Comparative analysis of the Pocillopora damicornis genome highlights role of immune system in coral evolution.

Comparative analysis of the expanding genomic resources for scleractinian corals may provide insights into the evolution of these organisms, with implications for their continued persistence under global climate change. Here, we sequenced and annotated the genome of Pocillopora damicornis, one of the most abundant and widespread corals in the world. We compared this genome, based on protein-coding gene orthology, with other publicly available coral genomes (Cnidaria, Anthozoa, Scleractinia), as well as genomes from other anthozoan groups (Actiniaria, Corallimorpharia), and two basal metazoan outgroup phlya (Porifera, Ctenophora). We found that 46.6% of P. damicornis genes had orthologs in all other scleractinians, defining a coral 'core' genome enriched in basic housekeeping functions. Of these core genes, 3.7% were unique to scleractinians and were enriched in immune functionality, suggesting an important role of the immune system in coral evolution. Genes occurring only in P. damicornis were enriched in cellular signaling and stress response pathways, and we found similar immune-related gene family expansions in each coral species, indicating that immune system diversification may be a prominent feature of scleractinian coral evolution at multiple taxonomic levels. Diversification of the immune gene repertoire may underlie scleractinian adaptations to symbiosis, pathogen interactions, and environmental stress.

Dynamic regulation of partner abundance mediates response of reef coral symbioses to environmental change.

Regulating partner abunclance may allow symmotic organisms to mediate interaction outcomes, facilitating adaptive responses to environmental change. To explore the capacity for-adaptive regulation in an ecologically important endosymbiosis, we studied the population dynamics of symbiotic algae in reef-building corals under different abiotic contexts. We found high natural variability in symbiont abundance in corals across reefs, but this variability converged to different symbiont-specific abundances when colonies were maintained under constant conditions. When conditions changed seasonally, symbiont abundance readjusted to new equilibria. We explain these patterns using an a priori model of symbiotic costs and benefits to the coral host, which shows that the observed changes in symbiont abundance are consistent with the maximization of interaction benefit under different environmental conditions. These results indicate that, while regulating symbiont abundance helps hosts sustain maximum benefit in a dynamic environment, spatiotemporal variation in abiotic factors creates a broad range of symbiont abundances (and interaction outcomes) among corals that may account for observed natural variability in performance (e.g., growth rate) and stress tolerance (e.g., bleaching susceptibility). This cost or benefit framework provides a new perspective on the dynamic regulation of reef coral symbioses and illustrates that the dependence of interaction outcomes on biotic and abiotic contexts may be important in understanding how diverse mutualisms respond to environmental change.

Differential effects of copper on three species of scleractinian corals and their algal symbionts (Symbiodinium spp.).

Land-based sources of pollution have been identified as significant stressors linked to the widespread declines of coral cover in coastal reef ecosystems over the last 30 years. Metal contaminants, although noted as a concern, have not been closely monitored in these sensitive ecosystems, nor have their potential impacts on coral-algal symbioses been characterized. In this study, three species of laboratory-reared scleractinian corals, Acropora cervicornis, Pocillopora damicornis, and Montastraea faveolata each containing different algal symbionts (Symbiodinium A3, C1 and D1a, respectively) were exposed to copper (ranging from 2 to 20microg/L) for 5 weeks. At the end of the exposure period, copper had accumulated in the endosymbiotic dinoflagellate ("zooxanthellae") and animal tissue of A. cervicornis and the animal tissue of M. faveolata; however, no copper accumulation was detected in the zooxanthellae or animal tissue of P. damicornis. The three coral species exhibited significantly different sensitivities to copper, with effects occurring in A. cervicornis and P. damicornis at copper concentrations as low as 4microg/L. Copper exposure affected zooxanthellae photosynthesis in A. cervicornis and P. damicornis, and carbonic anhydrase was significantly decreased in A. cervicornis and M. faveolata. Likewise, significant decreases in skeletal growth were observed in A. cervicornis and P. damicornis after copper exposure. Based on preliminary results, no changes in Symbiodinium communities were apparent in response to increasing copper concentration. These results indicate that the relationships between physiological/toxicological endpoints and copper accumulation between coral species differ, suggesting different mechanisms of toxicity and/or susceptibility. This may be driven, in part, by differences in the algal symbiont communities of the coral species in question.

Predilection of hemolytic anemia-associated leg ulcers for the medial malleolus.

BACKGROUND: Ischemic ulcers are usually found above the lateral, and venous stasis ulcers at the medial malleoli. Leg ulcers occur in at least 25% of sickle cell disease (SSD) patients in clinic populations, usually in the malleolar region. The function of the large leg veins in most SSD patients is unimpaired. PATIENTS AND METHODS: We determined leg ulcer location in 41 sickle cell anemia (SS), and 4 sickle-beta 0 thalassemic patients with longstanding chronic and/or recurrent leg ulceration, and reviewed published reports of leg ulcers in hereditary spherocytosis and thalassemias. RESULTS: Of the 57 legs of the 45 SSD patients with only 1 ulcer, 42 (74%) were medial and 15 lateral. The difference was significant (p < 0.001). Of patients with only a single ulcer, 22 were medial and 4 lateral. Of 15 reported patients with leg ulcers related to spherocytosis or thalassemia, 20/24 (83%) ulcers were medial. CONCLUSIONS: The medial malleoli are the most common site of leg ulceration in SSD and in other chronic hemolytic anemias. This suggests that stasis may play a role in the leg ulceration associated with chronic hemolytic anemia.

Nested case-control analysis of high pesticide exposure events from the Agricultural Health Study.

BACKGROUND: A nested case-control analysis of high pesticide exposure events (HPEEs) was conducted using the Iowa farmers enrolled in the Agricultural Health Study (AHS). METHODS: In the 12 months of the study, 36 of the 5,970 farmer applicators randomly chosen from the AHS cohort (six per 1,000 farmer applicators per year) met our definition of an HPEE, by reporting "an incident with fertilizers, weed killers, or other pesticides that caused an unusually high personal exposure" resulting in physical symptoms or a visit to a health care provider or hospital. Eligibility criteria were met by 25 HPEE cases and 603 randomly selected controls. RESULTS: Significant risk factors for an HPEE included: poor financial condition of the farm which limited the purchase of rollover protective structures OR = 4.6 (1.5-16.6), and having a high score on a risk acceptance scale OR = 3.8 (1.4-11.2). Other non-significant factors were also identified. CONCLUSIONS: The limited statistical power of this study necessitates replication of these analyses with a larger sample. Nonetheless, the observed elevated odds ratios of an HPEE provide hypotheses for future studies that may lead to preventive action.

Impaired venous hemodynamics in a minority of patients with chronic leg ulcers due to sickle cell anemia.

BACKGROUND: Chronic or recurrent leg ulceration occurs in 25% of sickle cell anemia patients, but not in the remaining 75%. Doppler studies of venous function were normal in 16 sickle cell anemia patients with leg ulcers. PATIENTS AND METHODS: Venous Duplex Ultrasound was used to study 33 sickle cell anemia patients with chronic leg ulcers. RESULTS: Six of the 33 patients had venous reflux in at least one leg. CONCLUSIONS: Venous insufficiency may contribute to the development of leg ulcers in a minority of sickle cell anemia patients. A minority of sickle cell anemia patients with chronic leg ulcers can be shown to have leg venous reflux by duplex ultrasound imaging.

Using 12-lead ECG and synthesized VCG in detection of right ventricular hypertrophy with terminal right conduction delay versus partial right bundle branch block in the pediatric population.

In pediatric electrocardiogram (ECG) analysis, mild right ventricular hypertrophy (RVH) and especially mild RVH with terminal right conduction delay (RVHtcd) are often confused with partial right bundle branch block (PRBBB). This is problematic for computer ECG analysis algorithms and even for most experienced pediatric cardiologists. This study was designed to achieve better classification of mild RVHtcd and PRBBB by combining the 12-lead synthesized vectocardiogram (VCG) transverse plane measurements with scalar ECG measurements. Pediatric ECGs used in the study were recorded with 15 leads and a 500 Hz sampling rate at the Lucile Salter Packard Children's Hospital, Stanford University Medical Center. Out of 4,200 ECGs collected consecutively over a period of 18 months, 447 RVH, 335 RBBB and 589 Normal were interpreted by expert pediatric cardiologists, and were included in the study. Statistical comparison of ECG and VCG measurements were done in stratified ECG sets (412) that have a visually indistinguishable waveform pattern, 117 RVHtcd, 96 PRBBB and 199 normal, showed significant differences in initial and terminal vectors in the transverse plane. The mean angle of the initial vector was anterior (57.2 degrees +/- 41.8) in the normal group, left anterior in the PRBBB group (34.4 degrees +/- 39.5) and in the RVHtcd group (31.9 degrees +/- 41.0) and. The mean angle of the terminal vector was right anterior (158.3 degrees +/- 36.8) in the PRBBB group, rightward (179.7 degrees +/- 29.9) in the RVHtcd group and right posterior (212.6 degrees +/- 37.8) in the normal group. These are clearly applicable features for a classification algorithm. Significantly improved classification results were obtained from a new algorithm using combined ECG and VCG measurements versus an existing algorithm. The limitation of this study stems from the unavailability of a more reliable gold standard. It may be necessary to used body surface potentials obtained with a large number of electrodes to accurately differentiate the study groups.

Atrioventricular block in a newborn with acquired long QT syndrome.

We report a case of 2:1 atrioventricular block associated with acquired long QT syndrome. A newborn presented to our neonatal intensive care unit with intermittent bradycardia due to 2:1 atrioventricular block. Initial evaluation showed QT prolongation and significant electrolytic abnormalities. After correction of the electrolytic imbalance, the QT interval normalized and atrioventricular block resolved. Compared to congenital long QT syndrome with 2:1 atrioventricular block, acquired long QT syndrome with comparable atrioventricular block has a benign prognosis, provided treatment is initiated quickly.

Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study.

BACKGROUND: Ventricular arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot are devastating complications in adult survivors of early surgery, but their prediction remains difficult. METHODS: We examined surgical, electrocardiographic, and late haemodynamic data, and their relation to clinical arrhythmia and sudden death occurring over 10 years, in a multicentre cohort of patients with repaired tetralogy, who were alive in 1985. RESULTS: Of 793 patients (mean age at repair 8.2 years [SD 8], mean time from repair 21.1 years [8.7]) who entered the study, 33 patients developed sustained monomorphic ventricular tachycardia, 16 died suddenly, and 29 had new-onset sustained atrial flutter or fibrillation. Electrocardiographic markers (QRS duration, QRS rate of change between 1985 and 1995) were significantly greater in the ventricular tachycardia and sudden-death groups. Older age at repair was associated with a higher risk of sudden death and atrial tachyarrhythmia. Pulmonary regurgitation was the main underlying haemodynamic lesion for patients with ventricular tachycardia and sudden death, whereas tricuspid regurgitation was for those with atrial flutter/fibrillation. Despite adverse haemodynamics, no patient who died suddenly had undergone late reoperation. CONCLUSION: Arrhythmia and sudden death are important late sequelae for patients after repair of tetralogy of Fallot. The electrophysiological and haemodynamic substrate of sudden death resembled that of sustained ventricular tachycardia, with pulmonary regurgitation being the predominant haemodynamic lesion. Preservation or restoration of pulmonary valve function may thus reduce the risk of sudden death. Furthermore, electrocardiographic markers can help to identify patients at risk.

Over-the-counter delta5 anabolic steroids 5-androsen-3,17-dione; 5-androsten-3beta, 17beta-diol; dehydroepiandrosterone; and 19-nor-5-androsten-3,17-dione: excretion studies in men.

Studies of urinary steroids were performed in males after oral administration of 5-androsten-3,17-dione; 5-androsten-3beta,17beta-diol; dehydroepiandrosterone; and 19-nor-5-androsten-3,17-dione. 5-Androsten-3,17-dione; 5-androsten-3beta,17beta-diol; and dehydroepiandrosterone amplify most endogenous steroids, but to a lesser extent than their delta4 analogues do. Especially affected are androsterone, etiocholanolone, dehydroandrosterone, dehydroepiandrosterone, and isomeric 5-androstendiols. 5-Androsten-3,17-dione; 5-androsten-3beta,17beta-diol; and dehydroepiandrosterone elevate the urinary testosterone to epitestosterone (T/E) ratio by a factor of 2-3 a few hours after administration. This may cause a positive T/E test (> 6) for individuals with normal T/E ratios higher than 2. Most of the steroids return to their original concentrations in less than 24 h. Etiocholanolone and 5beta-androstan-3alpha,17beta-diol remain elevated for several days. A reduced androsterone to etiocholanolone (A/E) ratio may be an indication of delta5 steroids abuse. 19-Nor-5-androsten-3,17-dione has a similar effect, except that all metabolites in urine are 19-nor exogenous steroids. Identification criteria for 19-nor-5-androsten-3,17-dione may be the same as nandrolone, that is, detection of 19-norandrosterone and 19-noretiocholanolone. Specific abundant metabolites of 19-nor-5-androsten-3,17-dione are 19-nordehydroandrosterone and 19-nordehydroepiandrosterone. In the later stages of excretion, higher concentration of 1 9-noreticholanolone relative to 19-norandrosterone specifically indicates administration of 19-nor delta5 steroids.

Over-the-counter anabolic steroids 4-androsten-3,17-dione; 4-androsten-3beta,17beta-diol; and 19-nor-4-androsten-3,17-dione: excretion studies in men.

Since the appearance of 4-androsten-3,17-dione (I) as a nutritional supplement in early 1997, we have frequently observed a characteristic deterioration of endogenous steroid profiles in athletes' urine in routine anabolic steroid testing in which concentrations of major endogenous urinary steroids and testosterone exceed normal. Human excretion studies are performed with I and newer, over-the-counter "supplements" 4-androsten-3beta,17beta-diol (II) and 19-nor-4-androsten-3,17-dione (III). Endogenous urinary steroids affected by I and II are androsterone, etiocholanolone, their hydroxylated derivatives 5alpha- and 5beta-androstan-3alpha,17beta-diols, testosterone, and epitestosterone. Their concentrations briefly increase by one to two orders of magnitude and return to normal 24 h after oral administration of I and II. The average male may test positive for testosterone because testosterone concentration rises faster than that of epitestosterone, causing the testosterone/epitestosterone (T/E) ratio to rise above the positive cutoff of 6:1. A remarkable distinction in excretion patterns was observed in eastern Asian men, for whom I and II did not affect urinary concentrations of testosterone and did not increase the T/E ratio. First-pass metabolism deactivates most of the orally administered drugs I and II, rapidly converting them into inactive androsterone and etiocholanolone. Drug II is a more effective testosterone booster because of its different metabolic pathway. After the use of III, a precursor of the potent anabolic nandrolone, high concentrations of norandrosterone and noretiocholanolone appear in urine, similar to nandrolone. These are detectable in urine for 7-10 days after a single oral dose of III (50 mg).

Significant complications can occur with ischemic heart disease and tilt table testing.

We present an elderly patient who had syncope, with known coronary artery disease and a conduction abnormality. Because of a possible vasovagal reaction, the patient underwent a tilt table test prior to evaluation of ischemia or her LV function. During the tilt table test on isoproterenol, the patient developed ventricular fibrillation which was corrected immediately by cardioversion. Subsequently, the patient was found to have significant coronary artery disease which was treated with stenting and angioplasty. After treatment, there were no inducible arrhythmias on full dose isoproterenol. This case reports a significant complication that may occur when tilt table testing with isoproterenol and ischemia.

QT dispersion in children with ventricular arrhythmia and a structurally normal heart.

In adults, increased QT dispersion has been shown to predict arrhythmic risk as well as risk of sudden death in several clinical settings. It is not known whether or not QT dispersion is increased in children with idiopathic ventricular arrhythmia. We studied three groups of children: (1) 20 patients with idiopathic VT (aged 3-18 years; mean 11.2 years); (2) 30 patients with benign PVCs (aged 1-20 years; mean 10.5 years); and (3) 30 control subjects (aged 4-17 years; mean 12 years). Standard ECGs were reviewed and the dispersion of both QT and JT intervals was compared. No patient had structural heart disease or long QT syndrome. The QT and QTc dispersion (QT delta, QTc delta) among the three groups did not differ: QTc delta of the VT group was 70 ms +/- 30 ms, QTc delta of PVC patients was 60 ms +/- 30 ms, and the QTc delta of the control group was 65 ms +/- 30 ms. The JTc delta among the three groups did not differ as well: JTc delta of the VT group was 70 ms +/- 30 ms, the JTc delta of the PVC group was 60 msec +/- 25 msec, and the JTc delta of the control group was 70 ms +/- 30 ms. We conclude that QT and JT dispersion are not significantly altered in children with idiopathic VT or benign PVCs when compared to control subjects. QT dispersion is not a reliable marker for arrhythmic risk in children with idiopathic ventricular arrhythmias and structurally normal hearts.

Catheter ablation of accessory pathways, atrioventricular nodal reentrant tachycardia, and the atrioventricular junction: final results of a prospective, multicenter clinical trial. The Atakr Multicenter Investigators Group.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of a temperature-controlled radiofrequency catheter ablation system. METHODS AND RESULTS: The patient population included 1050 patients who had undergone ablation of atrioventricular nodal reentrant tachycardia (AVNRT), an accessory pathway (AP), or the atrioventricular junction (AVJ). Ablation was successful in 996 patients. The probability of success was highest among patients who had undergone ablation of the AVJ, lowest in patients who had undergone ablation of an AP, and in between for patients who had undergone ablation of AVNRT. A major complication occurred in 32 patients. Four variables predicted ablation success (AVJ, AVNRT, or left free wall AP ablation and an experienced center). Four factors predicted arrhythmia recurrence (right free wall, posteroseptal, septal, and multiple APs). Two variables predicted development of a complication (structural heart disease and the presence of multiple targets), and 3 variables predicted an increased risk of death (heart disease, lower ejection fraction, and AVJ ablation). CONCLUSIONS: These findings may serve as a guide to clinicians considering therapeutic options in patients who are candidates for ablation.

Predictors of fluoroscopy time and estimated radiation exposure during radiofrequency catheter ablation procedures.

The objective of this study was to identify factors that predict fluoroscopy duration and radiation exposure during catheter ablation procedures. The patient population included 859 patients who participated in the Atakr Ablation System clinical trial at 1 of 9 centers (398 male and 461 female patients, aged 36 +/- 21 years). Each patient underwent catheter ablation of an accessory pathway, the atrioventricular junction, or atrioventricular nodal reentrant tachycardia using standard techniques. The duration of fluoroscopy was 53 +/- 50 minutes. Factors identified as independent predictors of fluoroscopy duration included patient age and sex, the success or failure of the ablation procedure, and the institution at which the ablation was performed. Catheter ablation in adults required longer fluoroscopy exposure than it did in children. Men required longer durations of fluoroscopy exposure than did women. The mean estimated "entrance" radiation dose was 1.3 +/- 1.3 Sv. The dose needed to cause radiation skin injury was exceeded during 22% of procedures. The overall mean effective absorbed dose from catheter ablation procedures was 0.025 Sv for female patients and 0.017 Sv for male patients. This degree of radiation exposure would result in an estimated 1,400 excess fatal malignancies in female patients and 2,600 excess fatal malignancies in male patients per 1 million patients.

Differential developmental effects of acute hypoxia on the rabbit atrioventricular conduction axis.

The differential developmental effects of hypoxia on antegrade fast and slow and retrograde conduction through the atrioventricular junction are unknown. This study describes the effects of hypoxia on fast and slow antegrade atrioventricular node, infra-Hisian and retrograde conduction in immature and mature hearts during premature pacing protocols in excise, perfused adult and neonatal rabbits. The results are: (1) antegrade conduction delay through the atrioventricular node is the same developmentally, but delay through the His-Purkinje system is greater in adults; (2) hypoxia reduces the extra delay in the His-Purkinje system in adults; (3) fast atrioventricular node conduction is more sensitive to hypoxia in neonates than in adults, and slow atrioventricular node conduction is more sensitive to hypoxia in adults than in neonates, and (4) retrograde atrioventricular node conduction is more resistant to hypoxia in neonates than in adults.

JT dispersion in Wolff-Parkinson-White syndrome: effect of eccentric ventricular depolarization on the dispersion of repolarization.

There is much interest in QT dispersion for noninvasive risk stratification of patients at risk of arrhythmias. However, little is known about the genesis of abnormal QT dispersion. In particular, whether eccentric ventricular depolarization, as seen in preexcitation, can lead to abnormal dispersion of repolarization is unknown. We studied 24 children aged 1-19 years (mean +/- SD, 11 +/- 5 years) with manifest preexcitation due to Wolff-Parkinson-White syndrome who had successful catheter ablation. Standard ECGs done preablation, early postablation (< 1 week), mid postablation (> 1 week, < 2 months), and late postablation (> 2 months) were reviewed. The QRS duration prior to ablation ranged from 90-160 ms (mean +/- SD, 123 +/- 21 ms). On the preablation ECG, the JT and JTc dispersions showed no relationship to the QRS duration (r = 0.04 and 0.07, respectively). There was no change in JT dispersion when the preablation (42 +/- 15 ms) ECG was compared to early (43 +/- 15 ms), mid (44 +/- 13 ms), and late postablation (48 +/- 19 ms) ECGs. There was no significant change in JTc dispersion as well. Thus, JT dispersion is unrelated to QRS duration and unaffected by catheter ablation in patients with Wolff-Parkinson-White syndrome. Eccentric ventricular depolarization does not lead to abnormal dispersion of repolarization.