Participation in genetic screening: testing different outreach methods across a diverse hospital system based patient population.

Introduction: Genomics has the potential to transform medicine by identifying genetic risk factors that predispose people to certain illnesses. Use of genetic screening is rapidly expanding and shifting towards screening all patients regardless of known risk factors, but research is limited on the success of broad population-level outreach for genetic testing and the effectiveness of different outreach methods across diverse populations. In this study, we tested the effectiveness of Digital Only (emailing and texting) and Brochure Plus Digital (mailed brochure, emailing, and texting) outreach to encourage a diverse patient population to participate in a large hospital system's whole genome sequencing program. Methods: Disproportionate stratified sampling was used to create a study population more demographically diverse than the eligible population and response rates were analyzed overall and by demographics to understand the effectiveness of different outreach strategies. Results: 7.5% of all eligible patients enrolled in the program. While approximately 70% of patients invited to complete genetic testing identified in their EHR as being Hispanic, Black or African America, Asian, or another non-White race, these patients generally enrolled at lower rates than the overall population. Other underrepresented groups had higher enrollment rates including people with Medicaid coverage (8.7%) and those residing in rural areas (10.6%). We found no significant difference in enrollment rates between our Digital-Only and our Brochure Plus Digital outreach approaches in the overall population, but enrollment rates were significantly higher for Asian patients and patients who resided in rural areas in the Brochure Plus Digital group. Across both outreach approaches, links provided in emails were most commonly used for enrollment. Discussion: Our study reveals expected enrollment rates for proactive outreach by a hospital system for genetic testing in a diverse population. As more hospital systems are adopting population-scale genetic testing, these findings can inform future outreach efforts to recruit patients for genetic testing including those patients traditionally underrepresented in genomics.

Maternal protein malnutrition: effects on prostate development and adult disease.

Well-controlled intrauterine development is an essential condition for many aspects of normal adult physiology and health. This process is disrupted by poor maternal nutrition status during pregnancy. Indeed, physiological adaptations occur in the fetus to ensure nutrient supply to the most vital organs at the expense of the others, leading to irreversible consequences in tissue formation and differentiation. Evidence indicates that maternal undernutrition in early life promotes changes in key hormones, such as glucocorticoids, growth hormones, insulin-like growth factors, estrogens and androgens, during fetal development. These alterations can directly or indirectly affect hormone release, hormone receptor expression/distribution, cellular function or tissue organization, and impair tissue growth, differentiation and maturation to exert profound long-term effects on the offspring. Within the male reproductive system, maternal protein malnutrition alters development, structure, and function of the gonads, testes and prostate gland. Consequently, these changes impair the reproductive capacity of the male offspring. Further, permanent alterations in the prostate gland occur at the molecular and cellular level and thereby affect the onset of late life diseases such as prostatitis, hyperplasia and even prostate cancer. This review assembles current thoughts on the concepts and mechanisms behind the developmental origins of health and disease as they relate to protein malnutrition, and highlights the effects of maternal protein malnutrition on rat prostate development and homeostasis. Such insights on developmental trajectories of adult-onset prostate disease may help provide a foundation for future studies in this field.

Characterization of structural and immunological properties of a fusion protein between flagellin from Salmonella and lumazine synthase from Brucella.

Aiming to combine the flexibility of Brucella lumazine synthase (BLS) to adapt different protein domains in a decameric structure and the capacity of BLS and flagellin to enhance the immunogenicity of peptides that are linked to their structure, we generated a chimeric protein (BLS-FliC131) by fusing flagellin from Salmonella in the N-termini of BLS. The obtained protein was recognized by anti-flagellin and anti-BLS antibodies, keeping the oligomerization capacity of BLS, without affecting the folding of the monomeric protein components determined by circular dichroism. Furthermore, the thermal stability of each fusion partner is conserved, indicating that the interactions that participate in its folding are not affected by the genetic fusion. Besides, either in vitro or in vivo using TLR5-deficient animals we could determine that BLS-FliC131 retains the capacity of triggering TLR5. The humoral response against BLS elicited by BLS-FliC131 was stronger than the one elicited by equimolar amounts of BLS + FliC. Since BLS scaffold allows the generation of hetero-decameric structures, we expect that flagellin oligomerization on this protein scaffold will generate a new vaccine platform with enhanced capacity to activate immune responses.

Effects of intra-articular injection of mesenchymal stem cells associated with platelet-rich plasma in a rabbit model of osteoarthritis.

The current study aims to evaluate the macroscopic and histological effects of autologous mesenchymal stem cells (MSC) and platelet-rich plasma on knee articular cartilage regeneration in an experimental model of osteoarthritis. Twenty-four rabbits were randomly divided into four groups: control group, platelet-rich plasma group, autologous MSC undifferentiated group, and autologous MSC differentiated into chondrocyte group. Collagenase solution was used to induce osteoarthritis, and treatments were applied to each group at 6 weeks following osteoarthritis induction. After 60 days of therapy, the animals were euthanized and the articular surfaces were subjected to macroscopic and histological evaluations. The adipogenic, chondrogenic, and osteogenic differentiation potentials of MSCs were evaluated. Macroscopic and histological examinations revealed improved tissue repair in the MSC-treated groups. However, no difference was found between MSC-differentiated and undifferentiated chondrocytes. We found that MSCs derived from adipose tissue and platelet-rich plasma were associated with beneficial effects in articular cartilage regeneration during experimental osteoarthritis.

[The use of transesophageal echocardiography to guide the trans-septal puncture. Practical guide, tips and tricks]. / Échocardiographie transœsophagienne pour guider la ponction transseptale. Guide pratique, astuces, particularités, pièges.

Transesophageal echocardiography is very useful to guide transseptal puncture for left atrial ablation procedures. This paper is a practical guide for the ultrasonographer who seeks to meet the expectations of the electrophysiologist, but also for young EP's in order to improve their understanding of the echocardiographical views and to ameliorate the communication between the two specialists. The tips and tricks of all the steps of the exam are presented.

[Usefulness of tricuspid annular displacement (TAD) to identify right ventricular dysfunction in normotensive patients with acute pulmonary embolism]. / Intérêt du tricuspid annular displacement (TAD) dans l'évaluation de la dysfonction ventriculaire droite au cours de l'embolie pulmonaire.

BACKGROUND: Echocardiographic criteria of right ventricular dysfunction (RVD) in acute pulmonary embolism (PE) differ among published studies. Assessment of RV systolic function remains difficult because of the RV's complex shape. We aimed to evaluate RV systolic function with TAD in patients (pts) with acute PE. TAD (QLAB, Philips Medical Imaging) was based on a tissue-tracking algorithm that is ultrasound beam angle independent for automated detection of tricuspid annular displacement. DESIGN: Prospective and observational study. METHODS: All adults' pts who were diagnosed with PE from December 2008 to December 2009 at Princess Grace Hospital, Monaco were eligible for this study after exclusion of history of heart failure. We evaluated 36 consecutive pts with PE (18 male, mean age 62.7 years), which underwent echocardiography, plasma BNP titration during the first day after admission, and a second echocardiography obtained within 48 hours before discharge. RESULTS: TAD value were significantly lower in pts with abnormal RV function by echocardiogram (15.9 ± 0.3 vs. 12.7 ± 0.2 ; P = 0.026). Pts with a normal BNP (<80 pg/ml) had an elevated TAD (16.4 ± 0.2 vs. 11.2 ± 0.3 mm ; P < 0.0001). At discharge, echocardiographic data were obtained from 33 pts (mean: 8.3 ± 3.5 days). RV end diastolic diameter, RV to LV diameter, pulmonary arterial systolic pressure, mean pulmonic valve acceleration time, RV FAC, Sa and TAD were significantly improved. There was no difference between TAD among pts with echocardiographic RVD at baseline vs. pts without RVD (14.9 ± 3.7 vs. 16.1 ± 2.9 mm ; P = 0.3). Four pts who deteriorated during short-term observation had substantially lower TAD values than those with uncomplicated courses (7.7 ± 0.4mm vs. 14.6 ± 0.2 mm ; P = 0.001). In conclusion, impaired TAD was associated with decreased RV systolic function in pts with acute PE. To identify the clinical meaning of decreased TAD, larger trials with longer follow-up periods are needed.

Retention of gases by hexadecyltrimethylammonium-montmorillonite clays.

Intercalated montmorillonite clays with different amounts of organic hexadecyltrimethylammonium (HDTMA) cations were studied to analyse their CO, CH(4), and SO(2) gas retentions. Equilibrium adsorption was measured by using a standard volumetric apparatus at 25 degrees C and 0.1 MPa. The solids were characterised by X-ray diffraction. The levels of adsorption of SO(2) by organo-montmorillonites (0.3595-1.6403 mmol/g) were higher than those of CO (up to 0.0202 mmol/g) and CH(4) (up to 0.0273 mmol/g) gases. HDTMA montmorillonites may be effective adsorbents for removing SO(2) and for its potential separation in the presence of CO and/or CH(4) molecules, which can be present in contaminated air.

[Arrhythmia and sport]. / Arythmies du sportif.

Sports arrhythmia has gained wide attention with the mediatization of the death of famous sports stars. Sport strongly modifies the structure of the heart with the development of left ventricular hypertrophy which may be difficult to differentiate from that due to doping. Intense training modifies also the resting electrocardiogram with appearance of signs of left ventricular hypertrophy whereas resting sinus bradycardia and atrioventricular conduction disturbances usually reverts upon exertion. Accordingly, arrhythmia may develop ranging from extrasystoles to atrial fibrillation and even sudden death. Recent data suggest that if benign arrhythmia may be the result of the sole intense training and are reversible, malignant ventricular arrhythmia and sudden death mostly occur in unknown structural heart disease. Hypertrophic cardiomyopathy is amongst the most frequent post mortem diagnosis in this situation. Doping is now present in many sports and further threatens the athlete in the safe practice of sport.

[New concepts in the diagnosis and treatment of atrial flutter]. / Nouveaux concepts dans la prise en charge diagnostique et thérapeutique du flutter atrial.

Atrial flutter may now be very frequently and definitely cured in a single session of radiofrequency ablation. However, the very name of atrial flutter gives rise to a certain confusion. Clinical experience from everyday activity in ablation laboratories, especially since the introduction of new mapping techniques, has shown that this entity is in fact multiple. Flutters may be classified by their electrocardiographic appearance and/or their electrophysiological mechanism with as many prognostic as therapeutic implications. This article reviews diagnostic features of typical and atypical flutter and the different treatments which may be proposed in different clinical situations.

[Sinus-like tachycardias]. / Tachycardies d'allure sinusale.

Various tachycardias presenting with positive P waves in the standard leads are described in this article. Sinus tachycardia may occur as a normal adaptation reaction to the environment or in the setting of autonomic dysregulation. It may also be mimicked by various arrhythmias which share the earliest depolarisation in the sinus node area. The authors expose a review of these mechanisms.

[Ventricular tachycardia "in salvoes"]. / Les tachycardies ventriculaires en salves.

The term of ventricular tachycardia "in salvoes" describes electrophysiographic appearances of several consecutive ectopic ventricular beats without interposition of sinus rhythm. This is an intermediate arrhythmic state between isolated ventricular extrasystoles and sustained ventricular tachycardia. The generally accepted definition of the term "sustained" implies a duration of over 30 seconds or poor haemodynamic tolerance. Strictly speaking, the term "salvoe" has no precise definition in cardiology. In the 1996 edition of the Petit Robert French dictionary, the term is defined as the simultaneous discharge of guns or successive blasts of canons. The Delaware medical dictionary does not provide a French definition of the term "salvoe". In practice, we use the term tachycardia in salvoes in the same meaning as ventricular tachycardia. Schematically, in clinical practice, two situations may be encountered. In the first case, salvoes of VT are recorded in apparently normal hearts; they are not life-threatening and, though often nearly asymptomatic, they may pose therapeutic problems. In the second case, the arrhythmia occurs in a diseased heart, with a low ejection fraction, in which the essential problem is the vital prognosis.

Availability of combination therapy for HIV: effects on sexual risk taking in a sample of high-risk gay and bisexual men.

The objective of this study was to assess the impact of successes in the medical treatment of HIV disease on the perceptions of high-risk gay and bisexual men attending an anonymous testing site towards becoming infected with HIV and on their decisions to have unsafe sex. A cross-sectional survey with a face-to-face interview and self-recorded information was used. A convenience sample of high-risk men seeking anonymous HIV antibody counselling was recruited for an intervention study. To be eligible, men had to have a history of at least one previous negative antibody test and unprotected anal intercourse within the last year. Upon enrollment, subjects were asked about the impact of new treatment developments on their decisions to engage in high-risk sex both in the recent past and in the future. In general, neither the recent successes in treating HIV nor the availability of combination therapy had any impact on the men's decisions about safe sex, although a minority of men reported less concern about becoming HIV-positive. Also, some men reported already having taken more risk. In conclusion, a small number of men in this high-risk population have increased risk behaviour as a result of recent treatment advances. These results merit continued monitoring.

[Sudden death and semi-automatic defibrillation]. / Mort subite et défibrillation semi-automatique.

While cardiac arrest in hospital poses few immediate management problems, this is not the case outside hospital. For this reason semi-automatic defibrillators are easy to handle devices designed to deliver an early electric shock in the context of usage by non-specialist people following minimum training. These devices have shown a clear improvement in survival compared to the exclusive use of a manual defibrillator by highly trained emergency services, especially in confined areas such as casinos or aircraft, or where a significant number of potential patients are concentrated, such as airports. It is now important to be able to improve public access to defibrillation by various means currently being studied, and probably by relaxing the rules which allow the use of these devices.

Atypical atrial flutters.

Typical atrial flutter is due to a counterclockwise macro-re-entry circuit localized in the right atrium with a surface ECG pattern showing predominantly negative F waves in the inferior leads and positive F waves in V1. Recently it has been proposed to classify atrial flutter on the basis of its cavo-tricuspid isthmus dependence rather than on the ECG pattern. Therefore some atrial flutters are considered typical even if the ECG does not exhibit a typical pattern. This is the case for reverse typical atrial flutter, lower loop re-entry and partial-isthmus-dependent short circuit flutter. The term atypical flutter refers to a non-isthmus dependent flutter. Usually these patients have had previous cardiac surgery with a right or left atriotomy. Flutter involving a spontaneous right atrial scar is not uncommon.

[Nodal conduction]. / La conduction nodale.

The existence of a single atrio-ventricular fascicle had been suggested in the 19th century by Wilhelm His junior. In 1906, Sunao Tawara described in details the existence of a specific muscular fascicle in charge of the atrio-ventricular conduction. Since, it has remained famous under the name of atrio-ventricular node. It is located in the apical part of the Koch triangle. It is 5 to 7 mm long and 2 to 5 mm wide and includes often an enlargement of its compact portion along the fibrous annulus to the coronary sinus ostium which seems to be associated with the development of a intra- or atrio-nodal re-entry circuit. Its action potentials are qualified as "slow response" and propagate with a speed of 0.02 to 0.05 m/sec (which is comparable to that present in the sinus node). This propagation slowness explains the PR interval on surface EKG tracings and the AH interval in intra-cardiac electrogram. When AV node cells are requested by a rapid atrial rhythm, their physiological response is made under the mode of beatings group described by Luigi Luciani and Karel Wenckebach, prior to the EKG's invention. The atrio-ventricular physiological relationship during the atrial acceleration is made according to the Luciani-Wenckebach mode and then 2/1 mode as described in the non-linear dynamics theory. The most frequent pathological of the nodal conduction are the atrio-ventricular blocks and nodal duality. They are described and commented in this article. The nodal conduction disturbances are currently accessible to different therapeutic patterns such as cardiac pacing or ablative techniques. Nonetheless the innermost mechanism are still incompletely identified and will for sure be a matter of numerous studies in the future.

Comparison of direct coronary stenting with and without balloon predilatation in patients with stable angina pectoris. BET (Benefit Evaluation of Direct Coronary Stenting) Study Group.

The purpose of this study was to compare the effects of stent placement with and without balloon predilatation on duration of the procedure, reduction of procedure-related costs, and clinical outcomes. Although preliminary trials of direct coronary stenting have demonstrated promising results, the lack of randomized studies with long-term follow-up has limited the critical evaluation of the role of direct stenting in the treatment of obstructive coronary artery disease. Between January and September 1999, 338 patients were randomly assigned to either direct stent implantation (DS+; 173 patients) or standard stent implantation with balloon predilatation (DS-; 165 patients). Baseline clinical and angiographic characteristics were similar in the 2 groups. Procedural success was achieved in 98.3% of patients assigned to DS+ and 97.5% of patients assigned to DS- (p = NS), with a crossover rate of 13.9%. Compared with DS-, DS+ conferred a dramatic reduction in procedure-related cost ($956.4 +/- $352.2 vs $1,164.6 +/- $383.9, p <0.0001) and duration of the procedure (424.2 +/- 412.1 vs 634.5 +/- 390.1 seconds, p < 0.0001). At 6-month follow-up, the incidence of major adverse cardiac events including death, angina pectoris, myocardial infarction, congestive heart failure, repeat angioplasty, or coronary artery bypass graft surgery was 5.3% in DS+ and 11.4% in DS- (p = NS). Multivariate analysis demonstrated that major adverse cardiac events rates were related to stent length of 10 mm (relative risk [RR] 3.25, 95% confidence intervals [CI] 1.36 to 7.78; p = 0.008), stent diameter of 3 mm (RR 2.69, 95% CI 1.03 to 7.06; p = 0.043), and complex lesion type C (RR 2.83, 95% CI 1.02 to 7.85; p = 0.045). Thus, in selected patients, this prospective randomized study shows the feasibility of DS+ with reduction in procedural cost and length, and without an increase in in-hospital clinical events and major adverse cardiac events at 6-month follow-up.

Frontal brain electrical activity in infants of depressed and nondepressed mothers: relation to variations in infant behavior.

In previous studies, infants of depressed mothers have been found to exhibit reduced left frontal brain electrical activity (EEG). The left frontal region has been hypothesized to mediate social approach behaviors and positive affective expression. These findings raise important questions about the cause and nature of atypical EEG patterns in infants of depressed mothers. The present study begins to address some of these questions by examining whether or not variations in patterns of frontal brain activity in infants of depressed and nondepressed mothers are related to variations in infant behavior as observed in naturalistic situations. If such relations exist, are they specific to certain behaviors hypothesized to be mediated by the frontal region (i.e., positive approach behaviors)? Frontal and parietal brain electrical activity was recorded from 14- to 15-month old infants of depressed versus nondepressed mothers during a baseline condition and during conditions designed to elicit interest and positive affect. Infant behavior was observed in naturalistic play conditions, with and without mother, on a separate day from EEG testing. Mothers provided information on infant temperament. Infants of depressed mothers showed less affection and touching of their mothers. For infants of depressed mothers only, reduced left frontal brain activity was found to be related to lower levels of affection toward mother, but not to infant temperament. Furthermore, increased generalized frontal activation was found to be related to higher levels of negative affect, hostility, and tantrums and aggression. Relations between infant brain activity and behavior were not found for parietal EEG activity. These results suggest that infant frontal electrical brain activity is related to variations in infant behavior, especially those involved in positive affiliative behavior and the expression and regulation of negative affect. The nature and cause of atypical patterns of brain activity and question of whether such atypical patterns of frontal brain activity predispose infants to affective disorders in later life are discussed.