews. Biomonitoring in different studies detected improvements for some restoration measures; other studies found minimal or no statistically significant increases in biotic assemblage richness, abundances or functions. In some cases, untreated stressors may have influenced the outcomes of the restoration, but in many cases, there were mismatches in the temporal or spatial scale of the restoration measure undertaken and associated monitoring. For example, either biomonitoring to measure restoration effects was conducted over a too short a time period after restoration for effects to be observed, or the sources and stressors needing remediation occurred at a larger catchment scale than the restoration. Also, many restoration measures lack observations from unimpaired reference sites for use in predicting how much of a beneficial effect might be expected.

Consideration of spatial and temporal scales in stream restorations and biotic monitoring to assess restoration outcomes: A literature review, Part 1.

Stream and river restoration practices have become common in many parts of the world. We ask the question whether such restorations improve freshwater biotic assemblages or functions over time, and if not, can general reasons be identified for such outcomes. We conducted a literature survey and review of studies in which different types of stream restorations were conducted and outcomes reported. These restoration types included culvert restoration; acid mine restoration or industrial pollutant restoration; urban stream restoration; dam removal, changes in dam operation, or fish passage structures; instream habitat modification; riparian restoration or woody material addition; channel restoration and multiple restorations. The streams ranged from headwater streams to large rivers, and the regions included North America, Europe, Australia and New Zealand, and a small number of sites in Asia and Africa. In this part of the review, we describe the methods used for the review and present reviews for the first three types of stream restorations. For culvert restorations, the small sample size and variable study design and biotic responses limited generalizing about temporal and spatial scale effects for that restoration type. The complex and often lengthy time to restore streams from acid mine drainage and industrial pollutants often resulted in positive biotic responses, but restored sites had reduced responses compared to reference sites. Most urban stream restorations had minimal or mixed improvements in biotic responses, with one mismatch in spatial scale evidenced by hydraulic structures used in a restoration unable to withstand peak discharge.

Paced ventricular electrogram fractionation predicts sudden cardiac death in hypertrophic cardiomyopathy.

AIMS: Paced electrogram fractionation analysis (PEFA) has been assessed for the prediction of sudden cardiac death (SCD) in a large-scale, prospective study of patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: We determined the positive predictive value (PPV) of PEFA in relation to other risk factors for SCD and outcomes in 179 patients with HCM and no prior history of cardiac arrest. Patients were followed over a mean 4.3 years (range: 1.1-6.3 years). Thirteen patients had SCD-equivalent events: four of these patients died suddenly, three were resuscitated from ventricular fibrillation (VF), and six had implantable cardioverter-defibrillator (ICD) discharges in response to VF. PEFA identified nine of these patients and another 14 non-VF patients yielding a censored PPV of between 0.19 and 0.59 that was greater than the PPV that was the formal stopping point of the trial (0.18). Eighty per cent of patients were followed for 4 years or more. The PPV for the identification of SCD in this group was 0.38 (0.17-0.59). The use of two or more conventional markers to predict SCD identified five patients with SCD-equivalent events in the 4-year follow-up group and 42 other patients without events yielding a PPV of 0.106 (confidence limits 0.02-0.15). CONCLUSION: PEFA identifies HCM patients at risk of SCD with greater accuracy than non-invasive techniques and may have an important role in determining indications for ICD prescription.

Zoonoses associated with petting farms and open zoos.

The popularity of open farms and petting zoos has increased markedly over the last 5 years, with most children in developed countries now having the opportunity to visit such a facility at some stage in their childhood, either through school or family visits. The open access policy of these establishments allows visitors to be in direct contact with animals such as sheep (lambs), goats, cats (kittens), dogs (puppies), and birds and to have the opportunity to feed such animals. This contact may lead to the transmission of microbial pathogens from animals to humans, e.g., Escherichia coli O157:H7, resulting in human disease. This review outlines the causal organisms associated with such zoonoses, a description of previous outbreaks at farms and zoos, as well as infection control measures to help prevent such zoonotic infections.

Verification of electrical isolation of pulmonary veins following left atrial circumferential ablation may require sinus rhythm.

A 67-year-old female with symptomatic paroxysmal atrial fibrillation (AF) underwent left atrial circumferential ablation, and during the procedure, she developed AF. Once the ablation was complete, the left upper pulmonary vein (LUPV) appeared to continue in a rapid disorganized rhythm, despite further attempts at isolating this vein. When the patient was electrically cardioverted to sinus rhythm to assist mapping, the LUPV remained in a disorganized rhythm, pulmonary vein (PV) fibrillation. This case illustrates a possible pitfall in confirming complete isolation of the PVs during AF.