The Turner syndrome research registry: Creating equipoise between investigators and participants

To address knowledge gaps about Turner syndrome (TS) associated disease mechanisms, the Turner Syndrome Society of the United States created the Turner Syndrome Research Registry (TSRR), a patient‐powered registry for girls and women with TS. More than 600 participants, parents or guardians completed a 33‐item foundational survey that included questions about demographics, medical conditions, psychological conditions, sexuality, hormonal therapy, patient and provider knowledge about TS, and patient satisfaction. The TSRR platform is engineered to allow individuals living with rare conditions and investigators to work side‐by‐side. The purpose of this article is to introduce the concept, architecture, and currently available content of the TSRR, in anticipation of inviting proposals to utilize registry resources.     

In vitro studies with recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1): production and activity of an AMA1 vaccine and generation of a multiallelic response

Apical membrane antigen 1 (AMA1) is regarded as a leading malaria blood-stage vaccine candidate. While the overall structure of AMA1 is conserved in Plasmodium spp., numerous AMA1 allelic variants of P. falciparum have been described. The effect of AMA1 allelic diversity on the ability of a recombinant AMA1 vaccine to protect against human infection by different P. falciparum strains is unknown. We characterize two allelic forms of AMA1 that were both produced in Pichia pastoris at a sufficient economy of scale to be usable for clinical vaccine studies. Both proteins were used to immunize rabbits, singly and in combination, in order to evaluate their immunogenicity and the ability of elicited antibodies to block the growth of different P. falciparum clones. Both antigens, when used alone, elicited high homologous anti-AMA1 titers, with reduced strain cross-reactivity. Similarly, sera from rabbits immunized with a single antigen were capable of blocking the growth of homologous parasite strains at levels theoretically sufficient to clear parasite infections. However, heterologous inhibition was significantly reduced, providing experimental evidence that AMA1 allelic diversity is a result of immune pressure. Encouragingly, rabbits immunized with a combination of both antigens exhibited titers and levels of parasite inhibition as good as those of the single-antigen-immunized rabbits for each of the homologous parasite lines, and consequently exhibited a broadening of allelic diversity coverage.     

Biometry of infrarenal inferior vena cava measured by cavography

Summary Placement of a transvenous vena cava filter has became a common way to control recurrent pulmonary embolism. However few studies have been reported on the diameter of the infrarenal inferior vena cava (IIVC) where the device is usually placed. This study based upon 100 cavographies has showed the calculated average diameter of IIVC was 20.9 mm (range 12–27 mm) in its middle part and 21.3 mm (range 10–31 mm) in its terminal end. The calculated average IIVC length was 96 mm (range 80.3–142 mm). There was no statistical correlation between caval size and age, sex, height, weight and corporeal area. There was a statistical difference of left renal vein location between patients presenting with lumbar arthrosis and those without. We discuss different methods to measure IIVC in particular tomodensitometry. CT scans reviewed in our department show that the largest diameter of IIVC is not in a frontal plane and that the width seen on cavography is the projection of the largest diameter on the film. Therefore, the range of the real caval diameters is greater than indicated above.

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Biométrie de la v. cave inférieure sous-rénale: mesure par cavographieApplication clinique

Résumé L'utilisation de filtre cave endoveineux pour prévenir une récidive d'embolie pulmonaire est devenue d'un usage courant. Cependant peu de travaux ont été faits sur le diamètre de la veine cave inférieure infrarénale (IIVC) où l'appareil est généralement situé. Cette étude a pour but d'étudier le diamètre transversal de la VCI sousrénale (VCISR) à partir de 100 cavographies réalisées dans des conditions techniques identiques. Le diamètre moyen de la VCISR est de 20.9 mm (extrême 12–27 mm) dans sa partie moyenne et de 21.3 mm (extrême 10–31 mm) au niveau de sa terminaison. La longueur moyenne de la VCISR est de 96 mm (extrême 80,3–142 mm). L'âge, le sexe, la taille, le poids, la surface corporelle n'influencent pas les dimensions de la VCISR. Il existe une différence statistiquement significative de l'abouchement de la v. rénale gauche entre les sujets ayant une arthrose lombaire et ceux qui en sont dépourvus.La cavographie reste un examen de base en matière d'exploration de la VCI. La connaissance des variations des dimensions de la VCISR qu'elle apporte est donc indispensable. L'intérêt de cette étude est cependant limité par le fait que l'image radiologique correspond en réalité à la projection du diamètre transversal réel. Des études complémentaires utilisant en particulier la tomodensitométrie sont donc nécessaire pour préciser une éventuelle relation entre le diamètre réel et le diamètre mesuré par cavographie.

     

Isolation of Bartonella washoensis from a dog with mitral valve endocarditis

We report the first documented case of Bartonella washoensis bacteremia in a dog with mitral valve endocarditis. B. washoensis was isolated in 1995 from a human patient with cardiac disease. The main reservoir species appears to be ground squirrels (Spermophilus beecheyi) in the western United States. Based on echocardiographic findings, a diagnosis of infective vegetative valvular mitral endocarditis was made in a spayed 12-year-old female Doberman pinscher. A year prior to presentation, the referring veterinarian had detected a heart murmur, which led to progressive dyspnea and a diagnosis of congestive heart failure the week before examination. One month after initial presentation, symptoms worsened. An emergency therapy for congestive heart failure was unsuccessfully implemented, and necropsy evaluation of the dog was not permitted. Indirect immunofluorescence tests showed that the dog was strongly seropositive (titer of 1:4,096) for several Bartonella antigens (B. vinsonii subsp. berkhoffii, B. clarridgeiae, and B. henselae), highly suggestive of Bartonella endocarditis. Standard aerobic and aerobic-anaerobic cultures were negative. However, a specific blood culture for Bartonella isolation grew a fastidious, gram-negative organism 7 days after being plated. Phenotypic and genotypic characterizations of the isolate, including partial sequencing of the citrate synthase (gltA), groEL, and 16S rRNA genes, indicated that this organism was identical to B. washoensis. The dog was seronegative for all tick-borne pathogens tested (Anaplasma phagocytophilum, Ehrlichia canis, and Rickettsia rickettsii), but the sample was highly positive for B. washoensis (titer of 1:8,192) and, according to indirect immunofluorescent-antibody assay, weakly positive for phase II Coxiella burnetii infection.     

β-Glucuronidase activation of latent aggression-promoting cues in mouse bladder urine

The present study was designed to investigate the chemical properties of the aggression-promoting cues present in bladder urine of male mice. The results of the first experiment confirmed earlier work by demonstrating the presence of an aggression-promoting chemosignal in bladder urine. In Experiment 2, behavioral assays were separately performed on the organic and aqueous layers of bladder urine obtained by repeated dichloromethane extractions. Only the combined organic layers of the initial three extractions demonstrated behavioral activity. A fourth extraction showed no behavioral activity for both organic and aqueous layers. However, the findings of Experiment 3 showed that incubation of the aqueous layer from the third CH₂Cl₂ extraction in β-glucuronidase can free additional aggression-promoting cues into a subsequent CH₂Cl₂ extraction. It is concluded that two forms of the aggression-promoting chemosignal are present in bladder urine. One is lipophilic and behaviorally active, whereas the other is conjugated, possessing latent chemosignal properties.     

Mauve: multiple alignment of conserved genomic sequence with rearrangements

As genomes evolve, they undergo large-scale evolutionary processes that present a challenge to sequence comparison not posed by short sequences. Recombination causes frequent genome rearrangements, horizontal transfer introduces new sequences into bacterial chromosomes, and deletions remove segments of the genome. Consequently, each genome is a mosaic of unique lineage-specific segments, regions shared with a subset of other genomes and segments conserved among all the genomes under consideration. Furthermore, the linear order of these segments may be shuffled among genomes. We present methods for identification and alignment of conserved genomic DNA in the presence of rearrangements and horizontal transfer. Our methods have been implemented in a software package called Mauve. Mauve has been applied to align nine enterobacterial genomes and to determine global rearrangement structure in three mammalian genomes. We have evaluated the quality of Mauve alignments and drawn comparison to other methods through extensive simulations of genome evolution.     

Clearance of Theiler's virus infection depends on the ability to generate a CD8+ T cell response against a single immunodominant viral peptide

Theiler's murine encephalomyelitis virus (TMEV) induces a chronic demyelinating disease in the central nervous system of susceptible mice. Resistance to persistent TMEV infection maps to he D locus of the major histocompatibility complex suggesting a prominent role of antiviral CTL in the protective immune response. Introduction of the D(b) gene into the FVB strain confers resistance to this otherwise susceptible mouse line. Infection of the FVB/D(b) mouse with TMEV provides a model where antiviral resistance is determined by a response elicited by a single class I molecule. Resistant mice of the H-2(b) haplotype mount a vigorous H-2D(b)-restricted immunodominant response to the VP2 capsid protein. To investigate the extent of the contribution of the immunodominant T cell population in resistance to TMEV, FVB/D(b) mice were depleted of VP2-specific CD8(+) T cells by peptide treatment prior to virus infection. Peptide-treated mice were not able to clear the virus and developed extensive demyelination. These findings demonstrate that the D(b)-restricted CD8(+) T cells specific for a single viral peptide can confer resistance to TMEV infection. Our ability to manipulate this cellular response provides a model for investigating the mechanisms mediating protection against virus infection by CD8(+) T cells.     

Digital peer‐to‐peer information seeking and sharing: Opportunities for education and collaboration in newborn screening

Parents use the internet to connect with their peers and access information about a multitude of health topics, including newborn screening (NBS). As the NBS system evolves, education about NBS must be evaluated and updated to remain accessible and beneficial to parents. In this article, we aim to describe parents' current NBS educational needs and highlight areas to improve newborn screening education by detailing an analysis of NBS posts on an online parenting discussion platform. We analyzed a total of 317 discussion posts on BabyCenter®, finding that parents had questions about and desired support around many aspects of NBS including processes, results, and follow‐up. As a result of this analysis, three recommendations to improve NBS education were developed. Through collaboration and by leveraging technology, we can provide parents with accessible, timely, and desired NBS informational and social support.