Comparative population genomics in animals uncovers the determinants of genetic diversity.

Genetic diversity is the amount of variation observed between DNA sequences from distinct individuals of a given species. This pivotal concept of population genetics has implications for species health, domestication, management and conservation. Levels of genetic diversity seem to vary greatly in natural populations and species, but the determinants of this variation, and particularly the relative influences of species biology and ecology versus population history, are still largely mysterious. Here we show that the diversity of a species is predictable, and is determined in the first place by its ecological strategy. We investigated the genome-wide diversity of 76 non-model animal species by sequencing the transcriptome of two to ten individuals in each species. The distribution of genetic diversity between species revealed no detectable influence of geographic range or invasive status but was accurately predicted by key species traits related to parental investment: long-lived or low-fecundity species with brooding ability were genetically less diverse than short-lived or highly fecund ones. Our analysis demonstrates the influence of long-term life-history strategies on species response to short-term environmental perturbations, a result with immediate implications for conservation policies.

Wolbachia, Cardinium and climate: an analysis of global data.

Bacterial endosymbionts are very common in terrestrial arthropods, but infection levels vary widely among populations. Experiments and within-species comparisons suggest that environmental temperature might be important in explaining this variation. To investigate the importance of temperature, at broad geographical and taxonomic scales, we extended a global database of terrestrial arthropods screened for Wolbachia and Cardinium. Our final dataset contained data from more than 117 000 arthropods (over 2500 species) screened for Wolbachia and more than 18 000 arthropods (over 800 species) screened for Cardinium, including samples from 137 different countries, with mean temperatures varying from -6.5 to 29.2°C. In insects and relatives, Cardinium infection showed a clear and consistent tendency to increase with temperature. For Wolbachia, a tendency to increase with temperature in temperate climates is counteracted by reduced prevalence in the tropics, resulting in a weak negative trend overall. We discuss the implications of these results for natural and introduced symbionts in regions affected by climate change.

Population genomics of eusocial insects: the costs of a vertebrate-like effective population size.

The evolution of reproductive division of labour and social life in social insects has lead to the emergence of several life-history traits and adaptations typical of larger organisms: social insect colonies can reach masses of several kilograms, they start reproducing only when they are several years old, and can live for decades. These features and the monopolization of reproduction by only one or few individuals in a colony should affect molecular evolution by reducing the effective population size. We tested this prediction by analysing genome-wide patterns of coding sequence polymorphism and divergence in eusocial vs. noneusocial insects based on newly generated RNA-seq data. We report very low amounts of genetic polymorphism and an elevated ratio of nonsynonymous to synonymous changes ­ a marker of the effective population size ­ in four distinct species of eusocial insects, which were more similar to vertebrates than to solitary insects regarding molecular evolutionary processes. Moreover, the ratio of nonsynonymous to synonymous substitutions was positively correlated with the level of social complexity across ant species. These results are fully consistent with the hypothesis of a reduced effective population size and an increased genetic load in eusocial insects, indicating that the evolution of social life has important consequences at both the genomic and population levels.

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is less accurate in patients with Type 2 diabetes when compared with healthy individuals.

AIMS: To analyse the performances of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and of Modification of Diet in Renal Disease (MDRD) study equations to estimate glomerular filtration rate (GFR) in patients with Type 2 diabetes mellitus with GFRs >60 ml/min and in healthy volunteers. METHODS: This cross-sectional study included 111 individuals (56 patients with Type 2 diabetes and 55 healthy volunteers), aged 58 ± 9 years; 54 individuals were men (49%) and ninety-eight (88%) were white. Glomerular filtration rate was measured by the (51) Cr-EDTA single-injection method ((51) Cr-GFR) and estimated according to the standardized MDRD and CKD-EPI equations. Serum creatinine was measured by a traceable Jaffe method. Bland-Altman analysis was used to examine the agreement between measured and estimated GFR. Bias, accuracy and precision were evaluated. RESULTS: In diabetic individuals, (51) Cr-GFR was 106 ± 27 ml/min/1.73 m(2) , CKD-EPI-estimated GFR 82 ± 18 ml/min/1.73 m(2) and MDRD-estimated GFR 80 ± 21 ml/min/1.73 m(2) (P < 0.001). In healthy volunteers, the corresponding values were 98 ± 20, 89 ± 13 and 84 ± 14 ml/min/1.73 m(2) (P < 0.001). The accuracy of CKD-EPI (P30) was higher in healthy volunteers than in diabetic patients (90 vs. 66%, respectively, P < 0.001). The MDRD equation performed as poorly as the CKD-EPI equation in individuals with Type 2 diabetes. CONCLUSIONS: The CKD-EPI equation is less accurate in patients with Type 2 diabetes when compared with healthy individuals, with a 2.5-fold greater bias.

Evaluation of alterations on mitral annulus velocities, strain, and strain rates due to abrupt changes in preload elicited by parabolic flight.

We tested the hypothesis that in normal subjects, cardiac tissue velocities, strain, and strain rates (SR), measured by Doppler tissue echocardiography (DTE), are preload dependent. To accomplish it, immediately preceding image acquisition, reversible, repeatable, acute nonpharmacological changes in preload were induced by parabolic flight. DTE has been proposed as a new approach to assess left ventricular regional myocardial function by computing tissue velocities, strain, and SR. However, preload dependence of these parameters in normal subjects still remains controversial. DTE images (Philips) were obtained in 10 normal subjects in standing upright position at normogravity (1 Gz), hypergravity (1.8 Gz), and microgravity (0 Gz) with and without -50 mmHg lower body negative pressure (LBNP). Myocardial velocity curves in the basal interventricular septum were reconstituted offline from DTE images, from which peak systolic (S'), early (E') and late (A') diastolic velocities, SR, and peak systolic strain (PSepsilon) were measured and averaged over four beats. At 1.8 Gz (reduced venous return), S', E', and A' decreased by 21%, 21%, and 26%, respectively, compared with 1-Gz values, while at 0 Gz (augmented venous return), E', A', and PSepsilon increased by 57%, 53%, and 49%, respectively. LBNP reduced E' and PSepsilon. In conclusion, our results were in agreement with those obtained in animal models, in which preload was changed in a controlled, acute, and reversible manner, and image acquisition was performed immediately following preload modifications. The hypothesis of preload dependence was confirmed for S', E', A', and PSepsilon, while SR appeared to be preload independent, probably reflecting intrinsic myocardial properties.

Objective evaluation of changes in left ventricular and atrial volumes during parabolic flight using real-time three-dimensional echocardiography.

We tested the feasibility of real-time three-dimensional (3D) echocardiographic (RT3DE) imaging to measure left heart volumes at different gravity during parabolic flight and studied the effects of lower body negative pressure (LBNP) as a countermeasure. Weightlessness-related changes in cardiac function have been previously studied during spaceflights using both 2D and 3D echocardiography. Several technical factors, such as inability to provide real-time analysis and the need for laborious endocardial definition, have limited its usefulness. RT3DE imaging overcomes these limitations by acquiring real-time pyramidal data sets encompassing the entire ventricle. RT3DE data sets were obtained (Philips 7500, X3) during breath hold in 16 unmedicated normal subjects in upright standing position at different gravity phases during parabolic flight (normogravity, 1 Gz; hypergravity, 1.8 Gz; microgravity, 0 Gz), with LBNP applied (-50 mmHg) at 0 Gz in selected parabolas. RT3DE imaging during parabolic flight was feasible in 14 of 16 subjects. Data were analyzed (Tomtec) to quantify left ventricular (LV) and atrial (LA) volumes at end diastole and end systole, which significantly decreased at 1.8 Gz and increased at 0 Gz. While ejection fraction did not change with gravity, stroke volume was reduced by 16% at 1.8 Gz and increased by 20% at 0 Gz, but it was not significantly different from 1 Gz values with LBNP. RT3DE during parabolic flight is feasible and provides the basis for accurate quantification of LV and LA volume changes with gravity. As LBNP counteracted the increase of LV and LA volumes caused by changes in venous return, it may be effectively used for preventing cardiac dilatation during 0 Gz.

An emerging zoonotic clone in the Netherlands provides clues to virulence and zoonotic potential of Streptococcus suis.

Streptococcus suis is a zoonotic swine pathogen and a major public health concern in Asia, where it emerged as an important cause of bacterial meningitis in adults. While associated with food-borne transmission in Asia, zoonotic S. suis infections are mainly occupational hazards elsewhere. To identify genomic differences that can explain zoonotic potential, we compared whole genomes of 98 S. suis isolates from human patients and pigs with invasive disease in the Netherlands, and validated our observations with 18 complete and publicly available sequences. Zoonotic isolates have smaller genomes than non-zoonotic isolates, but contain more virulence factors. We identified a zoonotic S. suis clone that diverged from a non-zoonotic clone by means of gene loss, a capsule switch, and acquisition of a two-component signalling system in the late 19th century, when foreign pig breeds were introduced. Our results indicate that zoonotic potential of S. suis results from gene loss, recombination and horizontal gene transfer events.

Use of color kinesis for evaluation of left ventricular filling in patients with dilated cardiomyopathy and mitral regurgitation.

OBJECTIVES: We tested the feasibility of using analysis of color kinesis images to objectively assess global and regional left ventricular (LV) diastolic function in patients with dilated cardiomyopathy (DCM). In addition, the ability of this technique to track drug-induced changes on LV diastolic properties was studied. BACKGROUND: Diastolic dysfunction contributes to symptomatology in patients with DCM. The assessment of LV diastolic function using conventional Doppler echocardiography is indirect and is confounded by multiple variables. Moreover, the noninvasive evaluation of regional diastolic properties is difficult. In contrast, color kinesis directly tracks and color-encodes regional diastolic endocardial motion. METHODS: We studied 24 patients with DCM and mitral regurgitation (MR) and 24 age-matched normal subjects. Transmitral and pulmonary vein flow velocities were measured using pulsed Doppler echocardiography. Diastolic color kinesis images were used to calculate indexes of magnitude and timing of global and regional diastolic function. Diastolic asynchrony was evaluated in different subgroups of patients with DCM. The effects of drug infusions (nitroprusside and dobutamine) were also studied. RESULTS: Color kinesis indexes of global diastolic function showed significant differences between patients with DCM and normal subjects. Compared with Doppler indexes, color kinesis was less confounded by MR and was capable of differentiating between drug-induced lusitropic and vasodilator effects. Diastolic asynchrony was increased in patients with DCM and severe MR. CONCLUSIONS: Quantitative analysis of global and regional LV diastolic function in patients with DCM using color kinesis is feasible.

Objective evaluation of regional left ventricular wall motion during dobutamine stress echocardiographic studies using segmental analysis of color kinesis images.

OBJECTIVES: To test the feasibility of objective and automated evaluation of echocardiographic stress tests, we studied the ability of segmental analysis of color kinesis (CK) images to detect dobutamine-induced wall motion abnormalities and compared this technique with inexperienced reviewers of conventional gray-scale images. BACKGROUND: Conventional interpretation of stress echocardiographic studies is subjective and experience dependent. METHODS: CK images were obtained in 89 of 104 consecutive patients undergoing clinical dobutamine stress studies and were analyzed using custom software to calculate regional fractional area change in 22 segments in four standard views. Each patient's data obtained at rest was used as a control for automated detection of dobutamine-induced wall motion abnormalities. Independently, studies were reviewed without CK overlays by two inexperienced readers who classified each segment's response to dobutamine. A consensus reading of two experienced reviewers was used as the gold standard for comparisons. In a subgroup of 16 patients, these consensus readings and CK detection of wall motion abnormalities were compared with coronary angiography. RESULTS: The consensus reading detected ischemic response to dobutamine in 43 of 1958 segments in 23 of 89 patients. Automated detection of stress-induced wall motion abnormalities correlated more closely with the standard technique than the inexperienced reviewers (sensitivity 0.76 vs. 0.55, specificity 0.98 vs. 0.94 and accuracy 0.97 vs. 0.92). When compared with coronary angiography in a subgroup of patients, analysis of CK images differentiated between normal and abnormal wall motion more accurately than expert readers of gray-scale images (accuracy of 0.93 vs. 0.82). CONCLUSIONS: Analysis of CK images allows fast, objective and automated evaluation of regional wall motion, sensitive enough for clinical dobutamine stress data and more accurate than inexperienced readers. This method may result in a valuable adjunct to conventional visual interpretation of dobutamine stress echocardiography.

Role of the beta 2 adrenoceptor in mediating positive inotropic activity in the failing heart and its relation to the hemodynamic actions of dopexamine hydrochloride.

In patients with severe congestive heart failure, it has been suggested that since myocardial beta 1 adrenoceptors are selectively down-regulated, activation of beta 2 receptors may be a preferable approach to augmenting contractility. Accordingly, dopexamine hydrochloride (1, 2 and 4 micrograms/kg/min) and dopamine (2 and 4 micrograms/kg/min) were administered to 8 patients with dilated cardiomyopathy. Left ventricular (LV) dimensions, thicknesses and pressures were obtained using simultaneous high-fidelity pressure measurements and echocardiographic recordings. LV contractility was assessed using the load-independent relation between LV end-systolic wall stress and rate-corrected velocity of fiber shortening. Cardiac index increased in a dose-related manner with both drugs, and was accompanied by a decline in systemic vascular resistance, a measure of peripheral arteriolar tone. LV end-diastolic pressure was unaltered except for a decrease from 29 +/- 6 to 19 +/- 5 mm Hg (p less than 0.017) at the highest dose of dopexamine hydrochloride. Heart rate was unchanged during the infusion of dopamine but increased significantly with dopexamine hydrochloride. LV end-systolic wall stress, a measure of LV internal load, decreased with both drugs. With dopamine, a dose-dependent positive inotropic effect was observed. Dopexamine hydrochloride, at the 4 micrograms/kg/min infusion dose, exerted a mild positive inotropic effect comparable to that noted with dopamine at 2 micrograms/kg/min. Thus, dopamine and dopexamine hydrochloride improved overall LV performance. With dopamine, a substantial positive inotropic effect occurred in association with a reduction in LV afterload. The increased cardiac index observed with dopexamine hydrochloride was due primarily to peripheral vasodilatation and a positive chronotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Feasibility of aortic diameter measurement by multiplane transesophageal echocardiography for preoperative selection and preparation of homograft aortic valves.

BACKGROUND: Preoperative knowledge of the aortic annular diameter could enable the preoperative selection and preparation of an appropriately sized homograft aortic valve. OBJECTIVE: The aims of this study were to prospectively determine whether the combined use of transthoracic and multiplane transesophageal echocardiography allows accurate preoperative aortic annular measurements for the selection and preparation of adequately sized homograft aortic valves and to retrospectively evaluate the influence of the echocardiographic approach (transthoracic vs transesophageal) and the reader's level of experience on the accuracy of these measurements. METHODS: Aortic annular measurements were performed before the operation by an experienced reader who used a combination of transthoracic and multiplane transesophageal images of 25 patients (mean age 52 +/- 13 years) referred for homograft aortic valve replacement. Measurements were also performed retrospectively by three additional readers with different levels of training in echocardiography. These readers acquired aortic annular diameters from prerecorded tapes and obtained measurements from each echocardiographic modality independently. All values were compared with the surgical measurement obtained with a ring valve sizer. RESULTS: With the combined echocardiographic approach, excellent agreement was found between preoperative echocardiographic and surgical measurements (mean difference +/- 2 standard deviations = 0.2 +/- 1.4 mm). All echocardiographic data were found to be within 2 mm of the surgical measurement. These measurements were used to select and prepare the aortic homograft valve before insertion. The accuracy of annular measurements appeared to increase in parallel to the level of experience. The aortic annular measurements obtained retrospectively by a second experienced reader were more accurate with the use of transesophageal than with transthoracic echocardiography (p < 0.01). In contrast, the echocardiographic modality had no influence on the accuracy of measurements of less experienced readers (p > 0.2). CONCLUSIONS: Preoperative measurement of the aortic annular diameter by transthoracic and multiplane transesophageal echocardiography is accurate and clinically feasible. Preoperative knowledge of the aortic annular diameter may be used to select and prepare the aortic homograft, improving valve availability and reducing ischemic time.

Venous air embolism. Diagnosis by spontaneous right-sided contrast echocardiography.

This report describes the definitive diagnosis of venous air-embolism by documentation of spontaneous echo contrast in the right cardiac chambers following removal of a jugular venous catheter in a patient with hepatic failure. This complication was potentiated by the presence of concurrent hepatic coagulopathy which prejudiced effective hemostasis at the central venous puncture site.

Pericardial window: mechanisms of efficacy.

Although the term implies a persistent communication through which fluid might drain, how a pericardial window works is not clear. We believe that the mechanism of success is not window but rather fusion of the epicardium to the pericardium with obliteration of the potential space. To evaluate this, we studied 28 patients, all of whom underwent a subxiphoid pericardial window procedure with tube drainage maintained until output was minimal. There were no operative deaths, and 26 patients (92.9%) obtained permanent relief. Postoperative echocardiograms demonstrated thickening of the pericardium/epicardium and obliteration of the pericardial space. Autopsy performed on 4 patients who died of their underlying malignancy confirmed this fusion, which begins as an inflammatory process. A subxiphoid pericardial window relieves effusions with a low operative mortality and good long-term success (92.9%, 26 of 28). This success is dependent on the inflammatory fusion of the epicardium to pericardium and not maintenance of a window. Tube decompression should be maintained until fluid output is minimal to allow apposition and fusion of the two surfaces.

Calcified right atrial mass in a woman receiving long-term intravenous phosphate therapy.

Right atrial masses are easily seen by 2-dimensional echocardiography and may represent primary tumors, secondary tumor invasion of the right atrium, tricuspid valve vegetations, or atrial thrombi. Calcification of right atrial masses is uncommon but easily identified by 2-dimensional echocardiography because of the high echogenicity of calcium deposits. We describe a patient with a heavily calcified right atrial thrombus caused by an indwelling central venous catheter and long-term intravenous phosphate infusion.

Identification of cardiac masses and abnormal blood flow patterns with harmonic power Doppler contrast echocardiography.

Power Doppler is an ultrasound technique that color-encodes the change in amplitude of the ultrasound signal, which reflects changes in the position of scatterers between ultrasound pulses. Power Doppler can be used with echocardiographic contrast agents in a harmonic imaging mode to opacify a cardiac chamber. The opacification of a cardiac chamber can aid in visualizing the silhouette of intracardiac masses and displaying blood flow patterns. Four cases are presented that demonstrate the use of harmonic power Doppler to aid in the identification of a left ventricular apical thrombus, a left atrial thrombus, and a left ventricular pseudoaneurysm.

Age dependency of left atrial and left ventricular acoustic quantification waveforms for the evaluation of diastolic performance in left ventricular hypertrophy.

We evaluated diastolic performance in 50 normal subjects and 50 patients with concentric left ventricular (LV) hypertrophy. Age-dependent normal values were determined for LV and left atrial (LA) acoustic quantification parameters. Pulsed wave Doppler echocardiography was also performed on all subjects. Patients with LV hypertrophy had higher peak velocities of atrial contraction and atrial contributions to filling. The acoustic quantification waveforms revealed lower rapid filling percentage of total filling and lower peak rapid filling rates. The LA acoustic quantification analysis confirmed the dependence on active atrial emptying in the patients with LV hypertrophy. There were significant correlations with age for most of the LV and LA acoustic quantification parameters. Acoustic quantification provided confirmatory results in subjects with an abnormal relaxation or restrictive Doppler pattern. In subjects with a normal Doppler pattern, the acoustic quantification was of added diagnostic value, identifying abnormalities in 77% to 80% of the patients.

Doppler echocardiographic evaluation of severe rheumatic submitral valve stenosis.

The submitral apparatus may play a predominant role in rheumatic mitral stenosis and should be evaluated aggressively with Doppler echocardiography, especially in patients in whom percutaneous mitral balloon valvotomy is being considered. The following case presents a patient with rheumatic mitral valve stenosis in whom some noninvasive clues alerted us to the presence of predominant submitral stenosis.

The role of echocardiographic harmonic imaging and contrast enhancement for improvement of endocardial border delineation.

Despite advances in imaging technology, many myocardial segments remain poorly visualized with echocardiography; however, both contrast enhancement and harmonic imaging have shown promise for improving endocardial definition. Fifty subjects with technically limited echocardiograms were studied with fundamental and harmonic imaging as well as during echocardiographic contrast injection. Overall endocardial visualization scores improved with both techniques compared with fundamental imaging. Harmonic imaging improved endocardial visualization in 43% of all segments and in 57% of segments nonvisualized with fundamental imaging. The benefit of harmonic imaging was seen in all segments. Contrast echocardiography had similar overall improvements in visualization (42% of all segments, 67% of segments nonvisualized with fundamental imaging) but was not helpful in all regions. Harmonic imaging outperformed contrast in 9 of 22 segments, whereas contrast was superior in 4 of 22. In a subgroup of patients with very poor images, contrast enhancement was superior, with a greater increase in overall score and a higher salvage rate than harmonic (68% vs 40%).

Effects of MPEG compression on the quality and diagnostic accuracy of digital echocardiography studies.

The advantages of digital echocardiography studies include ease of retrieval, review, comparison, duplication, and quantitation as well as the potential for moving studies over networks. However, the large amounts of data associated with digital echocardiography studies have posed new problems. Reduction of the amount of data can be accomplished with image compression, in particular MPEG-1 (Moving Pictures Expert Group), which is designed for dynamic image sequences. However the effects of different levels of compression on the quality and diagnostic content of echocardiographic images need to be established. Digital sequences of single cardiac cycles were acquired in 40 consecutive patients, MPEG-1-compressed at different effective ratios (60:1, 80:1, 120:1, 200:1, 300:1, 370:1, 500:1), reviewed, and scored for endocardial visualization. The overall visualization scores and percentages of nonvisualized segments in the compressed images were not different from the uncompressed images up to a compression ratio of 200:1. Differential effects of compression were noted on a segmental basis and also varied with baseline image quality. The ability to correctly identify regional wall motion abnormalities did not decrease until compression ratios of 1:200 or higher were used. Digital echocardiography loops, MPEG-1-compressed at an effective ratio of 200:1, demonstrate no degradation in endocardial visualization quality or diagnostic content. Compression at this ratio has the potential to reduce the storage size of digital echocardiography studies to less than 1% of their current size.

Electronic transmission of digital echocardiographic studies: effects of MPEG compression.

The acquisition, storage and retrieval of digital echocardiographic studies greatly facilitates image review and quantitation and permits the transmission of studies electronically. However, the considerable size of digital echocardiographic data files makes transmission over existing networks slow and impractical. Reduction in the size of these data files can be accomplished with digital image compression. We sought to evaluate the effects of MPEG-1 compression on the transfer time of digital echocardiographic studies over currently available network connections. Ninety consecutive routine clinical echocardiographic studies were randomly compressed at one of three compression ratios 60:1, 80:1, or 120:1 and sent to a receiving terminal using simulated transmission rates. Compression of digital echocardiographic studies at these ratios which, have been shown to maintain diagnostic image quality, reduced the size of digital echocardiographic studies to less than 1% of their original sizes which allowed transmission of echocardiographic studies over networks using 3ISDN or T1 lines with minimal waiting time.